Biovie Inc. · NASDAQ:BIVI
Biovie — Investor Presentation (December 2022)
47 slides from Biovie's investor presentation, Dec 7, 2022
Slide 1: Developing Transformative Therapies to Overcome Chronic Debilitating Diseases
Slide 2: Forward-looking statements
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 materia
Slide 3: Highlights
Highlights NE3107 is the only inhibitor, to our NE3107 i Parkinso! similar m anism of action BIV201 is the only drug to our knowledge, currently in development for refractory ascites, a condition with 50% mortality rate NE3107 reduced neuroinflammation and insulin resistance in a randomized, double-
Slide 4: Expected Catalysts & anticipated timelines (US)
Expected Catalysts & anticipated timelines (US) Alzheimer’s (NE3107) Parkinson's (nest0n o @ (BIV201) phases zi e ® @ 00 Q ve fing based on strong data from a single pivotal trial in indications with few therapeutic options. ©2022 BioVie Inc. | Corporate presentation | 4 * Two Phase 3 trials are usu
Slide 5: Alzheimer's Disease Pathways
Alzheimer’s Disease Pathways Tau mRNA TRx0237, Salsalate, lonis MAPTRx —- ABBV-8E12, BIIBO92,Semorinemab, AAV-th. 10h COR388 BIIBO76, Zagotenemab, Lu AF87908, ACI-35, JNJ-63733657 Phospho-Tau agipain Bryostatin 1, APH-1104, Avanex2-73 4 Azeliragon B aggregation ) Zo { < oe XPro1595 ABvac40, BAN2401,
Slide 6: Background on NE3107
Background on NE3107 + Small molecule; orally bioavailable First-in-class molecule with desirable characteristics * Crosses blood-brain barrier, thus CNS and peripheral applications + No safety issues identified to date in pre-clinical and clinical trials (up to Phase 2) Originated by Hollis-Eden Ph
Slide 7: NE3107 blocks inflammatory (but not homeostatic) ERK
NE3107 blocks inflammatory (but not homeostatic) ERK and NFkB, which play pivotal roles in AD pathogensis' Ras a? Ren MEK < Extracellular signals Insulin (e.g., cytokines, chemokines, AB, tangles, etc.) NE3107. ERK Cell/Synapse growth, Inflammatory factors repair, and regeneration TNFa 4 (€-g.. p38,
Slide 8: NE3107 modulates inflammation at the central hub
NE3107 modulates inflammation at the central hub, thereby reducing downstream inflammatory cascade Tau mRNA APP mRNA TRx0237, Salsalate, lonis MAPTRx Popsiphen 4 oe . ABBV-8E12, BIIB092,Semorinemab, ‘AAV-th. 10h ‘COR388 Tangle: E R ACI-35, JNJ-63733657 APP APOE4 Gingipains ( ) Bryostatin 1, APH-1104
Slide 9: Investigator-Sponsored Trial in MCI and Mild Alzheimer's Disease
Investigator-Sponsored Trial in MCI and Mild Alzheimer’s Disease, NCT05227820 An open-label, Investigator-Initiated exploratory biomarker study in patients who have MCI to Mild AD 55-89 years old, males and females experiencing cognitive decline with Clinical Dementia Rating (CDR) score of 0.5 to 1,
Slide 10: Large majority of patients improved significantly on the Global Rating of Change
Large majority of patients improved significantly on the Global Rating of Change (overall impression) All patients MMSE >=20 patients Improvement Absolute Change from Baseline (Mean #95% Cl) K fo} Absolute Change from Baseline (Mean +95% Cl) -3 ° - - 2 ~° . : Clinician Patient Partner Clinician Pati
Slide 11: Significant improvements in ADAS-Cog12 assessment of cognition
Significant improvements in ADAS-Cog12 assessment of cognition among MCI/Mild AD patients All patients MMSE >=20 patients 3 0 0 3 Ey i} = = Improvement Bavoine & Post reetment ‘Scores (Mean +95% Cl) WH Absolute Change from Baseline (Mean #95% Cl) Percentage Change from Baseline (Mean +95% Cl) - Base
Slide 12: Cognitive improvements consistent across multiple assessment scales
Cognitive improvements consistent across multiple assessment scales All Patients MCI/Mild AD Assessment (N=23) (n=18) ADAS-Cog12 =0:913 -2.167* MMSE -0.74 -0:39 MoCA -0.04 0.56 QDRS -0.54 1.56" CDR 0.04 -0.11* ADCOMS 0.0049 -0.07* ADAS-Cog12 = Alzheimer’s Disease Assessment Scale-Cognitive MMSE = Mi
Slide 13: Improvements on TNFa among MCI/Mild AD patients
