menin

BOSTON--( BUSINESS WIRE )-- Foundation Medicine, Inc. today announced a collaboration with Syndax Pharmaceuticals (Nasdaq: SNDX) to develop a companion diagnostic for the identification of acute myeloid leukemia (AML) patients harboring an NPM1 mutation. As part of the collaboration, Syndax will also support Foundation Medicine’s efforts to pursue regulatory approval of an assay based on the FoundationOne ® Heme platform. NPM1 mutations are unique to AML patients and are the most frequently found genetic alteration at approximately 30% of newly diagnosed AML. 1 There are currently no targeted treatments approved for patients with NPM1- mutated AML, 2 and the 5-year overall survival for patients with NPM1 -mutated AML is approximately 50%. 3 Menin inhibitors such as revumenib, currently under development by Syndax, are emerging as a promising targeted therapy option for NPM1 -mutated AML. 1 To date, only six biomarkers associated with hematologic malignancies have approved targeted therapies, 4 but more than 40 additional biomarkers are being studied in hematology clinical trials. 5 “Blood cancers have a devastating impact on the lives of so many patients and their families,” said Ashley Yocum, PhD, Executive Research Lead at The Leukemia & Lymphoma Society. “Thanks to advancements in comprehensive genomic profiling, and decades of scientific research for new treatments, we are seeing a paradigm shift in how many types of blood cancer are diagnosed and treated, allowing more patients to benefit from the promise of precision medicine with access to more personalized treatment options.” If approved, the assay could be the first next-generation sequencing companion diagnostic to detect genomic alterations in hematologic neoplasms, including enhancing the identification of patients with NPM1 mutations who may be eligible for revumenib. “As the number of biomarkers with targeted therapies in hematologic malignancies reaches a critical inflection point, it is essential for physicians to have access to high-quality tests to make informed treatment decisions for their patients,” said Troy Schurr, Chief Biopharma Officer at Foundation Medicine. “We are incredibly excited to work with Syndax to advance the FoundationOne Heme platform as a companion diagnostic, a potential first for the FoundationOne Heme platform, and if approved, help patients with AML access this potential therapy.” Foundation Medicine’s portfolio of FDA-approved diagnostic tests offer physicians both blood- and tissue-based testing options for detecting genomic alterations that help guide personalized treatment decisions. Foundation Medicine is the global leader in companion diagnostic approvals, with approximately 60% of all U.S. companion diagnostic approvals for next-generation sequencing (NGS) testing. Foundation Medicine ® and FoundationOne ® are registered trademarks of Foundation Medicine, Inc. About Foundation Medicine: Your Essential Partner in Cancer Care Foundation Medicine is a pioneer in molecular profiling for cancer, working to shape the future of clinical care and research. We collaborate with a broad range of partners across the cancer community and strive to set the standard for quality, scientific excellence, and regulatory leadership. Our deep understanding of cancer biology helps physicians make informed treatment decisions for their patients and empowers researchers to develop new medicines. Every day, we are driven to help our partners find answers and take action, enabling more people around the world to benefit from precision cancer care. For more information, please visit us on www.FoundationMedicine.com and follow us on LinkedIn and X . About FoundationOne ® Heme FoundationOne ® Heme is a laboratory developed test that was developed and its performance characteristics determined by Foundation Medicine. FoundationOne Heme has not been cleared or approved by the U.S. Food and Drug Administration. For more information on FoundationOne Heme, please see its Technical Specifications at foundationmedicine.com/heme . The test employs RNA sequencing in addition to DNA sequencing to simultaneously detect all classes of genomic alterations, including base pair substitutions, insertions and deletions, copy number alterations and rearrangements, and gene fusions. About Revumenib Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed by Syndax Pharmaceuticals for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Revumenib was granted Orphan Drug Designation for the treatment of AML, ALL and MPAL by the FDA and for the treatment of AML by the European Commission, and Fast Track designation by the FDA and is currently under review for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. A New Drug Application (NDA) for revumenib for the treatment of adult and pediatric R/R KMT2Ar acute leukemia is currently under review by the U.S. FDA with a PDUFA action date of December 26, 2024. 1 Swaminathan M, Bourgeois W, Armstrong SA, Wang ES. Menin inhibitors in acute myeloid leukemia—What does the future hold?. The Cancer J. 2022;28(1):62-66. https://doi.org/10.1097/PPO.0000000000000571 2 Ranieri R, Pianigiani G, Sciabolacci S, et al. Current status and future perspectives in targeted therapy of NPM1-mutated AML. Leukemia. 2022;36(10):2351-2367. https://doi.org/10.1038/s41375-022-01666-2 3 Angenendt L, Röllig C, Montesinos P, et al. Chromosomal abnormalities and prognosis in NPM1-mutated acute myeloid leukemia: A pooled analysis of individual patient data from nine international cohorts. J Clin Oncol. 2019;37(29):2632-2642. https://doi.org/10.1200/JCO.19.00416 4 List of Cleared or Approved Companion Diagnostic Devices. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools . 5 Multiple secondary sources used to cross validate information, including Trialtrove, clinicatrials.gov, EudraCT, ChiCTR; FDA approval timeline estimation based on Ph3 PCD + 8 months review; analysis based on current Phase 1/2, Phase 2 and Phase 3 trials with inclusion criteria requiring patient selection based on alterations to specific biomarkers.

