Aileron Therapeutics Announces Oral Presentation of

• New ex vivo information demonstrates safety towards cyclophosphamide-induced injury to hair follicles and their stem cells
• Encore presentation of information offered at Society for Investigative Dermatology in May 2022 exhibits:
  • ALRN-6924 quickly arrested the cell cycle in human scalp hair follicles and their stem cells
  • Ex vivo information demonstrated safety towards taxane-induced injury to hair follicles and their stem cells
• Nearly all breast most cancers sufferers receiving neoadjuvant or adjuvant chemotherapy, together with cyclophosphamide and taxanes, resembling docetaxel, expertise alopecia (hair loss)
• Aileron is evaluating ALRN-6924 as a novel chemoprotective agent to stop chemotherapy-induced bone marrow toxicities and alopecia in its ongoing Phase 1b breast most cancers trial

BOSTON, Sept. 30, 2022 (GLOBE NEWSWIRE) — Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology firm that aspires to make chemotherapy safer and thereby more practical to avoid wasting extra sufferers’ lives, at the moment introduced an oral presentation on the European Society for Dermatological Research (ESDR) Annual Meeting, going down September 28 – October 1, 2022 in Amsterdam.

This presentation contains non-clinical information initially offered on the Society for Investigative Dermatology in May 2022 in addition to new non-clinical information developed in collaboration with Professor Ralf Paus, M.D., DSc, FRSB and his colleagues on the Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery on the University of Miami Miller School of Medicine.

Details of the presentation are as follows:

“Until one is confronted personally with the loss of hair due to chemotherapy, I think it’s difficult to truly understand just how difficult this side effect can be for patients. It is yet another burden layered on top of their already-daunting fight against cancer,” mentioned Dr. Paus. “Cold caps, the only FDA-approved treatment for chemotherapy-induced alopecia, are unavailable in many institutions, can cause additional discomfort, and – while often quite useful – are of unpredictable efficacy in a given individual patient. One also cannot help wondering whether scalp micro-metastases might profit from scalp cooling.”

Dr. Paus continued, “Based on our hair follicle and scalp skin organ culture work with ALRN-6924, testing two of the most hair loss-inducing chemotherapies, paclitaxel and cyclophosphamide, we’re very encouraged by the potential this drug may hold to prevent alopecia in cancer patients, including for protecting the hair follicle’s sensitive stem cell compartment from permanent damage. We’re particularly excited by ALRN-6924’s highly innovative design, which selectively protects normal cells from the destructive effects of chemotherapy, but – in contrast to any other currently available alopecia-protective strategy – crucially, not the cancer cells.”

Aileron is presently creating ALRN-6924, a first-in-class MDM2/MDMX twin inhibitor, to selectively shield wholesome cells in sufferers with cancers that harbor p53 mutations to cut back or eradicate chemotherapy-induced negative effects whereas preserving chemotherapy’s assault on most cancers cells. The firm is conducting a Phase 1b medical trial of ALRN-6924 in sufferers with p53-mutated breast most cancers present process both neoadjuvant or adjuvant therapy with docetaxel, doxorubicin and cyclophosphamide, often known as TAC. Aileron’s imaginative and prescient is to deliver chemoprotection to all sufferers with p53-mutated most cancers regardless of the sort of most cancers or chemotherapy.

Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron, commented, “We’re excited about the results generated by Dr. Paus and his colleagues, particularly given their significant and widely recognized expertise in chemotherapy-induced alopecia. We have amassed a body of strong scientific evidence, including the data being presented at the ESDR meeting, which demonstrate ALRN-6924’s cell cycle arrest mechanism and support its potential to protect against chemotherapy-induced bone marrow toxicities and other toxicities, including alopecia. Collectively, these nonclinical and clinical data have informed the design of our breast cancer trial. We look forward to our anticipated data readouts from that trial later this year and into 2023.”  

About the Paus et al. Findings

Taxanes, resembling paclitaxel and docetaxel, are recognized to trigger extreme and infrequently everlasting chemotherapy-induced alopecia. Over 90% of sufferers handled with this chemotherapy class expertise alopecia, and roughly 10% (paclitaxel) to 25% (docetaxel) of sufferers expertise everlasting alopecia. Cyclophosphamide can be recognized to trigger alopecia: it’s generally co-administered with doxorubicin (Adriamycin) chemotherapy within the “AC” mixture, with better than 90% of sufferers experiencing hair loss.

