Biovie Inc. · NASDAQ:BIVI
Biovie — Corporate Update (September 2022)
65 slides from Biovie's corporate update, Sep 7, 2022
Slide 1: Slide 1
Slide 2: Forward-looking statements
Forward-looking statements This document contains forward-looking statements mace 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 * Topline results from the Phase 2 exploratory biomarker trial suggest directional and exciting signals of NE3107’s potential in Alzheimer’s Disease (AD) — The majority of patients (especially those with MMSE >=20) saw improvements in ADAS-Cog12 and the Global Rating of Change (an instrum
Slide 4: Expected Catalysts & anticipated timelines (US)
Expected Catalysts & anticipated timelines (US) Alzheimer’s (NE3107) Parkinson’s (NE3107) Ascites (BIV201) @ ev Q ve “Two Phase 3 trials are usvally required for registration. However, the FDA has allowed fling based on strong data from a single pivotal trial in indications with few therapeutic opti
Slide 5: Background
Background
Slide 6: Alzheimer's Disease cascade
Alzheimer’s Disease cascade Tau mRNA APP mRNA ; TRx0237, Salsalate, lonis MAPTRx a ABBV-8E12, BIIB092,Semorinemab, AAV-th. 10h COR388 Phospho-Tau BIIBO76, Zagotenemab, Lu AF87908, ACI-35, JNJ-63733657 Bryostatin 1, APH-1104, Azeliragon XPro1595 ‘ABvac40, BAN2401, Aducanumab, AR1001, Crenezumab, CAD
Slide 7: NE3107 provides a novel mechanism of action in AD research
NE3107 provides a novel mechanism of action in AD research * AD research has largely focused on Amyloid Beta (AB) and phospho-tau (p-tau) for decades and has resulted in a large number of trials in the AD drug development pipeline in 2021 focused on these mechanisms. ! * More recently, however, rese
Slide 8: Background on NE3107
Background on NE3107 + Small molecule; orally bioavailable First-in-class molecule with at * Crosses blood-brain barrier, thus CNS and peripheral applications desirable characteristics > peripheral app S + No safety issues identified to date in pre-clinical and clinical trials (up to Phase 2) Origin
Slide 9: NE3107 blocks inflammatory (but not homeostatic) ERK
NE3107 blocks inflammatory (but not homeostatic) ERK and NFkB, which play pivotal roles in AD pathogensis' Ras MEK \2 g Ran ; Ss Extracellular signals Insulin (e.g., cytokines, chemokines, AB, tangles, etc.) NE3107 ERK Cell/Synapse growth, Inflammatory factors _ repair, and regeneration INra oo” (@.
Slide 10: 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 —€ ABBV-8E12, BIIBO92,Semorinemab, AAV-th. 10h COR368 . an hospho-tau BIIBO76, Zagotenemab, Lu AF87908, ‘ACI-35, JNJ-63733657 Bryostatin 1, APH-1 104,
Slide 11: Topline results from Investigator-Sponsored Exploratory Biomarker Trial
Topline results from Investigator-Sponsored Exploratory Biomarker Ti Alzheimer’s Disease _—
Slide 12: 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-Sponsored exploratory biomarker study in patients who have MCI to Mild AD conducted in clinician’s practice . The study enrolled 23 patients 55-89 years old, males and females experiencing cogni
Slide 13: Key findings
Key findings « Vast majority of patients saw significant improvements with NE3107 treatment in the Global Rating of Change (overall impression of patient’s daily abilities) (o<0.0001 to p<0.05) * 82% of 17 patients with MMSE >=20 experienced a 2.6 points improvement in ADAS-Cog12 (p=0.0046) * Improv
Slide 14: 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 a 51 e . 54 e g 5 44 @ « coe e e a4 coe ecoe oo 2 8 Ss S e ° 34 a © e eco e ene 34 2 elem ec g ° g + § 274 oe je @ o 4 co ee § zt @lee - e + = 2 ¢ 14 e e £ 14 ee 7 |
Slide 15: 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 Worsen Improvement Baseline & Post-treatment Scores (Mean +95% Cl) Worsen 40 ° & 50 30 s 20 Absolute Change from Baseline (Mean +95% Cl) . ° bg Percentage Change from Baseline (M
Slide 16: ADAS-Cog comparative change
ADAS-Cog comparative change Study ADAS-Cog score change Drug = Bapineuzumab Salloway et al* ‘Salloway et al.** Salloway et al. *** Vandenberghe et a” Vandenberghe et a.** Vandenberghe etal. Random effects mode! 0.02 [-0.08; 0.04) 33.3% -0.07 [-0.20; 0.05] 8.5% 0.08 [-0.21; 0.04) 8.7% -0.07 [-0.15; 0
Slide 17: Cognition improvements also seen on the Quick Dementia Rating Scale
