On January 11, 2016 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body’s immune system to fight cancer, reported a clinical development update for bavituximab, the company’s investigational phosphatidylserine (PS)-targeting immunotherapy (Press release, Peregrine Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508756]). In the first quarter of 2016, Peregrine plans to initiate two new Phase II clinical trials in breast and lung cancer in combination with current standard of care treatments including both chemotherapy and immuno-oncology agents. In addition, the company has entered into a collaboration with the National Comprehensive Cancer Network (NCCN) to evaluate bavituximab in other tumor types and combinations. Additionally, the company is nearing completion of enrollment of an ongoing Phase III trial in non-small cell lung cancer (NSCLC) named SUNRISE.

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The planned trials include a Phase II NSCLC trial in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), and a Phase II trial in early stage triple negative breast cancer (TNBC). These are in addition to the recently initiated Phase II/III study in combination with chemotherapy in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The company expects that initial data from these trials may be available in late 2016 or early 2017. Additionally, the company looks forward to the initiation of additional trials of bavituximab combinations through its ongoing collaborations with AstraZeneca and NCCN.

"As we wrap up enrollment in the SUNRISE trial, we recognize that we are at an ideal juncture to continue expanding the potential of bavituximab with standard of care and immunotherapy combinations in multiple solid tumor types. Combined with the SUNRISE trial, the new studies we have planned can help solidify the potential of bavituximab in NSCLC while significantly expanding the market opportunity in breast cancer," said Steven W. King , president and chief executive officer of Peregrine. "Driving our strategy is the goal of further demonstrating that bavituximab can provide therapeutic benefit to available cancer treatments, regardless of whether those are traditional therapies such as chemotherapy and radiation, or the emerging novel class of immuno-oncology agents. In today’s update, it is evident that we are moving aggressively to compile a significant body of clinical evidence to support bavituximab’s utility in multiple cancers and across a range of treatment regimens. By doing so, we hope to optimally position bavituximab for success."

Bavituximab is an investigational immunotherapy designed to assist the body’s immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine’s PS targeted inhibitor, bavituximab, is thought to reverse the immunosuppressive environment that many tumors establish in order to proliferate and spread, while also fighting cancer by activating immune cells that target and fight cancer.

Updated details on Peregrine’s expanded bavituximab clinical development program include:

Bavituximab in NSCLC:

Phase III SUNRISE Trial
Peregrine’s Phase III SUNRISE (Stimulating ImmUne RespoNse thRough BavItuximab in a Pha SE III Lung Cancer Study) trial is evaluating the use of bavituximab and docetaxel in patients with previously treated locally advanced or metastatic non-squamous NSCLC. Peregrine expects that the first interim analysis (33% of targeted number of deaths) will be conducted in early 2016 and the second interim analysis (50% of targeted number of deaths) in mid-2016. The final analysis, which will trigger the unblinding of the study data, is currently projected to occur at the end of 2016.

Phase II NSCLC Trial in Combination with AstraZeneca’s Durvalumab
Peregrine expects to initiate a global Phase II study of bavituximab in combination with AstraZeneca’s durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with previously treated squamous or non-squamous NSCLC during the first quarter of 2016. The goal of this trial is to generate data on the combination of bavituximab and durvalumab to inform the potential advancement of this treatment regimen into later stage clinical trial. The study’s primary endpoints are overall response rate (ORR) and safety. The trial is also designed to retrospectively evaluate patients for the correlation between their PD-L1 levels and clinical outcomes, providing further critical data to guide future development.

The randomized, open-label trial will evaluate approximately 200 patients at sites in the U.S. and Europe. The company has filed a study protocol to its existing investigational new drug (IND) application for bavituximab in the U.S. and is currently working to open clinical trial sites.

Bavituximab in Breast Cancer:

Phase II/III HER2-Negative MBC Trial in Combination with Chemotherapy
In December 2015, Peregrine initiated an open-label, randomized Phase II/III study comparing the efficacy and safety outcomes for taxane monotherapy (paclitaxel or docetaxel at investigator discretion) versus taxane therapy in combination with bavituximab in HER2-negative MBC patients. The goal of the Phase II portion of this study is to generate mature data on the combination of bavituximab and chemotherapy in MBC to guide the design and execution of the trial’s Phase III component. The primary efficacy endpoint of the Phase II study is ORR, with secondary endpoints including progression free survival (PFS), overall survival (OS), duration of response and safety. The Phase II portion of the study will enroll approximately 150 patients at sites in the U.S. and Europe.

