Data published in Nature Communications show MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type T-cell Lymphomas
CAMBRIDGE, Mass., May 22, 2018 (GLOBE NEWSWIRE) — Aileron Therapeutics (Nasdaq:ALRN), the leader in the field of stapled peptide therapeutics for cancers and other diseases, today announced the publication of nonclinical results in Nature Communications demonstrating the anti-cancer potential of ALRN-6924 in models of T-cell lymphoma (TCL). ALRN-6924 is designed to reactivate p53-mediated tumor suppression by targeting the two primary p53 suppressor proteins, MDM2 and MDMX. ALRN-6924 is being evaluated in Phase 1 and Phase 2 clinical trials in patients with peripheral T-cell lymphoma (PTCL) and acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
As reported in the study, ALRN-6924 showed potent in vitro activity and superior in vivo activity across eight different patient-derived xenograft models, compared to the standard-of-care agent. Separately, it was noted in the publication that ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from preclinical models.
“These data independently confirm previous preclinical and clinical results that the stapled peptide ALRN-6924 possesses anti-cancer activity based on a novel mechanism of action—the dual inhibition of MDMX and MDM2, instead of the inhibition of MDM2 alone. In addition, these data further demonstrate that stapled peptides represent a new treatment modality with unique properties that enable the targeting of previously ‘undruggable’ targets,” said Manuel Aivado, MD, PhD, Chief Medical and Scientific Officer of Aileron.
“We were very gratified by these results,” said David Weinstock, MD, Principal Investigator and Associate Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School. “The xenograft models we created and tested provide significant insight into the activity of a drug like ALRN-6924 and how well it will work in patients. We’re excited to see this drug move forward in clinical trials and hope to better understand the best way to use it as either a single agent or in combinations.”
The study in Nature Communications is titled, “Targetable Vulnerabilities in T- and NK-cell Lymphomas Identified Through Preclinical Models.”
ALRN-6924 is a first-in-class product candidate designed to reactivate wild type p53 tumor suppression by disrupting the interactions between the two primary p53 suppressor proteins, MDMX and MDM2. Aileron believes ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the interaction of MDMX and MDM2 with p53. Based on preclinical data and preliminary evidence of safety and anti-tumor activity in its ongoing clinical trials, there may be a significant opportunity to develop ALRN-6924 as a monotherapy or combination therapy for a wide variety of solid and liquid tumors. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL). For information about its clinical trials, please visit www.clinicaltrials.gov.
Aileron is a clinical-stage biopharmaceutical company advancing stapled peptides, a novel class of therapeutics for cancers and other diseases. Stapled peptides are chemically stabilized alpha-helical peptides that are modified to improve their stability and cell penetrability while maintaining high affinity for large protein surfaces. Our goal is to use our proprietary stapled peptide drug platform to create first-in-class therapeutics, like ALRN-6924, that may be able to address historically undruggable targets and complex mechanisms that underlie many diseases with high unmet medical need. Our platform enables us to chemically stabilize and improve the performance and activity of a broad range of alpha-helical peptides that we believe can potentially activate and inhibit key cellular functions that are otherwise difficult to target with existing drug technologies, including small molecules and monoclonal antibodies. For more information, visit www.aileronrx.com.
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Source: Aileron Therapeutics
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