Combating Obesity: Innovative Oral Therapies Needed

In recent times, the spotlight has been on obesity treatments, particularly on injectable therapies that are based on incretins, such as GLP-1 agonists like Wegovy and Zepbound. This has underscored the urgent need for more comprehensive solutions to the global obesity crisis. The disease requires a deeper understanding, a more inclusive approach to patient diversity, and crucially, the development of new therapeutic options for the many individuals suffering from obesity who are not adequately served by current treatments.

Kallyope, a clinical-stage biotech firm, is at the forefront of this challenge, focusing on obesity as a critical chronic condition that impacts humanity on a massive scale. With over a billion people globally affected by obesity, it has become a global epidemic, contributing to 3-5 million deaths annually, as recognized by the World Health Organization.

In the United States, obesity rates have surged since the 1990s, with nearly 42% of adults and almost 20% of children now classified as obese. Obesity is linked to a range of serious health issues, including heart disease, stroke, osteoarthritis, and certain cancers. It is also the primary risk factor for the development of Type 2 diabetes mellitus (T2DM), with obese individuals facing an alarmingly higher risk of developing this condition.

Despite these alarming statistics, medical treatment for obesity in the U.S. remains limited, affecting only 2% of those affected. Challenges such as tolerability, cost, supply issues, reimbursement hurdles, and resistance to injectable treatments contribute to this low rate of treatment. There is a pressing need to discover safe, user-friendly, and well-tolerated oral medications that can effectively induce weight loss through unique mechanisms, either as standalone treatments or in combination with other therapies.

Kallyope is dedicated to pioneering new therapeutic approaches that overcome the limitations of existing treatments and meet the broader needs of patients. The company's lead clinical program is targeting obesity and T2DM, currently in Phase 2a trials for two treatment regimens: K-757 as a single therapy and a combination of K-757 and K-833. These drugs, known as oral nutrient receptor agonists, enhance the body's metabolic signals to stimulate the release of various appetite-suppressing hormones, including GLP-1 and other validated gut hormones that regulate appetite and glucose levels.

The novel mechanism of oral nutrient receptor agonists emulates the natural increase in appetite-suppressing hormones observed after bariatric surgery, leveraging the body's innate capacity to regulate appetite rather than relying on synthetic hormones. This approach is fundamentally different from the GLP-1 agonists currently available. K-757 and K-833 are the only oral nutrient receptor agonists being investigated for treating obesity, and Kallyope expects this method to offer advantages in terms of weight loss, glycemic control, ease of use, and tolerability compared to GLP-1s.

The Phase 1 clinical trials for K-757 and K-833 have already demonstrated weight loss and established proof of concept as a combination therapy for T2DM. Preclinical data also suggest that these drugs could be used in conjunction with existing GLP-1 agonists and for maintaining weight loss after GLP-1 agonist treatment.

Combating the obesity epidemic requires a multifaceted approach that extends beyond drug discovery. Understanding patient and community risk factors, implementing robust screening resources, educating the public and policymakers on the specifics of obesity, and developing new therapeutic interventions are all essential. It is crucial for healthcare professionals, scientists, insurers, and the general public to gain a better understanding of obesity and the complexities of managing it.

One of the significant challenges in treating obesity is the pervasive social stigma attached to it, with many viewing it as a "lifestyle choice" rather than a chronic disease that requires long-term medical management. Patients often lack guidance on how to effectively manage their obesity beyond general lifestyle change recommendations. There is a need to prioritize improved education on obesity for healthcare professionals and to convey the urgency of expanding obesity research.

Shifting societal perceptions of obesity is key to creating an environment where novel therapeutics can be developed and introduced effectively. By working together as an industry, we can foster a more receptive environment for combating this growing epidemic.