Biovie Inc. · NASDAQ:BIVI

Biovie — Longevity Biotech, Boston, MA (October 2025)

22 slides from Biovie's conference presentation, Oct 23, 2025

  1. Slide 1: Epigenetic modulation of age acceleration and Alzheimer's disease genes associated with bezisterim

    Epigenetic modulation of age acceleration and Alzheimer’s disease genes associated with bezisterim anti-inflammatory treatment Christopher Reading1*, Jiayan Yan1, Clarence Ahlem1, Penelope Markham1, Stephen O’Quinn1, Joseph M. Palumbo1, Varun B. Dwaraka2* 1BioVie Inc., Carson City, NV, USA , 2TruDia

  2. Slide 2: Bezisterim, aging and Alzheimer's

    Bezisterim, aging and Alzheimer’s Bezisterim • 17-ethynyl-androst-5-ene-3,7,17-triol • Anti-inflammatory insulin sensitizer • Binds ERK1/2, LRP1, RPS6KA3, and SIRT2 • Inhibits inflammatory NFκB activation, cytokine and chemokine transcription, with an attractive safety profile to date Age is the

  3. Slide 3: Study design and analysis of promoter methylation

    AD subjects 30-week Clinical Measures placebo-controlled clinical trial Whole blood DNA Bezisterim Placebo 895,323 CpG 895,323 CpG 31 clinical assessment Age  values  values acceleration values for both bezisterim and placebo Differential Average Promoter Methylation (DPM) PBO CpG between bezister

  4. Slide 4: Key findings of current work to be discussed

    Key findings of current work to be discussed Integrated analysis of molecular mechanisms • Bezisterim reduced EAA in an additional 13 clocks • Bezisterim altered average promoter CpG methylation of 448 genes compared to placebo o Increases in CpG promoter methylation of key AD-associated genes are l

  5. Slide 5: Bezisterim reduced epigenetic age acceleration (1 of 2)

    Bezisterim reduced epigenetic age acceleration (1 of 2) • Decelerated aging in 13 aging clocks after 30 weeks of bezisterim • Negative residuals of model-predicted biological age and chronological age indicate decelerated aging, whereas positive differences indicate accelerated aging First 5 of 13 C

  6. Slide 6: Bezisterim reduced epigenetic age acceleration (2 of 2)

    Bezisterim reduced epigenetic age acceleration (2 of 2) • Remaining 8 of 13 Clocks Stochastic EAA Clocks (PhenoAge, Zhang, and Horvath) Retroviral Integration EAA Clocks (Retroclock2 and Retroclock) Systems Age EAA Clocks (SystemsAge, Heart, and Lung) ©2025 BioVie Inc. 6

  7. Slide 7: Bezisterim altered average promoter CpG methylation

    Bezisterim altered average promoter CpG methylation IKBKG TGIF HDAC11 TRIM27 CUTA ZHX2 DGKZ FYN CDK16 JMJD6 GPD2 •HOXA4 CELF1 IRF5 •TYW3 DUSP22 ADK CSNK2B •B3GALT4 UBE2C •CRYZ PLSCR2 •CHPF NME3 SP140 LINC01816 PARD6G-AS1 SLC9B2 SSBP4 MAMSTR MIR4458HG FBXL16 SLC28A2-AS1 ISOC2 7 ©2025 BioVie Inc. FDR=

  8. Slide 8: Potentially Beneficial DPM Gene Examples

    Potentially Beneficial DPM Gene Examples ©2025 BioVie Inc. 8

  9. Slide 9: Bezisterim Potentially Beneficial DPM Epigenetic Age Acceleration Clock Genes

    Bezisterim Potentially Beneficial DPM Epigenetic Age Acceleration Clock Genes Shared with Aging, AD, and Metabolic Disease • 45 potentially beneficial DPM EAA clock genes were also associated with diseases of aging • 87% of these genes are associated with inflammation • 67% impact cognition • Red ci

  10. Slide 10: Potentially beneficial changes to 448 aging and disease risk gene promoters

    Potentially beneficial changes to 448 aging and disease risk gene promoters • Based on these data, we investigated additional DPM genes for reported associations with inflammatory, neurologic, and metabolic disease • In addition to the 45 clock genes we identified an additional 403 of the 2154 DPM g

