ABTL0812 is an anti-cancer compound that causes autophagy-mediated cancer cell death
ABTL0812 is a targeted therapy drug that kills cancer cells through the induction of robust cytotoxic autophagy. ABTL0812 binds and activates the transcriptional activity of the nuclear receptors PPARα and PPARγ, leading to the induction of endoplasmic reticular stress (ER-stress), and to the blockade of Akt activation, the central kinase of the PI3K/Akt/mTOR pathway. This dual action of ER-stress activation and Akt/mTOR axis blockade converge to strongly induce autophagy, which results in cancer cell death.

The first part of its mechanism of action was published at Clinical Cancer Research in May 2016, and the part describing the ER-stress was fully described in Autophagy journal in May 2020.

Preclinical efficacy
In animal cancer models ABTL0812 is efficacious as single agent with an excellent safety profile in a broad spectrum of cancer types: lung, endometrial and pancreatic cancer and neuroblastoma. ABTL0812 is also active on cells resistant to chemotherpay, on targeted therapies, on tumor stem cells, and it inhibits metastasis formation. Preliminary results show promising immunomodulatory effects.
 
Phase 1/1b first in human clinical trial
In the first in human phase 1/1b clinical trial (29 patients with advanced solid tumors), ABTL0812 showed and excellent safety and tolerability profile. Remarkably 2 patients had disease stabilizations over one year (14 and 18 months). Additionally, ABTL0812 showed high efficacy on biomarkers in the PI3K/Akt/mTOR pathway with PK/PD correlation. Due to its extremely low toxicity, the recommended phase 2 dose (RP2D) was determined by PK/PD, without reaching any dose limiting toxicity.
 
Phase 1/2a clinical trial in endometrial and lung cancer
AbilityPharma conducted a phase 1/2a clinical trial (80 patients) with ABTL0812 (at RP2D) as first-line therapy in endometrial cancer and in squamous NSCLC. After the chemotherapy cycles, the patients remain treated with ABTL0812 chronically. The basis for selecting this design is the high incidence of mutations in the PI3K/Akt/mTOR pathway in both cancer types together with ABTL0812 efficacy and security in preclinical models. The study concluded that the combination of ABTL0812 + chemotherapy is superior to chemotherapy alone.

The clinical trial was conducted in Vall d’Hebron Institute of Oncology (VHIO, Barcelona), Institut Català d’Oncologia (ICO, L'Hospitalet, Badalona and Girona), Institut Gustave Roussy (Paris), Centre Léon-Bérard (Lyon), Institut Paoli-Calmettes (Marseille), the INCLIVA (Valencia), and Hospital Universitario Virgen del Rocío (Sevilla). 

Phase 2b/3 clinical trial in pancreatic cancer
The company has a phase 2b placebo controlled clinical trial in pancreatic cancer currently recruiting in Spain, USA, France and Israel. The clinical trial assesses the safety and efficacy profile of ABTL0812 in combination with FOLFIRINOX in 150 patients with advanced pancreatic cancer as first-line treatment. 

The clinical trial is conducted at excellence centers in Spain, France, USA and Israel lead by Vall d’Hebron Institute of Oncology (VHIO, Barcelona), Institut Gustave Roussy (Paris), University of Cincinnati Cancer Center (Cincinnati) or Sheba MC Tel Hashomer (Tel-Aviv) among many others.