Improvements on TNFa among MCI/Mild AD patients Tumor Necrosis Factor Alpha (TNFa) is a cytokine identified as a major regulator of inflammation whereby its excessive activation is associated with chronic inflammation+ All patients MMSE >=20 patients S 00 3” =" : : 10 g 0 @ an 3 i : : f ‘ 3 Hy a so
Slide 14: Improvements in TNFa significantly correlated to improvements in ADAS-Cog12
Improvements in TNFa significantly correlated to improvements in ADAS-Cog12 All patients MMSE >=20 patients s. Correlation = 0.46 (p*=0.0542) | Correlation = 0.59 (p*=0.0259) 95% Cl [-0.008, 0.763] ! ! 95% Cl [.088, 0.854] ADAS-Cog12 Change from Baseline ADAS-Cog12 Change from Baseline 80 28 00 Abso
Slide 15: Significant improvements in the CSF p-tau : Aβ42 Ratio
Significant improvements in the CSF p-tau : AB,, Ratio, a predictive measure of PET amyloid status"... All patients MMSE >=20 patients Worsen Absolute Change from Baseline (Mean #95% Cl) Baseline & Post-treatment Scores (Mean 95% Cl) Percentage Change from Baseline (Mean +95% Cl) Absolute Change fro
Slide 16: Driven by significant improvements in CSF p-tau
«. Driven by a significant improvements in CSF p-tau All patients MMSE >=20 patients Worsen Baseline & Post-treatment Values, pg/ML (Mean #95% Cl) c a — Bassine Nonth 3 Month 3 Month 3 Percentage Change from Baseline (Mean +95% Cl) Percentage Change from Baseline (Mean +95% Cl) Baseline & Post-treat
Slide 17: Modest improvements in CSF Aβ42
Modest improvements in CSF AB, All patients MMSE >=20 patients D » F ‘ 0 ‘ any sm} % i 4 2 i 2 . 2 ° S = fol = Dy —— 1 B90 tl = 2 8 il i i ea = = 3 a = 2 Fa : : 2 3 : g,, £yt- 3, 8 wy 2 ot 18, ed a 5 Fa i 5 § a é 4 8 & i F : i 3 s e 3 é : 8 » |b g D ay Ba Ee ot 8» #4 i i : j j : A a} 5 i 2 |. é } y
Slide 18: Arterial Spin Label Imaging suggests NE3107 enhances blood flow in the brain
Arterial Spin Label Imaging suggests NE3107 enhances blood flow in the brain, a marker for brain activity ¢ Arterial Spin Label Imaging looks at the flow of oxygenated hemoglobin ¢ Yellow indicates the most relative enhancement of flow while red indicates enhancement Patient N08 - Global Rating of C
Slide 19: BOLD imaging shows NE3107 can reduce hyperactivation of the hippocampus
Blood Oxygen Level-Dependent (BOLD) imaging shows NE3107 can reduce hyperactivation of the hippocampus’ towards normal * BOLD imaging looks at the release of oxygen from blood to the tissues and characterizes network connectivity * Image coloration indicates hyperactivation by stressed cells seeking
Slide 20: The multifactorial nature of dementia pathology
The multifactorial nature of dementia pathology « AD drug development at BioVie is based on the evidence that AD pathology is multifactorial in nature — While AB and p-tau are important factors, decades of research on dozens of agents have not conclusively correlated improvements on these individual
Slide 21: NM101: Phase 3 trial in Mild to Moderate Alzheimer's Disease
NM101: Phase 3 trial in Mild to Moderate Alzheimer’s Disease, NCT04669028 A Phase 3, Double-blind, Randomized, Placebo-controlled, Parallel Group, Multicenter Study of NE3107 in 316 to 400 Patients who have Mild to Moderate AD + Pivotal study for Alzheimer’s disease. Two weeks each of 5 mg and 10 mg
Slide 22: Background on biological aging
Background on biological aging * Epigenetics is the study of how behavior (e.g., diet, exercise) and environment affect the way our genes work in addition to the genetic code itself * Increasing body of evidence that signs of aging are epigenetic in nature *« DNA methylation is the process of how me
Slide 23: NE3107's Impact on Biomarkers of Aging
NE3107’s Impact on Biomarkers of Aging * Blood samples were collected before and after 3 months of treatment with NE3107 in the completed Alzheimer’s Investigator- Sponsored Phase 2 trial * Samples analyzed by Dr. Horvath’s team S 90. 10: PS FA R u _ =) G 5 2 ss = Fa 2m pe = Bal 8 § oS o . 3 g 7 F F
Slide 24: Remarkable Similarities Between Neurodegenerative Diseases
Remarkable Similarities Between Neurodegenerative Diseases Neuroinflammation and oxidative stress are common features in the major neurodegenerative diseases, Alzheimer’s, Parkinson’s, frontotemporal lobar dementia and ALS Remarkable parallels exist between AD and PD P ( Activated microglia-inflamma
