tanruprubart (ANX005) / Annexon Biosci - LARVOL DELTA

Recent Corporate and Clinical Program Updates: Tanruprubart (ANX005) in GBS (GlobeNewswire) - "Next Milestones: (i) Tanruprubart MAA submission expected in January 2026; (ii) Update on FDA BLA submission upon further regulatory dialogue; (iii) Initial FORWARD data anticipated in 2026."

EMA filing • FDA filing • P3 data • CNS Disorders

GUILLAIN BARRÉ SYNDROME (WCN 2025) - "Fifth, recent studies provided first evidence for a positive effect on clinical recovery of two new treatments: imlifidase (IgG cleaving enzyme) and tanruprubart (C1q inhibitor)...Major challenges for the future include finding more effective and personalized treatments, which are also affordable in low- and middle-income countries, and to prepare for outbreaks of infections as potential triggers for GBS. Up to date information on the management of GBS is available via the knowledge hub at The Global Health Network."

CNS Disorders • NEFL

Therapeutic strategies for Huntington's disease: current approaches and future direction. (PubMed, Neurodegener Dis Manag) - "Additionally, the potential of VTX-003 and ANX005 in mitigating disease progression is explored. Despite these promising therapies, challenges persist, particularly in long-term assessment, delivery strategy, and off-target effects. Considering the future landscape and need, the review has strengthened the need of therapeutic interventions to enhance efficacy and safety, ultimately improving the quality of life of HD patients."

Journal • Review • CNS Disorders • Cognitive Disorders • Gene Therapies • Huntington's Disease • Movement Disorders • Psychiatry • Targeted Protein Degradation

An Open Label Clinical Study to Evaluate Tanruprubart (Also Commonly Known as ANX005) in Participants With Guillain-Barré Syndrome (FORWARD Study) (clinicaltrials.gov) - P3 | N=30 | Not yet recruiting | Sponsor: Annexon, Inc.

New P3 trial • Complement-mediated Rare Disorders

Microglia in the Rostral Ventromedial Medulla Mediate Synaptic Pruning via the C1q/C3-CR3 Signaling Pathway-A Mechanism for the Chronic Orofacial Pain. (PubMed, Mol Neurobiol) - "During the modeling process, administered daily stereotactic injections of ANX-005 and minocycline into the RVM, which resulted in a notable recovery in the rats' pain threshold and a significant increase in C1q/C3 and microglia in the RVM of CFA rats. This process results in a reduction in the proportion of excitatory synapses and a disruption in the physiological balance between RVM descending facilitation and descending inhibition. This leads to the predominance of descending facilitation in pain transmission in the RVM, which in turn facilitates the chronification of orofacial pain."

Journal • Pain • C1Q

Evolving understanding of Guillain-Barré syndrome pathophysiology and the central role of the classical complement pathway in axonal injury. (PubMed, Front Neurol) - "Given its evolutionary role in antibody binding and activating the classical complement pathway, the complement component C1q has been proposed as a therapeutic target in GBS. The clinical trial program of the C1q inhibitor ANX005, including placebo-controlled, double-blind phase 1b and phase 3 trials in GBS, provides insight into the pathophysiology of GBS and the efficacy of C1q inhibition regardless of neurophysiologic classification or geographic location."

Journal • Infectious Disease • Pain

RWE Findings Demonstrate Benefits with Tanruprubart over Current Standard of Care in Matched Patient Populations (GlobeNewswire) - "In the RWE study, tanruprubart showed a rapid increase in muscle function resulting in a sustained and more complete recovery compared to IVIg or PE: By Week 1, patients treated with tanruprubart showed approximately a ten-point improvement in muscle strength over patients treated with IVIg or PE, a clinically meaningful benefit as measured by Medical Research Council (MRC) sumscore and an indicator for future recovery potential; Patients treated with tanruprubart were approximately three times more likely to be in a better state of health than patients on IVIg or PE on the GBS-Disability Scale (GBS-DS) at Weeks 4, 8, and 26."

Real-world evidence • Immunology

New Pivotal Phase 3 Trial Analyses Reinforce the Rapid and Sustained Clinical Benefits of a Single Dose of Tanruprubart (GlobeNewswire) - P3 | N=242 | NCT04701164 | Sponsor: Annexon, Inc. | "Tanruprubart 30 mg/kg halted inflammation and nerve damage resulting in clinical benefits as early as Week 1, including rapid improvements in muscle strength, mobility, balance, and coordination that were maintained through Week 26; Tanruprubart-treated patients rapidly regained the ability to move independently, do personal tasks, and return to a range of routine daily living activities; Tanruprubart demonstrated a greater degree of efficacy amongst patients with disease characteristics more commonly observed in western countries, supporting the potential of tanruprubart to benefit patients worldwide."