Phase II Trial in Early Stage TNBC in Combination with Chemotherapy
Peregrine is planning to initiate a Phase II trial of bavituximab in combination with neoadjuvant chemotherapy in early stage TNBC. The primary endpoint of this study is to determine the pathologic complete response rate (pCR), an accepted surrogate endpoint in early stage TNBC. The concept for this neoadjuvant setting trial, which will be conducted at a few select U.S. sites, originated from Peregrine’s ongoing collaboration with Memorial Sloan Kettering Cancer Center (MSKCC). The company has filed a study protocol to its existing bavituximab IND application in the U.S. and is currently working to open clinical trial sites, including one that will be led by David B. Page, M.D., at the Providence Cancer Center in Oregon.

Bavituximab in Other Solid Tumor Indications:
Phase I/Ib Trial in Multiple Solid Tumors in Combination with AstraZeneca’s Durvalumab and Chemotherapy
As part of the company’s collaboration with AstraZeneca, Peregrine plans to initiate a Phase I/Ib study of bavituximab in combination with durvalumab and chemotherapy in multiple solid tumors in 2016. The Phase I part of the trial is designed to confirm the tolerability of the combination of bavituximab and durvalumab and establish a recommended dose regimen for the Phase Ib part of the trial, which will assess the safety and activity of the combination of bavituximab, durvalumab and chemotherapy.

Multiple Clinical and Translational Studies in Collaboration with NCCN
Peregrine recently announced a new research collaboration with NCCN to expand the company’s ongoing clinical research and development of bavituximab for the treatment of a range of tumors. NCCN, a not-for-profit alliance of 26 of the world’s leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Multiple investigator-initiated clinical and correlative studies with bavituximab in multiple cancers will be initiated at NCCN Member Institutions and their affiliate community hospitals through a $2 million research grant to NCCN’s Oncology Research Program (ORP). NCCN will be responsible for oversight and monitoring of the clinical studies through the research grant. The company expects results from this collaboration to further support the ongoing development of bavituximab as a key component of various combination cancer treatments.

About Bavituximab: A Targeted Investigational Immunotherapy
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab blocks PS and, in turn, is believed to remove this immunosuppressive signal and send an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.

On January 11, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported that the first patient has been enrolled and dosed in the Phase 1b portion of the Phase 1a/1b clinical trial of anti-RSPO3 (OMP-131R10) (Press release, OncoMed, JAN 11, 2016, View Source [SID:1234508754]). The Phase 1b portion of the trial will assess the safety, pharmacokinetics, pharmacodynamics and initial evidence of efficacy of anti-RSPO3 in combination with the chemotherapeutic standard of care in metastatic colon cancer, known as FOLFIRI (folinic acid, fluorouracil and irinotecan) in colorectal cancer patients who have received one prior treatment.

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"We are encouraged by the progress being made in our anti-RSPO3 clinical program and look forward to seeing the safety, biomarker effects and activity of this novel antibody in combination with chemotherapy," said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer. "In preclinical xenograft models, potent anti-tumor activity against colorectal cancers has been observed in combination with chemotherapy, as illustrated in our recent publication in Cancer Research. We are additionally interested to see how this first-in-class antibody combines with chemotherapy in patients with RSPO3 biomarker-positive colorectal cancer."

The company’s ongoing Phase 1a/1b clinical trial is initially enrolling patients with advanced refractory solid tumors to assess the safety, pharmacokinetics, pharmacodynamics and initial evidence of efficacy of the anti-RSPO3 antibody. Enrollment commenced on the single-agent portion of the anti-RSPO3 first-in-human clinical trial in July 2015. Now that several dose cohorts have been safely cleared the decision has been made by OncoMed and the investigators of the trial to initiate the combination phase of the study. Dose escalation of the single agent portion of the study continues in parallel. Once a single-agent dose has been identified, biomarker-selected patients will be enrolled in a Phase 1a expansion arm to evaluate possible anti-tumor activity. The trial is being conducted at five sites in the United States.

About Anti-RSPO3

OncoMed’s anti-RSPO3 (OMP-131R10) is the first drug in its class to target the R-spondin-LGR pathway, an important cancer stem cell pathway identified by OncoMed researchers. In preclinical studies OncoMed’s anti-RSPO3 antibody demonstrated robust in vivo anti-tumor efficacy as a single agent and in combination with standard of care across a range of solid tumors, including colon, lung, ovarian, and pancreatic cancers, among others. The anti-RSPO3 antibody delayed tumor recurrence following termination of chemotherapy, and decreased the frequency of cancer stem cells. Anti-RSPO3 antibody represents the third product candidate in the clinic that is part of OncoMed’s collaboration with Celgene.

