Biovie Inc. · NASDAQ:BIVI
Biovie — Investor Presentation (September 2023)
60 slides from Biovie's investor presentation, Sep 11, 2023
Slide 1: Unlocking the science of longevity to develop transformative therapies
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains statements about BioVie’s future expectations, plans, strategies and prospects which constitute forward-looking statements. These forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Refo
Slide 3: Overview
Overview ° We believe that TNFa-mediated inflammation — Initiates and perpetuates a forward-feeding pro-inflammatory cycle — Leads to insulin resistance — Accelerates the “DNA methylation” and the aging process * Our lead asset NE3107 modulates the production of TNFa. In clinical trials, many patien
Slide 4: Expected Catalysts & anticipated timelines
Expected Catalysts & anticipated timelines Om Qe Alzheimer’s (NE3107) Parkinson’s (NE3107) Ascites Phi (av201) _biovie | * Two Phase 3 wis are usualy required fr registration. However, the FDALhas allow 4 on strong data from a single pivotal alin indications with few therapeutic options. ©2023 .BioV
Slide 5: Far-reaching impact of TNFa-mediated chronic low-grade inflammation
Far-reaching impact of TNFa-mediated chronic low-grade inflammation TNFa KKB, JNK Serine kinases Insulin resistance Inflammatory factors Tau phosphorylation DNA Methylation * Cytokines =» APP SNCA + Chemokines + Others DNMT3a.p, TET Diabetes Alzheimer's Alzheimer's Systems dysregulation of gene expr
Slide 6: NE3107's mechanism of action
NE3107’s mechanism of action eute * 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) Ras A m2 Ras MEK €
Slide 7: NE3107 in Alzheimer's Disease
Slide 8: NE3107 modulates inflammation at the central hub
NE3107 modulates inflammation at the central hub, thereby potentially reducing downstream cascade Popsiphen aaverh10h ‘TRx0237, Salsalate, PU- lonis MAPTRx ABB\-8E12, BIB092 Semorinemab, BIBO76, Zagotenemab, Lu AFB7908, ACI- 35, IN-63733857 Gingipains i 401 aducenumsb, AROD1 Crenezumab, AD 106, leca
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
Slide 10: Significant improvements in ADAS-Cog12 assessment of cognition
Significant improvements in ADAS-Cog12 assessment of cognition among MCI/Mild AD patients MMSE >=20 patients 0 Zo 6 Sul ’ a Bs z- 5 i ' : Ea ‘ E a 2 ¢ "Ty : i ‘ Sevtncteeeene Hf tte & a Bx 5 4 3 & ' 2 s go. _ i 2° “ Ey 0 ‘ 4 i i : | 3 qo a Hf ‘ 8 tee my Wah Won E 13/18 improved (729)! Mean Absolute
Slide 11: Cognitive improvements consistent across multiple assessment scales
Cognitive improvements consistent across multiple assessment scales Improvement Assessment ADAS-Cog12 -0.913 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-Cogi2 = Alzheimer's Disease Assessment Scale-Cognitive MMSE = Mini-Mental State Examination MoCA =
Slide 12: Improvements in TNFa significantly correlated to improvements in ADAS-Cog12
Improvements in TNFoa significantly correlated to improvements in ADAS-Cog12 MMSE >=20 patients Correlation = 0.59 (p*=0.0259) 95% Cl [.088, 0.854] ‘ADAS-Cog12 Change from Baseline $0 as oo a ‘Absolute TNFa. Change from Baseline, pg/ML. Corporate presentation | 12
Slide 13: Significant improvements in CSF p-tau
Significant improvements in CSF p-tau MMSE >=20 patients i 0 2 = Basen wots wand 10/16 improved (63%)! Mean Absolute Change = -1.66 (p=0.0343) Mean % Change = -4.93% (p=0.0852) + NE3107 decreased CSF p-tau by 5% over 3 months among MCI/Mild AD patients * Due to NE3107’s mechanism, reduction in p-tau
Slide 14: Arterial Spin Label Imaging suggests NE3107 enhances blood flow
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 NO8 - Global Rating of Cha
Slide 15: 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 16: Phase 3 trial in Mild to Moderate Alzheimer's expected to read out in Q4 2023
