We have successfully navigated through one of the most challenging years for the biotech sector in its history, coupled with the waning of the COVID-19 pandemic threat, resulting in a change in regulatory urgency. Veru did so by cutting costs and prioritizing clinical programs to pivot and to transform Veru into a late clinical stage biopharmaceutical company focusing on developing novel medicines for the treatment of obesity and oncology.
Dear Shareholders
Why did we pivot into obesity? Glucagon-like peptide-1 receptor agonists (GLP-1 RA) like Ozempic® (semaglutide), Wegovy® (semaglutide), Zepbound™ (tirzepatide), and Mounjaro® (tirzepatide), are very effective weight loss drugs that result in significant weight loss. Unfortunately, up to 50% of the total weight loss comes from muscle, which is problematic, as muscle is necessary for metabolism, strength, and physical function. According to the CDC, 41.5% of older adults suffer from obesity in the United States and could benefit from a weight loss medication. Up to 34.4% of these obese patients over the age of 60 have sarcopenic obesity, which means patients are overweight or obese and have age-related low muscle mass at the same time. Sarcopenic obese patients are potentially at the greatest risk for developing critically low amounts of muscle mass when currently taking a GLP-1 RA medication for the treatment of obesity. Patients with critically low muscle mass may experience muscle weakness, leading to poor balance, decreased gait speed, mobility disability, loss of independence, falls, bone fractures, and increased mortality. We believe there is an urgent unmet medical need for a drug that when given in combination with a GLP-1 RA could prevent the loss of muscle, while preferentially reducing fat in sarcopenic obese or overweight elderly patients who are at-risk for developing muscle atrophy and muscle weakness, leading to frailty. We pivoted because we believe that enobosarm, our novel small molecule, oral selective androgen receptor modulator, may be the drug candidate to address this unmet medical need.
Enobosarm has been studied in five clinical studies involving 968 older men and postmenopausal women, as well as older patients who have cancer muscle wasting. Advanced cancer simulates a “starvation state” where there is significant loss or wasting of both muscle and fat mass similar to what is observed with a GLP-1 RA. The totality of the clinical data from these five clinical trials demonstrates that enobosarm treatment leads to dose-dependent increases in muscle mass with improvements in physical function as well as significant reductions in fat mass. In addition, enobosarm has a large safety database, which includes 25 clinical trials involving 1581 men and women dosed, with duration of treatment in some patients for up to three years. In this large safety database, enobosarm was generally well tolerated with no gastrointestinal side effects. This is important as there are already significant and frequent gastrointestinal side effects with a GLP-1 RA treatment alone. Although these studies were previously conducted by GTx or Merck, Veru is the exclusive licensee and owns all this clinical data as part of our enobosarm exclusive in-license agreement.
Because of these key clinical attributes, we believe that enobosarm may address this unmet medical need. Consequently, Veru plans to develop enobosarm as an obesity treatment to augment fat loss while preventing muscle loss, initially in sarcopenic obese or overweight elderly patients receiving a GLP-1 RA for weight loss who are at-risk for developing muscle atrophy and muscle weakness. We plan to submit an enobosarm IND for the treatment of obesity soon. Subject to receiving clearance of our IND, we plan to conduct a Phase 2b multicenter, double-blind, placebo-controlled, randomized, dose-finding clinical trial designed to evaluate the safety and efficacy of enobosarm 3mg, 6mg, or placebo as a treatment to augment fat loss and to prevent muscle loss in approximately 90 randomized sarcopenic obese or overweight elderly patients receiving a GLP-1 RA who are at-risk for developing muscle atrophy and muscle weakness. The primary clinical data from the clinical trial is expected in calendar Q4 2024. The purpose of the Phase 2b clinical trial is to select the optimal dose of enobosarm in combination with a GLP-1 RA that best preserves muscle and reduces fat after three months of treatment to advance to a Phase 3 clinical trial.
