Annexon planning proof-of-concept study of ANX1502 for CAD this year

A Phase 1 trial testing Annexon Biosciences’ oral treatment candidate ANX1502 — for complement-mediated autoimmune disorders such as cold agglutinin disease (CAD) — in healthy volunteers has moved to its multiple-dosing phase.

The company is planning to launch a proof-of-concept study of ANX1502 in people with CAD later this year.

“We’re prioritizing our focus and resources on well-supported, value creating programs, including … our potentially paradigm-shifting oral small molecule, ANX1502, for autoimmune indications,” Douglas Love, president and CEO of Annexon, said in a company press release.

Cold agglutinin disease is an autoimmune disorder in which the immune system attacks and destroys red blood cells that are needed to carry oxygen through the bloodstream. The classic complement pathway — a group of inflammatory proteins that are part of the immune system — are overactive in CAD.

C1q is the initiating molecule of the classical complement pathway that activates a powerful inflammatory cascade. In previous work, Annexon showed that blocking C1q with its experimental antibody-based therapy ANX005 reduced red blood cell destruction in blood samples from CAD patients.

ANX005, which is delivered directly into the bloodstream (intravenously), is now in development for the treatment of other diseases where the classical complement cascade plays a role. These include the neurodegenerative condition Huntington’s disease, and Guillain-Barré Syndrome, a neurodegenerative and autoimmune disorder.

Annexon also is testing ANX1502, a next-generation, orally-available small molecule that’s designed to block the activation of the classical complement pathway. The company is developing this treatment candidate for CAD and other complement-mediated autoimmune diseases.

We’re prioritizing our focus and resources on well-supported, value creating programs, including … our potentially paradigm-shifting oral small molecule, ANX1502, for autoimmune indications.

The ongoing two-part Phase 1 trial (NCT05521269) in healthy people primarily aims to evaluate the safety and pharmacological properties of ANX1502. It also is seeking to identify the maximum tolerated dose — that is, the highest dose of the therapy that can be given without unacceptable side effects.

Volunteers are being recruited at a site in the Netherlands. The study is open to individualsm ages 18 to 60, without any underlying health problems, who are up to date on their vaccinations.

In the first single-dosing part, participants are randomly assigned to receive a single dose of either ANX1502 at one of several dose levels or a placebo.

The therapy has so far been well-tolerated in this part of the study, according to Annexon, with no dose-limiting safety issues. The effects of food on the therapy’s pharmacological properties also will be assessed.

In the second multiple-dosing part, participants are being given either multiple doses of ANX1502 or a placebo, twice a day, for two weeks. This part of the Phase 1 trial has already begun to dose participants, the company noted.

“2022 was a year of focused execution at Annexon, establishing a strong foundation on which to drive near- and long-term value across our deep portfolio of complement therapeutics,” Love said, adding, “We expect this year to be even stronger for Annexon.”

The company is “well-positioned to continue executing our goals,” Love said, giving a timeframe of six to 18 months, and noting Annexon’s ultimate aim “to deliver game-changing medicines to patients.”