Slide 1: SARA Program: Preliminary Findings & Implications from SARA-OBS Study and Its Impact on SARA-INT Study
SARA PROGRAM: PRELIMINARY FINDINGS & IMPLICATIONS FROM SARA-OBS STUDY AND ITS IMPACT ON SARA-INT STUDY W. DIOH, C. TOURETTE, C. MARGALEF, A. CHEN, R. LAFONT, P. DILDA, S. VEILLET, AND S. AGUS
Slide 2: BIO101: Mechanism of Action
BIO101: MECHANISM OF ACTION MAS receptor activation 2
Slide 3: Target Engagement Studies In-Vitro
TARGET ENGAGEMENT STUDIES IN-VITRO Myoblast differentiation Myogenin E. ⇒ Dose-dependent effect of BIO101 on myoblast differentiation, based on effects observed on fusion index, number of nuclei per myotube and myotube diameter, as well as Myogenin protein expression. 3
Slide 4: Target Engagement Studies In-Vitro
TARGET ENGAGEMENT STUDIES IN-VITRO AKT signaling pathway Myostatin gene expression Control BIO101, 10µM qPCR 0 30’ 1h 5h 24h 30’ 1h 5h 24h p-AKT p-P70S6K GAPDH => BIO101 stimulates AKT signaling pathway and inhibits myostatin gene expression Myoblast protein synthesis and mitochondrial respiration P
Slide 5: Target Engagement Studies In-Vivo
TARGET ENGAGEMENT STUDIES IN-VIVO Mouse soleus, 6 weeks Rat tibialis anterior, 12 oral treatment weeks oral treatment Muscle protein content Gene expression Gene expression myostatin murf-1 atrogin 10 10 BIO101 causes an increase in muscle Chronic BIO101 treatment causes a dose- protein content in t
Slide 6: Proof of Concept
PROOF OF CONCEPT Age-related muscle wasting and loss of function BIO101 Adult: 16-month-old C57Bl6J female mice Old: 26-month-old C57Bl6J female mice Daily oral treatment for 14-weeks (50 mg/kg*day) ⇒ Significant protection against muscle function loss during ageing 6
Slide 7: The SARA Clinical Program
THE SARA CLINICAL PROGRAM SARA = SARcopenia and sarcopenic obesity in patients Aged ≥ 65 years SARA-PK • Phase 1 study • Safety and pharmacokinetic profiles of BIO101 in older adults • Selection of doses for SARA-INT SARA-OBS • An observational study to characterize the target population and main pa
Slide 8: SARA Program: Identification of the Target Population
SARA PROGRAM: IDENTIFICATION OF THE TARGET POPULATION Aiming to identify individuals who are at a high risk for mobility disability • In standard care, individuals with a chronic disease are often diagnosed 6 months when a bad thing happens. This is the Tipping Point • The tipping point is an untowa
Slide 9: SARA-OBS: An Observational Clinical Trial
SARA-OBS: AN OBSERVATIONAL CLINICAL TRIAL Characterizing Sarcopenia and sarcopenic obesity in patients Aged 65 years and over, at risk of mobility disability Objectives: Main endpoints: • To characterize sarcopenia, including • Primary endpoint: gait speed of the 400MW test sarcopenic obesity, in ol
Slide 10: SARA-INT: A Phase 2 Interventional Study
SARA-INT: A PHASE 2 INTERVENTIONAL STUDY Following the same outline as that of the SARA-OBS study Main differences from SARA-OBS: •Participants must perform the 400MWT within 15 Initial number of participants: 334 minutes •Exclusion of individuals with an active biliary-tract Currently randomized: 2
Slide 11: What We Learned from SARA-OBS (Preliminary Analysis on Completers)
WHAT WE LEARNED FROM SARA-OBS ( PRELIMINARY ANALYSIS ON 106 COMPLETERS) Disease progression and its impact on the A ‘promising zone’ interim analysis sample size • Re-confirm the statistical power BL M6 Change P 400WT 0.90 0.84 -0.05 0.0036 • Re-adjust the sample size – if needed SPPB score 6.67 6.9
Slide 12: Correlations
CORRELATIONS 400MWT to 4MWT 6minwt to 4MWT 400MWT to 6minwt (from SPPB) (from SPPB) R=0.53 Without outliers R=0.29 R=0.27 A high correlation between the 400MWT and the 6MWT, but not between either to the 4MWT (from the SPPB) R=0.86 12
Slide 13: Thank You!
THANK YOU! For more details on SARA-OBS study, please come and visit our poster CLINICAL TRIALS P167 Design and Population Baseline Features of the SARA-OBS Study: Characterizing SARcopenia and Sarcopenic Obesity in Patients Aged65 years and over, at Risk of Mobility Disability Waly Dioh, Cendrine T