8-K – Current report

On February 28, 2017 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported that it outperformed its financial guidance by ending 2016 with pro forma operating income of $25.8 million and $665.2 million in cash, cash equivalents and short-term investments (Press release, Ionis Pharmaceuticals, FEB 28, 2017, View Source [SID1234517888]). The Company also reported a GAAP loss from operations of $46.3 million.

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"2016 was a year of significant accomplishments for Ionis, culminating in the U.S. approval of SPINRAZA, in record time and with a very broad label. The approval of SPINRAZA is a testament to the efficacy, safety and tolerability that SPINRAZA demonstrated in multiple clinical studies in multiple SMA patient populations. We are pleased with Biogen’s early launch efforts in the U.S. and their actions directed to making SPINRAZA available to patients around the world as soon as possible," said B. Lynne Parshall, chief operating officer of Ionis Pharmaceuticals.

"In 2016, we reported positive clinical data from 11 studies with six drugs. We also continued to advance over 36 drugs in development, including our Phase 3 drugs, volanesorsen and IONIS-TTRRx, which will complete pivotal trials shortly. We also added five new drugs to our pipeline, including our first Generation 2.5 LICA drug and our first oral locally acting drug for gastrointestinal autoimmune diseases.

"In the first week of 2017, we and our subsidiary, Akcea, initiated a collaboration with Novartis to develop and co-commercialize AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx for patients with cardiovascular disease. Our partner for our Factor XI program, Bayer, is advancing IONIS-FXIRx and is expanding the program by initiating development of the LICA follow-on, IONIS-FXI-LRx. In addition, our broad strategic collaborations with Biogen and AstraZeneca continue to be productive. We believe our constellation of partnerships demonstrate the potential of our antisense drugs to address a wide variety of diseases with both large and small patient populations.

"In 2017, we expect to be breakeven or profitable at the operating line on a pro forma basis, driven in part by revenue from SPINRAZA. Biogen anticipates EU approval mid-year and has filed for regulatory authorization in Japan, Canada and Australia, and is planning to file additional applications in other countries this year. Approval in additional markets could broaden access to SPINRAZA and further bolster our revenues. We and Akcea expect to report Phase 3 data in March from the APPROACH study of volanesorsen in patients with familial chylomicronemia syndrome. Together with Akcea, we are preparing the regulatory submissions and plan to file for marketing authorization in the U.S., EU and Canada this year, provided the Phase 3 data are positive. Akcea has also made progress in preparing to launch volanesorsen. In the second quarter, we plan to report Phase 3 data from the NEURO-TTR study with IONIS-TTRRx in patients with familial amyloid polyneuropathy. We and our partner, GSK, are preparing to file an NDA before year end if the Phase 3 data are positive. While progress in these late-stage programs represents key visible catalysts for the year, we also plan to provide updates from our large and diverse pipeline throughout the year.

"We believe we have the key elements in place to achieve sustained, long-term financial growth. We have multiple drivers of revenue; a partnership strategy that leverages partner resources; a mature, broad and rapidly advancing clinical pipeline; and an innovative, more efficient drug discovery platform that enables us to continue developing new drugs with the potential for significant commercial opportunity in both rare and more prevalent diseases. We are now closer to achieving our goal of becoming a profitable, multi-product company delivering innovative medicines to patients with serious diseases," concluded Ms. Parshall.

Ionis’ 2017 goals and a list of corporate and drug development highlights can be found at the end of this press release prior to the financial tables.

Financial Results

"2016 was marked by continued progress, highlighted by the approval of SPINRAZA. We earned substantial license fees and milestone payments from our many achievements, which led us to significantly improve upon our revenue, pro forma net operating loss and cash guidance for 2016. In 2016, we generated $347 million of revenue, an increase of 45 percent compared to our guidance of $240 million. Importantly, we were able to achieve all of our 2016 accomplishments with only a nominal increase in our expenses over 2015. We ended 2016 with a GAAP loss from operations of $46 million, which included $72 million in non-cash compensation expense related to equity awards resulting in pro forma operating income of $26 million. In addition, we reported GAAP and pro forma net income for the third and fourth quarters. During the year, we received more than $190 million from our partners and ended the year with $665 million in cash, exceeding our year-end cash guidance by $65 million. This cash balance does not include more than $100 million that we earned in 2016 and received payment for in 2017," said Elizabeth L. Hougen, chief financial officer of Ionis Pharmaceuticals.

"We are pleased to add commercial revenue from SPINRAZA to our already significant revenue from partnerships. Over the past five years, we have consistently increased our revenue, reflecting the successes of our partnered programs and drugs. This R&D revenue provides a base of revenue that funds most of our pro forma operating expenses. While in any year the specific sources of our R&D revenue change, the consistent growth in revenue we have achieved over the last five years supports the sustainability of this component of our operating model. In 2017, we expect to continue to have a strong R&D revenue base that funds most of our pro forma operating expenses. To that revenue base, we are adding commercial revenue from SPINRAZA royalties. This revenue is nearly all profit to us, in other words we have only a nominal amount of corresponding expense associated with it. For 2017, we expect our operating expenses to be essentially flat compared to 2016; however, the composition of our expenses will change to reflect the evolution of our business. We plan to continue to increase our commercial spending for volanesorsen as our subsidiary, Akcea, prepares to launch volanesorsen globally in 2018. These increases will be offset by a decrease in our R&D expenses, reflecting the fact that our current Phase 3 programs are coming to a close. Because of the efficiency of our technology, we can advance our earlier stage drugs and add new drugs to our pipeline while still decreasing our research and development expenses. The combination of a solid base of R&D revenue, SPINRAZA commercial revenue and prudent spending, support our projection that we will be breakeven or profitable at the operating line on a pro forma basis for 2017. As we have more visibility on SPINRAZA sales, we will provide more detailed guidance. Already in 2017, we have generated more than $250 million in cash from our partnered programs. As such, we are projecting a year-end cash balance of over $825 million," concluded Ms. Hougen.

All pro forma amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of GAAP to pro forma measures, which is provided later in this release.

Revenue

Ionis’ revenue for the three and twelve months ended December 31, 2016 was $160.3 million and $346.6 million, compared to $51.6 million and $283.7 million for the same periods in 2015. Ionis’ revenue in 2016 consisted of the following:

·
$170 million from Biogen for FDA approval, licensing and advancing the Phase 3 program for SPINRAZA;
·
$53 million from AstraZeneca for advancing and licensing IONIS-KRAS-2.5Rx and selecting IONIS-AZ4-2.5-LRx to move into development;
·
$15 million from Janssen for licensing IONIS-JBI1-2.5Rx and validating an undisclosed target to treat patients with a gastrointestinal autoimmune disease;
·
$15 million from Kastle Therapeutics for acquiring Kynamro;
·
$8 million from Biogen for advancing IONIS-SOD1Rx, IONIS-BIIB4Rx and IONIS-BIIB6Rx;
·
$61 million from the amortization of upfront fees; and
·
$25 million primarily from its partners for the manufacturing services Ionis performed.

In comparison, Ionis’ revenue in 2015 included $115.7 million in milestone payments from partnered programs, $91.2 million in connection with Bayer’s exclusive license of IONIS-FXIRx, $56.2 million from the amortization of upfront fees and $20.6 million primarily from the manufacturing services Ionis performed for its partners.

Ionis’ revenue fluctuates based on the nature and timing of payments under agreements with its partners and consists primarily of revenue from the amortization of upfront fees, milestone payments and license fees.

Operating Expenses
Ionis’ operating expenses for the three and twelve months ended December 31, 2016 on a GAAP basis were $119.2 million and $392.9 million, respectively, and on a pro forma basis were $104.0 million and $320.8 million, respectively. This is compared to GAAP operating expenses of $114.5 million and $359.5 million and pro forma operating expenses of $97.1 million and $300.2 million for the same periods in 2015. The increase in operating expenses was primarily due to Phase 3 programs for SPINRAZA, IONIS-TTRRx and volanesorsen that Ionis conducted in 2016. The Company completed target enrollment in four of the Phase 3 studies at the end of 2015, and as a result, these studies were in their most expensive stage during 2016. In addition, Akcea continued to build a global organization and prepare for the launch of volanesorsen. In addition, Ionis’ operating expenses for 2016 on a GAAP basis increased due to an increase in non-cash compensation expense related to equity awards that resulted from an increase in the exercise price of the stock options the Company has granted over the past several years.

Loss on Retirement of Debt
In December 2016, Ionis refinanced a majority of its 2¾% convertible senior notes due 2019 (2¾% Notes). In the refinancing, Ionis reduced the interest rate to 1% by issuing an additional $185.5 million of its 1% convertible senior notes due 2021 (1% Notes). Ionis also significantly reduced the potential dilution from its convertible notes and extended the maturity to November 2021. As a result of the early repurchase of the 2¾% Notes, Ionis recognized a $4.0 million non-cash loss.

Income Tax Expense
Ionis recognized income tax expense of $2.9 million for the year ended December 31, 2016 compared to $0.4 million in 2015. Ionis’ tax expense increased in 2016 compared to 2015 primarily due to an increase in taxable income resulting from Ionis’ strong financial performance in 2016.

Net Income (Loss)
Ionis reported net income of $25.9 million and a net loss of $86.6 million for the three and twelve months ended December 31, 2016 on a GAAP basis, respectively, compared to a net loss of $71.4 million and $88.3 million for the same periods in 2015. Ionis recorded pro forma net income of $41.0 million for the three months ended December 31, 2016 compared to a pro forma net loss of $54.0 million for the same period in 2015. For the twelve months ended December 31, 2016, the Company had a pro forma net loss of $14.4 million compared to a pro forma net loss of $29.0 million in 2015. Basic and diluted net income per share for the three months ended December 31, 2016 on a GAAP basis was $0.21. Basic and diluted net loss per share for the twelve months ended December 31, 2016 was $0.72. This is compared to a basic and diluted net loss of $0.59 and $0.74 per share for the three and twelve months ended December 31, 2015, respectively.

Balance Sheet
As of December 31, 2016, Ionis had cash, cash equivalents and short-term investments of $665.2 million compared to $779.2 million at December 31, 2015. Ionis’ cash balance decreased in 2016 primarily due to spending to support the Company’s ongoing Phase 3 programs. Ionis’ cash balance at the end of 2016 did not include $107 million the Company earned in the fourth quarter of 2016 and received in 2017. Since the end of 2016, Ionis has generated more than $250 million primarily from its Novartis and Bayer partnerships. Ionis’ working capital was $664.1 million at December 31, 2016 compared to $688.1 million at December 31, 2015.

8-K – Current report

On September 8, 2016 The Food and Drug Administration ("FDA") has notified Clovis Oncology, Inc. (the "Company") that FDA is not currently planning to hold an advisory committee meeting to discuss the Company’s New Drug Application for rucaparib (Filing, 8-K, Clovis Oncology, SEP 8, 2016, View Source [SID:1234515002]). As previously announced by the Company, FDA has accepted the Company’s NDA for accelerated approval of rucaparib and granted priority review status to the application with a Prescription Drug User Fee Act (PDUFA) date of February 23, 2017.

8-K – Current report

On September 7, 2016 Agios Pharmaceuticals, Inc. (the "Company") reported that its collaboration partner Celgene Corporation ("Celgene") expects to submit a new drug application ("NDA") to the U.S. Food and Drug Administration ("FDA") for enasidenib (AG-221), a first-in-class, oral, selective, potent inhibitor of mutant isocitrate dehydrogenase-2 ("IDH2"), in relapsed and/or refractory acute myeloid leukemia ("AML") (Filing, 8-K, Agios Pharmaceuticals, SEP 7, 2016, View Source [SID:1234514978]).

The NDA will be based on data from the ongoing phase 1/2 study of AG-221 in patients with advanced hematologic malignancies with an IDH2 mutation. The NDA submission is expected to occur by year-end 2016. Celgene will be discussing the planned enasidenib NDA submission at the Citi 11th Annual Biotech Conference in Boston in a webcast event on Wednesday, September 7, 2016 at 12:00 pm ET.

Patients with isocitrate dehydrogenase 1 ("IDH1") mutant-positive AML whose disease has progressed after standard therapies also have limited treatment options, and the Company plans to explore a similar regulatory path for AG-120, its wholly-owned, first-in-class, oral, potent inhibitor of mutant IDH1, which could lead to a NDA submission in 2017 in the U.S. The Company plans to provide a regulatory update on AG-120 by the end of 2016.

The ongoing AG-221 phase 1/2 trial includes a dose-escalation phase and the following five expansion cohorts, all of which have completed accrual: (i) a cohort of 25 patients aged 60 years or older with IDH2 mutant-positive relapsed or refractory AML, or any IDH2-mutant positive AML patient, regardless of age, who has relapsed following a bone marrow transplant ("BMT"); (ii) a cohort of 25 patients aged less than 60 years with IDH2 mutant-positive relapsed or refractory AML, not including patients with AML who have relapsed following a BMT; (iii) a cohort of 25 patients aged 60 years or older with untreated IDH2 mutant-positive AML who decline standard of care chemotherapy; (iv) a cohort of 25 patients with IDH2 mutant-positive advanced hematologic malignancies not eligible for cohorts (i) to (iii); and (v) a cohort of approximately 125 patients with IDH2 mutant-positive AML who are in second or later relapse, refractory to second-line induction or reinduction treatment, or have relapsed after allogeneic transplantation.

8-K – Current report

On September 7, 2016 Epizyme, Inc. (the "Company") reported that the Independent Data Monitoring Committee (the "IDMC") convened on September 6, 2016 to assess the futility of tazemetostat in the follicular lymphoma with wild-type EZH2 cohort of the Company’s ongoing phase 2 study in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) (Filing, 8-K, Epizyme, SEP 7, 2016, View Source [SID:1234514982]). Based on review of the clinical experience to date, the IDMC has confirmed that the study cohort has surpassed its pre-specified futility hurdle, and the Company will continue to accrue patients to fully enroll this cohort. Multiple objective responses have been observed in this cohort of patients, including complete and partial responses, as well as stable disease in patients still on study beyond the first ten evaluated for futility. In addition, there were no safety concerns raised by the IDMC in their review of the study.

All five study cohorts have now surpassed their pre-specified futility hurdles, and enrollment continues in all study arms. The Company plans to present mature data from all five study cohorts in the first half of 2017, consistent with prior guidance.

8-K – Current report

On June 21, 2016, Epizyme, Inc. (the "Company") reported that it entered into a collaboration agreement with Genentech, a member of the Roche Group ("Genentech"), to conduct a phase 1b clinical trial to investigate the anti-cancer effects of the Company’s EZH2 inhibitor, tazemetostat, and Genentech’s recently approved anti-PD-L1 cancer immunotherapy, Tecentriq (atezolizumab), when used in combination (Filing, 8-K, Epizyme, JUN 22, 2016, View Source [SID:1234513503]).

The trial will evaluate this combination regimen for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Under the agreement, each company will supply its respective anti-cancer agent to support the trial and share equally in the trial’s costs. Genentech will manage study operations for the trial. The Company expects that patient enrollment in the trial will begin in the second half of 2016.

8-K – Current report

On May 24, 2016 a wholly-owned subsidiary of Spectrum Pharmaceuticals, Inc. ("Spectrum"), Allos Therapeutics Inc. (the "Company"), and Teva Pharmaceuticals USA, Inc. ("Teva"), reported that it has entered into a settlement agreement to resolve their patent litigation relating to Folotyn (pralatrexate injection) (Filing, 8-K, Spectrum Pharmaceuticals, MAY 25, 2016, View Source [SID:1234512774]).

As a result of the settlement, Teva will be permitted to market a generic version of Folotyn in the United States on December 1, 2022 or earlier under certain circumstances. Details of the settlement are confidential, and the parties will submit the agreement to the Federal Trade Commission and the Department of Justice. The parties will request that the court enter an order, in which it will dismiss the Company’s litigation against Teva. The Company’s litigation against other generic filers continues. This litigation is described in further detail in Part II, Item 1 of Spectrum’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2016, filed with the U.S. Securities and Exchange Commission on May 6, 2016.

8-K – Current report

On April 7, 2016 Heat Biologics, Inc. ("Heat") (Nasdaq: HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported that the company is implementing cost-saving measures and a focused corporate strategy to achieve, with its current cash on-hand, data readout in the fourth quarter of 2016 for its lead Phase 2 program evaluating HS-410 for the treatment of non-muscle invasive bladder cancer (Filing, 8-K, Heat Biologics, APR 7, 2016, View Source [SID:1234510529]).

These cost-saving measures include a workforce reduction of approximately 22% of the company’s headcount and a reduction in compensation for the remaining leadership team. Heat also announced the voluntary resignation of two members from its Board of Directors. In addition, Heat will further decrease operating expenses by advancing only the eight patients currently enrolled in its Phase 1b clinical trial evaluating HS-110 for the treatment of non-small cell lung cancer instead of enrolling the eighteen patients initially planned. Heat intends to focus its resources to achieve the important near-term milestones for these two product candidates, both of which are expecting topline data in the fourth quarter of 2016.

"We remain committed to advancing our lead clinical program for HS-410 and the focused reductions announced today extend our cash runway to reach significant inflection points expected later this year," said Jeff Wolf, Heat’s Founder and CEO. "While difficult, these cost-saving measures are necessary. We are truly grateful for the meaningful contributions of the talented individuals impacted."

8-K – Current report

On March 16, 2016 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or "The Company"), reported that the protocol for its phase 3 clinical trial for PV-10 as an investigational treatment for melanoma has been amended to reflect current and evolving standards of care and applicable patient population for a global study in melanoma (Filing, 8-K, Provectus Pharmaceuticals, MAR 16, 2016, View Source [SID:1234509578]).

Major amendments to the protocol include the addition of talimogene laherparepvec (ImlygicTM) as an option for use as comparator. The amended protocol also extends eligibility to include Stage IV M1a patients having no active nodal or distant cutaneous or subcutaneous metastatic disease. These patients have disease characteristics and prognosis similar to that of the Stage IIIB and IIIC patients that initially defined the study patient population.

In addition, the updated protocol clarifies eligibility for patients not having access to immune checkpoint inhibitors due to standard of care and those not having access to targeted therapy due to standard of care, as well as inclusion of patients who have failed targeted therapy. In the latter case, patients who have failed targeted therapy but meet study eligibility criteria have similar disease manifestations to the remaining study population but have limited treatment options.

Dr. Eric Wachter, CTO of Provectus, said, "These kinds of amendments are commonplace in phase 3 studies and serve to fine-tune the patient population and study procedures to match changing care standards for a large global study. They are the direct result of current and emerging options for these patients and have been developed with extensive input from global leading melanoma investigators. In particular, the most obvious amendment addresses approval in late October of Imlygic by the FDA as the first and only oncolytic viral therapy. As we implement the amended protocol we will assess potential impact on study timelines."

For further information about the study, please visit View Source

8-K – Current report

On March 8, 2016 Bio-Path Holdings, Inc., (NASDAQ: BPTH) ("Bio-Path"), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that it has entered a sponsored research agreement with The University of Texas MD Anderson Cancer Center ("MD Anderson") to evaluate Bio-Path’s clinical pipeline for its ability to modulate pancreatic cancer (Filing, 8-K, Bio-Path Holdings, MAR 8, 2016, View Source [SID:1234509416]).

Included in the evaluation will be BP1001 (Liposomal Grb2 antisense), Bio-Path’s lead product candidate, which is currently in a Phase II study for blood cancers.

