Arbutus Biopharma Stock

Arbutus Biopharma Corporation operates as a clinical-stage biopharmaceutical company.

The company is leveraging its extensive virology expertise to develop novel therapeutics that target specific viral diseases. The company’s focus areas include Hepatitis B virus (HBV), SARS-CoV-2, and other coronaviruses. To address HBV, the company is developing an RNA interference (RNAi) therapeutic, an oral PD-L1 inhibitor, and an oral RNA destabilizer to potentially identify a combination regimen with the aim of providing a functional cure for patients with chronic HBV infection (cHBV) by suppressing viral replication, reducing surface antigen and reawakening the immune system. The company’s lead compound, AB-729, is the only RNAi therapeutic with evidence of immune re-awakening. AB-729 is being evaluated in multiple phase 2 clinical trials. The company also has an ongoing drug discovery and development program directed to identifying novel, orally active agents for treating coronaviruses, including SARS-CoV-2, where it has nominated a compound and have begun IND-enabling pre-clinical studies. In addition, the company is also exploring oncology applications for its internal PD-L1 portfolio.

Strategy

The core elements of the company’s strategy include developing a broad portfolio of compounds that target cHBV; combining therapeutic product candidates with complementary mechanisms of action to find a functional cure for people with cHBV; and advancing small molecule antiviral product candidates to treat COVID-19 and future coronavirus outbreaks.

Product Candidates

The company’s product pipeline includes multiple product candidates that target various steps in the HBV viral lifecycle and pan-coronavirus compounds that target essential viral targets for replication. The company continues to explore expansion opportunities for its pipeline through internal discovery and development activities and through potential strategic alliances.

RNAi therapeutics represent a significant advancement in drug development. RNAi therapeutics utilize a natural pathway within cells to silence genes by eliminating the disease-causing proteins that they code for. The company is developing RNAi therapeutics that are designed to reduce HBsAg expression and other HBV antigens in people with cHBV. Reducing HBsAg is widely believed to be a key prerequisite to enable a patient’s immune system to reawaken and respond against the virus.

AB-729 is a subcutaneously-delivered RNAi single-trigger therapeutic targeted to hepatocytes using the company’s proprietary covalently conjugated GalNAc delivery technology. AB-729 reduces all HBV antigens and inhibits viral replication.

In this three-part clinical trial, the company investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multi-doses of AB-729 in healthy subjects and in cHBV patients with the goal of identifying the most appropriate doses and dosing intervals to take forward into Phase 2 clinical development.

The first two parts evaluated single ascending doses of AB-729 in healthy subjects and in patients with cHBV, respectively. Data showed that a 60mg or 90mg single dose of AB-729 results in robust HBsAg and HBV DNA declines in HBV DNA positive patients. Part 3 of the trial dosed HBV DNA negative/positive patients with 60mg or 90mg of AB-729 every 4, 8 or twelve weeks. Dosing of patients in Part 3 has been completed and the company is continuing to follow these patients.

At the AASLD Liver Meeting in November 2022, the company presented additional data from Part 3 of the AB-729-001 clinical trial, which included nine patients who had had previously completed 48 weeks of treatment with AB-729, and 24 weeks later met protocol-defined criteria to also stop NA therapy. These nine patients had completed 12 to 44 weeks of follow-up after discontinuing their NA therapy. None had met the protocol-defined criteria to restart NA therapy and there was no evidence of clinical or biochemical relapse. HBsAg levels remained at 1.05 log10 to 2.35 log10 below pre-trial levels in all nine patients. Three patients experienced transient HBV DNA elevations that spontaneously resolved without intervention, which further supports AB-729’s potential for immunological control. One patient restarted NA therapy at the investigator’s request after the week 20 visit; no alanine transaminase (ALT) elevation or safety signals were observed. There were no adverse events (AEs) reported and no ALT flares were observed in the clinical trial. Recently, one of the eight remaining patients met the protocol-defined HBV DNA criteria to restart NA therapy without evidence of any ALT flare. The company is continuing to follow the seven patients who remain off NA therapy and anticipate reporting additional off-treatment data in the first half of 2023.

The company has completed enrollment in a randomized, open label, multicenter Phase 2a proof-of-concept clinical trial investigating the safety and antiviral activity of AB-729 in combination with ongoing NA therapy and short courses of Peg-IFNa-2a in 43 stably NA-suppressed, HBeAg negative, non-cirrhotic patients with cHBV.

Through a clinical collaboration agreement with Vaccitech that the company entered into in July 2021, it is enrolling patients in AB-729-202, a Phase 2a proof-of-concept clinical trial evaluating the safety, antiviral activity and immunogenicity of Vaccitech’s VTP-300, a proprietary T-cell stimulating antigen-specific immunotherapeutic, administered after AB-729 in NA-suppressed patients with cHBV. The trial is designed to enroll 40 NA-suppressed, HBeAg negative or positive, non-cirrhotic cHBV patients. All patients will receive AB-729 (60mg every 8 weeks) plus NA therapy for 24 weeks. At week 24, treatment with AB-729 will stop. Patients will continue only their NA therapy and will be randomized to receive VTP-300 or placebo at Week 26, Week 30 and at Week 38 (if protocol-defined eligibility is met). At week 48, all patients will be evaluated for eligibility to discontinue NA therapy and will be followed for an additional 24-48 weeks.