Anti-RSPO3 is an investigational agent currently being evaluated in an ongoing clinical trial (ClinicalTrials.gov Identifier: NCT02482441 3). Patients interested in learning more about participating in one of OncoMed’s many clinical trials may call 1-866-914-7347 or email [email protected].

On January 11, 2016 Exelixis, Inc. (NASDAQ:EXEL) reported that it has submitted a Marketing Authorization Application (MAA) for cabozantinib as a treatment for patients with advanced renal cell carcinoma (RCC) who have received one prior therapy to the European Medicines Agency (EMA) (Press release, Exelixis, JAN 11, 2016, View Source [SID:1234508743]). The EMA will now conduct its standard validation process to determine whether the submission is sufficient to permit a substantive review for marketing authorization in the European Union.

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The EMA’s Committee for Medicinal Products for Human Use (CHMP) previously granted accelerated assessment to cabozantinib for advanced RCC. As a result, if validated, the MAA may be eligible for a 150-day review, versus the standard 210 days (excluding clock stops when information is requested by CHMP).

"The regulatory submission in the European Union follows our recent U.S. filing, and is an integral component of our plan to bring an important new treatment option for advanced kidney cancer to patients in need," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "As we seek to maximize the opportunity for the cabozantinib franchise on a worldwide basis, our discussions with potential partners for territories outside of the United States continue to advance. At the same time, we are making significant progress on our commercial readiness to market cabozantinib for advanced RCC in the United States, if approved."

The MAA is based on results of METEOR, a phase 3 pivotal trial comparing cabozantinib to everolimus in patients with advanced RCC who experienced disease progression following treatment with a VEGF receptor tyrosine kinase inhibitor. In July 2015, Exelixis announced top-line results from METEOR demonstrating that the trial had met its primary endpoint of improving progression-free survival; compared with everolimus, cabozantinib was associated with a 42% reduction in the rate of disease progression or death. These data were later presented at the European Cancer Congress in September 2015 and concurrently published in The New England Journal of Medicine.

In the United States, on December 23, 2015, Exelixis announced that it completed the submission of its rolling New Drug Application for cabozantinib as a treatment for patients with advanced RCC who have received one prior therapy; the U.S. Food and Drug Administration is currently conducting its preliminary review of the application’s suitability for full review and has not yet assigned a potential Prescription Drug User Fee Act date. The FDA previously granted Breakthrough Therapy and Fast Track designations to cabozantinib for its potential advanced RCC indication; in its NDA, Exelixis has requested Priority Review designation.

Cabozantinib is currently marketed in capsule form under the brand name COMETRIQ in the United States for the treatment of progressive, metastatic medullary thyroid cancer (MTC), and in the European Union for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. COMETRIQ is not indicated for patients with RCC. In the METEOR trial, and all other cancer trials currently underway, Exelixis is investigating a tablet formulation of cabozantinib distinct from the COMETRIQ capsule form. The tablet formulation of cabozantinib is the subject of the MAA for advanced RCC.

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2015 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; however, the five-year survival rate for patients with advanced or late-stage metastatic RCC is under 10 percent, with no identified cure for the disease.3

Until the introduction of targeted therapies into the RCC setting a decade ago, treatments for metastatic RCC had historically been limited to cytokine therapy (e.g., interleukin-2 and interferon). In the second and later-line settings, which encompass approximately 17,000 drug-eligible patients in the U.S. and 37,000 globally,4 two small-molecule therapies and an immune checkpoint inhibitor have been approved for the treatment of patients with advanced RCC who have received prior systemic therapy. The currently approved small-molecule agents have shown little differentiation in terms of efficacy and have demonstrated only modest progression-free survival benefit in patients refractory to sunitinib, a commonly-used first-line therapy.

The majority of clear cell RCC tumors exhibit down-regulation of von Hippel-Lindau protein function, either due to gene inactivation or epigenetic silencing, resulting in a stabilization of the hypoxia-inducible transcription factors and consequent up-regulation of VEGF, MET and AXL.5

The up-regulation of VEGF may contribute to the angiogenic nature of clear cell RCC, and expression of MET or AXL may be associated with tumor cell viability, a more invasive tumorphenotype and reduced overall survival. 6 Up-regulation of MET and AXL in clear cell RCC has also been shown to occur in response to treatment with VEGF receptor TKIs in preclinical models, indicating a potential role for MET and AXL in the development of resistance to these therapies.7

About Cabozantinib

Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGF receptors, AXL and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and maintenance of the tumor microenvironment.

