Recombinant GLP-1 receptor agonists (Beijing Lepu)

-- In 5 clinical studies involving 968 older men and postmenopausal women with and without muscle wasting, enobosarm has demonstrated the ability to decrease fat mass, increase muscle mass, and improve muscle strength and physical function -- -- Weight-loss drugs like Ozempic, Wegovy, Mounjaro and other GLP-1 drugs cause a significant loss of both fat and muscle; in older obese or overweight patients who may already have low muscle mass, the further drop in muscle mass of all-important muscles increases risk of muscle weakness, functional limitations, mobility disability, falls, higher hospitalizations, and greater mortality -- -- The Company plans to conduct a Phase 2b double-blind, placebo-controlled study to evaluate enobosarm and GLP-1 drug combination for weight loss to prevent muscle loss and to preferentially increase fat loss in patients who are overweight or have obesity -- -- Phase 2b clinical obesity study to be open for enrollment as early as calendar Q1 2024 -- MIAMI, FL, Oct. 04, 2023 (GLOBE NEWSWIRE) -- Veru Inc. (NASDAQ: VERU), a late clinical stage biopharmaceutical company focused on developing novel medicines for the treatment of obesity, breast cancer and for viral induced ARDS, today announced that the Company will advance its proprietary novel agent, enobosarm, a selective androgen receptor modulator (SARM), into a Phase 2b clinical trial in combination with weight-loss GLP-1 drugs, Ozempic (semaglutide), Wegovy (semaglutide), or Mounjaro (tirzepatide) to evaluate the efficacy and the safety of enobosarm to further increase fat loss while preventing the significant muscle wasting that occurs with weight-loss GLP-1 drugs. Weight loss from these medications results from the collective loss of fat mass and lean mass (muscle and bone). Muscle is critical for metabolism, muscle strength and physical function (mobility) and prevention of injury (falls) especially in an older population. According to the CDC, 42% of older adults have obesity and could benefit from weight loss medication, but the high amount of muscle wasting that occurs with weight-loss drugs reduces the muscle mass to sarcopenic, or critically low amounts, which may result in muscle weakness leading to poor balance, decreased gait speed, mobility disability, loss of independence, falls, bone fractures, higher hospitalizations, and increased mortality. Up to 30% of older obese patients have sarcopenic obesity, which means they have both obesity and age-related low muscle mass at the same time and are potentially at the greatest risk for developing critically low muscle mass and muscle weakness and functional limitations when taking weight-loss GLP-1 drugs. In a study by Wilding et al. reported in The New England Journal of Medicine, a subgroup analysis was conducted in 140 subjects from the Obesity (STEP 1) Trial which evaluated semaglutide 2.4 mg a week treatment compared to placebo for 68 weeks. In this analysis, semaglutide treatment resulted in the average loss of 10.43 kg (22.9 lbs) of fat and 6.92 kg (15.2 lbs) of muscle mass which means that muscle loss made up 40% of the total weight lost. Similarly, Sargeant et al. observed that treatment with GLP-1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2i) resulted in muscle loss that made up 20-50% of the total weight lost. Enobosarm treatment consistently prevents loss of muscle across 5 clinical studies (see Table) Enobosarm is an oral, new chemical entity, new class, selective androgen receptor targeting agent or modulator (SARM) that has demonstrated tissue-selective, dose-dependent increases in muscle mass (lean body mass), reduces fat mass, improves insulin resistance, while sparing other androgenic tissue with no masculinizing effects in women, with prostate neutral effects in men and without increases in hematocrit. Increases in muscle mass have resulted in improvements in muscle strength and physical function. In preclinical studies in male and female mice, enobosarm demonstrated the ability to prevent and treat bone loss. Enobosarm has extensive nonclinical and clinical experience having been evaluated in 25 separate clinical studies in approximately 1,500 subjects dosed. Five clinical studies for a total of 968 patients measured muscle mass endpoints, including two Phase 2 clinical studies in healthy older or sarcopenic subjects (168 subjects) and one Phase 2b and two Phase 3 studies in subjects with muscle wasting because of cancer (800 subjects). Muscle wasting caused by cancer creates a “starvation state” where there is significant loss of both lean body mass and fat mass which is similar to what has been observed with starvation and weight loss GLP-1 drugs. Enobosarm treatment in elderly men and postmenopausal women with and without active muscle wasting consistently resulted in the reduction in fat mass and significant increases in lean body mass (muscle) with improvements muscle strength and physical function. Enobosarm has a large safety database and was generally well tolerated and safe in both men and women. Table:Veru has clinical data: 5 clinical studies in 968 older subjects with and without muscle wasting Subjects(n=)PhasePopulationPurposeMuscle (LBM)Muscle strength/ functionFat MassDurationSource120 (24 received enobosarm 3mg)2Males over 60 years of age and