Current understanding provides optimism for the Phase 3 trial in Mild to Moderate Alzheimer’s expected to read out in Q4 2023 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 A
Slide 17: NE3107 in Parkinson's Disease
Slide 18: Parkinson's Disease Clinical Development Program
Parkinson’s Disease Clinical Development Program 40 patients with defined L-dopa “off state”, 1:1 active: placebo, 20 NM201 Phase 2 oo mg BID for 28 days * Satisfying FDA requirement for + Safety assessments: Standard drug-drug interaction study with measures of patient health, |-dopa L-dopa PK and
Slide 19: NE3107-treatment patients experienced fewer motor symptoms
NE3107-treatment patients experienced fewer motor symptoms before morning drug administration Day 28 Improvement in Motor Control vs. Day 1 All Patients Patients <70 years old Pag i”, ‘y \ 7” i Piesior J re | fet 4 “On" at t=0 6 0 04 ' Total patients 20 19 h t P-value* 0.02 54 * Fisher's exact test
Slide 20: 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 Percentage of patients experiencing >30% improvement at Day 28 vs. Day 0 100 4 Il Levodopa alone ao I NE3107+1evodopa 90 4 NE3107+Levodopa, <70 years old so 4 80:0) 778 778 70.0 70 4 66.7 66.7 2 65.0 63.6] £ 64
Slide 21: Desirable pharmacokinetics - no observed DDI
Desirable pharmacokinetics -— no observed DDI NE3107 Treated Plasma Levodopa 3 § 1500 0-8 hr 231 ngh/mL (SD 22.38) 1000 8 500 Mean NE3107 ng/mL in Plasma es ® g o oo 4 2 3 4 8 100.0 _ Hr post Levodopa administration 2 = ——Daylave —eDay 14 ave = 10.0 Placebo Treated Plasma Levodopa = _, 3000 Ss E 250
Slide 22: NE3107 in Longevity
Slide 23: Impact of wear & tear on a laser's ability to decode DVDs
Impact of wear & tear on a laser’s ability to decode DVDs Clean DVD leads to clear Scratches & smudges lead picture and sound to skips and blurs Quality of picture is dependent on the laser's ability to clearly decode the disk ... The same thing happens in our body Vieine. | Corporate presentation |
Slide 24: DNA methylation
DNA methylation ¢ DNA methylation happens when methyl groups are added to our DNA * DNAmethyltransferases add methyl groups to DNA * Functionally the equivalent of scratches and smudges ona DVD surface * The methyl groups interfere with RNA polymerase’s ability to decode DNA ¢ DNA methylation may ha
Slide 25: Observations about DNA methylation
Observations about DNA methylation * DNA methylation increases as we age ¢ DNA methylation can be affected by behavioral (diet, exercise) and environmental factors * DNA hypermethylation is associated with a large number of disease conditions, including various forms of cancers, age-related cognitiv
Slide 26: DNA methylation clocks measure extent of aging and biological function
DNA methylation “clocks” measure extent of aging and biological function Chronological clocks ! 5 CpGs (5 genes) X Blood (Bhane’s age predictor ‘514 CpGs (396 genes) Blood and Saliva Huang’s age predictor aces ee ( “aiacocatapapdi? predictor ) health Biological clocks Bocklandt clock 3 C965 (3 genes
Slide 27: NE3107 significantly reduced DNA methylation as measured by the SkinBloodAge Clock
NE3107 significantly reduced DNA methylation as measured by the SkinBloodAge Clock ¢ Dr Steve Horvath* developed an extremely precise Biological age DNA methylation clock, the DNAmethylation SkinBloodAge * The biological clock age was in close agreement with the chronological age (72.3 vs 71.6; +0.9
Slide 28: Lower DNA methylation of the CEP112 gene correlated with cognition
Lower DNA methylation of the CEP112 gene significantly correlated with measures of cognition CEP112 CEP112 cEP112 g g : ° 2 080 g g 0.50. . g . E oss. : eo : i 3 3 2 0.00. S E055. ‘ é 2 2 e 6 5 06s . 3 604+ 1. 2704 7; 7 4 40 05 00 05 10 45 04 02 00 02 04 08 ADAS.Cogtt cor ADCOMS 10.502 10.449 10458
Slide 29: >3,000 correlations between reductions in DNAm and clinical endpoints
