In this discussion with Steffen-Sebastian Bolz, MD, PhD, we explore Aphaia’s groundbreaking work in obesity treatment. With his dual expertise in clinical and molecular biology, Dr. Bolz shares insights on Aphaia’s novel oral coated glucose formulation. This innovative approach has the potential to transform current treatment paradigms by emphasizing physiological mechanisms and minimizing side effects.
Moe: What role does Aphaia’s approach play in the obesity treatment landscape?
Aphaia’s approach is fundamentally different from traditional hormone therapies like GLP-1 agonists, which often require high doses and can lead to significant side effects. These therapies act like a “bulldozer,” disrupting the body’s natural rhythms and causing adverse effects such as nausea and vomiting. In contrast, our method leverages glucose, the most prevalent biomolecule, to naturally stimulate the body’s natural hormone production. By delivering glucose to the distal small intestine, we activate enteroendocrine cells to release a balanced mix of hormones beyond GLP-1 agonists. These hormones engage endocrine, neuroendocrine, and neuronal signaling pathways to deliver a broad range of metabolic and behavioral effects, including control of hunger, satiety, and glucose metabolism, among others. Our physiological
approach mimics the body’s natural response to food, resulting in minimal side effects, as demonstrated in multiple trials to date. This allows for repetitive daily administrations and precise timing of drug intake to help retrain metabolic circadian rhythms – an approach believed to positively influence metabolic health and support weight loss. We trust that this innovative multilayered approach constitutes an effective, sustainable, and patient-friendly treatment modality. Initial signals from our Phase 2 trials confirm this positioning, highlighting our approach as a promising new alternative in the obesity treatment landscape.
Additionally, our coated glucose formulation would be highly accessible to patients since the components are economical, the synthesis is relatively simple, and the formulation’s production is easily scalable.
Moe: How might this therapy alter the approach to preventing pre-diabetes progression?
Our trials have shown that Aphaia’s formulation significantly improves glucose tolerance in pre-diabetic patients, with results comparable to long-term lifestyle interventions and GLP-1 mimetics. This is achieved by engaging the full spectrum of enteric hormones, not just GLP-1, which allows for a more comprehensive metabolic regulation. Given its safety profile and ease of use, this formulation could be widely adopted for early intervention in pre-diabetic individuals, potentially preventing the progression of type 2 diabetes. It’s a shift towards a preventive model in healthcare, focusing on maintaining metabolic health rather than just managing disease symptoms. The formulation’s simplicity—requiring only a sachet mixed with water to form a gel—makes it accessible and easy to integrate into daily life, which is crucial for widespread adoption. Moreover, the inherent potential to treat young children, who currently have limited options, could be a game-changer in addressing obesity from an early age.
Moe: How does targeted glucose release affect hormone secretion and metabolic regulation?
The targeted release of glucose in the distal jejunum allows us to stimulate nutrient-sensing intestinal cells to induce the release of a broad range of hormones, including GLP-1, GLP-2, and PYY, in their natural proportions. This orchestrated hormone release acts on multiple organs to regulate metabolism and behavior effectively. By using the body’s highly optimized physiological pathways, we aim to achieve significant metabolic benefits without the adverse effects associated with synthetic hormone therapies. This method was designed to support weight loss and enhance insulin sensitivity and overall metabolic health. The analogy of an orchestra is fitting here; while traditional therapies focus on a single instrument, we engage the entire ensemble, hoping to create a harmonious and effective metabolic response.
Moe: What are the key design elements of your phase two trial for obesity?
Our trial design is ambitious, focusing on obesity as an umbrella term to include various comorbidities like type 2 diabetes, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). This setup also allows us to explore how these conditions interact with weight loss. We’ve incorporated a bi-daily application scheme of the formulation to harness circadian effects and further enhance efficacy. The trial’s comprehensive approach has already generated lots of data to inform our future studies and helped us refine ou therapy with the aim to maximize efficacy while keeping risks minimal. We believe this positions us well to address the broader challenges in obesity treatment by offering a more holistic and patient-centered solution. The trial’s design reflects our commitment to understanding the complex interplay of metabolic factors and tailoring our approach to meet the diverse needs of patients suffering from metabolic diseases, including obesity. We aim to achieve weight loss and improve overall health outcomes and might add a new paradigm to the obesity treatment research landscape.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
