On November 7, 2016 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the Company and its research collaborators have presented data at two scientific conferences hosted by the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, DelMar Pharmaceuticals, NOV 7, 2016, View Source [SID1234516371]).

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AACR DNA Repair: Tumor Development & Therapeutic Response Conference. On Friday, November 4, 2016, DelMar and its collaborators from the University of British Columbia Prostate Cancer Research Center presented an abstract entitled: "Dissecting the Molecular Mechanism of Dianhydrogalactitol (VAL-083) in Cancer Treatment."
AACR New Horizons in Cancer Research: Delivering Cures through Cancer Research. Also, on Friday, November 4, 2016, DelMar and its collaborators from the University of Texas MD Anderson Cancer Center and the University of British Columbia presented an abstract entitled: "Assessment of dianhydrogalactitol in the treatment of relapsed or refractory non-small cell lung cancer."
The presentations can be accessed on DelMar’s website at View Source

Jeffrey Bacha, DelMar’s chairman & CEO, stated, "We continue to make great strides in understanding how VAL-083 targets cancer cells."

The data demonstrate that, upon treatment, VAL-083 rapidly forms cross-links on the DNA of cancer cells leading to cell cycle arrest in the S/G2 phase and lethal double-strand DNA breaks. This mechanism is distinct from other alkylating agents used in the treatment of cancer such as temozolomide, nitrosoureas or platinum-based chemotherapy. Because VAL-083’s mechanism differs from the others it is not subject to the same resistance mechanisms and therefore may be used to treat patients whose tumors are resistant to other therapies.

"We are leveraging clinical validation from prior NCI-sponsored research with a modern understanding of VAL-083’s unique anti-cancer mechanism to diversify our product development portfolio into new indications such as lung and ovarian cancer," added Mr. Bacha.

About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments.

VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer.

The Company has completed a successful end of Phase II meeting with the US FDA and plans to advance VAL-083 into a pivotal clinical trial for GBM patients following bevacizumab failure. DelMar presented data from its Phase I/II clinical trial in refractory GBM at the 2016 American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting demonstrating that the median survival of 22 patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months following bevacizumab (Avastin) failure compared to published literature where survival of approximately two to five months has been reported.

DelMar’s advanced development program will feature a single multi-center randomized Phase III study measuring survival outcomes compared to a "physicians’ choice" control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in the treatment of Avastin-failed GBM. The final pivotal trial design will be confirmed with the FDA following further discussions with the Company’s clinical advisors.

In addition to the pivotal trial, DelMar also plans to initiate two separate Phase II clinical trials in earlier-stage GBM patients.

In collaboration with the University of Texas MD Anderson Cancer Center: A non-comparative, biomarker-driven, Phase II study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 or CCNU improves overall survival at 9 months, compared to historical control in bevacizumab naïve patients. (clinicaltrials.gov identifier: NCT02717962)
In collaboration with Sun-Yat Sen University and Guangxi Wuzhou Pharmaceutical (Group) Co.: A single arm Phase II clinical trial to confirm the tolerability of DelMar’s dosing regimen in combination with radiotherapy (XRT) and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high levels of MGMT.
DelMar believes that data from these clinical trials, if successful, will form the basis of a new paradigm in the treatment for all GBM patients who fail, or whose tumors exhibit features that make them unlikely to respond to currently available chemotherapy.

In addition to its clinical research in GBM, DelMar believes that its research supports a unique mechanism of action for VAL-083 and that these data support the potential of VAL-083 as a new chemotherapy that may offer improved outcomes in the treatment of GBM and other solid tumors in patients whose tumors have failed or exhibit features that make them resistant to or unlikely to respond to current standard-of-care chemotherapy.

The company and its collaborators from the University of Texas MD Anderson Cancer Center recently presented data at the 11th Biennial Ovarian Cancer Research Symposium demonstrating that VAL-083 was able to overcome cisplatin-resistance in ovarian cancer cell lines with known p53 mutations and displays synergy with both cisplatin and AstraZeneca’s PARP inhibitor Olaparib against ovarian cancer in vitro.

