– Aileron is currently developing ALRN-6924 as a novel selective chemoprotective agent for p53 mutated cancer patients undergoing chemotherapy –
– Preclinical data demonstrated activation by ALRN-6924 of p21-induced cell cycle arrest in murine bone marrow cells and epithelial mucosal cells in the gastrointestinal (GI) tract –
– New preclinical findings support further study of ALRN-6924 as a potential radioprotective agent –
BOSTON, Oct 07, 2021 (GLOBE NEWSWIRE) – Aileron Therapeutics (Nasdaq: ALRN), a chemoprotective oncology company focused on the fundamental transformation of the chemotherapy experience for cancer patients, presented today See new preclinical data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2021 on ALRN-6924, currently in development as a novel selective chemoprotective agent. The new data demonstrated the activity of ALRN-6924 as a radioprotective agent in preclinical mouse models of acute radiation-induced toxicity, taking advantage of the same mechanism of action – activation of p53 and subsequent upregulation. p21 as well as cell cycle arrest induced by p21 – which has been clinically shown to protect against chemotherapy-induced toxicities.
âLike chemotherapy, ionizing radiation is associated with serious and often dangerous side effects, as chemotherapy and radiation destroy normal, healthy cells,â said Manuel Aivado, MD, Ph.D. âAlthough preliminary, these New preclinical data suggest that the mechanism of action of ALRN-6924, which has been shown to protect against chemotherapy-induced bone marrow toxicities, may also protect against radiation-induced toxicities. Furthermore, these preclinical studies provide our first evidence for ALRN-6924-mediated activation of p21 in epithelial mucosal cells of the gastrointestinal tract, protecting irradiated mice from body weight loss, and the potential for ALRN-6924 to protect multiple tissues beyond the bone marrow. chemotherapy and radiation-induced toxicities.
Dr Aivado continued, âThe development of ALRN-6924 as a selective chemoprotective agent in p53 mutated cancers continues to be our top priority. Nonetheless, these encouraging preclinical data point to a potential future secondary application of ALRN-6924 to complement our ongoing chemoprotection program, and we look forward to further research to further explore this possibility.
Aileron is currently developing ALRN-6924, a first-class dual MDM2 / MDMX inhibitor, to selectively protect healthy cells in cancer patients with p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving the attack of chemotherapy on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which interrupts the cell cycle in normal, healthy, and proliferating cells, but not in cancer cells mutated by p53.
In the AACR-NCI-EORTC poster titled “The Investigational Chemoprotection Drug ALRN-6924, a Dual Inhibitor of MDMX and MDM2, Shows Potential for Radioprotection” (poster # P211), Aileron presented the results of preclinical studies designed to assess whether p53 activation with ALRN-6924 can protect healthy proliferating cells in normal tissue from radiation-induced cellular toxicity.
In a non-lethal radiation exposure model, mice were exposed to a single dose of radiation targeted to the abdomen at 15 Gy after one or more doses / programs of ALRN-6924 or placebo, followed by their body weight was watched. Aileron assessed serum levels of macrophage inhibitory cytokine-1 (MIC-1), a biomarker of p53 activation, as well as biomarkers of p53-mediated cell cycle arrest (p21) and apoptosis. (cleaved poly-ADP-ribose polymerases, or cPARP) in mouse bone marrow and tissues of the gastrointestinal tract. Repeated doses of ALRN-6924 administered every eight hours resulted in a sustained elevation of MIC-1, correlated with increased positivity of p21 in the bone marrow and intestine, while treatment-dependent changes in the expression of cPARP were minimal. In addition, mice treated with ALRN-6924 had less radiation-induced body weight loss than untreated mice. Mice given one or more doses of ALRN-6924 eight hours before irradiation experienced an average body weight loss of 4%, while mice treated with placebo experienced a 10-15% body weight loss five days after irradiation. The poster will be archived on the Scientific Publications page of the Aileron website at: https://www.aileronrx.com/science/scientific-publications.
Aileron is currently conducting a randomized, double-blind, placebo-controlled Phase 1b study of ARLN-6924 as a chemoprotective agent in the United States and Europe. The study is recruiting patients with advanced non-small cell lung cancer mutated by p53 and receiving treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. The company is pursuing a clinical development strategy designed to advance its vision of providing selective chemoprotection to all patients with mutated p53 cancer, regardless of cancer type or chemotherapy.
About Aileron Therapeutics
Aileron is a clinical-stage chemoprotective oncology company focused on fundamentally transforming the chemotherapy experience for cancer patients. ALRN-6924, our first dual MDM2 / MDMX inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only chemoprotective agent reported in clinical development to use a biomarker strategy, in which we focus exclusively on the treatment of patients with p53 mutated cancers. Our targeted strategy is designed to selectively protect several types of healthy cells throughout the body from chemotherapy while being careful not to protect cancer cells. As a result, healthy cells are spared from chemotherapy destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating the multiple side effects of chemotherapy, ALRN-6924 can improve the quality of life of patients and help them tolerate chemotherapy better. Increased tolerance may lead to fewer dose reductions or delays in chemotherapy and the potential for improved efficacy.
Almost one million patients in the United States of all types of cancer are diagnosed with mutated p53 cancer each year. Our vision is to provide selective chemoprotection to patients with p53 mutated cancers, regardless of the type of cancer or chemotherapy. Visit us at aileronrx.com to learn more.
Forward-looking statements The statements contained in this press release concerning Aileron’s future expectations, plans and prospects, as well as any other statement concerning matters which are not historical facts, may constitute forward-looking statements within the meaning of the law. Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924 as a chemoprotective or radioprotective agent and the Company’s strategy and clinical development plans. The words “anticipate”, “believe”, “continue”, “could”, “estimate”, “foresee”, “intend”, “can”, “plan”, “potential”, “predict”, ” project “” should “,” target “,” would “and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by these forward-looking statements due to various important factors, including whether Aileron’s cash resources will be sufficient to fund its ongoing operations for the periods anticipated or with respect to the matters anticipated; whether the initial findings or the results of clinical trials will be indicative of the final results of those trials or of the results obtained in future clinical trials, including trials in different indications or with different chemotherapies; whether ALRN-6924 will progress through the clinical trial process in a timely manner, or not at all; whether the results of these tests will be accepted and submitted for approval to the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether ALRN-6924 will receive regulatory approval in a timely manner or not at all; whether, if ALRN-6924 obtains approval, it will be distributed and marketed successfully; uncertainties about the impact that the coronavirus pandemic could have on the timing of our clinical development, clinical supply and operations; and other factors discussed in the âRisk Factorsâ section of Aileron’s annual report on Form 10-Q for the quarter ended June 30, 2021, filed August 11, 2021, and the risks described in other documents that ‘Aileron may deposit with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. .