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]).

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"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.

On January 21, 2016 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company developing checkpoint modulator antibodies and cancer vaccines, reported that the U.S. Food and Drug Administration (FDA) cleared the company’s investigational new drug (IND) application for AGEN1884, an immune checkpoint modulator (CPM) antibody that binds to cytotoxic T-lymphocyte antigen-4 (CTLA-4) (Press release, Agenus, JAN 21, 2016, View Source [SID:1234508833]). Clearance was also received for a second CPM antibody partnered with Incyte (NASDAQ: INCY) for INCAGN1876, which targets glucocorticoid-induced TNFR-related protein (GITR). Clinical trials for both candidates are expected to begin in the first half of 2016.

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"We are pleased with the prospects of both CTLA-4 and GITR moving rapidly into and through the clinic, and in our efforts to bring profoundly effective medicines to cancer patients," said Garo Armen, PhD, Chairman and CEO of Agenus. "We are also diligently advancing several other product candidates into the clinic and are aiming to begin a number of clinical trials in 2016."

These two compounds were developed utilizing Agenus’ state-of-the-art monoclonal antibody platform capabilities and leverage the company’s world-class expertise in immuno-oncology and related drug discovery and development. The antibodies were discovered during an earlier collaboration with Ludwig Cancer Research. Recepta, a Brazilian biotech company, was also involved in the collaboration that led to the discovery of AGEN1884, which is partnered with Recepta for certain South American rights. INCAGN1876 is now being co-developed with Incyte.

"CTLA-4 is emerging as an important foundational target for immuno-oncology combination regimens, showing terrific promise when used with other CPMs and cancer vaccines. Our CTLA-4 antagonist antibody, AGEN1884, is a natural potential fit with our expanding vaccine portfolio. This includes Prophage, slated to enter a randomized placebo-controlled study in newly diagnosed GBM in the second half of 2016, and AutoSynVax, which we also plan to take into the clinic in the second half of 2016," said Robert B. Stein, MD, PhD, Agenus’ President, Research & Development. "I would like to acknowledge the research and development teams at Agenus, and Incyte for GITR, for their tireless efforts to achieve our goal of filing these INDs by the end of 2015."

About Checkpoint Modulators

Promising clinical data from studies employing monoclonal antibodies that bind to checkpoint molecules, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), have generated considerable excitement in the field of cancer immunotherapy. These molecules serve as checks employed by the body to prevent a runaway immune response, which can be debilitating, and even deadly. Unfortunately, these necessary mechanisms of control can hinder the anti-cancer immune response. They can be harnessed by cancer cells as a defense against immune attack. Agenus is developing a broad pipeline of antibodies that bind to key checkpoint proteins and activate or block their activities for use in cancer therapy.

On January 21, 2016 Asterias Biotherapeutics, Inc. (NYSE MKT: AST), reported that it has completed the transfer of its manufacturing processes to produce AST-VAC2 to Cancer Research UK (Press release, BioTime, JAN 21, 2016, View Source [SID:1234508832]).

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AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase permits enhanced stimulation of immune responses to the protein. The AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase which will target tumor cells.

To accelerate clinical development of AST-VAC2, Asterias has an ongoing partnership with Cancer Research UK and Cancer Research Technology, the charity’s development and commercialization arm, to execute the first clinical trial of AST-VAC2. As part of this partnership, Cancer Research UK will perform cGMP manufacture of AST-VAC2 at their Biotherapeutics Development Unit. In preparation for cGMP production, Asterias developed the production process for AST-VAC2 to support the transfer and further scale-up in Cancer Research UK’s manufacturing facility for the Phase 1/2 clinical study. To that end, Asterias has completed transfer of the AST-VAC2 manufacturing process information to Cancer Research UK. Cancer Research UK is now verifying and scaling up the production of AST-VAC2 in their facility in preparation for pilot and full cGMP campaigns. Upon successful completion of AST-VAC2 production campaigns, Cancer Research UK’s Centre for Drug Development ("CDD") will submit a Clinical Trial Authorisation application to the UK regulatory authorities for a Phase 1/2 clinical trial in non-small cell lung cancer, which will be sponsored, managed and funded by CDD. The clinical trial will examine the safety, immunogenicity and activity of AST-VAC2 and position the immunotherapy to be tested for numerous clinical indications.

"Transfer of the manufacturing process for AST-VAC2 marks an important milestone in our partnership with Cancer Research UK and is a critical step towards initiating the first clinical trial of AST-VAC2," said Pedro Lichtinger, Chief Executive Officer of Asterias. "The program with Cancer Research UK will assess the safety and activity of AST-VAC2 and serve as a foundation for further clinical development in lung and other cancers."

"The design of AST-VAC2 affords three unique properties to this dendritic cell immunotherapy," stated Jane S. Lebkowski, Ph.D., President of R&D and Chief Scientific Officer of Asterias. "Being produced from pluripotent stem cells, AST-VAC2 can be manufactured at batch-scale and be available on-demand for patient use. Second, the telomerase protein in AST-VAC2 is specifically engineered to target the two major pathways stimulating T cell immune responses, inducing more robust and durable cellular immune responses to telomerase. Lastly, the non-patient specific, allogeneic, nature of AST-VAC2 could potentially provide signals to further amplify immune responses."

"Based on its mode of action, AST-VAC2 is likely to be synergistic with immune checkpoint inhibitors and other adoptive immunotherapies that are being used for treatment now," stated Katy Spink Ph.D., Chief Operating Officer of Asterias. "The combination of the immunostimulatory activity of AST-VAC2 with the drugs that downregulate inhibitors of immune responses could provide a very powerful tool for the treatment of multiple cancers."

Dr. Nigel Blackburn, Cancer Research UK’s director of drug development, said: "This drug could potentially treat most tumour types as it targets the telomerase protein – which is faulty in 95 per cent of all cancers. The treatment’s design means it could also boost the effects of other immunotherapies and be used in combination.

"Lung cancer is the biggest cancer killer so we desperately need to find new treatments for the disease. And we’re pleased to be working with Asterias Biotherapeutics to develop this new treatment and to test it in clinical trials for non-small cell lung cancer for the first time."