On November 7, 2016 Caladrius Biosciences, Inc. (NASDAQ:CLBS) ("Caladrius" or the "Company"), a cell therapy company combining an industry-leading development and manufacturing services provider through its subsidiary PCT, LLC a Caladrius Company ("PCT") with a select therapeutic development pipeline, reported financial results for the three and nine months ended September 30, 2016 (Filing, Q3, Caladrius Biosciences, 2016, NOV 7, 2016, View Source [SID1234516370]).
Business and financial highlights for the third quarter of 2016 and recent weeks include:
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Achieved total quarterly revenues of $9.3 million, up 58% compared with $5.9 million for the third quarter of 2015;
•
Received Fast Track designation from the U.S. Food and Drug Administration (FDA) for CLBS03 (autologous expanded regulatory T cells, or Tregs) for the treatment of type 1 diabetes (T1D), making it the first known therapeutic candidate for the treatment of T1D to receive the designation;
•
Completed enrollment of the first patient cohort of The Sanford Project: T-Rex Study, the Company’s Phase 2 clinical trial of CLBS03 for the treatment of recent-onset T1D in adolescents;
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Received a favorable recommendation from the independent Data Safety Monitoring Board (DSMB) to proceed with enrollment of the second cohort of the T-Rex Study following the safety evaluation of the first cohort of 19 patients;
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Entered into a new five-year strategic manufacturing services agreement under which PCT will produce SPEAR T-cell therapies for Adaptimmune Therapeutics plc; and
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Entered into agreements with several accredited investors, including previous investors and strategic collaborator Sanford Health, to sell up to $25 million in common equity priced at market without warrants.
Management Commentary
"Throughout 2016, we consistently increased revenues at our PCT subsidiary and are poised to achieve our stated goal of 2016 annual revenue in excess of $30 million, which represents annual growth of more than 30%. In addition, year-to-date we secured over $50 million in strategic and/or committed financings, about half of which was non-dilutive with the remainder under favorable terms relative to the market rates for companies like ours. We also paid back to our lender over $9 million of long-term debt, significantly reduced our operating expenses and monetized non-core assets, all while advancing our key immune modulation program’s Phase 2 clinical study of CLBS03 to treat T1D," stated David J. Mazzo, Ph.D., Chief Executive Officer of Caladrius.
"We are particularly pleased with the progress of The Sanford Project: T-Rex Study in T1D. We completed enrollment of the first cohort of 19 patients and were delighted that the DSMB recommended continuation of the study based on a favorable safety assessment. We have begun enrolling patients into the second cohort of this 111-patient study earlier than originally expected and plan to reach the 50% enrollment mark in mid-2017. Enrollment of the 70th patient, which triggers an $8.4 million capital infusion under the terms of the September private placements, is expected to occur shortly thereafter. We continue to benefit from the support of Sanford Research. In addition to their equity investment, Sanford has agreed to extend operational support at their clinical sites for the remainder of the study. We continue to be excited by the promise of CLBS03, a novel therapeutic being developed to address the significant unmet medical need in this chronic disease that affects children and young adults. We have made significant achievements across a number of key areas that we believe position Caladrius for continued growth and success throughout the balance of 2016 and beyond," concluded Dr. Mazzo.
Third Quarter Financial Highlights
Total revenues for the third quarter of 2016 increased 58% to $9.3 million compared with $5.9 million for the third quarter of 2015 and increased 12% compared with $8.3 million for the second quarter of 2016. Gross margin on revenues was 8% in the third quarter of 2016 compared with 18% in the third quarter of 2015, directly impacted by the non-payment of approximately $600,000 in billings for work the Company performed and billed to a single customer during the third quarter of 2016, which customer is currently experiencing financial difficulties. Accordingly, the Company has delayed revenue recognition until such time as payment is reasonably assured. The Company continues to work with this client to obtain payment and will recognize any such receipts as revenue in the periods received.

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Research and development (R&D) expenses for the third quarter of 2016 decreased 58% to $2.6 million compared with $6.3 million for the third quarter of 2015. The majority of current quarter expenses were dedicated to the Company’s immune modulation platform and, specifically, costs related to the T-Rex Study. The decline in R&D expenses over the prior year quarter was primarily related to the discontinuation of non-core R&D programs announced at the beginning of 2016 and related reductions in R&D staffing and departmental costs.
Selling, general and administrative (SG&A) expenses for the three months ended September 30, 2016 were $4.9 million, a small reduction from $5.1 million reported for the same period in 2015. This reflected significantly lower operational and compensation-related costs during the current year quarter compared with the prior year quarter, partially offset by higher equity-based compensation expenses compared with the prior year quarter.
The operating loss for the third quarter of 2016 was $6.9 million compared with an operating loss of $10.4 million for the third quarter of 2015, reflecting higher revenues and lower R&D expenses.
The Company reported a net loss attributable to Caladrius common stockholders for the third quarter of 2016 of $6.9 million, or $1.09 per share, compared with a net loss attributable to Caladrius common stockholders for the third quarter of 2015 of $11.4 million, or $2.06 per share.
Nine Month Financial Highlights
Total revenues for the nine months ended September 30, 2016 increased 68% to $25.1 million compared with $14.9 million for the first nine months of 2015. Gross margin for the first nine months of 2016 was 13% compared with 6% for the first nine months of 2015.
R&D expenses for the first nine months of 2016 decreased to $12.5 million compared with $20.7 million for the first nine months of 2015. The decline in R&D expenses over the first nine months of 2015 was primarily related to the discontinuation of non-core R&D programs announced at the beginning of 2016 and related reductions in R&D staffing and departmental costs.
SG&A expenses decreased to $16.1 million for the first nine months of 2016 compared with $25.0 million for the same period in 2015. This reflected operational and compensation-related cost reductions, as well as equity-based compensation expenses that were significantly below the prior year SG&A expense levels.
The operating loss for the first nine months of 2016 was $25.4 million compared with an operating loss of $54.1 million for the first nine months of 2015.
The net loss attributable to Caladrius common stockholders for the nine months ended September 30, 2016 was $26.7 million, or $4.45 per share, compared with a net loss attributable to Caladrius common stockholders for the nine months ended September 30, 2015 of $47.7 million, or $10.40 per share.
Balance Sheet and Cash Flow Highlights
As of September 30, 2016, Caladrius had cash and cash equivalents of $18.6 million, which included $10.6 million received from the previously announced equity financing in September 2016 and the payment of $3.0 million to Oxford Finance LLC for repayment of long-term debt. Net cash used in operating activities for the nine months ended September 30, 2016 was $20.3 million, compared with $30.5 million for the nine months ended September 30, 2015. Caladrius also invested $2.3 million in capital expenditures, primarily related to improvements to PCT’s Allendale, N.J. manufacturing facility.
2016 Financial Guidance
The Company updates its previous 2016 guidance as follows:
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Consolidated 2016 Annual Revenues: affirms guidance to exceed $30 million or a greater than 30% increase compared with 2015.
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Capital Improvements at PCT’s Allendale, N.J. Facility: affirms guidance that improvements will be completed in 2017, and updates guidance that approximately $2 million will be spent in calendar 2016. Overall cost to complete capital improvements in 2017, including the implementation of commercial grade quality systems, to be provided when 2017 guidance is announced.
•
CLBS03 Phase 2 Study Costs in 2016: affirms guidance of $6 million to $7 million.
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Consolidated 2016 Operating Activities Cash Burn: affirms guidance of $25 million to $28 million, or between $5 million and $8 million in the fourth quarter of 2016, but with a trend toward the lower end of the range.

