Over the past year, obesity treatments have become the focus of intense media attention and discussion in healthcare — with increased focus on Wegovy and Zepbound. This attention has highlighted the need to address the global obesity epidemic.
Over the past year, obesity treatments have become the focus of intense media attention and discussion in healthcare — particularly incretin-based injectable therapies including glucagon-like peptide-1 (GLP-1) agonists such as Wegovy and Zepbound. This attention has highlighted how much more is needed to address the global obesity epidemic: a greater understanding of the disease, a broader focus on the diversity of the patient population, and most of all, the great need for new therapeutic classes that can benefit the many underserved patients living with obesity.
As a clinical-stage biotechnology company discovering and developing novel, oral small-molecule therapeutics for diseases with high unmet needs, Kallyope has a major focus on obesity as one of the most significant chronic health conditions currently facing humanity. With estimates that more than one billion people around the world are currently living with obesity, the disease is linked to 3-5 million deaths per year and is now classified as a global epidemic by the World Health Organization.
In the United States alone, the prevalence of obesity — defined as an individual with a body mass index (BMI) of 30 kg/m2 or more — has increased significantly since the 1990s, with 41.9 percent of adults and 19.7 percent of children currently considered obese. The health consequences are enormous: obesity is a risk factor for conditions including heart disease, stroke, osteoarthritis and certain types of cancer, and is the leading risk factor for developing Type 2 diabetes mellitus (T2DM), with obese people more than 80 times more likely to develop the disorder than individuals with a BMI of 22 or less.
Despite these staggering numbers, it is estimated that only two percent of people with obesity in the United States receive medical treatment with therapeutics, due in part to limitations such as tolerability, cost, supply disruptions, reimbursement, and patient and practitioner resistance to the use of injectables. In this regard, to address this massive unmet need, there is an imperative to identify safe, easy-to-use, well-tolerated oral agents that are effective for weight loss through differentiated mechanisms of action - both as stand-alone medicines and in combination with other drugs. New therapies with the potential to deliver meaningful weight loss and glycemic efficacy will help enable the widespread treatment needed to have a material impact on public health.
Kallyope is focused on innovative approaches to developing therapeutics that can address the limitations of current treatments and meet patients’ needs more broadly. The company’s lead clinical development program is focused on obesity and T2DM and is currently in a Phase 2a clinical trial evaluating two therapeutic regimens - K-757 as a monotherapy, and K-757 and K-833 in combination. K-757 and K-833 are drugs known as oral nutrient receptor agonists, which enhance the body’s natural metabolic signals to stimulate the secretion of multiple appetite-suppressing satiety hormones, or incretins. These include GLP-1, and several other well-validated gut hormones capable of regulating appetite and glucose, such as glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), Peptide YY (PYY), and oxyntomodulin (OXM), the latter of which is known to increase energy expenditure. The mechanism of action for oral nutrient receptor agonists mimics the increase of the natural appetite-suppressing hormones that is seen after bariatric surgery – leveraging the body’s natural capacity to regulate appetite (vs. synthetic hormones), which is fundamentally different from the GLP-1 agonists now on the market. K-757 and K-833 are the only known oral nutrient receptor agonists being studied for the treatment of obesity, and Kallyope anticipates that this approach will be beneficial for both weight loss and glycemic control and may be easier to take and better tolerated vs. GLP-1s.
The Phase 1 clinical program for K-757 and K-833 demonstrated weight loss and established proof of concept as a combination therapy for T2DM. Preclinical data also support the potential for K-757 and K-833 to be used in combination with existing GLP-1 agonists and for weight loss maintenance following GLP-1 agonist treatment.
As there is no one-size-fits-all therapeutic approach capable of stopping the obesity epidemic, these results mark an encouraging milestone in treating patients more comprehensively. The population of people living with obesity is highly diverse and only beginning to be understood, and it is essential to have differentiated options available to address patients’ varying needs.
Still, there is more that must be done, as this is an epidemic in need of innovative solutions that go well beyond drug discovery. Understanding patient and community risk factors, implementing rigorous screening resources, educating the public and policymakers on the specifics of the condition, and new therapeutic interventions will all be critical in fighting the obesity epidemic. It is vital for physicians, scientists, insurers and the general public to have a better insight into what obesity is and why it is so difficult to manage. One of the greatest challenges in treating obesity is the immense social bias against people who have it, with people thinking of the disease as a “lifestyle choice” that reflects negatively on those living with it, rather than as a chronic disease like diabetes or high blood pressure, where long-term medical management may be appropriate. Beyond the standard recommendation for lifestyle changes, patients are often left with little to no guidance on how to materially address their obesity. It is important to prioritize improved education on obesity for healthcare professionals and convey a sense of urgency in expanding obesity research.
Changing our society’s perception of obesity is the key here. If, together as an industry we can accomplish that, we will create an environment receptive to the development and introduction of novel therapeutics in which our efforts to combat this growing epidemic can be most effective.
Sponsored content is written and provided to BioSpace by the advertiser. It is published with the advertiser’s approval without contribution from BioSpace’s editorial and insights teams.
