Arbutus Forges HBV Collaboration with Vaccitech; Kura Partners with Novartis in Oncology

Arbutus Biopharma forged a clinical collaboration with U.K.-based Vaccitech plc to develop a new treatment for people infected with chronic hepatitis B virus who are already receiving standard-of--care therapy.

There are an estimated 250 million people in the world with HBV, including about 2 million people in the United States. Approximately 900,000 people die each year due to complications related to chronic HBV infection (CHB) despite the availability of effective prophylactic vaccines and current treatment options. Vaccitech and Arbutus believe a combination of Arbutus’s proprietary GalNAc delivered RNAi therapeutic, AB-729, followed by Vaccitech’s proprietary immunotherapeutic VTP-300 could become a cornerstone therapy for patients who are not progressing on the standard-of-care nucleotide reverse transcriptase inhibitor (NrtI) therapy.

The companies will assess the combination in a Phase IIa study in NrtI-suppressed subjects with CHB. In the Phase IIa meets endpoints, a larger Phase IIb study will be undertaken.

Gaston Picchio, chief development officer at Arbutus, said that, based on positive clinical data from an ongoing Phase Ia/Ib study of AB-729 in hepatitis B, the company is excited about the prospect of the RNA interference (RNAi) therapeutic. In preclinical studies, AB-729 has demonstrated the ability to inhibit viral replication and reduces all HBV antigens, including hepatitis B surface antigen. The company believes AB-729 has the potential to be a cornerstone therapeutic for multiple hepatitis indications.

“We are looking forward to initiating this proof-of-concept Phase 2a clinical trial, which will allow us to evaluate the combination of two promising clinical candidates with potential complimentary mechanisms of action. We believe combining AB-729, which is designed to reduce HBsAg resulting in increased HBV immune responses with VTP-300, an immunotherapeutic designed to elicit an HBV specific immune response, may offer patients with CHB a much-needed and durable functional cure,” Picchio said in a statement.

Vaccitech’s VTP-300 harnesses the company’s ChAdOx1-HBV/MVA-HBV prime-boost combination to produce an immune response against HBV. Vaccitech’s proprietary platform has demonstrated robust activation of cytotoxic CD8+ T cells (immune cells associated with clearance of HBV infected cells), which are believed to have the potential to lead to a functional cure for patients with CHB.

Vaccitech CSO Tom Evans said postulated that immune modulation could play a key role in treating CHB, which is characterized by T cell exhaustion primarily driven by HBsAg. Current CHB treatment can control viral replication, but not cure the disease, Evans said.

“We believe that a combination of immunotherapy, such as VTP-300, with agents that reduce hepatitis B surface antigen is a promising approach toward a functional cure,” Evans said in a statement. “This clinical trial will be evaluating that hypothesis. If successful, we believe that VTP-300, along with siRNA, such as AB-729, could be a foundation for CHB combination therapy.”

In addition to the collaboration between Arbutus and Vaccitech, San Diego-based Kura Oncology struck a clinical partnership with Swiss pharma giant Novartis. The two companies will assess the combination of tipifarnib and Piqray (alpelisib) in patients with head and neck squamous cell carcinoma (HNSCC) whose tumors have HRAS overexpression or PIK3CA mutation and/or amplification.

Kura’s tipifarnib is a farnesyl transferase inhibitor drug candidate currently being assessed as a monotherapy in patients with HRAS mutant HNSCC. Novartis’ Piqray is phosphatidylinositol-3-kinase (PI3K) inhibitor with inhibitory activity predominantly against the PI3Kα isoform.

Kura Chief Medical Officer Stephen Dale said preclinical data suggests that HRAS and PI3Kα are co-dependent pathways in certain populations of HNSCC patients. He said the collaboration with Novartis is expected to expand the availability of tipifarnib to a significantly higher percentage of patients with advanced HNSCC

“Combining tipifarnib with alpelisib has the potential to provide a clinically meaningful increase in anti-tumor activity compared to when inhibiting either pathway alone,” Dale said in a statement.

The combination study is expected to begin in the second half of this year. The Phase I/II KURRENT study is designed to evaluate the safety and assess early anti-tumor activity of tipifarnib and alpelisib for the treatment of HNSCC patients whose tumors are dependent on HRAS and/or PI3Kα pathways. It’s believed these patients make up about 50% of HSNCC patients, the companies said.