The AP1189 Development Program

Our Lead Program: AP1189

SynAct’s drug candidate, AP1189, is a once-daily oral selective melanocortin agonist. AP1189 selectively stimulates the melanocortin receptors that are directly involved in inflammation and its resolution without stimulating the adrenal glands to release cortisol. This selectivity enables AP1189 to exert its anti-inflammatory and immune resolution effects in a steroid-free manner without the significant safety, tolerability, and side effect issues associated with adrenocorticotropic hormone (ACTH) based therapies. AP1189 is also a biased agonist that does not stimulate melanocortin pathways that are responsible for off-target activity like skin hyperpigmentation.
The company is evaluating AP1189 in three Phase 2 clinical programs: rheumatoid arthritis (RA), idiopathic membranous nephropathy (iMN), a form of nephrotic syndrome, and virus-induced respiratory insufficiency (VIRI) like that seen in COVID-19. In 2021, SynAct successfully completed Phase 2a trials in early severe RA and in hospitalized patients with COVID-19-induced respiratory insufficiency. Also in 2021, SynAct successfully tested a new oral solid tablet formulation of AP1189 in healthy volunteers and filed additional composition patents that should provide molecule exclusivity past 2040.

In 2022, SynAct has initiated a Phase 2b trial in treatment naïve RA-patients and intend to start an additional Phase 2b trials in RA, which will be under a new US FDA IND that is in the process of being established. SynAct has also amended the iMN study protocol to allow for the use of the new oral solid tablet formulation and to increase the study duration from 1 month to 3 months which is enabled by the extended toxicology work conducted in 2021.

Phase 1 Development

In the Phase 1 clinical assessment, 2 weeks of once-daily dosing of AP1189 supported continued development as a once-daily orally dosed medication. The plasma concentration needed induce pharmacological efficacy was reached within 1.5 hours of dosing and daily exposure is increased until steady state has been reached following 5-6 days of treatment after which no further drug accumulation was observed.

Importantly, no treatment limiting adverse events were identified following multiple dosing and doses used in the ongoing Phase 2a studies (50 and 100 mg) were found to be safe and well tolerated. Read more in ACR 2021 Abstract.