On November 11, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that data for its drug candidates CB-839, the company’s novel glutaminase inhibitor, and CB-1158, the company’s novel arginase inhibitor, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2016 Annual Meeting, which is being held from November 9-13, 2016 in National Harbor, Maryland (Press release, Calithera Biosciences, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221726 [SID1234516491]).

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"Both CB-839 and CB-1158 have the distinction of targeting metabolic and immune checkpoints which we believe, through rational combinations, have the potential to be transformational in the treatment of cancer. CB-839 and CB-1158 are each in clinical trials with cohorts planned in combination with approved immunotherapy agents," said Susan Molineaux, Ph.D., President and Chief Executive Officer of Calithera. "We are pleased that CB-1158 shows significant pharmacodynamic effects in patients at the first dose level tested."

Preclinical CB-839 data will be presented in a poster titled, "Targeting tumor glutamine metabolism with CB-839 enhances the efficacy of immune checkpoint inhibitors," by Andy MacKinnon, Ph.D., Calithera Biosciences (Poster #230). Included in the presentation are data that provide further insights into the mechanism by which inhibition of glutaminase by CB-839 enhances T-cell activation and increases the anti-tumor activity of anti-PD-L1 and anti-PD-1 antibodies. Glutamine deprivation during T-cell activation was shown to block Myc expression and Myc-driven metabolic re-programming, and to promote expression of T-cell suppressive markers such as BTLA, CTLA-4, PD-1, and CD73. In two syngeneic animal models, CT26 (colon cancer) and B16 (melanoma) the combination of CB-839 and anti-PD-L1 or anti-PD-1 showed significantly enhanced anti-tumor activity over checkpoint inhibition alone resulting in increased tumor regressions in the CT26 model. Depletion of CD8+ T-cells from these tumor-bearing animals reversed the anti-tumor effects of the combination, confirming an immune-mediated mechanism of action.

CB-1158 data will be presented in a poster titled, "Arginase inhibitor CB-1158 alleviates immunosuppression and enhances anti-tumor responses as a single agent and in combination with other immunotherapies," by Amani Makkouk, Ph.D., Calithera Biosciences (Poster #231). Arginase is expressed in myeloid derived suppressor cells (MDSCs) and exerts an immunosuppressive effect on T-cells and NK cells by depleting arginine and blocking activation. Tumor cell infiltrates in patients with solid tumor cancers contain significant numbers of arginase-expressing MDSCs; as a result, these patients have increased levels of plasma arginase and decreased levels of plasma arginine compared to healthy individuals. CB-1158, a highly selective, orally bioavailable, small molecule inhibitor of human arginase with nanomolar potency, has single agent immune-mediated efficacy in multiple syngeneic animal models. Inhibition of tumor growth was accompanied by an increase in the local concentration of arginine, and the induction of multiple pro-inflammatory changes in the tumor microenvironment. Treatment with CB-1158 also enhanced the anti-tumor activity of adoptive T-cell therapy, checkpoint blockade and chemotherapy in these animal models. CB-1158 is currently being tested in a Phase 1 clinical trial in patients with solid tumors. Three patients in the first cohort were treated with 50 mg of CB-1158 twice daily. This dose was well-tolerated and was pharmacologically active, resulting in sustained elevation of arginine in the plasma of all three patients. The trial is continuing to enroll patients to complete the dose escalation phase of the study, to be followed by combination studies with a PD-1 antibody.

In addition, two posters describing trial design will be presented during the "Clinical Trials in Progress" session:

CX-1158-101: A first-in-human phase I study of a small molecule inhibitor of arginase (CB-1158) as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor in patients with solid tumors

Presenter: Siqing Fu, M.D., Ph.D., University of Texas, MD Anderson Cancer Center, Poster #155

CX-839-004: A phase I/II study of the safety, pharmacokinetics, and pharmacodynamics of the glutaminase inhibitor CB-839 combined with nivolumab in patients with renal cell carcinoma, melanoma, and non-small cell lung cancer

Presenter: Elaine Lam, M.D., University of Colorado, Denver, Poster #166

On November 11, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported a poster with updated interim results from its on-going Phase 1b/2 trial of aldoxorubicin in combination with ifosfamide/mesna in patients with advanced sarcomas at the 2016 Annual Meeting of the Connective Tissue Oncology Society (CTOS) being held in Lisbon, Portugal (Press release, CytRx, NOV 11, 2016, View Source;p=RssLanding&cat=news&id=2221789 [SID1234516494]).

