Aphaia Pharma Announces Positive Results from Phase 2 Trial Evaluating its Lead Drug Formulation for Prediabetes Treatment

• Primary endpoint met, showing that APHD-012 improves glucose tolerance in individuals with a pathological oral glucose tolerance test (OGTT) after 6 weeks of administration
• The results provide proof-of-concept for clinical efficacy of Aphaia’s oral glucose formulation, designed to restore endogenous nutrient-sensing pathways in the gastrointestinal tract
• The study confirms that APHD-012 is well tolerated, with no serious adverse events observed
• Additional results from a Phase 2 trial evaluating Aphaia’s formulation in individuals with obesity are expected in H2 2024

ZUG, Switzerland, SAN JUAN, Puerto Rico and TORONTO, June 20, 2024 (GLOBE NEWSWIRE) — Aphaia Pharma, a clinical-stage company harnessing precision-targeted drug formulations to restore endogenous endocrine balance for the treatment of obesity and associated metabolic diseases, today announced that its Phase 2 trial evaluating the company’s lead oral glucose formulation for prediabetes treatment met its primary endpoint. The trial showed a statistically significant improvement in glucose tolerance in individuals with a pathological Oral Glucose Tolerance Test (OGTT) after 6 weeks of APHD-012 administration compared to placebo, with a positive safety profile.

“We are excited to demonstrate for the first time that the mechanism of action of APHD-012 translates into clinical efficacy,” said Steffen-Sebastian Bolz, M.D., Ph.D., chief scientific officer of Aphaia Pharma. “In addition to showcasing the potential of our oral glucose formulation to manage prediabetes progression, it also underscores its promise to deliver clinical benefits across various indications (e.g., diabetes, obesity, among others), given its mechanism of action in restoring natural hormone release patterns in the intestine. We look forward to analyzing the upcoming data from our ongoing Phase 2 trial of APHD-012 in individuals with obesity and associated metabolic diseases to determine the best strategic path forward.”

Christian Sina, M.D., professor of Medicine at University of Luebeck, director of the Institute of Nutritional Medicine at UKSH, Germany, and principal investigator of the trial, added, “I am highly impressed with the data. It marks the first instance of a drug demonstrating effectiveness in OGTT with a positive safety profile, which is crucial for a medication aimed at disease prevention. Preventing diabetes is a priority in healthcare programs due to the significant health and economic burden associated with this disease. Despite efforts in diet and exercise, effective therapies to prevent or delay the onset of type 2 diabetes are currently lacking, posing a challenge for individuals who do not respond to lifestyle changes. I eagerly anticipate supporting the next steps for the program, which has the potential to open a new avenue for prediabetes treatment.”

Key Trial Results include:

• In a group of healthy, prediabetic and diabetic patients, APHD-012 (6 weeks treatment) reduced OGTT blood glucose levels at 120 minutes post-challenge from 9.00.6 to 7.90.6 mmol/L (n=23, p=0.01); placebo treatment in the same patients had no significant effect (8.80.4 mmol/L versus 8.50.6 mmol/L; p=0.33)
• A subgroup analysis appears to show that APHD-012 has a larger effect size in prediabetic patients (8.70.4 to 6.80.5 mmol/L; n=12, p=0.003); placebo had no significant effect in this subgroup (8.60.4 versus 8.20.6 mmol/L; p=0.25).
• In a further analysis of prediabetic patients, APHD-012 treatment reduced OGTT area under the curve (AUC 0-120 minutes) from 126147 to 116336 min*mmol/L (p=0.004, n=12); the placebo treatment had no significant effect on AUC in this subgroup (125045 to 122553 min*mmol/L; p=0.47).
• In all diabetic patients included, APHD-012 treatment reduced OGTT blood glucose levels at 120 minutes post-challenge (from 13.20.7 to 11.60.5 mmol/L; n=5, p=0.0006); placebo was not effective in this group (11.40.5 versus 12.00.6 mmol/L; p=0.59).
• A total of 13 adverse events (AEs) were reported for 8 subjects (27%) during the 6 weeks of APHD-012 treatment, while 7 AEs were reported for 5 subjects (17%) taking placebo treatment; no serious AEs occurred during the course of the study.

The Phase 2 trial (NCT05803772) (EudraCT 2022-003205-29) was a randomized, double-blind, placebo-controlled, multi-center proof-of-concept study that evaluated the safety and efficacy of APHD-012 (12g dose of Aphaia’s oral glucose formulation) in approximately 30 adults with prediabetes, diabetes or healthy individuals in a cross-over design. Patients were randomized to receive a once daily dose of either APHD-012 or APHD-012P, a matching placebo, for six weeks, followed by a washout period of 4 weeks, and subsequent crossover to the other opposite treatment arm for another 6 weeks. The primary endpoint of the trial is APHD-012’s ability to improve glucose tolerance in individuals with a pathological oral glucose tolerance test (OGTT) after 6 weeks of administration. The Oral Glucose Tolerance Test (OGTT) is a diagnostic test used to assess how well the body processes glucose by measuring blood glucose levels after consuming a glucose-rich drink. In individuals with diabetes and prediabetes, blood glucose levels are higher than normal due to their inability to metabolize glucose effectively.

About Prediabetes
Prediabetes is a serious health condition where blood sugar levels are elevated but not yet in the type 2 diabetes range. Prediabetes is becoming increasingly common and affects more than 10% of the population in Europe, the U.S. and Asia. Individuals with prediabetes are at increased risk of developing type 2 diabetes or associated complications, such as stroke or cardiovascular disease. While lifestyle changes can help prevent the progression from prediabetes to diabetes, there is a clear medical need for new therapeutic approaches to help control disease evolution before diabetes, cardiovascular disease and other metabolic disorders manifest.

About Aphaia’s drug candidate
Aphaia’s lead drug candidate is a proprietary oral glucose formulation designed to be released at discrete parts of the small intestine to restore endogenous nutrient-sensing signaling pathways and stimulate the release of the broad spectrum of enteric hormones that control multiple homeostatic functions like appetite, hunger, satiety, glucose metabolism and energy expenditure. This includes glucagon-like-peptide 1 (GLP-1), peptide tyrosine-tyrosine (PYY), glicentin and oxyntomodulin (OXM) among others.

About Aphaia Pharma
Aphaia Pharma is a clinical-stage biopharmaceutical company with headquarters in Switzerland, Canada and Puerto Rico. It harnesses proprietary precision-targeted drug formulations to restore endogenous hormone release from nutrient-sensing cells in the gastrointestinal tract to treat and prevent metabolic disorders such as obesity and associated diseases. Aphaia’s lead drug candidate, an oral glucose formulation, has been shown to safely restore endogenous hormone release in individuals with obesity. It is being evaluated in two Phase 2 trials, one for chronic weight management in individuals with obesity and the second to improve glucose tolerance in individuals with prediabetes. The versatile design of Aphaia’s technology platform provides an opportunity for the development of treatments for multiple disease patterns.

Aphaia Investor Contact
Günter Jucho
Chief Financial Officer
jucho@aphaiapharma.com

Media Contact
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LifeSci Communications
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