vosilasarm (EP0062) / Radius, Ellipses Pharma - LARVOL DELTA

Results of a phase 1 study of vosilasarm (EP0062), a first-in-class oral selective androgen receptor modulator (SARM) in patients with advanced or metastatic AR+/ER+/HER-2- breast cancer. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05573126 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2

The impact of a selective androgen receptor modulator (RAD140) on frailty and underlying mechanisms in older male and female C57Bl/6 mice. (PubMed, Mech Ageing Dev) - "Six-weeks of RAD140 treatment did not affect frailty in older male or female mice. The beneficial effects in lean mass, bone mineral density, and systemic inflammation warrant longer treatments to explore any positive impact on frailty in males. RAD140 may not be ideal for achieving these in females."

Journal • Preclinical • Inflammation • AR • IL6

Deep Learning-Based Drug Compounds Discovery for Gynecomastia. (PubMed, Biomedicines) - "DTI analysis and DeepPurpose predictions identified 12 potential drugs, including conteltinib, yifenidone and vosilasarm, with high predicted binding affinities to the target genes. The findings highlight the effectiveness of combining text mining and artificial intelligence in drug discovery. This innovative method provides a new avenue for developing specific treatments for gynecomastia and underscores the need for further experimental validation and optimization of prediction models to support novel drug development."

Journal • IGF1 • TGFB1

Phase 1/2 Study to Evaluate Vosilasarm (EP0062) as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Ellipses Pharma | N=128 ➔ 60 | Trial completion date: Mar 2025 ➔ Nov 2026 | Trial primary completion date: Dec 2024 ➔ Nov 2025

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A study to evaluate the safety and efficacy of vosilasarm (EP0062), an oral SARM, as monotherapy and in combination with standard of care regimens in patients with relapsed locally advanced or metastatic AR+/HER2-/ER+ breast cancer (SABCS 2024) - P1/2 | "Vosilasarm + elacestrant in patients with AR+/HER2-/ER+/ESR1mut + advanced/metastatic breast cancer that has progressed on one or two prior lines of endocrine therapy, including prior CDK4/6 inhibitor Cohort 2. Vosilasarm + everolimus + exemestane in patients with AR+/HER2-/ER+ advanced/metastatic breast cancer that has progressed on a prior endocrine therapy + CDK4/6 inhibitor Key inclusion criteria are as follows: Post-menopausal women, ≥18 years ECOG performance status of 0 to 1 Locally advanced or metastatic breast cancer ER+, HER2- as per ASCO CAP guidelines AR+, as defined as ≥ 10% AR nuclei staining by IHC Endocrine-therapy-sensitive breast cancer defined as: a) greater than 2 years of adjuvant endocrine therapy prior to development of advanced or metastatic disease, OR b) previous response (without disease progression for at least 6 months) to one of the following treatments in the advanced/metastatic setting: SERD +/- CDK 4/6 inhibitor, AI +/- CDK 4/6..."

Clinical • Combination therapy • Metastases • Monotherapy • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AR • ER • HER-2

Severe Drug-Induced Liver Injury Due to RAD-140 Use (ACG 2024) - "The case illustrates that healthcare providers should be aware that nonmedical supplement use like RAD-140 can cause severe hepatotoxicity, and developing acute liver failure necessitating liver transplantation is always a possibility. Patients usually require close outpatient monitoring as the recovery period can be prolonged, and it may take 3-5 months for liver biochemistries to normalize."

CNS Disorders • Cytomegalovirus Infection • Dermatology • Epstein-Barr Virus Infections • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Liver Failure • Pruritus

Severe Drug-Induced Liver Injury Due to Testolone, A Selective Androgen Receptor Modulator (ACG 2024) - "Empiric N-acetylcysteine, cholestyramine, and ursodiol were started. Figure: Figure 1A: Liver biopsy showing marked canalicular cholestasis consistent with DILI. Figure 1B: Budesonide treatment started on day 9 demonstrating a steady downtrend in total bilirubin."

Alzheimer's Disease • Cholestasis • CNS Disorders • Hepatology • Inflammation • Liver Failure • Muscular Dystrophy • Osteoporosis • Pruritus • Rheumatology

Identification of biomarkers of response and the mechanism of action of a selective androgen receptor modulator in estrogen receptor-positive breast cancer patient-derived xenografts (EORTC-NCI-AACR 2024) - "Adding the CDK4/6 inhibitor palbociclib enhanced the antitumor activity of EP0062 or fulvestrant in ESR1-mutant models but not in HER2-enriched or PTEN-mutant PDX models...EP0062 triggers an E2F1 downmodulation which mediates a potent antiproliferative activity. For EP0062-resistant tumors that remain ER-driven, the addition of palbociclib displays a potent antitumor effect."

