Cerdanyola del Vallès (Barcelona, Spain), September 9, 2024. AbilityPharma, a clinical-stage biopharmaceutical company specializing in the development of innovative oncology therapies, announced that the final data from its Phase 1/2 ENDOLUNG trial, evaluating ibrilatazar (ABTL0812) in combination with chemotherapy (paclitaxel/carboplatin) in 51 patients with advanced or recurrent endometrial cancer across 9 leading oncology hospitals in Spain and France, has been published in the prestigious scientific journal BMC Cancer. Ibrilatazar is an oral drug with a novel mechanism of action that induces autophagy through the induction of ER-stress and the inhibition of the PI3K/Akt/mTOR pathway, which is crucial for cellular function and is implicated in this cancer type.
 

The trial benefited from the contribution of leading key opinion leaders from select hospitals in Spain and France, including the Vall d'Hebron Institute of Oncology (VHIO) in Barcelona, Gustave Roussy in Paris, Clinic University Hospital in Valencia, Centre Léon Bérard in Lyon, Virgen del Rocío University Hospital in Seville, Paoli-Calmettes Institute in Marseille, and the Catalan Institute of Oncology (ICO) in Badalona, l'Hospitalet, and Girona.
 

This significant publication builds upon AbilityPharma's previous groundbreaking translational research, featured in Gynecologic Oncology. These advancements further establish the company's leadership in the development of autophagy-mediated oncology drugs.
 

Dr. Carles Domènech, AbilityPharma's CEO & Co-Founder, stated: "This publication represents a crucial development in the study of new drugs and combinations for advanced endometrial cancer, marking a significant milestone in AbilityPharma's mission to deliver transformative treatments to cancer patients."
 

The first author of the article is Dr. Alexandra Leary, deputy director of the Department of Clinical Oncology at the Gustave Roussy Institute, and the senior authors of the article, with equal contribution, are Dr. Alejandro Pérez-Fidalgo, oncologist at the Clínic University Hospital in Valencia, researcher at the INCLIVA Biomedical Research Institute's Oncology Department, and member of the Biomedical Research Network in Cancer (CIBERONC), and Dr. Ana Oaknin, Group Leader of VHIO's Gynecological Malignancies Group and Head of the Gynecologic Tumors Unit, Medical Oncology Department, at Vall d'Hebron University Hospital.
 

Dr. Alexandra Leary, of Institut Gustave Roussy, noted: "The PI3K pathway is almost universally altered in endometrial cancer and thus represents a very interesting target. Ibrilatazar is the first PI3K inhibitor demonstrating encouraging activity and an excellent side-effect profile in the capsule form now available."
 

Dr. Alejandro Pérez-Fidalgo, of Clínic University Hospital in Valencia, explained: "Ibrilatazar, when administered in combination with chemotherapy and subsequently as maintenance therapy, has shown a median survival of over 9 months in advanced endometrial cancer. These results are highly promising. If confirmed in a randomized study, ibrilatazar could become a treatment alternative for this complex disease."

Summary of main results reported in the publication

• The combination of ibrilatazar plus CP demonstrated an overall response rate (ORR) of 65.8%, comprising a 13.2% complete response and a 52.6% partial response, with a median duration of response (DOR) of 7.4 months (95% CI: 6.3–10.8 months). Median progression-free survival (PFS) was 9.8 months (95% CI: 6.6–10.6), a 40% increase over historical controls, with event-free rates of 73.3% at 6 months and 24.4% at 1 year. Median overall survival (OS) was 23.6 months (95% CI: 6.4–ND), with an event-free rate of 74.9% at 1 year. These results suggest increased efficacy over reference historical controls, where ORR, PFS, and OS were 51%, 7.1 months, and 20.4 months, respectively.
• The combination of ibrilatazar plus paclitaxel/carboplatin exhibited a good safety profile. Ibrilatazar aligned with the safety profile of historical controls and did not introduce additional significant adverse events beyond those associated with CP.
• Pharmacokinetic parameters aligned with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation for at least 28 days following the initiation of treatment.

Endometrial cancer is the sixth most common cancer among women worldwide, with over 400,000 new cases diagnosed each year. Its incidence has risen globally by 132% over the past 30 years and is expected to continue increasing due to an aging population and rising global rates of obesity and diabetes. More than 90% of cases occur in women over 50 years of age. In developed countries, it is the most prevalent gynecological cancer.

About IBRILATAZAR (ABTL0812):

Ibrilatazar is a first-in-class, fully differentiated oral targeted anticancer compound that induces cell death selectively in cancer cells, and not in normal cells, through autophagy (self-digestion). The mechanism of action of ibrilatazar is both unique and novel: robust autophagy results from the combined induction of PPAR-dependent endoplasmic reticulum stress (ER stress) and the inhibition of Akt activation, the central kinase in the PI3K/Akt/mTOR pathway. The mechanism of action was published in Clinical Cancer Research (2016) and in Autophagy (2020).
 

In clinical trials, ibrilatazar has shown clinical benefit in patients with endometrial and lung cancer, and it has shown robust preclinical proof-of-concept in animal models of several cancer types, including lung, endometrial, and pancreatic cancer, neuroblastoma, and glioblastoma.
 

AbilityPharma is currently evaluating ibrilatazar in metastatic pancreatic cancer through a Phase 2b PanC-ASAP clinical trial with 140 patients in the United States, Spain, France, and Israel. Recruitment was completed in January 2024, and an efficacy interim analysis was successfully passed in April 2024.
 

Ibrilatazar has received Orphan Drug Designations (ODD) for pancreatic cancer, biliary cancer, and the pediatric cancer neuroblastoma from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

About AbilityPharma:

AbilityPharma is a biopharmaceutical company focused on the development of innovative cancer therapies. Its lead asset, IBRILATAZAR (ABTL0812), acts through a unique mechanism of action based on the induction of selective cytotoxic autophagy in tumor cells.