Syndax Pharmaceuticals and Incyte Announce Positive Topline Results from the Pivotal AGAVE-201 Trial of Axatilimab in Chronic Graft-Versus-Host Disease

Syndax Pharmaceuticals (Nasdaq: NASDAQ: SNDX ) and Incyte (Nasdaq: NASDAQ: INCY ) today announced positive topline data from the pivotal AGAVE-201 trial of axatilimab, an anti-CSF-1R antibody, in adult and pediatric patients with chronic graft-versus-host disease (GVHD) following two or more prior lines of therapy.

The trial achieved its primary endpoint across all cohorts, with patients treated with axatilimab 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 demonstrating overall response rates (ORR) within the first six months of treatment of 74%, 67% and 50%, respectively (95% Confidence Interval [CI]: [63,83], [55,77] and [39,61], respectively). Responses were achieved across key patient subgroups, including those with prior exposure to ruxolitinib, belumosudil and/or ibrutinib.

Based on these results, and pending agreement from the U.S. Food and Drug Administration (FDA), Syndax and Incyte intend to submit a Biologics License Application (BLA) to the FDA by year-end 2023.

"Today marks an important day not only for Syndax and Incyte, but, more importantly, for patients suffering from chronic GVHD," said Michael A. Metzger, Chief Executive Officer of Syndax. "Axatilimab is the first investigational chronic GVHD treatment to target inflammation and fibrosis through the inhibition of disease associated macrophages, and the AGAVE-201 data demonstrates the potentially pronounced impact this mechanism, alone or in combination with standard of care therapies already available for the management of this disease, may have on patients suffering from chronic GVHD. These results underscore our belief that axatilimab could provide a valuable and highly differentiated therapeutic option for this devastating disease. We look forward to working with our partners at Incyte as we move axatilimab towards regulatory filing. On behalf of the entire Syndax team, I would like to thank the patients, their caregivers and the investigators who made this trial possible."

"The results from the AGAVE-201 study are extremely compelling and underscore the potential benefits axatilimab may offer appropriate patients facing the serious complications associated with chronic GVHD," said Steven Stein, M.D., Chief Medical Officer of Incyte. "At Incyte, we remain committed to advancing our research and understanding of this complex disease and will work closely with Syndax and regulatory authorities to bring this innovative medicine to chronic GVHD patients."

The AGAVE-201 pivotal study enrolled a total of 241 patients across 121 sites in 16 countries. Patients enrolled in the trial had received a median of four prior systemic therapies with 74% having previously received ruxolitinib, 23% having previously received belumosudil and 31% having previously received ibrutinib. 54% of these patients had at least four organs involved at baseline including 45% with lung involvement.

Among responders treated with 0.3 mg/kg of axatilimab, 60% of patients maintained a response at 12 months (measured from first response to new systemic therapy or death, based on the Kaplan Meier estimate). The median duration of response in this population has not been reached. Additionally, in the 0.3 mg/kg group, 55% of patients experienced a clinically meaningful improvement in symptoms, as measured by at least a seven-point decrease in the modified Lee chronic GVHD Symptom Scale score.

The most common adverse events were consistent with the on-target effects of CSF-1R inhibition and with what was previously observed with axatilimab treatment. In the overall population, adverse events in greater than 20% of patients include an increase in aspartate aminotransferase, blood creatine phosphokinase, lipase, blood lactate dehydrogenase, alanine aminotransferase and fatigue (n=239). Serious adverse events in the overall population occurred in 101 (42.3%) patients, with 37 (15.5%) patients experiencing adverse events leading to discontinuation of study treatment. In the 0.3 mg/kg dose group (n=79), fatigue was the only serious adverse event that occurred in greater than 20% of patients. Serious adverse events in the 0.3 mg/kg group occurred in 30 (38%) patients, with five (6.3%) patients experiencing adverse events leading to discontinuation of study treatment.

"Chronic GVHD is a very common complication post allogeneic hematopoietic stem cell transplant that can have profound effects on patient medical burden and quality of life. More effective treatment options for this significant complication are desperately needed," said Carrie Kitko, M.D., Medical Director of the Pediatric Stem Cell Transplant Program at the Vanderbilt-Ingram Cancer Center. "I am highly encouraged by these data which demonstrate robust responses in a heavily pre-treated patient population. These findings further support that axatilimab has the potential to provide a clinically meaningful response for patients suffering from this morbid condition."

Conference Call and Webcast
Syndax will host a conference call and webcast to discuss the results of the Phase 2 AGAVE-201 trial today, July 24, 2023 at 8:30 a.m. ET.

The live 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:

Conference ID: SNDXSPEC
Domestic Dial-in Number: 800-579-2543
International Dial-in Number: 785-424-1789
Live webcast: https://www.veracast.com/webcasts/syndax/events/specconf.cfm

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.