Benzinga | Sep 16, 2021 08:16AM EDT

Aileron Therapeutics Highlights Presentation Of ALRN-6924 Clinical Data At ESMO Virtual Congress 2021

* Final results from completed Phase 1b trial in patients with small cell lung cancer (SCLC) receiving second-line topotecan demonstrated ALRN-6924's ability to reduce neutropenia, thrombocytopenia and anemia caused by chemotherapy, as well as the need for transfusions

* Preliminary results from ongoing Phase 1 pharmacology study in healthy volunteers confirmed ALRN-6924's optimal dose (0.3 mg/kg), its mechanism of action, and demonstrated time to onset, duration and magnitude of its pharmacodynamic effects

* These new data will inform the design of anticipated future clinical studies to investigate ALRN-6924 as a chemoprotective agent in other p53-mutated cancers and with other types of chemotherapy

* A precision medicine-based chemoprotective agent, ALRN-6924 is designed to selectively activate p53 in normal cells, thereby upregulating p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells

BOSTON, Sept. 16, 2021 (GLOBE NEWSWIRE) -- Aileron Therapeutics (NASDAQ:ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, today presented new clinical data at the European Society of Medical Oncology (ESMO) Virtual Congress 2021 supporting ALRN-6924's best-in-class potential as a chemoprotective agent. The company presented final results from its completed Phase 1b trial of ALRN-6924 in patients with small cell lung cancer (SCLC) receiving second-line topotecan treatment, which demonstrated ALRN-6924's 'triple-play efficacy' for the reduction of neutropenia, thrombocytopenia and anemia, as well as a reduction of platelet and red blood cell transfusions, as compared to historical controls. Aileron today also presented preliminary results from its ongoing Phase 1 pharmacology study of ALRN-6924, which confirmed 0.3 mg/kg as the optimal dose for ALRN-6924 and confirmed its novel p53 biomarker-driven mechanism of action, as well as its pharmacodynamic effects, including time to onset, magnitude and duration.

Aileron is developing ALRN-6924 to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapy's attack on cancer cells. ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells.

"We are pleased to present final results from our completed Phase 1b trial of ALRN-6924 in patients with SCLC being treated with topotecan and preliminary results from our ongoing Phase 1 pharmacology study in healthy volunteers. The data presented at ESMO further strengthen our belief in ALRN-6924's best-in-class potential in the emerging chemoprotection space," said Manuel Aivado, M.D., Ph.D., President and CEO of Aileron. "With our precision medicine strategy, our vision is to bring the first selective chemoprotective agent to all patients with p53-mutated cancer while ensuring no interruption of chemotherapy. We believe chemoprotection during chemotherapy, ultimately, should be as compulsory as anesthesia during surgery."

ALRN-6924 Phase 1b SCLC Trial Final Results

Aileron conducted a Phase 1b open-label clinical trial to evaluate ALRN-6924 as a chemoprotective agent against bone marrow-related, chemotherapy-induced toxicities in patients with SCLC undergoing treatment with topotecan. The company reported the final results from this trial in a poster presentation at ESMO titled, "A Phase 1b Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Chemotherapy-induced Myelosuppression" (Abstract/Poster #: 1654P).

A total of 39 patients were enrolled in the trial, 38 of whom were evaluable per the trial protocol. Topotecan (1.5 mg/ m2) was administered on days 1 through 5 of every 21-day treatment cycle. 32 patients (31 evaluable) were treated with ALRN-6924 at 24 hours before each dose of topotecan at the following dose levels: 0.2 mg/kg (N=4), 0.3 mg/kg (N=16), 0.6 mg/kg (N=6; 5 evaluable) and 1.2 mg/kg (N=6). 7 patients were treated with 0.3 mg/kg of ALRN-6924 at 6 hours before each dose of topotecan.

In the Phase 1b SCLC trial, toxicities were evaluated using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Per the trial protocol, patients were not permitted to receive prophylactic G-CSF treatment in cycle 1. The median number of completed topotecan treatment cycles across all cohorts was 3. 13% of patients required topotecan dose reduction. No patients reported NCI CTCAE Grade ?3 events of nausea, vomiting, diarrhea; 5% had Grade 3 fatigue.

While chemoprotection effects were observed across all ALRN-6924 dose levels studied in the Phase 1b SCLC trial, the 0.3 mg/kg ALRN 6924 dose level given 24 hours prior to topotecan demonstrated the most robust chemoprotection results. None of the patients treated at the 0.3 mg/kg 24 hour ALRN-6924 dose level had a related serious adverse event (SAE). One patient (6%) at the 0.3 mg/kg 24 hour ALRN-6924 dose level required a red blood cell transfusion and a platelet transfusion. In the topotecan plus placebo arm of a recent third-party randomized Phase 2 trial in SCLC patients receiving topotecan (N=28), 41% and 31% of SCLC patients received red blood cell and platelet transfusions, respectively (Hart et al., ASCO 2019).

Summary of Final Key Efficacy Findings from ALRN-6924 Phase 1b SCLC Trial

Third Party

ALRN-6924 (given 24h prior to chemotherapy) Phase 1b Trial Randomized Phase 2

Bone Marrow-Related Key Toxicity Findings Trial in SCLC

Adverse Events (AEs)* NCI CTCAE ? Grade 3 Historical Control?

ALRN-6924 ALRN-6924

0.3 mg/kg + (All Dose Levels) Placebo

Topotecan Topotecan + Topotecan

Toxicity N (%) N (%) N (%)

N=16 N=39 N=28All AEs 14 (88) 35 (90) 27 (96)Neutropenia 13 (81) 34 (87) 24 (86)Thrombocytopenia 7 (44) 18 (46) 20 (70)Anemia 3 (19) 6 (15) 18 (63)Febrile Neutropenia 0 1 (3) 5 (17) ?Fatigue 1 (6) 2 (5) 2 (7)Nausea 0 0 1 (4)



Neutropenia 5 (31)** 14 (36)** 21 (76)Grade 4

*AEs based on laboratory values, as applicable

**For cycle 1

? Hart et al. ASCO 2019

? Febrile neutropenia assessed in 29 patients