Jason Fleming, M.D., F.A.C.S., professor of surgical oncology within the division of surgery at MD Anderson, will serve as the study’s principal investigator. Dr. Fleming initiated and developed the first direct xenograft program in gastrointestinal cancer. These xenografts were derived from malignant pancreatic tumors that Dr. Fleming and his surgical colleagues removed from patients at MD Anderson. Dr. Fleming is also director of the tissue acquisition and biorepository core for the Pancreas Cancer Research Program at MD Anderson, and is a board certified pancreatic surgeon.

"We are honored to collaborate with Dr. Fleming," said Peter Nielsen, President and Chief Executive Officer of Bio-Path. "His experience working with pancreatic xenografts makes him uniquely qualified to lead this study. We look forward to assessing whether Bio-Path’s drug candidates work in this ex vivo model before potentially moving into animal studies."

8-K – Current report

On March 3, 2016 Bio-Path Holdings, Inc., (NASDAQ: BPTH) ("Bio-Path"), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported positive results from the eighth and final cohort of the safety segment of Bio-Path’s Phase II trial assessing the toxicity of the Company’s lead product candidate, BP1001 (Liposomal Grb2 antisense), in combination with low-dose cytarabine (LDAC) chemotherapy in patients with advanced acute myeloid leukemia (AML) (Filing, 8-K, Bio-Path Holdings, MAR 3, 2016, View Source [SID:1234509382]).

Patients in Cohort 8 were treated with 90 mg/m2 of BP1001 twice a week over a four-week period, in combination with a standard regimen of frontline LDAC. Results were consistent with those seen in previous cohorts, demonstrating BP1001 to be safe and well tolerated, with signs of anti-leukemia activity. The Company saw no adverse events attributable to BP1001 treatment. In Cohort 8, two AML patients achieved partial remission. One patient continues to receive additional treatments.

"The encouraging results from the eighth and final cohort of the safety portion of this trial are exciting not just for Bio-Path, but also for patients suffering from blood cancers like AML," said Peter Nielsen, President and Chief Executive Officer of Bio-Path. "These results reinforce our confidence in BP1001 as a safe and effective treatment for AML in combination with frontline chemotherapy. We look forward to assessing the efficacy of BP1001 in the Phase II clinical trial."

With the closing of Cohort 8, the Phase II safety assessment of BP1001 in combination with low-dose cytarabine is complete. The safety assessment included two cohorts, which assessed six patients evaluated with 60 mg/m2 and 90 mg/m2 of BP1001 in combination with low-dose cytarabine. No toxic side effects attributable to BP1001 treatment were observed at either dose. Of the six evaluable patients included in both cohorts of the safety segment, two achieved complete remission, while two others achieved partial remission. Of the patients responding, their blood properties show improvement, suggesting BP1001’s potential efficacy as a combination therapy.

The Company is in the process of submitting these results to the U.S. Food and Drug Administration and is planning to open the efficacy portion of the Phase II trial of BP1001 in the second quarter of 2016.

8-K – Current report

On March 2, 2016 Sorrento Therapeutics, Inc. (NASDAQ: SRNE; Sorrento), an antibody-centric, clinical-stage biopharmaceutical company developing new treatments for cancer and other unmet medical needs, and Yuhan Corporation (000100.KS; Yuhan), one of the largest and most respected pharmaceutical companies in South Korea, reported that they have entered into an agreement to form a joint venture company (JVC), ImmuneOncia Therapeutics, LLC, to develop and commercialize a number of immune checkpoint antibodies against undisclosed targets for both hematological malignancies and solid tumors (Filing, 8-K, Sorrento Therapeutics, MAR 2, 2016, View Source [SID:1234509352]).

The creation of ImmuneOncia marks an important milestone in strengthening the presence of both companies in the dynamic field of immuno-oncology. Closing of the transaction is subject to customary closing conditions.

A recent report has predicted that the annual market for immunotherapies, consisting of anti-checkpoint antibodies, vaccines, and cell therapies, will exceed $35B while becoming the backbone of treatment for up to 60% of cancers over the next decade.1 ImmuneOncia will benefit from Sorrento’s leading immunotherapy product portfolio as well as its manufacturing capabilities. The joint venture will also take advantage of Yuhan’s world-class experience in clinical research and development. ImmuneOncia will focus on advancing novel immunotherapies consistent with its mission of bringing safe and effective treatments for unmet medical needs to patients worldwide.

"The formation of ImmuneOncia represents a significant milestone for Yuhan as this is our first research and development-based joint venture company. Reflecting this importance, we are committing significant resources to ImmuneOncia for the development of novel cancer immunotherapies, an area of significant unmet need not just in Korea but also globally. Our JV will benefit immensely from Korea’s world-renowned excellence and efficiency in clinical drug development. We have strong interest in investing in Sorrento and its innovative immuno-oncology mAb portfolio, and look forward to working closely with Sorrento’s outstanding team as well as further expanding our strategic relationship together," said Mr. Jung Hee Lee, President and CEO of Yuhan.

"We are excited to partner with Yuhan in jointly establishing ImmuneOncia," said Dr. Henry Ji, President and CEO of Sorrento. "This global joint venture enables Sorrento and Yuhan to combine our complementary strengths with the ultimate goal of developing and commercializing Sorrento’s innovative immune checkpoint mAbs. Through joint ventures and strategic alliances, we continue to accelerate the resource-efficient development of Sorrento’s diverse portfolio of immunotherapies into the clinic. We share Yuhan’s enthusiasm for the potential of ImmuneOncia to develop a deep pipeline of immuno-oncology products for cancer patients worldwide."

Under the terms of the joint venture agreement (JVA), Yuhan will contribute an initial investment of USD $10 million to ImmuneOncia, and Sorrento will grant the JV an exclusive license for one of their immune checkpoint antibodies for specified countries while retaining the rights for US, European, and Japanese markets, as well as global rights for the JV to two additional antibodies that will be selected by ImmuneOncia from a group of pre-specified antibodies from Sorrento’s immuno-oncology antibody portfolio. Yuhan will own 51% of ImmuneOncia, while Sorrento will hold the remaining 49%. Yuhan’s Chief Scientific Officer Dr. Su Youn Nam will be appointed CEO of ImmuneOncia. The first of the three immune checkpoint antibodies is expected to enter clinical trials next year.

8-K – Current report

On February 29, 2016 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or "The Company"), reported that it is initiating a protocol titled, "A Phase 1 Study to Assess the Safety, Tolerability and Effectiveness of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver in the Reduction of Biochemical Markers and Symptoms Caused by Secretory Products (Filing, 8-K, Provectus Pharmaceuticals, FEB 29, 2016, View Source [SID:1234509272])."

The 12-patient phase 1 study will run up to 48 months with interim data anticipated at the half-way point of the two-cohort study. Patients in the first of the two successive cohorts will receive PV-10 to a single NET tumor in their liver, while patients in the second cohort may receive PV-10 to multiple NET tumors.

Timothy Price, M.D. will serve as principal investigator for the study at The Queen Elizabeth Hospital in Woodville, South Australia.
Dr. Price explained, "The primary endpoint of our study will be assessment of safety and tolerability of PV-10 in the treatment of these metastatic NETs. Our secondary endpoints address preliminary efficacy, disease symptoms and biomarkers, and include assessments of Objective Response Rate (ORR) of injected and uninjected tumors; change in tumor biomarkers (somatostatin receptor expression, chromogranin A and 5-hydroxyindole acetic acid); change in NET symptoms assessed by standard quality of life instruments; and possible change in peripheral blood mononuclear cells (PBMCs)."

Dr. Eric Wachter, CTO of Provectus, noted, "This protocol is a natural complement to work ongoing in our initial study of hepatic cancers under protocol PV-10-LC-01, which has allowed us to assess PV-10 in a number of tumor types using the method of administration that will be used in this new study. In addition to providing further data on the overall safety of this approach, this study is tailored to NET patients and will allow us to assess potential clinical benefit in terms of objective response and changes in biomarkers and symptoms of these tumors. Patients with metastatic NET tumors are often plagued by persistent diarrhea, flushing, breathing difficulties, abdominal cramping and swelling of the arms and legs. It will be very useful to determine whether PV-10 ablates NET tumors and if ablation has a positive impact on quality of life for patients."

For further information, please visit View Source The study is expected to open for enrollment in March 2016.

About the Queen Elizabeth Hospital

The Queen Elizabeth Hospital (TQEH) is a 311 bed, acute care teaching hospital that provides inpatient, outpatient, emergency and mental health services to a population of more than 250,000 people living primarily in Adelaide’s western suburbs.

8-K – Current report

On February 29, 2016 Heron Therapeutics, Inc. (NASDAQ: HRTX), rreported that the U.S. Food and Drug Administration (FDA) would not take action on the New Drug Application (NDA) for SUSTOL (granisetron) Injection, extended release by the original Prescription Drug User Fee Act (PDUFA) goal date of January 17, 2016 and would delay taking action until late February 2016 (Filing, 8-K, Heron Therapeutics, FEB 29, 2016, View Source [SID:1234509303]).

The FDA has informed the Company that it has not concluded its review of the NDA and could not yet provide the Company with an anticipated action date, but indicated that they will communicate the new action date to the Company later this week.

SUSTOL is a long-acting formulation of the FDA-approved 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist granisetron being developed for the prevention of both acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). SUSTOL is formulated utilizing Heron’s proprietary Biochronomer drug delivery technology, and has been shown to maintain therapeutic drug levels of granisetron for at least five days with a single subcutaneous injection.

8-K – Current report

On February 26, 2016 Immunomedics, Inc., (Nasdaq:IMMU) reported receipt of a notice from UCB terminating the May 2006 Development, Collaboration and License Agreement for epratuzumab for all non-cancer indications worldwide. Under the terms of the Agreement, the companies will now begin the transition process in a timely and orderly fashion (Filing, 8-K, Immunomedics, FEB 29, 2016, View Source [SID:1234509304]).

"The return of the worldwide rights of epratuzumab for all non-cancer indications allows us to examine all options to maximize its value, not only in oncology but also in autoimmune diseases," commented Cynthia L. Sullivan, President and Chief Executive Officer of Immunomedics. "Epratuzumab is being studied in a Phase 3 clinical trial in pediatric patients with acute lymphoblastic leukemia sponsored by a European consortium, and Bayer has begun studying epratuzumab as a thorium-227-labeled antibody in patients with advanced non-Hodgkin lymphoma," Ms. Sullivan further remarked.

8-K – Current report

On January 25, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ: OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported an update on the Phase 2 ALPINE clinical trial following a pre-planned January 23 interim efficacy assessment of the clinical trial by an independent data safety monitoring board (DSMB) (Filing, 8-K, OncoMed, JAN 25, 2016, View Source [SID:1234508853]). The DSMB assessed data from 172 patients treated as of a January 6, 2016 data cutoff date.

From a safety standpoint, the DSMB recommended that the study proceed to completion without modification. No unexpected safety findings emerged from its review.

However, the DSMB informed OncoMed of several findings regarding futility of the trial, notably:

• A statistically significant worsening of response rate and progression-free survival (PFS) in the treatment arm in the overall intent-to-treat population, as well as a negative trend in each Notch biomarker subgroup

• A strong trend to lack of benefit in the treatment arm for overall survival (OS), regardless of Notch biomarker levels, suggesting a low probability of achieving a statistically significant OS benefit based on analyses reviewed by the DSMB

Based on this information, OncoMed is in the process of unblinding the trial to carefully assess the current results and determine appropriate next steps for this fully enrolled trial. Eighteen patients remain on study drug treatment (tarextumab or placebo) between 172 and 527 days.

"The findings communicated by the DSMB suggest a low likelihood of a statistically significant benefit in overall survival in the tarextumab ALPINE pancreatic cancer trial," said Paul J. Hastings, Chairman and CEO. "Our aim is to quickly unblind the trial and work with our clinical sites and investigators to verify, analyze, interpret, and fully understand the data, including Notch biomarker subgroup trends, and determine next steps."

The Phase 2 ALPINE trial is a randomized, double-blinded, multicenter clinical trial designed to evaluate the efficacy of tarextumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with previously untreated Stage IV pancreatic cancer. The ALPINE study completed enrollment of 177 patients in August 2015. The trial was designed to compare the overall survival of patients receiving tarextumab 15 mg/kg every two weeks versus placebo in combination with Abraxane plus gemcitabine. Secondary and exploratory endpoints, including progression-free survival and overall response rate, pharmacokinetics, safety and other biomarkers, are to be evaluated. Overall survival, progression-free survival and overall response rates will be assessed using a predictive biomarker for high tumor Notch3 expression. Increased Notch3 expression is estimated to occur in approximately 70 percent of pancreatic tumors and is associated with poor patient outcomes.

Conference Call Today

OncoMed management will host a conference call today beginning at 8:30 a.m. ET/5:30 a.m. PT to answer investor and analysts questions regarding the ALPINE Phase 2 program.

Analysts and investors can participate in the conference call by dialing 1-855-420-0692 (domestic) and 1-484-756-4194 (international) using the conference ID# 37742080. The web broadcast of the conference call will be available for replay through February 15, 2016 via a link in the Investor Relations section of the OncoMed website.

About Tarextumab (anti-Notch2/3, OMP-59R5)

Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment. Tarextumab is currently being studied in two randomized Phase 2 clinical trials. The "ALPINE" study (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) is assessing tarextumab with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients. The "PINNACLE" study (A Phase 1b/2 Study of OMP-59R5 in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer) is testing tarextumab in combination with etoposide and cisplatin and etoposide and carboplatin in first-line extensive-stage small cell lung cancer patients. Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.

8-K – Current report

On January 25, 2016 Lixte Biotechnology Holdings, Inc. (OTCQB: LIXT) reported that a major shareholder has purchased $1,750,000 of Convertible Preferred stock (Filing, 8-K, Lixte Biotechnology, JAN 25, 2016, View Source [SID:1234508859]). If fully converted, this purchase would convert to 2,187,500 common shares at a per share price of $0.80.

Lixte’s CEO, John S. Kovach, M.D., said, "This new investment allows Lixte to pursue opportunities that have emerged regarding our lead anticancer compound, LB-100.

First, in the Phase I trial, several solid tumor patients with a variety of recurrent progressive cancers had stabilization of their disease in the absence of dose-limiting toxicity as reported at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC International Conference in Boston. We had not anticipated that LB-100 alone would stop tumor progression in some solid tumor patients. This finding raises opportunities, currently being explored, to go directly to Phase 2 studies of LB-100 as a single agent.

Second, Lixte has licensed LB-100 to the Taiwan Medical University to determine the activity of LB-100 plus doxorubicin in Asian patients with hepatocellular cancer, beginning with a Phase 1b/2 trial planned to start this summer. This will test the ability of LB-100, demonstrated in several animal models, to enhance the effectiveness of a widely used anticancer drug against one of the most common and devastating cancers worldwide.

Third, scientists at the National Institutes of Health (NIH) reported that LB-100 enhances the anti-tumor activity of cisplatin and reduced cisplatin-resistance of human medulloblastoma cells in animal models. Previously, NIH investigators found that LB-100 enhanced the activity of cisplatin in models of cisplatin sensitive and cisplatin-resistant human ovarian cancer."

Dr. Kovach continued, "Because of these new developments, Lixte is considering several options for Phase 1b/2 trials, with recurrent platinum-resistant ovarian cancer at the top of the list. The most definitive trial design would be a randomized study of LB-100 plus a platinum compound versus the therapeutic choice of the treating doctor with an opportunity for those failing treatment with the ‘physician’s choice’ to receive the LB-100 regimen. The cost of a randomized trial would require additional financial resources beyond those of the private placement."

8-K – Current report

On January 21, 2016 Five Prime Therapeutics, Inc. (Nasdaq: FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported preliminary data from Part 1 of the ongoing Phase 1 clinical trial of FPA144 in patients with solid tumors, including gastric cancer, at a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) 2016 Gastrointestinal Cancers Symposium in San Francisco (Filing, 8-K, Five Prime Therapeutics, JAN 21, 2016, View Source [SID:1234508834]).

"These data suggest that FPA144 is well tolerated, and we were pleased to see early evidence of anti-tumor activity in two out of the six patients with 3+ FGFR2b-positive gastric cancer and in a patient with 2+ FGFR2b-positive bladder cancer enrolled in Part 1a of our Phase 1 trial," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "Based on these encouraging data, we plan to continue evaluating FPA144 as a monotherapy in refractory gastric cancer, as a combination therapy in the front-line gastric cancer setting and as a potential treatment for other types of cancer."

The poster titled, "FPA144-001: A first in human study of FPA 144, an ADCC-enhanced, FGFR2b isoform-selective monoclonal antibody in patients with advanced solid tumors," will be presented during the "Cancers of the Esophagus and Stomach" session on Thursday, January 21, 2016 from 12:30-2:00 pm and 5:30-7:00 pm, Pacific Time. The poster will be made available at View Source

FPA144 Phase 1 Safety and Pharmacokinetic Summary

• Safety data from 27 patients and pharmacokinetic (PK) data from 23 patients from Part 1a (3+3 dose escalation in solid tumor patients) and Part 1b (parallel escalating doses in gastric cancer patients)

• FPA144 was well tolerated in patients with advanced solid tumors up to 15 mg/kg

• No dose-limiting toxicities (DLTs) were observed and a maximum-tolerated dose (MTD) was not reached in Part 1

• The most common treatment-emergent adverse events were Grades 1 or 2 and self-limiting

• The safety profile appears differentiated from small molecule kinase inhibitors targeting FGF receptors; for example, no treatment-related hyperphosphatemia was observed

• The most common treatment-related adverse events were:

fatigue (25.9%), nausea (11.1%), diarrhea (7.4%), dizziness (7.4%) and dry eye (7.4%)

• PK characteristics support once every other week or less frequent dosing

Preliminary Data on Anti-tumor Activity

• Anti-tumor activity in patients with gastric cancer whose tumors overexpress the FGFR2b protein (the initial target patient population for FPA144):

o First radiographic assessment by RECIST 1.1 of anti-tumor activity in six patients with FGFR2b-positive gastric cancer in Part 1b

o 2 Partial Responses (1 confirmed who received 6 mg/kg, 1 unconfirmed who received 10 mg/kg)

o 3 Stable Disease (2 confirmed who received 3 mg/kg and 10 mg/kg, respectively; 1 unconfirmed who received 10 mg/kg)

o 1 Progressive Disease (who received 10 mg/kg)

o Patients were classified 3+ by an IHC molecular diagnostic test

• Anti-tumor activity in a patient with urothelial bladder cancer:

o A confirmed Partial Response by CT (RECIST 1.1) and metabolic response by PET was observed in a urothelial bladder cancer patient who received 3 mg/kg from Part 1a

o The patient’s tumor was classified 2+ by an IHC molecular diagnostic test, suggesting that FPA144 may be active in tumors with moderate levels of FGFR2b protein overexpression

o Encourages investigation of the potential for FPA144 therapy in tumor types other than gastric cancer

• All patients who showed anti-tumor activity received doses below the 15 mg/kg dose being assessed in Part 2 of the trial

"We at START are excited by these data and the ability to partner with Five Prime to create and rapidly execute an innovative trial design that can be used broadly to develop targeted cancer therapies efficiently," said Tony Tolcher, M.D., Director of Clinical Research at South Texas Accelerated Research Therapeutics (START), an active site in the Phase 1 trial. "FPA144 appears well tolerated and without the significant toxicities that have limited other drugs targeting this pathway. Gastric cancer patients have a significant unmet need and a drug like FPA144 could represent an important advancement in their treatment options."

