On December 11, 2017 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, reported data from the ongoing HGB-205 clinical study of its LentiGlobin gene therapy product candidate in patients with severe sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) (Press release, bluebird bio, DEC 11, 2017, View Source [SID1234522550]). The findings will be presented today in a poster session at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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"People with SCD and TDT experience serious complications and organ damage as a result of their disease and complications from chronic blood transfusions. Addressing the underlying genetic causes of these diseases has the potential to dramatically improve patient outcomes," said Dave Davidson, M.D., chief medical officer, bluebird bio. "All three patients with severe SCD in the HGB-205 study showed a steady increase in HbAT87Q production in the first six months following LentiGlobin therapy, with the longest-treated patient showing stable hemoglobin levels over two and a half years. All four patients with TDT are transfusion-free following therapy, up to almost four years in the first patient treated. The durable treatment effects observed to date in this study are encouraging, particularly given the manufacturing process improvements that we implemented across our subsequent clinical studies of LentiGlobin, and additional changes to the HGB-206 study protocol that we hope will further improve outcomes for patients with SCD."

These data will be presented by Marina Cavazzana, M.D., Ph.D., Professor of Medicine at Paris Descartes University and Research Director at the Centre for Clinical Research in Biotherapy, Necker Hospital, and at the Institute of Genetic Diseases, Imagine, Paris, France. Professor Cavazzana is the primary investigator of the HGB-205 study.

"All seven patients in this study continue to experience notable clinical improvement. Since being treated with LentiGlobin therapy, the four patients with TDT have been free of chronic transfusions with near normal and stable levels of total hemoglobin," said Professor Cavazzana. "While progress has been made with medications to treat SCD and TDT, we are in need of better options for our patients. This study suggests that LentiGlobin has the potential to be a transformational one-time therapy for people with SCD and TDT."

Longer Term Follow-up on the First Patients with Severe Hemoglobinopathies Treated with LentiGlobin Gene Therapy (Poster Abstract #4609)

Presenter: Marina Cavazzana, M.D., Ph.D. Necker-Enfants Malades Hospital, Paris, France

Poster Session Date & Time:Monday, December 11 at 6:00 p.m.

Location: Building A, Level 1, Hall A2

HGB-205 is an ongoing, open-label, single-center Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product (DP) in the treatment of patients with severe SCD and TDT. The study enrolled three patients with severe SCD and four patients with TDT, who have undergone infusion with LentiGlobin DP. Results as of September 20, 2017 include:

SCD:

All three treated patients showed rising HbAT87Q levels in the first six months.
Patient 1204 was 13 years old at study enrollment. At last follow-up (35.2 months), this patient had a total hemoglobin of 12.4 g/dL, of which 6.1 g/dL was HbAT87Q (52 percent anti-sickling Hb). HbAT87Q concentration in this patient has remained stable since approximately nine months post-infusion. The patient continues to show marked clinical improvement.
Patient 1207 was 16 years old at study enrollment. At last follow-up (8.9 months), this patient had a total hemoglobin of 10.0 g/dl, of which 0.7 g/dl was HbAT87Q (14 percent anti-sickling Hb). This patient had a pre-treatment history of frequent episodes of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) despite hydroxyurea prior to beginning regular transfusions. Patient 1207 had episodes of ACS and hospitalization at six and eight months post-treatment, and received three transfusions.
Patient 1208 was 21 years old at study enrollment. At last follow-up (6.0 months), this patient had a total hemoglobin of 10.6 g/dL, of which 2.7 g/dL was HbAT87Q (46 percent total anti-sickling Hb). This patient had a pre-treatment history of frequent episodes of VOCs and ACS prior to beginning regular transfusions, and was still symptomatic while receiving regular transfusions. Following LentiGlobin treatment, Patient 1208 has had no episodes of VOCs or ACS (with six months follow-up).
TDT:

