Veru Inc. · NASDAQ:VERU
Veru — 4th Edition of World Obesity and Weight Management Congress 2024
34 slides from Veru's conference presentation, Oct 24, 2024
Slide 1: Advancing enobosarm to avoid muscle loss and augment fat loss with GLP-1 RA
Veru Inc. Nasdaq:VERU Advancing enobosarm, an oral novel Selective Androgen Receptor Modulator (SARM), to avoid muscle loss and augment fat loss when combined with a Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) drugs for potentially higher quality weight loss Mitchell Steiner, MD Veru 4th Edi
Slide 2: Muscle loss significant side effect of GLP-1 receptor agonists weight loss drugs
Muscle loss significant side effect of GLP-1 receptor agonists weight loss drugs 2
Slide 3: GLP-1 RA drugs demonstrated significant loss of both fat and muscle
Currently approved GLP-1 receptor agonist drugs have demonstrated significant loss of both fat and muscle in overweight or obese patients • Weight loss drugs GLP-1 receptor agonists demonstrated a 6.2-17% average total weight loss1,2 • 20-50% of the total weight loss is from muscle loss1,3,4,5 1 pou
Slide 4: Currently GLP-1 RA drugs result in significant loss of both fat and muscle
Currently GLP-1 RA drugs result in significant loss of both fat and muscle The target population is the at risk obese or overweight patients with low muscle reserves Normal5 • Approximately 42% of older adults (>60 yo) have obesity or are overweight and could benefit from weight-loss drugs1 • Subpop
Slide 5: WEGOVY FDA label now shows fracture safety data from SELECT
WEGOVY FDA label now shows fracture safety data from SELECT Cardiovascular outcomes study 1 Wegovy PI page 4 5
Slide 6: GLP-1 receptor agonist drug seems to have stopped working?
GLP-1 receptor agonist drug seems to have stopped working? What do I do now and how do I stop? How do I keep the weight off after stopping? 6
Slide 7: Wegovy approval clinical studies: overweight and obese adult patients
Wegovy approval clinical studies1: overweight and obese adult patients Rate of weight loss reaches a plateau • Greatest amount of absolute total weight loss between weeks 0 and 20 • Patients who discontinued treatment at week 20 had significant weight gain (rebound) • The reported weight gain was al
Slide 8: Muscle produces myokines
Muscle produces myokines Myokines regulate appetite control and energy balance1,2 Depleted muscle - low energy balance Appetite Energy expenditure Lipid break-down Myokines 1 Dulloo A Obesity 25:277-279, 2017 | 2Grannell A et al. Muscles 1:26-47, 2022 8
Slide 9: Enobosarm is a novel oral selective androgen receptor modulator (SARM)
Enobosarm is a novel oral selective androgen receptor modulator (SARM) designed to reduce fat mass and increase lean mass (muscle and bone) • Enobosarm (Ostarine, MK2866, GTx-024) is a nonsteroidal, selective androgen receptor modulator1,2 • Data from clinical trials and preclinical studies support
Slide 10: Enobosarm clinical data from clinical trials approx. 1,000 patients
Enobosarm clinical data from 5 clinical trials approx. 1,000 patients conducted by GTx or Merck in subjects with and without muscle wasting Subjects Muscle strength/ Phase Population Purpose Muscle (LBM) Fat Mass Duration Source (n=) function 3mg Dalton JT 120 (24 Males over 60 years of 3mg=0.32 kg
Slide 11: Phase 2 G200501 trial: improved lean body mass and physical function
Healthy elderly men (>60 yo) and postmenopausal women receiving enobosarm in Phase 2 double-blind placebo controlled clinical trial (G200501) demonstrated improved lean body mass and physical function • 120 subjects enrolled • 12 weeks of treatment % Change in lean mass % Change in stair climb power
Slide 12: Effects of enobosarm on muscle and physical function in cancer patients
Reported effects of enobosarm on muscle and physical function in patients with cancer: a double-blind, randomized controlled Phase 2b (G200502) clinical trial conducted by GTx1 • Mean age >60 yo • 159 subjects enrolled • 16 weeks of treatment Change in stair climb time and power at Day 113/EOS compa
Slide 13: Phase 3 trial of enobosarm on muscle wasting in lung cancer