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Forty-two patients have been enrolled to date and 36 were evaluable as of the data cutoff. Of the 36 evaluable patients receiving either 170mg/m2 (n=7) or 250mg/m2 (n=29) of aldoxorubicin plus ifosfamide and mesna, 14 of 36 (39%) achieved a partial response of the target lesion by RECIST 1.1 criteria, 21 of 36 (58%) had stable disease, and one patient had progressive disease. As previously reported in October at the 2016 ESMO (Free ESMO Whitepaper) Congress, median progression-free survival has not yet been reached. Dose-limiting toxicities were not observed in either cohort, and no clinically significant cardiac toxicities were seen. The most common Grade 3 or 4 adverse events were neutropenia (71%), anemia (54%), thrombocytopenia (17%) and febrile neutropenia (14%). There were nine treatment-related serious adverse events, and no treatment-related deaths. The trial has been expanded to allow continued enrollment of additional sarcoma patients at the 250 mg/m2 dose of aldoxorubicin with ifosfamide and mesna.

"The CTOS annual meeting is the preeminent medical conference focused on sarcomas and provides an opportunity to update the international sarcoma community with the latest results for aldoxorubicin, said Sant Chawla, M.D., F.R.A.C.P., the trial’s principal investigator and Director of the Sarcoma Oncology Center in Santa Monica, California. "Our poster highlights that nearly 40% of the sarcoma patients receiving the combination of aldoxorubicin with ifosfamide and mesna achieved a partial response of the target lesion by RECIST criteria, and half of those had greater than 50% shrinkage of their tumors. This is important because it allowed some patients who initially could not have surgery to become eligible for surgery."

The Phase 1b/2 clinical study is a single-center trial that has enrolled 42 patients to date with locally advanced, unresectable, and/or metastatic soft tissue sarcoma, intermediate-grade or high-grade chondrosarcoma or osteosarcoma. In the dose escalation phase, patients received either 170mg/m2 or 250mg/m2 of aldoxorubicin in combination with up to a 14-day continuous infusion of ifosfamide (1g/m2/day) plus mesna over a 28-day cycle. Up to six cycles of ifosfamide/mesna with aldoxorubicin can be administered, and aldoxorubicin may be continued until tumor progression or unacceptable toxicity occurs. The expansion phase is enrolling patients at the 250mg/m2 dose of aldoxorubicin and will allow for patients that had received prior chemotherapy to be included. The primary endpoint of the study is safety, and secondary endpoints include overall response rates and progression-free survival.

About Aldoxorubicin

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of doxorubicin in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized global Phase 2b clinical trial in first-line STS.

On November 11, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that a poster featuring preclinical data related to its tetravalent anti-GITR agonist antibody, FPA154, was presented today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in National Harbor, Maryland (Press release, Five Prime Therapeutics, NOV 11, 2016, View Source [SID1234516495]). Poster #175 titled, "Novel tetravalent anti-GITR antibody is a potent anti-tumor agent in vivo," is available at View Source

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"With our lead anti-GITR candidate, FPA154, now in pre-IND enabling studies, we are pleased to highlight our first preclinical data supporting the development and differentiation of this novel, tetravalent antibody," said Luis Borges, Ph.D., Senior Vice President of Research, at Five Prime. "In vitro data demonstrates that our tetravalent antibody has agonistic activity in the absence of Fc-mediated crosslinking. In vivo, the antibody has potent anti-tumor activity in various murine tumor models and it confers long-term anti-tumor immunity. It alters the ratio of Tregs to effector T cells, creating a favorable environment for an effective anti-tumor immune response. These findings suggest the potential for FPA154 to activate T cell immunity against various tumors and we are working to move this program rapidly toward clinical development."

FPA154 has been designed using single-domain antibodies in a tetravalent format, inducing effector T cell stimulation in vitro that is superior to a conventional bivalent antibody format and conferring agonistic activity even in the absence of Fc-mediated crosslinking. The poster features preclinical data provided by a mouse-reactive surrogate molecule that demonstrate potent inhibition of tumor growth in mouse tumor models:

Potent anti-tumor activity following a single dose: A single dose of tetravalent anti-GITR significantly inhibited tumor growth in multiple models including CT26 and MC38. Treatment was capable of inducing complete tumor rejection, and activity was observed at doses as low as 0.08 mg/kg in both models.

