BioVie Investor Deck, June 2020
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Biovie is developing BIV201, a novel therapy for treating refractory ascites caused by advanced liver cirrhosis, aimed at addressing a significant medical need given the lack of approved medications specifically for this condition. The therapy employs continuous infusion of terlipressin to manage fluid accumulation, with preliminary studies showing promise in reducing complications and paracentesis procedures. Biovie is pursuing FDA approval and market exclusivity through orphan drug designations, with a planned Phase 2/3 clinical trial to further assess the therapy's efficacy and safety.
BioVie Investor Deck, June 2020
- 1. 1 Pioneering therapies for patients suffering from advanced liver cirrhosis Corporate Presentation | June 2020
- 2. 2 Forward-looking statements This document contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 that involve risks, uncertainties and assumptions that could cause BioVie’s actual results and experience to differ materially from anticipated results and expectations expressed in these forward- looking statements. BioVie has in some cases identified forward-looking statements by using words such as "anticipates," "believes," "hopes," "estimates," "looks," "expects," "plans," "intends," "goal," "potential," "may," "suggest," and similar expressions. Among other factors that could cause actual results to differ materially from those expressed in forward-looking statements are BioVie’s need for, and the availability of, substantial capital in the future to fund its operations and research and development. Other risks are that BioVie’s compounds may not successfully complete pre-clinical or clinical testing, or be granted regulatory approval to be sold and marketed in the United States or elsewhere. BioVie cannot guarantee the effectiveness of its patents or Orphan Drug designations. A more complete description of these risk factors is included in BioVie’s filings with the Securities and Exchange Commission. In addition to the risks described above and in BioVie’s filings with the Securities and Exchange Commission, other unknown or unpredictable factors also could affect BioVie’s results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. You should not place undue reliance on any forward- looking statements. BioVie undertakes no obligation to release publicly the results of any revisions to any such forward-looking statements that may be made to reflect events or circumstances after the date of that these slides are posted to BioVie’s website or to reflect the occurrence of unanticipated events, except as required by applicable law or regulation.
- 3. 33 $600M 20,000 US patients targeted for BIV201 therapy 0/0 Number of FDA- approved drugs to specifically treat ascites; Number of direct competitors Phase 2; Ph3 in 2021 Mid-stage Phase 2 Orphan drug candidate; FDA Fast Track and will seek Breakthrough Therapy status Orphan Drug Orphan Drug designations for ascites and HRS with potential 7 years market exclusivity**; Patent- pending liquid formulations BioVie Overview Addressable US ascites market size*; Projected BIV201 US peak sales of $400 M with 67% penetration Sources/Notes: * D'Amico 2014; Gines 2004; Third party market assessment, published 2015; US Patient Hospital Discharge Data, 2005; Assumes three 28-day treatment regimens annually. ** If first to market.
- 4. 4 Our initial target is ascites due to advanced liver cirrhosis • Cirrhosis is the 8th leading cause of death in the US1 • Resulted in 49,500 US deaths in 20101 • Ascites is the most common major complication2 • For refractory ascites the mean one-year survival rate is only 50%3 Our first disease target is ascites, the accumulation of 5+ liters of fluid in the abdomen. Fluid in the peritoneal cavity (ASCITES) 1Burden of Disease Collaborators 2013 2Ge and Runyon 20161US 3Bureau et al. 2017
- 5. 5 No effective medication options: Primed for disruption No drugs approved by FDA specifically for treating ascites Refractory ascites patients have frequent paracentesis procedures: • Withdrawal of ~5–10L of ascites fluid from abdomen every week to 10 days with a large bore needle* • Provides short-term relief, but the kidneys will eventually “burn out” • Patients worsen with life-threatening complications • No remaining options except for TIPS** surgery or liver transplant * Wong 2012 ** TIPS = transjugular intrahepatic portosystemic shunt to channel blood flow around the liver
- 6. 6 Ascites patients incur $5 billion+ in annual treatment costs Source: HCUP Nationwide Readmissions Database 2016. Average length of stay and charges for patients requiring paracentesis.