Phase 3 randomized, double-blind, placebo-controlled 504 clinical trial of evaluating the effects of enobosarm on muscle wasting in patients with non-small cell lung cancer on first line platinum plus a taxane chemotherapy1 3mg enobosarm treatment in 321 subjects enrolled for 21 weeks Lean body mass
Slide 14: Post-hoc analysis of obese subpopulation
Phase 3 randomized, placebo-controlled 504 clinical trial of evaluating enobosarm on muscle wasting in patients with non-small cell lung cancer on first line platinum plus a taxane chemotherapy1 Post-hoc analysis of obese subpopulation (BMI ≥ 30) Total lean body mass Total fat mass Total body weight
Slide 15: Enobosarm +/- GLP-1 RA for the treatment of obesity
Enobosarm +/- GLP-1 RA for the treatment of obesity Clinical and regulatory strategy for all patients who are overweight or obese • New drug in combination with GLP-1 RA should show incremental increase in weight loss • Enobosarm potential direct effects: • Prevents muscle loss: active protein synth
Slide 16: If muscle is preserved, can there still be significant weight loss?
If muscle is preserved, can there still be significant weight loss? The amount of fat mass compartment is greater Preventing muscle loss (FFM deficit) blocks than the muscle mass one1,2 the trigger to increase in appetite3 1 Fui et. al., BMC Med. 2016 Oct 7; 14:153 |2Baglietto et. al., Frontiers in
Slide 17: If muscle is preserved, no muscle deficit, there could be significant weight loss
If muscle is preserved, no muscle deficit, there could be significant weight loss 1 Enobosarm monotherapy? + Enobosarm? Greater amount of fat loss and Prevent rebound fat and weight gain resultant weight loss on GLP-1RA? and maintain weight loss when off GLP-1RA? 1 FDA Wegovy Package Insert 17
Slide 18: If muscle is preserved, could there be greater weight loss without a plateau?
If muscle is preserved, could there be greater weight loss without a plateau? SELECT Trial: Effect of long-term testosterone in hypogonadal men with obesity Effect of semaglutide vs placebo on body weight (8 years)2 (4.25 years)1 BMI 30-34.9 BMI 35-39.9 BMI >40 1Lincoff AM, Brown-Frandsen K, Colhoun
Slide 19: Sarcopenic obese or overweight elderly patients at risk of muscle weakness
Sarcopenic obese or overweight elderly patients at risk for developing muscle weakness and functional limitations when receiving GLP-1 RA for weight loss 1 Taken from Malandrino N et al. Endocrinol Metab Clin N Am 52 (2023) 317–339 19
Slide 20: Phase 2b QUALITY Trial design
Phase 2b QUALITY Trial- Phase 2 double-blind, placebo controlled, randomized, dose finding trial of enobosarm in preventing muscle loss and increasing fat loss in patients receiving a GLP-1 RA for weight loss - Enrollment completed Primary endpoint of LBM at 16 weeks Primary endpoint: Induction Main
Slide 21: Time course of tirzepatide loss of fat-free mass and fat mass
Time course of for tirzepatide loss of FAT-Free mass(FFM) and Fat mass 21
Slide 22: Physical function endpoint
Physical function endpoint 22
Slide 23: Physical function: testosterone as an anabolic agent
Physical function: testosterone as an anabolic agent1-3 Muscle Physical Lean mass Muscle Mass Strength QOL Function TEAAM: p<0.001 TEAAM: p<0.001 • Testosterone replacement in men TOM: p<0.001 TOM: p<0.001 • Increase in lean mass and muscle mass • Increase in quadriceps muscles –weight bearing muscl
Slide 24: Physical function: enobosarm is a potent anabolic agent
Physical function: enobosarm is a potent anabolic agent Muscle Physical Lean mass Muscle Mass QOL Strength Function + LBM/muscle: DEXA and/or MRI + Leg press + Stair climb: speed & power + FAACT and FACIT-F • Phase 1b 003 in PM women • Phase 2 501 in men & PM women • Phase 2b 502 cancer men & women
Slide 25: LBM and stair climb test results from 501, 502, and 504 studies
LBM and stair climb test results from 501, 502, and 504 enobosarm clinical studies Phase 2 5011 Phase 2b 5022 Phase 3 5043 Elderly men & women Multiple cancers wasting Late-stage lung cancer patients • Mean age >60 yo • Mean age >60 yo • Mean age >60 yo • 120 subjects • 159 subjects • 321 subjects •
Slide 26: What do we know about the obesity population receiving GLP-1 RA?