Fc-independent activity: Tetravalent anti-GITR antibody retained partial tumor growth inhibition activity even in the absence of Fc-mediated crosslinking or effector function, whereas a conventional bivalent antibody (DTA-1) required Fc function.
Pharmacodynamic responses: Tetravalent anti-GITR antibody treatment reduced the number of T cells in the peripheral blood 3 days post-treatment. In the tumor, Treg and conventional CD4 T cells decreased, but CD8 T cell numbers were maintained. This resulted in a ratio of CD4 and CD8 effector T cells to Treg that created a favorable environment for an effective anti-tumor immune response.

Induction of long-term immunity: Mice that eliminated CT26 tumors in response to tetravalent anti-GITR were resistant to tumor regrowth upon re-challenge with the same tumor, but not to an antigenically-unrelated tumor.

On November 10, 2016 Halozyme Therapeutics, Inc. (NASDAQ: HALO), an oncology biotech developing novel oncology and drug-delivery therapies, and Genentech, a member of the Roche Group, reported an agreement to collaborate on clinical studies evaluating up to eight different tumor types beginning in 2017 (Press release, Halozyme, NOV 10, 2016, View Source [SID1234516465]).

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The first study will be a Phase 1b/2 open-label, multi-arm randomized global study, led by Genentech to evaluate their cancer immunotherapy Tecentriq (atezolizumab), an anti-PD-L1 monoclonal antibody, in combination with Halozyme’s investigational drug, PEGPH20 in six tumor types. Halozyme will supply drug only for the Genentech study. This study will have an initial focus on gastrointestinal malignancies, including pancreatic and gastric cancers.

The second study will be a Phase 1b open-label randomized study led by Halozyme to assess Tecentriq in combination with PEGPH20 and chemotherapy in advanced or metastatic biliary and gallbladder cancers.

"High levels of hyaluronan (HA) have been shown in retrospective clinical reviews to be associated with a poor prognosis when compared to low-HA and in animal models to potentially impede the access of cancer therapy," said Dr. Helen Torley, president and chief executive officer of Halozyme. "We look forward to exploring this combination therapy with our partner in a range of tumors given our shared focus on the tumor microenvironment and longstanding relationship working together on the development of Roche’s Herceptin SC and MabThera SC products for the EU market."

PEGPH20 is an enzyme that temporarily degrades HA, a dense component of the tumor microenvironment that can accumulate in higher concentrations around certain cancer cells, potentially constricting blood vessels and impeding the access of other therapies.

Following the phase 1b portions to assess safety and tolerability of the combinations, the study designs may scale to registration trials. The Halozyme-led study will enroll only patients who are prospectively identified as having tumors with high levels of HA, while initial phases of the Genentech-led study will focus on an all-comer population with a target number of HA-high patients to be enrolled.

– See more at: View Source#sthash.wuN4xaEy.dpuf

On November 10, 2016 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported its financial results and provided a general business update for the third quarter and nine months ended September 30, 2016 (Press release, Heat Biologics, NOV 10, 2016, View Source [SID1234516526]).

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"We look forward to reporting top-line data in both our bladder and lung cancer trials within the next few weeks," commented Jeff Wolf, Heat’s Founder and CEO. "Our results come on the heels of encouraging interim study findings from our Phase 1b trial evaluating HS-110 in combination with the Bristol-Myers Squibb anti-PD-1 checkpoint inhibitor, nivolumab. Our data in lung cancer suggest HS-110 may improve response rates for patients with ‘cold tumors’ who typically have lower response rates to checkpoint inhibitor monotherapy. We are also encouraged by our early data in bladder cancer that suggest we are activating a robust antigen-specific immune response.

"Moreover, we are pleased to announce the expansion of our gp96 platform into the infectious disease arena. We recently formed a new subsidiary, Zolovax, which will focus exclusively on developing gp96-based vaccines for Zika and other infectious diseases, such as HIV, West Nile, dengue and yellow fever. Preclinical studies suggest that our gp96 platform may have a role as a broad-based infectious disease vaccine. Importantly, in the case of Zika, the robust mucosal immune response generated by gp96 in ongoing oncology studies may suggest that a gp96 vaccine could also stimulate a Zika-specific immune response in the placenta, thus protecting the fetus from virus transmission.