The global obesity and overweight drug market is projected to be $100 billion by 2030 (Barclays analyst 2023). Drugs used for weight loss like Ozempic, Wegovy, Zepbound, Mounjaro, and other GLP-1 receptor agonists cause a significant loss of both fat and muscle. Again, in the US, 42% of older adults (>60 years of age) have obesity (CDC) and 34% of these patients also have sarcopenia, or low muscle reserve. Accordingly, enobosarm is targeting at-risk older obese or overweight patients who may already have low muscle mass, also known as sarcopenic obesity, and 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. Enobosarm may potentially be combined with any GLP-1 RA. The combination of enobosarm with a GLP-1 receptor agonist represents a potential multi-billion-dollar global opportunity. We are very excited about the prospects of enobosarm to address this new and important unmet medical need.
Our oncology drug pipeline is focused on the clinical development of enobosarm, an oral, selective androgen receptor modulator designed to activate the AR in AR+ ER+ HER2- metastatic breast cancer and thereby suppress tumor growth without the unwanted masculinizing side effects. As we have prioritized our clinical programs to focus on enobosarm for obesity, the continued clinical development of enobosarm for the treatment of metastatic breast cancer is subject to the availability of sufficient funding. We completed the Stage 1a portion of our Phase 3 ENABLAR-2 clinical trial in October 2023. If sufficient funding is available, we plan to continue the Phase 3 ENABLAR-2 study, which is evaluating enobosarm 9mg in combination with abemaciclib for the treatment of AR+ ER+ HER2- metastatic breast cancer in the second line setting.
In our infectious disease program, we are developing sabizabulin 9mg, which has both host-targeted antiviral and broad anti-inflammatory properties, as a two-pronged approach to the treatment of hospitalized patients with viral lung infection at high risk for ARDS and death. We have completed positive Phase 2 and positive Phase 3 COVID-19 clinical trials, which have demonstrated that sabizabulin treatment resulted in a significant mortality benefit in hospitalized moderate to severe patients with COVID-19 viral lung infection at high risk for ARDS and death. The FDA granted Fast Track designation to our COVID-19 program in January 2022. On May 10, 2022, we had a pre-EUA meeting with the FDA to discuss next steps including the submission of an EUA application regarding sabizabulin for COVID-19. In June 2022, we submitted a request for FDA Emergency Use Authorization. In February 2023, the FDA declined to grant our request for Emergency Use Authorization for sabizabulin. In September 2023, we received positive feedback from the FDA on the design of a Phase 3 clinical trial broadly evaluating sabizabulin in any viral-induced ARDS. However, for the development of sabizabulin as a treatment for viral-induced ARDS, we will continue to seek external funding through government grants, pharmaceutical partnerships, and similar sources. Without such external funding, we do not plan to advance the development of sabizabulin as a treatment for viral-induced ARDS and will not commence our Phase 3 clinical trial to evaluate sabizabulin in viral-induced ARDS.
We currently plan to prioritize the use of the net proceeds of our recent successful financing for the development of enobosarm, with a primary near-term focus on funding the proposed Phase 2b clinical trial to evaluate the safety and efficacy of enobosarm as a treatment to augment fat loss and to prevent muscle loss in sarcopenic obese or overweight elderly patients receiving a GLP-1 RA who are at-risk for developing muscle atrophy and muscle weakness with clinical data expected in Q4 2024. We are very proud of our recent financing as we have attracted strong financial backing by high-quality biotech institutional funds.
Although we had to make hard choices in 2023, we believe we are now in a great position with the resources to advance enobosarm as an important drug to be used in combination with GLP-1 RA drugs to avoid the loss of muscle and augment the loss of fat for weight loss in the management of overweight or obese patients. The overweight and obesity market opportunity will be $100 billion by the end of the decade, and with the combination treatment with enobosarm and GLP-1 RA drugs may potentially avoid the loss of muscle and preferentially reduce fat for high quality and safe weight loss. We are looking forward to a very successful 2024.
Sincerely,
Mitchell Steiner, M.D.
Chairman, President and Chief Executive Officer