Slide 25: Parkinson's Disease Clinical Development Program
Parkinson’s Disease Clinical Development Program NM201 Phase 2 * Satisfying FDA requirement for drug-drug interaction study with L-dopa * Detect efficacy signal for NE3107’s pro-motoric activity 40 patients with defined L-dopa “off state”, 1:1 active: placebo, 20 mg BID for 28 days * Safety assessme
Slide 26: NE3107's impact on motor control
NE3107’s impact on motor control UPDRS Part 3 Score - Day 28 change from Day 0 204 234 Day 28 Improvement in Motor Control vs. Day 0 All Patients Patients <70 years old Improvement T T T T T 1 T T T T T 0 1 2 3 4 8 0 1 2 3 4 8 Hours post administration —*- NE3107 + Levodopa--*—- Levodopa alone ©2022
Slide 27: Larger proportion of patients treated with NE3107 had >30% improvements in motor control
Larger proportion of patients treated with NE3107 had >30% improvements in motor control Percent of patients 100 36.4 Percentage of patients experiencing >30% improvement at Day 28 vs. Day 0 35.0 33.3 65.0 66.7 HB Levodopa alone I NE3107+Levodopa NE3‘107+Levodopa, <70 years old 77.8 77.8 66.7 0 | 1
Slide 28: BIV201 Disease Target: Refractory Ascites
BIV201 Disease Target: Refractory Ascites Refractory ascites patients typically undergo paracentesis to remove ascites fluid every week to 10 days Paracentesis: Withdrawal of 5-10L of ascites fluid (on average) from abdomen using a large bore needle Provides a few days of symptomatic relief The kidn
Slide 29: Prefilled Syringe with Patent-pending Liquid Formulation
Prefilled Syringe with Patent-pending Liquid Formulation BIVv201* Our liquid formulation of terlipressin. We will seek patent protection in the US, Europe, China and Japan Accurate dosing Eliminates mixing minute quantities of powder terlipressin that could result in medication errors or sterility l
Slide 30: BIV201 Development Plans
BIV201 Development Plans * Qtrial sites are activated and screening/enrolling patients * 20 ascites patients to receive BIV201 therapy + standard of care (SOC); 10 to receive SOC only (control group) — Co-primary endpoints: Incidence of ascites-related complications over 180 days following randomiza
Slide 31: Leadership Team
Leadership Team Deep expertise provides a strong foundation for success Cuong Do, President & Chief Executive Officer 30+ years in biopharma & technology President, Samsung Global Strategy Group Chief Strategy Officer for Merck Senior partner at McKinsey & Company Joseph Palumbo, MD, Chief Medical O
Slide 32: Thank You
Slide 33: Portfolio Revenue Potential
Portfolio Revenue Potential Company Estimates? Use liatleavel US Patient Population US Peak Sales Potential _ Global Sales Potential Property NE3107: Alzheimer’s Cee eee) 6.1 million $7 billion >$10 billion by . ., Compound patent through ae . aye ar NE3107: Parkinson's 20311 1.0 million $1.5 billio
Slide 34: Prior NE3107 Clinical Studies
Prior NE3107 Clinical Studies * Improved insulin-stimulated glucose disposal, assessed by hyperinsulinemic, euglycemic glucose Obese, impaired clamp procedures glucose tolerant * Decreased C-reactive protein (CRP?) and increased HDL and adiponectin (both associated with healthy volunteers benefit in
Slide 35: NE3107's ability to enhance insulin sensitivity reproduced in Phase 1 trial
NE3107’s ability to enhance insulin sensitivity reproduced in humans in Phase 1 trial with impaired glucose tolerance patients Improved insulin-dependent glucose disposal in 48 obese, inflamed subjects Placebo HE3286 3 Baseline M % o 9 34 +5 6 7 8 © 2 o ae - 2 5 ¥ o1 § v v o & -1 = 0 re) —z y S. g Y
Slide 36: Insulin sensitizing improvement also brought improvements in AD indicators
Insulin sensitizing improvement also brought improvements in AD indicators In a Phase 1 study 48 obese subjects with impaired glucose tolerance, NE3107 ... Increased insulin _.. increased HDL ... ... decreased CRP... and increased itivity ... adiponectin * g Placebo Adi i iponectin HE3286 F “ (Day 2