On November 7, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI), reported financial results for the third quarter ended September 30, 2016 and provided an update on the Company’s clinical development activities (Press release, ChemoCentryx, NOV 7, 2016, View Source [SID1234516363]).

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"We have made significant progress in our orphan and rare diseases portfolio — building upon our positive Phase II results in the CLEAR and CLASSIC trials in ANCA vasculitis earlier this year, we have also reported positive results in the aHUS pilot Phase II study, as well as improvement of renal function in a C3G patient who had few, if any, other treatment options. All of this provides mounting evidence that avacopan has the potential to change treatment paradigms in these rare and debilitating diseases," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "With avacopan in AAV, we continue to make progress regarding our regulatory discussions and remain on track to initiate our Phase III development program by the end of this year. Our scientific approach forms the foundation of a broad pipeline of promising chemoattractant-based drug candidates which we believe will transform patient care."

Pipeline Developments Across Key Therapeutic Areas

Orphan and Rare Diseases: Avacopan, an orally-administered complement inhibitor targeting the C5a receptor (C5aR), is the cornerstone of an orphan and rare diseases portfolio addressing multiple unmet medical needs. These diseases include ANCA vasculitis (AAV), atypical Hemolytic Uremic Syndrome (aHUS) and Complement 3 Glomerulopathy (C3G). Avacopan acts by blocking the destructive action of neutrophils that are activated as a consequence of the complement protein known as C5a binding to C5aR on neutrophils during autoimmune inflammatory events including the destruction of blood vessels in AAV.

Announced positive data from a pilot Phase II study designed to assess the effects of orally-administered avacopan on thrombus formation from the serum of aHUS patients with end-stage renal disease. The aHUS patients in the study are on stable chronic hemo-or peritoneal dialysis. Avacopan (30 mg) was administered twice daily for two weeks. Five patients have been treated to date. Highlights of the presentation that will take place at the American Society of Nephrology (ASN) Kidney Week 2016 include:
After 14 days of dosing the mean decrease in thrombus size was 83%. Three patients showed 100% inhibition of thrombus formation and one patient showed greater than 30% inhibition. Additionally, one patient who received only two days of avacopan treatment showed greater than 30% inhibition at that time;
Treatment appeared to be mechanism specific: when avacopan treatment was stopped, the thrombus size returned to pre-treatment levels; and
Avacopan treatment appeared to be safe; there was one serious adverse event, not considered related to avacopan use, in a patient with long-standing cardiovascular and renal disease of cardiac asystole.
Reported improvement in renal physiology and stabilization in renal function following treatment with avacopan in a patient with refractory C3G. Under a "Special Needs" protocol (similar to the compassionate use program in the United States), a C3G renal transplant recipient with deteriorating kidney function responded well to treatment with avacopan. Prior to receiving treatment with avacopan, the C3G patient had received treatment with a wide spectrum of immunosuppressant drugs including rituximab, cyclophosphamide, mycophenolate mofetil, tacrolimus and glucocorticosteroids, all of which had failed to prevent disease recurrence or progression. Highlights of the results are as follows:
After one month of avacopan treatment, renal function, based on estimated glomerular filtration rate (eGFR) stabilized, and has remained stable for over a year. Decline in a patient’s eGFR is a negative and often life-threatening effect of C3G;
Sequential kidney biopsies taken after the patient had been on avacopan for two and seven months showed continued improvement in kidney histology based on a decrease in glomerular endocapillary proliferation and a marked reduction in the number of glomerular inflammatory macrophages, as compared to the pre-treatment biopsy; and
Avacopan was shown to be safe and well tolerated. The patient has now entered month 15 of treatment and continues to tolerate avacopan well with no serious adverse events.
Conducted End-of-Phase II and scientific advice meetings with U.S. and EU regulatory agencies, respectively, regarding the avacopan AAV Phase III development plan.
Immuno-Oncology and Other Therapeutic Areas: CCX872 is a selective inhibitor of the chemokine receptor known as CCR2, and is designed to block the infiltration of immune suppressor cells in the tumor microenvironment. CCX872 is being evaluated in patients with non-resectable pancreatic cancer in an ongoing, multi-center clinical trial. The primary outcome measurement of the study is progression-free survival (PFS) after at least 24 weeks of treatment. The Company’s immuno-oncology efforts include research to identify potential drug candidates targeting additional receptors that are believed to play an important role in the tumor microenvironment. Inhibiting CCR2 may be effective in therapeutic areas beyond immuno-oncology, including decreasing inflammatory macrophage infiltration into the liver, thus reducing hepatic inflammation and fibrosis.

