Aileron Therapeutics Presents Results of Phase 1 Study in Healthy Volunteers Demonstrating ALRN-6924-Induced Cell Cycle Arrest in Bone Marrow and Hair Follicle Stem Cells at EORTC-NCI-AACR International Conference

Aileron Therapeutics Presents Results of Phase 1 Study in Healthy Volunteers Demonstrating ALRN-6924-Induced Cell Cycle Arrest in Bone Marrow and Hair Follicle Stem Cells at EORTC-NCI-AACR International Conference
Aileron Therapeutics, Inc.

Aileron Therapeutics, Inc.

  • Results of p53-mediated cell cycle arrest demonstrate the potential of ALRN-6924 to prevent chemotherapy-induced neutropenia, thrombocytopenia and anemia, as well as chemotherapy-induced alopecia (hair loss)

  • Study showed a greater degree and duration of effect for ALRN-6924 at higher doses, supporting the 1.2 mg/kg dose selection for the ongoing ALRN-6924 breast cancer trial

  • The 3-minute IV bolus and the 1-hour IV infusion demonstrated similar safety, pharmacokinetic, and pharmacodynamic profiles, providing a foundation for future development of simplified bolus administration.

BOSTON, Oct. 26, 2022 (GLOBE NEWSWIRE) — Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company focused on fundamentally transforming the chemotherapy experience for cancer patients, today reported detailed results from its study of phase 1 of ALRN-6924 in healthy volunteers at the EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics 2022 that took place in Barcelona from October 26 to 28, 2022. The poster entitled, “ALRN-6924 induces cell cycle arrest in bone marrow stem cells and hair follicles with a dose-dependent degree and duration of effects after a single infusion in healthy volunteers” (Poster #136) is also available in the Science Resources section of the linked Aileron website here.

ALRN-6924 is a first-in-class dual MDM2/MDMX inhibitor currently in development as a new selective chemoprotective agent for p53-mutated cancer patients. Findings presented at the EORTC-NCI-AACR conference, which showed that ALRN-6924 induced p53-mediated cell cycle arrest in bone marrow stem cells and hair follicles, demonstrate the potential of ALRN-6924 to prevent neutropenia, thrombocytopenia, and anemia, as well as chemotherapy-induced alopecia.

“While earlier this year we previewed some of these new findings from our now completed Phase 1 study of ALRN-6924 in healthy volunteers, we are pleased to present the full results at an international scientific conference,” said Manuel Aivado, MD, Ph.D., President and CEO of Aileron. “These results contribute to the substantial body of scientific evidence that we believe has reliably and reproducibly demonstrated the potential of ALRN-6924 as a biomarker-driven chemoprotective agent, prompting us to work diligently to address the significant impact induced toxicities have. by chemotherapy in cancer patients. treatment experience and outcomes.

ALRN-6924 is designed to activate p53, which in turn increases p21, a known inhibitor of the cell replication cycle, inducing cell cycle arrest to protect normal, healthy cells from chemotherapy-induced damage. The phase 1 study in healthy volunteers was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ALRN-6924. Aileron previously presented study data showing that a 1-hour intravenous (IV) infusion of ALRN-6924 at 0.3 mg/kg and 0.6 mg/kg was well tolerated and transiently increased p21 in bone marrow cells human with minimal signal of apoptosis (n=37; Voors-Pette et al., ESMO 2021).

In the new findings presented today, cell cycle arrest was measured directly in the bone marrow and hair follicles of 41 other women. ALRN-6924 was administered as a single 1-hour IV infusion or 3-minute bolus injection at 0.3, 0.6, or 0.9 mg/kg to cohorts of 3 to 9 subjects and compared to placebo. Plasma and serum samples were obtained to determine PK and levels of macrophage inhibitory cytokine-1 (MIC-1), a biomarker of p53 activation. Bone marrow samples were taken 12 hours post-dose to directly measure cell cycle arrest by flow cytometry in CD34+ negative lineage bone marrow stem cells. Occipital scalp skin samples were taken by 2-mm punch biopsy for p21 immunohistochemistry in hair follicles.

