- p53-mediated cell cycle arrest outcomes display potential of ALRN-6924 to forestall chemotherapy-induced neutropenia, thrombocytopenia, and anemia, in addition to chemotherapy-induced alopecia (hair loss)
- Study confirmed better diploma and longer length of impact for ALRN-6924 at larger doses, supporting dose number of 1.2 mg/kg for ongoing ALRN-6924 breast most cancers trial
- 3-minute IV bolus and 1-hour IV infusion demonstrated related security profiles, pharmacokinetics, and pharmacodynamics, offering rationale for future growth of a simplified bolus administration
BOSTON, Oct. 26, 2022 (GLOBE NEWSWIRE) — Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology firm centered on basically reworking the expertise of chemotherapy for most cancers sufferers, right now offered detailed outcomes from its accomplished Phase 1 examine of ALRN-6924 in wholesome volunteers on the EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics 2022 happening in Barcelona October 26 – 28, 2022. The poster titled, “ALRN-6924 Induces Cell Cycle Arrest in Bone Marrow Stem Cells and Hair Follicles with Dose-Dependent Degree and Duration of Effects after a Single Infusion in Healthy Volunteers” (Poster #136) can also be out there in the Scientific Resources part of Aileron’s web site linked right here.
ALRN-6924 is a first-in-class MDM2/MDMX twin inhibitor that’s at present in growth as a novel, selective chemoprotective agent for sufferers with p53-mutated most cancers. The findings offered on the EORTC-NCI-AACR convention, which confirmed that ALRN-6924 induced p53-mediated cell cycle arrest in bone marrow stem cells and hair follicles, display the potential of ALRN-6924 to forestall chemotherapy-induced neutropenia, thrombocytopenia, and anemia, in addition to chemotherapy-induced alopecia.
“While we previewed some of these new findings from our now completed Phase 1 study of ALRN-6924 in healthy volunteers earlier this year, we’re pleased to present the comprehensive results at an international scientific conference,” mentioned Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. “These results contribute to the substantial body of scientific evidence that we believe has reliably and reproducibly demonstrated ALRN-6924’s potential as a biomarker-driven chemoprotective agent, driving us to work diligently to address the significant impact chemotherapy-induced toxicities have on cancer patients’ treatment experience and outcomes.”
ALRN-6924 is designed to activate p53, which in flip upregulates p21, a recognized inhibitor of the cell replication cycle, thereby inducing cell cycle arrest to guard regular, wholesome cells from chemotherapy-induced harm. The Phase 1 examine in wholesome volunteers was carried out to judge the protection, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ALRN-6924. Aileron beforehand offered information from the examine displaying {that a} 0.3 mg/kg and 0.6 mg/kg 1-hour intravenous (IV) ALRN-6924 infusion was effectively tolerated, and transiently upregulated p21 in human bone marrow cells with minimal sign for apoptosis (n=37; Voors-Pette et al., ESMO 2021).
In the brand new findings offered right now, cell cycle arrest was instantly measured in the bone marrow and hair follicles of an extra 41 females. 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 three to 9 topics and in comparison with placebo. Plasma and serum samples had been obtained to find out PK and ranges of macrophage inhibitory cytokine-1 (MIC-1), a biomarker of p53 activation. Bone marrow was sampled 12 hours post-dose to instantly measure cell cycle arrest by move cytometry in CD34+, lineage-negative bone marrow stem cells. Occipital scalp pores and skin was sampled by a 2 mm punch biopsy for p21 immunohistochemistry in hair follicles.
In addition to the cell cycle arrest findings, ALRN-6924 continued to display a good tolerability profile, with topics experiencing solely gentle, transient adversarial occasions (AEs), with nausea/vomiting as essentially the most frequent associated AE. The diploma and length of serum MIC-1 elevation was dose-dependent, indicating extra sturdy p53 activation at larger ALRN-6924 doses. At 12 hours post-dose, the proportion of biking bone marrow stem cells was considerably lowered in any respect dose ranges. Blinded pathology evaluate steered ALRN-6924-dependent p21 induction in anagen-phase hair follicles. Safety profiles, PK and PD had been related for each the 3-minute bolus and 1-hour infusion, offering rationale for future growth of ALRN-6924 bolus administration.
“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 both chemotherapy-induced neutropenia and alopecia in that trial,” mentioned Allen Annis, Ph.D., Senior Vice President, Research at Aileron. (*1*)
About Aileron Therapeutics
Aileron is a medical stage chemoprotection oncology firm that aspires to make chemotherapy safer and thereby simpler to save lots of extra sufferers’ lives. ALRN-6924, our first-in-class MDM2/MDMX twin inhibitor, is designed to activate p53, which in flip upregulates p21, a recognized inhibitor of the cell replication cycle. ALRN-6924 is the one reported chemoprotective agent in medical growth to make use of a biomarker technique, in which we solely give attention to treating sufferers with p53-mutated cancers. Our focused technique is designed to selectively shield a number of wholesome cell sorts all through the physique from chemotherapy with out defending most cancers cells. As a outcome, wholesome cells are spared from chemotherapeutic destruction whereas chemotherapy continues to kill most cancers cells. By lowering or eliminating a number of chemotherapy-induced unwanted side effects, ALRN-6924 could enhance sufferers’ high quality of life and assist them higher tolerate chemotherapy. Enhanced tolerability could outcome in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.
Our imaginative and prescient is to convey chemoprotection to all sufferers with p53-mutated cancers, which symbolize roughly 50% of most cancers sufferers, no matter sort of most cancers or chemotherapy. Visit us at aileronrx.com to be taught extra.
Forward-Looking Statements
Statements in this press launch about Aileron’s future expectations, plans and prospects, in addition to every other statements relating to issues that aren’t historic information, could represent forward-looking statements throughout the that means of The Private Securities Litigation Reform Act of 1995. These statements embody, however will not be restricted to, statements in regards to the potential of ALRN-6924 as a chemoprotective agent and the Company’s technique and medical growth plans. The phrases “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and related expressions are supposed to determine forward-looking statements, though not all forward-looking statements include these figuring out phrases. Actual outcomes could differ materially from these indicated by such forward-looking statements because of numerous essential elements, together with whether or not Aileron’s money sources can be enough to fund its persevering with operations for the durations anticipated or with respect to the issues anticipated; whether or not preliminary outcomes of medical trials can be indicative of ultimate outcomes of these trials or outcomes obtained in future medical trials, together with trials in totally different indications; whether or not ALRN-6924 will advance by the medical trial course of on a well timed foundation, or in any respect; whether or not the outcomes of such trials can be accepted by and warrant submission for approval from the United States Food and Drug Administration or equal international regulatory businesses; whether or not ALRN-6924 will obtain approval from regulatory businesses on a well timed foundation or in any respect or in which territories or indications ALRN-6924 could obtain approval; whether or not, if ALRN-6924 obtains approval, will probably be efficiently distributed and marketed; what impression the coronavirus pandemic could have on the timing of our medical growth, medical provide and our operations; and different elements mentioned in the “Risk Factors” part of Aileron’s annual report on Form 10-Ok for the 12 months ended December 31, 2021, filed on March 28, 2022, and quarterly report on Form 10-Q for the quarter ended June 30, 2022, filed on August 15, 2022, and dangers described in different filings that Aileron could make with the Securities and Exchange Commission. Any forward-looking statements contained in this press launch converse solely as of the date hereof, and Aileron particularly disclaims any obligation to replace any forward-looking assertion, whether or not due to new info, future occasions or in any other case.