- 7. 7 How our therapy is intended to work: • Vasoconstricts the central region, forcing blood flow through the liver • This restores effective blood volume in the arteries, which • Shuts down the RAAS signaling pathway, so the kidneys no longer retain excessive salt and water • Thereby halting ascites fluid production Therapeutic goal: Halt the downward spiral Adapted from: Wong 2012
- 8. 8 Exploring the potential for terlipressin Terlipressin is approved in 40+ countries for treating two related complications of liver cirrhosis: HRS & BEV1 • Used for decades in hospitals dosed by IV bolus injection (1-2 mg every 4-6 hours) • Well understood mechanism of action2 with hundreds of publications • Not approved in the US or Japan • Not yet approved to treat ascites in any country BioVie advisor Dr. Paolo Angeli invented a new dosing method as a continuous infusion in the outpatient setting 1. HRS = Hepatorenal syndrome; BEV = Bleeding esophageal varices 2. Ding 2013
- 9. 9 BIV201 clinical development program BIV201 key clinical objectives are to: • Deliver terlipressin safely via continuous infusion with a portable pump and novel patent-pending liquid formulation in a pre-filled syringe • Reduce ascites fluid accumulation • Reduce ascites-related complications requiring hospitalization • Enable at-home therapy • Long-term bridge to liver transplant, or potentially avoid the need for transplant* Continuous infusion dosing: a new treatment paradigm “Terlipressin given by continuous infusion is better tolerated than intravenous boluses in the treatment of type 1 HRS. Moreover, it is effective at lower doses**” BIV201 is an investigational therapy BIV201 ** HEPATOLOGY 2016;63:983-992. * Based on Australian study results; will require US clinical trials to support this use.
- 10. 1010 Retrospective study results from P.Angeli, MD (Italy 2015) Continuous infusion terlipressin in 6 refractory ascites/HRS patients Source: Adapted from BioVie US Patent application 16/379,446 Angeli et al. No drug-related side effects were reported in this study. Terlipressin is not available in the US
- 11. 1112 Prospective study by Chapman et al. (Australia 2018) Continuous infusion terlipressin in 19 refractory ascites/HRS patients Pre-therapy: • 70% of patients required weekly large volume paracentesis (LVP) • 70% poor muscle strength Results: • Median duration of CI terlipressin treatment: 51 days • 43% average reduction in frequency of paracentesis • Significantly improved nutritional intake and muscle strength • No complications directly attributable to terlipressin Decreased Need for Paracentesis Change in frequency of paracentesis procedures Source: JHEP 2019. Terlipressin is not available in the US
- 12. 12 BIV201 Phase 2a study results in 6 refractory ascites patients (completed April 2019) Principal Investigator: Jasmohan Bajaj, MD at McGuire VA in Richmond, VA Primary objectives to assess safety, tolerability and pharmacokinetics (PK) Results1: • Pharmacokinetics (PK) of continuous terlipressin infusion matched our predicted model2 • Serious complications observed over 2-month period during/after BIV201 therapy: • Recurrence of hepatic encephalopathy (HE): 1 patient – possibly due to dehydration in conjunction with strong response to terlipressin in conjunction with diuretics (protocol modified to avoid this) • Leaking umbilical hernia: 1 patient (pre-existing) – not drug-related • Other adverse events observed: bacteremia3, asymptomatic hyponatremia, abdominal pain, headache, diarrhea, dizziness • BIV201 therapy maintained for 28 days in 3 of 6 patients 1. Large-scale clinical trial(s) will be required to confirm results. 2. Source: BioVie poster presentation at AASLD 2019. 3. On day 28 possibly related to a chronic non-healing leg ulcer wound (one patient).
- 13. 13 BioVie Phase 2a trial results: Timing of next paracenteses procedure 4 of 6 patients achieved ≥ 50% increase in days until next ascites fluid withdrawal (paracentesis) after starting BIV201 therapy Source: BioVie poster presentation at AASLD 2019. BIV201 is an investigational therapy
- 14. 14 BioVie Phase 2a trial results: Change in serum creatinine 4 of 6 patients experienced a reduction in serum creatinine (clearance of SCr is an indicator of kidney function) Source: BioVie poster presentation at AASLD 2019. BIV201 is an investigational therapy
- 15. 15 Advancing the BIV201 clinical program • June 2019: Type C Guidance Meeting with FDA • July: FDA meeting minutes received • October: Submitted Phase 2b/3 Clinical Trial Protocol to FDA • February 2020: Submitted FDA pre-meeting information package • April 2020: FDA feedback received and trial design finalized • Clinical study planned this summer: A Phase 2 Randomized, Controlled, Dose-Titration, Open-Label Study Evaluating the Safety and Efficacy of BIV201 in Addition to Standard of Care Compared to Standard of Care to Reduce the Recurrence of Ascites and Complications in Patients with Refractory Ascites Secondary to Decompensated Liver Cirrhosis (Clinicaltrials.gov NCT identifier 04112199)
- 16. 16 Phase 2 & 3 clinical trial plan • US Phase 2 trial with 24 refractory ascites patients: ‒ 16 will receive BIV201 + standard of care (SOC); 8 receive SOC only (control group) • Primary composite endpoint: Incidence of ascites-related complications, at least grade 2, over 180 days following randomization • Secondary endpoint: Ascites fluid removed over 90 days ‒ Dosing: start at 3 mg/day for 28 days (titrate between 1-6 mg/day if needed) ‒ Enrollment: ~6 sites enrolling ~4 subjects on average ‒ Timeframe: 2 cycles BIV201 within 4 months and follow for 60 days; long-term follow-up • Following completion of Phase 2, conduct a single pivotal Phase 3 randomized, controlled trial at ~20 US study sites Source: clinicaltrials.gov (identifier: NCT04112199). The FDA provided additional guidance in April 2020; certain risks associated with yet to be validated quality of life measures will be explored in Phase 2 trial.