About the FPA144 Phase 1 Trial
Parts 1a and 1b of the Phase 1 study evaluated the safety and pharmacokinetics (PK) of escalating doses of FPA144 in 27 patients with solid tumors, including gastric cancer patients. Enrollment at the recommended dose of 15 mg/kg is underway in Part 2 of the Phase 1 trial, evaluating the safety, PK and efficacy of biweekly infusions of FPA144 in up to 70 gastric cancer patients, with the additional aim of exploring the correlation between efficacy and FGFR2 gene amplification and FGFR2b protein overexpression. Tumor testing for FGFR2b protein overexpression is being conducted centrally, using a proprietary immunohistochemistry assay. Tumors are also being assessed for FGFR2 gene amplification by FISH analysis. Trial endpoints include safety, PK, response rate and duration of response.

About FPA144
FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FPA144 is designed to block tumor growth through two distinct mechanisms. First, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. Second, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

About Gastric Cancer
Globally, gastric cancer is the sixth most common malignancy with the third highest mortality. Globally, the prevalence of gastric cancer is approximately 1.5 million patients, of which an estimated 5%, or approximately 80,000, have FGFR2 gene-amplified tumors that overexpress FGFR2b. Given the relatively small population of gastric cancer patients that overexpress the FGFR2b protein and the poor survival of these patients, this indication is expected to be an orphan indication in the U.S.

8-K – Current report

On January 20, 2016 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported that data from the Phase 2 Spruce trial evaluating the combination of apatorsen with carboplatin and pemetrexed in patients with untreated metastatic non-small cell lung cancer (NSCLC) did not reach the statistical significance required to demonstrate a progression-free survival (PFS) benefit (Filing, 8-K, OncoGenex Pharmaceuticals, JAN 20, 2016, View Source [SID:1234508826]).

A potential PFS benefit was observed in patients with high baseline serum Hsp27 status when treated with apatorsen. The study is ongoing and overall survival results are expected in the second half of 2016.

Treatment and maintenance therapy with apatorsen was well tolerated. Adverse events were comparable between the arms and as expected for the study chemotherapy treatment.

"We look forward to following the Spruce study through overall survival this year to determine if apatorsen can provide a treatment benefit for this population of lung cancer patients," said principal investigator David Spigel, director, lung cancer research program and chief scientific officer for Sarah Cannon Research Institute. "Despite recent advances including exciting immunotherapies, patients with lung cancer still have a significant need for new treatment options that extend survival. Chemotherapy remains a standard of care and an important option for people with advanced disease."

Spruce is a placebo-controlled, double-blind, randomized trial sponsored and conducted by Sarah Cannon Research Institute. Approximately 155 patients with non-squamous NSCLC received either apatorsen plus carboplatin and pemetrexed therapy or placebo plus carboplatin and pemetrexed therapy in the Spruce trial. In addition to PFS and OS, other analyses are being conducted to evaluate tumor response rates, safety, tolerability, and the effect of therapy on Hsp27 levels. Detailed results will be presented at an upcoming medical meeting.

"PFS can provide an early signal of activity in lung cancer trials, yet overall survival continues to be the benchmark for determining both clinical and regulatory significance," said Scott Cormack, President and CEO of OncoGenex. "Overall survival results from Spruce expected later this year will inform the future development of apatorsen in lung cancer. We plan to continue to evaluate a potential correlation between Hsp27 and survival benefit in this and other apatorsen trials."
Lung cancer is the most common cancer worldwide, with approximately 1.8 million new cases per year. It is the leading cause of cancer death among both men and women in the U.S., with approximately 160,000 Americans expected to die from the disease in 2016. Non-squamous histology NSCLC includes adenocarcinoma and large cell carcinoma and accounts for more than half of all diagnoses.

About Apatorsen and ORCA

Apatorsen (OGX-427) is designed to inhibit production of heat shock protein 27 (Hsp27), disable cancer cells’ defenses and overcome treatment resistance. Hsp27 is an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Both the potential single-agent activity and synergistic activity of apatorsen with cancer treatments may increase the overall benefit of existing therapies and augment the durability of treatment outcomes, which could lead to increased patient survival.

The ORCA (Ongoing Studies Evaluating Treatment Resistance in Cancer) program encompasses clinical trials of apatorsen. Phase 2 clinical trials are underway in bladder, lung and prostate cancers. For more information on apatorsen and ORCA, please visit www.OncoGenex.com.

8-K – Current report

On January 11, 2016 Five Prime Therapeutics, Inc. (Nasdaq: FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported an update on GlaxoSmithKline’s (GSK) ongoing Phase 1b clinical trial of FP-1039/GSK3052230, an FGF ligand trap, in patients with squamous non small cell lung cancer (sqNSCLC) and mesothelioma (Filing, 8-K, Five Prime Therapeutics, JAN 11, 2016, View Source [SID:1234508716]).

GSK presented preliminary clinical safety and efficacy data from the Phase 1b trial at the World Conference on Lung Cancer on September 9, 2015. At the time, data from Arm A in treatment-naïve squamous sqNSCLC patients were encouraging, Arm B in second line sqNSCLC had few patients enrolled, and data from Arm C were immature because few mesothelioma patients were then evaluable. Based on preliminary data, GSK and Five Prime have agreed to continue to enroll up to 30 mesothelioma patients at the expansion dose of 15 mg/kg in Arm C of the trial. GSK plans to submit data for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in June. The companies have also agreed to stop enrolling the sqNSCLC patient study cohorts given the change in treatment paradigms following approvals of immuno-oncology agents and the increasingly competitive landscape.

"We are encouraged by the preliminary data we have recently reviewed from the mesothelioma arm of the study and look forward to seeing the results as additional patients are enrolled and followed," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "The majority of mesothelioma tumors express high levels of FGF-2, so our FGF ligand trap represents a rational therapeutic approach, and patients currently have limited treatment options. If we see similar results once we have full, mature data for Arm C, we will seek to regain rights for FP-1039 in the U.S., Canada and the E.U. from GSK, as mesothelioma could represent a potentially attractive market opportunity for Five Prime."

About the Phase 1b Trial
The Phase 1b clinical trial of FP-1039 is being conducted by GSK and is designed as a three-arm, multicenter, non-randomized, parallel-group, uncontrolled, open-label trial. This clinical trial was designed to evaluate the safety, tolerability, dosage, response rate and duration of response of FP-1039:

• in combination with paclitaxel and carboplatin in previously untreated metastatic sqNSCLC (Arm A);

• in combination with docetaxel in metastatic sqNSCLC that has progressed after previous therapy (Arm B); or

• in combination with front-line pemetrexed and cisplatin in mesothelioma (Arm C), a tumor in which the FGF-2 ligand is overexpressed.

About FP-1039
FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF-2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells where they would otherwise stimulate cancer cell division and/or angiogenesis. However, FP-1039 does not bind to certain "hormonal" FGFs, including FGF-23, which regulates phosphate levels in the blood. As a result, treatment with FP-1039 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23.

About Mesothelioma
Mesothelioma is a disease with high unmet medical need and high mortality rate. A majority of mesothelioma patients have tumors with abnormally high levels of FGF-2. In preclinical testing, Five Prime observed inhibition of mesothelioma tumor growth with single-agent FP-1039. Mesothelioma is an orphan indication in the United States with a prevalence of about 4,000 patients and incidence of about 3,000 patients. Worldwide, there are a total of approximately 14,000 cases of mesothelioma diagnosed each year.

8-K – Current report

On January 11, 2016 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations and a primary focus in Hematology and Oncology and Servier Canada Inc., an affiliate of Servier a research-oriented pharmaceutical company which is pioneering new therapies primarily for cancer and cardiovascular diseases, reported the signing of a strategic partnership (Filing, 8-K, Spectrum Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508730]).

As part of this partnership, Spectrum will grant the exclusive rights to develop and commercialize in Canada a franchise of four Spectrum hemato-oncology drugs: Zevalin (ibritumomab tiuxetan) Injection for intravenous use, Folotyn(pralatrexate injection), Beleodaq (belinostat) for Injection and Marqibo (vinCRIStine sulfate LIPOSOME injection) for intravenous infusion. Spectrum will receive $6 million in upfront payments, plus development milestone payments and royalties based on net product sales.

"We are pleased to announce this strategic partnership with Servier, a leading company in Canada," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "This deal allows us to continue to focus on our core priorities including SPI-2012, Poziotinib, Apaziquone and Evomela. This year we plan to initiate two key trials with drugs that target blockbuster markets and we are looking forward to hearing from the FDA on two of our NDA submissions. We believe that our pipeline has never been as strong as it is today, and we continue to focus on executing on our key priorities."

"This strategic partnership between Spectrum Pharmaceuticals and Servier Canada will contribute to consolidate our global strategy in Oncology. Our ambition is to become a benchmark player in this field," said Frédéric Sesini, Executive Vice-President International Operations of Groupe Servier. "We are fully committed in providing Canadian patients with innovative treatment options. With this key partnership, Servier Canada Oncology will start operating and will work to make these treatments available soon," underlined Frederic Fasano, Chief Executive Officer of Servier Canada Inc.

8-K – Current report

On January 11, 2016 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported an update on its evofosfamide program including that Threshold and Merck KGaA, Darmstadt, Germany have agreed upon key terms for the licensing back of all rights to evofosfamide to Threshold (Filing, 8-K, Threshold Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508731]). The companies have a global license and co-development agreement for evofosfamide, an investigational hypoxia-activated prodrug for the treatment of cancer, which was discovered and initially developed by Threshold.

The decision to return rights to evofosfamide to Threshold follows the unblinding of two Phase 3 clinical trials of evofosfamide (TH-CR-406 and MAESTRO) and a previously unplanned, subsequent interim futility analysis of a Phase 2 clinical trial of evofosfamide in patients with non-squamous non-small cell lung cancer (n-s NSCLC). As previously announced, both Phase 3 trials failed to meet the primary endpoint of demonstrating a statistically significant improvement in overall survival. The results of the MAESTRO trial will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Gastrointestinal Cancers Symposium during an oral presentation session scheduled to begin at 2:00 p.m. Pacific Time on Friday, January 22, 2016 (Abstract #193).

Following the topline results from the two Phase 3 clinical trials, Threshold and Merck KGaA, Darmstadt, Germany decided to unblind the Phase 2 clinical trial in n-s NSCLC and conduct an interim futility analysis. The Phase 2 trial was designed to enroll 440 patients with advanced n-s NSCLC. A total of 265 patients were enrolled and 112 events (deaths) were reported at the time of the interim analysis. An independent Data Safety Monitoring Board conducted the analysis and concluded that the trial is unlikely to reach its primary endpoint of improving overall survival with statistical significance. As a result, further enrollment in this trial will be closed. Additional findings from the interim analysis indicated that evofosfamide plus pemetrexed demonstrated longer progression-free survival (PFS) associated with a reduction in the risk of progression or death by approximately 30%. No new safety findings were reported. Data for this trial will be finalized and results presented at a future medical meeting.

"We are pleased to have agreed to key terms for the licensing back of all rights to evofosfamide to Threshold and we will share our plans for the future development of evofosfamide once our ongoing analyses of the data from the recently unblinded clinical trials are complete," said Barry Selick, Ph.D., Chief Executive Officer of Threshold. "In parallel, we continue to focus on prosecuting two Phase 2 clinical trials of tarloxotinib, our hypoxia-activated EGFR tyrosine kinase inhibitor, and to assess other strategic options for the company."

About Evofosfamide

Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. Threshold previously announced the outcomes of two Phase 3 studies (MAESTRO and TH-CR-406/SARC021) of evofosfamide stating that neither study met its primary endpoint. The related news release dated December 7, 2015, can be accessed on the company’s website in the Investors/News Releases section View Source

About Tarloxotinib Bromide

Tarloxotinib bromide (the proposed International Nonproprietary Name), or "tarloxotinib", is a prodrug designed to selectively release a covalent (irreversible) EGFR tyrosine kinase inhibitor under severe hypoxia, a feature of many solid tumors. Accordingly, tarloxotinib has the potential to effectively shut down aberrant EGFR signaling in a tumor-selective manner, thus potentially avoiding or reducing the systemic side effects associated with currently available EGFR tyrosine kinase inhibitors. Tarloxotinib is currently being evaluated in two Phase 2 proof-of-concept trials: one for the treatment of patients with mutant EGFR-positive, T790M-negative advanced non-small cell lung cancer progressing on an EGFR tyrosine kinase inhibitor, and the other for patients with recurrent or metastatic squamous cell carcinomas of the head and neck or skin. Threshold licensed exclusive worldwide rights to tarloxotinib from the University of Auckland, New Zealand, in September 2014.

8-K – Current report

On January 6, 2016 TetraLogic Pharmaceuticals Corporation (Nasdaq: TLOG), a clinical-stage biopharmaceutical company focused on discovering and developing novel small molecule therapeutics in oncology and infectious diseases, reported the results of the interim analyses of two clinical studies (Filing, 8-K, TetraLogic Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508768]).

In a placebo controlled Phase 2 study of birinapant co-administered with azacitidine in first line higher risk patients suffering from myelodysplastic syndromes (MDS), birinapant did not demonstrate any clinical benefit over placebo on the primary endpoint of response rate after four months of therapy and met the bounds for futility. This interim analysis included the first 62 patients randomized in the trial. This study will now be terminated.

TetraLogic has undertaken an interim analysis of a randomized Phase 2 clinical study of SHAPE, the company’s proprietary topical HDAC inhibitor. The clinical trial was designed to investigate the safety and efficacy of three different dosing regimens of SHAPE in patients suffering from earlier stage cutaneous T-cell lymphoma (CTCL). All patients in the study had received prior therapy either in the form of topical steroids, UV light therapy, topical nitrogen mustard, or some other agent. Twenty-eight of 34 patients were evaluable for response at the 6 month time point. After six months of treatment, 8 of 34 patients exhibited a response to treatment as assessed by CAILS, the primary endpoint, and a further 18 had stable disease. Using the mSWAT, a secondary endpoint in the study, 11 of 34 patients responded and a further 14 patients had stable disease at the 6 month endpoint.

SHAPE also showed improvement in pruritus (itch), a significant symptom associated with CTCL. Thirty-eight percent of patients demonstrated a clinically meaningful decrease in pruritus during the study as measured by a Visual Analog Scale. The drug was well tolerated by patients in the study. The 60 patient study is now fully enrolled, and the company expects that final results will be available in mid-2016.

"Whilst the results of the birinapant study in MDS are disappointing, the results we achieved with SHAPE provide an interesting product profile with activity observed on both the CAILS and mSWAT endpoints and the potential to reduce pruritus, one of the more difficult symptoms to treat in CTCL," said J. Kevin Buchi, TetraLogic CEO. "We are exploring our strategic alternatives based upon the results seen in these studies."

8-K – Current report

On January 11, 2016 Sorrento Therapeutics, Inc. (NASDAQ: SRNE; Sorrento), an antibody-centric, clinical-stage biopharmaceutical company developing new treatments for cancer and other unmet medical needs, reported that it has formed an exclusive partnership with the world-renowned Karolinska Institutet (KI) in Stockholm, Sweden, to perform cutting-edge immuno-oncology research and to develop new natural killer (NK) cell-based therapies (Filing, 8-K, Sorrento Therapeutics, JAN 11, 2016, View Source [SID:1234508774]).

Under the agreement, Sorrento will sponsor preclinical and clinical research & development programs focused on NK biology as well as adoptive NK cell therapies and, in return, obtain full rights to the resulting discoveries and developments. The research will be performed at KI, but there will also be an active research exchange with Sorrento R&D in San Diego. A joint steering committee with members from both Sorrento and KI will guide the program activities.

"Given the fact that NK cells were discovered at Karolinska Institutet, it is of course now exciting to take part in the ongoing developments involving these cells in settings of adoptive immunotherapies targeting human malignancies", said Professor Hans-Gustaf Ljunggren, Dean of Research at Karolinska Institutet. "We look forward to teaming up our world-leading NK cell experts with Sorrento’s outstanding scientific team to gain new insights into NK biology and applying these to develop novel cellular therapies."
"We are honored to work with the distinguished KI faculty on discovering and developing new adoptive NK cell immunotherapies", said Dr. Henry Ji, President and CEO of Sorrento. "Through this partnership, Sorrento further establishes its subsidiary, TNK Therapeutics, as one of the premier companies in the cellular therapy space. Building upon the academic and clinical excellence at KI and Sorrento’s expertise in antibody research and development, our partnership will stimulate innovation and may ultimately lead to new ground breaking therapies to improve the lives of cancer patients and their caretakers."

8-K – Current report

On January 11, 2016 Shire plc (LSE: SHP, NASDAQ: SHPG) and Baxalta Incorporated (NYSE: BXLT) reported that the boards of directors of both companies have reached an agreement under which Shire will combine with Baxalta (Filing, 8-K, Shire, JAN 11, 2016, View Source [SID:1234508775]). Under the agreement, Baxalta shareholders will receive $18.00 in cash and 0.1482 Shire ADS per Baxalta share. Based on Shire’s closing ADS price on January 8, 2016, this implies a total current value of $45.57 per Baxalta share, representing an aggregate consideration of approximately $32 billion. The exchange ratio was based on Shire’s 30-day trading day volume weighted average ADS price of $199.03 as of January 8, 2016, which implies a total value of $47.50 per Baxalta share.

The value of the offer, as of Shire’s January 8, 2016 closing ADS price, represents a premium of approximately 37.5% to Baxalta’s unaffected share price on August 3, 2015, the day prior to the public announcement of Shire’s initial offer for Baxalta. This will provide Baxalta shareholders with approximately 34% ownership in the combined company. The parties expect the transaction to close mid-2016.

Shire Chief Executive Officer Flemming Ornskov, M.D., M.P.H., commented:

"This proposed combination allows us to realize our vision of building the leading biotechnology company focused on rare diseases. Together, we will have leadership positions in multiple, high-value franchises and become the clear partner of choice in rare diseases. Our expanded portfolio and presence in more than 100 countries will drive our growth to over $20 billion in anticipated annual revenues by 2020. Our due diligence has reinforced our belief in the combination, and we look forward to welcoming Baxalta colleagues to a shared entrepreneurial, patient-driven culture."

Susan Kilsby, Chairman of Shire, commented:

"Together, Shire and Baxalta create a platform for sustainable innovation, growth and value creation. Shire is an experienced and disciplined acquirer with a track record of delivering shareholder value. Stakeholders of both companies are expected to benefit from the enhanced growth prospects, superior operational scale and efficiency and the strong financial and organizational profile of the combined entity."

Baxalta Chief Executive Officer Ludwig N. Hantson, Ph.D., commented:

"Today’s announcement marks a new path forward for our organization and is a testament to the significant progress we have made in achieving our strategic business priorities. This transaction presents a unique opportunity for Baxalta shareholders, who will receive substantial immediate value as well as an ongoing stake in a combined global leader in rare diseases with strong growth prospects. We bring to Shire a strong portfolio and pipeline of market-leading products, high-quality manufacturing capabilities and a talented global workforce that places patients at the center of everything we do. The combined organization will be well positioned to accelerate innovation and deliver enhanced value for all stakeholders."

Wayne T. Hockmeyer, Ph.D., Chairman of Baxalta, commented:

"We launched Baxalta to focus on purpose-driven performance, sustainable growth, and continuing our leadership in developing treatments for orphan and underserved diseases. While we have made great progress to date and have had a measurable impact across all our businesses, I look forward to joining the board of the combined company to help ensure that we infuse the best of both organizations and foster a new shared culture that has the resources, the passion, and the commitment to continue to make a meaningful difference in the lives of our patients and their families."

Baxter International Chairman and Chief Executive Officer José E. Almeida commented:

"Baxter fully supports the proposed combination of Shire and Baxalta, which will create a major biotechnology company and global leader in rare diseases. Baxter is pleased to support this value enhancing transaction."