Presented data at the American College of Gastroenterology (ACG) 2016 Annual Meeting demonstrating that treatment with CCX872 reduced hepatic inflammation, steatosis, and scarring in models of non-alcoholic steatohepatitis (NASH). Highlights of the results are as follows:
Two models of NASH were used to determine the efficacy of CCX872 in reducing fibrosis; in both models, treatment with CCX872 achieved a statistically significant reduction in liver fibrosis as compared to placebo control;
CCX872 was more efficacious than a CCR2/CCR5 dual inhibitor, being advanced elsewhere in clinical development, in reducing liver fibrosis in a model which is known to induce NASH;
Reported initial 12 week overall response rate (ORR) results from an ongoing open label, single arm Phase Ib clinical trial with CCX872 in patients with advanced pancreatic cancer; and
Presented preclinical data at the CRI-CIMT-EATI-AACR 2016 Annual Meeting demonstrating that blocking CCR2 with CCX872 decreases tumor burden by blocking monocyte infiltration, creating a microenvironment that is more favorable for CD8+ T-cell activity. This provides a mechanistic rationale for investigating the combination of CCX872 and an immune checkpoint inhibitor for the treatment of pancreatic cancer.
Corporate Development

Announced the appointment of Henry A. McKinnell, Jr., Ph.D., retired chairman and chief executive officer of Pfizer Inc., to our Board of Directors. Dr. McKinnell brings significant leadership in operations and international strategic alliances, as well as commercial experience to ChemoCentryx.
Anticipated Milestones

Orphan and Rare Diseases:

Present detailed results from the Phase II CLEAR and CLASSIC trials of avacopan in AAV in oral presentations at ASN Kidney Week and the American College of Rheumatology (ACR) 2016 Annual Meeting, respectively;
Present results from the pilot Phase II study of avacopan in aHUS patients with end-stage renal disease at ASN Kidney Week;
Present CRISPR-Cas9 data at ASN Kidney Week, which include details of the creation of a colony of genetically unique mice that are designed to assess the effects of inhibiting the C5aR with avacopan on diseases characterized by unregulated complement activation, such as aHUS and C3G;
Finalize development plan and initiate Phase III development program of avacopan for the treatment of AAV by year end;
Initiate a clinical endpoint study with avacopan in patients with C3G in the first half of 2017; and
Initiate a clinical endpoint study with avacopan in patients with aHUS in 2017.
Immuno-Oncology and Other Therapeutic Areas:

Report PFS data from pancreatic cancer trial of CCX872 in combination with FOLFIRINOX early in the first quarter of 2017, potentially at a major medical meeting; and
Initiate a Phase II trial with CCX872 in combination with a checkpoint inhibitor in 2017.
Third Quarter 2016 Financial Results and Outlook

Cash, cash equivalents and investments totaled $131.6 million at September 30, 2016.

Revenue was $4.1 million for the three months ended September 30, 2016 compared to zero in the same period in 2015. The increase in revenue from 2015 to 2016 was due to: (i) amortization of the upfront payment from Vifor Pharma pursuant to the avacopan agreement and (ii) grant revenue from the FDA to support the clinical development of avacopan for the treatment of patients with AAV.

Research and development expenses were $8.4 million for the three months ended September 30, 2016 compared to $7.9 million reported for the same period in 2015. The increase in research and development expenses from 2015 to 2016 was primarily attributable to higher expenses associated with avacopan for start-up activities related to the Phase III development program in patients with AAV. This increase was partially offset by lower expenses associated with Phase II development of avacopan, due to the completion of the CLEAR and CLASSIC Phase II clinical trials in 2016.

General and administrative expenses were $3.2 million for the three months ended September 30, 2016 compared to $3.8 million for the comparable period in 2015. The decrease from 2015 to 2016 was primarily due to lower stock-based compensation and intellectual property filing expenses.

Net loss was $7.1 million for the second quarter ended September 30, 2016 compared to $11.7 million in the same period in 2015.

Total shares outstanding at September 30, 2016 were approximately 47.8 million shares.

On November 7, 2016 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported business and financial highlights for the third quarter ended September 30, 2016 (Press release, Celldex Therapeutics, NOV 7, 2016, View Source [SID1234516361]).

