Biophytis Sa · EURONEXT:ALBPS
Biophytis Sa — Investor Presentation (December 2024)
48 slides from Biophytis Sa's investor presentation, Dec 6, 2024
Slide 1: Biophytis
bfophytis
Slide 2: Investor Call, Washington D.C., December 6th, 2024
Investor Call Washington D.C. December 6th, 2024
Slide 3: Agenda
Agenda GLP-1 RA Weight loss therapy-induced muscle loss: A Medical need to explore ? Moderated by Rob Van Maanen CMO Biophytis Make a life-changing impact for people suffering from obesity Stanislas Veillet - CEO Biophytis The underappreciated role of skeletal muscle in health and disease: implicati
Slide 4: Make a life-changing impact for people suffering from obesity
Make a life-changing impact for people suffering from obesity Stanislas Veillet CEO Biophytis
Slide 5: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements. Forward-looking statements include all statements that are not historical facts. In some cases, you can identify these forward-looking statements by the use of words such as «outlook », «believes», «expects», «potentia
Slide 6: A clinical-stage biotechnology company for muscular and metabolic diseases
A clinical-stage biotechnology company specialized in the development of therapeutics for muscular and metabolic diseases HQ location: Paris, France Multiple partnerships Other locations in Sao Paulo, BR and Cambridge, MA US Academical Founded: partnerships 2006 Industrial Euronext growth Paris (ALB
Slide 7: Our Clinical Pipeline
Our Clinical Pipeline 20 3 Stargardt xxx orphan diseases
Slide 8: BIO101 (20-hydroxyecdysone): First-in-class drug candidate
BIO101 (20-hydroxyecdysone): First-in-class drug candidate OH HO New molecular target H OH 1 Activation of MAS receptor (renin-angiotensin system) Regulation of smooth, cardiac and skeletal muscle HO metabolism H OH Stimulation of muscular and respiratory functions HO H O POC & safety in clinical st
Slide 9: Muscle wasting associated with pharmacology treatment of obesity: a medical need
Muscle wasting associated with pharmacology treatment of obesity: A medical need to explore Obesity burden 1 Adults and 2 The global 3 The global cost of prevalence of treating obesity- 1bn children are currently living with obesity globally. 3x obesity has more than tripled since 1975. 4tn$ related
Slide 10: BIO101 is the only muscle agent in development focusing on muscle strength
BIO101 is the only muscle agent in development focusing on muscle strength Main Administration Drug Company Mode of action Safety & Side effects Status Endpoints route Muscle strength BIO101 has been very well MAS Receptor (knee extension tolerated in 277 individuals BIO101 activator across multiple
Slide 11: Key BIO101 development Milestones in Obesity (2024)
Key BIO101 development Milestones in Obesity (2024) Strategic Regulatory Clinical Operations Partnership Milestone Phase 2 OBA Trial Licence deal with IND approval Readiness Blanver Pharma from FDA Investor Call March 2024 Launch of BIO101 BIO101 in Obesity : ✓ New Obesity Ad Board Development ✓ Stu
Slide 12: The underappreciated role of skeletal muscle in health and disease
The underappreciated role of skeletal muscle in health and disease: implications for weight loss therapies. Pr Roger Fielding PhD Senior Scientist Metabolism and Basic Biology of Aging Directive Tufts University
Slide 13: Disclosures
Disclosures Consultancies: Merck, Eli Lilly, Axcella Health, Embion Biophytis, Amazentis, Pfizer, Nestlé’ Inc., Rejuvenate Biomed, Epirium Bio. Advisory board memberships: Cytokinetics, Segterra, Aging in Motion, Ammonett, Biophytis. Grant support: NIH (NIA, NHLBI, NIDDK), USDA.
