Axatilimab-csfr

– Trial met its primary endpoint across all dose cohorts with 74% of patients at the 0.3 mg/kg every 2 weeks dose achieving a complete or partial response within the first six months of treatment – – Niktimvo approved by U.S. FDA for the treatment of chronic graft-versus-host disease after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg – – Niktimvo added to latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of chronic GVHD – WILMINGTON, Del. and WALTHAM, Mass., Sept. 18, 2024 /PRNewswire/ -- Incyte (Nasdaq:INCY) and Syndax Pharmaceuticals (Nasdaq:SNDX) today announced that results from the pivotal Phase 2 AGAVE-201 trial of Niktimvo™ (axatilimab-csfr), an anti-CSF-1R antibody, in adult and pediatric patients with recurrent/refractory active chronic graft-versus-host disease (GVHD) who had received at least two prior lines of systemic therapy were published in The New England Journal of Medicine.1 The publication, entitled "Axatilimab in Recurrent or Refractory Chronic Graft-Versus-Host Disease" can be found online here. "Niktimvo is the first FDA approved treatment that targets the disease-modifying macrophages involved in both the fibrotic and inflammatory processes driving chronic GVHD," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "Following the launch of this new medicine, clinicians will be able to offer patients an agent that targets a distinct pathway and has demonstrated broad and durable responses in patients with chronic GVHD who progressed after at least two prior lines of therapy." "The publication of the pivotal AGAVE-201 data in The New England Journal of Medicine underscores the importance of this dataset and the practice-changing potential of Niktimvo," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "Together with the Incyte team, we look forward to delivering this important new medicine to patients with chronic GVHD and exploring its potential application in earlier lines of chronic GVHD treatment and other diseases." The AGAVE-201 pivotal trial enrolled 241 patients with recurrent or refractory chronic GVHD who had received two or more prior systemic therapies, with 74% having previously received ruxolitinib, 31% having previously received ibrutinib and 23% having previously received belumosudil. Patients were enrolled across 121 sites in 16 countries. The results show that the trial met the primary endpoint across all cohorts receiving Niktimvo at doses of 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks and 3.0 mg/kg every four weeks. Patients in the 0.3 mg/kg every two weeks cohort (n=80) achieved the highest overall response rate (ORR) of 74% within the first six months of treatment (95% CI: 63-83). Patients in this cohort experienced a median time to response to Niktimvo of 1.7 months (range: 0.9-8.1). Among the patients who had a response in the 0.3 mg/kg dose cohort, an estimated 60% of patients maintained a response at 12 months (measured from first response until new systemic therapy or death, based on the Kaplan Meier estimate). "Results from the AGAVE-201 trial show rapid, durable responses in all organs studied and patient subgroups, with clinically meaningful symptom burden reduction reported by most of these heavily-pretreated patients who had not responded to previous lines of treatment," said Daniel Wolff, M.D., Ph.D., Head, Senior Physician, and Professor at University Hospital Regensburg. "As patients with chronic GVHD often cycle through the currently available therapies in the pursuit of relief from this debilitating disease, with nearly 50% of patients requiring more than two lines of therapy, I am pleased that Niktimvo will soon be available for these patients in need." Clinically meaningful reduction in chronic GVHD symptoms (>5-point reduction in the modified Lee Symptom Scale) was reported by 60% of patients in the 0.3 mg/kg dose cohort. In the same cohort, organ-specific responses, including complete responses (CRs), were seen across all organs studied, including lower gastrointestinal (GI), upper GI, esophagus, joints/fascia, mouth, lungs, liver, eyes and skin. Additionally, responses were notable in fibrosis-dominated organs, including the esophagus (78%), joints and fascia (76%), lungs (47%) and skin (26%). Responses were observed across key patient subgroups, including objective response rates ≥75% in the 0.3 mg/kg cohort who received prior ibrutinib, ruxolitinib, and/or belumosudil. The most common treatment-emergent adverse events (TEAEs) were consistent with the on-target effects of CSF-1R inhibition and with what was previously observed with Niktimvo treatment. TEAEs in greater than 20% of patients in the overall population (n=239) include transient laboratory abnormalities of increases in aspartate aminotransferase (AST), blood creatine kinase, lipase, lactate dehydrogenase, and alanine aminotransferase (ALT), as well as fatigue, and infections. In the 0.3 mg/kg dose cohort, grade ≥3 adverse events were reported in 49% of patients, with 6% experiencing TEAEs leading to discontinuation of treatment, based on the data cut that was analyzed for publication. On August 14, 2024, Incyte and Syndax announced the U.S. Food and Drug Administration's (FDA) approval of 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), with a recommended dosage of 0.3 mg/kg, up to a maximum dose of 35 mg, as an intravenous infusion over 30 minutes every two weeks until progression or unacceptable toxicity. On August 30, 2024, axatilimab-csfr (Niktimvo) was added to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 2A recommendation for the treatment of chronic GVHD after the failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg.2 Treatments are classified as category 2A when there is uniform NCCN consensus that the intervention is appropriate, based on lower level evidence. The updated NCCN guidelines are available at . 