  11. Slide 11: Are bezisterim changes associated with clinical benefit? (1 of 2)

    Are bezisterim changes associated with clinical benefit? (slide 1 of 2) The sum of promoter methylation for each potentially beneficial DPM gene was investigated for correlation to previously reported clinical measures: • Chronologic age • Neurologic assessments: ADCOMS, ADL, CDR-SB, CGIC, GST, NPI

  12. Slide 12: Are bezisterim changes associated with clinical benefit? (2 of 2)

    Are bezisterim changes associated with clinical benefit? (slide 2 of 2) For bezisterim subjects, there were 72 significant (FDR < 0.05) correlations of clinical measures with differential sums of promoter methylation beta values • 48 genes with increased DPM sum • One gene with decreased DPM sum For

  13. Slide 13: Bezisterim and placebo potentially beneficial clinical measure and gene correlations

    Bezisterim and placebo potentially beneficial clinical measure and gene correlations Potentially beneficial clinical measure Potentially beneficial gene correlations correlations Bezisterim Correlations Placebo Correlations Gene Sum Beneficial Sum Beneficial Bezisterim Correlations Placebo Correlati

  14. Slide 14: ADCS-ADL with JMJD6 was the most significant correlation with DPM genes

    Activities of Daily Living (ADCS-ADL) with JMJD6 was the most significant correlation with DPM genes • For bezisterim, JMJD6, an epigenetic regulator and driver of AD, was correlated with ADL (R = 0.83, P = 3.3e-5, FDR P 0.0010) o This was significantly different from placebo (z score P = 0.0007) Pl

  15. Slide 15: Additional examples of bezisterim potentially beneficial DMP gene correlations

    Additional examples of bezisterim potentially beneficial DMP gene correlations with clinical measures Correlations Different Sum Correlations Z score Sum Different Promoter P = 0.004 Sum Sum Promoter Z score P = 0.039 Promoter Promoter Correlations Different Sum Z score Sum P = 0.018 Promoter Sum Su

  16. Slide 16: Placebo promoter methylation correlations with clinical measures

    Placebo promoter methylation correlations with clinical measures • For placebo, there were 13 significant correlations with 11 genes o Systolic blood pressure was correlated with 6 genes (CSNK1D, CTSL, ETV1, MTHFR, SMARCD2 and TUBA4A) o GFAP RISK was correlated with 3 genes (GPD2, IRF1, and P2RX1);

  17. Slide 17: Examples of placebo potential risk DMP gene correlations (1 of 2)

    Examples of placebo potential risk DMP gene correlations with clinical measures (1 of 2) Correlations Different Z score P = 0.024 Correlations Different Z score P = 0.017 Sum Sum Sum Promoter Promoter Promoter Correlations Different Z score P = 0.024 Placebo GFAP Z' vs P2RX1 Bezisterim GFAP Z' vs P2

  18. Slide 18: Examples of placebo potential risk DMP gene correlations (2 of 2)

    Examples of placebo potential risk DMP gene correlations with clinical measures (2 of 2) Correlations Trend Different Z score P = 0.055 Correlations Trend Different Z score P = 0.055 Placebo ADCOMS Z' vs NINJ2 Bezisterim ADCOMS Z' vs NINJ2 1.0 1.0 0.8 0.8 Sum Sum 0.6 0.6 Promoter Promoter 0.4 0.4 0.

  19. Slide 19: Correlations with systolic blood pressure suggest detection of underlying disease pathology

    Correlations with systolic blood pressure suggest detection of underlying disease pathology • Previously reported imaging data from an open-label study of 23 subjects with mild cognitive impairment and mild AD1 • Bezisterim was associated with clinician-rated improvements in relative cerebral blood

  20. Slide 20: Potentially improved rCBF with bezisterim

    ©2025 BioVie Inc. 20 Potentially improved rCBF with bezisterim

  21. Slide 21: Summary and conclusions (1 of 2)

    Summary and conclusions (1 of 2) • Clinical benefit in bezisterim subjects was associated with epigenetic modulation of age and disease-related genes • Bezisterim modulated epigenetic effects in a group of 448 genes associated with inflammatory responses and diseases of aging • Promoter-wide methyla

  22. Slide 22: Summary and conclusions (2 of 2)

    Summary and conclusions (2 of 2) • Bezisterim decreased epigenetic age acceleration in a total of 18 biological aging clocks that have been shown to be associated with aging in general o In particular, bezisterim decreased EAA in 3 stochastic clocks, which are based on random methylation changes in

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