Aileron Therapeutics Initiates Phase 1 Cancer Study of ALRN-6924 in Advanced Hematologic and Solid Malignancies with Wild Type p53

Aileron Therapeutics Initiates Phase 1 Cancer Study of ALRN-6924 in Advanced Hematologic and Solid Malignancies with Wild Type p53

- First-in-class stapled peptide selectively targets both p53 suppressors, MDM2 and MDMX, to fully engage essential anti-tumor mechanism -

CAMBRIDGE, Mass., February 12, 2015Aileron Therapeutics, Inc., a clinical stage biopharmaceutical company that is the leader in the emerging field of stapled peptide drug development, announced today that the first cancer patients have been dosed in a Phase 1 clinical trial of ALRN-6924. 

ALRN-6924 is a potent and specific re-activator of wild type p53, a tumor suppressor protein that has been long referred to as "the guardian of the genome."  P53 represents one of the most sought after oncology drug targets by clinical oncologists due to its central role in preventing the initiation and progression of most liquid and solid tumors.   ALRN-6924 is the first clinical drug candidate that binds equipotently and inhibits both of the p53 suppressor proteins, MDM2 and MDMX, in contrast to other p53-targeting small molecule drugs in clinical development that only inhibit MDM2.  

"This clinical study represents a very ambitious undertaking for Aileron and is an exciting time for our team and collaborators.  The ultimate goal of this trial is to demonstrate our ability to safely and effectively engage one of the most important targets in all of oncology, p53, and further establish the druggability of transcription factors that have been shown to be some of the most important but difficult-to-target oncogenic drivers. Per our stapled peptide platform, this study will demonstrate the first systemic administration of a cell-penetrating stapled peptide and will further establish the potential of this new class of medicines for a wide range of therapeutic areas," said Joseph A. Yanchik III, President and Chief Executive Officer of Aileron Therapeutics.

"It is estimated that over 10 million people are living with a cancer that has wild type p53 signaling inactivated.  Our ability to directly engage the full mechanism with ALRN-6924 could have unprecedented impact not only in treating a broad range of liquid and solid tumors that test positive for wild type p53, but our drug could also expand the efficacy of many current therapies that rely on a functional p53 pathway," said Dr. Manuel Aivado, Chief Medical Officer of Aileron Therapeutics.  "With the Phase 1 study well underway, we expect to have a steady flow of important insights into the safety and activity of ALRN-6924 in patients throughout the year."

About the Phase 1 Study

The Phase 1, multicenter, dose-escalation study of ALRN-6924 is intended to assess the safety and tolerability of ALRN-6924 as a single agent.  The study is expected to enroll cancer patients with advanced hematologic and solid malignancies that test positive for the presence of wild type p53.  The objectives of the trial include determining maximum tolerated dose, pharmacokinetics, pharmacodynamics (including showing the inhibition of MDM2 and MDMX and the re-activation of p53) and preliminary indications of anti-tumor activity.  The study design also provides for tumor specific expansion cohorts that will test the maximally tolerated or optimal biological dose.

About P53 and ALRN-6924

P53 is known as "the guardian of the genome" because it is the body's cellular first line of defense that enables the repair of damaged DNA or, if unsuccessful, triggers cell death.  It is one of the most studied and pursued tumor suppressor proteins, as it is known to be inactivated in virtually all human cancers.  As half of all cancers circumvent p53's protective mechanisms by the inhibitory proteins MDM2 and MDMX, Aileron's stapled peptide, ALRN-6924, is novel in that it can selectively bind to and inhibit both proteins equally, thereby restoring p53 function and the  cancer cell's ability to trigger its innate cell death mechanism.

About Stapled Peptides

Stapled peptides (stabilized alpha-helical peptides) are an emerging class of drugs that engage intracellular and extra-cellular targets.  Stapled peptides have a unique set of properties that capitalize on the ability of the alpha helix, one of the most common structures in nature, to bind to and modulate complex protein-protein interactions and other targets that are not addressable by existing drug technologies.  Aileron's stapled peptides closely replicate endogenous proteins and are able to capitalize on the emerging understanding of the biology of disease and the molecular mechanisms that drive the disease process. Aileron's proprietary stapled peptide drug platform locks peptides into their biologically active shape and imparts unprecedented pharmacokinetic and pharmaceutical stability. This new class of drugs represents a fundamentally new therapeutic approach to modulate signaling pathways to treat human disease.

About Aileron Therapeutics

Aileron Therapeutics is a clinical stage biopharmaceutical company that is developing first-in-class therapeutics based on its proprietary stapled peptide drug platform. Aileron's lead drug candidate is ALRN-6924, a p53 re-activator for the treatment of cancer, and is currently in clinical testing. As an industry leader in stabilized peptides, Aileron aims to dramatically improve the treatment of a wide range of diseases including cancer, endocrine/metabolic disorders and infectious diseases. For more information, please visit www.aileronrx.com.

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