All four patients with TDT have remained free of chronic transfusions since shortly after receiving LentiGlobin DP.
Patient 1201 (β0/βE genotype) has been free of transfusions for 45.2 months with total hemoglobin of 10.1 g/dL, of which 6.7 g/dL was HbAT87Q.
Patient 1202 (β0/βE genotype) has been free of transfusions for 40.1 months with total hemoglobin of 12.9 g/dL, of which 10.1 g/dL was HbAT87Q.
Patient 1206 (β0/βE genotype) has been free of transfusions for 23.8 months with total hemoglobin of 11.1 g/dL, of which 8.0 g/dL was HbAT87Q.
Patient 1203, who is homozygous for the severe β+ mutation IVS1-110, has been free of transfusions for 20.9 months with total hemoglobin of 8.7 g/dL, of which 6.7 g/dL was HbAT87Q.
Three of four patients (1201, 1202 and 1206) were able to begin therapeutic phlebotomy. Patient 1202 subsequently discontinued iron chelation and phlebotomy.
The safety profile of LentiGlobin DP continues to be consistent with myeloablative conditioning with single-agent busulfan. No DP-related adverse events have been observed, and there is no evidence of clonal dominance.
About SCD
Sickle cell disease (SCD) is an inherited disease caused by a mutation in the beta-globin gene, that produces βS-globin. High levels of HbS in patients with SCD are responsible for the characteristic chronic anemia, vaso-occlusive crises, and other acute and chronic manifestations of SCD which lead to significant morbidity and early mortality.

Where adequate medical care is available, common treatments for patients with SCD largely revolve around prevention of infection and management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Allogeneic hematopoietic stem cell transplant (HSCT) is currently the only available option to address the underlying genetic cause of SCD, though it carries significant risk. Complications of allogeneic HSCT include a risk of treatment-related mortality, graft failure, graft-versus-host disease (GvHD) and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.

About TDT
Transfusion-dependent β-thalassemia (TDT) is a severe genetic disease characterized by reduced or absent hemoglobin levels that results in severe anemia and ineffective red blood cell production. Supportive care for people with TDT consists of a lifelong regimen of chronic blood transfusions to enable survival and suppress symptoms of the disease, and iron chelation therapy to manage iron overload that results from the transfusions. Despite the availability of supportive care, many people with TDT experience serious complications and organ damage due to underlying disease and iron overload.

Allogeneic HSCT is currently the only available option to address the underlying genetic cause of TDT, though it carries significant risks. Complications of allogeneic HSCT include a risk of treatment-related mortality, graft failure, GvHD and opportunistic infections, particularly in patients who undergo non-sibling matched allogenic HSCT.

About the HGB-205 Study
HGB-205 is an ongoing, open-label Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin in the treatment of subjects with TDT and SCD. The study enrolled seven subjects who will be followed to evaluate safety and transfusion requirements post-transplant. Among patients with sickle cell disease only, efficacy will also be measured based on the number of vaso-occlusive crises or acute chest syndrome events. For more information on the HGB-205 study, please visit clinicaltrials.gov using identifier NCT02151526.

On December 11, 2017 Oscotec reported that shares of Oscotec rebounded on the company’s announcement that it has launched a clinical trial in the U.S. on SKI-G-801, a treatment for acute myeloid leukemia (AML) (Press release, Oscotec, DEC 11, 2017, View Source [SID1234573544]).

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The biotech company said in a public regulatory filing on Monday that its phase-1 clinical trial on SKI-G-801 will begin at six U.S. hospitals.

Oscotec’s shares, which had slid since Dec. 4, rebounded to 10,250 won ($9.4) as of noon on Monday, up 150 won from the previous trading day. Compared with early this year’s stock price of 7,390 won per share, it was up 38 percent.

SKI-G-801 is a treatment that selectively inhibits fms-like tyrosine receptor kinase 3 (FLT3). The company hopes that the new drug candidate will lower side effects and recurrence rate, compared to existing chemotherapies.

The U.S. study will check safety and drug tolerance, after administering SKI-G-801 to recurring or non-reacting AML patients and raising doses in a phased way. The trial will also test the drug’s appropriate doses and efficacy in AML patients with FLT3 mutations.

"Compared to the existing FLT3 inhibitors, SKI-G-801 has excellent pharmacologic activation and long-acting efficacy. Besides, we confirmed its efficacy on FLT3 mutations, which existing inhibitors had no effectiveness, as well as in the drug-resistant environment," Oscotec said.

It went on to say,"If we confirm the safety, drug tolerance, and oncolytic efficacy in the clinical trial, we expect that we will be able to transfer our technology to a multinational pharmaceutical company."

In July 2015, Oscotec transferred its investigational non-small cell lung cancer therapy YH25448 to Yuhan Corp. under an income-sharing contract.

Oscotec’s revenue reached 3.25 billion won ($2.99 million) in the first three quarters this year, with an operating loss of 992 million won.

Its flagship product is InduCera, a material for bone transplant, which takes up about 30 percent of the total sales.