postmenopausal women(Study G200501)Dose-finding(0.1mg-3mg)3mg=1.25 kg increase(p< 0.001 compared to placebo)3mgIncrease SCP(p=0.049 compared to placebo)3mg=0.32 kg decrease(p=0.049 compared to placebo)Representing a 2-5% decrease of total fat mass12 weeksDalton JTJ Cachexia Sarcopenia Muscle 2:153, 2011 and CSR48 (12 received enobosarm 3mg)2Sarcopenic postmenopausal women(Study 003)Double-blind placebo controlled (3mg)3mg=1.54 kg increase(p<0.001 compared to placebo)Bilateral leg press3mg 21.86 lbs. increase from baseline vs placebo 1.5 lbs. increase from baselineNot collected12 weeksMerck study Clinical study report (on file)159 (41 received enobosarm 3mg)2bMuscle wasting cancer(Study G200502)Double-blind placebo controlled(1 and 3 mg)3mg = 1.3 kg increase(p=0.046 compared to baseline)3mg16.8 watt increase SCP.(p=0.001 compared to baseline)3mg= 0.76 kg decrease in total fat mass(p=0.086 compared to placebo)16 weeksDobs AS Lancet Oncology 14:335, 2013And CSR321 (160 received enobosarm 3mg)3Lung cancer muscle wasting receiving cisplatin + taxane chemotherapy(Study G300504)Double-blind placebo controlled(3mg)0.8 kg Increase in LBM at Day 84 (p<0.001 from baseline) Higher mean slope of the change from baseline than placebo (p=0.0002 Day 84 and p<0.0001 Day 147)5.17% Increased in SCP at Day 84 vs. -1.27% in the placebo Higher mean slope of the change from baseline (p=0.0147 at Day 84, p=0.049 at Day 147)Not collected21 weeksClinical study report (on file)320 (159 received enobosarm 3mg)3Lung cancer muscle wasting receiving cisplatin + nontaxane chemotherapy(Study G300505)Double-blind placebo controlled(3mg)0.73 kg Increase in LBM Day 84 and 0.67 kg increase at Day 147 (p=0.013) Higher mean slope of the change from baseline compared to placebo(p=0.0111 at Day 84, and p=0.0028 at Day 147)SCP N.S.Not collected21 weeksClinical study report (on file)Sarcopenic= presence of low muscle mass; LBM= lean body mass; SCP= stair climb power (Watts), power exerted in a 12-step stair climb; CSR=clinical study report; N.S.= not significant Phase 2b Enobosarm + GLP-1 weight loss drug combination to treat obesity and protect against muscle loss clinical study design Given the extensive clinical experience with enobosarm, in both older patients and in patients with initial and ongoing muscle wasting caused by a starvation state (cancer induced muscle wasting), the combination of enobosarm and semaglutide or tirzepatide therapy for weight loss or diabetes may provide additional clinical benefit and ameliorate adverse muscle wasting effects of GLP-1 agents. Specifically, enobosarm therapy could augment the preferential loss of fat mass while preventing the loss of critical muscle mass and bone mineral density. Enobosarm treatment could also preserve or improve muscle strength and physical function in older adults being treated with a weight loss drug. Veru intends to conduct a Phase 2b multicenter, double-blind, placebo-controlled, randomized, and dose-finding obesity or overweight clinical study in approximately 75 patients who qualify for treatment with a GLP-1 receptor agonist, Ozempic (semaglutide), Wegovy (semaglutide), or Mounjaro (tirzepatide), for weight loss and are at risk for muscle loss. Patients will be randomized in a 1:1 ratio to a GLP-1 receptor agonist plus enobosarm 3mg, GLP-1 receptor agonist plus enobosarm 6mg, or a GLP-1 receptor agonist plus placebo for 4 months. The primary endpoint of the study will be change in total lean body mass (muscle) from baseline to 4 months. Key secondary endpoints will be change from baseline to 4 months in total fat mass, insulin resistance (HOMA-IR), and body weight. After completing this study, participants will then continue into a separate Bone Mineral Density (BMD) extension study for an additional 5 months (total of 9 months) to determine the effects of GLP-1 + enobosarm 3mg, GLP-1 + enobosarm 6mg, or GLP-1 + placebo on bone mineral density measured by DEXA. "While GLP-1 agonists have been very effective in inducing substantial weight loss, there is growing concern about the potential deleterious effects of the associated loss of muscle and bone mass in older adults," said Dr. Dennis Villareal, Professor of Medicine, Baylor College of Medicine and Chief, Division of Endocrinology, Diabetes and Metabolism. "Therefore, there is an urgent unmet need for a clinical trial to test whether a muscle anabolic drug such as enobosarm that can effectively preserve muscle mass during weight-loss therapy of older patients with obesity." “It has become apparent that the total body weight loss caused by weight loss GLP-1 drugs is the result of not only the loss of fat, but also the loss of significant amounts of muscle. This muscle wasting adverse effect of GLP-1 drugs places elderly overweight or obese patients with sarcopenic obesity at risk as they already have low muscle mass and may develop muscle weakness, functional limitations, mobility disability, and falls. Given the extensive clinical experience of enobosarm, Veru has decided to advance enobosarm into Phase 2b clinical development in combination with GLP-1 agents (semaglutide or tirzepatide). The Phase 2b clinical study will aim to maximize the preferential loss of fat loss while preventing muscle wasting and bone loss caused by GLP-1 agents (semaglutide or tirzepatide),” said Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer of Veru. “Another potential indication for enobosarm is for the treatment of older obese patients that have stopped treatment with GLP-1 agent (semaglutide or tirzepatide) and now have critically low muscle mass. As fat will return before muscle, these elderly patients are at risk for muscle weakness and functional limitations. The potential market for enobosarm in combination with weight-loss drugs is a large and growing multi-billion dollar market.” References Dalton JT et al. The selective androgen receptor modulator (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of double blind, placebo -controlled Phase 2 trial. J Cachexia Sarcopenia Muscle 2:153-161, 2011. Dobs AS et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double blind, randomized controlled phase 2 study. Lancet Oncol 14:335-345, 2013. Ida S et al. Effects of antidiabetic drugs on muscle mass in type 2 diabetes mellitus. Curr Diabetes Rev 17:293-303, 2021. Madison Muller and Bloomberg. Fortune Well: Weight-loss drugs like Ozempic and Wegovy may be risky for older people because they melt away all-important muscles. September 27, 2023. Sargeant JA et al. A review of the effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors on lean body mass in humans. Endocrinol Metab 34:247-262, 2019 Villareal DT, Chode S, Parimi N, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med 3/31/2011 2011;364(13):1218-1229. doi:10.1056/NEJMoa1008234 Villareal DT, Aguirre L, Gurney AB, et al. Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults. N Engl J Med 5/18/2017 2017;376(20):1943-1955. doi:10.1056/NEJMoa1616338 Wennamethee SG et al. Sarcopenic Obesity and cardiometabolic health and mortality in older adults: a growing health concern in an aging population. Current Diabetes Reports 2023. Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 384: 989-1002, 2021. Supplementary appendix. About Veru Inc.Veru is a late clinical stage biopharmaceutical company with the following programs. Oncology program: metastatic breast cancer The Company’s late-stage breast cancer development portfolio comprises enobosarm, a selective androgen receptor targeting agonist. Phase 3 clinical ENABLAR-2 study – enobosarm +/- abemaciclib combination versus estrogen blocking agent (active control) as a 2nd line treatment in AR+ ER+ HER2- metastatic breast cancer is open and active. The Company and Eli Lilly and Company have entered into a clinical study collaboration and supply agreement for the ENABLAR-2 study. Lilly supplies Verzenio (abemaciclib). Infectious disease program: viral ARDS Sabizabulin is an oral, first-in-class, new chemical entity, microtubule disruptor that has dual anti-inflammatory and host mediated antiviral properties. Veru has conducted a positive double-blind, randomized, placebo-controlled Phase 3 COVID-19 clinical trial in 204 hospitalized moderate to severe COVID-19 patients at high risk for ARDS and death. In April 2023, the Company reached agreement with FDA on design of the Phase 3 confirmatory COVID-19 clinical trial to evaluate sabizabulin in hospitalized moderate to severe COVID-19 patients at high risk for ARDS. Although the Company reached agreement with FDA for the design of Phase 3 confirmatory COVID-19 clinical trial, the Company met with FDA in September 2023 and reached agreement on the design of Phase 3 study design evaluating sabizabulin 9mg for the broader treatment of hospitalized adult patients who have any type of viral ARDS. Smallpox virus: The Company had a preIND meeting in August with FDA to discuss the development of sabizabulin for smallpox virus. FDA agreed that the Animal Rule pathway is acceptable for evaluating the efficacy of smallpox virus. The Company will work with FDA to develop a plan for the nonclinical studies that could support a smallpox indication. Sexual health program – Urev Veru has a commercial sexual health division called Urev that is comprised of FC2 Female Condom® (internal condom), for the dual protection against unplanned pregnancy and the transmission of sexually transmitted infections which is sold in the U.S. and globally. The Company has launched its own independent, FC2-dedicated direct to patient telehealth and pharmacy services portal. The Company is focused on executing new contracts with additional telehealth partners and has internet fulfillment pharmacy partners that provide coverage in all 50 states in the U.S. Forward-Looking StatementsThe statements in this release 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 release include statements regarding: the planned design, enrollment, timing, commencement, interim and full data readout timing, scope, regulatory pathways, and results of the Company’s current and planned clinical trials, including the planned Phase 2b study of enobosarm with GLP-1 drugs in obesity studies, planned Phase 3 study of sabizabulin in hospitalized adult patients with viral induced ARDS, the Phase 3 study of enobosarm alone or in combination with abemaciclib for the 2nd line treatment of AR+ ER+ HER2 metastatic breast cancer, the Phase 3 study of enobosarm in bone-only non-measurable hormone receptor and HER2- metastatic breast cancer, the Phase 3 study of sabizabulin in hospitalized influenza patients at high risk of ARDS, and studies of sabizabulin in smallpox virus and Ebola virus, and whether