Shots: 

• Steffen shared the details of the first patient enrolled in the P-II study of Aphaia Pharma’s lead product APH-012 to induce weight loss in individuals with obesity 

• He briefed the PharmaShots team about the study design of the P-II trial and also elaborated on the results from the P-I study

• The interview shows how Aphaia Pharma is working to develop targeted drug-delivery technologies for the treatment and prevention of metabolic diseases 

Smriti: Please provide some details about your lead product APH-012 (its MOA, ROA, formulation, pathway, etc.) and how it differentiates from other drugs available or in development for the treatment of obesity.  

Steffen-Sebastian Bolz: APH-012 is a proprietary oral glucose formulation as part of a coated bead designed to be released at discrete parts of the small intestine to stimulate nutrient-sensing cells and restore hormonal and neuronal signaling pathways that control appetite, hunger, satiety, and glucose metabolism.  

We are currently developing APH-012 for the treatment of metabolic disorders such as obesity and pre-type 2 diabetes. Many of these metabolic disorders are associated with perturbations of hormonal balance resulting from an unbalanced diet, sedentary lifestyle, genetic or other environmental factors. In these patients, almost complete absorption of nutrients occurs in the upper parts of the small intestine following food intake, promoted by the highly refined nature and the slow passage of food, depriving the nutrient-sensing cells in the distal portions of the intestine of contact with food. This leads to a lack of key hormone release, which derails metabolic homeostasis and promotes the progression of disease. 

Current treatments for people with obesity only partially address the underlying disease pathology by supplementing the missing hormones or aggressive surgical procedures such as bypass surgery. As such, they cause side effects that may limit treatment eligibility or long-term use. 

APH-012 is designed to restore metabolic balance for patients by stimulating the simultaneous release of a diverse portfolio of endogenous metabolically active hormones to restore a healthy metabolism. 

Smriti: Give our readers a brief about the study design of the P-II Trial evaluating APH-012 in patients with obesity 

Steffen-Sebastian Bolz: The ongoing Phase 2 proof-of-concept study is evaluating APH-012 in 150 patients with obesity in several sites in the U.S. and Germany. Patients will receive a once-daily oral dose of either APH-012 or placebo prior to main daily meals for 6 or 12 months. While the primary endpoint of the trial is the change from baseline in percent weight compared to placebo, the study will evaluate exploratory secondary endpoints, which are hallmarks of multiple metabolic diseases closely associated with obesity. These include waist circumference, blood pressure, heart rate, triglyceride levels, cholesterol, and fasting plasma glucose levels, among others. Should trial outcomes be positive, this design will help expedite pipeline expansion into other metabolic disease indications with high unmet medical needs.  

Smriti: What results are you expecting from the APH-012 Phase 2 trial? 

Steffen-Sebastian Bolz: Given APH-012’s mechanism of action and Phase 1 results demonstrating its ability to restore a broad spectrum of enteric hormones, we hope to see a significant reduction in body weight and an improvement in the other secondary endpoints compared to those who received the placebo. In addition, given the natural aspect of APH-012, we expect to see a positive safety profile, similar to the Phase 1 trial.   

Smriti: Please elaborate on your results obtained from the Phase 1 study 

Steffen-Sebastian Bolz: Our phase I clinical trial showed that APH-012 safely restored endocrine balance and improved metabolic health in the 20 people with obesity who participated. APH-012 induced therapeutically relevant release of a broad spectrum of enteric hormones, including glucagon-like-peptide 1 (GLP-1), peptide tyrosine-tyrosine (PYY), glicentin and oxyntomodulin (OXM) among others. 

The onset and release kinetics were similar for all hormones, suggesting simultaneous release. Approximately 70% of patients reached their maximal GLP-1 response between 2.5 and 3.5 hours, indicating targeted glucose release. Glucose released from APH-012 was not absorbed and did not induce adverse events. 

This effect has not previously been achieved with any other drug-based therapy, as hormone-based therapies only partially correct the endocrine deficiency and induce unphysiological serum concentration peaks of hormones. The hormones released by APH-012 were comparable to those measured after ROUX-Y Gastric Bypass surgery (RYGB). Currently, RYGB is the only treatment solution that addresses the underlying condition of obesity, but with massive side effects that negatively impact the quality of life, well-being and prognosis.  

Treatment with APH-012 did not induce any adverse events that differed from those in the placebo group. As such, it has the potential to mimic the metabolic effects of bypass surgery without adverse effects. 

Smriti: What are the other indications for which APH-012 is being assessed? 

Steffen-Sebastian Bolz: We are working to initiate an additional Phase 2 trial evaluating APH-012 in patients with prediabetes by Q4 2022. The trial will assess the ability of APH-012 to improve glucose tolerance in individuals with a pathological Oral Glucose Tolerance Test (OGTT) after 6 weeks of APH-012 administration. In parallel, we continue to explore new indications for APH-012 and expansion into new age groups, such as children, to drive pipeline growth.  

In addition, our beads are versatile. They are designed to enable variations in cargo formulations and target areas of the intestine. Aphaia continues to create additional bead formulations to broaden its product portfolio to potentially enhance treatment efficacy for other metabolic diseases and patient populations in the future.  

Source: Canva 

About the Author: 

Steffen-Sebastian Bolz is a scientist, physician, and entrepreneur. He is the Co-Founder and Chief Scientific Officer (CSO) of Aphaia Pharma and the Founder, CSO, and Chief Medical Officer (CMO) of Qanatpharma. Dr. Bolz holds a full professorship at the University of Toronto, is a Principal Investigator at the Ted Rogers Centre for Heart Research, and is the Director of the Toronto Centre for Microvascular Medicine. His research program has contributed novel signaling paradigms, and methodological advancements and validated innovative molecular/therapeutic targets in the emerging field of microvascular medicine. Dr. Bolz holds a medical degree and a doctorate from the universities of Lübeck and Munich, Germany. 

Related Post: Suresh Kannan, Chief Product Officer at Model N Shares Insights on the Fall 2022 Product Release of the Model N Revenue Cloud