On December 11, 2017 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that IND-enabling production of FT500 has commenced at University of Minnesota, Molecular and Cellular Therapeutics, a state-of-the-art, FDA-registered Good Manufacturing Practice (GMP) facility (Press release, Fate Therapeutics, DEC 11, 2017, View Source [SID1234526859]). Jeffrey S. Miller, M.D., Professor of Medicine, Deputy Director of the Masonic Cancer Center, University of Minnesota presented an overview today at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition of the clinical translation of FT500, a first-of-kind natural killer (NK) cell cancer immunotherapy generated from a self-renewing clonal master pluripotent cell line (MPCL). The clonal MPCL was created from a single induced pluripotent stem cell (iPSC) using the Company’s proprietary iPSC product platform. The Company expects to file an Investigation New Drug (IND) application in the first quarter of 2018 for the clinical testing of multiple dosing cycles of FT500 in combination with FDA-approved checkpoint inhibitor therapies for advanced solid tumors in the outpatient setting.

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"Preclinical studies demonstrate that FT500 has direct anti-tumor activity and the capacity to secrete inflammatory cytokines and chemokines upon activation. This enables the cell product to potentially exploit both innate and adaptive immunity and elicit a broad, multi-targeted immune response against tumor cells by engaging a diverse set of stress ligands, recruiting a polyclonal T-cell population to the tumor site and augmenting T-cell activation in the tumor microenvironment," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "While checkpoint inhibitors have transformed the cancer therapy landscape by inducing long term remissions in multiple solid tumor indications, many tumor subtypes are resistant to checkpoint blockade therapy and non-responsiveness remains a significant concern. We thank the FDA for considering the unique therapeutic value of FT500 in combination with checkpoint inhibitors and its supportive feedback on our ongoing clinical translation and planned 1Q18 IND submission."

In November 2017, Fate Therapeutics received a Type B Pre-IND meeting written response from U.S. Food & Drug Administration (FDA) for FT500. The written response and subsequent FDA correspondence aligned the Company’s approach to safety testing, product manufacture, quality assessment and clinical trial design in support of IND submission. FT500 is manufactured in a first-of-kind paradigm that uses a clonal MPCL as a renewable cell source for large-scale, cost-effective manufacture of a homogeneous NK cell product that can be reliably administered as a multi-dose, off-the-shelf cell product without patient matching restrictions. The Company estimates that a single manufacturing campaign conducted in one cGMP suite can yield hundreds of doses of up to 1×109 NK cells per dose. This novel approach to cell therapy has the potential to mediate safer, more effective pharmacologic activity, including in combination with cycles of other cancer treatments.

In preclinical studies conducted by the Company, FT500 displays multiple potential mechanisms by which it may synergize with T cells to activate the immune system in patients with tumors that are non-responsive to checkpoint inhibitors alone. FT500 has shown augmented secretion of cytokines and chemokines capable of enhancing T-cell activation in vitro. In addition, localized administration of FT500 into the peritoneal cavity results in the migration of circulating T cells into the peritoneal cavity. Finally, utilizing a three-dimensional tumor spheroid model in vitro, infiltration of activated T cells into tumor spheroids was significantly enhanced in the presence of FT500.

Fate Therapeutics has built an extensive intellectual property portfolio broadly covering the genomic engineering of iPSCs and off-the-shelf NK and T-cell cancer immunotherapies. Its proprietary portfolio includes compositions and methods for engineering iPSCs to modify their biological properties using CRISPR and other nucleases, and for manufacturing cells of all hematopoietic lineages from iPSCs including NK cells. In addition, the Company has an exclusive license from the University of Minnesota covering iPSC-derived NK cells expressing targeting receptors, including modified CD16 Fc receptors and chimeric antigen receptors for human therapeutic use.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables large-scale generation of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event, and selecting a single iPSC for maintenance as a clonal master pluripotent cell line (MPCL). Similar to master cell lines used for the manufacture of monoclonal antibodies, clonal MPCLs can serve as a renewable cell source for the consistent and repeated manufacture of homogeneous cell products with the potential to treat many different diseases and many thousands of patients in an off-the-shelf manner. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 90 issued patents and 100 pending patent applications.

On December 11, 2017 Hookipa Biotech AG ("Hookipa"), a clinical stage biotech company pioneering an innovative class of immune activation therapies for oncology and infectious diseases, reported that it has raised $59.6 million (€50.0 million) in an oversubscribed Series C financing (Press release, Hookipa Biotech, DEC 11, 2017, View Source [SID1234522515])

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The round was led by an undisclosed blue chip U.S. public investment fund specializing in life sciences, alongside other new investors HBM Partners, Hillhouse Capital, Sirona Capital and strategic investor Gilead. All current Hookipa investors, Sofinnova Partners, Forbion Capital Partners, Boehringer Ingelheim Venture Fund, Takeda Ventures and BioMedPartners participated in the round.

