An HBV program built on ingenuity, vision and experience
Our goal is to discover and develop finite and curative therapies for those chronically infected with hepatitis B virus (HBV), and we believe we have unique capabilities that will enable us to bring the first therapeutic innovation in decades and improve cure rates for individuals with chronic HBV infection. Our strong scientific expertise in discovering small molecules targeting the HBV core protein has made us a leader in the field.
HBV—one of the world’s most prevalent diseases
Chronic hepatitis B virus (HBV) infection is a debilitating disease of the liver that afflicts approximately 270 million people worldwide, as estimated by the World Health Organization. HBV is a global epidemic that affects more than twice the number of people than hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection combined—with a higher morbidity and mortality rate. HBV is a leading cause of chronic liver disease and need for liver transplantation, and up to one million people worldwide die every year from HBV-related causes.
The current standard of care for patients with chronic HBV infection is life-long suppressive treatment with medications that reduce, but do not eliminate, the virus, resulting in very low cure rates and enormous unmet need.
Our unique approach attacks HBV at multiple points in the viral replication cycle
Assembly Bio is advancing a number of core inhibitors (CIs), a novel class of oral antivirals, into preclinical and clinical development. Each of these CI product candidates has been derived from distinct and novel chemical scaffolds to optimize their ability to effectively disrupt both viral replication and prevent the establishment and replenishment of new covalently closed circular DNA (cccDNA)—a viral component that drives HBV’s life-long persistence in patients. The current standard of care can only inhibit production of new virus – and may do so incompletely.1
1Marcellin, et al, AASLD 2014, Poster 1861
A pipeline strategy designed to free patients from lifelong therapy
In our relentless pursuit to bring finite and curative treatments to HBV patients in need, our pipeline strategy is focused on three key areas:
- More potent, next generation core inhibitors
- Proof-of-concept combinations exploring a core inhibitor with multiple other mechanisms
- New compounds with novel targets and mechanisms
Potent next generation core inhibitors
VBR is our most advanced CI product candidate, however we continue to develop more potent, next generation CI product candidates. These include ABI-H2158 (2158), ABI-H3733 (3733), which have demonstrated 10-fold and 40- to 50-fold higher potency than VBR, respectively, in inhibiting cccDNA formation in preclinical studies. A Phase 2 trial of 2158 and a Phase 1 study of 3733 are ongoing. We are also aiming to nominate a fourth-generation CI candidate with a potential, best-in-class profile, including greater potency against cccDNA formation.
Proof of concept combinations with multiple mechanisms
Assembly Bio is exploring the potential to combine three or more therapeutic candidates with differing mechanisms of action, an approach that has proven successful in the treatment of other diseases, including chronic viral infections. Our first two triple combination studies in individuals with chronic HBV infection include a Phase 2 clinical trial evaluating the addition of interferon to the antiviral backbone of VBR and standard-of-care nucleos(t)ide (Nrtl) therapy and a Phase 2 clinical trial evaluating the addition of Arbutus Biopharma’s RNAi candidate (AB-729), to the VBR+Nrtl antiviral backbone
Research programs advancing new compounds with novel targets and mechanisms
Our research collaboration with Door Pharmaceuticals is focused on developing a novel class of HBV cccDNA disruptors that target different phases of the HBV replication cycle distinct from and complementary to those targeted by Assembly Bio’s existing pipeline compounds. Our internal team is also focused on proprietary research that has the potential to accelerate progress toward HBV cures. We are currently advancing two novel research programs against undisclosed targets that we believe are differentiated in the field.
More information about our clinical trials can be found at www.clinicaltrials.gov.