Cardiometabolic Obesity Drug Program

According to the Centers for Disease Control and Prevention, 41.5% of older adults have obesity and could benefit from weight reduction medication. Up to 34.4% of people over the age of 60 with obesity in the United States have sarcopenic obesity which means they have both obesity and low muscle mass at the same time and are potentially at the greatest risk for developing critically low muscle mass when taking a currently approved GLP-1 RA.

The Company believes there is an urgent unmet need for a drug that can preserve lean mass and physical function as well as cause preferential loss of fat mass during weight reduction especially in at-risk elderly patients with obesity.

Enobosarm, an oral, novel selective androgen receptor modulator, has demonstrated in 6 clinical trials in over 1100 patients tissue-selective positive changes in body composition with increases in lean mass and decreases in fat mass, and improvements in muscle strength and physical function. The safety database for enobosarm is large, consisting of 27 clinical trials and over 1700 patients. Enobosarm had a favorable safety profile with no observed masculinizing effects in women and neutral prostate effects in men.

A weight loss plateau occurs when the patient with obesity stops losing weight while on a GLP-1 RA. In the SURMOUNT-1 clinical study conducted by Eli Lilly and Company, about 88% of patients with obesity receiving the GLP-1 RA drug tirzepatide reached the weight loss plateau by 72 weeks. Unfortunately, 62.6% of these patients are still clinically overweight or have obesity at 72 weeks, and patients that had a baseline BMI ≥ 35 on average still had obesity. We believe patients being treated with semaglutide, when combined with enobosarm, will experience additional fat loss by preserving muscle and physical function and directly burning fat leading to incremental weight reduction.

The Phase 2b PLATEAU clinical trial is a double-blind, placebo-controlled study designed to evaluate the effect of enobosarm 3mg on total body weight, fat mass, lean mass and physical function, bone mineral density and safety in approximately 200 older patients (age ≥ 65 yo) who have obesity (BMI ≥ 35) and are initiating semaglutide (Wegovy®) GLP-1 RA treatment for weight reduction. The primary efficacy endpoint of the study is the percent change from baseline in total body weight at 68 weeks. The key secondary endpoints for the overall study are total fat mass, total lean mass, physical function (stair climb test), mobility-disability assessment, bone mineral density, and patient reported outcome questionnaires for physical function (SF-36 PF-10, and IWQOL-lite CT physical function), HbA1c, and insulin resistance.

The Phase 2b PLATEAU study is also designed to assess whether enobosarm, by preserving lean mass and physical function, can achieve clinically meaningful incremental weight reduction in patients with obesity receiving GLP-1 RA treatment by 68 weeks. An interim analysis for the clinical study, after all patients are treated for 32 weeks, is planned for the first quarter of calendar 2027 and will assess the patient’s lean body mass and total fat mass as measured by DXA scan.

A Phase 2b, multicenter, double-blind, placebo-controlled, randomized, dose-finding QUALITY clinical trial was conducted to evaluate the safety and efficacy of enobosarm 3mg, enobosarm 6mg, or placebo as a treatment to augment fat loss and to prevent muscle loss in 168 patients with obesity (≥60 years of age) receiving semaglutide (Wegovy®) for weight reduction. The primary endpoint was the percent change from baseline in total lean body mass, and the key secondary endpoints were the percent change from baseline in total body fat mass, total body weight, and physical function as measured by stair climb test at 16 weeks. After completing the active weight loss 16 week portion of the Phase 2b QUALITY clinical trial, the participants continued into a Phase 2b extension maintenance trial where all patients stopped treatment with semaglutide (Wegovy®), but continued taking placebo, enobosarm 3mg, or enobosarm 6mg in a blinded fashion for 12 additional weeks. The Phase 2b extension clinical trial 12 week period evaluated whether enobosarm can maintain lean mass and prevent the fat regain that generally occurs after discontinuing a GLP-1 RA.

The Phase 2b QUALITY study is the first human study to report the effects of a muscle preservation drug candidate on body composition in older patients who have obesity or are overweight receiving a GLP-1 receptor agonist

Active weight loss period (16 weeks)

The primary endpoint was met with a statistically significant and a clinically meaningful benefit in the preservation of total lean body mass in patients receiving enobosarm 3mg + semaglutide versus placebo + semaglutide at 16 weeks (100% relative reduction in lean mass loss, p<0.001).

