Biovie Inc. · NASDAQ:BIVI
Biovie — Investor Day (May 2021)
67 slides from Biovie's investor day presentation, May 17, 2021
Slide 1: R&D Day May 19, 2021
biovie Developing Transformative Therapies to Overcome Chronic Debilitating Di R&D Day May 19, 2021
Slide 2: Forward-looking statements
Forward-looking statements biovie ‘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 diffe
Slide 3: Agenda
Agenda Welcome & Overview + Liver Cirrhosis Programs + Inflammation & NE3107 + Alzheimer’s Disease Program + Parkinson's Disease Program * Oncology Programs
Slide 4: Core themes for today
Core themes for today Advanced Liver Disease Program + No FDA-approved product for Ascites. BIV201 is a safe and efficacious orphan drug with high PTRS* and near-term readout Neurodegeneration Programs + Inflammation > insulin resistance > disease pathology + NE3107 selective inhibits ERK activation
Slide 5: Slide 5
Slide 6: Liver Cirrhosis Progression and Onset of Complications
Liver Cirrhosis Progression! and Onset of Cove Ascites Typical patient experience: + Liver cirrhosis worsens over decades + Ascites (detected by ultrasound) is the most common first major complication? ~ Initial treatment is off-label diuretics + Signals iver decompensation and patients at risk of:
Slide 7: Ascites & HRS Epidemiology Estimates
Ascites & HRS Epidemiology Estimates ‘Company Estimates (000s)
Slide 8: Disease Target: Refractory Ascites
Disease Target: Refractory Ascites Refractory ascites patients typically undergo paracente: to remove ascites fluid every week to 10 days Paracentesis: + Withdrawal of 5-101 of ascites fluid (on average) from abdomen using a large bore needle + Provides a few days of symptomatic relief + The kidneys
Slide 9: BIV201: Continuous Infusion Terlipressin
BIV201: Continuous Infusion Terlipressin biovie + Terlipressin was first approved in Germany in 1980s, to treat bleeding esophageal varices (BEV) + Approved for BEV and hepatorenal syndrome (HRS) in European & Asian hospitals (40+ countries) + Administered via 1-2 mg bolus injections every 4-6 hours
Slide 10: Novel Prefilled Syringe with Patent-pending Liquid Formulation
Novel Prefilled Syringe with Patent-pending Liquid Formulation + Global PCT filed to protect our novel liquid formu: + Improved safety: Eliminates mixing minute quantities of powder terlipressin that could result in medication errors or sterility loss + Enhanced convenience: Simply inject fluid into
Slide 11: BioVie Phase 2a trial results: BIV201 Pharmacokinetics
BioVie Phase 2a trial results: BIV201 Pharmacokinetics Comparison of the PK Profile of Terlipressin Administered by Continuous infusion or Intermittent IV Boluses. Continuous low blood levels of terlipressin versus potentially dangerous spikes with IV- bolus dosing Source: Bie poster presentation at
Slide 12: Continuous Infusion Terlipressin in Refractory Ascites/HRS Patients
Continuous Infusion Terlipressin in 6 Refractory Ascites/HRS Patients (Data licensed from Dr. P. Angeli) Decreased ascites fluid Improved renal function Mean amount in liters Mean serum creatinine value aad 250 in umoV/lter 30 200 ra 150 Ex 3 55% cad 47% 10 50 ° ° Baseline Treatment Month Baseline T
Slide 13: Continuous Infusion Terlipressin in Refractory Ascites/HRS Patients (Chapman et al.)
