JPM23: Annexon looks for '2 ways to win' in upcoming Huntington's trial

Annexon Biosciences CEO Douglas Love said the company is giving itself "two ways to win” in the upcoming pivotal phase 2/3 trial for Huntington’s disease therapy ANX005 during remarks at the J.P. Morgan Healthcare Conference Wednesday morning.

The company has previously shown that patients who entered an earlier phase 2 study with higher baseline complement activity had a higher clinical benefit when treated with the monoclonal antibody, which is designed to fully inhibit C1q and the entire classical complement pathway. About 75% of these patients showed improvement, which Love called an “outsized outcome,” compared to 36% in the low complement group. Complement activity was measured by elevated levels of C4a serum in cerebral spinal fluid, which is a marker of Huntington’s disease.

Love said even the low complement group was impressive, and he believes those patients may simply take longer to respond in line with the higher group. So for the upcoming study, Annexon is focusing on the high complement group, although the study will still include other populations.

“What we're looking to do is ensure that we have an [appropriately powered] study where we can capture a win solely in the high complement group, while also looking at the full cohort,” Love said.

Annexon previously used this design in a study of ANX007 in geographic atrophy.

Love previewed the year ahead, which includes initiating ANX1502 in phase 1 studies for autoimmune indications, completing phase 3 enrollment for ANX005 in Guillain-Barre syndrome (GBS) and initiating the phase 2/3 trial for Huntington’s disease.

Annexon also has three other “next wave” programs in the works. ANX005 is being tested in amyotrophic lateral sclerosis, which should have phase 2 data this year. ANX009 is due for a phase 1 readout in the first half for lupus nephritis. Finally, data from a phase 1 study of ANX105 in autoimmune/neuro indications are expected this year as well.

All of that is included in Annexon’s cash runway, Love noted. The company reported cash and equivalents of $269.5 million as of Sept. 30, 2022, in its third-quarter earnings release last year.

Just prior to the JPM meet up, Annexon revealed a slight pipeline retool and a narrowed focus on three lead assets, ANX005, ANX007, and ANX1502. ANX005 was deprioritized in warm autoimmune hemolytic anemia after “an assessment of the market opportunity,” the company said in a Sunday press release.

Annexon also expanded the phase 3 GBS trial for ANX005 after conversations with the FDA. The patient population will be upped by 40, for a total of 220. Love said the move will help show the therapy’s impact across the range of disability associated with the autoimmune disease.