- 17. 17 BIV201 is an investigational therapy BIV201 projected clinical timeline Phase 2a Trial + PK Analysis Completed April 2019 Phase 2/3 Clinical Trials YE/2018 YE/2020 YE/2021 Dose 1st Patient Target NDA*Filing 2022 * New Drug Application YE/2019 BIV201 is an investigational therapy
- 18. 18 Novel BIV201 home care delivery system BIV201 Premixed/ Prefilled Syringe Needle-free Connector 50 mL bag of saline for insertion into pump Portable pump (carried in small satchel)
- 19. 19 Filed formulation PCT & will apply for patent coverage in US, Japan, Europe, and China US Orphan Drug designations for both ascites (Sept ‘16) and HRS (Nov ‘18) to enable up to 7 years of market exclusivity FDA Fast Track status; will seek Breakthrough Therapy designation FDA Creating global patent estate to cover proprietary liquid terlipressin formulations USPTO IP protection and FDA Fast Track status
- 20. 20 Estimated US Patients (000s) Total Addressable Market (TAM) Projected Peak US Sales Refractory Ascites 19.81 $600 M $ 400M* Bleeding Esophageal Varices (BEV) 6.63 $166 M $83 M Catecholamine-Resistant Hypotension/Shock 125,0002 $150 M $75 M Hepatorenal Syndrome (HRS) 16.83 $67 M $34 M TOTAL: $792 MSources/Notes: * Planned US sales force: 30 reps/mgrs targeting 3,000 US liver disease specialists @$200K full cost per person = $6M per year 1. D'Amico 2014; Gines 2004 2. Third party market assessment, published 2015 3. US Patient Hospital Discharge Data, 2016 Note: Ascites & BEV assumes three 28-day treatment regimens annually; CRH assumes 3 days of therapy (Auchet, 2017); HRS Assumes 10 days of therapy BIV201 revenue potential – US only
- 21. 21 Will Seek Patent Coverage Patients Diagnosed with Cirrhosis Estimated Ascites Patients (000s) Est’d Refractory/ Intractable Ascites (000s) Japan 270,0001 541 10.8 Europe 800,0002 164 33 China 2 million3 500 100 Sources/Notes: 1. Third party market assessment, published 2013 2. BioVie assessment based on multiple sources 3. Minimum based on reported prevalence rates of cirrhosis in US/EU (China has highest prevalence of Hepatitis B worldwide) BIV201 international ascites treatment opportunity Potential to increase BIV201 revenues by >2X (excluding China) ✓ ✓ ✓
- 22. 22 Experienced and effective management team Terren Peizer, Chief Executive Officer, Chairman of the Board Mr. Peizer is an entrepreneur, investor, and financier with a particular interest in healthcare, having founded and successfully commercialized several healthcare companies. Mr. Peizer is the founder of Catasys, Inc., a leader in behavioral and mental health management services. He has served as the Chairman of the Board of Directors and CEO of Catasys since inception in 2004. Mr. Peizer is the Founder, Chairman, CEO and majority shareholder of NeurMedix, Inc., a biotechnology company with a focus on inflammatory, neurological and neuro-degenerative diseases. He is also the Chairman of Acuitas Group Holdings, LLC, his personal holding company that owns all his portfolio company interests, including BioVie, NeurMedix and Catasys. Acuitas is an industry leader in investing in micro and small capitalization public equities, having invested over $1.2 billion directly into portfolio companies. Previously he was Chairman of Cray, Inc., the leading supercomputing company, and held senior executive positions with the investment banking firms Goldman Sachs, First Boston, and Drexel Burnham Lambert. He received his B.S.E. in finance from The Wharton School of Finance and Commerce. Jonathan Adams, President & Chief Operating Officer, Director In 2007 founded the predecessor company to BioVie with over 29 years of biopharma industry experience including finance, M&A and licensing deals, technology commercialization, global product launches, drug marketing and sales force management. Mr. Adams was a member of Searle Pharma’s global launch team for Celebrex and worked on the commercialization of follow-on COX-2 inhibitors. After Searle was acquired, he was a vice president/account supervisor for healthcare advertising agencies and developed expertise covering a wide range of drugs and medical devices. Subsequently he became a leader of Mission Pharmacal’s urology division. Mr. Adams earned a BS at Cornell University and an MBA at the Tuck School at Dartmouth.