Shire will host a conference call for investors and analysts today, January 11, 2016 at 1:30 p.m. GMT / 8:30 a.m. EST / 5:30 a.m. PST. (Details below)

Combination Creates the Global Leader in Rare Diseases with a Sustainable Platform for Future Innovation, Growth and Value Creation

The combination of Baxalta and Shire will create the number one rare diseases platform in revenue and pipeline depth, with best-in-class products in each of the following growing, multi-billion-dollar franchises: Hematology; Immunology; Neuroscience; Lysosomal Storage Diseases; Gastrointestinal / Endocrine; and Hereditary Angioedema (HAE). The combined company will also possess a growing franchise in Oncology, with approved products and innovative compounds in development, as well as a robust late-stage Ophthalmics pipeline.

The combined portfolio will have an expanded range of therapeutic areas with more than 60 programs in development, including over 50 that will address rare diseases and the newly-approved Baxalta products ADYNOVATE, VONVENDI and OBIZUR. Shire anticipates more than 30 recent and planned product launches from the combined pipeline, contributing approximately $5 billion in annual revenues by 2020.

Further, the combined company will benefit from expanded geographic reach across more than 100 countries, with a high-quality commercial organization and world-class manufacturing operations.

Through a balanced portfolio and expanded therapeutic expertise and capabilities, the combination will enhance revenue diversification and optionality for the business, while strong cash flows will increase financial and operational scale. In total, the proposed combination will create a sustainable platform for future innovation and growth, yielding projected near- and long-term value for shareholders.

Leading Franchises, Each with Best-in-Class Products and a Foundation for Sustained Category Leadership in Rare Diseases

The portfolio will include over 20 leading brands and a robust pipeline of expected new product launches with complementary positions across growing multi-billion-dollar franchises:

Hematology

• Baxalta has a well-established hematology portfolio based on its heritage and legacy of leadership in hemophilia. Baxalta offers a comprehensive portfolio of innovative therapeutics, including ADYNOVATE, Antihemophilic Factor (Recombinant), PEGylated, an extended circulating half-life recombinant factor VIII (rFVIII) treatment for hemophilia A which was recently approved in the U.S., and is focused on introducing new treatments for hemophilia and other rare chronic bleeding disorders to further reduce patient burdens

Immunology

• Baxalta is contributing the broadest portfolio of immunoglobulin (IG) products in the industry, most notably the recently launched HYQVIA, a next generation subcutaneous IG treatment for patients with primary immunodeficiency, as well as a pipeline of innovative products across a broad range of potential new indications
Neuroscience

• Shire has over 20 years of experience in neuroscience with a strong, growing ADHD franchise and pipeline, including a new VYVANSE indication for adults with moderate-to-severe Binge Eating Disorder

Lysosomal Storage Diseases

• Shire brings industry-leading capabilities in the development and commercialization of a wide range of therapies for multiple rare and devastating genetic diseases including: VPRIV for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease; ELAPRASE for patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II); and REPLAGAL for long-term ERT in patients with a confirmed diagnosis of Fabry disease

Gastrointestinal / Endocrine

• Shire’s Gastrointestinal / Endocrine portfolio is built on the strength of its 5-ASA products, LIALDA, for the treatment of mild to moderate ulcerative colitis, and PENTASA, for the treatment of mildly to moderately active ulcerative colitis, and recent additions of GATTEX/REVESTIVE, for adults with short bowel syndrome who are dependent on parenteral support, and NATPARA, as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism

HAE

• Shire brings HAE leadership through its currently approved prophylactic and acute therapies, CINRYZE and FIRAZYR, respectively, and—pending completion of the Dyax acquisition—a Phase 3, potentially transformative prophylactic therapy
Ophthalmics

• Shire is focused on building franchise leadership in ophthalmology with the 2016 projected launch of Lifitegrast, contingent upon regulatory approval, for dry eye disease; SHP640 for infectious conjunctivitis entering Phase 3 trials in 2016, and SHP607 for the treatment of retinopathy of prematurity, generating results from its Phase 2 trials which are expected in 2016
Oncology

• Baxalta brings a growing oncology business and a broad platform that positions the combined company at the leading-edge of discovery and development of innovative therapies in hematological and other cancers. The portfolio includes ONCASPAR (pegaspargase), a marketed biologic treatment for acute lymphocytic leukemia, and late-stage, partnered products such as pacritinib, an investigational oral kinase inhibitor for the treatment of patients with myelofibrosis, and ONIVYDE (irinotecan liposome injection) for the treatment of patients with metastatic pancreatic cancer
Financial Highlights

Shire anticipates that it will realize more than $500 million in annual cost synergies (expected to be achieved within the first three years post-closing). These annual cost synergies will be achieved by increasing efficiencies, leveraging the scale of the combined business, aligning to Shire’s lean operating model and optimizing the combined R&D portfolio. Further, Shire expects to generate additional revenue synergies and a combined non-GAAP effective tax rate of 16-17% by 2017. Growth is expected to be accelerated by combining capabilities and establishing a global infrastructure that will include a "best of both" commercial model and a presence in over 100 global markets.

The transaction is expected to be accretive to non-GAAP diluted EPS in 2017, the first calendar year of ownership, and beyond. The combined company is expected to generate annual operating cash flow of $6.0 billion beginning in 2018, underpinning an attractive ROIC that will exceed Shire’s cost of capital in 2020.

Shire has conducted additional tax due diligence, and based on this diligence, Shire and its tax advisor have concluded that a merger with the proposed cash consideration of $18 per Baxalta share will maintain the tax-free status of the Baxalta spinoff from Baxter.

Shire has secured an $18 billion fully underwritten bank facility to finance the combination. The new bank facility has a one year life, with a one-year extension available at Shire’s option. Shire intends to refinance the bank facility through capital market debt issuances in due course. The financing of the transaction has been structured with the intention of maintaining an investment grade credit rating for the combined entity. Shire is committed to de-levering rapidly post-close by deploying free cash flow to repay debt. Shire is targeting a net debt to EBITDA range of between 2.0x and 3.0x 12-18 months post-closing.

Transaction Details

Under the agreement, Baxalta shareholders will receive $18.00 in cash and 0.1482 Shire ADS per Baxalta share. Based on Shire’s closing ADS price on January 8, 2016, this implies a total current value of $45.57 per Baxalta share, representing an aggregate consideration of approximately $32 billion. The exchange ratio was based on Shire’s 30-day trading day volume weighted average ADS price of $199.03 as of January 8, 2016, which implies a total value of $47.50 per Baxalta share.

The value of the offer as of Shire’s January 8, 2016 closing ADS price represents a premium of approximately 37.5% to Baxalta’s unaffected share price on August 3, 2015, the day prior to the public announcement of Shire’s initial offer for Baxalta. This will provide Baxalta shareholders with approximately 34% ownership in the combined company.

Closing

The transaction has been approved by the boards of directors of both Shire and Baxalta. Closing of the transaction is subject to approval by Baxalta and Shire shareholders, certain regulatory approvals, redelivery of tax opinions delivered at signing and other customary closing conditions. The transaction is a class 1 transaction for Shire for the purposes of the UK Listing Rules requiring the approval of Shire shareholders. A shareholder circular, together with notice of the relevant shareholder meeting, will be distributed to Shire shareholders in due course. The parties expect the transaction to close mid-2016.

8-K – Current report

On January 5, 2016 Cellectar Biosciences, Inc. (NASDAQ:CLRB), an oncology-focused biotechnology company reported data from the first cohort of patients enrolled in its orphan drug-designated Phase 1 study of CLR 131 in patients with relapsed or refractory multiple myeloma (Filing, 8-K, Cellectar Biosciences, JAN 5, 2016, View Source [SID:1234508665]).

Based on safety and efficacy data from the first cohort, the trial’s Data Monitoring Committee approved enrollment of the second cohort of patients with a 50 percent escalation in dose level of CLR 131.

The primary objective of the multi-center, open label, Phase 1 dose escalation study is to characterize the safety and tolerability of CLR 131 in patients with relapsed or refractory multiple myeloma. Secondary objectives include establishment of the recommended Phase 2 dose, both with and without dexamethasone, as well as an assessment of therapeutic activity.

Prior to their participation in this study, patients in the first cohort had received a minimum of three systemic regimens and up to 12 lines of therapy.

"Judging by the results of the first cohort, I believe there is significant potential for CLR 131 as a safe and tolerable treatment modality for relapsed or refractory multiple myeloma," stated Sikander Ailawadhi, MD, senior associate consultant, Division of Hematology/Oncology, Department of Medicine, The Mayo Clinic, Jacksonville, Florida, and the site’s lead investigator. "I believe initiating the second cohort of the trial will provide additional useful information, both in terms of establishing an appropriate treatment dose, as well as further understanding the compound’s potential in this indication."

Data from the first cohort of patients in the Phase 1 study demonstrated safety and tolerability with a favorable adverse event profile. Additionally, stable disease was achieved in four of five treated patients with two of these patients maintaining stable disease throughout the 85-day study monitoring period.

"Importantly, these data collectively demonstrate safety and tolerability in heavily pre-treated multiple myeloma patients as well as provide promising signals of activity," said Jim Caruso, president and CEO of Cellectar Biosciences. "These early outcomes and feedback from the investigators are encouraging and we look forward to further evaluating CLR 131 in the second cohort to determine optimal dose and regimen. More globally, these results provide us with further confirmation on the utility of our PDC delivery platform, which we believe is instrumental to these outcomes."

The company is developing CLR 131, its lead radiotherapeutic phospholipid drug conjugate (PDC), for the treatment of multiple myeloma through the targeted delivery of iodine-131 to myelomatous cells.

8-K – Current report

On December 8, 2015 Bio-Path Holdings, Inc., (NASDAQ: BPTH) ("Bio-Path"), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that data from the Phase I and safety segment of the Phase II clinical trials of its lead product candidate BP-100-1.01 (or BP1001, Liposomal Grb2 antisense) in the treatment of blood cancers were presented yesterday by Dr. Jorge Cortes, Deputy Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center and Chair of Bio-Path’s Scientific Advisory Board, during a poster session at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida (Filing, 8-K, Bio-Path Holdings, DEC 8, 2015, View Source [SID:1234508508]).

The poster, titled "Safety, Pharmacokinetics, and Efficacy of BP-100.1.01 (Liposomal Grb2 Antisense Oligonucleotide) in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML), Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (CML), Acute Lymphoid Leukemia (ALL), and Myelodysplastic Syndrome (MDS)," included data from the first seven cohorts of the study. The eighth and final cohort is ongoing.

Data from Cohorts 1 through 6 of the dose-finding monotherapy study demonstrated that BP1001 at doses up to 90 mg/m2 is well tolerated and suggests possible anti-leukemia activity. Of the evaluable patients, all showed a transient drop in circulating blast percentage.

Cohort 7 was the first cohort in the safety segment of the Phase II clinical trial (also referred to as Phase Ib) and evaluated the toxicity of BP1001 at the 60 mg/m2 dose level, combined with low-dose cytarabine (LDAC) chemotherapy in patients with advanced acute myeloid leukemia (AML). Bio-Path previously reported that one evaluable patient in Cohort 7 had achieved complete remission (CR) during treatment, and a second patient who demonstrated improvement in bone marrow blasts at the end of the first treatment cycle was continuing BP1001 treatment as part of an additional treatment cycle. The second patient has achieved CR after two treatment cycles and is continuing therapy in a fourth treatment cycle.

"We are thrilled that two of the three evaluable patients suffering from advanced AML in our first cohort of the safety segment of the Phase II trial have now achieved complete remission during treatment with Liposomal Grb2 combined with low-dose cytarabine," said Peter Nielsen, President and Chief Executive Officer of Bio-Path. "The data we have seen to date are especially encouraging because the patients evaluated in our study were refractory and treatment resistant, having been on an average of four prior therapies. We continue to make progress with the eighth cohort of the trial, which is evaluating three patients being treated with 90 mg/m2 of Liposomal Grb2 antisense in combination with frontline LDAC, and look forward to successfully completing the safety portion of the Phase II clinical study."

About BP1001

BP1001 is a neutral-charge, liposome-incorporated antisense drug substance designed to inhibit Grb-2 protein expression. The protein Grb-2 is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. Suppressing the function or expression of Grb-2 should interrupt its vital signaling function and have a therapeutic application in cancer.

8-K – Current report

On December 6, 2015 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported the outcomes of two Phase 3 cancer studies (MAESTRO and TH-CR-406/SARC021) of evofosfamide (previously known as TH-302), an investigational hypoxia-activated prodrug, which is being evaluated for first-line treatment of advanced pancreatic adenocarcinoma and advanced soft tissue sarcoma, in combination with chemotherapy (Filing, 8-K, Threshold Pharmaceuticals, DEC 7, 2015, View Source [SID:1234508460]).

The Phase 3 studies are being conducted under Threshold’s collaboration with Merck KGaA, Darmstadt, Germany.

In the Phase 3 MAESTRO study, patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma treated with evofosfamide in combination with gemcitabine did not demonstrate a statistically significant improvement in overall survival (OS) compared with gemcitabine plus placebo (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.71 – 1.01; p=0.0589).

In the Phase 3 TH-CR-406/SARC021 study being conducted in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC), patients with locally advanced unresectable or metastatic soft tissue sarcoma treated with evofosfamide in combination with doxorubicin did not demonstrate a statistically significant improvement in OS compared with doxorubicin alone (HR: 1.06; 95% CI: 0.88 – 1.29).

Patient safety was monitored in MAESTRO and TH-CR-406/SARC021 by independent data monitoring committees throughout the conduct of each study. No new clinically significant safety findings were observed.

Detailed results from both studies will be submitted for presentation at upcoming international scientific meetings and for publication in peer-reviewed journals. Threshold will not be pursing further development of evofosfamide in soft tissue sarcoma and pancreatic cancer.

"We are surprised and disappointed that these studies did not show that evofosfamide could extend the lives of patients with these two difficult-to-treat diseases," said Barry Selick, Ph.D., Chief Executive Officer at Threshold. "Threshold has been pursuing evofosfamide for over ten years in collaboration with world-class scientists and investigators throughout the world. While we believe there remains substantial data to support the role of hypoxia in cancer treatment resistance, we are deeply frustrated with our inability in these trials to impact that in a meaningful way. I would like to thank all of the patients and their families, and the physicians, nurses, and support staff who participated in these studies."

Conference Call and Webcast
At 8:30 a.m. Eastern Time on Monday December 7, 2015, Threshold’s management will host a conference call and a simultaneous webcast. The webcast can be accessed on the company’s website in the Investors/Webcasts section View Source Alternatively, please call 1- (888) 767-9745 (U.S) or (440) 996-5547 (international). The conference ID number is 99761325. The webcast will be archived on Threshold’s website for at least 30 days.

About TH-CR-406/SARC021
TH-CR-406/SARC021 is a randomized, open-label, global, multicenter Phase 3 study, that was designed to assess the efficacy and safety of evofosfamide (300 mg/m2) in combination with doxorubicin (75 mg/m2) compared with doxorubicin alone, in patients with locally advanced unresectable or metastatic soft tissue sarcoma previously untreated with chemotherapy. A total of 640 patients were randomized in the study. The primary endpoint of the study is OS. Secondary endpoints include progression-free survival (PFS), response rate, safety and pharmacokinetics.

About MAESTRO
MAESTRO (MetAstatic or unrESectable pancreaTic adenocaRcinOma) is a randomized, placebo-controlled, international, multicenter, double-blind Phase 3 study, that was designed to assess the efficacy and safety of evofosfamide (340 mg/m2) in combination with gemcitabine (1000 mg/m2), compared with gemcitabine and placebo, in patients with previously untreated, locally advanced, unresectable or metastatic pancreatic adenocarcinoma. A total of 693 patients were randomized in the study. The primary endpoint of the study is OS. Secondary endpoints include PFS, overall response rate, disease control rate, quality of life based on patient-reported outcomes, safety and tolerability, pharmacokinetics and biomarkers.

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a
bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic.

Evofosfamide is being studied in patients with locally advanced unresectable or metastatic soft tissue sarcoma and in patients with locally advanced unresectable or metastatic pancreatic cancer. Evofosfamide is also being investigated in a Phase 2 study designed to support registration for the treatment of non-squamous non-small cell lung cancer, and in earlier-stage clinical studies of other solid tumors and hematological malignancies.
Threshold has a global license and co-development agreement for evofosfamide with Merck KGaA, Darmstadt, Germany.

8-K – Current report

On November 13, 2015 GenSpera, Inc. (OTC/QB: GNSZ), a biotech company developing a novel prodrug therapeutics for the treatment of cancer, reported it is providing an update on its clinical development programs and corporate developments (Filing, 8-K, GenSpera, NOV 13, 2015, View Source [SID:1234508236]).

The Company also announced that a poster entitled "Phase II study of mipsagargin (G-202), a PSMA-activated prodrug targeting the tumor endothelium, in adult patients with recurrent or progressive glioblastoma" will be presented at the 20th Annual Society for Neuro-Oncology Annual Scientific Meeting and Education Day on Friday, November 20, by Principal Investigator David Piccioni, MD, PhD, of the University of California, San Diego.

Mipsagargin Clinical Development

Glioblastoma (brain cancer)

· The Phase II data observed in the first 12 glioblastoma patients exceeded criteria required to expand enrollment and commence the second stage of the Phase II trial. Encouraging interim Phase II data demonstrated clinical benefit in a subset of patients with high levels of prostate-specific membrane antigen (PSMA) expression in the primary tumor. Three of 11 evaluable patients experienced stable disease for at least two months and a reduction in tumor volume. Additionally, an immediate reduction in edema was observed in one patient who remains on study 10 months after initiation of treatment.

· The U.S. Food and Drug Administration (FDA) granted $1.6 million for the study of PSMA and other biomarkers to better identify the subset of patients that will receive the most therapeutic benefit with mipsagargin treatment. Santosh Kesari, MD, PhD, of the John Wayne Cancer Institute will lead this initiative.

· A total of 18 patients have been treated by early November. Additional interim results of the Phase II trial are expected in first quarter of 2016 and final data, evaluating six-month progression-free survival, is expected in the fourth quarter of 2016.

Hepatocellular Carcinoma (liver cancer)

· Discussions and preparations for a Phase IIa dose-escalation trial evaluating safety, tolerability and efficacy focused in East Asian patients are ongoing. Previously presented data showed 63% of patients experienced disease stabilization at two months. Mipsagargin was considered safe with minimal and manageable side-effects and demonstrated decreased blood flow in liver tumors as measured by DCE-MRI.

"We believe that the positive clinical activity we observe is due to mipsagargin’s ability to attack the PSMA-expressing cells within solid tumors, which is a highly differentiated approach from conventional chemotherapy," said Craig Dionne, PhD, CEO of GenSpera. "Mipsagargin does not need to cross the blood-brain barrier to be effective, which further distinguishes the drug from other agents in development for glioblastoma. The company will strategically focus efforts on the glioblastoma trial while continuing to be opportunistic to additional collaborations and partnerships for further research and development advances through 2016."

Third Quarter and Recent Corporate Highlights

· In October, Dr. Santosh Kesari a recognized leader in neurology and neuro-oncology, joined our Scientific Advisory Board. Dr. Kesari is Chair of the Department of Translational Neuro-Oncology and Neurotherapeutics at the John Wayne Cancer Institute and Director of Neuro-Oncology at Providence Saint John’s Health Center.