WILMINGTON, DE & WALTHAM, MA, USA I August 14, 2024 I Incyte (Nasdaq:INCY) and Syndax Pharmaceuticals (Nasdaq:SNDX) today announced that the U.S. Food and Drug Administration (FDA) has approved Niktimvo™ (axatilimab-csfr), an anti-CSF-1R antibody, for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs.). “The approval of Niktimvo represents a significant treatment advancement for patients with chronic GVHD who have failed at least two lines of previous therapy” “With the approval of Niktimvo, patients with chronic GVHD whose disease has progressed after prior therapies, now have a new treatment option with a novel mechanism of action to help address the serious and devastating complications associated with this disease,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “Niktimvo is Incyte’s second approved treatment for chronic GVHD, underscoring our continued commitment to advancing the development of new medicines on behalf of patients with this disease and the medical community.” Chronic GVHD is a serious condition that can occur after an allogeneic stem cell transplant (the transfer of stem cells from a donor) in which the donated cells initiate an immune response and attack the transplant recipient’s organs. Chronic GVHD is a leading cause of significant morbidity and mortality after an allogeneic stem cell transplant and is estimated to develop in approximately 42% of transplant recipients, affecting approximately 17,000 patients in the U.S. 1 Of those patients who develop chronic GVHD, nearly 50% require at least three lines of treatment, emphasizing the need for additional effective treatment options. 2 “The approval of Niktimvo represents a significant treatment advancement for patients with chronic GVHD who have failed at least two lines of previous therapy,” said Michael A. Metzger, Chief Executive Officer, Syndax. “We look forward to bringing this first-in-class anti-CSF-1R antibody to patients in need of new treatment options, while also continuing to explore axatilimab’s potential in combination with other standard of care therapies for chronic GVHD and in other indications.” The FDA approval was based on data from the global AGAVE-201 study evaluating the safety and efficacy of Niktimvo in 241 adult and pediatric patients with refractory chronic GVHD who received at least two prior lines of systemic therapy. The trial met the primary endpoint across all cohorts receiving Niktimvo. Results from the study showed durable responses across all organs studied and patient subgroups. Among patients who received Niktimvo at the approved dose of 0.3 mg/kg every two weeks (N=79), 75% achieved an overall response rate (ORR) within the first six months of treatment, with a median time to response of 1.5 months. Additionally, 60% maintained a response at 12 months (measured from first response to new systemic therapy or death, based on the Kaplan Meier estimate). The trial also met a key exploratory endpoint, with a majority (56%) of patients achieving a ≥7-point improvement in the modified Lee Symptom Scale (mLSS) score. Organ-specific complete and partial responses were demonstrated across all organs studied that are affected by chronic GVHD, including lower gastrointestinal (GI), upper GI, esophagus, joints/fascia, mouth, lungs, liver, eyes and skin. Serious adverse reactions occurred in 44% of patients who received Niktimvo (N=79). Serious adverse reactions observed in >2 patients included infection (pathogen unspecified), viral infection and respiratory failure. Permanent discontinuation of Niktimvo due to an adverse reaction occurred in 10% of patients and dose reduction due to adverse reaction occurred in 8% of patients. Dose interruptions due to an adverse reaction occurred in 44% of patients. The adverse reactions leading to dose interruption in >2 patients were viral infection, infection (pathogen unspecified), bacterial infection, musculoskeletal pain and pyrexia. The most common (≥15%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase (AST), infection (pathogen unspecified), increased alanine aminotransferase (ALT), decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase (CPK), increased alkaline phosphatase (ALP), nausea, headache, diarrhea, cough, bacterial infection, pyrexia and dyspnea. “Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” said Daniel Wolff, M.D., Ph.D., Head of the GVHD Center at the University Hospital Regensburg. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pre-treated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.” The Biologics License Application (BLA) for Niktimvo for the treatment of chronic GVHD after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs) was reviewed by the FDA under Priority Review. The FDA grants Priority Review designation to applications for medicines that, if approved, would treat a serious condition and provide significant improvements in the safety or effectiveness of the treatment. In the United States, Niktimvo will be co-commercialized by Incyte and Syndax Pharmaceuticals. Incyte has exclusive commercialization rights for Niktimvo outside of the U.S. To facilitate patient dosing and limit product waste, following the FDA’s approval of Niktimvo (as a 50mg vial), Incyte and Syndax will seek approval to launch two smaller vial sizes. Following FDA approval of the new vial sizes, the Companies anticipate launching Niktimvo in the U.S., no later than early first quarter 2025. Syndax Conference Call Information Syndaxwill host a conference call and live audio webcast at 6:00 p.m. ET, today, August 14, 2024. The live audio webcast may be accessed through the Events & Presentations page in the Investors section of the Company’s website. Alternatively, the conference call may be accessed through the following: Domestic Dial-in Number: 1-800-860-2442 International Dial-in Number: 1-412-858-4600 Please ask to be joined into the Syndax Pharmaceuticals call. Live webcast: https://event.choruscall.com/mediaframe/webcast.html?webcastid=6M3ZcewG For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call. About AGAVE-201 The global AGAVE-201 dose-ranging trial evaluated the efficacy, safety and tolerability of axatilimab in 241 adult and pediatric patients with recurrent or refractory active chronic GVHD whose disease had progressed after two prior therapies. Patients were randomized to one of three treatment groups that investigated a distinct dose of axatilimab administered at 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks or 3.0 mg/kg every four weeks. The trial’s primary endpoint was the proportion of patients in each dose group who achieved an objective response as defined by 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1. Secondary endpoints include duration of response, percent reduction in daily steroids dose, organ specific response rates and validated quality-of-life assessments using the modified Lee Symptom Scale. For more information about AGAVE-201, visit https://www.clinicaltrials.gov/study/NCT04710576 . About Niktimvo™ (axatilimab-csfr) Niktimvo (axatilimab-csfr) is a first-in-class anti-CSF-1R antibody approved for use in the U.S. for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs). In 2016, Syndax licensed exclusive worldwide rights to develop and commercialize axatilimab from UCB. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab in cGVHD and any future indications. Axatilimab is being studied in frontline combination trials in chronic GVHD – a Phase 2 combination trial with ruxolitinib (NCT06388564) and a Phase 3 combination trial with steroids are expected to initiate by year end. Axatilimab is also being studied in an ongoing Phase 2 trial in patients with idiopathic pulmonary fibrosis (NCT06132256). Niktimvo is a trademark of Incyte. Please see the full Prescribing Information for Niktimvo . About Incyte A global biopharmaceutical company on a mission to Solve On. , Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia. For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn , X , Instagram , Facebook, YouTube . About Syndax Syndax Pharmaceuticals is a commercial stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company’s pipeline include revumenib a highly selective menin inhibitor, and Niktimvo™ (axatilimab-csfr), a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment for both revumenib and Niktimvo. For more information, please visit www.syndax.com/ or follow the Company on X (formerly Twitter) and LinkedIn . SOURCE: Incyte

– Pivotal AUGMENT-101 trial met its primary endpoint at interim analysis of patients with KMT2Ar AML and ALL (p-value = 0.0036) – – NDA filing for revumenib in R/R KMT2Ar acute leukemia is being reviewed under RTOR; PDUFA action date of December 26, 2024 – WALTHAM, Mass., Aug. 12, 2024 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that data from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib, a first-in-class menin inhibitor, in adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) have been published in the Journal of Clinical Oncology. "Publication of the pivotal AUGMENT-101 dataset in KMT2Ar acute leukemia allows for a broader dissemination of these important data and highlights revumenib's impressive and consistent clinical profile that has led to meaningful results for these advanced patients," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "These data serve as the foundation for the NDA filing that is currently being reviewed by the FDA under its RTOR program. As we approach the potential FDA approval of revumenib, we are actively preparing for a successful commercial launch to enable us to deliver this important medicine to patients in need." "Despite an increased understanding of the mechanisms governing development of KMT2Ar acute leukemia, no available therapies adequately serve this population," said Ghayas C. Issa, M.D., Assistant Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "The high rate of deep, MRD negative responses along with a safety