Biovie Inc. · NASDAQ:BIVI

Biovie — 2023 Society of Biological Psychiatry Annual Meeting

23 slides from Biovie's conference presentation, Apr 27, 2023

1. Slide 1: Effects of NE3107 on Depression and Multi-modal Outcomes in a Phase 2, Open-label Study

   Effects of NE3107 on Depression and Multi-modal Outcomes in a Phase 2, Open-label Study in Patients With Cognitive Decline Due to Degenerative Dementias Joseph Palumbo1, Kelly Johnston2, Jonathan Haroon3, Elizabeth Merikle2, Kaya Jordan3, Elisabeth Rindner3, Kennedy Mahdavi3,4, Victoria Venkatraman3

2. Slide 2: Background

   Background • Chronic neuroinflammation is thought to have pathogenic roles in neurodegenerative disorders,1 such as Alzheimer’s disease (AD) and Parkinson’s disease (PD); insulin resistance and diabetes2,3; and mood disorders, such as depression3 – TNF-α, a master regulator of pro-inflammatory respo

3. Slide 3: Background (cont.)

   Background (cont.) • In an exploratory, open-label, phase 2 study with 23 patients with mild to moderate dementia, NE3107 was associated with the following improvements: – Increased perfusion and functional connectivity in several regions of the brain (primary endpoint) – Reduced inflammation (lower

4. Slide 4: Objectives

   Objectives • This exploratory, phase 2, open-label, 3-month study explored the potential effects of anti-inflammatory NE3107 treatment on neurophysiological health, neurocognitive function, biomarker status, oxidative stress, depression symptoms, and functional improvement (GRC), as well as the over

5. Slide 5: Methods

   Methods Study Design • This was a single-arm, open-label, phase 2 trial evaluating the efficacy and safety of 20-mg oral NE3107 administered twice daily (approximately 12 hours apart) to patients with clinical dementia over a duration of 3 months (Figure 1) Study Population Key inclusion criteria •

6. Slide 6: Figure 1. Study design

   Figure 1. Study design Post-treatment assessments Inclusion criteria Active Treatment • 50-89 years old • Neuroimaging • Cognitive decline due to • Cognitive performance dementia NE3107 BID • Biomarkers • QDRS score: 1.5-12.5 20 mg 12 hours apart • GRC • CDR score: 0.5 (MCI) or • Depression severity

7. Slide 7: Methods (cont.)

   Methods (cont.) Assessments Primary – change from baseline to treatment completion • Multi-modal brain MRIs performed at baseline and treatment completion assessed structural and functional cerebral alterations associated with AD Secondary – changes from baseline to treatment completion • Serologica

8. Slide 8: Results

   Results • 23 patients were enrolled in the study and received 20-mg oral NE3107 twice daily for 3 months • Table 1 shows the demographic and baseline characteristics of the study patients 7

9. Slide 9: Table 1. Baseline characteristics

   Table 1. Baseline characteristics Characteristic All patients (N=23) Age, mean (SD) 71.1 (9.50) Gender, n (%) Female 16 (70) Male 7 (30) Family history, n (%) AD 5 (22) AD, dementia, unspecified etiology 2 (9) AD, PD 1 (4) Dementia, unspecified etiology 4 (17) PD 1 (4) QDRS score, mean 5.07 CDR scor

10. Slide 10: Results (cont.)

    Results (cont.) Neuroimaging analyses • NE3107 was associated with clinician-rated improvements from baseline in functional connectivity within the NBM, the precuneus, and the hippocampus • MRS analysis showed that 59% (n=13) of all 22 patients analyzed and 67% (n=12) of patients with MCI or mild de

11. Slide 11: Results (cont.)

    Results (cont.) Multi-modal correlation analyses • For the total patient population, we observed statistically significant correlations in changes from baseline between the following parameters: ‒ ADCOMS and Aβ42 (r=0.53) ‒ ADCOMS and P-tau levels (r=0.49) ‒ ADAS-Cog11 scores and brain glutathione l