· Phyton Biotech announced that its international patent application WO 2015/0892978 A1 "PRODUCTION OF THAPSIGARGINS BY THAPSIA CELL SUSPENSION CULTURE" was published by the World Intellectual Property Organization (WIPO). The invention described in the patent application provides, for the first time, a suspension cell culture suitable for mass production of thapsigargin and offers a potential alternative route to commercial-scale production of this starting material for synthesis of mipsagargin.

· In October Dr. Dionne acquired 262,500 shares of GenSpera by electing to convert $105,000 of notes due to him by the Company at $0.40 per share and waiving outstanding accrued interest.

8-K – Current report

On October 27, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported results for the third quarter of 2015, which were highlighted by strong global sales, key regulatory and clinical milestones in Immuno-Oncology and the completion of several business development transactions strengthening the company’s diversified pipeline (Filing, 8-K, Bristol-Myers Squibb, OCT 27, 2015, View Source [SID:1234507796]).

"In the third quarter we advanced our leadership position in Immuno-Oncology with two accelerated approvals in the U.S. and the presentation of important new clinical data that demonstrates the breadth and depth of our development program," said Giovanni Caforio, M.D., chief executive officer, Bristol-Myers Squibb. "We delivered strong operational performance driven by top-line growth, the successful launch of Opdivo and continuing positive trends for Eliquis. I remain confident in our strategy and that we are entering our exciting next chapter in a position of strength."

THIRD QUARTER FINANCIAL RESULTS

• Bristol-Myers Squibb posted third quarter 2015 revenues of $4.1 billion, an increase of 4% compared to the same period a year ago. Global revenues increased 11% adjusted for foreign exchange impact.

• U.S. revenues increased 4% to $2.0 billion in the quarter compared to the same period a year ago. International revenues increased 4%, or 19% adjusted for foreign exchange impact.

• Gross margin as a percentage of revenues was 73.0% in the quarter compared to 74.3% in the same period a year ago.

• Marketing, selling and administrative expenses decreased 4% to $983 million in the quarter.

• Advertising and product promotion spending increased 13% to $193 million in the quarter.

• Research and development expenses increased 15% to $1.1 billion in the quarter.

• The effective tax rate was 26.0% in the quarter, compared to 27.4% in the third quarter last year.

• The company reported net earnings attributable to Bristol-Myers Squibb of $706 million, or $0.42 per share, in the quarter compared to net earnings of $721 million, or $0.43 per share, a year ago.

• The company reported non-GAAP net earnings attributable to Bristol-Myers Squibb of $648 million, or $0.39 per share, in the third quarter, compared to $750 million, or $0.45 per share, for the same period in 2014. An overview of specified items is discussed under the "Use of Non-GAAP Financial Information" section.

• Cash, cash equivalents and marketable securities were $10.0 billion, with a net cash position of $2.8 billion, as of September 30, 2015.

THIRD QUARTER PRODUCT AND PIPELINE UPDATE

Bristol-Myers Squibb’s global sales in the third quarter included Daklinza and Sunvepra, which grew by $353 million, Opdivo, which grew by $304 million, Eliquis, which grew by $250 million, Orencia, which grew 9%, and Sprycel, which grew 7%.

Opdivo
• In October, the U.S. Food and Drug Administration (FDA) approved Opdivo for the treatment of previously treated patients with non-squamous (NSQ) non-small cell lung cancer (NSCLC) regardless of PD-L1 expression, which expands upon the current indication for Opdivo in patients with previously treated squamous (SQ) NSCLC. Opdivo is the only PD-1 inhibitor approved for previously treated metastatic SQ and now NSQ NSCLC patients regardless of PD-L1 expression and the only PD-1 inhibitor approved by the FDA to deliver superior overall survival compared to docetaxel in previously treated metastatic NSCLC. The accelerated approval was based on data from CheckMate -057, a Phase 3 study that evaluated the survival of patients with NSQ NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen.

• In October, the FDA approved Opdivo in combination with Yervoy for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma. The approval marks the first and only FDA approval of a regimen of two Immuno-Oncology agents in cancer. The indication was approved under accelerated approval based on tumor response rate and durability of response data from CheckMate -069. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

• In September, the FDA granted Breakthrough Therapy Designation to Opdivo for the potential indication of advanced or metastatic renal cell carcinoma (RCC). This designation is based on results of CheckMate -025, a Phase 3 study that evaluated the survival of patients with previously treated advanced or metastatic clear-cell RCC versus everolimus. The trial was stopped early in July 2015 because an assessment conducted by the independent Data Monitoring Committee concluded that the study met its primary endpoint of overall survival.

• In September, the FDA accepted for filing and review a Supplemental Biologics License Application (sBLA) for the Opdivo +Yervoy regimen to include clinical data from CheckMate -067, a landmark Phase 3 trial in patients with previously untreated advanced melanoma. If approved, this application would expand upon the initial Opdivo+Yervoy regimen, which was approved based on tumor response rate and safety data from the Phase 2 randomized trial, CheckMate -069. The FDA granted Priority Review for this application with a target action date of January 23, 2016.

• In September, the company announced results from two Phase 3 clinical trials at the 2015 European Cancer Congress:

◦ CheckMate -025 – In this study comparing Opdivo to everolimus in patients with advanced RCC after prior anti-angiogenic treatment, Opdivo demonstrated significant overall survival (OS) benefit compared to the standard of care with a median OS benefit of 25 months compared to 19.6 months for everolimus and clinical benefit regardless of level of PD-L1 expression. The safety profile shown was consistent with previously reported Opdivo trials. The results were published in The New England Journal of Medicine (NEJM).

◦ CheckMate -057 – In this study evaluating Opdivo vs. docetaxel in previously treated patients with advanced NSQ NSCLC, Opdivo continued to demonstrate superior OS with an estimated 39% of patients alive at 18 months versus 23% for docetaxel, based on a minimum follow-up of 17.1 months. Opdivo also continued to demonstrate a reduction in the risk of death by 28%. Grade 3-4 treatment-related adverse events were reported in 10% of patients treated with Opdivo versus 54% in the docetaxel arm. The results were published in NEJM.

• In September, the company announced results from multiple clinical trials at the World Conference on Lung Cancer in Denver:

◦ CheckMate -017 and CheckMate -063 – In these two studies evaluating patients with previously treated SQ NSCLC, Opdivo demonstrated sustained survival benefit with an estimated 18 month OS rate of 27% (CheckMate -063) to 28% (CheckMate -017); survival benefit was independent of PD-L1 expression. The safety profile of Opdivo was consistent with previously-reported trials, and in CheckMate -017, was also favorable compared to docetaxel.

◦ CheckMate -012 – In this multi-arm Phase 1b study evaluating Opdivo in patients with chemotherapy-naïve advanced NSCLC, new dosing schedules of the Opdivo+Yervoy arms confirmed objective response rates (ORR) ranging from 13% to 39% depending on the administered regimen, and encouraging efficacy with highest ORR for the Opdivo 3 mg and Yervoy 1 mg (31% to 39%) regimen. Median duration of response was not reached in any of these arms with a median follow-up of 6.2 months to 16.6 months, and median progression-free survival ranged from 4.9 months to 10.6 months. Treatment-related serious adverse events reported in these cohorts for CheckMate -012 were consistent with other previously reported Opdivo+Yervoy cohorts of this trial, and the new dosing schedules resulted in less toxicity than previously-reported dosing schedules, and an acceptable tolerability profile with 10% or fewer subjects discontinuing for grade 3-4 adverse events.

• In August, the company announced that the FDA extended the action date for the sBLA for Opdivo for the treatment of patients with previously untreated advanced melanoma. The company submitted additional data from the Opdivo clinical trial program to ensure the broadest data set, irrespective of BRAF status, was available for review. This submission constitutes a major amendment that will require additional time for review and the new projected FDA action date is November 27, 2015.

Yervoy
• The company announced today that a Yervoy Phase 3 trial, Study -104 in subjects with stage IV/recurrent NSCLC, which compared the efficacy of Yervoy in combination with paclitaxel and carboplatin versus placebo, and versus paclitaxel and carboplatin alone did not meet the primary endpoint of overall survival for the Yervoy treatment arms and has been discontinued. No new safety concerns with Yervoy were identified in either study. The company will complete a full evaluation of the data and work with investigators on the future publication of the results.

Elotuzumab
• In August, the FDA accepted for priority review the Biologics License Application for elotuzumab, an investigational Signaling Lymphocyte Activation Molecule (SLAMF7)-directed immunostimulatory antibody, for the treatment of multiple myeloma as combination therapy in patients who have received one or more prior therapies. Elotuzumab was previously granted Breakthrough Therapy Designation. The filing acceptance was primarily supported by data from ELOQUENT-2, a Phase 3, randomized, open-label study, which evaluated elotuzumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone. Additionally, the filing was supported by data from study CA004-009, a Phase 2, randomized, open-label study that evaluated elotuzumab with bortezomib and dexamethasone versus bortezomib and dexamethasone alone.

• In July, the European Medicines Agency (EMA) validated for review the Marketing Authorization Application for elotuzumab for the treatment of multiple myeloma as combination therapy in adult patients who have received one or more prior therapies. The application was granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use. Elotuzumab previously obtained orphan drug designation in the European Union (EU). The filing acceptance includes data from ELOQUENT-2 and Study CA004-009.

Sprycel
• In August, the company and its partner Otsuka America Pharmaceutical, announced that the FDA approved an update to the Sprycel product labeling to include five-year efficacy and safety data in adult patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) and seven-year data in the same patient population who are resistant or intolerant to prior therapy, including imatinib.

Daklinza
• In October, the FDA accepted for priority review three supplemental New Drug Applications (sNDAs) for Daklinza for use with sofosbuvir with or without ribavirin. The applications are for the treatment of patients with chronic hepatitis C (HCV) coinfected with human immunodeficiency virus (HIV-1), patients with advanced cirrhosis (including decompensated cirrhosis), and for patients with post-liver transplant recurrence of HCV. The new sNDAs accepted by the FDA for review include data from the ALLY-1 and ALLY-2 clinical trials.

• In October, the company announced that the National Institute for Health and Care Excellence (NICE) has recommended Daklinza in England and Wales for the treatment of adult patients with chronic HCV infection genotypes 1, 3 and 4.

• In September, the company announced the European Commission approved an updated label for Daklinza for the treatment of chronic HCV genotype 3, one of the most difficult-to-treat genotypes. The update allows the use of Daklinza in combination with sofosbuvir for 12 weeks in patients without cirrhosis in all 28 Member States of the EU, and marks the first time these patients with genotype 3 HCV have a once-daily, all-oral treatment regimen of this shorter duration. The approval is based on data from the Phase 3 open-label ALLY-3 clinical trial.

• In July, the FDA approved Daklinza for the treatment of patients with chronic HCV genotype 3. The approval marks the first time patients in the U.S. have a 12-week, once-daily, all-oral treatment option, and is the first approval for Daklinza in the U.S. The approval is based on data from the Phase 3 open-label ALLY-3 clinical trial.

HIV
• In October, the company announced overall antiviral activity and safety results from a three-part Phase 2a proof-of-concept study of BMS-955176, a novel investigational therapy designed to prevent the maturation of HIV-1. The overall results of the study demonstrate BMS-955176’s antiretroviral activity against the HIV-1 virus as both monotherapy and in combination with other antiretroviral medicines, and across patient subtypes (B, C), including those infected with the HIV-1 virus with changes in a critical protein ("Gag polymorphisms") that were not responsive to a previously investigated maturation inhibitor. Results were presented at the European AIDS Clinical Society’s 15th European AIDS Conference (EACS) in Barcelona.

BUSINESS DEVELOPMENT UPDATE

• In October, the company announced an exclusive worldwide license and collaboration agreement with Five Prime Therapeutics, Inc. for the development and commercialization of Five Prime’s colony stimulating factor 1 receptor (CSF1R) antibody program, including FPA008 which is in Phase 1 development for immunology and oncology indications. The agreement replaces the existing clinical collaboration agreement between both companies to evaluate the safety, tolerability and preliminary efficacy of combining Opdivo with FPA008 in six tumor types.

• In August, the company announced the establishment of the Immuno-Oncology Rare Population Malignancy (I-O RPM) program in the U.S. The I-O RPM program is a multi-institutional initiative with academic-based cancer centers focused on the clinical investigation of Immuno-Oncology therapeutics as potential treatment options for patients with high risk, poor prognostic cancers, defined as a rare population malignancy. As part of the I-O RPM program, Bristol-Myers Squibb subsequently announced two collaborations:

◦ In August, the company announced an agreement with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (Lurie Cancer Center) and the Northwestern Medicine Developmental Therapeutics Institute (NMDTI) whereby the Lurie Cancer Center and NMDTI will conduct a range of early phase clinical studies and Bristol-Myers Squibb will fund positions within the NMDTI Developmental Therapeutics Fellowship program.

◦ In September, the company announced an agreement with Moffitt Cancer Center in which Bristol-Myers Squibb and Moffitt will conduct a range of early phase clinical studies, including clinical investigations by young investigators to strengthen their development as clinical research scientists.

• In August, the company announced an agreement that grants Bristol-Myers Squibb an exclusive right to acquire Promedior, a company pioneering the development of targeted therapeutics to treat fibrotic diseases, and gain worldwide rights to its lead asset PRM-151, a recombinant form of human pentraxin-2 protein in Phase 2 development for the treatment of idiopathic pulmonary fibrosis (IPF) and myelofibrosis (MF). PRM-151 has been granted Fast Track designation in the U.S. and Orphan Designation in the U.S. and Europe for the treatment of MF, and Orphan Designation in the U.S. and Europe for the treatment of IPF.

• In August, the company announced a research collaboration and license agreement with QIMR Berghofer Medical Research Institute to discover novel therapeutic antibodies against an undisclosed Immuno-Oncology target.

• In July, the company announced a clinical trial collaboration agreement with Kyowa Hakko Kirin Co., Ltd., to conduct a Phase 1/Phase 2 combination study of Opdivo and mogamulizumab, an anti-CCR4 antibody. The study, which will be conducted in the U.S., will focus on evaluating the safety, tolerability and anti-tumor activity of combining mogamulizumab and Opdivo as a potential treatment option for patients with advanced or metastatic solid tumors.

2015 FINANCIAL GUIDANCE

Bristol-Myers Squibb is refining its 2015 GAAP EPS guidance range from $1.02 – $1.12 to $1.02 – $1.07. The company is increasing its non-GAAP EPS guidance range from $1.70 – $1.80 to $1.85 – $1.90. Both GAAP and non-GAAP guidance assume current exchange rates and that the R&D tax credit will be extended by Congress in 2015. Key revised 2015 non-GAAP line-item guidance assumptions include:

• Worldwide revenues between $16.0 and $16.4 billion.
• An effective tax rate of approximately 20%.

The financial guidance for 2015 excludes the impact of any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The non-GAAP 2015 guidance also excludes other specified items as discussed under "Use of Non-GAAP Financial Information." Details reconciling adjusted non-GAAP amounts with the amounts reflecting specified items are provided in supplemental materials available on the company’s website.

8-K – Current report

On October 19, 2015 Galectin Therapeutics, Inc. (Nasdaq: GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, reported that Providence Cancer Center has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to study GR-MD-02 in combination with Keytruda (pembrolizumab), an immune checkpoint inhibitor, in a Phase 1b study of patients with advanced refractory metastatic melanoma (Filing, 8-K, Galectin Therapeutics, OCT 19, 2015, View Source [SID:1234507733]). GR-MD-02 binds to and inhibits galectin proteins, predominantly galectin-3 (Gal-3). Galectin will provide GR-MD-02 to the investigators, who are funding the costs of this study.

The IND filing was prompted by findings from preclinical studies led by tumor immunology expert William L. Redmond, Ph.D. of the Providence Cancer Center’s Earle A. Chiles Research Institute. That study found that GR-MD-02 increased tumor shrinkage and enhanced survival in immune competent mice with multiple types of cancers when combined with one of the immune checkpoint inhibitors, anti-CTLA-4 or anti-PD-1. Pembrolizumab (anti-PD-1) was approved by the FDA in September 2014 to treat patients whose melanoma had progressed after treatment with Yervoy (ipilimumab) or targeted therapy in melanomas that have a BRAF mutation. GR-MD-02 is also the subject of an ongoing Phase 1b study in combination with Yervoy in patients with malignant melanoma, also by Providence Cancer Center. Details of the study design can be found at clinicaltrials.gov: here

"This proposed study will be the second involving a checkpoint inhibitor in combination with GR-MD-02, and we are very pleased to reach this milestone with the investigators at the Portland Cancer Center," said Peter G. Traber, M.D., president, chief executive officer and chief medical officer of Galectin Therapeutics. "Preclinical data show that GR-MD-02 holds potential to increase the effectiveness of other therapies and represents a promising approach to enhance cancer immunotherapy."

Pending FDA review of the IND, the Phase 1b study will be conducted by the Providence Cancer Center under principal investigator Brendan D. Curti, M.D., director of the Providence Biotherapy Program. Providence Cancer Center researchers have been leaders in immunotherapy research and translational clinical trials in melanoma and other cancers.

"Clinical research has shown that therapeutic combinations involving checkpoint inhibitors have improved outcomes in patient survival. The Phase 1b study will determine if GR-MD-02 enhances the probability of melanoma response with pembrolizumab by inducing proliferation, activation and memory function of CD8+ T cells," said Dr. Curti. "The combination of GR-MD-02 and pembrolizumab has a strong scientific rationale based on Dr. Redmond’s laboratory work. This study represents a novel approach for patients with metastatic melanoma and complements our similar study of GR-MD-02 in combination with Yervoy."

Study Design
The proposed Phase 1b study is expected to enroll 16 to 22 patients with advanced melanoma whose disease has progressed after treatment with ipilimumab and/or BRAF-targeted therapy in melanomas with a BRAF mutation, and is designed to determine a safe dose of GR-MD-02 in combination with the approved dose of pembrolizumab (2 mg/kg). The study will employ a 3+3 Phase 1 design with dose escalation of GR-MD-02 beginning with 2 mg/kg in the first cohort and increasing to 8 mg/kg, depending on toxicity. In addition to monitoring for toxicity and clinical response, blood samples will be obtained to assess immunologic measures relevant to galectin biology and pembrolizumab T-cell checkpoint inhibition. Galectin Therapeutics will supply researchers with supporting analysis of the pharmacokinetics of GR-MD-02 and the right to reference the Company’s open IND on GR-MD-02.
Yervoy is a registered trademark of Bristol-Myers Squibb. Keytruda is a registered trademark of Merck.

About Metastatic Melanoma
Melanoma, the most dangerous form of skin cancer, is one of the most widespread cancers among young adults. Metastatic melanoma occurs when the cancer cells spread (or metastasize) through the lymph nodes to other parts of the body. The liver, lungs, bones and brain are most often affected by these metastases. The American Cancer Society estimates that there were more than 76,000 new diagnoses and 9,100 deaths from melanoma in the United States in 2012.

8-K – Current report

On September 17, 2015 TG Therapeutics, Inc. (Nasdaq: TGTX) reported that it has reached an agreement with the U.S. Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design of a Phase 3 clinical trial for its proprietary combination of TG-1101 (ublituximab), its glycoengineered anti-CD20 monoclonal antibody, plus TGR-1202, the Company’s once-daily PI3K-delta inhibitor, for the treatment of Chronic Lymphocytic Leukemia (CLL) (Filing, 8-K, Manhattan Pharmaceuticals, SEP 17, 2015, View Source [SID:1234507484]). The SPA provides agreement that the Phase 3 trial design adequately addresses objectives that, if met, would support the regulatory submission for drug approval of both TG-1101 and TGR-1202 in combination.

