BioVie Inc. (NASDAQ:BIVI) is a clinical-stage biopharmaceutical company developing innovative drug therapies to treat chronic debilitating conditions including neurological and neurodegenerative disorders, as well as liver disease. The company's lead drug candidates, bezisterim (NE3107) and BIV201, have shown promising results in clinical trials and hold significant potential to address unmet medical needs.
Business Overview
BioVie's pipeline is primarily focused on two key therapeutic areas: neurodegenerative diseases and liver disease. In the neurodegenerative space, the company's lead candidate bezisterim (NE3107) is being evaluated for the treatment of Alzheimer's disease (AD) and Parkinson's disease (PD). Bezisterim is a novel, orally administered small molecule that is thought to inhibit inflammation-driven insulin resistance and major pathological inflammatory cascades. There is growing scientific evidence that both inflammation and insulin resistance play fundamental roles in the development of AD and PD.In the liver disease segment, BioVie's investigational drug candidate BIV201 (continuous infusion terlipressin) is being evaluated for the treatment of ascites due to chronic liver cirrhosis. BIV201 has been granted both FDA Fast Track designation and Orphan Drug status, and the company is currently finalizing the protocol design for a Phase 3 study following guidance received from the FDA.
Neurodegenerative Disease Program
Alzheimer's Disease (NCT05083260)
BioVie recently announced the analysis of topline efficacy data from its Phase 3 clinical trial (NCT04669028) of bezisterim (NE3107) in the treatment of mild to moderate AD. The study had co-primary endpoints evaluating cognition using the Alzheimer's Disease Assessment Scale-Cognitive Scale (ADAS-Cog 12) and function using the Clinical Dementia Rating-Sum of Boxes (CDR-SB).During the unblinding process, the company discovered significant deviations from the study protocol and current good clinical practices (cGCPs) at 15 study sites, leading to the exclusion of all patients from these sites. This resulted in the trial being left underpowered for the primary endpoints, with only 81 patients remaining in the Modified Intent to Treat population and 57 in the Per-Protocol population.
Despite the reduced sample size, the Per-Protocol population showed an observed descriptive change from baseline that suggested a slowing of cognitive loss. These patients also experienced an advantage in age deceleration versus placebo, as measured by a non-primary/secondary endpoint using a DNA epigenetic test. The company is now exploring options to potentially continue enrolling patients to achieve statistical significance or design a new Phase 3 study leveraging the latest data and understanding of bezisterim's potential effects in AD.
Parkinson's Disease (NCT05083260)
The Phase 2 study of bezisterim (NE3107) for the treatment of PD (NCT05083260) was completed in December 2022. This double-blind, placebo-controlled trial evaluated the safety, tolerability, and pharmacokinetics of bezisterim in PD patients treated with carbidopa/levodopa. The study met its primary objectives of assessing safety and potential drug-drug interactions, as well as its secondary objective of determining if preclinical indications of promotoric activity and apparent enhancement of levodopa activity could be seen in humans.Long COVID Program
In April 2024, BioVie announced the grant of a clinical trial award of up to $13.1 million from the U.S. Department of Defense (DOD) to assess bezisterim (NE3107) for the treatment of neurological symptoms associated with long COVID. The company anticipates the Phase 2b trial to commence by early 2025.Liver Disease Program
In the liver disease segment, BioVie's investigational drug candidate BIV201 (continuous infusion terlipressin) is being evaluated for the treatment of ascites due to chronic liver cirrhosis. BIV201 has been granted both FDA Fast Track designation and Orphan Drug status.In June 2021, the company initiated a Phase 2 study (NCT04112199) to evaluate the efficacy of BIV201 combined with standard-of-care (SOC), compared to SOC alone, for the treatment of refractory ascites. While enrollment was paused in March 2023, the initial data from the first 15 patients treated with BIV201 plus SOC showed at least a 30% reduction in ascites fluid during the 28 days after treatment initiation compared to the 28 days prior. Patients who completed the treatment with BIV201 experienced a 53% reduction in ascites fluid, which was sustained (43% reduction) during the three months after treatment initiation.
In June 2023, the company received guidance from the FDA regarding the design and endpoints for a definitive Phase 3 study of BIV201 for the treatment of ascites due to chronic liver cirrhosis, and is currently finalizing the protocol.
Financial Overview
For the fiscal year ended June 30, 2023, BioVie reported an annual net loss of $50,255,815, with no revenue generated. The company's annual operating cash flow and free cash flow were both $-40,252,881.In the most recent quarter ended March 31, 2023, the company reported a net loss of $8,067,830. Research and development expenses were $5,700,447, while selling, general, and administrative expenses were $1,974,264. The company had $30,350,337 in cash and cash equivalents as of March 31, 2023.
Liquidity and Capital Resources
As of March 31, 2023, BioVie had working capital of approximately $18.1 million, cash and cash equivalents totaling $30.4 million, and stockholders' equity of $18.9 million. The company's future operations are dependent on the success of its ongoing development and commercialization efforts, as well as its ability to secure additional financing.During the nine months ended March 31, 2023, BioVie raised approximately $9.3 million in net proceeds from the sale of common stock under its Controlled Equity Offering Sales Agreement. Additionally, on March 6, 2023, the company closed a best efforts public offering, raising approximately $21.0 million in gross proceeds before deducting placement agent fees and offering expenses.
Management expects that future sources of funding may include sales of equity, obtaining loans, or other strategic transactions. However, there is no assurance that the company will be successful in obtaining sufficient financing on terms acceptable to the company to fund continuing operations. These circumstances raise substantial doubt about the company's ability to continue as a going concern.
Risks and Challenges
BioVie faces several risks and challenges in the development and commercialization of its drug candidates. The company relies heavily on third-party contract research organizations (CROs) and clinical trial sites to conduct its clinical trials. Any failure by these third parties to successfully carry out their contractual duties or meet expected deadlines could significantly impact the company's ability to obtain regulatory approval for its product candidates.The company's Alzheimer's disease trial (NCT04669028) was significantly impacted by the exclusion of patients from 15 study sites due to suspected scientific misconduct and protocol deviations, leaving the trial underpowered. This could call into question the validity of the data and potentially delay or derail the development of bezisterim (NE3107) for AD.
Additionally, BioVie operates in a highly competitive and regulated industry, and the company's success is dependent on its ability to navigate the complex regulatory landscape and secure necessary approvals. The company also faces the risk of potential litigation, as evidenced by the recent shareholder class action lawsuit filed against the company and certain officers and directors.
Outlook
Despite the challenges faced by BioVie, the company's drug candidates, bezisterim (NE3107) and BIV201, hold significant promise in addressing unmet medical needs in neurodegenerative diseases and liver disease, respectively. The positive data seen in the bezisterim trials for AD and PD, as well as the promising results from the BIV201 Phase 2 study, suggest that the company's pipeline has the potential to deliver meaningful clinical benefits to patients.The company's recent capital raises have strengthened its balance sheet, providing the necessary resources to advance its clinical programs. However, the company's ability to continue as a going concern remains dependent on its success in securing additional financing.