Continuous Infusion Terlipressin in 19 Refractory Ascites/HRS Patients biovie (Chapman et al.) Pre-therapy: Decreased Need for Paracentesis. + 70% of patients required weekly large volume ‘Change in frequency of paracentesis procedures, paracentesis (VP) + 63% poor muscle strength 29) Results: + Med
Slide 14: BIV201 Ascites Development Plan
BIV201 Ascites Development Plan biovie + USPhase2 trial with 30 refractory ascites patients 20toreceive BIV201 therapy + standard of care (SOC); 10 to receive SOC only (control group) + Primary composite endpoint: Incidence of asctes-related complications over 180 days following randomization + Seco
Slide 15: BIV201 HRS-AKI Development Plan
BIV201 HRS-AKI Development Plan (Hepatorenal Syndrome - Acute Kidney Injury) + Planning a registrational Phase 3 trial for BIV201 in HRS-AKI + Mallinckrodt recently completed the CONFIRM Phase 3 trial of terlipressin in type-1 HRS: ~ Efficacy objective was achieved, but safety concerns precluded FDA
Slide 16: BIV201 Projected US Clinical Timeline
| BIV201 Projected US Clinical Timeline mA aN
Slide 17: Slide 17
Slide 18: Inflammation
Inflammation biovie * Inflammation is the result of the body’s natural protective processes Insults Responders Master Alarms —_—Pro-inflammatory Pathogens + Blood proteins + NxBtansenption factors sTrauma = Platelets factors soytokines. ‘Ischemia Granulocytes + Oxidative sess? Chemoxines. *Suress +
Slide 19: Neuroinflammation drives disease pathology
Neuroinflammation drives disease pathology — -t +e = inflammation a Se yokines ‘nd CNS i (TN ALA) intteation i
Slide 20: Extracellular Signal-Related Kinase (ERK)
Extracellular Signal-Related Kinase (ERK) Homeostatic Inflammatory Pathways Pathways via Ras/Raf/Mek via NFkB Critical player for both homeostasis and inflammation (and resulting inflammation-induced insulin resistance) 20
Slide 21: NE3107: A Differentiated Molecule
NE3107: A Differentiated Molecule + First-in-class molecule with desirable characteristics + Small molecule * Crosses blood-brain barrier * Excellent safety profile demonstrated in pre-clinical and clinical trials + Blocks neuroinflammation and insulin-resistance at the right time/place in pathologi
Slide 22: NE3107 binds ERK
| NE3107 binds ERK Stable isotope Inbeling in culture (SILAC) ‘Macrophage cells labeled with light or heavy isotope amino acids and lysed ouure ad - caltysis sre E5107 tan Wo beads Mice rt Meanie ; i SILAC a le Analysis of specifieally SIMS Anais dt = —— aepege — Ee SE = an Binding to ERK was confir
Slide 23: NE3107 Selectively Inhibits ERK Pathological Inflammatory Cascade (EPIC)
NE3107 Selectively Inhibits ERK Pathological biovi Inflammatory Cascade (EPIC) = NE3107 reduces ERK activation... 3 PERK ous 3. yng HES206 moons aie a Hl. " i 2, H = e 80m nti 8 & Breaking the cascade reduces inflammation and restores insulin Wag 2010 Poet Te 38970 sensitivity mediators 23
Slide 24: NE3107 inhibits systemic inflammation across different disease models
NE3107 inhibits systemic inflammation Bnew across different disease models Decreased FN 19.1123, 1-4, TNFa NFeBinanendotoxinshockmodel... and flammatory cellinitatesand Sed ele Sa RA bal imyloperonidase nCOPD models
Slide 25: NE3107 blocks inflammatory, but not homeostatic ERK signaling
NE3107 blocks inflammatory, but not homeostatic ERK signaling o + Insulin Receptor Substrate (IRS) IRS1/2 can be activated by insulin via tyrosine phosphorylation, requires homeostatic ERK eo + IRS1/2 also phosphorylated by proinflammatory serine AA kinases p38 and JNK, requires inflammatory ERK x +
Slide 26: By blocking ERK activation, NE3107 prevents downstream impact