profile that supports prolonged time on therapy and maintained remission post-stem cell transplant gives me confidence that revumenib could serve as a paradigm-changing treatment." The FDA has granted Priority Review for the New Drug Application (NDA) for revumenib for the treatment of adult and pediatric R/R KMT2Ar acute leukemia. The NDA is being reviewed under the FDA's Real-Time Oncology Review Program (RTOR) and has a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2024. In March 2024, the Company announced the completion of enrollment in the final AUGMENT-101 pivotal trial cohort in patients with R/R mutant nucleophosmin (mNPM1) AML. Topline data is expected in the fourth quarter of 2024 and could support a supplemental NDA filing for revumenib in R/R mNPM1 AML in the first half of 2025. About the data The publication entitled "Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)" includes positive data from a total of 94 acute leukemia patients with KMT2Ar in the pivotal trial as of the July 2023 data cutoff, 57 of whom had central confirmation of their KMT2Ar status, sufficient follow-up and were in the efficacy analysis. The AUGMENT-101 trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the KMT2Ar acute leukemia population. The CR + CRh rate was 23% (10/44; 95% CI: 11.5, 37.8) in adult patients and 23% in pediatric patients (3/13; 95% CI: 5.0, 53.8). The median time to CR + CRh in the overall efficacy-evaluable population was 1.9 months (range: 0.9, 4.6) and the CR + CRh responses were durable with a 6.4-month (95% CI: 3.4, NR) median duration and 46% (6/13) remaining in response at the time of data cutoff. Minimal residual disease (MRD) status was assessed in 10 of the 13 patients who achieved a CR + CRh, 70% (7/10) of whom were MRD negative. In the efficacy evaluable patients, the overall response rate1 was 63% (36/57; 95% CI: [49.3, 75.6]), and the composite response rate (CRc) was 44% (25/57). MRD status was assessed in 22 of the 25 patients who achieved a CRc, 68% (15/22) of whom were MRD negative. Responses were observed in all major subgroups, including across the number of prior treatments and prior stem cell transplant, and across a broad age range with the youngest responder aged 1 year and oldest aged 75 years. A total of 14 (39%) patients who achieved an overall response underwent HSCT, eight of whom did not achieve a CR or CRh prior to transplant. Half (7/14) of the patients who had an HSCT resumed revumenib treatment post-transplant. Median overall survival at the time of data cutoff was 8.0 months (95% CI: 4.1, 10.9). Revumenib was well tolerated and the safety profile was consistent with the Company's previously reported data. In the pivotal AUGMENT-101 trial safety population (n=94), treatment-emergent adverse events (TEAEs) of Grade ≥3 that occurred in ≥10% of patients included febrile neutropenia (37%), neutropenia (29%), thrombocytopenia (21%), anemia (18%), differentiation syndrome (16%), QTc prolongation (14%), sepsis (12%), and hypokalemia (11%). TEAEs leading to dose reduction or discontinuation were low at 9.6% (9/94) and 12.8% (12/94) of patients, respectively. Grade 3 DS was observed in 15% (14/94) of patients while one patient (1%) experienced Grade 4 DS and no patients experienced Grade 5 DS. No Grade 4 or 5 QTc events occurred. There were no discontinuations related to DS, cytopenias or QTc prolongation as of the July 2023 data cutoff. About Revumenib Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology Annual Meeting, and full data have now been published in the Journal of Clinical Oncology. Revumenib was granted Orphan Drug Designation for the treatment of AML and ALL by the FDA and for the treatment of AML by the European Commission, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. About Syndax Syndax Pharmaceuticals is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a highly selective menin inhibitor, and axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. For more information, please visit or follow the Company on X (formerly Twitter) and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "believe," "could," "estimate," "expects," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" or the negative or plural of those terms, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, and the potential use of its product candidates to treat various cancer indications and fibrotic diseases. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. References 1 Overall response rate includes CR, CRh, CRp, CRi, MLFS, and PR; Composite complete remission (CRc) includes CR, CRh, CRp, and CRi CR = Complete remission CRh = Complete remission with partial hematologic recovery CRp = Complete remission with incomplete platelet recovery CRi = Complete remission with incomplete count recovery MLFS = Morphologic leukemia-free state PR = Partial response Syndax Contact Sharon Klahre Syndax Pharmaceuticals, Inc. [email protected] Tel 781.684.9827 SNDX-G SOURCE Syndax Pharmaceuticals, Inc.