Slide 14: Skeletal Muscle: an underappreciated tissue in health and disease
Skeletal Muscle: an underappreciated tissue in health and disease Makes up 45-50% of body mass Fundamental role in locomotion, O2 consumption, whole-body energy metabolism, and substrate turnover and storage Secretory organ (“myokines”) Energy utilization can increase 10-fold Contractile performance
Slide 15: Mobility across species (highly conserved motor proteins)
Mobility across species (highly conserved motor proteins) Dickinson et al. Science 2000;288:5463
Slide 16: Aging and physical performance
Aging and physical performance Drosophila Rats Miller et al. Biophys J 2008;95:2391 Carter et al. J Gerontol 2002; 57:B193
Slide 17: Age-related loss in muscle size and strength
Age-related loss in muscle size and strength From Lauretani et al. 2003
Slide 18: Sarcopenia: Age-associated loss in muscle mass and function
Sarcopenia: Age-associated loss in muscle mass and function Male Male 43 years 76 years BMI = 25 BMI = 25 Components: “A syndrome characterised by progressive, generalized • Muscle mass loss of skeletal muscle mass and strength with the risk of • Muscle strength adverse outcomes such as physical dis
Slide 19: Muscle Mass is a Component of Total Body Lean Mass
Muscle Mass is a Component of Total Body Lean Mass Dual Energy X ray Absorptiometry (DXA) Based on attenuation of bone mineral free lean tissue (not muscle mass) Precision 1-4% Radiation (1 mrem; 3 days background) Machines are widely available Analytical differences across manufacturers and models
Slide 20: Imaging Techniques to Assess Muscle Size
Imaging Techniques to Assess Muscle Size Computed Tomography (C-T) Magnetic Resonance Imaging (MRI) Measures direct physical property of muscle Similar principles of measurement (e.g.: CSA) Precision 1-3% Precision 1-3% Agreement with C-T (r=0.97-0.99; SEE 5-10%) Density of muscle area (association
Slide 21: Changes in lean mass with diet-induced weight loss in older adults
Changes in lean mass with diet-induced weight loss in older adults Age Duration Weight Loss (Kg) Lean Mass Loss (Kg) Villareal, 2006 166: 860-6, > 65 yrs 6 months -8.2 + 5.7 -1.2 + 2.1 Arch Int Med Frimel, 2008 40: 1213-29, Med Sci > 70 yrs 6 months -10.7 + 4.5 -3.5 + 2.1 Sports Exerc Lambert, 2008
Slide 22: Changes in muscle cross sectional area with diet-induced weight loss
Changes in muscle cross sectional area with diet-induced weight loss in older adults Effect of Exercise Modality during Weight Loss on Changes in Muscle and Bone Quality in Older Adults with Obesity Madrid et al. Exp Gerontol 2023 Muscle Cross Baseline (n=55) Weight Loss Weight Loss + AT (n=13) Weig
Slide 23: Changes in muscle cross sectional area with diet-induced weight loss
Changes in muscle cross sectional area with diet-induced weight loss in older adults Effect of Exercise Modality during Weight Loss on Changes in Muscle and Bone Quality in Older Adults with Obesity Weiss et al. J Appl Physiol 2007 CR (n=18) EX (n-16) Between group P value Lean Mass kg Baseline 49.1
Slide 24: Effect of diet-induced weight loss on muscle strength
Effect of diet-induced weight loss on muscle strength in adults with overweight or obesity – a systematic review and meta-analysis of clinical trials Dynamic knee extensor strength Isometric handgrip strength (isokinetic dynamometry) Obesity Reviews 2016
Slide 25: Muscle function and physical performance
Muscle function and physical performance Leg Power 0.35 Leg Strength 0.3 0.25 0.2 0.15 0.1 0.05 0 Stair Chair Tandem Gait Max Gait SPPB Physical Performance Multivariate models adjusted for Age, BMI, Gender, Chronic Conditions. (also adjusted for Falls Efficacy with HG) Bean et al. J Am Geriatr Soc
Slide 26: Summary
Summary Skeletal muscle plays a critical role in metabolic balance, insulin action, locomotion, and energy metabolism. Muscle function is ubiquitous across species and declines with advancing age. Assessments of body composition vary with regard to their ability to detect specific properties of skel
Slide 27: Effects of Incretin-Based Therapies on Lean and Skeletal Muscle Mass
Effects of Incretin-Based Therapies on Lean and Skeletal Muscle Mass: What’s the Clinical Evidence? Pr Marc-Andre Cornier Professor of Medicine James A. Keating Endowed Chair in Diabetes Director, Division of Endocrinology, Diabetes & Metabolic Diseases Medical University of South Carolina
Slide 28: Objectives
Objectives There is a big unmet need in the medical management of obesity Review the data on the effects of incretin-based therapies on weight loss and body composition changes Discuss the data on the effects of incretin-based therapies total on metabolic and functional outcomes Begin to discuss way
Slide 29: Incretin-Based Therapies - Mechanisms of Action
Incretin-Based Therapies - Mechanisms of Action Samms et al, Trends in Endocrinol Metab 2020.
Slide 30: Once-Weekly Semaglutide in Adults with Overweight or Obesity
Once-Weekly Semaglutide in Adults with Overweight or Obesity Wilding et al, N Engl J Med 2021.
Slide 31: Once-Weekly Semaglutide in Adults with Overweight or Obesity
Once-Weekly Semaglutide in Adults with Overweight or Obesity 39% of weight loss is lean body mass Wilding et al, NEJM, 2021.
Slide 32: Roles of Skeletal Muscle as a Structural and Metabolic Organ
Roles of Skeletal Muscle as a Structural and Metabolic Organ Prado et al, Lancet Diabetes Endocrinol, 2024.