| By blocking ERK activation, NE3107 prevents downstream impact Inflammatory stimuli initiates... [ERK and NFxB activation perpetuates leading toinflammation _..resultingin aE pro-inflammatory cascade. and insulin resistance, disease pathology ‘Alpha NE3107, aaa Inhibits “lds es ae resistance 1) Chr
Slide 27: Slide 27
Slide 28: Forgetting the "Past" So that We Can Remember the "Now"
Forgetting the “Past” So that We Can Remember the “Now” - KoL Panel Excerpts from B. Riley Neuroscience Conference, 2024 “| saw that there was a drug by NeurMedix called NE3107 which was just authorized for a pivotable Alzheimer’s Phase 3 trial. What intrigued me about it is because it affects all t
Slide 29: 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 ont reaper eens ib pases EE chemin tenant ett Mena ‘Sits chee cpnierogn Chess | ‘rome emepo
Slide 30: NE3107 decreased systems dysregulation in advanced T2D patients
NE3107 decreased systems dysregulation in advanced T2D patients + Heteroscedasticity* investigated by analyzing =“ _ data distributions for normality (Shapiro- co Wilks W test) * Deviations from normal distribution represents war # dysregulation seria * Placebo patients had significantly abnormal da
Slide 31: Systemic inflammation and co-morbidity as drivers of cognitive decline
Systemic inflammation and co-morbidity breve as drivers of cognitive decline —_ aa INFLAMMATORY CO-MORBIOTY prolong & | PRIOR STATE 4sease progression INCREASED DEMENTIA RISK a
Slide 32: NE3107's neuroprotective properties
NE3107’s neuroprotective properties biovie Decreased neurotrophin receptor (7 S)and DecressedactvatedmicroglaSmvoid precursor protan APD) jbicietanalnnas (tot opereedan 0087" p0027 Decreased Inflammatory NFxB in inflamed optic nerve head; increased homeostatic NFxB in retina EE on Decreased inflamma
Slide 33: NE3107 preserves ganglion cell function in Optic Neuritis
NE3107 preserves ganglion cell function bene in Optic Neuritis Decreases opticnervehead inflammation. ~-and reduced activated microglia in optienerves ag $ 250. 20 Ne14 3 se g $ 200. Net4 § 1 e 3 ¢ Ne14 B50. e S10 S N=14 z 5 100 = 05: i =] Neto $B 5) N=10 — oo 0.0. 3 0 CONTROL = EAE-—EAE+HE3286 CONT
Slide 34: NE3107 enhances insulin sensitization in animal models
NE3107 enhances insulin sensitization in brew animal models HE3286 suppresses development of hyperglycemia in diabetic db/db mice... ‘Weare and the levels of insulin and glucose in oral tolerance tests genetielyobeseZDF rats eHes206 4
Slide 35: NE3107's ability to enhance insulin sensitization confirmed in Phase 2 trial with impaired glucose tolerance
NE3107’s ability to enhanc: ‘ization confirmed in Phase 1 trial with impaired glucose tolerance patients Improved insulin-dependent glucose disposal in 48 obese, inflamed subjects HE3286 Placebo Baseline M 5 F2=0,004, P<0.9) Day 29 M Value Change 67 8 9 0 3 4234 5 Baseline M 4 Day 29 Glucose disposa
Slide 36: NE3107's ability to enhance insulin sensitization confirmed in Phase 2 trial with T2D patients
NE3107’s ability to enhance insulin sensitization confirmed in Phase 2 trial with T2D patients Improved the homeostatic model s-decreased postprandial glucose... .. decreased HbA1c assessment of insulin resistance... rR sagas seni Poser anders stor 84 a 112. tale BM» han? 26
Slide 37: Insulin sensitizing improvement also brought improvements in AD indicators
Insulin sensitizing improvement also brought improvements in AD indicators Ina Phase 2 study 48 obese subjects with impaired glucose tolerance, NE3107 ... Inreasedinsulinsenstty.. winreasedHDL decreased CRP sand increased adiponectin i 1 Adiponectin Hi Placebo (Day 28 Change) } BB res286 2 i t z 2 H
Slide 38: Proceeding to Pivotal Phase for Alzheimer's Disease
