Barcelona (Catalonia, Spain), November 7, 2018. Ability Pharmaceuticals, a drug development biopharmaceutical company specialized in oncology, announced today that it has received orphan-drug designation (ODD) for ABTL0812 from the US Food and Drug administration (FDA) for the treatment of biliary tract cancer.
 
The ODD program of the FDA grants special status to medicines and biological products intended to treat, diagnose or prevent rare diseases, which affect fewer than 200,000 people in the USA. This designation establishes a period of exclusivity for seven years of commercialization against competition, as well as certain incentives, such as federal grants, tax credits, a decrease in regulatory fees in the drug approval process, and clinical development advice.
 
The biliary tract refers to the organs and ducts that make, store and release the bile into the small intestine, and includes the liver, gall bladder and bile ducts located inside and outside the liver. Biliary tract cancer is a rare, highly fatal and heterogenous malignancy that arises from different locations within the biliary tree and comprises less than 1% of all human cancers and around 10-15% of all primary liver cancers. It is a life-threatening disease with a significant unmet medical need and treatment options are very limited due to its poor response to chemotherapy, radiation therapy and surgery conventionally used.
 
In preclinical studies, ABTL0812 has shown efficacy in biliary tract cancer as single agent and synergistic effect in combination with taxanes, platinum compounds and gemcitabine, with induction of tumor regression without increasing the toxicity associated with chemotherapy. First-line therapy in patients with biliary tract cancer includes these compounds, and administered in combination with ABTL0812 could greatly improve the treatment outcome. Besides, in the phase 1 study evaluating ABTL8012 as monotherapy with advanced cancer patients, one patient with biliary tract cancer remained stable for 18 months.
 
"We are particularly excited about the opportunity to provide benefit to patients with biliary tract cancer following the outstanding response of one patient that remained stable during 18 months in the phase 1 study with ABTL0812." said Carles Domenech, PhD, CEO of Ability Pharmaceuticals. "Receiving another orphan designation represents an important milestone as we evaluate to start the clinical program in biliary tract cancer and other cancer types."

About ABTL0812 

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

ABTL0812 is currently in phase 2a open-label clinical trials in Europe in patients with endometrial cancer or squamous cell lung cancer, as a first-line treatment in combination with chemotherapy and as a maintenance treatment after the chemotherapy cycles. The study is being conducted in leading cancer hospitals in Spain and France.
This same phase 2 study was also approved by the US FDA in December 2017. In addition, the FDA approved the protocol for a phase 2 study in pancreatic cancer in January 2018.

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.

A phase 1/1b clinical trial was previously conducted (29 patients with advanced solid tumors), in which ABTL0812 showed great safety and tolerability and no dose-limiting toxicities were identified. There were signs of efficacy, and notably two patients had long-term disease stabilizations, for more than one year (14 and 18 months). In addition, ABTL0812 showed activity on biomarkers with dose-response.

The mechanism of action of ABTL0812 is unique and novel. 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 mechanism of action was published partially in Clinical Cancer Research in May 2016, and fully described in Autophagy journal in May 2020.

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 glioma. Likewise, it also enhances chemotherapy (taxanes, platinum compounds and gemcitabine) with a synergistic effect without increasing its toxicity.
 
About Ability Pharmaceuticals

Ability Pharmaceuticals (www.abilitypharma.com) is a biopharmaceutical company with a product, ABTL0812 in phase 2 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 the biotech venture firms Inveready, Fitalent and SODENA, its founders and private investors, and has the financial support from ACCIO (Government of Catalonia), and CDTI, ENISA and MINECO (Government of Spain).