Full details of the Phase 3 clinical trial, called the UNITY-CLL trial, will be released at the launch of the study. The general study design is a randomized controlled clinical trial that includes two key objectives: first, to demonstrate contribution of each agent in the TG-1101 + TGR-1202 regimen (the combination sometimes referred to as "1303"), and second, to demonstrate superiority in Progression Free Survival (PFS) over the standard of care to support the submission for full approval of the combination. The study will randomize patients into four treatment arms: TG-1101 + TGR-1202, TG-1101 alone, TGR-1202 alone, and an active control arm of obinutuzumab + chlorambucil. An early interim analysis will assess contribution of each single agent in the TG-1101 + TGR-1202 combination regimen, which, if successful, will allow early termination of both single agent arms. A second interim analysis will be conducted following full enrollment into the study, which, if positive, the Company plans to utilize for accelerated approval. Assuming early termination of the TG-1101 and TGR-1202 single agent arms, the study will enroll approximately 450 patients.

Dr. John Gribben, Professor of Medicine and the Gordon Hamilton Fairley Chair of Medical Oncology at St. Bartholomew’s Hospital, Barts Cancer Institute in London, UK, will lead the UNITY-CLL Phase 3 as Study Chair. Dr. Gribben commented, "The recent introduction of novel targeted agents has already dramatically improved the standard of care for patients with relapsed or refractory CLL, and we have seen even greater activity when these agents are used in combination. Both ublituximab and TGR-1202 have demonstrated unique activity and tolerability as single agents, and in combination together. We are excited to lead this important and innovative trial, which has the potential to bring greater advances to patients in both the front-line and relapsed/refractory CLL setting."

Michael S. Weiss, Executive Chairman and Interim Chief Executive Officer of TG Therapeutics, stated, "Our number one goal has always been to accelerate the development of novel non-chemotherapy-based combination treatments for patients with B-cell malignancies. The UNITY-CLL study and the related SPA marks a major milestone for the Company and, if successful, could lead to a very broad label in the treatment of CLL, providing patients and physicians a new treatment option, and the Company a platform to build additional proprietary combinations in our continued effort to drive towards a cure. Our path to achieving this SPA, which we believe is the first for two novel investigational agents in the oncology division, was the result of a true collaboration with the FDA, for which we would like to recognize and thank the agency for its invaluable guidance throughout this process." Mr. Weiss continued, "Our clinical team has been hard at work preparing for the launch of this study, and we look forward to enrolling our first patients as soon as possible. Lastly, we are thrilled to have Dr. Gribben, a world-renowned authority in CLL, lead this important international study and share in his excitement in bringing our novel, non-chemotherapy combination regimen to patients in need."

8-K – Current report

On September 1, 2015 Heat Biologics, Inc. (NASDAQ: HTBX), a clinical stage cancer immunotherapy company, reported that it has enrolled the first patient in a Phase 1b clinical trial investigating the combination of its HS-110 therapeutic vaccine and the Bristol-Myers Squibb PD-1 inhibitor nivolumab (Opdivo) in non-small cell lung cancer (NSCLC) (Filing, 8-K, Heat Biologics, SEP 1, 2015, View Source [SID:1234507369]). HS-110 is the Company’s first product candidate in a series of proprietary ImPACT based immunotherapies designed to stimulate patient’s own T-cells to attack cancer. Additionally, as the FDA approval of nivolumab and anticipated approval of other checkpoint inhibitors is dramatically changing the standard of care in lung cancer treatment, Heat is winding down its ongoing Phase 2 trial with HS-110, which does not include a checkpoint inhibitor combination, to instead focus on combinations with checkpoint inhibitors.

This multicenter trial is evaluating the safety and efficacy of HS-110 in combination with nivolumab in patients with NSCLC whose cancers have progressed after first-line therapy. Primary and secondary trial endpoints include safety and tolerability, immune response, overall response rate and progression-free survival.

"Checkpoint inhibitors such as nivolumab are rapidly becoming standard of care in the treatment of NSCLC and many other types of cancer," stated Jeff Wolf, CEO of Heat Biologics. "Substantial evidence is emerging regarding the benefits of combining checkpoint inhibitors and therapeutic vaccines. Heat had previously reported synergy between ImPACT and anti-PD-1 therapy. This important clinical study is among the first trials to explore the combination of a checkpoint inhibitor and therapeutic vaccine in NSCLC and will enable us to more fully evaluate this combination with other checkpoint inhibitors, such as Merck’s pembrolizumab, as they become available."

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"We reported earlier this year, in a clinical trial for HS-410 for bladder cancer, that patients with low levels of tumor-infiltrating lymphocytes (TILs) at baseline appeared to respond better," said Taylor Schreiber, M.D., Ph.D., Heat’s Chief Scientific Officer. "This is consistent with emerging clinical evidence demonstrating that while responses to checkpoint inhibitor therapy are biased toward patients with pre-existing TILs, the optimal patient population for therapeutic vaccines in conjunction with checkpoint inhibitors may in fact be the checkpoint unresponsive (and TIL negative) population. Currently, only 20% to 30% of NSCLC patients respond to nivolumab. This trial will specifically investigate whether HS-110 can broaden the base of patients who respond to nivolumab and other checkpoint inhibitors."

"This trial is expected to initially enroll 18 patients, and is designed to accommodate rapid cohort expansion as positive clinical data emerge," stated Melissa Price, Ph.D., Heat’s VP of Product Development. "We will be working with Yale Cancer Center’s Translational Immuno-Oncology Laboratory on the analysis of the TILs biomarker data for patient selection. We expect to release top-line objective response rate and 6-month progression free survival (PFS) data on these first 18 patients by the end of 2016, which should enable us to reach a clinical readout for HS-110 with a checkpoint-focused clinical trial, on the same schedule that we had forecasted for our previous trial. Our expectations around the timing of an HS-110 registration-directed study in NSCLC remain unchanged."

Nivolumab (Opdivo) was approved by the US Food and Drug Administration (FDA) for the treatment of NSCLC in March 2015 and is marketed by Bristol-Myers Squibb. Another anti-PD-1 drug candidate, Merck’s pembrolizumab (KEYTRUDA) is currently under FDA Priority Review for NSCLC.

8-K – Current report

On August 10, 2015 Sorrento Therapeutics, Inc. (NASDAQ: SRNE; Sorrento) reported that its wholly-owned subsidiary, TNK Therapeutics, Inc., has acquired multiple preclinical and clinical stage chimeric antigen receptor (CAR)-T immunotherapy programs as well as underlying CAR-T technology through the acquisition of two privately-held biotechnology companies (Filing, 8-K, Sorrento Therapeutics, AUG 10, 2015, View Source [SID:1234507183]). The CAR-T programs focus on targeting solid tumors as well as infectious diseases.

"We are very pleased to enter the dynamic CAR-T immunotherapy field with these clinical stage assets targeting solid tumors, an area of great unmet medical need", said Dr. Henry Ji, President and CEO of Sorrento. "Especially exciting is the potential of combining the CAR-T therapies with Sorrento’s immune-oncology programs, such as anti-PD1 and anti-CTLA4 monoclonal antibodies (mAbs). We recently in-licensed late clinical stage biobetter mAbs of the marketed antibodies infliximab, cetuximab, and basiliximab, as well as a biosimilar mAb of omalizumab. Utilizing these assets, combination therapies of our biobetter mAb of basiliximab, an anti-CD25 mAb that has been used to target and deplete immunosuppressive regulatory T cells1, or cetuximab, an anti-EGFR (epithelial growth factor receptor) mAb, may work synergistically with our CAR-T and CAR.TNK programs for the treatment of solid tumors.
With these acquisitions of clinical and pre-clinical CAR constructs, TNK Therapeutics is now positioned to accelerate the development of in-house adoptive immunotherapies, including the "off-the-shelf" CAR.TNK programs in our exclusive partnership with NantKwest. This breadth of complementary clinical programs and enabling technologies truly positions TNK Therapeutics to be a leader in the field of adoptive immunotherapies."

Information about these CAR-T programs, underlying technologies as well as the biosimilar/biobetter antibodies will be detailed in Sorrento’s updated corporate presentation later this month.

8-K – Current report

On August 4, 2015 GlobeImmune, Inc. announced today that Celgene Corporation exercised its option under the 2009 Collaboration and Option Agreement to exclusively license GI-6207, a Tarmogen product candidate targeting cancers that express carcinoembryonic antigen (CEA) (Filing, 8-K, GlobeImmune, AUG 4, 2015, View Source [SID:1234507002]).

GI-6207 is the second Tarmogen product candidate licensed by Celgene under the collaboration. Under the terms of the agreement, GlobeImmune will receive an option exercise payment of $1.9 million, and is eligible for regulatory and sales milestones, as well as royalties on product sales in exchange for a worldwide license. GI-6207 is currently being evaluated in a Phase 2 clinical trial at the National Cancer Institute (NCI) to evaluate GI-6207 in subjects with medullary thyroid cancer (MTC).

"We are very pleased that Celgene has exercised their option to license this program," said Timothy C. Rodell, M.D., FCCP, President and CEO of GlobeImmune, Inc. "We look forward to results from the MTC phase 2 trial in the second half of 2016."

GI-6207-02 – Phase 2 MTC Trial
GI-6207-02 is a 34 patient, randomized Phase 2 study being conducted at the NCI, which is approximately 80% enrolled. Under the protocol, patients are administered either GI-6207 for one year or observed for six months and then administered GI-6207 for one year. The primary endpoint for the trial will be the effect of GI-6207 on changes in calcitonin levels. Calcitonin is a tumor marker that correlates with tumor size in MTC. Elevated calcitonin values after surgery indicate persistent or recurrent disease. [www.clinicaltrials.gov; NCT01856920]

Medullary Thyroid Cancer
Thyroid cancer is the most common type of endocrine malignancy in the U.S. with approximately 62,450 new cases estimated in 2015. Medullary thyroid cancer, a subtype of thyroid cancer has a poor prognosis with approximately 25 percent and 10 percent of patients alive at five and ten years, respectively. Furthermore, metastatic MTC is largely unresponsive to conventional chemotherapy and radiotherapy. Two drugs have been approved for the treatment of metastatic MTC. Both of these products were approved on the basis of improved progression free survival; neither has yet shown improved overall survival, and both of them have substantial side effects that limit their use.
GI-6207

The GI-6207 is a Tarmogen that expresses a modified version of CEA protein as the target cancer antigen. CEA is over-expressed in multiple human epithelial cancers, including MTC, where studies have indicated CEA is almost universally expressed and is a diagnostic marker of the disease. Preclinical studies have shown that GI-6207 can induce an immune response to CEA as well as therapeutic anti-tumor responses. In a previous Phase 1 study of monotherapy GI-6207, 20% of subjects (5/25) had stable or decreased CEA levels and stable disease after receiving GI-6207.

8-K – Current report

On July 20, 2015 Agenus reported that it has acquired rights to antibodies targeting Carcinoembryonic Antigen Cell Adhesion Molecule 1 (CEACAM1), a glycoprotein expressed on T cell and NK cell lymphocytes from Diatheva s.r.l., an Italian biotech company controlled by SOL S.p.A (Filing, 8-K, Agenus, JUL 20, 2015, View Source [SID:1234506507]).

CEACAM1 is overexpressed in melanoma, bladder, lung, colon, pancreas, and gastric cancers and has been shown to modulate innate and adaptive immune suppression in pre-clinical studies. Antibodies targeting CEACAM1 are thought to have the potential to effectively treat cancer alone or in combination with other checkpoint modulator antibodies, including those in Agenus’ development pipeline.

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"CEACAM1 is emerging as a powerful immune modulator, with significant evidence that blocking its interactions could strengthen immune cells’ attack on cancer," said Robert Stein, M.D., Ph.D., Chief Scientific Officer of Agenus. "Diatheva’s anti-CEACAM1 monoclonal antibodies expand and complement our broad portfolio of checkpoint modulators and personalized cancer vaccines, with the potential to create best-in-class combination therapies for treating patients with cancer."

Under the license agreement, Agenus receives exclusive, worldwide rights for development and commercialization of CEACAM1 antibodies from Diatheva. Agenus is responsible for certain upfront, early development, clinical trial and regulatory milestone payments for the successful development of CEACAM1 antibodies totaling as much as $44 million. Diatheva is also eligible to receive additional sales milestones and royalties.

Professor Mauro Magnani, Ph.D., Founder and Scientific Director of Diatheva, stated, "Agenus’ proven immuno-oncology and development capabilities, represents an exciting opportunity for Diatheva’s most advanced human monoclonal antibodies. Agenus’ selection of our anti-CEACAM1 antibodies is indicative of the quality of Diatheva’s research and will support reinvestment in our company’s pipeline."

8-K – Current report

July 9, 2015 Sorrento Therapeutics and NantBioScience, a majority owned subsidiary of NantWorks reported that they have established a joint venture to focus on the development of ‘first-in-class’ small molecules against targets that have eluded the pharmaceutical industry to date and which may address important drivers of cancer growth including cancer stem cells (Filing, 8-K, Sorrento Therapeutics, JUL 9, 2015, View Source [SID:1234506196]).

Sorrento will contribute key small molecule programs (lead inhibitors of the proto-oncogenes c-Myc, and the master metabolism regulator HIF-1 alpha, and an inducer of the tumor suppressor cytokine TRAIL) to the joint venture which will be 60% owned by NantBioScience and 40% owned by Sorrento, and funded accordingly.

This joint venture follows on the previously announced acquisition by NantPharma of the rights to Cynviloq, a nanoparticle-based paclitaxel cytotoxic therapeutic, now renamed Nant-paclitaxel, as well as the formation of NantiBody, a joint venture focused on immunotherapeutics. Both entities are affiliated with Dr. Soon-Shiong’s ecosystem of companies at NantWorks.

"Sorrento’s mission is to expeditiously and efficiently bring innovative therapies to cancer patients in need," said Dr. Henry Ji, President and CEO. "This partnership focused on the development of our innovative small molecules will allow us to realize Sorrento’s vision, align our resources on our immuno-oncology and cell therapy assets, and puts Sorrento at the forefront of cancer therapy."

"Treatment of patients with cancer will require a multi-faceted approach involving chemotherapy, immunotherapy, adoptive cellular therapy and next-generation precision medicine platforms," said Dr. Patrick Soon-Shiong, NantWorks founder. "We are committing significant resources to the development of novel and innovative cancer therapies, including small molecules as components of targeted combination therapy strategies. At NantBioScience, we are pursuing the equivalent of the moonshot in the oncology space by developing drugs targeting mutant KRAS, RAL, and now cMyc, and HIF-1 alpha, as well as drugs inducing TRAIL expression and p53 activity. Only by developing drugs for these widely-considered "undruggable" targets do we have a hope of winning our war against cancer. Through this joint venture and the other ongoing collaborations we have with Sorrento, we are focused on transforming cancer therapy as we know it today and provide cancer patients with innovative treatment options for their thus far unmet medical needs."

8-K – Current report

On June 15, 2015 Heat Biologics reported the development of its next-generation combination immunotherapy platform, which combines a pan-antigen T cell priming vaccine and T cell co-stimulator in a single product (Filing, 8-K, Heat Biologics, JUN 15, 2015, View Source [SID:1234505436]).

This platform, named ComPACT, has been engineered to incorporate various fusion proteins targeting co-stimulatory receptors (OX40, ICOS, 4-1BB), enabling the combination of two important immunotherapy pathways in a single therapy. Data generated using the ComPACT platform are being presented today at the Cell Symposia, ‘Cancer, Inflammation and Immunity’ in Sitges, Spain. The Company will also be hosting a Webcast today to present these data.

Taylor Schreiber, MD, PhD, Heat’s Vice President of Research, who led development of ComPACT, commented: "It is now widely recognized in the clinical community that combinations between checkpoint inhibitors, T cell co-stimulators, and vaccines can provide superior benefits to any single modality as monotherapy. The first challenge in developing these combinations is to systematically identify synergistic pathways from redundant or antagonistic ones. Another challenge is to deploy combination immunotherapies that may limit systemic toxicity and offer an advantageous overall cost structure compared to combining multiple biologic therapies. Heat’s ComPACT therapy is designed to achieve these goals."

The presentation by George Fromm, PhD, Heat’s Director of Research, reveals the first preclinical analysis of ComPACT, incorporating OX40L-Fc, demonstrates significant benefits as compared to traditional OX40 agonistic antibodies. Dr. Fromm commented: "The magnitude of T cell stimulation with ComPACT was somewhat unexpected, but clearly demonstrates substantial increases for both primary and memory immune response to those seen by co-administration of a vaccine and OX40 agonist antibody." The data illustrate that systemic OX40 stimulation through antibody therapy led to increased off-target T cell activation, and that the beneficial response with ComPACT may be due to increased specificity.

Although the data presented include combinations between gp96-Ig vaccination and stimulation of OX40, the platform has also been developed to target other T cell co-stimulatory receptors including ICOS, 4-1BB and other undisclosed co-stimulatory targets. Heat’s ComPACT therapy has the potential to provide a product that achieves the envisioned benefits of combination immunotherapy in a single therapy, without the need for multiple independent biologic products. Heat expects to file its first IND with the ComPACT platform in 2H, 2016.

8-K – Current report

On May 15, 2015 Sorrento Therapeutics reported that NantPharma, founded by Dr. Patrick Soon-Shiong and a member of the NantWorks ecosystem of companies, agreed to acquire the rights to Cynviloq through the acquisition of Igdrasol, Inc., a wholly-owned subsidiary of Sorrento, which has been developing Cynviloq (paclitaxel nanoparticle polymeric micelle) in a bio-equivalence trial. Dr. Soon-Shiong was the founder of Abraxis BioScience and inventor and developer of the blockbuster drug Abraxane (albumin-bound paclitaxel), currently approved for the treatment of breast, lung, and pancreatic cancers (Filing, 8-K, Sorrento Therapeutics, MAY 15, 2015, View Source [SID:1234504357]). Under the terms of the agreement, Sorrento will receive more than $90 million in an up-front cash payment plus the potential for more than $600 million in regulatory and $600 million in sales milestone payments. Sorrento will also receive additional transfer pricing payments from total unit sales. Furthermore, Sorrento has the option to co-develop and/or co-market Cynviloq on terms to be negotiated.

"We are extremely pleased with the recent Cynviloq TRIBECA study results and excited that Dr. Patrick Soon-Shiong and his NantPharma team plan to expand Cynviloq into multiple cancer indications, as well as combine it with immunomodulatory antibodies and cell therapies from Sorrento’s pipeline." said Dr. Henry Ji, President and CEO. "This major transaction will enhance Sorrento’s mission of bringing innovative therapies to patients in need quickly and efficiently. It puts our lead program into the hands of a team that has the experience, commitment and resources to develop and launch a major cancer drug. This transaction not only validates our prior Igdrasol acquisition, it also delivers significant financial return, while potentially offering much more in the long run to our shareholders. Moving forward, Sorrento plans to focus on truly innovative immuno-oncology and cellular therapies and position us as the leader in the emerging immunotherapy space."

"Precision cancer medicine will require a multi-faceted treatment approach involving chemotherapy, immunotherapy, adoptive cellular therapy and next-generation precision medicine technologies, including such as genomics and proteomics diagnostics which NantWorks is developing," said Dr. Soon-Shiong. "We are committing significant resources to the development of novel cancer therapies, including combination therapies, an area of significant unmet need. Chemotherapy is an important pillar to the combination with immunotherapy and natural killer cells, and the opportunity to develop combination regimens of low-dose metronomic use of this active drug is an important step in transforming cancer care as we know it today."