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"Celldex continues to demonstrate our commitment to combining therapeutic approaches to drive innovation in immuno-oncology for patients and their families," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "In the third quarter, we presented important data from our Phase 2 study of glembatumumab vedotin in checkpoint-refractory metastatic melanoma at ESMO (Free ESMO Whitepaper), meeting the primary overall response endpoint and demonstrating clinically meaningful duration of response in this difficult-to-treat setting. Building on these promising signals, we are now enrolling a combination arm with our CD27 agonist, varlilumab, and are in the process of finalizing an additional arm to explore a glembatumumab vedotin and checkpoint inhibitor combination."

"Last week, we also announced the proposed acquisition of Kolltan Pharmaceuticals. This transaction would add a highly compatible platform of unique antibodies targeting receptor tyrosine kinases to our pipeline that we believe can be developed both independently and in combination with Celldex’s existing product candidates. We are in the process of finalizing our integrated clinical development strategy and look forward to outlining these plans after closing the transaction. As multi-drug combination regimens become the standard in oncology, we fully recognize that the development programs to explore these opportunities become increasingly complex. We believe Celldex is well positioned to meet this challenge and will draw upon the leadership and expertise of Elizabeth Crowley, whom we promoted to the newly created role of Chief Product Development Officer in the third quarter," concluded Marucci.

Business Update:

Proposed Acquisition of Kolltan Pharmaceutics

On November 1, 2016, Celldex announced that the Company entered into a definitive agreement to acquire Kolltan Pharmaceuticals, Inc., a privately held clinical-stage company focused on the discovery and development of novel, antibody-based drugs targeting receptor tyrosine kinases (RTKs). Kolltan has reported clinical and preclinical data that its drug candidates can help overcome tumor resistance mechanisms associated with current tyrosine kinase inhibitors and seen in patients who have failed other cancer therapies. Celldex believes Kolltan’s clinical candidates and preclinical platform are highly compatible with the Company’s scientific approach and can be developed independently and in combination with Celldex’s existing product candidates. The transaction, which is subject to the receipt of Kolltan stockholder approval and other customary closing conditions, is expected to be completed by year-end. Upon closing, the following programs would be included in Celldex’s pipeline:
KTN0158 — a humanized monoclonal antibody that is a potent inhibitor of KIT activation and receptor dimerization in tumor cells and mast cells, which is currently in a Phase 1 dose escalation study in refractory gastrointestinal stromal tumors (GIST).
KTN3379 — a human monoclonal antibody designed to block the activity of ErbB3 (HER3), which recently completed a Phase 1b study with combination cohorts where meaningful responses and stable disease were observed in cetuximab (Erbitux) refractory patients in head and neck squamous cell carcinoma and in BRAF-mutant non-small cell lung cancer (NSCLC).
A multi-faceted TAM program — a broad antibody discovery effort underway to generate antibodies that modulate the TAM family of RTKs, comprised of Tyro3, AXL and MerTK, which are expressed on tumor-infiltrating macrophages, dendritic cells and some tumors. Research supports TAMs having broad application and potential across immuno-oncology and inflammatory diseases.
Program Updates:

Glembatumumab vedotin ("glemba"; CDX-011), an antibody-drug conjugate (ADC) targeting gpNMB in multiple cancers

Enrollment continues in the Company’s Phase 2b randomized study (METRIC) of glembatumumab vedotin in patients with metastatic triple negative breast cancers that overexpress gpNMB, a molecule associated with poor outcomes for triple negative breast cancer patients and the target of glembatumumab vedotin. Enrollment is open across the United States, Canada, Australia and the European Union. Enrollment rates have increased, and the Company anticipates providing guidance in early 2017 on projected enrollment completion.

Data from the Phase 2 single-agent study of glembatumumab vedotin in metastatic melanoma, post-progression on checkpoint therapy, were presented in October at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The primary endpoint of the study (6 or more objective responses in the first 52 patients enrolled) was exceeded. 7 of 62 (11%) patients experienced a confirmed response, and an additional 3 patients also experienced single time-point responses. The median duration of response in this heavily pre-treated patient population was 6.0 months, and the median progression-free survival (PFS) for all patients was 4.4 months.

As previously announced, the Company has amended the protocol to add a second cohort of patients to a glembatumumab vedotin and varlilumab combination arm to assess the potential clinical benefit of the combination and to explore varlilumab’s potential biologic and immunologic effect when combined with an ADC. This additional cohort is open to enrollment. The Company is exploring opening a new arm in the study to assess a glembatumumab vedotin and checkpoint inhibitor combination. This rationale is strongly supported by preclinical data that suggest that the anti-tumor activity may be enhanced with the combination.

Celldex is also evaluating glembatumumab vedotin in other cancers in which gpNMB is expressed.

Celldex has entered into a collaborative relationship with PrECOG, LLC, which represents a research network established by the Eastern Cooperative Oncology Group (ECOG), and PrECOG, LLC is conducting a Phase 1/2 study in squamous cell lung cancer. This study opened to enrollment in April 2016.