"During the third quarter, we strengthened our balance sheet and benefitted from the exercise of warrants and substantial pay down of our existing debt. I am pleased to report we ended the quarter with approximately $8.5 million of cash on hand. This year through November 10, 2016, we have generated over $3.1 million in cash from the exercise of our March 23, 2016 warrants. Meanwhile, we continue to carefully manage our expenses as we await important top-line data this quarter."

Recent Developments & Third Quarter 2016 Corporate Highlights

In late October, Heat announced that it entered into an agreement with the University of Miami for the license and development of a portfolio of patents leveraging its gp96 platform to target the Zika virus and other infectious diseases including HIV, West Nile, dengue and yellow fever.
In October, Heat announced that it has advanced its biomarker discovery collaboration with Adaptive Biotechnologies. Adaptive will use its patented immune profiling assay, immunoSEQ, to enable an in-depth characterization of the immune response to Heat’s ImPACT and ComPACT-based immunotherapies, including HS-410, Heat’s Phase 2 product candidate for non-muscle invasive bladder cancer.
In September, Heat announced that it had resumed enrollment in its Phase 1b trial evaluating HS-110 in combination with nivolumab (Opdivo), a Bristol-Myers Squibb anti-PD-1 checkpoint inhibitor, for the treatment of non-small cell lung cancer (NSCLC). The decision to resume trial enrollment was based on the encouraging data reported in June, including two clinical responses in "cold tumor" patients. There are currently 15 patients enrolled and the Company expects to report topline 6-month data on the first eight of these patients before year end.
In July, Heat announced that preclinical findings from its ComPACT platform technology were published online in the journal "Cancer Immunology Research." Heat demonstrated that its ComPACT technology secreting the co-stimulator OX40L enhanced tumor rejection in two cancer tumor types compared to OX40 agonist antibody treatment. Heat also reported that ComPACT-enhanced antigen-specific T cell infiltration into tumors improved memory T cell responses and demonstrated greater specificity than OX40 agonist antibody treatments.
Third Quarter 2016 Financial Highlights

Research and development (R&D) expenses decreased to approximately $0.6 million in the third quarter of 2016 compared to approximately $0.7 million in the third quarter of 2015, a decrease of approximately $0.1 million. The decrease is primarily attributable to reductions in consultant fees and a decrease in compensation costs attributable to deferral of salary as part of our cost-savings plan.
Clinical and regulatory expenses decreased to approximately $1.1 million in the third quarter of 2016 compared to approximately $3.7 million in the third quarter of 2015, a decrease of approximately $2.6 million. The decrease is primarily attributable to reductions in clinical trial execution costs.
General and administrative (G&A) expenses decreased to approximately $0.8 million in the third quarter of 2016 compared to approximately $0.9 million in the third quarter of 2015, a decrease of $0.1 million. The decrease is attributable to a reduction in compensation costs and work force reductions as part of the cost-savings plan.
Net loss for the third quarter of 2016 was $1.7 million compared to a net loss of $5.4 million for the third quarter of 2015.
Nine Months Ended September 30, 2016 Financial Highlights

R&D expenses decreased to approximately $1.5 million for the nine months ended September 30, 2016 compared to approximately $1.8 million for the nine months ended September 30, 2015, a decrease of approximately $0.3 million. The decrease is attributable to reductions in patent, license and other professional fees, as well as a decrease in consultant expense and a decrease in compensation costs attributable to deferral in salary as part of our cost-savings initiatives.
Clinical and regulatory expenses decreased to approximately $5.6 million for the nine months ended September 30, 2016 compared to approximately $9.2 million for the nine months ended September 30, 2015, a decrease of approximately $3.6 million. The decrease is primarily attributable to reductions in clinical trial execution expenses.
G&A expenses decreased to approximately $2.9 million for the nine months ended September 30, 2016 compared to approximately $3.1 million for the nine months ended September 30, 2015, a decrease of approximately $0.2 million. The decrease is primarily attributable to a decrease in compensation costs attributable to deferral of salary and work force reductions as part of our cost-savings plan.
Net loss for the nine months ended September 30, 2016 was $9.4 million compared to a net loss of $14.4 million for the nine months ended September 30, 2015.
Cash and cash equivalents totaled approximately $8.5 million at September 30, 2016 compared to cash, cash equivalents and short-term investments which totaled approximately $11.6 million at December 31, 2015.