The AP1189 Development Program

Our Lead Program: AP1189

SynAct’s lead 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) and steroid therapies. AP1189 is also a biased agonist that does not stimulate melanocortin pathways that are responsible for off-target activity like skin hyperpigmentation.

AP1189 is currently being tested in 2 Phase 2a clinical proof of concept (POC) trials in rheumatoid arthritis (RA), and in idiopathic membranous nephropathy (iMN, an autoimmune disease associated with the development of nephrotic syndrome), both of which are expected to readout by year-end. SynAct recently completed a P2a POC trial in COVID-19 infected patients to speed the time to respiratory recovery and prevent severe acute respiratory stress syndrome (ARDS) and the results were encouraging for further development. Read more about the results here.

With all 3 phase 2a POC trials are expected to be completed in this year, 2021 is an exciting year for SynAct and AP1189 and bringing us closer to our goal of helping patients resolve debilitating inflammation.

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 was 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.