Celldex and the National Cancer Institute (NCI) have entered into a Cooperative Research and Development Agreement (CRADA) under which the NCI is sponsoring two studies of glembatumumab vedotin—one in uveal melanoma and one in pediatric osteosarcoma. Both studies are currently open to enrollment.
Varlilumab ("varli"; CDX-1127), a fully human monoclonal agonist antibody that binds and activates CD27, a critical co-stimulatory molecule in the immune activation cascade

Preclinical data on combination regimens with varlilumab are expected to be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2016.

The Phase 2 portion of the varlilumab and nivolumab (Opdivo) study opened to enrollment in April 2016 and includes cohorts in colorectal cancer (n=18), ovarian cancer (n=18), head and neck squamous cell carcinoma (n=48), renal cell carcinoma (n=75) and glioblastoma (n=20). The study is being conducted by Celldex under a clinical trial collaboration with Bristol-Myers Squibb Company. The companies are sharing development costs.

Enrollment has been completed in the Phase 1 dose-escalation portion of the Phase 1/2 study of varlilumab and Tecentriq (atezolizumab) in patients with multiple solid tumors. This study is being conducted by Celldex under a clinical trial collaboration with Roche. Roche is providing study drug, and Celldex is responsible for conducting and funding the study.

Enrollment is expected to complete by year-end in the Phase 1 portion of a Phase 1/2 safety and tolerability study examining the combination of varlilumab and sunitinib (Sutent) in patients with metastatic clear cell renal cell carcinoma.

As discussed above, a Phase 2 study of varlilumab and glembatumumab vedotin in metastatic melanoma (post-progression on checkpoint therapy) continues to enroll patients.

A Phase 1/2 safety and tolerability study examining the combination of varlilumab and ipilimumab (Yervoy) in patients with stage III or IV metastatic melanoma was opened to enrollment in April 2015. Since initiating the study, the standard of care has evolved, and there has been increasing physician reluctance to use Yervoy in this setting. As such, given the broad development strategy in place for varlilumab, the Company has decided to close this study.
CDX-1401, an NY-ESO-1-antibody fusion protein for immunotherapy

Celldex continues to support several external collaborations, including an NCI sponsored Phase 2 study of CDX-1401 and CDX-301 for patients with metastatic melanoma (n=60 patients; not selected for NY-ESO-1 expression). Data from this study were presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The data confirmed that CDX-1401 is effective at driving NY-ESO-1 immunity and further demonstrated the value of CDX-301 as a combination agent for enhancing tumor-specific immune response. Based on results to date, plans for additional studies are being considered, including a targeted study in NY-ESO-1 positive disease to determine if these enhanced immune responses can translate to improved clinical outcomes.

Additionally, Roswell Park Cancer Center is conducting an investigator sponsored study evaluating CDX-1401, poly-ICLC (Hiltonol) and the IDO1 inhibitor epacadostat (INCB24360) in patients in remission with ovarian, fallopian tube or primary peritoneal cancer. Patients’ tumors must have expressed NY-ESO-1 or the LAGE-1 antigen to be eligible for the study. Celldex is providing CDX-1401 and poly-ICLC in support of this study.
CDX-301 (recombinant human Flt3L), a potent hematopoietic cytokine that uniquely expands the number of dendritic cells to prime the immune system for more robust immune responses to cancer antigens

As outlined above, data were presented from the Phase 2 study of CDX-1401 and CDX-301 in metastatic melanoma that further demonstrated the value of CDX-301 as a combination agent for enhancing tumor-specific immune response. CDX-301 greatly expanded peripheral blood dendritic cells and was highly effective at increasing cancer antigen specific T cells and antibodies when combined with CDX-1401. These results, which also showed rapid cellular immune responses in a majority of patients, suggests that pre-treatment with CDX-301 could provide a highly applicable, effective immunologic approach.

CDX-301’s potential activity is also being explored in a Phase 1/2 study of CDX-301 and poly-ICLC in combination with low-dose radiotherapy in patients with low-grade B-cell lymphomas conducted by the Icahn School of Medicine at Mount Sinai. Data from this study will be shared in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2016.
CDX-014, an antibody-drug conjugate (ADC) targeting the transmembrane protein T-cell immunoglobulin mucin-1 (TIM-1) in renal cell carcinoma

Enrollment continues in the Phase 1 dose-escalation portion of the Phase 1/2 study of CDX-014 in advanced clear cell and papillary renal cell carcinoma (RCC). The Phase 1 study is evaluating cohorts of patients receiving increasing doses of CDX-014 to determine the maximum tolerated dose and a recommended dose for Phase 2 study.
RINTEGA ("rindopepimut"; "rindo"; CDX-110), an EGFRvIII(v3)-specific therapeutic vaccine for glioblastoma (GBM)

As previously disclosed, in March, during a pre-planned interim analysis, the independent Data Safety and Monitoring Board (DSMB) recommended discontinuation of the Phase 3 ACT IV study of RINTEGA (rindopepimut) in patients (n=745) with newly diagnosed EGFRvIII-positive glioblastoma. Data from this study will be presented in a plenary session at the Society for Neuro-Oncology Annual Meeting in November. The Company continues to guide that it will not incur substantial additional costs related to RINTEGA at this time.
CDX-1140, a fully human antibody targeted to CD40 that has demonstrated potent agonist activity.

