Highlights

1. Completely new mechanism of action：

(1) Activation of the 5-HT1F receptor could inhibit the release of CGRP, thus preventing vasodilation.

(2) Activation of the Aδ5-HT1F receptor could hyperpolarize the Aδnerve fibers and inhibit nerve transmission, thus preventing pain signaling.

(3) Has no effect on 5-HT_1B/1Dreceptor and is safer for patients with cardiovascular disease, could benefit for patients with low response to triptans (40%).

2. Pre-clinical research：

(1) Better activity and high selectivity (in vitro): the affinity of 5-HT1F is stronger than that of lamidethan in vitro, and EC50 is equivalent to that of lamidethan. High selectivity target 5-HT1F (the affinity with 1A, 1B, 2A, 2C is much lower than that with 1F).

(1) Better results shown in animal models（In vivo）：(1) The pharmacodynamics of migraine model in rats induced by electrical stimulation of trigeminal ganglion showed that the compound could significantly inhibit dural protein extravasation and c-fos expression in trigeminal caudate nucleus; (2) Efficacy studies on CGRP release induced by KCl showed that the compound could significantly inhibit the release of CGRP in dura and trigeminal caudate nucleus. (3) Efficacy of capsaicin-induced migraine in rats showed that the compound could significantly inhibit middle meningeal artery vascular dilatation; (4) In addition, efficacy studies on the tension of rabbit saphenous vein ring showed that the compound had no obvious effect on the contraction of rabbit saphenous vein ring.

3. Bright Market Prospects：

(1) The incidence of migraine in European and American countries is 10%-15%, and the incidence of migraine in China is about 9.3%.

(2) Global migraine medicine sales increased significantly in recent years, foreign markets in 2020 sales of $4.503 billion, up 27%; The migraine drug market is expected to grow significantly in the next few years to more than $11 billion, according to analysts.

Research Progress

1) Clinical Phase 1 is ongoing.