>3,000 correlations between reductions in DNAm of various CpGs and cognitive, biomarker and neuroimaging endpoints Frequency of significant Spearman correlations between changes in DNAm (individual CpG residues) and clinical measures after 14 weeks of treatment sr wal A Insulin signaling" Anti-oxida
Slide 30: Summary of findings
Summary of findings ¢ We believe the data suggest that observed clinical findings and measured changes in DNA methylation and biomarkers are not accidental ¢ Data show that patients treated with NE3107 experienced reduced DNA methylation * Data also show that NE3107 may have changed the expression o
Slide 31: BIV201 in Ascites
Slide 32: 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 alarge bore needle Provides a few days of symptomatic relief The kidne
Slide 33: 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 34: BIV201 Phase 2b trial
BIV201 Phase 2b trial * Originally targeted 30 patients randomized 2:1 ¢ Paused enrollment based on encouraging data from the first 15 patients informing next steps * 10 randomized to BIV201; 5 randomized to standard of care * 5 completed 2 X 28-day cycles ¢ 5 discontinued treatment during or at end
Slide 35: Change in ascites volume 28d pre- vs post-treatment
Change in ascites volume 28d pre- vs post-treatment 53% reduction in ascites volume among e patient completing BIV201 treatment g oo ik a Sal * 15% reduction among patients who 1 started but did not complete treatment 4 * 3.1% increase for SOC patients ie | + p<0.001 g -80: BIV201 Completed _B1V201
Slide 36: Expected Catalysts & anticipated timelines
Expected Catalysts & anticipated timelines Om Qe Alzheimer’s (NE3107) Parkinson’s (NE3107) Ascites Phi (av201) _biovie | * Two Phase 3 wis are usualy required fr registration. However, the FDALhas allow 4 on strong data from a single pivotal alin indications with few therapeutic options. ©2023 BioVi
Slide 37: Commercial potential in US market alone
Commercial potential in US market alone* Alzheimer’s $30B Annual sales for every 1 million people treated * 15% market penetration ¢ $30K/year — much lower all-in cost vs. competition biovie ‘ei Parkinson's $3B Annual sales for every 100,000 people treated 10% penetration of US market ¢ $30K/ year $
Slide 38: 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
Slide 39: Recap
Recap We believe that TNFa-mediated inflammation — Initiates and perpetuates a forward-feeding pro-inflammatory cycle — Leads to insulin resistance — Accelerates the “DNA methylation” and the aging process Our lead asset NE3107 modulates the production of TNFa. In clinical trials, many patients trea
Slide 40: Thank You
Slide 41: Background on NE3107
Background on NE3107 Small molecule; orally bioavailable First-in-class molecule with desirable characteristics brain barrier, thus ( nd peripheral application: identified to date in pre-clinical and clinical trials (up to Phase 2) Originated by Hollis-Eden Pharmaceuticals (renamed Harbor Therapeuti
Slide 42: Prior NE3107 Clinical Studies
Prior NE3107 Clinical Studies + Improved insulin-stimulated glucose disposal, assessed by hyperinsulinemic, euglycemic glucose clamp Obese, impaired Procedures glucose tolerant + Decreased Creactive protein (CRP) and increased HDL and adiponectin (both associated with benefit in AD) healthy voluntee
Slide 43: 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 HE3286 3 o ° o 2 2 = 6 1 Zo 1 54 = Q 24 = 0.54, P < 0.0001) z-3 Qo a a 4° 12 3 4 5 6 7 8 9 10 Base
Slide 44: Insulin sensitizing improvement also brought improvements in AD indicators
Insulin sensitizing improvement also brought improvements in AD indicators Ina Phase 1 study 48 obese subjects with impaired glucose tolerance, NE3107 ... ie aa iponectin Placebo g Adiponectin A 4 . 91 HES286 (1 ay 98 Change) $ O g 75 73 : id - = 7 3 58 2 : 52 52 50 50 z 45 a1 2 36 z © Placebo ES =
