Annexon (NASDAQ:ANNX) executives outlined a series of expected clinical and regulatory updates across the company’s complement-focused pipeline during a session at the Jefferies Conference, highlighting programs in geographic atrophy, Guillain-Barré syndrome and cold agglutinin disease.
Douglas Love, Annexon’s president and chief executive officer, said the company is focused on “the next generation of complement therapies” for neuroinflammatory diseases by targeting C1q, which he described as the initiator of the classical complement pathway. Love said the company’s approach is differentiated from downstream complement targets such as C3 and C5.
Love said Annexon expects catalysts from three programs this year: phase III data in geographic atrophy, additional data from a Guillain-Barré syndrome study in Western patients and early data from its oral small-molecule complement program, ANX1502.
Geographic Atrophy Readout Expected in Q4
Annexon’s most closely watched near-term catalyst is a phase III geographic atrophy study expected to read out in the fourth quarter. Love said the trial is designed to replicate findings from the company’s phase II study, which he said showed significant vision preservation and preservation of photoreceptor cells.
Lloyd Clark, senior vice president of ophthalmology at Annexon and a retina specialist, said the company’s C1q inhibitor is intended to protect photoreceptors, particularly in the central macula, which is important for central visual acuity.
Clark said the phase II study showed a 73% risk reduction in 15-letter vision loss in the monthly treatment group compared with sham. He said Annexon’s phase III primary endpoint is confirmed 15-letter loss at two consecutive visits, which he described as a standard endpoint in retina clinical trials.
Clark said the phase II study also showed directional benefit across multiple functional measures, including visual acuity and low-luminance visual acuity, as well as a dose response between monthly and every-other-month treatment. During the final six months of the phase II study, when patients were off treatment, vision loss continued across treatment groups, which Clark said was consistent with a disease-modifying effect.
Asked how Annexon’s results compared with approved geographic atrophy therapies from Apellis and Iveric, Love said, “Neither have demonstrated visual protection in their programs.”
Phase III Design and Regulatory Approach
Clark said the geographic atrophy study is event-driven, with an event defined as a confirmed loss of 15 letters of vision at two consecutive visits. For example, he said, a patient who loses 15 letters at month eight must have that loss confirmed at month nine for it to count as an event.
Clark said Annexon modeled expected event rates using its phase II data and the lampalizumab natural history cohort, and said masked event rates remain in line with estimates. Love added that the study is about two-thirds complete and “very much on track.”
Love said Annexon has a regulatory agreement in Europe based on a single-protocol study of 659 patients. In the United States, the same protocol is divided into two pre-specified sub-analyses aligned with the Food and Drug Administration. Love said each sub-analysis is powered at greater than 90%.
Clark said Annexon enriched the phase III population by excluding patients with very poor vision, including the bottom 20% of patients from phase II who did not have 15-letter loss events. The company also targeted enrollment of patients with foveal involvement, who have higher rates of vision loss.
On safety, Clark said Annexon saw no evidence of occlusive vasculitis in phase II and no increased rate of choroidal neovascularization. He said the company hopes to replicate that profile in phase III.
GBS Filing Plans and FORWARD Study
Love said Annexon has already filed for approval in Europe for its Guillain-Barré syndrome program and expects to file a biologics license application in the United States in 2026. Before the U.S. filing, the company plans to release data from its ongoing FORWARD study, which is evaluating GBS patients in the U.S. and Europe.
Love said the FORWARD data set is expected to include roughly five to 10 patients and will be released before the geographic atrophy phase III readout. He said the data are intended to show consistency between Western patients and the pivotal phase III study conducted in Southeast Asia.
Love said Annexon will examine pharmacokinetics, pharmacodynamics and efficacy at multiple time points, including week one, week four and week eight on the GBS disability scale. He said some patients will have data out to week 26, which he described as important because the company’s phase III study showed a two-and-a-half-times greater likelihood of full recovery by week 26.
Love said GBS affects about 8,000 patients annually in the U.S. and 15,000 in Europe. He said 90% to 95% of patients are treated off-label with IVIG or plasma exchange. Love also said the disease costs the U.S. healthcare system more than $7 billion annually to manage 8,000 patients, and said Annexon’s treatment was associated with patients getting on their feet 30 days sooner, coming off ventilators 28 days sooner and leaving the ICU 10 days sooner.
Love said the company has not disclosed pricing, but noted that covering analysts have estimated $100,000 to $150,000 per course of therapy.
Oral Complement Program Also Set for Data
Annexon also expects data before the geographic atrophy readout from ANX1502, which Love described as the first small-molecule oral program in the classical complement space. The initial data set is expected to include up to six patients with cold agglutinin disease.
Love said success would include normalization of excess complement activity and normalization of bilirubin, which he described as a key marker related to anemia in the disease. He said the company will also look at hemoglobin, though he described that measure as more variable and potentially slower to respond in a four-week study.
Love said the company has seen a food effect related to the current tablet formulation, which uses an enteric coating intended to release the drug after passing through the gut. He said the current cohort is being dosed under fully fasted conditions, and Annexon will decide after reviewing the data whether to advance the current formulation or address the enteric-coated formulation before a later-stage study.
About Annexon (NASDAQ:ANNX)
Annexon Inc is a clinical-stage biotechnology company focused on the discovery and development of complement-targeted therapies for patients with neurodegenerative and neuroimmune diseases. The company's research platform centers on the inhibition of the C1 complex, a key initiator of the classical complement pathway implicated in several rare and life-threatening disorders. By selectively targeting upstream complement activation, Annexon aims to prevent the aberrant immune-mediated damage that characterizes conditions such as Guillain-Barré syndrome (GBS) and autoimmune neuropathies.
At the core of Annexon's pipeline is ANX005, a humanized monoclonal antibody directed against the C1q subcomponent, currently in Phase 2 clinical trials for acute GBS and chronic neurodegenerative indications.
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