8-K – Current report

On May 11, 2015 CEL-SCI reported that Spain’s Agency for Medicinal Products and Medicinal Devices has authorized the Company to commence patient enrollment for its ongoing Phase 3 trial of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) in patients with advanced primary squamous cell carcinoma of the oral cavity/soft palate, a type of head and neck cancer (Filing, 8-K, Cel-Sci, MAY 11, 2015, View Source [SID:1234504177]). Spain is the 22nd country to authorize CEL-SCI’s Phase 3 trial for patient enrollment.

CEL-SCI recently announced it had reached a key milestone of receiving authorization to conduct the Phase 3 study from 21 countries, as originally planned. The Company is aiming to expand the trial into a total of approximately 100 clinical centers in about 25 countries. As of April 30, 2015, 437 patients had been enrolled in the global Phase 3 study.

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About the Multikine Phase 3 Study

The Multikine Phase 3 study is enrolling patients with advanced primary squamous cell carcinoma of the head and neck. The objective of the study is to demonstrate a statistically significant improvement in the overall survival of enrolled patients who are treated with the Multikine treatment regimen plus standard of care ("SOC") vs. subjects who are treated with SOC only.

About Multikine

Multikine (Leukocyte Interleukin, Injection) is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. CEL-SCI has also entered into two co-development agreements with Ergomed Clinical Research Limited to further the development of Multikine for cervical dysplasia/neoplasia in women who are co-infected with HIV and HPV and for peri-anal warts in men and women who are co-infected with HIV and HPV.

8-K – Current report

On May 6, 2015 Juno Therapeutics and Fate Therapeutics reported that they have executed a strategic research collaboration and license agreement to identify and utilize small molecules to modulate Juno’s genetically-engineered T cell product candidates to improve their therapeutic potential for cancer patients (Filing, 8-K, Fate Therapeutics, MAY 6, 2015, View Source [SID:1234503625]). The collaboration brings together Juno’s industry-leading expertise in the development of chimeric antigen receptor (CAR) and T cell receptor (TCR) based cellular immunotherapies and Fate’s innovative platform for programming the biological properties and in vivo therapeutic potential of hematopoietic cells.

"A deep understanding of T cell biology is the basis of Juno’s approach to creating best-in-class cellular immunotherapies," said Hans Bishop, Chief Executive Officer of Juno Therapeutics. "Partnering with Fate Therapeutics, and accessing its strong science and leading platform for modulating the properties of immunological cells, enables interrogation of new avenues of T cell manipulation and provides an opportunity to enhance the therapeutic profile of our genetically-engineered T cell product candidates."

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Through the four-year research and development collaboration, Fate will be responsible for screening and identifying small molecules that modulate the biological properties of engineered T cells. Juno will be responsible for the development and commercialization of engineered T cell immunotherapies incorporating Fate’s small molecule modulators. Juno has the option to extend the exclusive research term for two years through an additional payment and continued funding of collaboration activities.

"We are excited to establish this strategic alliance with Juno, a company that shares our deep commitment to developing transformative cellular therapeutics for patients afflicted with life-threatening disorders," said Christian Weyer, M.D., M.A.S., President and Chief Executive Officer of Fate Therapeutics. "This partnership exemplifies the extension of our small molecule programming platform to additional hematopoietic cell types, such as T cells, as we continue to build and advance our innovative pipeline of programmed hematopoietic cellular therapeutic candidates."

Financial terms of the agreement include an upfront payment to Fate of $5 million and the purchase by Juno of one million shares of Fate common stock at $8.00 per share. Juno will fund all mutual collaboration activities for an exclusive four-year research term. For each product developed by Juno that incorporates modulators identified through the collaboration, Fate is eligible to receive approximately $50 million in target selection fees and clinical, regulatory and commercial milestones, as well as low single-digit royalties on sales. Fate retains exclusive rights to its intellectual property for all purposes outside of programmed CAR and TCR immunotherapies.

About Chimeric Antigen Receptor (CAR) Technology

Juno’s chimeric antigen receptor (CAR) technology genetically engineers T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. When the engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell.

8-K – Current report

On May 4, 2015 Sorrento Therapeutics reported positive results from recently analyzed pharmacokinetic (PK) data from its TRIBECA (TRIal establishing BioEquivalence between Cynviloq and Albumin-bound paclitaxel) registrational tria l(Filing, 8-K, Sorrento Therapeutics, MAY 4, 2015, View Source [SID:1234503568]). Data analysis suggests that Cynviloq meets the bioequivalence (BE) criteria for both total and unbound paclitaxel. The ongoing safety assessment from treated patients continues to reveal no unexpected adverse events and the safety data is consistent with the toxicity profile reported in the literature with albumin-bound paclitaxel.

8-K – Current report

On April 29, 2015 Bellicum Pharmaceuticals reported it has entered into a license agreement with Leiden University Medical Center (LUMC), Netherlands, for worldwide rights to develop, manufacture and commercialize high-affinity TCR (T cell receptor) product candidates targeting solid tumors expressing the preferentially-expressed antigen in melanoma, or PRAME (Filing, 8-K, Bellicum Pharmaceuticals, APR 29, 2015, View Source [SID:1234503221]).

TCRs are engineered T cells that are activated when in the presence of target antigens in cancer cells. The lead TCRs under this license agreement have been shown to have a high affinity to PRAME, a cancer antigen that is preferentially expressed in melanomas, sarcomas, neuroblastomas and other solid tumors, but generally not expressed in normal tissue.

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Bellicum’s first TCR product candidate under this agreement, BPX-701, targets PRAME and is expected to enter Phase 1/2 clinical trials before the end of 2015. BPX-701 incorporates Bellicum’s proprietary safety mechanism, CaspaCIDe, for improved control over the cells.

Bellicum also exclusively licensed LUMC’s TCR technology targeting POU-2AF1. These TCRs have a high affinity to the B cell transcription factor expression product of POU-2AF1, which is present in primary chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), mantle cell lymphoma and multiple myeloma.

"TCRs are demonstrating broad potential for the treatment of solid tumors," said Tom Farrell, President and Chief Executive Officer of Bellicum Pharmaceuticals. "The cancer targets under this license, combined with our CaspaCIDe safety mechanism, form the basis of a growing portfolio of differentiated T cell therapies with the potential to address a wide range of cancers."

8-K – Current report

On April 28, 2015 Bio-Path Holdings reported that they have received orphan drug designation from the U.S. Food and Drug Administration (FDA) for its lead compound Liposomal Grb-2 for the treatment of acute myeloid leukemia (AML) (Filing, 8-K, Bio-Path Holdings, APR 28, 2015, View Source [SID:1234503201]). Orphan drug status provides Bio-Path with seven years of exclusivity after receiving formal marketing approval, as well as additional development incentives. The FDA grants this designation to certain drugs that are targeting diseases affecting fewer than 200,000 people in the United States.

"This designation from the FDA demonstrates the unmet need for an effective therapy for patients suffering from AML," said Peter Nielsen, President and Chief Executive Officer of Bio-Path. "It also marks a key regulatory milestone for Bio-Path and will be valuable as we continue to progress Liposomal Grb-2 through clinical trials and toward potential commercialization."

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Liposomal Grb-2 is currently in a safety segment of a Phase 2 trial in combination with Ara-C, for acute myeloid leukemia; and is being evaluated for chronic myelogenous leukemia.

Pre-clinical development is underway for triple negative and inflammatory breast cancers.

About Acute Myeloid Leukemia

AML is a fast-growing cancer of the blood and bone marrow where the bone marrow makes many cancerous cells called leukemic blasts. Normal blasts develop into white blood cells that fight infection. In AML, the leukemic blasts do not develop properly and cannot fight infections. These leukemic blasts grow quickly and crowd out the bone marrow, preventing it from making the normal red blood cells, white blood cells, and platelets that the body needs.
Nearly 15,000 people in the United States are diagnosed with AML each year.

About Growth Receptor Bound protein-2 (Grb-2)

The adaptor protein Growth Receptor Bound protein-2 (Grb-2) is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. Suppressing the function or expression of Grb-2 should interrupt its vital signaling function and have a therapeutic application in cancer. BP-1001 is a neutral-charge, liposome-incorporated antisense drug substance designed to inhibit Grb-2 expression.

8-K – Current report

On April 14, 2015 Argos Therapeutics and Lummy reported they have entered into a license agreement. Under the terms of the agreement, Lummy HK will license from Argos the rights to manufacture, develop and commercialize AGS-003, Argos’ investigational immunotherapy for the treatment of cancer, in China, Hong Kong, Taiwan and Macau (Filing, 8-K, Argos Therapeutics, APR 14, 2015, View Source [SID:1234502991]).

In connection with the license agreement, Tianyi Lummy International Holdings Group Ltd., an affiliate of Lummy HK ("Tianyi Lummy"), and the China BioPharma Capital I Fund ("China BioPharma Capital") have purchased an aggregate of one million shares of Argos’ common stock at a premium of 12.5% for a purchase price of approximately $10 million. Lummy HK has agreed to pay Argos a royalty on net sales of AGS-003 at a rate in the teens and up to an aggregate of $20 million for regulatory and commercial milestones. In addition, Tianyi Lummy and China BioPharma Capital have agreed to purchase an additional $10 million of Argos’ common stock following and subject to the interim data analysis from Argos’ pivotal phase 3 ADAPT trial of AGS-003 by the Independent Data Monitoring Committee expected in late 2015 that will occur at approximately 50% of events in the trial and certain other conditions. China BioPharma Capital recently announced its first closing and is focusing on investments in pharmaceutical life science innovation in Western companies with the objective to obtain licenses for development and commercialization in China.

"We are excited about the potential for Arcelis-based products to advance the treatment of cancer throughout Greater China and in markets around the world," said Jeff Abbey, president and CEO of Argos. "Our agreement with Lummy HK is another reflection of the strong clinical data that we have observed with AGS-003 and our ability to attract outstanding partners to support commercialization in the years ahead."

Argos’ proprietary Arcelis technology platform uses a patient’s own dendritic cells and tumor sample to create a fully personalized immunotherapy. AGS-003, Argos’ lead product candidate, is currently being tested in the pivotal phase 3 ADAPT clinical trial for the treatment of metastatic renal cell carcinoma (mRCC).

Under the license agreement, Lummy HK also acquires rights to develop Arcelis-based products for additional oncology indications, potentially including pancreatic, lung, liver, stomach, rectal, gastric, and esophageal cancers. Lummy HK will be responsible, at its expense, for all development costs that are necessary for regulatory approval in all markets covered in the license agreement.

"Our agreement with Argos to develop AGS-003 in China, Hong Kong, Taiwan and Macau is another example of our ongoing commitment to develop and market new therapies that can address serious unmet needs in the treatment of cancer in China and throughout Asia," said Mr. Qiu Yu, chairman of Lummy HK. "The Arcelis technology platform also holds great promise for automating the manufacturing and commercialization of a portfolio of fully personalized immunotherapies and we look forward to working with Argos to initiate our own development programs to bring products based on this innovative technology to the patients we serve."

About the Arcelis Technology Platform

Arcelis is a fully personalized immunotherapy technology that captures mutated and variant antigens that are specific to each patient’s disease. It is designed to overcome immunosuppression by producing a durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to a wide range of different cancers, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized cancer immunotherapies. The Arcelis process uses only a small tumor or blood sample and the patient’s own dendritic cells, which are collected and optimized following a single leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease specific antigens. The activated, antigen-loaded dendritic cells are then formulated into the patient’s plasma and administered via intradermal injection.

8-K – Current report

On April 14, 2015 Teva Pharmaceutical and Eagle Pharmaceuticals reported that the New Drug Application (NDA) for a liquid bendamustine hydrochloride (HCl) rapid infusion product has been accepted for filing by the U.S. Food and Drug Administration (FDA) (Filing, 8-K, Eagle Pharmaceuticals, APR 14, 2015, View Source [SID:1234502996]). The Prescription Drug User Fee Act (PDUFA) goal date for a decision on this NDA by the FDA is December 2015.

This NDA requests FDA approval of the rapid infusion bendamustine HCl product for the treatment of patients with chronic lymphocytic leukemia (CLL) and patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. This product candidate has received Orphan Drug Designations for both CLL and indolent B-cell NHL, and therefore may be eligible for seven years of exclusivity upon approval. The NDA is supported by data from a clinical trial completed in November 2014, which demonstrated that the rapid infusion bendamustine HCl product can be administered in ten minutes in a low-volume, 50 mL admixture.

"The rapid infusion bendamustine product, if approved, will be an important new treatment option for patients with CLL or indolent B-cell NHL that has progressed and their healthcare providers," said Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals. "We look forward to continuing to work closely with the FDA through the review process, and to their decision on the NDA in December of this year."

"We are very pleased the FDA has accepted the rapid infusion bendamustine NDA for review," stated Paul Rittman, Vice President and General Manager, Teva Oncology. "Teva looks forward to the opportunity to bring this product to market, if approved, and we believe it represents an important and improved benefit to both patients and healthcare providers."
In February 2015, Eagle and Teva Pharmaceutical Industries Ltd. entered into an exclusive license agreement for the rapid infusion bendamustine product. Teva will be responsible for all U.S. commercial activities for the product including promotion and distribution. Eagle has responsibility for obtaining all regulatory approvals, conducting post-approval clinical studies, if required, and initially supplying drug product to Teva.

8-K – Current report

On April 14, 2015 Puma Biotechnology reported that it has expanded the second cohort from its Phase II clinical trial of its lead drug candidate PB272 (neratinib) as a single agent in patients with solid tumors who have an activating HER2 mutation (basket trial) (Filing, 8-K, Puma Biotechnology, APR 14, 2015, View Source [SID:1234502999]). The cohort that has been expanded is the cohort that includes patients with metastatic non-small cell lung cancer and whose tumors have a HER2 mutation.

The Phase II basket trial, which was initiated in October 2013, is an open-label, multicenter, multinational study to evaluate the safety and efficacy of PB272 administered daily to patients who have solid tumors with activating (driver) ERBB mutations, including epidermal growth factor receptor (EGFR), HER2 and HER3. The cohorts (baskets) included in the study are (1) bladder/urinary tract cancer; (2) breast cancer; (3) colorectal cancer; (4) endometrial cancer; (5) gastric/esophageal cancer; (6) ovarian cancer; (7) all other solid tumors with a HER2 mutation; (8) EGFR mutated and/or amplified primary brain cancer; and (9) solid tumors with a HER3 mutation. The non-small cell lung cancer (NSCLC) patients initially entered the study in the "other solid tumors with a HER2 mutation" basket and due to the preliminary activity seen in the trial the Company has expanded the basket, as per the protocol for the trial. The expanded HER2 mutant NSCLC basket will now enroll a total of 18 patients.

Last year at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2014 Congress, Puma presented initial data from the Phase II clinical trial of PB272 (neratinib) for the treatment of patients with NSCLC with somatic HER2 mutations. The efficacy results from the trial showed that for the 13 patients in the trial who received neratinib monotherapy, no patient experienced a partial response, 7 (54%) patients achieved stable disease and 4 (31%) patients achieved clinical benefit (defined as a partial response or stable disease for 12 or more weeks). In addition, the median progression free survival of the neratinib monotherapy arm was 2.9 months. In that study, the majority of the patients had the YVMA exon 20 mutation and there was less representation from other HER2 mutations. In the patients with NSCLC who have been treated in the basket study thus far, a much more diverse and a broader representation of HER2 mutations has been seen. The Company believes that although it is early and difficult to draw definitive conclusions, it appears that neratinib may be more selectively active in some HER2 mutated NSCLC tumors compared to others, which may account for the difference in activity being seen in the HER2 mutated NSCLC patients treated in the basket trial compared to those treated in the prior trial. The Company will continue to monitor this activity as the trial progresses.

"We are pleased to expand the second cohort in the basket trial. Although it is early, we are pleased with the initial activity that we are seeing in the patients with HER2 mutated non-small cell lung cancer in the trial," said Alan H. Auerbach, Chief Executive Officer and President of Puma. "We look forward to continuing enrollment into this initially expanded cohort and we look forward to expanding additional cohorts from the basket trial, which we anticipate being able to do later this year."

About Puma Biotechnology

Puma Biotechnology, Inc. is a development stage biopharmaceutical company that acquires and develops innovative products for the treatment of various forms of cancer. The Company focuses on in-licensing drug candidates that are undergoing or have already completed initial clinical testing for the treatment of cancer and then seeks to further develop those drug candidates for commercial use. The Company is initially focused on the development of PB272 (oral neratinib), a potent irreversible tyrosine kinase inhibitor, for the treatment of patients with HER2-positive breast cancer and patients with non-small cell lung cancer, breast cancer and other solid tumors that have a HER2 mutation.

8-K – Current report

On February 19, 2015 Kite Pharma reported that it has entered into a lease agreement for a commercial manufacturing facility in El Segundo, California, which is adjacent to Los Angeles International Airport (Filing 8-K , Kite Pharma, FEB 19, 2015, View Source [SID:1234501710]). Kite also recently secured a lease for a clinical manufacturing facility in Santa Monica, California. The two facilities will not only support the planned clinical trials of Kite’s product candidates, but also will prepare Kite for the commercial launch and supply of its lead product candidate, KTE-C19, anticipated in 2017.

“We are committed to the rapid advancement of KTE-C19, which has the potential to address the significant, unmet needs of patients with aggressive, refractory B cell lymphomas and leukemias,” said Arie Belldegrun, M.D., FACS, Kite Pharma’s President and Chief Executive Officer. “We are initiating pivotal studies for KTE-C19 in multiple indications and believe our new facilities will help ensure the timely completion of these studies as well as our commercial launch. We also expect the facilities to support clinical trials and potential commercialization of our other eACT based product candidates, including both chimeric antigen receptor (CAR) and T cell receptor (TCR) based product candidates.”

The Santa Monica facility has approximately 18,000 square feet and will provide space for clinical manufacturing, research and development, and offices upon completion. In addition, Kite plans to continue to utilize its contract manufacturer to support clinical trials of eACT based product candidates.

The El Segundo facility has approximately 44,500 square feet, and, under the lease agreement, Kite has an expansion option for an additional 17,000 square feet until July 1, 2017. Kite was represented in the negotiation of the lease by Andrew Riley and Jeff Pion of CBRE. Kite anticipates the El Segundo facility will be operational to support the planned commercial launch of KTE-C19 in 2017.

Commenting on the new leases, Cynthia Butitta, Kite’s Chief Operating Officer and Chief Financial Officer, said, “Securing these manufacturing facilities fits strategically with our expansion and is an exciting and necessary step as we advance multiple clinical trials and prepare for commercialization of our product candidates.”

8-K – Current report

On December 31, 2014, Kite Pharma entered into a Research Collaboration and License Agreement (the “Agreement”) with Amgen pursuant to which Kite and Amgen expect to develop and commercialize chimeric antigen receptor (“CAR”) T cell immunotherapies based on Kite’s engineered autologous cell therapy (eACT) platform and a number of Amgen cancer targets (Filing 8-K , Kite Pharma, JAN 5, 2015, View Source [SID:1234501272]).

Under the terms of the Agreement, Kite and Amgen will jointly create preclinical development plans through investigational new drug application (“IND”) filing with the U.S. Food and Drug Administration for the research and development of CAR-based product candidates that target certain antigens (each, a “target”) expressed on the cell surface of various cancers. Kite and Amgen expect to progress multiple Amgen programs (“Amgen Programs”), each consisting of the development of one or more CAR-based product candidates directed against a certain Amgen selected target. Kite and Amgen also expect to progress multiple Kite programs (“Kite Programs”), each consisting of the development of one or more CAR-based product candidates directed against a certain Kite selected target. Under certain circumstances, the collaboration may be expanded to include the research and development of other product candidates.