12. Slide 12: Results (cont.)

    Results (cont.) Changes in depression symptoms • Out of a total of 22 patients who were evaluated using the PHQ-9, 15 (68%) patients had a baseline score of ≥5, indicating mild, moderate, or severe depression11 (Table 1) • 64% (n=14) of all 22 patients analyzed had a lower PHQ-9 score after NE3107 t

13. Slide 13: Figure 2. Change from baseline in PHQ-9 scores

    Figure 2. Change from baseline in PHQ-9 scores A B Change from baseline: −2.91 (95% CI: −5.318, −0.500) Change from baseline: mean ± 95% CI P=0.0203 Mean ± 95% CI BETTER BETTER BETTER CI, confidence interval. 12

14. Slide 14: Figure 3. Change from baseline in individual domains of the PHQ-9

    Figure 3. Change from baseline in individual domains of the PHQ-9 A All patients (n=22) B Patients with baseline PHQ-9 score ≥5 (n=15) 13

15. Slide 15: Results (cont.)

    Results (cont.) Outcomes of exit interviews • 48% (n=11 of 23) of patients completed an exit interview; their baseline demographics and clinical characteristics are shown in Table 2 – Average age and family history of AD or dementia were similar to the overall study population – Slightly more female

16. Slide 16: Results (cont.)

    Results (cont.) • Study partners (n=7) reported an average of 4 (SD=1.53; range 2-6) problems related to the patient’s degenerative dementia prior to NE3107 treatment ‒ These included mood problems (n=7; 100%), cognitive difficulties (n=7; 100%), ability of the patient to think clearly (n=6; 86%), a

17. Slide 17: Table 2. Baseline characteristics of patients who completed the exit interviews

    Table 2. Baseline characteristics of patients who completed the exit interviews Characteristic All patients (n=11) Characteristic All patients (n=11) Demographic Clinical, n (%) Age, y, mean (SD) 70.4 (6.32) Traumatic brain injury 1 (9) Gender, n (%) Concussion 2 (18) Female 9 (82) Male 2 (18) Strok

18. Slide 18: Table 3. Changes after NE3107 treatment

    Table 3. Changes after NE3107 treatment Patient-Elicited Study Partner–Elicited Meaningful Difference, Meaningful Difference, Improvement, n (%) Improvement, n (%) n (%) n (%) n=11 n=7 Concept n=9 n=6 Memory 8 (73) 7 (78) 5 (71) 3 (50) Clarity 6 (55) 5 (56) 4 (57) 3 (50) Engagement 6 (55) 5 (56) 4 (

19. Slide 19: Results (cont.)

    Results (cont.) • All patients (n=11; 100%) who completed the exit interviews noted that the study medication was easy to take ‒ Most of the patients (n=10; 91%) had no issues taking the study medication at the frequency directed (BID) and noted that it was easy to remember to take the medication at

20. Slide 20: Conclusions

    Conclusions • In this phase 2, single-arm, open-label study, we investigated the anti-inflammatory effects of oral NE3107 treatment on the neurophysiology and neuropsychology of 23 patients with mild to moderate dementia over 3 months. We qualitatively characterized the pre-trial disease burden and

21. Slide 21: Conclusions (cont.)

    Conclusions (cont.) • Given its oral, twice-daily regimen, most patients agreed that NE3107 was easy to take and adhere to • Thus, we demonstrated changes indicative of an overall reduction in depression symptoms after treatment with NE3107 and successfully characterized treatment benefits that are

22. Slide 22: References

    References 1. Jung YJ, Tweedie D, Scerba MT, Greig NH. Neuroinflammation as a factor of neurodegenerative disease: thalidomide analogs as treatments. Front Cell Dev Biol. 2019;7:313. doi: 10.3389/fcell.2019.00313 2. Draznin B. Molecular mechanisms of insulin resistance: serine phosphorylation of ins

23. Slide 23: Acknowledgments and Disclosures

    Acknowledgments and Disclosures Acknowledgments p-value communications provided editorial support. Funded by BioVie Inc. Disclosures JP, NO, CA, and CR are employees of BioVie Inc. JJ and EM are employees of Labcorp Drug Development. JH, EM, KJ, ER, KM, VV, SB, JRS, and SJ have received grant suppor

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