DDW Editor Reece Armstrong speaks to Michael Metzger, CEO of Syndax, about its work on developing therapeutics for challenging cancer targets. 

RA: What are the unmet needs in relapsed or refractory acute leukaemia. How great is this unmet need in paediatric patients?  

MM: Syndax is initially focused on two forms of aggressive, life-threatening acute leukaemia known as KMT2A-rearranged acute leukaemia and mutant NPM1 (mNPM1) acute myeloid leukemia (AML). Despite recent advances in cancer care, long-term outcomes unfortunately remain poor for many of these patients, especially for those who relapse or do not respond to their initial therapy. 

NPM1 mutations are the most common genetic alteration observed in AML, occurring in approximately 30% of cases. KMT2A rearrangements are observed in approximately 10% of acute leukaemias, including both AML and acute lymphoblastic leukaemia (ALL). KMT2A rearrangements are found in patients of all ages but are most frequently observed in children, particularly infants. For instance, KMT2A rearrangements are observed in approximately 80% of infants with ALL, the most common type of childhood leukaemia. The high prevalence of this genetic alteration among such a vulnerable population underscores the tremendous patient need.  

RA: Your company is developing therapies based on menin inhibition. Could you explain how this approach differs from the standard treatments currently available?

MM: Menin inhibitors are small molecules that work by disrupting the specific protein-protein interactions that are driving leukaemic cell growth in patients with certain types of genetic alterations. By disrupting this interaction, menin inhibitors can remove the ‘block’ that was preventing cells in the bone marrow from differentiating into normal blood cells. This is a targeted approach, as opposed to chemotherapy, the conventional treatment approach for many patients. Chemotherapy works by broadly killing cells that are multiplying quickly, including both cancerous and healthy cells.  

RA: You’ve received two approvals for drugs in both cancer care and GvHD. In oncology, what have been some of the lessons you’ve learned when bringing a drug to market?  

MM: We have clearly seen the benefits of delivering novel medicines supported by compelling clinical data and strong commercial execution. As expected, all the work we and our partners did prior to launch has been crucial to the success of both launches. For example, with our menin inhibitor, Revuforj (revumenib), we did extensive work understanding the workflows at priority accounts and educating payers on the urgent unmet need. We also established advanced data analytics that could be leveraged after approval to help our field team identify and engage HCPs at the time when they may have an appropriate patient in their care. These efforts helped ensure that we were able to effectively support our accounts once we received approval and secure robust market access, with formulary coverage for revumenib quickly exceeding industry benchmarks.     

RA: In such a contested field as cancer, how does a company become and remain competitive? Does it purely come down to good science?  

MM: To ensure Syndax is successful we focus on delivering first-in-class medicines that address major unmet needs. However, that is just one of the crucial factors for success. We also make it a top priority to provide the best possible experience for patients, clinicians, and other key stakeholders. By focusing on these two priorities, we are driving long-term brand loyalty and competitive immunity. For instance, physicians often tell us how much they appreciate that their patients can easily and rapidly access revumenib, often within just a few days. Speed and a focus on delivering for every appropriate patient is essential when you have a medicine like revumenib which is approved for such an aggressive cancer.  

RA: What’s your approach to working with the patient community and how does this inform your therapeutic development?  

MM: The opportunity to make a profound difference for patients and their loved ones is what drives the Syndax team. The needs of patients are at the centre of everything we do and are our north star. To ensure that we understand those needs, we are frequently engaging with patient advocacy groups and patient advocates. Through these interactions we gain important insights that allow us to implement plans and resources that aim to meet the needs and priorities of patients. This type of collaboration between companies and the patient community fosters trust, promotes transparency, and ultimately leads to therapies that better reflect what is important to patients and the physicians who treat them.  

RA: What are the company’s remaining plans for 2025 and beyond?  

MM: We are very excited about what is still ahead for Syndax in 2025 and beyond. Building on the initial approval of revumenib in 2024 for the treatment of R/R acute leukaemia with a KMT2A translocation, we recently announced that our supplemental New Drug Application (sNDA) in R/R mNPM1 AML was granted Priority Review by the FDA and assigned a PDUFA target action date of October 25, 2025. The approval of our sNDA would represent another major milestone for Syndax and, most importantly, for patients and clinicians, given that there are currently no targeted therapies available for this patient population.   

Looking further ahead, we are focused on advancing our clinical development programmes that are studying our medicines in additional patient populations with high unmet need. Building on the compelling results we have shown in patients with R/R acute leukaemias, we and our clinical collaborators have multiple ongoing and planned trials that will evaluate revumenib across the treatment continuum, including in combination with standard of care therapies in newly diagnosed AML patients with NPM1 mutations or KMT2A rearrangements. Ultimately, we estimate that 50% or more of AML patients have a genetic alteration which may make their cancer sensitive to menin inhibition. This highlights the significant opportunity we have to make a major impact for patients through our development programs.   

In addition to continuing to pioneer the development of menin inhibition, we are equally excited about the ongoing studies evaluating axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor, in patients with newly diagnosed chronic graft-versus-host disease and idiopathic pulmonary fibrosis. Both revumenib and axatilimab hold tremendous promise for patients, and we look forward to elucidating their full therapeutic potential through the ongoing clinical trials.   

From DDW Volume 26 – Issue 4, Fall 2025 – Read the digital issue

Biography:  

Michael A Metzger currently serves as Chief Executive Officer of Syndax Pharmaceuticals. He served as President and Chief Operating Officer since May 2015 and as a member of the board of directors since July 2019. He received a BA from George Washington University and an MBA in Finance from the New York University Stern School of Business.