The proceeds of the fundraising will be primarily used to progress two proof-of concept clinical trials of Hookipa’s lead development programs, a phase 2 study of the Company’s prophylactic Cytomegalovirus ("CMV") vaccine in solid organ transplant patients, and a phase 1 study of its TheraT based active immunization therapy in patients with head & neck squamous cell carcinoma. In addition, Hookipa plans to expand its technology platform into other disease areas, such as prostate cancer.

Hookipa’s arenavirus-based vector technologies TheraT and Vaxwave have been designed to infect dendritic cells and stimulate potent and long-lasting immune responses. HB-101, the Company’s Vaxwave-based CMV vaccine successfully completed a phase 1 trial earlier this year, demonstrating safety and immunogenicity. TheraT has been shown to elicit uniquely potent antigen-specific CD8+ cytotoxic T cell responses and strong tumor control in mice. TheraT works by delivering tumor-associated antigen-specific immunization alongside the release of the alarmin interleukin-33 (IL-33), which is key in stimulating potent and protective CD8+ cytotoxic effector T lymphocytes.

Joern Aldag, Chief Executive Officer of Hookipa said: "Our vision is of a world in which the immune system actively controls infectious diseases and cancer, using monotherapy or combinations of medications. We welcome the funding and support from this group of leading current and new investors, who have recognized the potential, versatility, and uniqueness of our novel viral vector platform in this context. This financing allows us to progress two lead development programs through the major inflection points of clinical proof of concept, and to expand our clinical work to additional virology and oncology indications."

On December 11, 2017 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported data from two studies evaluating ivosidenib (AG-120) and an investigational use of IDHIFA (enasidenib) in patients with newly diagnosed acute myeloid leukemia (AML) and an isocitrate dehydrogenase (IDH)1 or IDH2 mutation (Press release, Agios Pharmaceuticals, DEC 11, 2017, View Source [SID1234522573]). The data were presented as part of the scientific program at the 59thAmerican Society of Hematology Annual Meeting in Atlanta.

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"The totality of the data presented at ASH (Free ASH Whitepaper) demonstrate the potential benefit of IDHm inhibitors in the frontline setting for patients with AML," said Eytan Stein, M.D., study investigator and attending physician in the leukemia service at Memorial Sloan Kettering Cancer Center. "The Phase 1 frontline combination trials showed that ivosidenib and enasidenib are well tolerated when combined with standard induction chemotherapy or azacitadine and both trials demonstrated early encouraging signs of efficacy. I look forward to evaluating both ivosidenib and enasidenib in late-stage, placebo-controlled clinical trials to understand the full impact of these medicines on newly diagnosed AML patients."

Combination with Standard Induction Chemotherapy
The first presentation, given by Dr. Stein, evaluated ivosidenib or enasidenib in combination with standard induction chemotherapy in patients with newly diagnosed AML and an IDH1 or IDH2 mutation. During induction, patients received either 500 mg of ivosidenib and 7 + 3 standard chemotherapy (daunorubicin 60 mg/m2/day or idarubicin 12 mg/m2/day x 3 days with cytarabine 200 mg/m2/day x 7 days) (n=32) or 100 mg of enasidenib and 7 + 3 standard chemotherapy (n=56). Of these patients, 69% in the ivosidenib arm and 57% in the enasidenib arm had de novo AML, while the remaining patients had secondary AML (sAML). For patients with sAML, 40% in the ivosidenib arm and 63% in the enasidenib arm had received prior hypomethylating agent therapy. After induction, patients could receive up to four cycles of consolidation chemotherapy while continuing ivosidenib or enasidenib. Patients who achieved a complete response (CR) or a complete response with incomplete neutrophil or platelet recovery (CRi/CRp) after consolidation could continue to take single agent ivosidenib or enasidenib daily for up to two years from day one of induction.

Ivosidenib Results
In the ivosidenib arm, the most common Grade 3 or higher non-hematologic adverse events during the induction period were febrile neutropenia (60%), blood bilirubin increased (9%), hypertension (9%), colitis (9%), increased alanine aminotransferase (9%) and increased aspartate aminotransferase (9%). The 30 and 60-day mortality rates were both 6%, and there were no dose-limiting toxicities. The median time to absolute neutrophil count (ANC) recovery (>500/µL) was 28.5 days (95% CI 27,34). Median time to platelet recovery (>50,000/µL) was 28 days (95% CI 26,34).