- 23. 23 Accomplished Board of Directors Chairman of the Board: Terren Peizer Director: Jonathan Adams Cuong Do President, Samsung Global Strategy Group; former Chief Strategy Officer at Merck; former partner at McKinsey who led their healthcare practice. Michael Sherman Former managing director at Barclays and Lehman Brothers; significant experience in health care finance; previously a securities attorney. Richard J Berman Former Chairman of National Investment Managers with $12 billion pension administration assets; director of Catasys, Inc., Advaxis, Inc., Cryoport Inc. and Immuron Ltd. Previously started the M&A and Leveraged Buyout Departments for Bankers Trust Company. Jim Lang CEO of Eversana, and health services company. Former CEO of healthcare analytics firm Decision Resources Group; active investor and advisor to several healthcare companies.
- 24. 24 Experienced and effective clinical & financial team Penelope Markham, PhD, Chief Scientific Officer Dr. Markham led the development of modified terlipressin compounds for LAT Pharma LLC, the predecessor company to BioVie, for 7 years prior to its acquisition by BioVie. Previously, she spent 15 years in immunology, infectious disease, bacteriology and drug discovery research. Dr. Markham was a co-founder and Research Director for Influx, Inc. engaged in antibiotic drug discovery. She has been a member of NIH grant review panels and consulted in a variety of therapeutic areas including Orphan drug development. Dr. Markham has more than 20 publications in peer- reviewed journals and three patents. Patrick Yeramian, MD, Chief Medical Officer Dr. Yeramian brings over three decades of drug research and medical device experience to BioVie. He has served as a medical director for multiple organizations including Searle Pharmaceuticals (now Pfizer) and TapImmune Inc. During his career, he has helped companies to file more than 20 investigational new drug and device applications (IND/CTX/CTAs), and won regulatory approvals for five new drugs and devices. J. Wendy Kim, CPA, Chief Financial Officer Over 25 years of experience in accounting and finance. As a CFO she managed corporate finance and operational groups, closed M&A transactions and secured bank financings. Denise Smith, MS, Vice President of Manufacturing Managed the development laboratory for a large CMO, including analytical development and validation, and established manufacturing processes for parenteral products (liquid, lyophilized, liposomes, emulsions) for new chemical entities for the National Cancer Institute and other contract customers. Leslie Koehler, RAC, MBA, Vice President of Regulatory Affairs Former Director, Global Regulatory Affairs for Baxter Healthcare’s pharmaceuticals division. Serves as a regulatory consultant for several pharmaceutical companies.
- 25. 25 World-leading medical advisory team Paolo Angeli, MD Head of the Unit of Hepatic Emergencies and Liver Transplantation at the University of Padova, Italy. He has participated in more than 15 clinical trials (Phase II – IV) in the treatment of clinical complications of portal hypertension and liver transplant. Currently he is Secretary of the International Ascites Club and, as a member of EASL, has participated in drafting guidelines for the management of patients with cirrhosis and ascites. Dr. Angeli has pioneered the use of continuous infusion terlipressin as a safer alternative to the traditional approach of intermitted IV bolus dosing in the treatment of hepatorenal syndrome. He is a frequent speaker on liver disease and has been widely published. Lead medical advisor
- 26. 2628 Company highlights • BIV201 is a novel therapeutic approach to a severe unmet medical need • Mid-stage drug candidate in US development for ascites - No drugs ever approved by FDA to treat ascites - Similar therapy currently in practice in Australia* • Clinical development plan: - Commence Phase 2 clinical study this summer - Commence pivotal Phase 3 trial in 2021 - Submit NDA for US marketing approval in 2022 • IP estate includes two Orphan drug designations and formulation patent application • High cost of patient care creates strong economic rationale for drug therapy • $400 million sales opportunity for ascites in US alone • Additional revenue opportunities for related conditions and global expansion * Source: ABC News Australia, March 5, 2018
- 27. 2727 Capitalization table Capital structure as of June 1, 2020 Common shares outstanding (Ticker: BIVI) 5,199,346 Warrants (WAEP: $4.52) 1,374,666 Options (WAEP: $10.50) 68,400 Fully-diluted shares 6,642,412
- 28. 28 Pioneering therapies for patients suffering from advanced liver cirrhosis Corporate Presentation