Biomarker • Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AR • E2F1 • ER • FOXA1 • GATA3 • HDAC2 • HER-2 • PIK3CA • PTEN

Selective Androgen Receptor Modulators Leading to Liver Injury: A Case Report. (PubMed, Cureus) - "Discontinuation of RAD-140 appears to reverse liver injury, but the long-term effects and risks of SARM use remain unclear. This case highlights the need for caution and monitoring when considering SARMs for performance enhancement."

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure

Myopericarditis Following Use of Selective Androgen Receptor Modifier "RAD-140". (PubMed, JACC Case Rep) - "We report the case of a 16-year-old boy who had myopericarditis following the first dose of a selective androgen receptor modulator called Testolone ("RAD-140"). These drugs are widely abused by physically active young adults; however, the drugs' side effects, which can be life-threatening, are not well characterized."

Journal • Cardiovascular • Inflammation • AR

Reversible Gynecomastia and Hypogonadism Due to Usage of Commercial Performance-Enhancing Supplement Use. (PubMed, JCEM Case Rep) - "These performance-enhancing supplements were found to contain amounts of RAD-140, a selective androgen receptor modulator, MK-677, a GH secretagogue and cardarine, all of which are banned PEDs. Cessation of these supplements led to full resolution of symptoms including normalization of hypogonadotropic hypogonadism. This case highlights the need for clinicians to consider commercially available performance-enhancing supplements as potential sources of PEDs and exogenous steroid hormones that can have adverse clinical consequences."

Journal • Endocrine Disorders

Detection of nonsteroidal and steroidal selective androgen receptor modulators in equine hair after oral administrations. (PubMed, Drug Test Anal) - "To better control the misuse of RAD140 and YK-11 in horses, two separate oral administration studies of RAD140 (0.3 mg/kg daily for 3 days) and YK-11 (0.2 mg/kg daily for 3 days) were previously conducted to investigate their metabolism and to identify target analyte(s) with the longest detection time in urine and plasma for doping control. In this work, segmental analyses of post-administration hair samples have revealed that (i) RAD140 and YK-11 could be detected in horse mane after oral administration and (ii) internal incorporation of RAD140 into hair via bloodstream and external incorporation through sweat or sebum were both observed, whereas YK-11 was primarily incorporated into hair via sweat or sebum."

Journal

Selective androgen receptor modulator abuse induced heart failure: catastrophic effects of RAD-140 (Testolone). (PubMed, Pol Arch Intern Med) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

DIFFERENTIAL EFFECTS OF RAD140 TREATMENT ON RAT TIBIALIS ANTERIOR AND PLANTARIS MUSCLE CROSS-SECTIONAL AREAS (ACSM 2024) - "These data may suggest that muscle recruitment, activation patterns, load challenge, or muscle fiber type composition may also play key roles in the differential response on fiber CSA secondary to RAD140 treatment."

Preclinical • Cachexia • Oncology • Sarcopenia

Social Interest Data as a Proxy for Off-Label Performance-Enhancing Drug Use: Implications and Clinical Considerations. (PubMed, Cureus) - "Several significant trends were identified for non-FDA-regulated compounds (i.e., selective androgen receptor modulators such as RAD-140) and off-label indications for FDA-regulated drugs (i.e., SERMs such as tamoxifen). A significant increase in interest regarding selective androgen receptor modulators, mirrored by anecdotal reports in clinical settings and online forums, is coupled with stagnant or decreasing interest in both post-cycle therapies and anabolic steroids. Ultimately, we propose a call to action for utilizing social data and/or prescription data as a proxy for clinicians to better understand trends in these compounds and thus refine their treatment protocols in a concordant manner."

Journal

Detection of anabolic agents including selective androgen receptor modulators in samples outside of sport. (PubMed, Drug Test Anal) - "The top three SARMs found were LGD-4033 followed by RAD140 and ostarine. Our results indicate that SARM use might be a concern outside of sport. Subsequently, in addition to AAS, the healthcare system should also be informed about SARM abuse and the associated adverse side effects."

Journal

RAD140 (Testolone) negatively impacts skeletal muscle adaptation, frailty status and mortality risk in female mice. (PubMed, Clin Exp Pharmacol Physiol) - "Torque did not differ between groups after 2-3 weeks of recovery (p ≥ 0.135). In conclusion, long-term RAD140 supplementation reduced indices of overall health and failed to improve strength in female mice, suggesting that RAD140 (at a 5mg/kg dosage) may be more detrimental than beneficial in delaying or preventing sarcopenia."

