WALTHAM, Mass. and WILMINGTON, Del. – Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX) and Incyte (Nasdaq: INCY) announced today that they have entered into an exclusive worldwide collaboration and license agreement to develop and commercialize axatilimab, Syndax’s anti-CSF-1R monoclonal antibody.
“This partnership has the potential to significantly expand and maximize the axatilimab program across multiple lines of treatment in chronic graft-versus-host Disease (cGVHD), as well as additional indications in which the monocyte-macrophage lineage plays a vital role in the fibrotic disease process, such as idiopathic pulmonary fibrosis (IPF),” said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. “Incyte is a proven leader in the development and commercialization of many important innovative therapies, including a treatment for GVHD. We are thrilled to be working alongside this talented and determined team to combine our expertise as we strive to provide new treatment options for patients in desperate need of effective interventions.”
“We are excited to partner with Syndax and for the opportunity to bring another potential treatment to patients with life-threatening conditions, like GVHD,” said Hervé Hoppenot, Chief Executive Officer of Incyte. “Collaborations between companies like Incyte and Syndax, who are both dedicated to scientific advancement, contribute to the development of new innovative medicines that may benefit patient communities around the world.”
Syndax and Incyte are seeking to develop axatilimab as a backbone therapy for patients with cGVHD as well as in additional immune-mediated diseases where CSF-1R-dependent monocytes and macrophages are believed to contribute to organ fibrosis. Syndax recently completed a Phase 1/2 trial of axatilimab in patients with cGVHD. Data from the Phase 1 portion of the trial highlighting the tolerability and high response rate of axatilimab in cGVHD patients refractory to multiple therapeutic agents were reported during an oral presentation at the American Society of Hematology Annual Meeting in December 2020. Updated results from the Phase 1 portion and preliminary results from the Phase 2 expansion portion of the study, which evaluated 1 mg/kg of axatilimab every two weeks, are expected to be presented at a medical meeting in the fourth quarter of 2021.
Enrollment continues in the ongoing global pivotal Phase 2 AGAVE-201 trial of axatilimab monotherapy in patients with cGVHD, with topline data expected in 2023. The companies also plan to initiate additional trials of axatilimab in patients with cGVHD in 2022, including a Phase 2 trial in combination with a JAK inhibitor in patients with steroid-refractory cGVHD. Beyond cGVHD, Syndax plans to commence a Phase 2 proof of concept trial of axatilimab early next year in patients with IPF, a serious, life-limiting orphan disease for which axatilimab could represent a much-needed treatment option with a novel mechanism of action.
Terms of the Collaboration
Under the terms of the agreement, Incyte will lead global commercial activities for axatilimab across all indications. The companies will participate in a 50:50 profit share in the U.S., and Syndax will receive double-digit royalties on sales outside of the U.S. Syndax will retain the option to co-promote axatilimab for any approved indications in the U.S. In connection with the agreement, Syndax will receive an upfront payment of $117 million plus a $35 million equity investment, which will be purchased at $24.62 per share, a 30% premium to the volume weighted average price over the 10 days prior to September 24, 2021. Syndax will also be eligible to receive up to an additional $450 million in potential regulatory, development and commercial milestone payments.
The companies will share development costs associated with global and U.S.-specific trials for all agreed upon trials at a rate of 55% (Incyte) and 45% (Syndax), with Incyte responsible for 100% of future development costs for trials that are specific to ex-U.S. countries. Syndax will fund the initial development of axatilimab in IPF and Incyte will have the option to co-fund late-stage development for this indication.
The agreement between Syndax and Incyte, including the upfront payment and equity investment, is subject to clearance by the U.S. antitrust authorities under the Hart-Scott-Rodino Act and will become effective as soon as these conditions have been met.
Goldman Sachs & Co. LLC is acting as the exclusive financial advisor to Syndax.
About Chronic Graft-Versus-Host Disease
Chronic graft-versus-host disease (cGVHD), an immune response of the donor-derived hematopoietic cells against recipient tissues, is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) which can last for years. Chronic GVHD is estimated to develop in approximately 40% of transplant recipients, and affects approximately 14,000 patients in the U.S., Chronic GVHD typically manifests across multiple organ systems, with skin and mucosa being commonly involved, and is characterized by the development of fibrotic tissue.
About Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis (IPF) is a serious, life-limiting chronic lung disease characterized by fibrosis and scarring of lung tissue with a median survival of 3-5 years after diagnosis. Patients with IPF experience debilitating symptoms including progressive shortness of breath, particularly with exertion, chronic cough, fatigue, weakness, and chest discomfort. Currently approved drugs slow but do not halt disease progression and the only curative therapy is lung transplant, which is an option for less than 5% of patients. Estimates indicate that IPF could affect approximately 150,000 patients in the U.S. and approximately 260,000 patients across the seven major pharmaceutical markets (U.S., Japan, UK, Spain, Germany, Italy, and France).
Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In pre-clinical models, inhibition of signaling through the CSF-1 receptor has been shown to reduce the number of disease-mediating macrophages along with their monocyte precursors, which has been shown to play a key role in the fibrotic disease process underlying diseases, such as chronic graft-versus-host disease (cGVHD) and idiopathic pulmonary fibrosis (IPF). Axatilimab data has demonstrated deep, durable responses and multiorgan clinical benefit in patients with cGVHD refractory to multiple therapeutic agents, and is currently being evaluated in the global pivotal Phase 2 AGAVE-201 trial in patients with cGVHD. Axatilimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with cGVHD and IPF. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.
Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development, and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.
About Syndax Pharmaceuticals, Inc.
Syndax Pharmaceuticals is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. The Company’s pipeline includes SNDX-5613, a highly selective inhibitor of the Menin–MLL binding interaction, axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor, and entinostat, a class I HDAC inhibitor. For more information, please visit www.syndax.com or follow the Company on Twitter and LinkedIn.
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2. Bachier, CR. et al. ASH annual meeting 2019; abstract #2109 Epidemiology and Real-World Treatment of Chronic Graft-Versus-Host Disease Post Allogeneic Hematopoietic Cell Transplantation: A U.S. Claims Analysis.
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4. SMARTImmunology Insights. “Idiopathic Pulmonary Fibrosis.” Presentation, March 2020.