Cognition improvements also seen on the Quick Dementia Rating Scale All patients MMSE >=20 patients 3 100 3 100 = = ° . 2 9 55 s s P 2! B5 s 3 2 B i 3 ra 8 50 H : r A ee 8 2 5 ee 2 / 3 ES ‘ 2 FY 2 8 rs 2 . ‘ 8 rf 2 $ 8 10 & oe Ss 3 8 10 £ 3 : Pope--Seafet---] J op----- teres : : Bo ote--eanenne 5 (
Slide 18: Improvements in cognition correlates with improvements in Global Rating of Change
Improvements in cognition correlates with improvements in Global Rating of Change Global Rating of Change Clinician Patient Partner ADAS-Cog12 observation Reported Reported 4202 4 4 20 2 4 a a AS. Lo Lo R=-0.52 (40.05) _ LS o — ; + 4 ° Doctor [5 Fh @ 0 a+ wo * aN _ R=-0.46 (p¢0.05) a4 00 ° 4 oe 20:
Slide 19: 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 8 s 200 | és 8 3s 3 200 3 i Z : i og § § g § Hy
Slide 20: 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 = 0.70 (p*=0.0077) Z », Correlation = 0.45 (p*=0.0596) 95% Cl [.24, 0.90] 95% Cl [-0.2, 0.76] ADAS-Cog12 Change from Baseline ADAS-Cog12 Change from Baseline 1 1 ‘ 1 1 ' 1 ' ' 1
Slide 21: Trending improvements in the CSF p-tau : Aβ42 Ratio
Trending improvements in the CSF p-tau : AB,, Ratio, a predictive measure of PET amyloid status’ All patients MMSE >=20 patients 2 os 40 045 40 = Ss = s = = = : j » |e” a 3 qm = 0.10 § & $ 010 § g 5 s< i 4 8 z 2 , ) 8 3 Ey 8 H owt--e--Sty--4 8 ob--4--p-----4 € S a 8 € a 0 a e o a g o ° e 5 é é 2 | §
Slide 22: Modest improvements in CSF p-tau
Modest improvements in CSF p-tau All patients MMSE >=20 patients 100 40 40 Worsen| WOK | Change from Baseline: Mean +- 95%Cl 75 20 mean +- 95%CI 25 = Baseline & Post-treatment Values, pg/ML (Mean +95% Cl) s Absolute Change from Baseline, pg/ML (Mean #95% Cl) Percentage Change from Baseline (Mean +95
Slide 23: Modest improvements in CSF Aβ42
Modest improvements in CSF AB,. All patients MMSE >=20 patients 2000 400 40 2000- 400 40 Increased ° Increased] 1500 ——— 200 20 1500- ——— 200 20 1000 1000- 500 200 20 o..¥$—_ = 20 Baseline & Post treatment Values, pg/ML (Mean +95% Cl) ‘Absolute Change from Baseline, pg/ML (Mean #95% Cl) ‘Absolute Ch
Slide 24: Early examination of imaging data shows promising results
Early examination of imaging data shows promising results * Quantitative scoring of imaging data is currently underway ¢ Review of imaging scans and data by the study's Principal Investigator (who is an imaging expert) indicates that NE3107 treatment in patients with MMSE >=20 is associated with cer
Slide 25: 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 26: 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 27: NMR spectroscopy shows NE3107 is associated with increased glutathione in the brain
NMR spectroscopy shows that NE3107 is associated with increased glutathione in the brain « Nuclear magnetic resonance spectroscopy is used to detect the presence of specific chemicals « NMR spectroscopy was used to quantify the level of glutathione (referred to as the master antioxidant and regulato
Slide 28: 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 29: Recap
Recap * This Investigator-Sponsored Phase 2 exploratory biomarker study was initiated to explore how NE3107’s role in neuroinflammation and insulin resistance may link to the biomarkers historically used by the AD research community. * This single-arm open-label study cannot isolate the placebo effe
Slide 30: Ongoing Phase 3 for Alzheimer's Disease
Ongoing Phase 3 for Alzheimer's Disease
Slide 31: 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 Patients who have Mild to Moderate AD + Pivotal study for Alzheimer’s disease. Two weeks each of 5 mg and 10 mg BID dose t
Slide 32: Trial update
Trial update ¢ Trial has enrolled one-half of targeted patients ¢ In blinded data, no drug-related adverse events have been seen in daily medical reviews * DSMB will review data later this year to recommend whether the company should increase study size beyond targeted 316 patients sI0V) biovie ©202
Slide 33: Phase 2 Drug-Drug Interaction and early Efficacy Trial in Parkinson's Disease
Phase 2 Drug-Drug Intera and early Efficacy Trial Parkinson’s Disease _
Slide 34: 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 / \ ( Activated microglia-inflam