P3 data • Immunology

Annexon Reports First Quarter 2025 Financial Results, Portfolio Progress and Key Anticipated Milestones (GlobeNewswire) - "FDA Meeting for Tanruprubart (formerly ANX005), the First Potential Targeted Therapy for GBS, Scheduled for Second Quarter 2025 Ahead of Planned BLA Submission; Open-Label Tanruprubart FORWARD Study Designed to Broaden Patient and Healthcare Community Experience in North America and Europe, Initiating in Second Quarter 2025; Accelerated Enrollment in Phase 3 ARCHER II Trial on Pace for Completion in Third Quarter 2025 for ANX007, the First Potential Treatment for Dry AMD with GA; Pivotal Topline Data Expected in the Second Half of 2026."

FDA event • New trial • P3 data: top line • Age-related Macular Degeneration • Immunology

Annexon Highlights Pivotal Data on First Potential Targeted Therapy for Guillain-Barré Syndrome (GBS) and Showcases New GBS Education Campaign at American Academy of Neurology (AAN) 2025 Annual Meeting (GlobeNewswire) - P3 | N=242 | NCT04701164 | Sponsor: Annexon, Inc. | "New efficacy findings consistently demonstrated rapid recovery and durable benefits of tanruprubart across muscle strength, mobility and disability measures: At Week 1, treated patients rapidly gained motor function and were 14-fold more likely to perform the Timed Up and Go (TUG) test, a standardized measure of mobility, balance and lower limb capacity; At Week 1, treated patients rapidly gained motor ability and showed more than a 2-point improvement on the Overall Neuropathy Limitation Scale (ONLS), a tool used to assess limitations in everyday activities of the upper and lower limbs....The new findings build upon previously reported Phase 3 trial results that showed an improvement in the primary endpoint of GBS-DS at Week 8, as well as that twice the number of patients treated with tanruprubart fully recovered to normal (GBS-DS = 0) at Week 26, compared to placebo."

P3 data • Immunology

Annexon Announces Presentations on the Clinical Advancement of Tanruprubart as the First Potential Targeted Therapy for Guillain-Barré Syndrome (GBS) at the 2025 PNS Meeting (GlobeNewswire) - "First Oral Presentation by the International Guillain-Barré Syndrome Outcomes Study (IGOS) of the Real-World Evidence (RWE) Results Showing Improved Outcomes with Tanruprubart (formerly ANX005) Compared to Current Standards of Care in Matched Patient Populations. New Analyses of Phase 3 Trial Highlight Tanruprubart’s Early and Durable Treatment Effect and Improvement in Quality of Life in Patients with GBS....Annexon, Inc....today announced oral and poster presentations highlighting improved outcomes with tanruprubart (formerly ANX005) at the 2025 Peripheral Nerve Society (PNS) Annual Meeting at the Edinburgh International Conference Centre being held May 17-20, 2025 in Edinburgh, UK."

Clinical data • P3 data • Immunology

Efficacy and Safety of Targeted Immunotherapy with ANX005 in Treating Guillain-Barré Syndrome: A Phase 3 Multicenter Study (PL5.006). (PubMed, Neurology) - P3 | "Dr. Deen Mohammad has nothing to disclose."

Clinical • Journal • P3 data • Immunology • Infectious Disease • Inflammation

Efficacy and Safety of Targeted Immunotherapy with ANX005 in Treating Guillain-Barré Syndrome: A Phase 3 Multicenter Study (AAN 2025) - P3 | "A single dose of ANX005 30 mg/kg rapidly inhibited C1q, leading to a significant and sustained improvement in patient health over 6 months versus placebo, and was generally well-tolerated. ANX005 has the potential to transform GBS management."

Clinical • P3 data • Immunology • Infectious Disease • Inflammation

Industry Therapeutic Update from Annexon Biosciences: Advancing GBS Care: Latest Insights into the role of classical complement pathway in GBS (AAN 2025) - "Data from the clinical development program of the novel C1q inhibitor ANX005 will also be reviewed, followed by time for Q&A.This program is NOT accredited for continuing education by any organization...The AAN cannot affirm claims pertaining to FDA off-label medication, research use of pre-FDA drugs, or other research information that might be discussed. Industry Therapeutic Updates are industry events."

Annexon Reports Fourth Quarter and Year-End 2024 Financial Results, Portfolio Progress and Key Anticipated Milestones (GlobeNewswire) - "ANX005 in Guillain-Barré Syndrome (GBS):...Next Milestone: Pre-BLA meeting targeted for first half of 2025 ahead of planned BLA submission."

FDA event • Immunology • Rare Diseases

Results From a Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ANX005, a C1q Inhibitor, in Patients With Guillain-Barré Syndrome. (PubMed, J Peripher Nerv Syst) - "These results support ANX005 as a targeted therapy for GBS that modulates the classical complement pathway. Further investigation in a larger Phase 3 trial is warranted to confirm these results and assess the long-term benefits of complement inhibition in patients with GBS."