Slide 45: 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 7 = eee response ee Os 40 a Sy 3 z & AHOMA2IR AnHbAL¢ (%HB) HE3286 Placebo 3 HE3286 Placebo HE3286 Placebo Geil fbesiee UCP 1 Sprit niecietsinged dinces 5 Pooled coh
Slide 46: Inflammation drives systems dysregulation
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: treatmen
Slide 47: 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 ee pace normality (Shapiro-Wilks W test) oe Si hast cohort Afastingglucore 30102 * Deviations from normal distribution represent
Slide 48: 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) E E ‘Absolute Change from Baseline (Mean +959 ()) All patients MMSE >=20 patients 2 ccee ore ore gs ode of. - - = | ‘= “4 . a : seed Ea ee | ze eel | ee ce | need we | ere we oe |. Be - : - 3-3 - 2
Slide 49: 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* MMSE >=20 patients Baseline & Posttreatment Values, pg/. Mean:295% C) "Absolute C
Slide 50: 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’... MMSE >=20 patients Baseline & Post-treatment Scores (Mean +95% C) ‘Absolute Change from Baseline (Mean +95% C1) Percentage Change from Bi 7/11 improved (64%)? Mean Absolute Change = -0.0024 (p=0.040
Slide 51: Modest improvements in CSF Aβ42
Modest improvements in CSF AB,. MMSE >=20 patients a0 00} i ..@$==—— i Ey ; 3 i i 3 ‘ot ' i 0 H 0 i é 7 i F ; Mb —— 7 : 0} 3 0 00} Beseine ‘Moni 3 Month Werth 3 9/13 decreased (69%) Mean Absolute Change = -8.69 (p=ns) Mean % Change = -0.92% (p=ns) ©2023 .BioVie Inc. | Corporatepresentation | 51
Slide 52: NE3107 May Be Associated With Reduced Oxidative Stress in the Brain
NE3107 May Be Associated With Reduced Oxidative Stress in the Brain % change from baseline in brain glutathione assessed by MRS of precuneus Precuneous Glutathione MCI/Mild AD 400 e® 300-4 200-4 © % change from baseline For all patients, there were significant correlations between glutathione and TN
Slide 53: 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. * . . Insulin Baseline Insulin Post-Treatment Placebo Baseline Placebo Post-
Slide 54: Inflammation's Role in LID
Inflammation’s Role in LID Reduction of TNF-i reduces LID d inflammati B x c @ Veh+L-DOPA D zs 90: 20, ——2ora © cPz+cBp+L-DOPA 60: ppork 515 = g 60: E 2 E 40: 5 2 ie + 3 = < 30: Zz € = 20 5 0. Ven CPE 0. oO. pm fe cPz+ + CBD veh eo TNF-ot (pg/me) Veh cap rate presentation | 54
Slide 55: NE3107 decreases L-Dopa-induced dyskinesia (LID) in marmosets
NE3107 decreases L-Dopa-induced dyskinesia (LID) in marmosets Distribution of AIMS Scores Score Frequency Dyskinesia Abnormal Involuntary Movement Scale (AIMS)
Slide 56: 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 4 a * q 200 > O Placebo 2 3 NE3107 y 150 8 3. a 3 4 @ L-Dopa es a a @ NE3107+L-Dopa a § = 50: < 1 L-dopa and NE3107 combination is H better than either drug alone 0. 0 T T T T Sa
Slide 57: NE3107 preserved TH+ neurons in MPTP marmosets
NE3107 preserved TH+ neurons in MPTP marmosets Control moneys (M09100 and M11008) p=0.0013* p=0.163 . a _. ee e . an 3 HE3286 (M11007) Amantadine (M10084) e 8 % Surviving Neurons vs. Vehicle So
Slide 58: BIV201
BIV201 ¢ Terlipressin administered as a continuous infusion * Outpatient treatment with small ambulatory infusion pump * Targets the pathophysiology of ascites * Multiple small trials and Phase 2a support efficacy in reducing ascites * Orphan and Fast Track Designations for the treatment of ascites
Slide 59: 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 — Terressinv Bots 1 mg 06H (ngimt) 28 10 3 3 5 E i i :
Slide 60: Ascites volume (L) 28d pre- vs 28d post-treatment BIV201 + SOC
Ascites volume (L) 28d pre- vs 28d post-treatment 2 BIV201 + SOC 7 SERa SSeeee css CEM mIe Mean: 34 % reduction 5/10 (50%) with >40% reduction P=0.0046 SOC only a Mean: 3.1 % increase e 0/5 (0%) with >40% reduction P=0.8 % Change from Baseline: Mean +~ 90%Cl BIV201 vs SOC P value = 0.05 for differen