Preclinical data supporting this program will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2016 and at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2016.
Third Quarter and First Nine Months 2016 Financial Highlights and Updated 2016 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2016 were $203.2 million compared to $220.1 million as of June 30, 2016. The decrease was primarily driven by our third quarter cash used in operating activities of $24.0 million. At September 30, 2016, Celldex had 101.2 million shares outstanding.

Revenues: Total revenue was $2.2 million in the third quarter of 2016 and $4.9 million for the nine months ended September 30, 2016, compared to $1.0 million and $3.7 million for the comparable periods in 2015. Total revenue was primarily derived from our clinical trial collaboration with Bristol-Myers Squibb and our research and development agreement with Rockefeller University.

R&D Expenses: Research and development (R&D) expenses were $25.0 million in the third quarter of 2016 and $78.2 million for the nine months ended September 30, 2016, compared to $24.7 million and $76.3 million for the comparable periods in 2015.

The increase in R&D expenses of $0.4 million between the three-month periods was primarily due to higher contract manufacturing of $1.7 million and personnel costs of $1.1 million, including higher stock-based compensation of $0.3 million, offset in part by lower clinical costs of $2.4 million.

The $1.9 million increase in R&D expenses between the nine-month periods was primarily due to higher contract manufacturing costs of $4.0 million and personnel costs of $4.9 million, including higher stock-based compensation of $1.6 million, offset by lower clinical costs of $8.1 million.

G&A Expenses: General and administrative (G&A) expenses were $7.0 million in the third quarter of 2016 and $24.0 million for the nine months ended September 30, 2016, compared to $8.5 million and $22.8 million for the comparable periods in 2015.

The decrease in G&A expenses of $1.5 million between the three-month periods was primarily due to lower commercial planning costs of $0.4 million and lower personnel costs of $0.6 million, including lower stock-based compensation of $0.4 million.

The $1.2 million increase in G&A expenses between the nine-month periods was primarily due to higher stock-based compensation of $1.4 million, offset by lower commercial planning costs of $0.3 million.

Net Loss: Net loss was $29.6 million, or ($0.29) per share, for the third quarter of 2016 and $96.2 million, or ($0.97) per share, for the nine months ended September 30, 2016, compared to a net loss of $32.0 million, or ($0.32) per share and $94.5 million, or ($0.98) per share for the comparable periods in 2015.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at September 30, 2016 combined with the anticipated proceeds from future sales of our common stock under the Cantor agreement, are sufficient to meet estimated working capital requirements and fund planned operations, including the proposed acquisition and integration of Kolltan Pharmaceuticals, through 2018; however, this could be impacted if we elected to pay Kolltan’s shareholders contingent milestones in cash.

RINTEGA is a registered trademark of Celldex Therapeutics. Opdivo and Yervoy are registered trademarks of Bristol-Myers Squibb. Sutent is a registered trademark of Pfizer. Tecentriq is a registered trademark of Genentech. Hiltonol is a registered trademark of Oncovir. Erbitux is a registered trademark of Eli Lilly & Co.

On November 7, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported third quarter highlights and reported financial results for the quarter ended September 30, 2016 (Press release, Cascadian Therapeutics, NOV 7, 2016, View Source [SID1234516359]).

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"We continue to make strides on the clinical development front as we advance tucatinib in combination for patients with metastatic HER2+ breast cancer, including those with and without brain metastases," said Scott Myers, CEO of Cascadian Therapeutics. "There is significant need for improved therapies in this disease, and we continue to be impressed by the favorable safety profile observed in the tucatinib combination studies to date when compared with other HER2 therapies, as well as its potential to treat systemic disease and positively impact brain metastases."

Mr. Myers added, "We are looking forward to the presentation of updated clinical data from our ongoing Phase 1b ‘Triplet’ study of tucatinib plus capecitabine and trastuzumab at the San Antonio Breast Cancer Symposium in December, as well as updating everyone on our clinical and regulatory plans later this quarter."

THIRD QUARTER AND RECENT HIGHLIGHTS

Clinical Development

HER2CLIMB, continues to be on track with enrollment of Phase 2 tucatinib (ONT-380) combination trial. This randomized, double-blind, placebo-controlled study is evaluating the safety and efficacy of tucatinib versus placebo in combination with capecitabine and trastuzumab in late stage HER2+ breast cancer patients, with and without brain metastases, who have previously been treated with a taxane, trastuzumab, pertuzumab and T-DM1. Tucatinib, which has Fast Track designation from the FDA in this setting, is expected to enroll approximately 180 patients at sites in the U.S., Canada and select countries in Western Europe. Previously reported results from the ongoing Phase 1b study of the tucatinib "Triplet" combination demonstrated promising systemic activity, a favorable safety profile and activity against brain metastases, which represents a significant unmet medical need.

Data presented at ESMO (Free ESMO Whitepaper) 2016 show early evidence of activity of tucatinib combination therapy in patients with cutaneous HER2+ metastases. In a poster presentation, Dr. Alison Conlin, study author and Medical Oncologist, Providence Cancer Center, Portland, OR, presented data on eight patients with HER2+ metastases to the skin who received the maximum tolerated tucatinib dose in combination with capecitabine and/or trastuzumab from the Company’s Phase 1b combination study. Patients had previously received a median of six lines of drug therapy. Responses observed in skin lesions in these patients included one complete response, four partial responses and three patients with stable disease, including one partial response of a patient receiving tucatinib and trastuzumab only.

