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Cerulean Announces Results from Phase 2 Clinical Trial of CRLX101 and Avastin® Combination in Relapsed Renal Cell Carcinoma

On August17, 2016 Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), reported top-line results from the Company’s Phase 2, randomized, multi-center clinical trial of its lead candidate, CRLX101, in combination with Avastin (bevacizumab) in the treatment of patients with advanced renal cell carcinoma (RCC) (Press release, Cerulean Pharma, AUG 17, 2016, View Source [SID1234514632]).

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The trial was conducted at 43 sites in the US and South Korea, and enrolled 115 patients with RCC who progressed through two or three prior lines of therapy. Patients were randomized to receive CRLX101 in combination with Avastin or investigator’s choice standard of care (SOC) therapy. SOC agents included axitinib, bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. The primary endpoint was progression free survival (PFS) in the clear cell population (n=102) assessed by independent radiological review. Secondary endpoints included overall response rate, duration of response and overall survival.

The study demonstrated no statistically significant difference in median PFS and objective response rate for the CRLX101 combination compared to SOC. Median PFS was 3.7 months for the CRLX101 combination compared with a median PFS of 3.9 months for SOC (hazard ratio: 1.25, p=0.822). The 95% confidence interval for PFS for the CRLX101 combination was 2.0 months to 4.3 months and for SOC was 2.2 months to 5.4 months. Objective response rate by independent radiological review for patients who received the CRLX101 combination was 5% (2/42) compared to 14% (6/43) for SOC (p=0.836). The CRLX101 and Avastin combination appeared to be safe and well-tolerated and the safety and tolerability profile of the combination was consistent with that observed in previous studies. The full data set from the trial are expected to be submitted for presentation at an upcoming medical conference.

"We are disappointed with this outcome and will undertake a thorough analysis of the data to understand why CRLX101 plus Avastin underperformed compared to the results we saw in an earlier investigator-sponsored trial," said Christopher D. T. Guiffre, President and Chief Executive Officer of Cerulean. "This outcome did not support our hypothesis that targeting hypoxia inducible factor (HIF) in combination with VEGF inhibitor in RCC, a HIF-overexpressing tumor type, would be beneficial, so we will not pursue HIF as a target going forward. We will continue to focus on the potent topoisomerase 1 inhibition of CRLX101’s payload, camptothecin, in topoisomerase 1-sensitive tumors. Our combinations with weekly paclitaxel and LYNPARZA (olaparib) are examples of ongoing trials that leverage CRLX101’s topoisomerase 1 inhibition in combination with chemotherapies and DNA damage repair agents."

Conference Call Details

Cerulean will host a conference call today at 4:30 pm Eastern Daylight Time to discuss the results and provide an update on the CRLX101 development program. The call can be accessed by dialing (844) 831-3031 or (443) 637-1284 prior to the start of the call and referencing conference ID: 67807137. The conference call will also be webcast live over the Internet and can be accessed on the "Investors" section of the Cerulean website, www.ceruleanrx.com. The webcast will be available on Cerulean’s website for two weeks.

About CRLX101

CRLX101 is a nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication. CRLX101 has shown activity in multiple tumor types, both as monotherapy and in combination with other cancer treatments. CRLX101 is in Phase 2 clinical development and has been dosed in more than 400 patients. The U.S. FDA has granted CRLX101 Orphan Drug designation for the treatment of ovarian cancer, Fast Track designation in combination with paclitaxel for platinum-resistant ovarian carcinoma, fallopian tube or primary peritoneal cancer, and Fast Track designation in combination with Avastin in metastatic renal cell carcinoma.

Inspyr Therapeutics Announces the Initiation of a Phase 2 Clinical Trial of Mipsagargin for Newly Diagnosed Prostate Cancer Patients

On August 17, 2016 Inspyr Therapeutics, Inc. (OTCQB: NSPX), a biotech company developing a novel prodrug therapeutic for the treatment of cancer, today reported that the first patient has been treated in a Phase 2 investigator-sponsored clinical trial to evaluate the safety and activity of mipsagargin in patients newly diagnosed with prostate cancer (Press release, Inspyr Therapeutics, AUG 17, 2016, View Source [SID:1234514631]). The trial is being conducted at The University of Texas Health Science Center (UTHealth) at Houston with Robert Amato, D.O., Professor and Director, University of Texas/Memorial Hermann Cancer Centers, as principal investigator. Mipsagargin is a first-in-class agent with a novel mechanism of action that targets prostate-specific membrane antigen (PSMA), a highly expressed enzyme on the surface of prostate cancer cells.