Slide 35: 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 Insulin Baseline Insulin Post-Treatment Placebo Baseline @eogzo Placebo Post-Tre
Slide 36: NE3107 Impact in Parkinson's Mice Models
NE3107 Impact in Parkinson’s Mice Models Leads to a decrease in pro-inflammatory factors and preserves dopaminergic neurons Reduced iNOS, TNF-a, and IL1p a I Saline MPTP + vehicle MPTP +HE3286 @) da MPTP | vehicle MPTP 1 HE3286 *P = 0.02 Saline MPTP + vehicle MPTP + HE3286 Nicoletti 2012 Parkinson's
Slide 37: Inflammation's Role in LID
Inflammation’s Role in LID Reduction of TNF-induced inflammation reduces LID i] B j Cc @ Veh+L-DOPA , 90 0, ——SEOPA:_ @ cPz+CBD+L-DOPA 60: EDOES 80 = 15 70 = 2 60 e + = e = 40 g e 3 8 60 3 é 3 10 2 i = < 30 Pa 2 50 3 20 Fa 2 = 40 r=0.95 +4 Ld p< 0.0001 0 cPz+ * 0 Veh cBD ° Veh CPZ+ 0 5S 10 15 20 25
Slide 38: 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 ei Abnormal Involuntary Movement Scale (AIMS) DIOVIE ©2022 BioVie Inc. | Corporate presentation | 38
Slide 39: 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 =~ 200: 3 aaa i 150 2 : 100: j 50. o+— Saline bovie ve MPTP MPTP+ MPTP+ MPTP+ MPTP + NE3107_ L-dopa Vehicle L-dopa + NE3107 MPTP Marmoset treated at Week 8 Mean Disease Score 4 - + Placebo 5 NE3107 L-Dopa on ~
Slide 40: 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 = 250% e > gi 200+ * « > —. 2 1504 oe . 5 eg HE3286 (M11007) Amantadine (M10084) 3 1004 —ey2— e 2 ° . = 4 2 a 0 T T T 3 vehicle amantadine HE3286 Note: NE3107 was originally known as HE3286 from Hol
Slide 41: Proceeding to Clinical Development for Parkinson's Disease
Proceeding to Clinical Development for Parkinson’s Disease FDA requires a drug-drug interaction study before proceeding to later phase trials in patients that might use or need levodopa ¢ No indications of DDI in animal studies have been observed Our Phase 2 is a combined DDI and efficacy program to
Slide 42: Parkinson's Disease Clinical Development Program
Parkinson’s Disease Clinical Development Program NM201 Phase 2 * Assess NE3107 pro-motoric activity while satisfying FDA requirement for drug-drug interaction study with L-dopa 40 patients with defined L-dopa “off state”, 1:1 active: placebo, 20 mg BID for 28 days * Safety assessments: Standard meas
Slide 43: Trial Update
Trial Update * Trial should be fully enrolled over the next couple of months and read out by the end of 2022 * No drug-related adverse events have seen in daily medical reviews ¢ Seeing signal resembling results previously seen in marmosets * Detecting a signal from patients who have completed 28 da
Slide 44: Phase 2b Trial for BIV201 in Refractory Ascites
Phase 2b Trial for BIV2 Refractory Ascites
Slide 45: 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 46: Prefilled Syringe with Patent-pending Liquid Formulation
Prefilled Syringe with Patent-pending Liquid Formulation BIV201* Our liquid formulation of terlipressin. Seeking 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 loss En
Slide 47: 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 Comparison of the PK Profile of Terlipressin Administered by Continuous Infusion or Intermittent IV Boluses. 50 & sence Tetipressin IV Infusion 4 mg/24 h es a 8 8 sa
Slide 48: Continuous Infusion Terlipressin in Refractory Ascites/HRS Patients
Continuous Infusion Terlipressin in 19 Refractory Ascites/HRS Patients Pre-therapy: Decreased Need for Paracentesis Change in frequency of paracentesis procedures * 70% of patients required weekly large volume paracentesis (LVP) 2.9 * 63% poor muscle strength = 5 = Results: a oO ¢ Median duration of
Slide 49: Terlipressin Efficacy in Outpatients CIT-001
Terlipressin Efficacy in Outpatients CIT-001 * Terlioressin (2- 4 mg/day) administered for 28 days by continuous infusion in 6 patients with refractory ascites ¢ Data from 28d treatment period compared to 28d pre-treatment period — Mean ascites volume removed decreased by 66% on average — 4/6 patien
Slide 50: Terlipressin Safety in Outpatients CIT-001
Terlipressin Safety in Outpatients CIT-001 ¢ Treatment generally well tolerated — no cardiac or ischemic issues — 3/6 patients completed 28d of treatment ¢ Vital signs, AEs of interest, clinical laboratory findings, and ECG monitoring unremarkable ¢ SAEs consistent with patient population with advan
