Ability Pharmaceuticals announces regulatory milestones for ABTL0812 in pediatric cancer neuroblastoma

Ability Pharmaceuticals, a drug development biopharmaceutical company specialized in oncology, today announced that it has received from the U.S. Food and Drug Administration (FDA), orphan-drug designation (ODD) for ABTL0812, its PI3K/Akt/mTOR pathway inhibitor, for the treatment of the pediatric cancer neuroblastoma and that it has received positive Scientific Advice from the European Medicines Agency (EMA) for its development in the same indication. These two regulatory milestones come after the ODD in neuroblastoma granted by EMA in April this year. ABTL0812 has successfully completed its Phase 1/1b trial in adult advanced cancer patients in Europe.

Carles Domenech, PhD, CEO of Ability Pharmaceuticals stated “We are very pleased with ABTL0812 gaining orphan-drug designation for neuroblastoma from the FDA, especially as it comes after the ODD granted by EMA earlier this year, as it would provide it with extra market exclusivity protection”. Carles Domenech continued "The EMA's Scientific Advice for ABTL0812 represents a significant step toward the development of the compound in Europe".

Jose Alfon, PhD, VP of Research and Development of Ability Pharmaceuticals said “Development of novel drugs directed at specific pathways is necessary to change the outcome of neuroblastoma and to improve its current therapeutic options”. José Alfon "We wish to thank the FDA for its fast review of the ODD application (just 6 weeks) and the EMA's Scientific Advice and the ODD Working Party for its fast resolution and their input and guidance."

The design of the clinical study for the Scientific Advice was done in collaboration with Dr. Soledad Gallego, Hospital Materno-infantil Vall d’Hebron in Barcelona, and Dr. Victoria Castel, Dr. Adela Cañete and Dr. Pablo Berlanga, Hospital Universitari I Politecnic La Fe in Valencia.

ABTL0812 is a first-in-class PI3K/Akt/mTOR (PAM) signaling pathway inhibitor with a novel mechanism of action, fully differentiated from other PAM inhibitors.

Neuroblastoma is a rare cancer of the nervous system that affects children and infants, mostly happening in the abdomen. It comprises 6-10% of all childhood cancers and causes about 15% of cancer-related deaths in children.

About FDA’s Orphan Drug Designation

Orphan drug designation is granted by the FDA Office of Orphan Products Development to novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 patients in the U.S or that are not expected to recover the costs of developing and marketing a treatment. Orphan qualifies the sponsor of the drug for various commercial and development incentives of the Orphan Drug Act, including tax credits for clinical research costs.

About EMA’s Scientific Advice

Scientific Advice is a procedure offered by the Scientific Advice Working Party (SAWP), which was established by the Committee for Medicinal Products for Human Use (CHMP) of the EMA. The Scientific Advice is offered from EMA to its stakeholders for clarification of questions arising during development of medicinal products. Scientific Advice is legally non-binding and its scope of is limited to scientific issues and focuses on development strategies rather than pre-evaluation of data to support an MAA.

About ABTL0812

ABTL0812 is a first-in-class investigational small molecule which inhibits the PI3K/Akt/mTOR (PAM) signaling pathway by a novel mechanism of action, fully differentiated from other PAM inhibitors under development, and with cell death mediated by autophagy. In preclinical models ABTL0812 has shown activity similar or higher than reference compounds, but with higher safety. Additionally, ABTL0812 potentiates the antitumor effect of several standards of care chemotherapeutic agents, while still maintaining its safety profile. Moreover ABTL0812 keeps its potency and efficacy in tumor cells that have become resistant to standard chemotherapy or targeted therapies, with superiority over other PAM inhibitors.

ABTL0812 has completed its First in Humans Phase 1/1b clinical trial in patients with advanced solid tumors by the oral route in Europe. The study has confirmed ABTL0812 predicted high safety profile with signals of efficacy with several long-term disease stabilizations and with inhibition of the PAM pathway as monitored with biomarkers.

The scientific data that allowed to identify ABTL0812 as a promising tool for the treatment of neuroblastoma was generated with the successful research collaborations Ability Pharmaceuticals has with Jose Miguel Lizcano, PhD, Coordinator of the Research Group on Mechanisms of Cell Signaling and its Alteration in Disease, at UAB Universitat Autònoma de Barcelona and with Miquel F. Segura, PhD of the Laboratory of Translational Research in Pediatric Cancer, led by Dr. Josep Sánchez de Toledo, at VHIR Vall d'Hebron Research Institute in Barcelona.

About Ability Pharmaceuticals

Ability Pharmaceuticals (www.abilitypharma.com) is a clinical-stage biopharmaceutical company with headquarters in Bellaterra (Barcelona, Catalonia, Spain). The company develops a highly differentiated new class of cancer drugs, with a novel mechanism of action. The company has two drug candidates in development: ABTL0812, which has finalized its first-in-humans phase 1/1b clinical trial with 27 patients, and ABTL0815 in preclinical development.

Current shareholders include the biotech venture firm Inveready Seed Capital, its founders and private investors, and has the financial support from ACCIO (Government of Catalonia), CDTI and MINECO (Government of Spain).

Ability Pharmaceutics is currently raising funds in a Series A financing round of 10 million Euros to advance in the Phase 2 development program.

About Neuroblastoma

Neuroblastoma is a rare cancer that mostly affects young children. Neuroblastoma develops from neural crest-derived cells which, among other locations, are found in the suprarenal glandules or in lymph nodes on the paravertebral sympathetic chain. In many cases, neuroblastoma first develops in the adrenal glands and can spread to other organs such as bone marrow, bones, liver and skin. The annual mortality rate is 10 per million children in the 0- to 4-year-old age group, and 4 per million in the 4- to 9-year old age group. The highest incidence is in the first year of life. Initial symptoms most common are aches and pains, loss of energy and loss of appetite. Additionally, the symptoms depend on where the cancer is and whether it has spread. An example is the appearance of an abdominal mass originated in the retro-peritoneum having hard consistency and difficult delimitation.

relatively late sign is a lump or swelling in the abdomen, as this is where the cancer commonly starts.

Given the high toxicity of the treatments, based on chemotherapy combinations, radiotherapy and immunotherapy, it is critical to accurately stratify patients to administer the most deleterious treatments only to those patients who are more likely to progress on the disease. Low risk group represents approximately 35% of the new diagnosed patients and surgical resection is the treatment commonly used, however in the cases of organ dysfunction due to tumor mass, chemotherapy is used, as well as in the intermediate risk group, however the long-term deleterious adverse effects associated to the exposure to the genotoxic chemotherapy drugs should ideally be minimized when possible. Standard therapy for high-risk tumors generally includes four consecutive phases: induction therapy, local control, consolidation therapy and biological treatments to treat minimal residual disease.