Proceeding Pivotal Phase 3 for . . biovie Alzheimer’s Disease —— * NE3107 Reduces inflammation and enhances insulin sensitivity, both of which have been shown to reduce AD pathology. NE3107 blocks EPIC, which is upstream from Amyloid beta and phospho-tau, and thus further reduces inflammation + Has
Slide 39: NM101: a Phase 3 trial in mild to moderate Alzheimer's disease
NM101: a phase 3 trial in mild to moderate blovie Alzheimer’s disease, NCT04669028 ——_—. A Phase Double-blind, Randomize, Placebo-conrole, Parallel Group, Multicenter Study of NE107in Patents who have Mito * Plvta study or Alieimers dea. Two west echo Smg and 10g BID dose tiation followed by 26 week
Slide 40: Slide 40
Slide 41: Remarkable similarities between neurodegenerative diseases
Remarkable similarities between movie neurodegenerative diseases + Neuroinflammation and oxidative stress are common features in the major neurodegenerative diseases, Alzheimer’s, Parkinson’s, frontotemporal lobar dementia and ALS (and TBI) + Remarkable parallels exist between AD and PD + Activated
Slide 42: A low dopamine environment alone does not drive parkinsonism
ee A low dopamine environment alone does brow not drive parkinsonism... PO micehad dramaticloss of dopaminergic »-but id not show motor behavior deficits neurons. comparedwith control mice 7 TH-positive Neurons umcavimens © a tovng to9p---------Contol 100% =--=---= r i H owes 1 F lo xe Em acne Fon P
Slide 43: Low Dopamine and inflammation required for parkinsonism in patients
... Low Dopamine and inflammation required for parkinsonism in patients Intranasal Insulin treatment reduced inflammation and improved motor activity regu tH gy = eee <a nk ra
Slide 44: NE3107 impact in mice models of Parkinson's
| NE3107 impact in mice models of Parkinson's... ReducediNOS, TNFa and 3p and preserved dopaminesienewrons ow En
Slide 45: Striatal inflammation drives LID
Striatal inflammation drives LID L-Dopa drives striatal inflammation... _..resultingin L-Dopa induced dyskinesia (LID) 5 tWealolme) > sateen) wa ume
Slide 46: Reduction of TNF-induced inflammation reduces LID
Reduction of TNF-induced inflammation reduces LID A oor 8 oom evi op vcore so) $2008 a» Sesson Pea) 80% ® we, . | : ey os 2 " 2 3m * = 5 30) 2 3 20) E | 2098 ba! < 0.0001 o cr o! sol__° _p 0.0001 ol wm om re ee we eatated =
Slide 47: 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 3 ‘sao i] £3 ices _— better than either drug alone Mean Disease Score Siiee | MPTP rrp. MPI prs MPTP ‘Week ® Week 9 Week 10 Week 11 Mine MESO? Eide Lope > NE3107's promotoric e
Slide 48: NE3107 decreases L-Dopa-induced dyskinesia (LID)
NE3107 decreases L-Dopa-induced dyskinesia (LID) Distribution of AIMS Scores 307 NE3107 Score Frequency ° 123 45 67 8 9 10111213 14 15 16 17 18 19 20 ese <————— yskinesia —__—_—+ tore Abnormal Involuntary Movement Scale (AIMS) 4
Slide 49: NE3107 preserved TH+ neurons in MPTP marmosets
NE3107 preserved TH+ neurons in MPTP marmosets Control moneys (M09100 and M1200) E3286 M11007) ‘Amantadine (410084)
Slide 50: Proceeding to clinical development for Parkinson's disease
Proceeding to clinical development for bowne Parkinson’s disease + NE3107 reduces inflammation and enhances insulin sensitivity, both of which has been shown to reduce PD pathology + Reduction of inflammation itself may be beneficial since bot! dopamine environment are required for Parkinsonism + NE
Slide 51: Parkinson's disease clinical development program
eas . Parkinson’s disease clinical wave development program + NM201 Phase 4b: Satisfy FDA requirement for drug-drug interaction study with L- Dopa and assess NE3107 promotoric and anti-LID activity as a go/no-go decision for Phase 2 * Part A: 30 patients with defined L-Dopa “off state’, 2:1 active:p
Slide 52: Slide 52
Slide 53: Inflammation drives cancer progression