Enobosarm + semaglutide treatment resulted in dose dependent greater loss of fat mass compared to placebo + semaglutide with the enobosarm 6mg dose having a 42% greater relative loss of fat mass compared to placebo + semaglutide group at 16 weeks (p=0.017) and the enobosarm 3mg dose having a 12% greater fat loss.

Although enobosarm + semaglutide significantly preserved lean mass, the additional loss of fat mass experienced by patients taking enobosarm treatment compensated for the preserved lean mass resulting in a similar net mean weight loss as measured by a DXA scan with semaglutide at 16 weeks. Accordingly, the tissue composition of the total weight loss shifted to a greater and selective loss of fat with enobosarm treatment, with the mean percentage of total body mass loss in the placebo + semaglutide group that was due to lean mass was 34% and estimated fat loss was 66%. In contrast, in the enobosarm 3mg + semaglutide group, the total weight loss due to lean mass was 0% and estimated fat loss was 100%.

Physical function was measured by the stair climb test, which is an activity of daily living. Declines in performance, which may be measured by a stair climb test, often predicts in older patients a higher risk for mobility disabilities, gait difficulties, falls and bone fractures, hospitalizations, and mortality. As a point of reference, stair climb power declines by -1.38% annually with aging according to Van Roie E. PLOS ONE 14:e0210653, 2019.

Phase 2b QUALITY clinical trial is the first human study to demonstrate that older patients who have obesity are at higher risk for accelerated loss of lean mass with physical function decline with significant weight reduction. A responder analysis was conducted using a greater than 10% decline in stair climb power as the cut off at 16 weeks which represents an approximate 7-to-8-year loss of stair climb power that naturally occurs with aging. In our Phase 2b QUALITY study, the loss of lean mass mattered as 44.3% of patients on placebo + semaglutide group had at least a 10% decline in stair climb power physical function at 16 weeks.

Patients treated with enobosarm in the Phase 2b QUALITY study preserved lean mass (muscle) which translated into a reduction in the proportion of patients that had a clinically significant stair climb physical function decline versus subjects receiving GLP-1 RA alone. The patients in the enobosarm 3mg + semaglutide group had a statistically significant and clinically meaningfully 59.8% relative reduction in the proportion of subjects that lost at least 10% stair climb power compared to placebo + semaglutide group (p=0.0006). In enobosarm 6mg + semaglutide, there was a 44.1% relative reduction in the proportion of patients with at least a 10% decline in stair climb power from baseline vs. placebo + semaglutide group (p=0.051).

Enobosarm is a novel drug candidate that resulted in tissue selective quality weight reduction as an adjunct to GLP-1 receptor agonist, that is, enobosarm + semaglutide improved changes in body composition which resulted in more selective and greater loss of adiposity (fat mass) than in subjects receiving placebo + semaglutide alone.

After completing the efficacy dose-finding and active weight reduction 16-week portion of the Phase 2b QUALITY clinical trial, participants continued into a Phase 2b maintenance extension study where all patients discontinued semaglutide treatment, but continued receiving placebo, enobosarm 3mg, or enobosarm 6mg as monotherapy in a double-blind fashion for 12 weeks.

As a point of reference, body weight loss at the end of the Phase 2b QUALITY study active weight loss 16-week period was similar across treatment groups with the semaglutide + placebo group losing an average of 11.88 lbs. After the 12-week maintenance extension study period, where all treatment groups discontinued the use of semaglutide, the placebo monotherapy group regained 43% of body weight that was previously lost during the Phase 2b QUALITY for a mean percent change of 2.57% (5.06 lbs) in body weight, compared to 1.41% (2.73 lbs) for the 3mg enobosarm group (p=0.038) and 2.87% (5.29lbs) for the 6mg enobosarm group. The patients in the 3mg enobosarm monotherapy group significantly reduced the body weight regained by 46%. On average, the placebo monotherapy group regained 2.27% in fat mass, while the enobosarm monotherapy cohorts had a loss of fat mass of -0.27% for the 3mg and -0.50% for the 6mg doses. The mean tissue composition of body weight regained was 28% fat and 72% lean mass in the placebo group, versus 0% fat and 100% lean mass in both the 3mg and the 6mg enobosarm groups.

By the end of the study at 28 weeks (Day 1 to Day 196), the placebo + semaglutide followed by placebo monotherapy group experienced a loss of lean mass, while both enobosarm + semaglutide followed by enobosarm monotherapy groups (3 mg and 6 mg doses) significantly preserved more than 100% of lean mass (enobosarm 3mg p<0.001 and enobosarm 6mg p=0.004). The enobosarm + semaglutide followed by enobosarm monotherapy patients had a 58% greater loss of fat with enobosarm 3mg (p=0.085) and a 93% greater loss of fat with enobosarm 6mg (p=0.008) compared to placebo + semaglutide followed by placebo monotherapy.

