A Multi-Disease Therapeutic Platform

CgA Therapeuticals is developing catestatin (CST) and next-generation CST-based peptides and peptidomimetics as potential therapeutics for diseases involving dysregulated neuroendocrine signaling, inflammation, metabolism, gastrointestinal function, cardiovascular homeostasis, and neurodegeneration.

CST is an endogenous regulatory peptide with pleiotropic biological actions. Rather than acting on a single disease-associated target, CST influences multiple interconnected pathways involved in maintaining physiological homeostasis. This provides the scientific foundation for a platform-based therapeutic strategy spanning several areas of unmet medical need.

Gastroparesis and Gastrointestinal Disorders

Gastroparesis is currently a major translational focus of CgA Therapeuticals. Preclinical studies have identified CST and optimized CST derivatives as potential therapeutic candidates for restoring impaired gastric function.

This program is now supported by an NIH/NIDDK SBIR Phase I award (1R43DK148298-01), “Peptide and Peptidomimetic Therapy for Gastroparesis.” The project is advancing CST-based candidates through preclinical efficacy, dose-response, pharmacokinetic, safety, and therapeutic-development studies.

The objective is to identify an optimized CST-based therapeutic candidate capable of providing sustained improvement in gastric function while overcoming limitations associated with native peptide stability and duration of action.

Alzheimer's Disease and Related Neurodegenerative Disorders

CgA Therapeuticals is also developing CST-based therapeutics for Alzheimer's disease and related tauopathies.

Preclinical studies indicate that CST acts on several major processes associated with neurodegeneration, including abnormal Tau phosphorylation and aggregation, amyloid pathology, neuroinflammation, and dysregulated adrenergic signaling. In experimental models, CST treatment has also been associated with improvements in cognitive and motor function.

These findings provide the foundation for developing CST and next-generation CST analogs as multi-pathway therapeutic candidates designed to address both proteinopathy and the inflammatory and neurochemical mechanisms that contribute to neurodegenerative disease progression.

Cardiometabolic Disease

The CST therapeutic platform originated from discoveries demonstrating the peptide's important roles in blood-pressure regulation, glucose and lipid metabolism, insulin sensitivity, inflammation, and cardiovascular homeostasis.

Preclinical studies have shown that CST can reduce elevated blood pressure, improve glucose tolerance and insulin sensitivity, promote lipid utilization, reduce hepatic lipid accumulation, and attenuate inflammatory responses.

These findings support continued development of CST-based therapeutics for hypertension, obesity, diabetes, and associated cardiovascular and metabolic disorders.

Oncology and Emerging Applications

The CST platform is also being investigated in oncology and other disease areas in which metabolic dysregulation, inflammation, cellular stress, and altered signaling contribute to disease progression.

These emerging programs broaden the potential therapeutic applications of CST, its peptidomimetics, and related small-molecule approaches and form part of CgA Therapeuticals' expanding intellectual property and discovery portfolio.

Advantages of Next-Generation CST Therapeutics

Native CST has potent biological activity but, like many endogenous peptides, has a relatively short circulating half-life. CgA Therapeuticals is therefore developing next-generation CST analogs and peptidomimetics designed to improve stability, pharmacokinetics, therapeutic exposure, and dosing characteristics.

One lead candidate is retro-inverso CST (RI-CST), in which sequence reversal combined with D-amino-acid stereochemistry provides increased resistance to proteolytic degradation. Our preclinical studies demonstrate that RI-CST has a substantially prolonged pharmacokinetic profile compared with native CST while retaining biological activity.

The broader development platform includes native CST, naturally occurring human CST variants, RI-CST, D-amino-acid derivatives, and additional peptide and peptidomimetic candidates. Candidate selection is based not simply on stability, but on an integrated assessment of biological activity, efficacy, pharmacokinetics, safety, tissue exposure, manufacturability, and formulation potential.

From Preclinical Discovery Toward Clinical Translation

CgA Therapeuticals' development strategy is designed to systematically advance promising CST-based candidates from preclinical proof-of-concept through lead optimization, pharmacology and toxicology, formulation and manufacturing development, and ultimately regulatory evaluation for human clinical studies.

The company's recently executed exclusive therapeutic license covering defined UC San Diego patent rights provides an intellectual-property foundation for development and commercialization of CST-related therapeutic technologies. The license encompasses inventions in cardiometabolic disease, neurodegeneration and cognitive decline, and oncology, subject to its terms and applicable government rights.

The license's development framework also anticipates progression through preclinical toxicology and manufacturing development toward IND submission and subsequent clinical development.

CST, RI-CST, and other CST-based therapeutic candidates are investigational. They have not been approved by the U.S. Food and Drug Administration for the treatment of gastroparesis, Alzheimer's disease, cardiometabolic disease, cancer, or any other condition.