Peptides are making an impact in a wide range of applications including Alzheimer’s disease, diabetes, cancer and the treatment of infections. Chemists have applied innovative approaches to peptides in order to broaden their applicability as therapeutics. For example, the clinical pipeline of peptides includes peptides with more than one pharmacological activity such as dual agonists or multiple biological functions such as antimicrobial peptides that heal wounds and stimulate the immune system. In addition, there is an increase in the development of oral formulations that offer increased patient compliance and ease of administration.

Alzheimer’s disease

AD is a global concern with an estimated 50 million people living with AD or other dementias worldwide. An increasing prevalence of AD, advances in diagnostic capabilities and heightened awareness of the disease are projected to expand the need for AD treatments (1). Amyloid β peptide has become an important therapeutic target in AD and tau-based therapies have raised interest. Companies such as Araclon Biotech, Axon Neuroscience and AC Immune have focused on this area and amyloid β peptide vaccines and tau peptide containing candidates have reached clinical development.

Araclon Biotech is developing ABvac40, an immunotherapy for AD that uses the C-terminal fragment of the amyloid β 40 peptide as an immunogen. In 2018, the company announced a partnership with TFS International to bring ABvac40 into Phase II. In addition, Araclon Biotech is developing amyloid β peptide (1-42), ABvac42, as a therapeutic vaccine for Alzheimer’s disease. ABvac42 is in Phase I stage of development (2).

Axon Neuroscience is developing AADvac1, a vaccine containing a peptide fragment, amino acids 294 to 305 of the tau sequence, coupled to KLH. Axon Neuroscience’s vaccine is designed to stimulate patients’ immune systems to attack dysfunctional tau proteins and thereby stop the progression of AD. In 2020, the company reported positive results of the Phase II trial of AADvac1 indicating that the vaccine prevents further neuronal damage in patients and maintains levels similar to those more typically observed in healthy elderly individuals (2).

ACI-24 is a liposome-based vaccine under development by AC Immune. The vaccine contains Aβ peptide (1-15) and is designed to produce beta-sheet conformation-specific antibodies that prevent plaque deposition or enhance clearance. In 2018, the company initiated a Phase II study of ACI-24 in patients with mild AD. AC Immune is also developing ACI-35, a Phase II candidate targeting tau. ACI-35 is a liposomal vaccine containing a phosphorylated human tau protein fragment. In 2015, AC Immune partnered with Janssen Pharmaceuticals to develop ACI-35 and the vaccine is currently in a Phase Ib/IIa clinical study in patients with mild to moderate AD (2).

Diabetes

There are currently 30 synthetic peptide drug candidates in Phase I to pre-registration for diabetes. The most advanced candidate is ITCA-620, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, which is under development by Intarcia Therapeutics for the treatment of type 2 diabetes. Eli Lilly and Co is developing tirzepatide, a dual GLP-1 and Gastric Inhibitory Peptide (GIP) receptor agonist, which is in Phase III of development for the treatment of type 2 diabetes and obesity. Tirzepatide is also in Phase II stage of development for non-alcoholic steatohepatitis (NASH). Additional peptide candidates are in Phases I and II for the treatment of diabetes as shown in Figure 1.