Slide 51: BIV201 Development Plans
BIV201 Development Plans Ascites * 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 randomization and change in ascites fluid removed over 90 days
Slide 52: Trial update
Trial update ¢ 11 trial sites are activated and screening/enrolling patients ¢ No treatment-related SAEs have been observed ¢ The trial is taking much longer than expected ¢ Patient recruitment has been hampered by Covid, which appears to have disproportionately affected this population of very sick
Slide 53: Recap
Recap * Topline results from the Phase 2 exploratory biomarker trial suggest directional and exciting signals of NE3107’s potential in Alzheimer’s Disease (AD) — The majority of patients (especially those with MMSE >=20) saw improvements in ADAS-Cog12 and the Global Rating of Change (an instrument t
Slide 54: Slide 54
Slide 55: 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 56: NE3107 Inhibits Systemic Inflammation
NE3107 Inhibits Systemic Inflammation Decrease in pro-inflammatory factors across several different preclinical disease models Decreased IFNy, IL-1, IL23, IL-4, TNFa Decreased NF«B in an Endotoxin Decreased Inflammatory Cell Infiltrates and IL-17 Expression in an RA Model? Shock Model and Myeloperox
Slide 57: NE3107 Effect on Inflammatory ERK via IRS1/2
NE3107 Effect on Inflammatory ERK via IRS1/2 Targets inflammatory, but not homeostatic, ERK signaling * Insulin Receptor Substrate (IRS) IRS1/2 can be activated by insulin via tyrosine phosphorylation, requires homeostatic ERK 4 oe | i « IRS1/2 also phosphorylated by proinflammatory serine kinases ©
Slide 58: NE3107 Decreases Neuroinflammation
NE3107 Decreases Neuroinflammation Decrease in several markers of neuroinflammation displayed in preclinical models Decreased Neurotrophic Receptor (p75) and Decreased Activated Microglia Amyloid Precursor Protein (APP) Rescued Axonal Transport 30. ONH 1. ONH 10. Retina ‘a = t t 0. Pa 3" z° 5 50. E
Slide 59: NE3107 Preserves Neuronal Function
NE3107 Preserves Neuronal Function Evidence of preserved ganglion cell function in Optic Neuritis in preclinical models Decreases Optic Nerve Head Reduced Activated Microglia in Optic Inflammation Nerves KK 2 = = 250- 2.0 N=14 4 kK g g 2004 N=14 8 1.54 @ 3 F N=14 8 150- % 1.07 Ow iS 2 100+ E r) we 0
Slide 60: NE3107 Enhances Insulin Sensitization
NE3107 Enhances Insulin Sensitization Suppresses development of hyperglycemia in multiple preclinical animal models HE3286 Suppresses Development of Hyperglycemia in Diabetic db/db Mice 6-week-old males 8-week-old males (0 Vehicle © 20me/ke HES206 O 4omeke HES286 mi 80me/kg HES286 A.25mp/kg rosiglit
Slide 61: NE3107 Phase 1 Trial Results
NE3107 Phase I Trial Results Enhanced insulin sensitivity in a phase | clinical trial with impaired glucose tolerance patients Improved Insulin-Dependent Glucose Disposal in 48 Obese, Inflamed patients HE3286 Placebo & Baseline M 2 3 4 5 6 7 8 5 . it H Hi o£ © v (s) a v o § v v 2 £A WG 3) —wt Y > o
Slide 62: NE3107 Phase 2 Trial Results
NE3107 Phase 2 Trial Results Enhanced insulin sensitivity reproduced in phase 2 trial with Type II Diabetes patients Improvement in Homeostatic Decreased Postprandial Glucose Decreased HbA1c Model Assessment of Insulin 3 a : : a 2 a“ z= aad a = A x a) 1 aA a ar VOC ae 3 3 10 Sa = 2 > agra 3-1 * go Z
Slide 63: Increased Insulin Sensitization Effect on AD
Increased Insulin Sensitization Effect on AD Insulin sensitizing improvement also brought improvements in AD indicators Proportion of patients with improvements (%) In a Phase 2 study 48 obese patients with impaired glucose tolerance, NE3107 ... Increased Insulin Sensitivity Increased HDL Decreased
Slide 64: Inflammation drives systems dysregulation
Inflammation drives systems dysregulation ¢ Patients with increasing metabolic disease show 7 .: ll ig : greater variability for individual hematology, E i l ! I 3 |. Li a l L 3 . 5 5 3 5 metabolic and chemistry values ; 2 Joe Sok « Indicates increasing dysregulation . me ‘ = ms gadis ‘bGeb dea DL:
Slide 65: 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 Waa? Wee? normality (Shapiro-Wilks W test) iene sei 200001 Gaiveet Fasting glucose >0.1 0.02 * Deviations from normal distributi