The Phase 2b QUALITY and maintenance extension clinical trial confirmed that preserving lean mass with enobosarm plus semaglutide led to greater fat loss during the active weight loss period, and after the use of semaglutide was discontinued, enobosarm monotherapy significantly prevented the regain of both weight and fat mass during the maintenance period such that by end of study there was greater loss of fat mass while lean mass was preserved for a higher quality weight reduction compared to the placebo group.

Phase 2b QUALITY clinical study that showed the enobosarm + semaglutide combination had a positive safety profile.

The primary adverse events for the placebo + semaglutide group was constipation, diarrhea, nausea, and GERD. In the enobosarm + semaglutide groups compared to placebo + semaglutide, there were no increases in gastrointestinal side effects, and no increases in obstructive sleep apnea at any dose of enobosarm. There were no adverse events of increases in prostate specific antigen in men. There were no adverse events related to masculinization in women. There were no reports of suicidal ideation observed (Columbia-Suicide Severity Rating Scale). The enobosarm 3mg + semaglutide combination group had the added benefit of fewer gastrointestinal side effects (diarrhea, nausea, and gastroesophageal reflux disease) compared to patients receiving semaglutide alone. There was no evidence of drug induced liver injury (as defined by Hy’s law): one patient (2%) in the enobosarm 3mg group had an ALT increase that was graded as mild in severity; levels returned to baseline while on drug, no associated increase in alkaline phosphatase or total bilirubin. The enobosarm 6mg group had 7 (11%) ALT increases that were all graded as mild in severity; all returned to or toward baseline/upper limit of normal, no associated increases in alkaline phosphatase or total bilirubin. There were five non-treatment related serious adverse events equally distributed between the treatment groups.

Enobosarm monotherapy had a positive safety profile (Table 10). After discontinuation of semaglutide, there were essentially no gastrointestinal side effects, and no increases in obstructive sleep apnea observed at any dose of enobosarm compared to placebo monotherapy. No evidence of drug induced liver injury (as defined by Hy’s law): one patient (2%) in the enobosarm 3mg group had an ALT increase that was graded as mild in severity; levels returned to baseline, no associated increase in alkaline phosphatase or total bilirubin. There were no adverse events of increases in prostate specific antigen in men. There were no adverse events related to masculinization in women. There were no reports of suicidal ideation observed (Columbia-Suicide Severity Rating Scale).

In August 2025, the Company announced selection of a novel modified release oral formulation for enobosarm, a selective androgen receptor modulator, for chronic weight loss management, following confirmation of pharmacokinetic endpoints in a clinical study. The single dose, open label pilot study evaluated the plasma concentration versus time profile of a proprietary, patentable modified release formulation of enobosarm 3mg. The new formulation demonstrated the intended distinct target product release profile, which includes a reduction in maximum plasma concentration (Cmax), a delayed time to maximum plasma concentration (Tmax), a distinct secondary peak plasma concentration, and similar extent of absorption (AUC) compared to historical values for enobosarm immediate release capsules. The novel modified release oral formulation of enobosarm was developed in collaboration with Laxxon Medical using smart delivery systems, including the company’s proprietary patented SPID®-Technology to create advanced, unique oral delivery release profiles, as well as an innovative additive manufacturing process.

According to The Wall Street Journal, more than one billion people worldwide are living with obesity. The World Health Organization (WHO) estimates that approximately 2.5 billion adults globally are either overweight or obese, with the rate of adult obesity having more than doubled since 1990. Despite the size of this population, current obesity therapies from Eli Lilly and Novo Nordisk are estimated to reach less than 2% of eligible patients.

Within this broader population, the market for sarcopenic obesity represents a substantial and growing unmet need. Sarcopenic obesity, characterized by obesity accompanied by low lean muscle mass, is estimated to affect nearly 30 million adults in the United States alone, highlighting the need for therapies that address both weight loss and preservation of lean body mass.

The market for adults 65 years of age and older with obesity is particularly significant given the high prevalence of obesity among Medicare-covered individuals. Data from Medicare Part D indicate that obesity prevalence is 41.5% among the 47.4 million people enrolled in Medicare Part D plans. More broadly, approximately 40% of the 70 million people enrolled in Medicare are estimated to have obesity, underscoring the substantial burden of obesity among older adults.