The CR+CRi/CRp rate for de novo patients was 91% (19/21) and 44% (4/9) for sAML patients. The overall best response of CR+ CRi/CRp rate for all patients was 77% (23/30).

Enasidenib Results
In the enasidenib arm, the most common Grade 3 or higher non-hematologic adverse events during the induction period were febrile neutropenia (63%), blood bilirubin increased (9%), hypertension (9%) and bacteremia (9%). The 30 and 60-day mortality rates were 5% and 7%, respectively. There was one dose-limiting toxicity in the enasidenib combination arm consisting of persistent Grade 4 thrombocytopenia lasting beyond 42 days from the start of induction. The median time to ANC recovery (>500/µL) was 34 days (95% CI 29,35). Median time to platelet recovery (>50,000/µL) was 33 days (95% CI 29,50).

The CR+CRi/CRp rate for de novo patients was 67% (18/27) and 57% (13/23) for sAML patients. The overall best response of CR+CRi/CRp rate for all patients was 62% (31/50).

"The early results from these studies of ivosidenib and enasidenib in combination with traditional frontline AML treatment are highly encouraging and support the strategy to advance IDHm inhibitors into the newly diagnosed setting," said Chris Bowden, M.D., chief medical officer of Agios. "We are focused on evaluating the IDHm inhibitors in late-stage studies that span the entire frontline setting with our ongoing Phase 3 AGILE study of ivosidenib in combination with azacitidine versus azacitidine and a planned Phase 3 study of ivosidenib and enasidenib in combination with 7+3 intensive chemotherapy."

Combination with Azacitidine
The second presentation, given by Courtney DiNardo, M.D., evaluated an investigational use of enasidenib or ivosidenib in combination with azacitidine in patients with newly diagnosed AML unable to receive intensive chemotherapy. In the study, patients received 100mg (n=3) or 200mg (n=3) of enasidenib daily plus azacitidine or 500 mg of ivosidenib (n=11) plus azacitidine. At the data cutoff, 11 patients remained on the study (3 enasidenib, 8 ivosidenib).

Enasidenib Results

For patients receiving the enasidenib combination, the most common Grade 3-4 hematologic adverse event was neutropenia (33%, 2/6). The most common Grade 3-4 non-hematologic adverse events were pneumonia (33%, 2/6) and hyperbilirubinemia (33%, 2/6). IDH differentiation syndrome was reported in one patient.

Four of six patients had a response, including two CRs, one partial response (PR) and one morphologic leukemia-free state (MLFS).

Ivosidenib Results
For patients receiving the ivosidenib combination, the most common Grade 3-4 hematologic adverse events were anemia (18%, 2/11) and febrile neutropenia (18%, 2/11) with neutropenia and thrombocytopenia each with one event (9% each). The most common Grade 3-4 non-hematologic adverse event was pneumonia (18%, 2/11). IDH differentiation syndrome was reported in one patient.

Eight of 11 patients had a response, including four CRs, one CRi, one PR and two MLFS.

Neither IDHIFA nor ivosidenib are approved for the treatment of patients with newly diagnosed AML or approved in combination with azacitidine.

About IDHIFA

IDHIFA (enasidenib) is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation as detected by an FDA-approved test.

Important Safety Information

WARNING: DIFFERENTIATION SYNDROME
Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5 months after IDHIFA initiation. Symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia and need for supplemental oxygen; pulmonary infiltrates and pleural effusion; renal impairment; fever; lymphadenopathy; bone pain; peripheral edema with rapid weight gain; and pericardial effusion. Hepatic, renal, and multi-organ dysfunction have also been observed. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity: Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 1 month after the last dose. Pregnant women, patients becoming pregnant while receiving IDHIFA, or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) included total bilirubin increased (81%), calcium decreased (74%), nausea (50%), diarrhea (43%), potassium decreased (41%), vomiting (34%), decreased appetite (34%), and phosphorus decreased (27%)
The most frequently reported ≥Grade 3 adverse reactions (≥5%) included total bilirubin increased (15%), potassium decreased (15%), phosphorus decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and nausea (5%)
Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure
LACTATION
Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with IDHIFA and for at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

Investor Event and Webcast Information
Agios will host an investor event on Monday, December 11, 2017 beginning at 8:00 p.m. ET in Atlanta to review data presented at ASH (Free ASH Whitepaper). The event will be webcast live and can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com.