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The open-label, single-arm Phase 2 clinical trial will enroll patients with treatment-naïve prostate cancer prior to surgical removal of the tumor. Patients in the trial will be administered mipsagargin by intravenous infusion on the first three consecutive days of a 28-day cycle, over a total of three cycles. The trial will evaluate the effect of mipsagargin on the perfusion and volume of the prostate. Inspyr expects top-line results in mid 2017.

"Mipsagargin presents a novel tumor-targeting approach to treating patients newly diagnosed with prostate cancer," said Dr. Amato. "My colleagues at UTHealth are focused on improving treatment options for prostate cancer patients, and we look forward to evaluating mipsagargin’s effectiveness in disrupting the blood supply of prostate tumors and killing prostate cancer cells, which could lead to tumor regression and potentially improved survival rates for patients diagnosed with this type of cancer."

"Dr. Amato and his colleagues at UTHealth have identified a potentially novel application of mipsagargin for prostate cancer patients, and we look to continuing our collaboration," said Chris Lowe, Inspyr’s President and Chief Executive Officer. "We believe mipsagargin’s unique mechanism of action delivers a potent therapy to the tumor site while maintaining an attractive safety profile. We look forward to reviewing the results from this study."

About the University of Texas Health Science Center at Houston

Established in 1972 by The University of Texas System Board of Regents, the University of Texas Health Science Center at Houston (UTHealth) is Houston’s Health University and Texas’ resource for health care education, innovation, scientific discovery and excellence in patient care. The most comprehensive academic health center in The University of Texas System and the U.S. Gulf Coast region, UTHealth is home to schools of biomedical informatics, biomedical sciences, dentistry, medicine, nursing and public health and includes The University of Texas Harris County Psychiatric Center and a growing network of clinics throughout the region. For more information, visit www.uth.edu.

Genmab Announces Submission of Supplemental Biologics License Application to FDA for Daratumumab in Relapsed Multiple Myeloma

On August 17, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its licensing partner, Janssen Biotech, Inc. has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for the use of daratumumab (DARZALEX) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who received at least one prior therapy (Press release, Genmab, AUG 17, 2016, View Source [SID:1234514628]).

In July 2016, daratumumab was granted a Breakthrough Therapy Designation (BTD) in this patient population. The submission of the application triggers milestone payments totaling USD 15 million to Genmab from Janssen. The milestone payments were included in Genmab’s financial guidance for 2016 that was published on August 9, 2016. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"We are thrilled that an application to expand the current label to include treatment of multiple myeloma patients who received at least one prior therapy has been submitted so soon after the initial FDA approval of daratumumab in November 2015. The data from the Phase III CASTOR and POLLUX studies on which the submission is based was unprecedented, meriting a Breakthrough Therapy Designation from the FDA. We believe that if approved, daratumumab has the potential to make a substantial positive impact in the treatment of patients with multiple myeloma who have relapsed on their previous therapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

A request for Priority Review has been submitted by Janssen with this sBLA. The FDA will inform Janssen whether a Priority Review has been granted by calendar day 60 of their review starting today. If the FDA grants Priority Review, the review should be completed within 6 months from today.

The submission includes data from two Phase III studies: the CASTOR study of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma, and the POLLUX study of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma. The submission also included data from the Phase I study of daratumumab in combination with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma. These data will also be used as the basis for a potential regulatory submission to the European Medicines Agency (EMA).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,7,8 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,7,8 antibody-dependent cellular phagocytosis9,10 and antibody-dependent cellular cytotoxicity.7,8 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.7,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor.

Funding Includes Support of Clinical Development of Anti-CD47 Antibody Program in Multiple Cancer Immunotherapy Trials

On August 16, 2016 Tioma Therapeutics, Inc., a venture-stage biopharmaceutical company developing anti-CD47 antibodies for the treatment of solid and hematologic cancers, reported it has raised $86 million in Series A venture financing (Press release, Tioma Therapeutics, AUG 16, 2016, View Source [SID:1234514627]). Proceeds from this financing will be used to further develop Tioma’s antibody portfolio, including its lead drug candidate – an anti-CD47 immune checkpoint inhibitor – through advanced proof-of-concept in human clinical trials.

