ABTL0812, is a First in Class small molecule, orally administered, targeted anticancer compound inhibiting the PI3K/Akt/mTOR pathway without being a direct kinase inhibitor. ABTL0812 induces the overexpression of TRIB3, an endogenous negative regulator of Akt, with subsequent induction of cell death by autophagy. Its unique mechanism of action was published at Clinical Cancer Research in May 2016.
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 other targeted therapies, on tumor stem cells and inhibits metastasis formation. Preliminary results show promising immunomodulatory effects.

In the first in human phase 1/1b clinical trial (29 patients with advanced solid tumors), ABTL0812 showed the best safety and tolerability compared to other PI3K/Akt/mTOR pathway inhibitors. The efficacy in patients was comparable to the best PI3K/Akt/mTOR inhibitors in similar clinical trials. 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.

With the CTA approved in September 2016, AbilityPharma is conducting 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 clinical trial is led by Vall d’Hebron Institute of Oncology (VHIO, Barcelona) and Institut Català d’Oncologia (ICO, Hospitalet, Badalona and Girona). The study also includes the INCLIVA (Valencia), Institut Gustave Roussy (Paris), Centre Léon-Bérard (Lyon) and Institut Paoli-Calmettes (Marseille).
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