Cabozantinib, marketed under the brand name COMETRIQ, is currently approved by the U.S. Food and Drug Administration for the treatment of progressive, metastatic medullary thyroid cancer (MTC).

The European Commission granted COMETRIQ conditional approval for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. Similar to another drug approved in this setting, the approved indication states that for patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions.

Important Safety Information, including Boxed WARNINGS

WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE

Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQ-treated patients.

Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.

COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.

Wound complications have been reported with COMETRIQ.

COMETRIQ treatment results in an increase in hypertension.

Osteonecrosis of the jaw has been observed in COMETRIQ-treated patients.

Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients treated with COMETRIQ.

The kidneys can be adversely affected by COMETRIQ. Proteinuria and nephrotic syndrome have been reported in patients receiving COMETRIQ.

Reversible Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ.
Avoid administration of COMETRIQ with agents that are strong CYP3A4 inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or severe hepatic impairment.
COMETRIQ can cause fetal harm when administered to a pregnant woman.

Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

Please see full U.S. prescribing information, including Boxed WARNINGS, at www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf

Please refer to the full European Summary of Product Characteristics for full European Union prescribing information, including contraindication, special warnings and precautions for use at www.sobi.com once posted.

On January 11, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported regulatory milestones and program updates on its CAR T and TCR product candidates (Press release, Bellicum Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508738]).

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Bellicum is preparing for the initiation of clinical studies in 2016 of its three most advanced CAR T and TCR adoptive cell therapy product candidates, BPX-701, BPX-601, and BPX-401. Today the Company submitted required documentation, including clinical trial protocols, for BPX-701 and BPX-601 for review by the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC). If selected for public review, such review would be expected to take place at the next RAC meeting scheduled for March 8-10, 2016.

The Company further announced that it expects to begin enrolling patients in Phase 1 trials of BPX-701 and BPX-601 in mid-2016, and BPX-401 in the second half of 2016, with IND filings to follow RAC review in each case.

BPX-701 is a CaspaCIDe-enabled natural high affinity T cell receptor (TCR) product candidate designed to target malignant cells expressing the preferentially-expressed antigen in melanoma (PRAME). Initial planned indications for BPX-701 development are Refractory or Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) with an additional study planned for metastatic uveal melanoma. Each of these are orphan indications where PRAME is highly expressed and for which current treatment options are limited. The Company expects to submit European regulatory filings to allow initiation of clinical development at a European site after the U.S. IND has been allowed.

BPX-601 is a GoCAR-T product candidate containing Bellicum’s proprietary iMC (inducible MyD88/CD40) activation switch, designed to treat solid tumors expressing prostate stem cell antigen (PSCA). As reported at ASH (Free ASH Whitepaper), preclinical data shows enhanced T-cell proliferation, persistence and in vivo anti-tumor activity compared to traditional CAR T therapies. The initial planned indication for BPX-601 development is non-resectable pancreatic cancer.

BPX-401 is a CIDeCAR product candidate incorporating Bellicum’s proprietary MC co-stimulatory domain and the CaspaCIDe safety switch, designed to target blood cancers expressing CD19.

"Throughout 2015, we made significant progress across all of our adoptive cell therapy programs," said Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "We’re now poised to bring three novel CAR T and TCR product candidates into the clinic in 2016, utilizing our molecular switch and proprietary co-stimulatory domain technologies. Importantly, we have in place the financial and management resources needed not only to bring these novel programs forward but also to continue discovering exciting new ways that our technologies can potentially improve the treatment of cancers and other diseases."

Background on the NIH RAC Process

Clinical trial protocols and other required information for product candidates that involve gene transfer are reviewed by both the FDA and the NIH, through the Recombinant DNA Advisory Committee or RAC. The NIH’s Office of Biotechnology Activities (OBA) convenes quarterly RAC meetings to make recommendations and selectively elicit public discussion of scientific, safety or ethical issues. The OBA notifies the FDA of the outcome of RAC reviews and reports are posted to the OBA website.

On January 11, 2016 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported the company’s 2016 strategy and expected clinical development and research milestones in conjunction with the 34th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Agios Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508737]). The presentation will outline three strategic priorities for 2016: continue rapid and broad late-stage clinical development for its lead isocitrate dehydrogenase (IDH) mutant inhibitors in hematologic malignancies and solid tumors; demonstrate clinical activity of its wholly owned, global pyruvate kinase-R (PKR) activators in patients; and advance research and initiate preclinical development of a program from the next wave of research.

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"We expect each of our programs to achieve important catalysts in 2016 that will bring us closer to our vision of helping people with cancer and rare genetic disorders," said David Schenkein, M.D., chief executive officer at Agios. "We believe these milestones, coupled with our growing late-stage development and commercial capabilities, set Agios firmly on the path to become a sustainable, multi-product biopharmaceutical company with a strong research core and broad pipeline of first-in-class medicines."

