Syndax Pharmaceuticals and Incyte Announce Axatilimab Phase 1/2 Data in Patients with Chronic Graft-Versus-Host Disease Published in the Journal of Clinical Oncology

– Treatment with axatilimab resulted in an overall response rate (ORR) of 67% across all patients; and an ORR of 82% in patients dosed at 1 mg/kg every 2 weeks in the Phase 2 portion of the trial –

– Broad multi-organ clinical benefit including in lung, skin, and joints and fascia observed in heavily pretreated patient population –

WALTHAM, Mass. and WILMINGTON, Del., Dec. 5, 2022 /PRNewswire/ -- Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX) and Incyte (Nasdaq: INCY) today announced that results from the Phase 1/2 trial of axatilimab, Syndax's anti-CSF-1R antibody, in patients with recurrent or refractory chronic graft-versus-host disease (cGVHD) following two or more prior lines of therapy, were published in the Journal of Clinical Oncology.

A total of 40 patients with refractory disease who received a median of four prior systemic therapies, some of which included ibrutinib, ruxolitinib and belumosudil, were treated in the Phase 1/2 dose escalation trial. Thirty-nine patients were evaluable for response as of the data cutoff. All study participants were treated for a median duration of 29 weeks, with all responding patients treated for a median duration of 38 weeks at the time of data cut-off. Results showed:

• Overall response rate by cycle 7 day 1 was 82% (18/22) in the Phase 2 cohort (1mg/kg every two weeks) and 67% (26/39) among all evaluable patients treated in the dose escalation study. Best ORR (complete response + partial response) observed at any point during the study in all patients treated was 69% (27/39).
• Median duration of response for Phase 2 responding patients was not reached; 33% of patients experiencing sustained response lasting 20 weeks or longer.
• A decrease in glucocorticoids doses was observed in 52% of responding patients.
• Responses were observed across a range of organ systems with difficult to treat manifestations such as lung (5/16), skin (5/35), and joints and fascia (19/31).
• A clinically meaningful disease improvement using the Lee Symptom Score of at least 7 points was seen in 58% (21/36) of all evaluable patients.

Axatilimab was well tolerated with a favorable safety profile in this refractory population. The most common adverse events were consistent with on-target effects of CSF-1R inhibition. In the Phase 1 cohort, two dose limiting toxicities were reported, both at the 3 mg/kg every two weeks dose. There were no ≥Grade 3 on-target toxicities of CSF-1R blockade seen in the Phase 2 cohort. There was no incidence of cytomegalovirus or other viral reactivation, and no apparent increases in risk for infection. Serious adverse events occurred in 40% (16/40) of patients, with seven (18%) patients discontinuing the study intervention due to adverse events, four (10%) of which were deemed treatment-related.

"We believe axatilimab is well positioned to potentially be a first- and best-in-class anti-CSF-1R antibody for cGVHD," said Kate Madigan, M.D., Chief Medical Officer of Syndax. "The robust, durable responses and multi-organ clinical benefit observed in this Phase 1/2 trial in refractory patients support the potential for axatilimab to serve as an effective intervention in this underserved population."

"The results of this Phase 1/2 dose finding study are very encouraging regarding the ability of axatilimab to provide meaningful clinical responses in chronic GVHD patients that have been refractory to multiple prior therapies" said Carrie Kitko, M.D., Medical Director of the Pediatric Stem Cell Transplant Program at the Vanderbilt-Ingram Cancer Center, and the corresponding author of the Phase 1/2 publication. "Combining both anti-inflammatory and anti-fibrotic effects through the targeting of disease associated macrophages would be particularly exciting for this patient population that would benefit from a reduction in sclerotic and fibrotic manifestations of chronic GVHD. In the past simply stopping further progression of those manifestations was considered a "win", but some of these patients are actually having improvements in joint range of motion and skin tightening."

The article, titled "Axatilimab for chronic graft-versus-host disease after failure of at least two prior systemic therapies: results of a Phase 1/2 study," is available online.

About Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease, 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 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.1,2 Chronic GVHD typically manifests across multiple organ systems, with skin and mucosa being commonly involved, and is characterized by the development of fibrotic tissue.3

About Axatilimab

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 cGVHD and IPF. Phase 1/2 data of Axatilimab in cGVHD demonstrating its broad activity and tolerability was last presented at the 63rd American Society of Hematology Annual Meeting. Axatilimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with cGVHD and IPF. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.

Enrollment in the Company's global pivotal Phase 2 AGAVE-201 Phase 2 study evaluating the efficacy, safety, and tolerability of axatilimab in patients with recurrent or refractory active cGVHD who have received at least two prior lines of systemic therapy is complete, and topline data is expected mid-2023. Additionally, a Phase 1 combination trial of ruxolitinib and axatilimab, led by Incyte, is in preparation and expected to initiate by end of the first quarter of 2023, and a Phase 2b trial of axatilimab in patients with idiopathic pulmonary fibrosis led by Syndax is expected to begin in the fourth quarter of 2022.

For more information about AGAVE-201, visit https://clinicaltrials.gov/ct2/show/NCT04710576

About Syndax Pharmaceuticals, Inc.

Syndax Pharmaceuticals is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib (SNDX-5613), a highly selective inhibitor of the Menin–MLL binding interaction, and axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor, both currently in pivotal trials. For more information, please visit www.syndax.com or follow the Company on Twitter and LinkedIn.

About Incyte

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.

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, 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; the COVID-19 pandemic may disrupt our business and that of the third parties on which we depend, including delaying or otherwise disrupting our clinical trials and preclinical studies, manufacturing and supply chain, or impairing employee productivity; 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.

Incyte Forward-looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding the potential of axatilimab to treat patients with chronic graft-versus-host disease or for any other indication, the AGAVE-201 study and other clinical trials involving axatilimab, contain predictions, estimates and other forward-looking statements.

These forward-looking statements are based on Incyte's current expectations and are 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; the effects of the COVID-19 pandemic and measures to address the pandemic on Incyte's clinical trials, supply chain, other third-party providers and development and discovery operations; determinations made by regulatory authorities; Incyte's dependence on its relationships with its collaboration partners; the efficacy or safety of Incyte's products and the products of Incyte's collaboration partners; the acceptance of Incyte's products and the products of Incyte's collaboration partners 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 and its quarterly report on Form 10-Q for the quarter ended September 30, 2022. Incyte disclaims any intent or obligation to update these forward-looking statements.

References

1. SmartAnalyst 2020 SmartImmunology Insights chronic GVHD report.
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.
3. Kantar 2020 GVHD Expert Interviews N=32 interviews.

Syndax Contact

Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827

Incyte Contacts:
Media
Catalina Loveman
cloveman@incyte.com
+1 302 498 6171

Investors
Christine Chiou
cchiou@incyte.com
+1 302 274 4773

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SOURCE Syndax Pharmaceuticals, Inc.