Many metabolic disorders such as obesity or type 2 diabetes are associated with perturbations of the enteroendocrine response resulting from an unbalanced diet, sedentary lifestyle, genetic or other environmental factors. Current treatments only partially address the underlying disease pathology or cause side effects that may limit treatment eligibility or long-term use.


Our goal is to restore metabolic balance to prevent and treat metabolic diseases while doing so with natural and safe treatment alternatives that can be applied to broad populations and enable long-term use.

Individuals with healthy enteroendocrine systems have a balanced nutrient absorption, where an excess of nutrients not absorbed in the upper parts of the small intestine (i.e., duodenum and proximal jejunum) stimulates nutrient-sensing endocrine cells and their broad repertoire of signaling mechanisms (i.e., endocrine, neuroendocrine and neuronal) in the distal parts of the small intestine (i.e., distal jejunum and ileum). The broad portfolio of mechanisms (including the release of incretin hormones) regulates various homeostatic functions like appetite and metabolic activity.

Healthy enteroendocrine system

In patients with reduced enteroendocrine responses, an almost complete absorption of nutrients occurs in the upper parts of the small intestine following food intake, promoted by the highly refined nature and slow passage of food, which deprives distal nutrient-sensing cells from contact with food. This leads to a lack of endocrine, neuroendocrine and neuronal stimulation, which derails metabolic homeostasis and promotes the progression of metabolic diseases.

Reduced enteroendocrine responses


We have developed proprietary drug formulations that enables targeted delivery of natural compounds to discrete parts of the digestive tract to restore nutrient-sensing signaling pathways that stimulate the endogenous release of metabolically active hormones.

  • Natural and targeted: Coated bead formulations are designed to transport natural substances and release their cargo at pre-determined discrete parts of the small intestine. The strict limitation to natural substances as cargo should translate into excellent safety profiles.
  • Reproducible and reliable: Coated beads enablehighly reproducible transit patterns with low inter-individual variability, translating into treatment reproducibility and reliability (has already been demonstrated with APH-012).
  • Versatile: Coated beads are designed to enable variations in cargo formulations and target areas of the intestine, with the potential to address multiple indications.


Aphaia’s lead candidate, APH-012, is an oral glucose formulation designed to be released at discrete parts of the small intestine to stimulate nutrient-sensing cells and induce endocrine, neuroendocrine and neuronal signaling pathways that control multiple homeostatic and metabolic functions like appetite, hunger, satiety, glucose metabolism, energy expenditure, etc.

By design of the beads, the glucose released from APH-012 is not absorbed in the upper parts of the small intestine and is not systemically available, which is a key safety feature in general but particularly in diabetic patients.

APH-012 Mechanism of Action


In a Phase 1 trial in individuals with obesity, targeted release of glucose with 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.

This effect has not previously been achieved with any other drug-based therapy, as incretin-based therapies only partially correct the endocrine deficiency and induce unphysiological serum concentration peaks of hormones that lead to side effects that limit long-term use [i].

The levels of hormones released by APH-012 were comparable to those measured after ROUX-Y Gastric Bypass surgery (RYGB). RYGB is the only treatment solution at present that addresses the underlying condition of obesity but with massive side effects, that negatively impact quality of life, well-being and prognosis.

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

APH-012’s Competitive Advantage

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[i] Chou C-Y, Chang Y-T, Yang J-L, et al. Effect of long-term incretin-based therapies on ischemic heart diseases in patients with type 2 diabetes mellitus: A network meta-analysis. Scientific Reports. 2017;7(1). doi:10.1038/s41598-017-16101-1