Syndax Pharmaceuticals (NASDAQ:SNDX) used a company R&D event to outline expansion plans for its approved medicines Revuforj and Niktimvo while introducing two pipeline assets aimed at non-small cell lung cancer and myelofibrosis.
Chief Executive Officer Michael Metzger said the company is now a “fully integrated commercial organization” with approved drugs on the market and a pipeline that management believes includes multiple potential blockbuster opportunities. Metzger said Revuforj and Niktimvo are “annualizing about $200 million in revenue” as Syndax works toward profitability.
Revuforj Expansion and Menin Inhibition
Nick Botwood, Syndax’s chief medical officer and head of R&D, said the company remains focused on expanding Revuforj in acute leukemia, including pivotal frontline acute myeloid leukemia studies. He highlighted EVOLVE-2, a study in patients unfit for intensive chemotherapy combining Revuforj with venetoclax, and a 7+3 combination study in frontline patients fit for intensive chemotherapy.
Botwood also pointed to two additional studies: MAINTAIN, a randomized post-transplant maintenance study in collaboration with Dana-Farber Cancer Institute, and RAVEN, a study in KMT2A-rearranged AML combining Revuforj with venetoclax with the goal of getting patients to transplant without intensive chemotherapy.
Syndax also detailed its move into myelofibrosis with menin inhibition. John Crispino, director of the Division of Experimental Hematology at St. Jude Children’s Research Hospital, reviewed preclinical work recently published in Cancer Cell. He said myelofibrosis affects about 20,000 people in the U.S., and that stem cell transplant is the only curative option, though about 90% of patients are not transplant candidates due to age or comorbidities.
Crispino said current JAK inhibitors reduce symptoms and splenomegaly but do not meaningfully reduce fibrosis or mutant allele burden, and most patients stop responding within two to three years. In preclinical models, he said Revuforj suppressed megakaryopoiesis, reduced atypical megakaryocytes and fibrosis, and showed antitumor effects both alone and in combination with ruxolitinib.
Botwood said Syndax plans to begin a Revuforj proof-of-principle trial in myelofibrosis in the fourth quarter. The planned phase 1/2 study, in partnership with the Myeloproliferative Neoplasm Research Consortium, is expected to enroll about 30 patients across two cohorts, including Revuforj after prior JAK inhibitor treatment and Revuforj added to ruxolitinib in patients with inadequate response.
Syndax is also advancing SNDX-62122, a wholly owned next-generation menin inhibitor for myelofibrosis. Botwood said the company expects to submit an IND in 2027 and begin a phase 1 study in myelofibrosis that year. He described the molecule as having high potency, increased selectivity, limited expected drug-drug interactions and activity against common resistance mutations.
Niktimvo in GVHD and IPF
Peter Ordentlich, Syndax’s chief scientific officer and founder, reviewed Niktimvo, also known as axatilimab, a CSF1R-blocking monoclonal antibody approved for chronic graft-versus-host disease after two prior lines of systemic therapy. He said Syndax and partner Incyte launched Niktimvo in early 2025 and that the launch has “gone extremely well.”
Ordentlich said Incyte is leading two frontline chronic GVHD studies. One combines axatilimab with ruxolitinib as a steroid-sparing approach, with data expected by the end of the year. The other is a phase 3 study of steroids with or without axatilimab, which Ordentlich said could read out in 2028.
Syndax is also testing axatilimab in idiopathic pulmonary fibrosis through the phase 2 MAXPIRe trial. Ordentlich said enrollment was completed earlier this year and that top-line data are expected in the fourth quarter. If results are positive, the company intends to move quickly into a phase 3 trial using the intravenous formulation, while subcutaneous development continues with Incyte.
Toby Maher, professor of clinical medicine and director of interstitial lung disease at the Keck School of Medicine of USC, described IPF as a deadly progressive lung disease with a major unmet need despite approved antifibrotic therapies. He said patients continue to die from respiratory failure and that tolerability issues have limited uptake of existing treatments.
Maher said the macrophage-monocyte axis is important in pulmonary fibrosis and that axatilimab’s mechanism gives him “true reason for being optimistic,” particularly because of observed lung responses in chronic GVHD patients. Company executives said the study remains blinded, though Maher said a safety monitoring committee had not identified safety concerns.
New EGFR Lung Cancer Program
Syndax also introduced SNDX-4321, an in-licensed mutant-selective allosteric EGFR inhibitor from Dana-Farber Cancer Institute for non-small cell lung cancer. Botwood said Syndax expects to file an IND by the end of the year and begin a phase 1 trial in 2027 in patients with L858R or atypical EGFR mutations who have progressed after EGFR tyrosine kinase inhibitor treatment, most likely osimertinib.
Michael Eck, professor at Dana-Farber Cancer Institute and Harvard Medical School, said SNDX-4321 binds outside the ATP binding pocket and can co-bind with certain ATP-competitive inhibitors, including osimertinib. He said that “double-drugging” approach could enhance efficacy, delay resistance and improve selectivity compared with wild-type EGFR inhibition.
Eck said the molecule is orally bioavailable, brain penetrant and active in multiple tumor models, including L858R models, models with C797S resistance and an intracranial xenograft model. He also said SNDX-4321 has shown activity against at least some atypical mutations, including L861Q, but has essentially no activity against exon 19 deletions or exon 20 insertions.
Metzger closed the event by saying Syndax expects multiple data readouts across its portfolio, including two phase 2 readouts this year and four assets in the clinic in 2027.
About Syndax Pharmaceuticals (NASDAQ:SNDX)
Syndax Pharmaceuticals is a clinical-stage biopharmaceutical company dedicated to developing novel therapies for the treatment of cancer. Headquartered in Waltham, Massachusetts, the company focuses on small-molecule inhibitors that target key epigenetic and protein interaction pathways. Syndax’s research platform aims to enhance the effectiveness of existing therapies and address high unmet medical needs in oncology.
The company’s lead investigational candidate, entinostat, is a selective class I histone deacetylase (HDAC) inhibitor being evaluated for multiple solid tumor and hematologic indications.