| Inflammation drives cancer progression biovie Inflammatory cell signaling is at the were heart of cancer progression + Tumor cells + Hematopoietic + Immune + Vascular + Stromal cells 50
Slide 54: Macrophage and MDSC inflammation in cancer
Macrophage and MDSC inflammation in cancer
Slide 55: Myeloma and Prostate Cancer (PCa)
Myeloma and Prostate Cancer (PCa) + Stem cell diseases + Myeloma initiated in CD34+ hematopoietic stem cells and have a clonal Ig rearrangement. Initial indolent course with MGUS. Plasma cells are the result of myeloma stem cell maturation. + Prostate cancer initiated in prostatic epithelial stem ce
Slide 56: NE3107 in Myeloma
NE3107 in Myeloma + NE3107 inhibits activation of NF«kB/ERK, TNFa. and MCP-1. + NE3107 inhibits IFNa-stimulated IL6 in human myeloma cells. + NE3107 has potential to inhibit proliferation and induce apoptosis in MM by two mechanisms: + Inhibiting cytokine and chemokine production in myeloma-associat
Slide 57: Current preclinical study in myeloma
Current preclinical study in myeloma * Studying effects of NE3107 on human myeloma cells in culture + Growth + Apoptosis * Combination with proteasome inhibitor * Studying effects of NE3107 on transplanted syngeneic MM cells in mice + Tumor growth + Effects on MM microenvironment + Effects on macrop
Slide 58: Prostate Cancer
Prostate Cancer * The progression of PCa is also critically dependent on accessory cells in their microenvironment + NF«B/ERK activation promotes initial tumors in the prostatic epithelium, drives their progression, and is critical in their transition to castrate- resistant prostate cancer (CRCP) +
Slide 59: Androgen deprivation therapy (ADT)
Androgen deprivation therapy (ADT) + PCais treated by starving the tumor of androgens, leading to temporary cessation of growth + We now know that the action of ADT stimulates inflammation in the tumor microenvironment. ADT activates macrophages and MDSC + PCa release “alarmins’” that activate infla
Slide 60: NE3107 in PCa: several ways to win
NE3107 in PCa: several ways to win biovie Early (rising PSA) + NE3107 has been shown to decrease prostate inflammation in mice, and may block the progression of PCa *+ Delaying the initiation of ADT prolongs life in PCa Localized disease + Decreasing the inflammatory milieu in the PCa microenvironme
Slide 61: Preclinical studies in PCa
Preclinical studies in PCa + Developing protocols and reviewing investigators for preclinical studies + Early + Effects of NE3107 on spontaneous tumor progression in TRAMP mice Localized disease + Effects of NE3107 on syngeneic transplanted androgen-dependent PCa cells CRCP + Effects of NE3107 in vi
Slide 62: Slide 62
Slide 63: Catalysts & Anticipated Timelines (US)
| Catalysts & Anticipated Timelines (US)
Slide 64: Portfolio Revenue Potential
Portfolio Revenue Potential BIV201: Refractory Ascites BIV201: HRS-AKI NE3107: Alzheimer’s NE3107: Parkinson's NE3107: Oncology ‘Orphan Drug Patent- ‘Bending formation ‘orphan Drug Patent- ‘ending formation Compound patent ‘thru 2034+ ‘Compound patent thru 2034+ ‘Compound patent thru 2034+ biovie Co
Slide 65: Multiple shots on goal focused on unmet medical needs
| m Multiple shots on goal focused on unmet medical needs: neurodegenerative, advanced liver disease, oncology BIV201: Orphan drug in Phase 2b for refractory Ascites; HRS-AK| trials planned. Ascites readout anticipated in early 2022 without toxicity and immunosuppression. Alzheimer’s Phase 3 startin
Slide 66: Slide 66
Slide 67: NE3107 vs. Others
NE3107 vs. Others Senate ACh 28) ronotscenace ‘Boerne ads nant ial eran ‘Aan atid stmt mop apostate amr i ‘hesabatcodshoe xem onneetanson Papen ANS ech rene APP lt oes ono ene ‘Sanat linens nde eae open eho posatonctapasyar li wih has cera nFaion's Dec nstopcny ‘Sydnee Rt ATH 1047 eae aman ae pay Ar