In addition to the cell cycle arrest findings, ALRN-6924 continued to demonstrate a favorable tolerability profile, with subjects experiencing only mild and transient adverse events (AEs), with nausea/vomiting as the most common related AEs. The degree and duration of serum MIC-1 elevation were dose-dependent, indicating more durable p53 activation at higher doses of ALRN-6924. At 12 hours post-dose, the proportion of cycling bone marrow stem cells was significantly reduced at all dose levels. Blind pathology review suggested ALRN-6924-dependent induction of p21 in anagen-phase hair follicles. The safety, pharmacokinetic, and pharmacokinetic profiles were similar for both the 3-minute bolus and the 1-hour infusion, justifying the future development of bolus administration of ALRN-6924.

“These findings are particularly compelling as they support our selection of the 1.2 mg/kg dose for our ongoing Phase 1b trial in patients with p53-mutated breast cancer, as well as our evaluation of protection against neutropenia and chemotherapy-induced alopecia in that trial,” said Allen Annis, Ph.D., senior vice president of research at Aileron. “Beyond informing the dose and schedule of our current trial evaluating ALRN-6924 in breast cancer patients receiving treatment with docetaxel, doxorubicin, and cyclophosphamide, or TAC, these results suggest that this dosing regimen can be applied consistently. uniformly when ALRN-6924 is developed as a chemoprotective agent. with other chemotherapies and for patients with other indications of cancer with p53 mutation”.

About Aileron Therapeutics

Aileron is a clinical-stage chemoprotection oncology company that aspires to make chemotherapy safer and therefore more effective to save more patients’ lives. ALRN-6924, our first-in-class 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 reported chemoprotective agent in clinical development that employs a biomarker approach, in which we focus exclusively on treating patients with p53-mutated cancers. Our targeted approach is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to destroy cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 can improve patients’ quality of life and help them better tolerate chemotherapy. Improved tolerability may result in fewer dose reductions or delays in chemotherapy and the potential for improved efficacy.

Our vision is to provide chemoprotection to all patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of cancer type or chemotherapy. visit us in Learn more.

Forward-Looking Statements

Statements in this press release about Aileron’s future expectations, plans and prospects, as well as any other statements about matters other than historical fact, may constitute forward-looking statements within the meaning of the Securities Litigation Reform Act. Private 1995. These statements include, but are not limited to, statements regarding the potential of ALRN-6924 as a chemoprotective agent and the Company’s strategy and clinical development plans. The words “anticipate”, “believe”, “continue”, “could”, “estimate”, “expect”, “intend”, “may”, “plan”, “potential”, “predict”, “project”, “should”, “target”, “could” 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 such forward-looking statements as a result of various important factors, including whether Aileron’s cash resources will be sufficient to fund its continuing operations for the periods anticipated or with respect to the matters anticipated; whether the initial 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; whether ALRN-6924 will advance through the clinical trial process in a timely manner, or at all; whether the results of such trials will be accepted by the US Food and Drug Administration or equivalent foreign regulatory agencies and will ensure their submission for approval; whether ALRN-6924 will receive approval from regulatory agencies in a timely manner or at all, or in what territories or indications ALRN-6924 may receive approval; yes, if ALRN-6924 gains approval, it will be successfully distributed and marketed; what impact the coronavirus pandemic may have on our clinical development, clinical supply, and operations at the time; and other factors discussed in the “Risk Factors” section of Aileron’s annual report on Form 10-K for the year ended December 31, 2021, filed March 28, 2022, and the quarterly report on Form 10 -Q for the quarter ended June 30, 2022, filed on August 15, 2022, and the risks described in other filings Aileron may make with the Securities and Exchange Commission. Any forward-looking statement contained in this press release speaks only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether due to new information, future events or otherwise.

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