The resomelagon (AP1189) Development Program

Our Lead Program: Resomelagon (AP1189)

SynAct’s drug candidate, resomelagon (AP1189), is a once-daily oral selective melanocortin agonist. resomelagon (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 resomelagon (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. Resomelagon (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 resomelagon (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 resomelagon (AP1189) in healthy volunteers and filed additional composition patents that should provide molecule exclusivity past 2040.

In 2022, the Company initiated two new Phase 2 clinical trials in RA: EXPAND a Phase 2b trial in newly diagnosed RA patients experiencing severe disease activity and RESOLVE a Phase 2a/b trial in RA patients experiencing an incomplete or loss of response to methotrexate. In addition, the ongoing Phase 2a iMN trial was amended in 2022 to introduce the new oral tablet dosage form and to increase the treatment period to 3 months. Topline results from all three studies are expected in the second half of 2023.

Phase 1 Development

In the Phase 1 clinical assessment, 2 weeks of once-daily dosing of resomelagon (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.