• Glioblastoma multiforme is the most malignant adult brain tumor type.

•  A study published in Frontiers in Oncology has shown the therapeutic effect of ABTL0812 in preclinical models of glioblastoma as monotherapy or in combination with the standard of care therapies.

•  This study was led by the Laboratory of Radiobiology of the University of l´Aquila and by AbilityPharma.

Glioblastoma multiforme (GBM) is the most malignant adult brain tumor. Current standard of care treatments has very limited efficacy, being the patients´ overall survival 14 months and the 2-year survival rate less than 10%. Therefore, the treatment of GBM is an urgent unmet clinical need.

The aim of this study was to investigate the potential of ABTL0812 as a novel therapy for GBM.

The study results have shown that ABTL0812 inhibits cell proliferation of glioblastoma cells and glioblastoma stem cells by activating autophagy-mediated cancer cell death through the inhibition of the inhibition of Akt/mTORC1 axis and the activation of endoplasmic reticulum (ER) stress/unfolded protein response (UPR). In in vivo intra-brain models it has been shown that ABTL0812 as single therapy impairs tumor growth and increases disease-free survival and overall survival of mice. Moreover, the combination of ABTL0812 with the standard of care treatments for glioblastoma radiotherapy and the chemotherapy drug temozolomide has shown that ABTL0812 potentiates the efficacy of both treatments and that the strongest effect is obtained with the triple combination of ABTL0812+radiotherapy+temozolomide.

In conclusion, the present study demonstrated the anticancer efficacy of ABTL0812 as single agent and in combination with standard of care treatments in models of glioblastoma and supports the clinical investigation of ABTL0812 as a potential novel therapy for this aggressive brain tumor type.

 

About ABTL0812

ABTL0812 is a first-in-class fully differentiated oral targeted anticancer compound causing cell death by autophagy (self-digestion).

ABTL0812 has demonstrated clinical efficacy in an open-label phase 2 clinical study in patients with endometrial cancer or squamous cell lung cancer, as a first-line treatment in combination with chemotherapy (CT) and as a maintenance treatment after CT cycles. The results show a significant increase in efficacy over first-line standard of care (carboplatin + paclitaxel) both in overall response rate (ORR) and progression free survival (PFS). Patients in the endometrial cancer group had an increase of over 30% in ORR compared to standard of care treatment (66% ABTL0812 + Chemotherapy vs 51% Chemotherapy alone) and of 38% in PFS (7.1 months à 9.8 months). In the sqNSCLC group, ORR increased over 40% compared to standard of care (53% vs 32%) and PFS increased 44% (4.2 months à 6.2 months). Additionally, overall survival (OS) analysis shows an increase of 100% going from 11,3 months in the best historical control to 22.5 months in sqNSCLC patients treated with ABTL0812 + Chemotherapy. The study was led by Vall d’Hebron Institute of Oncology, VHIO (Barcelona), Institut Gustave-Roussy (Paris) and Centre Léon Bérard (Lyons) and included other sites in Spain and France.

ABTL0812 has also received Orphan Drug Designations (ODD) for pancreatic cancer, biliary cancer, and the pediatric cancer neuroblastoma by the FDA in the USA and by the EMA in Europe.

The mechanism of action of ABTL0812 is unique and novel. ABTL0812 is a first-in-class small molecule, orally administered, that binds to the nuclear receptors PPARα and PPARγ inducing PPAR-dependent Endoplasmic Reticular Stress (ER-stress) and blocking Akt activation, the central kinase of the PI3K/Akt/mTOR pathway. The combination of inhibition of the PI3K/Akt/mTOR pathway and the ER-Stress induction results in an autophagy-mediated cancer cell death. The mechanism of action was published in Clinical Cancer Research in May 2016 and in Autophagy in May 2020. Additional immunomodulatory antitumor effects show that ABTL0812 transforms “cold” tumors into “hot” immunogenic tumors. These effects were presented at AACR congress in April 2021. Publication is under way.

In preclinical cancer models, ABTL0812 is effective as a single agent with an excellent safety profile in a broad spectrum of cancer types, including lung, endometrial and pancreatic cancer, neuroblastoma, and glioblastoma. Likewise, it also enhances chemotherapy and immunotherapy with a synergistic effect without increasing its toxicity. Translational results have been published in Gynecologic Oncology (2019), International Journal of Cancer and Cell Death and Disease (2020), Cancer Communications (2022) and Frontiers in Oncology (2022).

About Ability Pharmaceuticals

Ability Pharmaceuticals (www.abilitypharma.com) is a biopharmaceutical company with a product, ABTL0812 in phase 2b clinical trials, focused on improving the future of oncology by developing innovative therapies that address unmet medical needs. In April 2016, AbilityPharma signed a territorial license agreement for ABTL0812 with SciClone Pharmaceuticals (Hong Kong) Development Co. Limited to develop and market the product in China.

Ability Pharmaceuticals is headquartered in Parc Tecnològic del Vallès and Parc de Recerca UAB (Cerdanyola del Vallès, Barcelona, Catalonia, Spain). Current shareholders include its founders, private investors, CDTI, the biotech venture capital firms Inveready, Fitalent and SODENA, the EIC Fund and SciClone Pharmaceuticals, and has the financial support from ACCIO (Government of Catalonia), CDTI, ICO, ENISA, the Ministry of Science & Innovation (Government of Spain) and the European Commission (H2020 Program, European Innovation Council).

Contact information:

Carles Domènech, PhD

Executive Chairman and CEO

Ability Pharmaceuticals

E-mail: media.relations@abilitypharma.com

Tel.: +34 935 824 411

www.abilitypharma.com