Amgen will fund the research and development costs for all programs with certain limitations through any IND filing. Kite will reimburse Amgen for the research and development costs for any Kite Program that progresses to an IND filing. Each company will then be responsible for clinical development and commercialization of their respective CAR therapeutic candidates, including all related expenses. Kite will be responsible for the manufacturing and processing of Amgen Program product candidates for a certain period following the completion of Phase 2 clinical trials.

Amgen will pay Kite $60.0 million as an upfront payment pursuant to the Agreement. Kite will be eligible to receive up to $525.0 million in milestone payments for each Amgen Program based on the successful completion of regulatory and commercialization milestones, plus tiered high single to double digit royalties for sales and the license of Kite’s intellectual property for CAR T cell products. Amgen will be eligible to receive up to $525.0 million in regulatory and commercial milestone payments per Kite Program plus tiered single digit sales royalties.

The term of this Agreement will continue on a target-by-target basis until the later of (i) the date on which the product candidates directed against the target are no longer covered by certain intellectual property rights, (ii) the loss of certain regulatory exclusivity and (iii) a defined term from the first commercial sale of the first product candidate directed against the target. Either Kite or Amgen may terminate the Agreement on a target-by-target basis for their respective programs with prior written notice. Either party may also terminate the agreement with written notice upon material breach by the other party, if such breach has not been cured within a defined period of receiving such notice.

The Agreement is subject to customary anti-trust clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended.

The foregoing description of the Agreement is only a summary and is qualified in its entirety by reference to the Agreement. Kite intends to file a copy of the Agreement as an exhibit to its Annual Report on Form 10-K for its fiscal year ending December 31, 2014, portions of which will be subject to a FOIA Confidential Treatment Request to the Securities and Exchange Commission pursuant to Rule 24b-2 under the Securities Exchange Act of 1934, as amended, for certain portions of the Agreement. The omitted material will be included in the request for confidential treatment.

8-K – Current report

On December 30, 2014 OncoGenex Pharmaceuticals reported that it has executed an initial agreement with Teva Pharmaceutical Industries to regain rights to custirsen, an investigational compound currently being evaluated in Phase 3 clinical development as a treatment for prostate and lung cancers (Filing 8-K , OncoGenex Pharmaceuticals, DEC 30, 2014, View Source [SID:1234501256]). This transfer of rights would occur in connection with the termination of the collaboration agreement between OncoGenex and Teva executed in 2009.

The initial agreement reached by OncoGenex and Teva provides that, following execution of the final agreement to terminate the collaboration between the parties, OncoGenex will receive a $27 million payment from Teva, subject to certain adjustments. In addition, OncoGenex will take over responsibility for all custirsen related expenses, including those related to the ENSPIRIT trial, as well as manufacturing and regulatory activities for custirsen programs, which are currently being managed by Teva. OncoGenex expects that the $27 million payment from Teva will allow for the completion and final results from the AFFINITY trial, as well as continuation of the ENSPIRIT trial through the second interim futility analysis expected in the first half of 2015.

“Teva’s strategic focus has shifted away from oncology research and development. However, OncoGenex remains committed to the continued investigation of custirsen, particularly in patients who have advancing disease despite previous treatments,” said Scott Cormack, President and CEO of OncoGenex. “This agreement provides OncoGenex with greater control of custirsen’s development, including the modification of the ENSPIRIT statistical analysis plan to involve a more rigorous second interim futility analysis to be completed in the second quarter of 2015 that, if passed, would enable the trial to continue with a smaller enrollment requirement, increased confidence in success and shorter time to regulatory submission.”

The Company expects that the $27 million payment from Teva and the Company’s current resources should enable the completion of the AFFINITY trial through data readout in late 2015/early 2016, allow for the continuation of the ENSPIRIT trial through the second interim futility analysis that is expected in the first half of 2015 and the achievement of key apatorsen clinical milestones, such as the completion of patient enrollment in the Borealis-2 trial and final data from the Spruce and Rainier clinical trials.

The Company anticipates a final agreement will be executed in January 2015. Additional terms of the initial agreement with Teva can be found in the Company’s Form 8-K filed today and available at View Source

8-K – Current report

On December 15, 2014 Sorrento Therapeutics reported that it has entered into a binding agreement with NantWorks founder, physician scientist, and biotechnology entrepreneur Dr. Patrick Soon-Shiong (Filing 8-K , Sorrento Therapeutics, DEC 15, 2014, View Source [SID:1234501189]).

Under the terms of the agreement, NantWorks and Sorrento will establish a global strategic collaboration to jointly develop next generation immunotherapies for the treatment of cancer and auto-immune diseases. NantWorks, through a subsidiary, and Sorrento intend to establish the first joint venture – “The Immunotherapy Antibody JV” – as an independent biotechnology company with $20 million initial joint funding. As part of a strategic investment, Dr. Soon-Shiong’s affiliated entity will acquire a 19.9% equity stake in Sorrento by purchasing common stock priced at $5.80 per share, Sorrento’s closing sale price on Friday, December 12, 2014. In addition, Sorrento granted the purchaser a 3-year warrant to purchase 1,724,138 shares of common stock at an exercise price of $5.80 per share.

The Immunotherapy Antibody JV will focus on accelerating the development of multiple immuno-oncology monoclonal antibodies (mAbs) for the treatment of cancer, including but not limited to anti-PD-1, anti-PD-L1, anti-CTLA4 mAbs, and other immune-check point antibodies as well as antibody drug conjugates (ADCs) and bispecific antibodies. The immuno-oncology field has emerged as the one of most exciting and fastest developing pharmaceutical market. Immunomodulatory antibodies help the cancer patient’s own immune system to fight the disease and are being developed for the treatment of a number of solid tumors. They have demonstrated therapeutic potential in difficult-to-treat cancers, such as metastatic melanoma and non-small cell lung cancer (NSCLC). A recent forecast by Citigroup predicts this market to become the biggest blockbuster drug class in history with potential sales of up to $35 billion a year over the next 10 years.

“We are extremely pleased to be working with Dr. Patrick-Soon Shiong and NantWorks. The investment into Sorrento and future formation of the JV with NantWorks further validate our G-MAB antibody technology and underscore Sorrento’s commitment to seeking strategic alliances in bringing its diverse portfolio of fully human monoclonal antibodies, ADCs, and bispecific antibodies into the clinic,” said Dr. Henry Ji, President and CEO of Sorrento. “Our innovative collaboration will unite Sorrento’s capability to develop complex biologics with NantWorks proprietary genomic and personalized medicine technologies. We share NantWorks’ enthusiasm for the potential of our JV to produce a pipeline of immuno-oncology products to address unmet needs of cancer treatment.”

“Combining NantWorks’ cutting edge expertise in genomic and molecular profiling of cancer patients and Sorrento’s industry-leading G-MAB antibody technology, we believe will enable us to develop multiple novel therapies for malignant disorders where there is currently a significant unmet need. Through this partnership, it is our goal to provide relief for millions of people who today have limited treatment options. This will be a model relationship aligned to accelerate development and production of novel cancer immunotherapies. We look forward to working closely with Sorrento’s team,” said Dr. Patrick Soon-Shiong, CEO and Founder of NantWorks.

8-K – Current report

On November 13, 2014 Puma Biotechnology reported top line results from a Phase II clinical trial of Puma’s investigational drug PB272 (neratinib) for the treatment of first-line HER2-positive locally recurrent or metastatic breast cancer (NEfERTT trial) (Filing 8-K , Puma Biotechnology, NOV 13, 2014, View Source [SID:1234500962]). The NEfERTT trial is a randomized, two-arm Phase II trial of neratinib plus the anticancer drug paclitaxel versus trastuzumab (Herceptin) plus paclitaxel as a first-line treatment for HER2- positive locally recurrent or metastatic breast cancer.

The NEfERTT trial enrolled 479 patients in 33 countries with locally recurrent or metastatic breast cancer who had not received prior anticancer therapy for locally recurrent or metastatic disease. Patients were randomized to receive first-line treatment with either paclitaxel plus neratinib or paclitaxel plus trastuzumab. The primary endpoint of the trial was progression free survival (PFS). The secondary endpoints of the study included objective response rate (ORR) and the incidence of central nervous system (CNS) metastases, including brain metastases.

The safety results of the study showed that the most frequently observed adverse event for the patients who received the combination of paclitaxel plus neratinib was diarrhea, with approximately 30% of the patients experiencing grade 3 diarrhea. The rate of grade 3 diarrhea in the patients who received the combination of paclitaxel plus trastuzumab was approximately 4%. Patients who received neratinib in this trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib related diarrhea. Puma’s recently reported clinical data from a Phase II trial of neratinib in HER2 mutated non-small cell lung cancer demonstrated that the use of high dose loperamide greatly reduces the rate of grade 3 diarrhea with neratinib. In that trial the grade 3 diarrhea rate was 8% in the patients who received neratinib monotherapy. In all of its current ongoing studies Puma is instituting the use of high dose loperamide in order to continue to reduce the neratinib related diarrhea.

The primary endpoint of the NEfERTT trial was progression free survival. The results of the trial demonstrated that the progression free survival for the patients who received the combination of paclitaxel plus neratinib was 16.6 months and the progression free survival for the patients who received the combination of paclitaxel plus trastuzumab was 16.7 months (p=0.35). The objective response rate in the trial for the patients who received the combination of paclitaxel plus neratinib was 74.8% and the objective response rate for the patients who received the combination of paclitaxel plus trastuzumab was 75.1% (p=0.94). These results did not demonstrate a statistically significant difference between the PFS and ORR results for the two treatment arms, which was consistent with expectations.

With respect to the incidence of central nervous system metastases (e.g., brain metastases), treatment with the combination of paclitaxel plus neratinib resulted in a 52.6% reduction in the incidence of CNS metastases compared to the incidence of CNS metastases in patients who received the combination of paclitaxel plus trastuzumab. The incidence of CNS metastases was 7.4% in the patients who received paclitaxel plus neratinib, while the incidence of CNS metastases in the patients who received the combination of paclitaxel plus trastuzumab was 15.6% (p=0.006). These results reflect a statistically significant difference between the two treatment arms.

Full results of the NEfERTT trial for PB272 will be presented at a future scientific meeting in 2015.

“We are very pleased with the results of the NEfERTT trial with neratinib,” said Alan H. Auerbach, Chief Executive Officer and President. “As expected, there was no statistically significant difference in progression free survival and objective response rate for the paclitaxel plus neratinib arm compared to the paclitaxel plus trastuzumab arm. However, the paclitaxel plus neratinib arm showed a statistically significant decrease in the incidence of CNS metastases compared to the paclitaxel plus trastuzumab arm. This represents the first randomized trial with a HER2 targeted agent that has shown a statistically significant reduction in the incidence of CNS metastases, which we believe provides a meaningful point of differentiation for neratinib in the treatment of HER2 positive breast cancer. While the development of other HER2 targeted drugs has produced a clinically meaningful benefit to patients with HER2 positive breast cancer, these drugs have had little impact on CNS metastases. As a result, we believe that there remains an unmet clinical need for reducing the incidence of CNS metastases and the results of the NEfERTT study demonstrate that we may be able to provide this type of improvement with neratinib.”

8-K – Current report

On November 11, 2014 Threshold Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for TH-302, an investigational anticancer drug, for the treatment of previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcoma (STS) (Filing 8-K , Threshold Pharmaceuticals, NOV 12, 2014, View Source [SID:1234500955]).

The FDA established the Fast Track designation process to facilitate the development and expedite the review of drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An important feature of Fast Track is that the FDA may consider a “rolling review” of completed sections of the New Drug Application (NDA) before the complete application is submitted.

“We are pleased that FDA has granted Fast Track status for TH-302 for the treatment of previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcoma,” said Barry Selick, Ph.D., Chief Executive Officer of Threshold. “Our ongoing Phase 3 trial of TH-302 in these patients is being conducted under a Special Protocol Assessment with the FDA. If successful, the Fast Track designation may provide an added benefit of facilitating the NDA review process. Currently, we anticipate the primary analysis of overall survival of the Phase 3 trial to be conducted in the first quarter of 2016.”

About the Phase 3 Trial

Threshold is conducting this international, randomized pivotal Phase 3 clinical trial in partnership with the Sarcoma Alliance for Research through Collaboration (SARC) and under a Special Protocol Assessment (SPA) agreement with the U.S. FDA. The trial is designed to investigate the efficacy and safety of TH-302 in combination with doxorubicin, compared with doxorubicin alone, in previously untreated patients with metastatic or locally advanced unresectable STS. The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival, overall response rate, pharmacokinetics and safety. Patients were randomized to either doxorubicin alone or to receive TH-302 300 mg/m2 administered intravenously on Days 1 and 8 with doxorubicin 75 mg/m2 on Day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302 according to the same dosing schedule, 300 mg/m2 Days 1 and 8 of each 21-day cycle. The trial enrolled a total of 640 patients across 81 study sites in Europe, Israel, North America and the Russian Federation.

8-K – Current report

On May 19, 2014 Sophiris Bio reported it has entered into a common stock purchase agreement with Aspire Capital Fund. The Company intends to use the initial proceeds to support a proof of concept study of PRX302 as a treatment for localized prostate cancer (Filing 8-K , Sophiris Bio, MAY 19, 2014, View Source [SID:1234500532]). Aspire Capital has completed an initial purchase of 604,320 common shares at $3.31 per share for proceeds of $2 million and has committed to purchase up to $13 million in additional shares over the next 30 months at prices based on market price at the time of each sale, subject to a Sophiris registration statement being declared effective by the Securities and Exchange Commission (“SEC”).

“While we remain focused on our Phase 3 trial in benign prostatic hyperplasia (BPH), this financing provides us with additional financial flexibility and supports the advancement of PRX302 into another important, underserved indication. The highly targeted mechanism by which PRX302 selectively destroys prostate tissue in BPH also represents a promising treatment approach for localized prostate cancer,” said Randall E. Woods, president and chief executive officer. “The $2 million proceeds from this transaction will enable us to fund an investigator-sponsored proof of concept study in localized prostate cancer. The remaining $13 million available under the purchase agreement, if drawn down at the Company’s option, will be utilized to fund future development of PRX302 in BPH and localized prostate cancer as well as general corporate purposes.”

The Company will provide additional details around the design of the proof of concept study in localized prostate cancer upon the initiation of the study. Localized prostate cancer is a disease that is confined to the prostate gland and has not spread to the tissue and lymph nodes that surround the prostate gland or other parts of the body. PRX302 has been engineered to be activated by enzymatically active prostate specific antigen (PSA), which is found in the transition zone of the prostate as well as in prostate cancer cells. In the 126 patients studied in completed BPH clinical trials, PRX302 appears to be safe and well tolerated with no impact on erectile function.

Under the terms of the common stock purchase agreement, Sophiris will control the timing and amount of any sale of common shares to Aspire Capital. Aspire Capital has no right to require any sales by Sophiris but is obligated to make purchases as Sophiris directs, in accordance with the purchase agreement. There are no limitations on the use of proceeds, financial covenants or restrictions on future financings and there are no rights of first refusal, participation rights, penalties or liquidated damages in the purchase agreement. The purchase agreement may be terminated by Sophiris at any time, at its discretion, without any additional cost or penalty. Sophiris has issued 90,635 common shares to Aspire Capital as a commitment fee in connection with the execution of the purchase agreement. The common shares issued or to be issued under the purchase agreement will be registered for resale pursuant to a registration statement to be filed by Sophiris with the SEC. A complete and detailed description of the purchase agreement and related registration rights agreement is set forth in the Company’s Current Report on Form 8-K, filed today with the SEC.

8-K – Current report

On April 11, 2014, The Regents of the University of California (“UCLA”) filed a complaint against Medivation, Inc. and its subsidiary Medivation Prostate Therapeutics, Inc. (“MPT”) in the Superior Court of the State of California, County of San Francisco (Filing 8-K , Medivation, APR 14, 2014, View Source [SID:1234500414]). The complaint arises from the parties’ 2005 Exclusive License Agreement (“ELA”), which grants to MPT rights in certain UCLA patents, including the UCLA patents covering XTANDI. The complaint centers on two allegations. The first allegation is that Medivation and MPT have failed to pay UCLA ten percent of “Operating Profits” Medivation has received (and will continue to receive) from Astellas Pharma, Inc. as a result of the 2009 Collaboration Agreement between Medivation and Astellas. UCLA alleges that such Operating Profits are “Sublicensing Income” under the ELA and that UCLA is entitled to ten percent of such payments. The second allegation is that Medivation has breached its fiduciary duties to UCLA, as a minority shareholder of MPT. UCLA owns a fraction of one percent of the outstanding shares of MPT. The complaint seeks a declaration and judgment for breach of contract related to the allegation that “Operating Profits” payments received from Astellas are “Sublicensing Income” under the ELA, a judgment that Medivation has breached its fiduciary duties and an injunction requiring Medivation to comply with its fiduciary duties. The complaint does not seek termination of the ELA.

Medivation and MPT deny UCLA’s allegations and will vigorously defend the litigation.

8-K – Current report

On April 6, 2014 Agios Pharmaceuticals announced that data from its lead, first-in-class program AG-221 will be presented at a Clinical Trials Symposium titled “Novel Immune and Targeted Therapies for Hematological Malignancies and Solid Tumors” at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2014 (Filing 8K, Agios Pharmaceuticals, APR 7, 2014, View Source [SID:1234500369]). These preliminary data demonstrate the clinical activity, tolerability and unique mechanism of action of AG-221 in patients with advanced hematologic malignancies with an isocitrate dehydrogenase-2 (IDH2) mutation.
The preliminary data to be presented by Dr. Stein show that in the first two cohorts of the Phase 1 trial of AG-221 (NCT01915498), six of seven evaluable patients had objective responses, including three complete remissions (CR) and two complete remissions with incomplete platelet recovery (CRp). AG-221 also substantially lowered plasma levels of the oncometabolite 2-hydroxyglutarate (2HG) with a favorable exposure profile and good tolerability to date.
AG-221 is an orally available, selective, potent inhibitor of the mutated IDH2 protein. As of March 20, 2014, this ongoing Phase 1 dose-escalation study had enrolled 22 patients with acute myeloid leukemia (AML) or myelodysplastic syndrome, all of whose cancers harbored an IDH2 mutation. Patient cohorts received AG-221 administered at 30 mg twice a day, 50 mg twice a day, 75 mg twice a day or 100 mg once a day.

8-K – Current report

On March 2014 NewLink Genetics reported the continuation of the Phase 3 IMPRESS clinical study (NCT01544179) of algenpantucel-L for patients with surgically resected pancreatic cancer following the first of two planned interim data analyses (Filing 8K, NewLink Genetics, MAR 7, 2014, View Source [SID:1234500254]).
As part of the planned interim analysis, scheduled to occur following 222 patient events, the independent data safety monitoring committee (DSMC) met to review available patient data. Following their review, the DSMC recommended that the study should proceed as planned, without modification. A second interim analysis is planned upon reaching 333 patient events and, if needed, a final analysis is planned at 444 patient events.

8-K – Current report

Orphan Drug Status
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Radio/chemotherapy-induced peripheral neuropathy
USA (2014); KRN5500 for the parenteral treatment of painful, chronic, chemotherapy-induced peripheral neuropathy that is refractory to conventional analgesics (US FDA, FEB 21, 2014, View Source & Filing 8K , Dara Biosciences, FEB 25, 2014, View Source [SID:1234500151]).