Slide 33: Semaglutide Cardiometabolic Benefits
Once-Weekly Semaglutide in Adults with Overweight or Obesity Cardiometabolic Benefits: Glycemia ↓A1c ↓ Fasting Glucose ↓ Blood Pressure Lipids ↓ Triglycerides ↑HDL ↓ LDL ↓ VLDL ↓ Fatty Acids Inflammation ↓ C-reactive protein Wilding et al, NEJM 2021.
Slide 34: SELECT Trial: Semaglutide and Cardiovascular Outcomes in Obesity
SELECT Trial: Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes Lincoff et al. NEJM 2023.
Slide 35: Semaglutide in Overweight or Obesity – Physical Function
Once-Weekly Semaglutide in Adults with Overweight or Obesity – Physical Function Wilding et al, NEJM, 2021.
Slide 36: Tirzepatide Once Weekly for the Treatment of Obesity
Tirzepatide Once Weekly for the Treatment of Obesity Jastreboff et al, NEJM, 2022.
Slide 37: Tirzepatide Once Weekly for the Treatment of Obesity
Tirzepatide Once Weekly for the Treatment of Obesity Jastreboff et al, NEJM, 2022.
Slide 38: Tirzepatide Cardiometabolic and Functional Benefits
Tirzepatide Once Weekly for the Treatment of Obesity Cardiometabolic Benefits: Glycemia ↓A1c ↓ Fasting Glucose ↓ Diabetes prevention Fonctional Benefits: ↓ Insulin ↑ SF-36 physical function score ↓ Blood Pressure Lipids ↓ Triglycerides OSA Benefits ↑ HDL ↓ Non-HDL cholesterol ↓ LDL cholesterol Infla
Slide 39: Summary and Conclusions
Summary and Conclusions Incretin-based therapies are associated with significant loss of total and fat mass Incretin-based therapies are also associated with significant loss of lean mass It is unclear, however, how much of this lean mass loss is due to skeletal muscle loss and whether this is a gre
Slide 40: Muscle Mass and Weight Loss: Implications for Aging Populations
Muscle Mass and Weight Loss: Implications for Aging Populations Pr William Evans Department of Nutritional Sciences & Toxicology University of California, Berkeley
Slide 41: Body Composition: DXA + D3Cr (MrOS cohort)
Body Composition: DXA + D3Cr (MrOScohort: > 1,300 men >80y) Lean body mass and Muscle Mass Lean Body Mass Muscle Mass
Slide 42: Muscle mass is strongly associated with outcomes at all BMI levels
Conclusion: “When an accurate assessment of muscle mass (rather than lean mass) is used, reduced muscle mass is highly associated with important outcomes and the negative effects of adiposity are minimal, suggesting that obesity has little relevance for the understanding of important outcomes of sar
Slide 43: Muscle mass, physical performance and incidence of falls
Strong relation between muscle mass determined by D3-creatine dilution, physical performance and incidence of falls and mobility limitations Q1 – 4 lowest to highest quartiles of population
Slide 44: Effects of reduction of energy and protein intake on muscle protein synthesis
J Nutr. 2021 doi: 10.1093/jn/nxab181. Effects of reduction of energy and protein intake on the rate of muscle protein synthesis – myofibrillar (contractile), sarcoplasmic, and mitochondrial synthesis rates are profoundly reduced ER: energy-restricted-high protein fed AL: ad libitum-standard protein
Slide 45: Muscle protein synthesis and energy expenditure before and after weight loss
Contribution of rate of muscle protein synthesis to energy expenditure before and after weight loss (bariatric surgery) Wolfe, B et al, Resting metabolic rate, total daily energy expenditure, and metabolic adaptation 6 months and 24 months after bariatric surgery, Obesity, 26: 862, 2018 Decreased En
Slide 46: Regulatory Guidance for Addition of a Drug to Preserve Muscle Mass
Regulatory Guidance for Addition of a Drug to Preserve Muscle Mass Resulting From GLP-1 Induced Weight Loss Additional Weight Loss Compared to GLP-1 Agonist Monotherapy -No guidance (as yet) on the composition of the additional weight loss -Concern that by preserving muscle and increasing fat loss,
Slide 47: Muscle Mass/Body Weight % Muscle Mass
Muscle Mass/Body Weight % Muscle Mass “Preservation of muscle mass to combat sarcopenia may prove to be the most effective strategy to preserve independence and face advancing age with dignity. A simplified definition available to all health care providers will go a long way to meet this goal.” Loss
Slide 48: Investor Call Q&A Session
Investor Call Q&A Session Washington D.C. December 6th, 2024