What do we know about the obesity population receiving GLP-1 RA? Expected physical function outcomes with enobosarm • Patients with obesity receiving semaglutide GLP-1 RA treatment • Actively losing muscle and fat mass and induces low energy state and decreases appetite • 20-50% of weight loss consi
Slide 27: Loaded stair climb test
Loaded stair climb test1 Stair climb power (Watts)= (Body weight + load carried (kg)) X 9.81 m/s2 X total stair rise (m) time (s) • 8 step staircase with a timer computer switch pad placed at base and top step • Subject is loaded by placing iron plates in a backpack equal to 10% of body weight e nc
Slide 28: Enobosarm is a muscle drug
Enobosarm is a muscle drug Muscle should be the target for greater high quality weight loss (precision weight loss) • Prevent loss of muscle to preserve physical function • Older adults with sarcopenic obesity are at risk for developing physical function decline; accelerated development of frailty1,
Slide 29: Enobosarm has an extensive safety database
Enobosarm has an extensive safety database Combined safety data from double-blind, placebo controlled clinical trials with enobosarm Treatment-emergent adverse events in at least 2% of patients in placebo or enobosarm 3mg and at least 1% or higher in one of the two groups with a frequency of ≥0.5% P
Slide 30: Enobosarm studies have generated an extensive safety database
Enobosarm studies have generated an extensive safety database • Evaluated in 27 clinical trials comprising >1580 subjects dosed (235 subjects dosed at > 9mg) • Data reported from 12 Phase 1 studies: • No QT effects • No significant drug-drug interactions1 • No significant food effect • No significan
Slide 31: Enobosarm: Lipid profile
Enobosarm: Lipid profile Safety of special interest: Elderly healthy volunteers G200501 Phase 2 study conducted by GTx1 Lipid profile change from baseline Day 84 PBO 3mg Lipids n=24 n=24 3mg vs. PBO HDL (total)(mg/dL) 1.5 3.10% -16.2 -29.60% -17.6 -32.70% VLDL + chylomicron triglycerides (total) (mg
Slide 32: Time course of testosterone replacement effects on lipids
Time course of testosterone replacement effects on lipids 1 Saad F et al. Eur J Endo 165:675-685, 2011 (Review) 32
Slide 33: Cardiovascular safety of long-term testosterone replacement therapy
Cardiovascular safety of long-term testosterone replacement therapy1 2-year cardiovascular study in 5246 men 45 to 80 years of age who had pre- existing or high risk of cardiovascular disease with follow-up of 33 months • Conclusions: • Testosterone therapy was noninferior to placebo with respect to
Slide 34: Enobosarm and GLP-1 receptor agonists: target product profile
Enobosarm and GLP-1 receptor agonists Target product profile • Enobosarm is a nonsteroidal, selective androgen receptor modulator that targets the androgen receptor, a well-established mechanism of action1,2 • Data from clinical trials and preclinical studies support enobosarm’s potential: • Adminis
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