Slide 1: Advancing enobosarm, an oral novel SARM, to avoid muscle loss and augment fat loss with GLP-1 RA
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 Chairman and CEO Veru, Inc. May 16
Slide 2: Forward looking statements and safe harbor
Forward looking statements and safe harbor The statements in this document that are not historical facts are “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this document include statements regarding: the pla
Slide 3: 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 4: GLP-1 receptor agonist drugs therapy results in significant loss of both fat and muscle
GLP-1 receptor agonist drugs therapy results in 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 pound of muscle for 1
Slide 5: GLP-1 RA drugs result in significant loss of both fat and muscle
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 overweight and could benefit from weight-loss drugs1 • Subpopulation: older
Slide 6: WEGOVY FDA label now has hip and pelvic fracture safety data from SELECT
WEGOVY FDA label now has hip and pelvic fracture safety data from SELECT cardiovascular outcomes study 1 Wegovy PI page 4 5
Slide 7: 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? 6
Slide 8: 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 9: Muscle produces myokines
Muscle produces myokines Myokines regulate appetite control and energy balance1,2 Depleted muscle- low energy balance Normal muscle – normal energy balance Appetite Appetite Energy expenditure Energy expenditure Lipid break-down Myokines Lipid break-down Myokines 1 Dulloo A Obesity 25:277-279, 2017
Slide 10: 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 11: 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 12: Phase 2 trial G200501 in healthy elderly men and postmenopausal women
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 13: Effects of enobosarm on muscle and physical function in cancer patients, Phase 2b
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 14: Phase 3 trial of enobosarm on muscle wasting in non-small cell lung cancer
Phase 3 randomized, double-blind, placebo-controlled 504 clinical trial 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 (muscle) Stair climb powe
Slide 15: Post-hoc analysis of obese subpopulation (BMI ≥ 30)
Phase 3 randomized, placebo-controlled 504 clinical trial of 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* Up to Day
Slide 16: Enobosarm +/- GLP-1 RA for the treatment of obesity: strategy 1
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 at 1 year • Enobosarm potential direct effects: • Prevents muscle loss: active pro
Slide 17: 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 one the trigger to increase in appetite1 1 Dulloo A Obesity 25:277-279, 2017 16
Slide 18: 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 Enobosarm monotherapy? + Enobosarm? Greater amount of fat loss and weight loss ? Prevent rebound fat and weight gain? 1 FDA Wegovy PI |2 Dulloo AG et al. Eur J Clin Nutrition 71:353-357, 2017; 3 Dulloo A Obesity 25:277
Slide 19: If muscle is preserved, could there be greater weight loss without a plateau?
If muscle is preserved, could be 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, Col
Slide 20: Sarcopenic obese or overweight elderly patients at risk for 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 21: Enobosarm +/- GLP-1 RA for the treatment of obesity: strategy 2
Enobosarm +/- GLP-1 RA for the treatment of obesity Clinical and regulatory strategy for older patients with low muscle reserve • New drug in combination with GLP-1 RA should show incremental increase in weight loss and physical function benefit • Enobosarm potential direct effects: • Prevents muscl
Slide 22: Enobosarm and GLP-1 RA combination study design
Enrolling - 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 Enobosarm and GLP-1 RA combination study Primary endpoint of LBM Primary endpoint: at 16 weeks • LBM (m
Slide 23: 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 frailty •
Slide 24: Enobosarm has an extensive safety database
Enobosarm has an extensive safety database Combined Safety data from 5 Phase 2 and 3 clinical trials in cancer and healthy subjects and Phase 1 studies Percentage of healthy and cancer subjects in all 5 clinical and Percentage of healthy and cancer subjects in all 5 clinical and Phase 1 clinical tri
Slide 25: Enobosarm has an extensive safety database
Enobosarm has an extensive safety database Safety of special interest: Elderly healthy volunteers G200501 Phase 2 study conducted by GTx1 • 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 sign
Slide 26: 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