Slide 37: NE3107's ability to enhance insulin sensitivity in Phase 2 trial with T2D patients
NE3107’s ability to enhance insulin sensitivity reproduced in humans in Phase 2 trial with T2D patients Improved the homeostatic model ... decreased postprandial glucose ... ... decreased HbA1c ... assessment of insulin resistance 3 40 a - re 5 aa 1 £ 30 a . aad ar) a = ry = kc] a —@ 0 Rajat 2 3 —Aa
Slide 38: Inflammation drives systems dysregulation
Saag Inflammation drives systems dysregulation « Patients with increasing metabolic disease show greater variability for individual hematology, metabolic and chemistry values * Indicates increasing dysregulation DL: dyslipidemic placebo group, IGT: impaired glucose tolerant placebo group, Naive: tre
Slide 39: NE3107 decreased systems dysregulation in a Phase 2 study in advanced T2D patients
NE3107 decreased systems dysregulation in a Phase 2 study in advanced T2D patients Heteroscedasticity* investigated by analyzing data distributions for Group Day Parameter Wa? WiiP normality (Shapiro-Wilks W test) ical Te Giion i Fasting glucose 20.1 0.02 * Deviations from normal distribution repres
Slide 40: The Role of Reduced Insulin Signaling in Parkinson's Disease
The Role of Reduced Insulin Signaling in Parkinson’s Disease Stimulation of insulin signaling improves motor function in Parkinson’s patients Intranasal Insulin Treatment Reduced Inflammation and Improved Motor Activity 60-4 * v7 O_Insulin Baseline 40-44 @ Insulin Post-Treatment © O Placebo Baseline
Slide 41: Inflammation's Role in LID
Inflammation’s Role in LID Reduction of TNF-induced inflammation reduces LID B L-DOPA Cc @ Veh+L-DOPA 90 207 ————__ @ CPZ+CBD+L-DOPA 80 215 70 2 60 e * E e g e 3 $ 60 2 = 10: a 2 £ a 2 50 < 30 2 < é a 40 r=0.95 40 } p< 0.0001 0 CPZ+ 0: = 1 15 20.2! Veh CBD Veh CPZ+ 0 5 0 5 0 5 CBD TNF-a (pg/mg) AIM:
Slide 42: NE3107 decreases L-Dopa-induced dyskinesia (LID) in marmosets
NE3107 decreases L-Dopa-induced dyskinesia (LID) in marmosets Distribution of AIMS Scores 30 7 NE3107 Score Frequency Less More Dyskinesia Abnormal Involuntary Movement Scale (AIMS) ©2022 BioVie Inc. | Corporate presentation | 42
Slide 43: NE3107 has similar promotoric activity to L-dopa in rodent and marmoset models
NE3107 has similar promotoric activity to L-dopa in rodent and marmoset models MPTP Mouse MPTP Marmoset treated at Week 8 N 8 5 * * Placebo NE3107 g L-Dopa NE3107+L-Dopa 100: L-dopa and NE3107 combination is better than either drug alone 50: Mean Disease Score i Mean latency to fall (sec) 0. T T T T
Slide 44: NE3107 preserved TH+ neurons in MPTP marmosets
NE3107 preserved TH+ neurons in MPTP marmosets Control moneys (M09100 and M11008) p=0.0013* 3 p=0.163 = 2504 e > gi 200+ Ld e > —. 2 1504 ee . 5 og HE3286 (M11007) Amantadine (M10084) 3 1004 —ey2— . 2 ° . Se 2 a 0 T T T 3 vehicle amantadine HE3286 Note: NE3107 was originally known as HE3286 from Hol
Slide 45: BioVie Phase 2a trial results: BIV201 Pharmacokinetics
BioVie Phase 2a trial results: BIV201 Pharmacokinetics Continuous low blood levels of terlipressin versus spikes with IV-bolus dosing ster presentation at ASLO Comparison of the PK Profile of Terlipressin Administered by Continuous Infusion or Intermittent IV Boluses. om) — Tetipressin IV Bolus 1 mg
Slide 46: Continuous Infusion Terlipressin in Refractory Ascites/HRS Patients
Continuous Infusion Terlipressin in 6 Refractory Ascites/HRS Patients* Improved renal function Decreased ascites fluid Mean serum creatinine value Mean amount in liters 40 250 in umol/liter 30 ~ 200 a 2 w = 150 fe) — 20 2 5 -55% = 100 -47% 10 a 50 ie) 0 Baseline Treatment Month Baseline Treatment Mo
Slide 47: Continuous Infusion Terlipressin in Refractory Ascites/HRS Patients
Continuous Infusion Terlipressin in 19 Refractory Ascites/HRS Patients Pre-therapy: * 70% of patients required weekly large volume paracentesis (LVP) * 63% poor muscle strength Results: * Median duration of Cl terlipressin treatment: 51 days * 46% average reduction in frequency of paracentesis * Sig