Dr. Paus and his crew beforehand demonstrated that paclitaxel damages human scalp hair follicles by inducing large mitotic defects and apoptosis in hair matrix keratinocytes in addition to bulge stem cell DNA injury, and that pharmacological induction of transient cell cycle arrest can shield hair follicles and stem cells (Purba et al. EMBO Molecular Medicine 2019). Aileron beforehand carried out in vitro research exhibiting that ALRN-6924 protected human fibroblasts in cell tradition from a number of chemotherapies, however not p53-mutant breast most cancers cells.

In the non-clinical findings offered on the ESDR and SID conferences, when organ-cultured anagen (i.e., lively progress part) scalp hair follicles from human donors had been pre-treated with ALRN-6924 or car (i.e., placebo), adopted by paclitaxel or car, ALRN-6924 considerably elevated the quantity of p21-positive hair matrix keratinocytes and bulge stem cells in comparison with car or paclitaxel alone, confirming cell cycle arrest ex vivo. Further, pretreatment of paclitaxel-treated human hair follicles with ALRN-6924, led to a discount within the quantity of melanin clumps, a marker of hair follicle cytotoxicity and dystrophy, in addition to a discount in apoptosis, pathological mitosis, and DNA injury. In new information offered on the ESDR assembly, these assays additionally yielded constructive findings for 4-HC (4-hydroperoxy cyclophosphamide), the lively metabolite of cyclophosphamide that’s shaped in vivo and generally used for in vitro research. Aileron believes that these findings assist medical investigation of ALRN-6924’s means to stop each acute and everlasting chemotherapy-induced alopecia, along with its ongoing analysis of ALRN-6924’s means to guard towards chemotherapy-induced bone marrow and different toxicities.

About Aileron’s Breast Cancer Clinical Trial

Aileron is underway with a Phase 1b, open-label, single-arm, multicenter trial designed to guage the protection, tolerability and chemoprotective impact of ALRN-6924 in as much as 24 sufferers with p53-mutated breast most cancers present process both neoadjuvant or adjuvant therapy with docetaxel, doxorubicin and cyclophosphamide, often known as TAC. The major endpoints are period and incidence of extreme neutropenia (Grade 4) in cycle 1. Secondary endpoints embody the chemoprotective impact of ALRN-6924 on chemotherapy-induced alopecia, in addition to different hematologic and non-hematologic toxicities. Planned readouts from the breast most cancers trial embody information from preliminary sufferers within the trial within the fourth quarter of 2022; an interim evaluation on 12 sufferers within the second quarter of 2023; and topline outcomes from 20 sufferers within the third quarter of 2023.

About Aileron Therapeutics

Aileron is a medical stage chemoprotection oncology firm that aspires to make chemotherapy safer and thereby more practical to avoid wasting 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, during which we completely 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 negative effects, ALRN-6924 might enhance sufferers’ high quality of life and assist them higher tolerate chemotherapy. Enhanced tolerability might end in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.

Our imaginative and prescient is to deliver chemoprotection to all sufferers with p53-mutated cancers, which symbolize roughly 50% of most cancers sufferers, regardless of kind of most cancers or chemotherapy. Visit us at aileronrx.com to be taught extra.

Forward-Looking Statements

Statements on this press launch about Aileron’s future expectations, plans and prospects, in addition to every other statements concerning issues that aren’t historic information, might represent forward-looking statements inside the which means of The Private Securities Litigation Reform Act of 1995. These statements embody, however aren’t restricted to, statements concerning 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 comparable expressions are supposed to establish forward-looking statements, though not all forward-looking statements include these figuring out phrases. Actual outcomes might differ materially from these indicated by such forward-looking statements because of this of numerous necessary components, together with whether or not Aileron’s money sources shall be ample to fund its persevering with operations for the intervals anticipated or with respect to the issues anticipated; whether or not preliminary outcomes of medical trials shall be indicative of ultimate outcomes of these trials or outcomes obtained in future medical trials, together with trials in several indications; whether or not ALRN-6924 will advance via the medical trial course of on a well timed foundation, or in any respect; whether or not the outcomes of such trials shall be accepted by and warrant submission for approval from the United States Food and Drug Administration or equal overseas regulatory businesses; whether or not ALRN-6924 will obtain approval from regulatory businesses on a well timed foundation or in any respect or during which territories or indications ALRN-6924 might obtain approval; whether or not, if ALRN-6924 obtains approval, it is going to be efficiently distributed and marketed; what influence the coronavirus pandemic might have on the timing of our medical growth, medical provide and our operations; and different components mentioned within the “Risk Factors” part of Aileron’s annual report on Form 10-Ok for the yr 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 might make with the Securities and Exchange Commission. Any forward-looking statements contained on this press launch communicate solely as of the date hereof, and Aileron particularly disclaims any obligation to replace any forward-looking assertion, whether or not as a result of of new data, future occasions or in any other case.