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. The Companies anticipate launching Niktimvo in the U.S. no later than early first quarter 2025. 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 (cGVHD) whose disease had progressed after two or more 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 cGVHD by cycle 7 day 1. Secondary endpoints included 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 . 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 Niktimvo from UCB. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for Niktimvo 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. All other trademarks are the property of their respective owners. Niktimvo (axatilimab-csfr) is licensed from Syndax. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Infusion-Related Reactions Niktimvo™ (axatilimab-csfr) can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received Niktimvo in the clinical trial (AGAVE-201), with Grade 3 or 4 reactions in 1.3%. Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to Niktimvo. Monitor patients for signs and symptoms of infusion-related reactions, including fever, chills, rash, flushing, dyspnea, and hypertension. Interrupt or slow the rate of infusion or permanently discontinue Niktimvo based on severity of the reaction. Embryo-Fetal Toxicity Based on its mechanism of action, Niktimvo may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with Niktimvo and for 30 days after the last dose. ADVERSE REACTIONS Serious adverse reactions occurred in 44% of patients who received Niktimvo (N=79). Serious adverse reactions in >2 patients included infection (pathogen unspecified) (14%), viral infection (14%) and respiratory failure (5.1%). 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. Clinically relevant adverse reactions in <10% of patients who received Niktimvo included: Eye disorders: periorbital edema Skin and subcutaneous skin disorders: pruritus Vascular disorders: hypertension Immunogenicity: Anti-Drug Antibody–Associated Adverse Reactions Across treatment arms in patients with cGVHD who received Niktimvo in clinical trials, among the patients who developed anti-drug antibodies (ADAs), hypersensitivity reactions occurred in 26% (13/50) of patients with neutralizing antibodies (NAb) and in 4% (2/45) of those without NAb. USE IN SPECIFIC POPULATIONS Lactation Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 30 days after the last dose of Niktimvo. Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating Niktimvo. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Niktimvo and for 30 days after the last dose of Niktimvo. DOSAGE AND ADMINISTRATION Dosage Modifications for Adverse Reactions Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK), amylase, and lipase prior to the start of Niktimvo therapy, every 2 weeks for the first month, and every 1 to 2 months thereafter until abnormalities are resolved. See Table 1 in the Prescribing Information for more recommendations. 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 or follow the Company on X (formerly Twitter) and LinkedIn. Incyte Forward-Looking Statements Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding whether and when Niktimvo might provide a successful treatment option for patients with chronic GVHD and statements regarding the potential for axatilimab to treat other conditions, contain predictions, estimates and other forward-looking statements. These forward-looking statements are based on Incyte's current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the U.S. FDA and other regulatory authorities outside of the U.S.; the efficacy or safety of Incyte and its partners' products; the acceptance of Incyte and its partners' products in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; and other risks detailed from time to time in Incyte's reports filed with the Securities and Exchange Commission, including its annual report on form 10-K for the year ended December 31, 2023 and its report on form 10-Q for the quarter ended June 30, 2024. Incyte disclaims any intent or obligation to update these forward-looking statements. Syndax 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 "may," "will," "expect," "plan," "anticipate," "estimate," "intend," "believe" 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, the acceptance of Syndax and its partners' products in the marketplace, sales, marketing, manufacturing and distribution requirements, and the potential use of our 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. 1 Wolff D, et al. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med 2024;391:1002-14. DOI: 10.1056/NEJMoa2401537. 2 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hematopoietic Cell Transplantation (HCT). Version 2.2024 – August 30, 2024. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Incyte Contacts: Media [email protected] Investors [email protected] Syndax Contact: Sharon Klahre [email protected] Tel 781.684.9827 SNDX-G SOURCE Syndax Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Having an in-house PD-1 allows Incyte to test novel combinations with fewer costs and faster R&D timelines than it otherwise could, CEO Hervé Hoppenot said. Incyte’s late PD-1 entrant Zynyz has chalked up a unique clinical win. Yet company CEO Hervé Hoppenot views the antibody molecule not necessarily as a major revenue driver but as an aide to the company’s oncology pipeline.In a first-in-class win, Zynyz and chemotherapy slashed the risk of progression or death by 37% compared with chemo alone in patients with previously untreated, inoperable advanced squamous cell anal carcinoma (SCAC), according to results from the phase 3 POD1UM-303 trial presented at the annual European Society for Medical Oncology Congress (ESMO).Patients in the Zynyz arm went a median 9.3 months without tumor progression versus 7.4 months for the control group.Incyte plans to file Zynyz with the FDA by the end of the year in the indication, potentially making it the first PD-1 inhibitor approved for first-line anal cancer, Hoppenot said in an interview with Fierce Pharma.Anal cancer is not a large oncology market from a financial perspective, Hoppenot acknowledged. Zynyz’s target patient population in the potential use has about 10,000 new diagnoses per year across the U.S. and Europe.Even before an official FDA approval, some doctors have been using PD-1 inhibitors such as Merck & Co.’s Keytruda off label to treat anal cancer patients, Hoppenot explained. These uses aren’t always covered by insurance because of the absence of a regulatory approval. Now, Incyte hopes Zynyz can fill that niche market. The company’s original bid to get Zynyz approved as a post-chemo second-line anal cancer treatment was rejected by the FDA in 2021 because of a low tumor response rate and some patient deaths unrelated to disease progression.Besides the progression-free survival result in the POD1UM-303 trial, Zynyz has shown a preliminary trend toward improving patient survival. While the data are immature, Zynyz was linked to a 30% reduction in the risk of death, as patients who took the PD-1 agent survived a median 29.2 months versus 23 months for the control arm. Zynyz showed the advantage despite the trial allowing patients in the control arm to cross over to receive the PD-1 inhibitor after progression.Given the effect size and statistical considerations, Hoppenot said he’s confident that Zynyz will show a statistically significant overall survival benefit at the final analysis, which he said is coming “very soon” next year. The value of an in-house PD-1 drugZynyz entered the market last year with an FDA approval in Merkel cell carcinoma, another rare cancer type. In addition, Incyte announced a positive phase 3 trial, POD1UM-304, for Zynyz’s combination with chemo in first-line non-small cell lung cancer (NSCLC). But that indication faces some regulatory uncertainty given the trial’s comparator arm is chemotherapy alone, when Keytruda in combination with chemo is the current standard of care.Incyte will speak with the FDA to discuss the drug’s best path forward in first-line NSCLC, and the company is prioritizing the anal cancer filing first, Hoppenot said.Even if Zynyz eventually secures its first-line NSCLC nod, the drug’s market potential there seems limited given Keytruda’s dominance, and because the PD-1 king is nearing its patent cliff in 2028.Still, Zynyz could provide Incyte some returns in the niche indications. But, more importantly, “we believe that the optionality value of being able to develop our other pipeline products in combination with [an] approved PD-1 is very valuable,” Hoppenot said.Having an in-house PD-1 allows Incyte to test its novel agents in combinations without having to buy Keytruda, the CEO said. That translates into millions of dollars in savings and faster R&D timelines.“It’s basically giving me strategic flexibility in a way that would be very difficult if I had to do it with another product,” Hoppenot said. “So, after approval, is it going to be used with biosimilar of Keytruda? I don’t really care.” Oncology's place at IncyteGeneral oncology isn’t Incyte’s biggest business area. The company is best known for its Novartis-partnered myelofibrosis and graft-versus-host disease drug Jakafi, and that department just got bigger with the FDA approval for its Syndax-partnered CSF-1R antibody Niktimvo last month.Investors are also focused on the launch of Incyte’s Opzelura cream in autoimmune skin conditions and potential phase 3 readouts for the JAK1 inhibitor povorcitinib, which is being developed in a broad range of inflammatory diseases.In oncology beyond the bone marrow cancer myelofibrosis, Incyte in February gained full rights to CD19 antibody Monjuvi from former partner MorphoSys and in August announced a positive phase 3 readout in previously treated follicular lymphoma. At ESMO 2024, the company is also sharing for the first time early-phase data for its CDK2 inhibitor, INCB123667, in certain gynecological cancers. Still, Hoppenot argued that the three business areas are essentially equal in their importance to the company. The key is optionality, the CEO said, so that success from one of the drugs could more than compensate for the expected decline of Jakafi, which faces its own patent cliff in 2028.Incyte is interested in striking deals to access external innovations, having recently bought immunology biotech Escient Pharmaceuticals for $750 million. In oncology dealmaking, the company doesn’t have specific guardrails around tumor types but is more focused on whether the mechanism in question is unique, Hoppenot said.Being realistic about the price of a first- or best-in-class drug in late-stage development, Hoppenot said Incyte is focusing on earlier-stage assets, especially around targets where the company has done some internal research.