Data: ATSP-7041 as first-in-class p53 pathway re-activator for solid/ hematologic cancers

(Press-News.org) CAMBRIDGE, Mass., August 15, 2013 – Aileron Therapeutics, Inc., a clinical stage biopharmaceutical company that is developing first-in-class therapeutics based on its proprietary Stapled Peptide drug platform, announced today the publication of preclinical data on ATSP-7041, a potent and selective stapled peptide re-activator of the wild type p53 tumor suppressor protein. P53, known as "the guardian of the genome" because it repairs damaged DNA or triggers cell death in pre-cancerous cells, is one of the most important known tumor suppressors, as it is shown to be inactivated in virtually all human cancers. As 50% of all cancers circumvent P53's protective mechanisms by the over-expression of the inhibitory proteins MDM2 and MDMX, Aileron's stapled peptide is novel in that it can selectively bind to and inhibit both proteins equally and, thereby, restore the P53 function. The research, published in Proceedings of the National Academy of Sciences (PNAS), provides the first detailed publication by Aileron of one of its cell penetrating peptides that is a precursor molecule to one that the company is developing for the treatment of both liquid and solid tumors. The paper, entitled "Stapled α−Helical Peptide Drug Development: A Potent Dual Inhibitor of MDM2 and MDMX for p53-Dependent Cancer Therapy," expands on data reported by the company in poster presentations at the 2012 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics and the 2013 International MDM2 workshop in Cambridge, England.

"As evidenced by the multitude of research and clinical efforts, the full activation of p53 has been the goal of cancer researchers for decades given its [ubiquitous] role in all human cancers" said Joseph A. Yanchik III, president and chief executive officer of Aileron Therapeutics. "Our stapled peptide drug will be the first full-activator of wild type p53 of its kind to our knowledge to enter clinical trials. Our unique approach to restore p53 activity through direct inhibition of both MDM2 and MDMX has the potential to deliver greater efficacy and safety than existing small molecule approaches, which are primarily limited to inhibition of just MDM2. We look forward to advancing the p53 program into clinical trials next year that will represent our second stapled peptide drug to enter human clinical trials."

Key findings from the paper showed that ATSP 7041:

suppressed tumor growth in animal models of multiple human xenograft models, including breast cancer and bone cancer

is an equipotent dual inhibitor of MDM2 and MDMX that restores p53 specific activity

is a peptide that efficiently penetrated cell membranes and exhibited a more durable on mechanism effect on p53 signaling than small-molecule MDM2-selective inhibitors

exhibited favorable drug-like and pharmacokinetic properties that can support convenient clinical dosing regimens [including the potential for once-weekly dosing]

### About ATSP-7041 ATSP-7041 is a precursor molecule to a more potent and selective molecule that is currently undergoing IND enabling studies and is planned for entry into Phase 1 clinical testing in 2014. It is anticipated that the clinical molecule will be studied in both liquid and solid tumor patients who test for wild-type p53. Examples of p53 dependent cancers include, AML, CML, breast cancer, liposarcoma, melanoma, and colon cancer.

About Stapled Peptides Stapled Peptides is an emerging class of drugs with a unique set of properties that fully capitalize on 25 years of genetic research to attack drivers of complex diseases, including cancer, endocrine/metabolic disorders and inflammation. Aileron's proprietary Stapled Peptide drug platform locks peptides into their biologically active shape and imparts unprecedented pharmaceutical stability within the body. Stapled Peptide drugs are derived from natural peptides and are designed to potently and specifically target protein-protein interactions both inside and outside the cell. 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. With its proprietary Stapled Peptide platform, Aileron aims to dramatically improve the treatment of a wide range of diseases – including cancer and metabolic and endocrine conditions – and positively impact the lives of millions of patients. Aileron's lead drug development programs are its p53 re-activator for the treatment of cancer, and ALRN-5281, a long-acting, growth hormone releasing hormone (GHRH) for adult growth hormone deficiency that is currently in Phase 1 clinical trials. For more information, please visit http://www.aileronrx.com.