The company amended the AB-729-202 protocol to include an additional arm with an approved PD-1 inhibitor, nivolumab (Opdivo). Upon regulatory approval of the amendment, 20 patients will receive AB-729 (60mg every 8 weeks) plus NA therapy for 24 weeks, followed by administration of VTP-300 plus a low dose of nivolumab in conjunction with the booster dose(s) only while remaining on their NA therapy. At week 48, all patients will be evaluated for eligibility to discontinue NA therapy, and will be followed for an additional 24-48 weeks. The company anticipates dosing the first patient in this arm in the first half of 2023, subject to regulatory approval.

Through a clinical collaboration agreement with Assembly Biosciences, Inc. (Assembly) that the comopany entered into in August 2020, Assembly conducted a clinical trial evaluating AB-729 in combination with its first-generation HBV core inhibitor (capsid inhibitor) candidate VBR and standard-of-care NA therapy for the treatment of cHBV in HBeAg negative patients with cHBV.

In June 2022, the company presented a poster at the 2022 EASL ILC highlighting data from a study that was designed to assess the preclinical activity of AB-101 and the compound’s ability to reinvigorate patient HBV-specific T-cells. Studies were conducted using a transgenic MC38 tumor mouse model and peripheral blood mononuclear cells (PBMCs) from cHBV patients. The company anticipates initiating a Phase 1 healthy subject clinical trial with AB-101 in the first half of 2023 with data from the single-ascending dose portion of the clinical trial expected in the second half of 2023.

The company is also exploring potential oncology applications for its internal PD-L1 portfolio. Preclinical data was selected for publication at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2022 showing that the company’s oral small-molecule PD-L1 inhibitors in development, which possess a novel mechanism of action, have the ability to mediate T-cell activation in primary human immune cells. The anti-tumor efficacy seen in vivo was comparable to anti-PD-L1 antibodies. The data is published in the Journal of Clinical Oncology.

AB-161 is the company’s next-generation oral small molecule RNA destabilizer specifically designed to target the liver. The company has conducted extensive non-clinical safety evaluations with AB-161 that provide confidence in this molecule’s ability to circumvent the peripheral neuropathy findings seen in non-clinical safety studies with its first-generation oral RNA destabilizer, AB-452. The company presented preclinical data at the 2022 Discovery on Target Conference showing that AB-161 reduced HBV RNA and HBsAg in multiple preclinical models, with favorable liver centricity and lack of observed peripheral neuropathy.

AB-343 is the company’s lead coronavirus drug candidate that inhibits Mpro. In its pre-clinical research conducted to date, AB-343 has shown pan-coronavirus antiviral activity, no reduction in potency against known SARS-CoV-2 variants, robust activity against SARS-CoV-2 Mpro resistant strains, and a favorable drug-drug interaction profile with no need for ritonavir boosting. The company anticipates completing IND-enabling studies and initiating a Phase 1 clinical trial with AB-343 in the second half of 2023. The company also intends to nominate a nsp12 clinical candidate and initiate IND-enabling studies in the second half of 2023. An nsp12 viral polymerase could potentially be combined with AB-343 to achieve better patient treatment outcomes and for use in prophylactic settings.

In March 2021, the company entered into a discovery research and license agreement, as amended, with X-Chem, Inc. (X-Chem) and Proteros biostructures GmbH (Proteros) to focus on the discovery of novel inhibitors targeting the SARS-CoV-2 nsp5 main protease (Mpro).

In December 2021, the company entered into a technology transfer and license agreement (the License Agreement) with Qilu Pharmaceutical Co., Ltd. (Qilu), pursuant to which it granted Qilu a sublicensable, royalty-bearing license, under certain intellectual property owned by it, which is non-exclusive as to development and manufacturing and exclusive with respect to commercialization of AB-729, including pharmaceutical products that include AB-729, for the treatment or prevention of hepatitis B in China, Hong Kong, Macau and Taiwan (the Territory).

The company has two royalty entitlements to Alnylam’s global net sales of ONPATTRO.

In 2012, the company entered into a license agreement with Alnylam Pharmaceuticals, Inc. (Alnylam) that entitles Alnylam to develop and commercialize products with its lipid nanoparticle (LNP) delivery technology. Alnylam’s ONPATTRO, which represents the first approved application of its LNP technology, was approved by the United States FDA and the European Medicines Agency (EMA) during the third quarter of 2018 and was launched by Alnylam immediately upon approval in the United States.

Patents and Proprietary Rights

In addition to its proprietary expertise, the company owns a portfolio of patents and patent applications directed to HBV core/capsid protein assembly inhibitors, HBV surface antigens secretion inhibitors, coronavirus main protease inhibitors, coronavirus Nsp12 inhibitors, LNP inventions, LNP compositions for delivering nucleic acids, such as mRNA and RNAi, the formulation and manufacture of LNP-based pharmaceuticals, chemical modification of RNAi molecules, and RNAi drugs and processes directed at particular disease indications. In the United States, the company’s patents might be challenged by inter partes review or opposition proceedings. In Europe, upon grant, a period of nine months is allowed for notification of opposition to such granted patents.

The company owns more than 65 patent families related to its compounds, formulations, and technology.

History

The company was formerly known as Tekmira Pharmaceuticals Corporation and changed its name to Arbutus Biopharma Corporation in 2015.