any of such studies will meet any of its primary or secondary endpoint; whether enobosarm will demonstrate sufficient effect in preventing muscle wasting in patients taking GLP-1 drugs, whether enobosarm will augment fat loss in such patients and whether enobosarm will become a potential treatment for patients taking GLP-1 drugs or suffer from muscle wasting generally; whether the results of the planned sabizabulin ARDS study will be sufficient to support the submission of an NDA and the timing of any such data reading out; whether the Company will pursue any Phase 3 study of sabizabulin for COVID-19 alone; whether and when the Company will receive the future installment payments of the ENTADFI purchase price or sales milestone payments; and the outlook for growth in the Company's FC2 business through telehealth customers, our direct to patient telehealth portal and the global public health sector. These forward-looking statements are based on the Company’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: the development of the Company’s product portfolio and the results of clinical studies possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical studies and the ability to enroll subjects in accordance with planned schedules; the ability to fund planned clinical development as well as other operations of the Company; the timing of any submission to the FDA or any other regulatory authority and any determinations made by the FDA or any other regulatory authority; the possibility that as vaccines, antivirals and other treatments become widely distributed the need for new COVID-19 or other ARDS treatment candidates may be reduced or eliminated; government entities possibly taking actions that directly or indirectly have the effect of limiting opportunities for sabizabulin as a COVID-19 or other ARDS treatment, including favoring other treatment alternatives or imposing price controls on COVID-19 or other ARDS treatments; the Company’s existing products, including FC2 and, if authorized, sabizabulin, and any future products, if approved, possibly not being commercially successful; the ability of the Company to obtain sufficient financing on acceptable terms when needed to fund development and operations; demand for, market acceptance of, and competition against any of the Company’s products or product candidates; new or existing competitors with greater resources and capabilities and new competitive product approvals and/or introductions; changes in regulatory practices or policies or government-driven healthcare reform efforts, including pricing pressures and insurance coverage and reimbursement changes; risks relating to the Company's development of its own dedicated direct to patient telemedicine and telepharmacy services platform, including the Company's lack of experience in developing such a platform, potential regulatory complexity, development costs, and market awareness and acceptance of any telehealth platform we develop; risks relating to our ability to increase sales of FC2 after significant declines in recent periods due to telehealth industry consolidation and the bankruptcy of a large telehealth customer; the Company’s ability to protect and enforce its intellectual property; the potential that delays in orders or shipments under government tenders or the Company’s U.S. prescription business could cause significant quarter-to-quarter variations in the Company’s operating results and adversely affect its net revenues and gross profit; the Company’s reliance on its international partners and on the level of spending by country governments, global donors and other public health organizations in the global public sector; the concentration of accounts receivable with our largest customers and the collection of those receivables; the Company’s production capacity, efficiency and supply constraints and interruptions, including potential disruption of production at the Company’s and third party manufacturing facilities and/or of the Company’s ability to timely supply product due to labor unrest or strikes, labor shortages, raw material shortages, physical damage to the Company’s and third party facilities, product testing, transportation delays or regulatory actions; costs and other effects of litigation, including product liability claims and securities litigation; the Company’s ability to identify, successfully negotiate and complete suitable acquisitions or other strategic initiatives; the Company’s ability to successfully integrate acquired businesses, technologies or products; and other risks detailed from time to time in the Company’s press releases, shareholder communications and Securities and Exchange Commission filings, including the Company’s Form 10-K for the fiscal year ended September 30, 2022 and subsequent quarterly reports on Form 10-Q. These documents are available on the “SEC Filings” section of our website at www.verupharma.com/investors. The Company disclaims any intent or obligation to update these forward-looking statements. Ozempic® and Wegovy® are trademarks owned by or licensed to Novo Nordisk A/S, its subsidiaries, or affiliates. Mounjaro® is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates. Investor and Media Contact:Samuel FischExecutive Director, Investor Relations and Corporate CommunicationsEmail: veruinvestor@verupharma.com