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The Series A financing was co-led by RiverVest Venture Partners (including 3×5 RiverVest Fund), Novo Ventures, Roche Venture Fund and S.R. One, Limited (the corporate venture capital arm of GlaxoSmithKline). Pursuant to this financing, John McKearn, PhD, of RiverVest Venture Partners, Peter Moldt, PhD, of Novo Ventures, Carole Nuechterlein of Roche Venture Fund and Jill Carroll of S.R. One will serve on the company’s board of directors, with Dr. McKearn serving as Chairman of the Board.

"We find CD47 to be an extremely interesting target in the evolving cancer immunotherapy landscape," said Peter Moldt, PhD, Partner at Novo Ventures. "We believe Tioma Therapeutics, with its portfolio of diverse, functionally heterogeneous antibodies, is well positioned to test the CD47 hypothesis in the clinic."

The company also announced today that John Donovan will lead the Tioma executive management team as President, Chief Executive Officer and member of the board of directors. John has more than two decades of industry experience, first as an investment banker and then as a member of senior leadership within several biotechnology companies. Most recently, he was a co-founder of Alios BioPharma and served as its Chief Business Officer and Chief Financial Officer through its acquisition by Johnson & Johnson.

"We are delighted to have John’s strong leadership skills, extensive corporate strategy experience and financial expertise to guide Tioma’s management team during this new phase of the company’s development," commented John McKearn, PhD, Managing Partner, RiverVest Venture Partners.

"We’re pleased by the degree of investor interest in this financing and thrilled to have enabled the robust advancement of our therapeutic antibodies well into clinical development," stated John Donovan, President and Chief Executive Officer of Tioma Therapeutics. "We’re particularly excited by the prospect of using these compounds in combination with other therapeutic agents, such as PD-L1/PD-1 inhibitors. We believe we have the ability to meaningfully improve outcomes for patients suffering from a variety of debilitating cancers."

About Immunotherapy and CD47

There are two distinct but interdependent arms of the immune system that work in concert to recognize cancer cells and destroy them. Both the innate and adaptive immune responses are capable of recognizing and destroying cancer cells but tumors evolve mechanisms to evade them.

Immunotherapy is intended to "wake" the immune system so that it can recognize and destroy cancer cells. Currently approved immuno-oncology therapies have been effective in a subset of patients despite harnessing only the adaptive immune response. Anti-CD47 antibodies have the potential to promote coordination by the innate and adaptive immune systems with both acting in concert to attack tumors.

TRILLIUM THERAPEUTICS RECEIVES FDA CLEARANCE TO PROCEED WITH TTI-621 IN CLINICAL TRIAL TARGETING SOLID TUMORS AND MYCOSIS FUNGOIDES

On August 17, 2016 Trillium Therapeutics Inc. (NASDAQ: TRIL; TSX: TR), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that the US Food and Drug Administration (FDA) has provided the company clearance to initiate a Phase 1 clinical trial of its lead drug candidate, TTI- 621 (SIRPaFc), in solid tumors and mycosis fungoides (Press release, Trillium Therapeutics, AUG 17, 2016, View Source [SID:1234514625]). Patient enrollment is anticipated to commence by the end of the year. Trillium is developing TTI-621 as a novel checkpoint inhibitor of the innate immune system, and the drug is currently being evaluated in an ongoing Phase 1 dose escalation study in patients with relapsed or refractory hematologic malignancies.

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"The FDA’s acceptance of this IND application is another important milestone for our company, as the study of TTI-621 in select tumor types could lead to a more thorough understanding of its mechanism of action, and may bring us one step closer to a much needed treatment option for patients," said Dr. Niclas Stiernholm, chief executive officer of Trillium Therapeutics. "We seek to gain insight into the tumor micro-environment before, during and after treatment with TTI- 621. This will help us learn how to best use TTI-621 CD47 blockade in combination with other anti-cancer drugs and better design the commercial development path for this agent."

In the multicenter, open-label, Phase 1 trial, TTI-621 will be delivered by intratumoral injection in patients with relapsed and refractory, percutaneously-accessible cancers. Patients will be enrolled in sequential dose cohorts to receive intratumoral injections of TTI-621 that increase in dose and dosing frequency to characterize safety, pharmacokinetics, pharmacodynamics and preliminary evidence of antitumor activity. In addition, detailed evaluation of serial, on-treatment tumor biopsies of both injected and non-injected cancer lesions will help characterize tumor microenvironment changes anticipated with CD47 blockade.