Aileron Advances First Stapled Peptide Drug Candidate That Targets Newly-Discovered BAX Activation Mechanism

Main Category: Cancer / Oncology
Article Date: 23 Oct 2008 - 8:00 PDT

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Aileron Therapeutics announced today that one of its proprietary Stapled Peptide compounds, referred to as "BIM-SAHB" in an article published today in Nature, was shown to uniquely target a new and fundamental activation mechanism of the programmed cell death or "apoptotic" pathway. Aileron has advanced an optimized version of the published Stapled Peptide compound into late-stage preclinical studies.

In the Nature article, "BAX Activation is Initiated at a Novel Interaction Site," Dana-Farber chemical biologist and pediatric oncologist Loren Walensky, M.D., Ph.D and colleagues, identified a previously unknown trigger site on the death protein BAX that regulates its activation. This critical binding site on BAX was discovered - and directly activated - by the use of a novel Stapled Peptide compound. Consistent with the independent research published in Nature, Aileron's Stapled Peptide drug engages all known targets on the apoptotic pathway, including BAX. Stapled Peptides are the first drug modality capable of fully exploiting and modulating the entire apoptotic pathway for the treatment of cancer, autoimmune diseases, neurodegenerative and immunoproliferative disorders.

"By restoring the bioactive shape of the BH3 signaling peptide, the hydrocarbon stapling technology not only generated the compound to achieve this discovery, but provides the first drug candidate to target this site for therapeutic purposes," said Loren Walensky, M.D., Ph.D., who is also an Assistant Professor of Pediatrics at Harvard Medical and a scientific co-founder of Aileron Therapeutics. "As Aileron advances stapled BH3 peptides toward clinical trials, we move closer to seeing this basic science discovery translated into clinical benefit for patients suffering from a wide range of diseases."

At the 2008 American Association for Clinical Cancer Research (AACR) annual meeting, Aileron Therapeutics presented data showing excellent in vivo efficacy for one Stapled Peptide drug candidate; specifically, inducing apoptosis in a variety of lymphoid and solid tumor lines. In a xenograft leukemia model, the stapled peptide suppressed cancer cell growth in a dose dependent sequence specific manner and exhibited excellent pharmacological properties including terminal half-lives well in excess of 3 hours.

"The identification of this key activation mechanism explains why certain Aileron Stapled Peptides have demonstrated powerful cell killing capabilities across a broader range of tumors in contrast to any other therapeutic modalities including small molecules and monoclonal antibodies," said Joseph Yanchik, III, Chief Executive Officer of Aileron Therapeutics. "We are excited by the incredible potential Stapled Peptides represent to fundamentally change the landscape of peptide therapeutics. We are moving aggressively to advance our lead compound into human clinical studies in approximately 12 months. Given the far-reaching potential of Stapled Peptides as a completely new therapeutic modality that can exploit a very large and presently undruggable collection of targets we are also investigating their use for inflammatory, metabolic and infectious diseases."

Aileron Therapeutics has a broad intellectual property estate on Stapled Peptides that includes exclusive licenses from Dana-Farber Cancer Institute, Harvard University and New York University, with a significant component of the estate based on the work of Dr. Loren Walensky.

Online copies of the article can be obtained at http://www.nature.com.

About Stapled Peptides

AILERON's Stapled Peptides are synthetically locked, or 'stapled', into an alpha-helical shape with an optimized cross-linking chemistry to mimic the structure found at the interface of many protein-protein interactions. To achieve this, Aileron has deployed a comprehensive cross-linking tool-kit to install single staples, multiple staples and contiguous staples to achieve desired efficacy and pharmacokinetic profiles. The resulting Stapled Peptide drugs are endowed with unique properties, including efficient cell penetration, high affinity binding to large target protein surfaces, and excellent stability and pharmacokinetic properties within the body.

About Aileron Therapeutics

Aileron Therapeutics is a biopharmaceutical company leading the development of a completely new therapeutic modality and class of drugs called Stapled Peptides, and with deep and broad knowledge and experience around this new technology. Stapled Peptide drugs represent the first solution for modulating intracellular protein-protein interactions, which have been identified as critical control points for most human diseases. As such, Stapled Peptide drugs offer a unique opportunity to exploit potentially thousands of currently "undruggable" targets across all human diseases. Aileron is building a robust pipeline of therapeutics for the treatment of cancer, infectious disease, metabolic disease and immune/inflammatory diseases. Aileron Therapeutics was founded in 2005 and is based in Cambridge, Massachusetts. For additional information, please visit http://www.aileronrx.com.

Source
Kathryn Morris
Yates Public Relations
Aileron Therapeutics