Continue to advance novel Chk1 cell cycle inhibitor with goal of conducting IND-enabling studies. Preclinical research has shown that select Cascadian Chk1 inhibitors display cellular potency in in vitro models against Chk1, are active against a diverse range of cancer cell lines, and demonstrate synergistic activity in combination with certain chemotherapeutic drugs.
Corporate Update

Cascadian’s board of directors has called a Special Stockholder Meeting to vote on a reverse split of the Company’s common stock and a reduction of the authorized common stock. The objective is to make the stock accessible to a wider range of institutional investors, benefiting all stockholders, and ensure that the necessary financial structure is in place to execute product development and other necessary corporate initiatives. The stockholder vote on the proposal will be held on November 18, 2016. For details, see the proxy statement at www.sec.gov/edgar.
THIRD QUARTER 2016 FINANCIAL HIGHLIGHTS

Cash, cash equivalents and investments totaled $71.6 million as of September 30, 2016, compared to $56.4 million at December 31, 2015, an increase of $15.2 million, or 27.0%. The increase was primarily the result of net proceeds of $43.3 million from the Company’s June 2016 financing offset by cash used to fund operations of $28.1 million.

Net loss attributable to common stockholders for the three months ended September 30, 2016 was $11.8 million, or $0.09 per basic and diluted share, compared with a net loss attributable to common stockholders of $4.6 million, or $0.05 per basic and diluted share, for the comparable period in 2015. The increase in net loss attributable to common stockholders for the quarter was primarily due to increases in research and development expenses of $2.2 million primarily due to greater activity related to the development of the Company’s product candidates and increases in general and administrative expenses of $1.4 million primarily due to expenses related to the Company’s Retention Payment Plan and higher professional fees associated with legal and regulatory compliance. The Company also recognized a non-cash $1.0 million deemed dividend due to the beneficial conversion feature on the Series D convertible preferred stock. In addition, the increase in net loss attributable to common stockholders was due to lower non-cash income from the change in the fair value of the Company’s warrant liability, which was zero for the three months ended September 30, 2016 compared to $2.6 million for the three months ended September 30, 2015. The change in the fair value of warrant liability was due to the expiration of September 2010 warrants, which expired in October 2015.

Net loss attributable to common stockholders for the nine months ended September 30, 2016 was $49.8 million, or $0.46 per basic and diluted share, compared with a net loss attributable to common stockholders of $23.5 million, or $0.24 per basic and diluted share, for the comparable period in 2015. The increase in net loss attributable to common stockholders for the nine months ended September 30, 2016 was primarily due to the intangible asset impairment charge of $19.7 million during the nine months ended September 30, 2016, which was the result of the mutual termination of the STC.UNM agreement. In addition, the increase in net loss attributable to common stockholders was due to increases in research and development expenses of $3.4 million primarily due to greater activity related to the development of the Company’s product candidates, and increases in general and administrative expenses of $7.5 million primarily related to the retirement and separation agreement that Cascadian entered into with its former chief executive officer in January 2016, expenses related to the Company’s Retention Payment Plan and higher professional fees associated with legal and regulatory compliance. The Company also recognized a non-cash $2.6 million deemed dividend due to the beneficial conversion feature on the Series D convertible preferred stock. The increase in the net loss attributable to common stockholders was partially offset by a $6.9 million tax benefit during the nine months ended September 30, 2016.
Financial Guidance
Cascadian Therapeutics believes the following financial guidance to be correct as of the date provided. Cascadian Therapeutics is providing this guidance as a convenience to investors and assumes no obligation to update it.

Cascadian Therapeutics currently expects cash used in operations in 2016 to be approximately $38.0 million to $40.0 million. With cash, cash equivalents and investments of $71.6 million as of September 30, 2016, Cascadian Therapeutics estimates that its cash, cash-equivalents and investments will be sufficient to fund operations for at least the next 12 months.

About Cascadian Therapeutics
Cascadian Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative product candidates for the treatment of cancer. Our lead product candidate, tucatinib, is an orally active and selective small molecule HER2 inhibitor, which has been studied in approximately 200 patients to date. Preliminary results from two ongoing Phase 1b studies of tucatinib in combination showed promising systemic activity, a favorable safety profile and encouraging activity against brain metastases. Cascadian Therapeutics is also conducting a randomized, double-blind, placebo-controlled Phase 2 study called HER2CLIMB. The study is evaluating tucatinib versus placebo in combination with capecitabine and trastuzumab in late stage HER2+ breast cancer patients, with and without brain metastases, who have previously been treated with a taxane, trastuzumab, pertuzumab and T-DM1. This study is expected to enroll 180 patients with and without brain metastases across approximately 100 clinical sites in the U.S., Canada, and Western Europe. The Company is also developing a cell cycle inhibitor, Chk1, and plans to move the program forward through IND-enabling studies in 2017. For more information, visit www.cascadianrx.com.