Journal • Preclinical • Sarcopenia

Harm From SARMs: RAD-140, A Selective Androgen Receptor Modulator Leading to Acute Liver Injury (ACG 2023) - "Despite the FDA warning against SARM use in body-building products, SARM abuse is a rising problem among athletes. Clinicians should strongly recommend against recreational SARM use and educate patients about the negative effects of these unregulated substances."

Autoimmune Hepatitis • Breast Cancer • Cholestasis • CNS Disorders • Fibrosis • Hepatology • Immunology • Liver Failure • Oncology • Pain • Pruritus • Solid Tumor

A rapid synthesis of molecularly imprinted polymer nanoparticles for the extraction of performance enhancing drugs (PIEDs). (PubMed, Nanoscale Adv) - "With the SARMs-based nanoMIPs being able to rebind 94.08 and 94.46% of their target molecules (andarine, and RAD-140, respectively), while the steroidal-based nanoMIPs were able to rebind 96.62 and 96.80% of their target molecules (estradiol and testosterone, respectively)...While the non-imprinted control polymer (NIP) shows a decrease in affinity with K values of 3.40 × 10, 1.01 × 10, 1.83 × 10, and 4.00 × 10 M, respectively. The nanoMIPs also demonstrated good selectivity and specificity of binding the targets from a complex matrix of river water, showing these functional materials offer multiple uses for trace compound analysis and/or sample clean-up."

Journal

Comparison of in vitro approaches for predicting the metabolism of the selective androgen receptor modulator RAD140. (PubMed, Anal Bioanal Chem) - "In the organ on a chip samples, the highest number of metabolites were detected. The subcellular liver fractions and organ on a chip techniques are deemed complementary to predict metabolites of RAD140, as both techniques produce distinct metabolites that are also found in an anonymized human in vivo urine sample."

Journal • Preclinical • Metabolic Disorders

Phase 1/2 Study to Evaluate EP0062 in Patients With Relapsed Locally Advanced or Metastatic Androgen Receptor Positive (AR+)/HER2-/ER+ Breast Cancer (clinicaltrials.gov) - P1/2 | N=128 | Recruiting | Sponsor: Ellipses Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Idiosyncratic drug-induced liver injury related to use of novel selective androgen receptor modulator RAD140 (Testalone): a case report. (PubMed, J Med Case Rep) - "Novel selective androgen receptor modulators such as RAD140 may be associated with idiosyncratic drug-induced liver injury. Workup of new liver injury in young and middle-aged males should involve asking about use of these novel compounds, for if missed and use continues, it can likely lead to fulminant liver failure or decompensated liver cirrhosis."

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Pain

Novel mechanisms of action of selective androgen receptor modulator RAD140 in AR+/ER+ breast cancer models (SABCS 2019) - P1; "RAD140 (3 mg/kg twice daily), elacestrant (30 mg/kg once daily), and palbociclib (10 mg/kg once daily) were administered via oral gavage for the duration of study...The selective ER degrader (SERD) fulvestrant had TGI of 7%, while the oral SERD elacestrant (RAD1901) had TGI of 60%...The AR antagonist apalutamide was found to partially reverse the apoptosis induced by RAD140 and DHT, further supporting the on-target effect... Our data suggest the anti-tumor activity of RAD140 may be mediated through suppression of ER signaling as well as additional mechanisms. The effect of RAD140 on DNA damage and apoptosis implies the potential for combination therapy with agents targeting cell survival and DNA damage repair pathways. RAD140 is being studied in a Phase 1, first-in-human trial in postmenopausal women with hormone receptor positive BC (NCT03088527)."

IO biomarker • Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AR • BCL2 • CASP3 • CASP7 • ER • PARP

Selective androgen receptor modulator RAD140 inhibits the growth of endocrine-resistant breast cancer models with defined genetic backgrounds (SABCS 2018) - P1; "In PDX models harboring ESR1 amplification or fusion, RAD140 inhibited tumor growth to a greater degree than fulvestrant, a standard-of-care selective ER degrader (SERD). These results lend support to a clinical hypothesis that AR/ER+, endocrine-resistant tumors with these genetic Background: s may benefit from AR agonist-based treatment. RAD140 is currently being evaluated in hormone receptor positive (HR+) breast cancer patients (NCT03088527). "

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A phase 1/2 study to evaluate the safety and efficacy of EP0062, an oral Selective Androgen Receptor Modulator (SARM), for the treatment of AR+/HER2-/ER+ advanced breast cancer (SABCS 2022) - "Clinic follow-up will be at 2 and 4 weeks, then every 4 weeks until disease progression. Recruitment is scheduled to initiate in Q4 2022."

Clinical • P1/2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ER • HER-2