IDH Mutant Inhibitors

Dr. Schenkein continued, "We remain focused on executing on our ‘speed and breadth’ clinical development strategy for AG-221 and AG-120 in hematological malignancies, with the intent to complete enrollment of both 125-patient expansion cohorts this year. Further understanding the potential of our IDH mutant inhibitors in solid tumors remains a priority with several new and ongoing trials in 2016."

AG-221, AG-120 and AG-881 are part of Agios’ global strategic collaboration with Celgene Corporation.

Expected 2016 milestones for IDH mutant inhibitors in hematologic malignancies:

Complete enrollment of both 125-patient expansion cohorts for the Phase 1/2 study of AG-221 and Phase 1 study of AG-120 in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in the second half of 2016
Initiate a global, registration-enabling Phase 3 study of AG-120 in frontline AML patients with an IDH1 mutation in the second half of 2016

Initiate an expansion arm in high-risk myelodysplastic syndrome patients for AG-221 in 2016
Initiate a Phase 1/2 frontline combination study of AG-221 or AG-120 with VIDAZA (azacitidine) in newly diagnosed AML patients not eligible for intensive chemotherapy in the first quarter of 2016

Continue to enroll patients in the following ongoing clinical trials:
Phase 3 IDHENTIFY study of AG-221 vs. standard of care chemotherapy in R/R AML
Phase 1b frontline combination study of AG-221 or AG-120 with standard-of-care intensive chemotherapy in AML
Phase 1 dose-escalation and expansion study of AG-881 in IDH mutant positive hematologic malignancies

Expected 2016 milestones for IDH mutant inhibitors in solid tumors:

Initiate a randomized Phase 2 study of AG-120 in IDH1 mutant positive cholangiocarcinoma in the second half of 2016
Continue to enroll patients in the following ongoing clinical trials:

Expansion phase of the ongoing Phase 1 study of AG-120 in advanced IDH1 mutant positive solid tumors
Phase 1 dose-escalation and expansion study of AG-881 in IDH mutant positive solid tumors

PKR Activators

"Having initiated dosing in the Phase 1 healthy volunteer study of AG-519, we’ve completed the first of several key clinical milestones expected from our PKR activators in the first half of this year," said Dr. Schenkein. "Notably, we expect to present the first data from this study and the Phase 2 DRIVE PK study for AG-348 in PK deficiency patients. There are currently no approved or disease-modifying treatments for PK deficiency, which drives our focus on advancing potential new treatment options for these patients."

Milestone announced today:

Dosing was initiated in an integrated single ascending dose (SAD) and multiple ascending dose (MAD) placebo-controlled Phase 1 study of AG-519 in healthy volunteers

Expected 2016 milestones for PKR activators:

Present the first data from DRIVE PK, a global Phase 2, open-label safety and efficacy trial of AG-348 in adult, transfusion-independent patients with PK deficiency in the first half of 2016

Present data from Phase 1 study of AG-519 in healthy volunteers as well as preclinical findings about the molecule in the first half of 2016

Outline the clinical development plans for Agios’ PKR activators in beta-thalassemia in the second half of 2016

Present new findings from the Natural History Study of PK deficiency being conducted with Boston Children’s Hospital in the second half of 2016

Research Programs

"We continue to focus on discovering and validating first-in-class targets that meet our high bar for development and align with our precision medicine strategy," said Scott Biller, Ph.D., chief scientific officer at Agios. "We are excited to move the first program in our next wave of investigational medicines into preclinical development this year."

Agios scientists have discovered a novel pathway comprised of multiple targets with a shared vulnerability in MTAP-deleted tumors and have demonstrated that this pathway can be modulated by small molecule inhibitors, resulting in robust anti-tumor activity in animal models
MTAP (methylthioadenosine phosphorylase) is a metabolic enzyme that is deleted in approximately 15 percent of all cancers. This deletion is readily detected by a simple genomic test, thus allowing the selection of patients predicted to be sensitive to the therapy.

Expected 2016 milestones for research:

Publish preclinical findings on a new cancer metabolism program
Initiate preclinical development activities for the first molecule in the next wave of novel investigational medicines
Presentation at 34th Annual J.P. Morgan Healthcare Conference
Agios will webcast its corporate presentation from the 34th Annual J.P. Morgan Healthcare Conference in San Francisco on Monday, January 11, 2016 at 3:30 p.m. PST (6:30 p.m. EST). A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.