Clinical • Journal • P1 data • PK/PD data • Immunology • Pain • C1Q • NEFL

Annexon Provides 2025 Outlook with Strong Momentum Accelerating into Breakthrough Year (GlobeNewswire) - "ANX005 for GBS: Next Milestone: BLA Submission targeted for first half of 2025....ANX007 in GA: Phase 3 ARCHER II trial enrollment to be completed in second half of 2025; data expected in second half of 2026....ANX1502 for Autoimmune Conditions: Next Milestone: Clinical proof of concept data in CAD and update on future target indications in first quarter of 2025."

Clinical data • Enrollment status • FDA filing • P3 data • Immunology • Ophthalmology • Rare Diseases

Efficacy and Safety of ANX005 in Subjects With Guillain-Barré Syndrome (clinicaltrials.gov) - P3 | N=242 | Completed | Sponsor: Annexon, Inc. | Recruiting ➔ Completed

Trial completion • Complement-mediated Rare Disorders

Study of ANX005 in Adults With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P2 | N=17 | Completed | Sponsor: Annexon, Inc. | Recruiting ➔ Completed | Phase classification: P2a ➔ P2 | Trial completion date: Jan 2024 ➔ Apr 2024 | Trial primary completion date: Oct 2023 ➔ Jan 2024

Phase classification • Trial completion • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Annexon Reports First Quarter 2024 Financial Results and Key Anticipated Milestones (GlobeNewswire) - "ANX005 in GBS: Topline data from the pivotal, randomized, placebo-controlled Phase 3 trial expected in the second quarter of 2024. Initial data from RWE comparability protocol with IGOS expected in first half 2025 to support a planned BLA submission. ANX007 in GA: Global pivotal Phase 3 ARCHER II trial vs. sham control expected to initiate in mid-2024. Pivotal Phase 3 head-to-head ARROW trial vs. SYFOVRE (pegcetacoplan injection) planned to initiate in the second half of 2024. Expect to host an R&D Day on GA and therapeutic potential of ANX007 in mid-2024. ANX1502 in CAD: POC trial evaluating the pharmacodynamics and efficacy of an oral tablet formulation in CAD anticipated to provide initial data in the second half of 2024....R&D expenses were $21.0 million for the quarter ended March 31, 2024, reflecting the advancement of the Company’s priority programs, including GBS, GA and ANX1502, compared to $32.3 million for the quarter ended March 31, 2023."

Clinical data • Commercial • New P3 trial • P3 data: top line • Immunology • Ophthalmology • Rare Diseases

Understanding Pharmacy Costs and the Changing Treatment Landscape in Huntington's Disease (HD) in the US: A Systematic Literature Review (SLR) and Database Review for Disease-Modifying Therapies (DMT) in Development (ISPOR 2024) - "Motor symptoms incur the greatest annual drug cost, with high median costs per patient (2019) for tetrabenazine ($24,996), deutetrabenazine ($69,972), and valbenazine ($76,908). Ten clinical trials are investigating potential future DMTs: two-antisense oligonucleotides (n=5; Tominersen [RO7234292, ISIS 443139], WVE-003), two-RNA-targeting small molecules (n=2; PTC518, Branaplam), monoclonal antibodies (n=2; ANX005, VX15/2503), and gene therapy (n=1; rAAV5-miHTT). Pharmacy costs for symptomatic treatment are substantial in HD, with these costs increasing as HD progresses and symptom severity increases. This significant burden illustrates the importance of developing new DMTs that can prevent or slow disease progression for patients with HD."

Review • CNS Disorders • Depression • Gene Therapies • Huntington's Disease • Mood Disorders • Movement Disorders • Psychiatry

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity. (PubMed, Cell Biosci) - "Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • C1Q

Annexon Reports Significant Progress with its Priority Programs and Third Quarter 2023 Financial Results (GlobeNewswire) - "ANX005 in Amyotrophic Lateral Sclerosis (ALS): Following encouraging preliminary results which showed slowing of disease progression, full on-treatment data from the Phase 2a trial are expected by early 2024. ANX005 in Huntington’s Disease (HD): Annexon is assessing the initiation of a planned late-stage trial in HD in 2024 as the company prioritizes near-term pivotal development activities for GBS, GA and ANX1502."

New trial • P2a data • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease • Immunology

C1q inhibition reduces neurodegenerative damage preserves neuromuscular junctions and improves compound muscle action potential in the SOD1G93A mouse model (ALS-MND 2023) - P2a | "Treatment reduced C1q levels in plasma, spinal cord, and muscle tissue, along with inhibiting downstream classical complement activation. Treated mice showed significant preservation of NMJ density, as measured by bungarotoxin labelling of the gastrocnemius muscle, and improvement in the amplitude of compound muscle action potential, potentially demonstrating that C1q inhibition led to increased synaptic connectivity at the NMJ. Furthermore, anti-C1q treatment reduced NfL levels in the CSF and plasma of SOD1G93A mice compared to untreated SOD1G93A mice, marking reduction in neuronal damage in this model."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • CSF NfL • NEFL • Plasma NfL

C1q inhibition reduces neuronal damage, preserves neuromuscular junctions, and improves compound muscle action potential in the SOD1G93A mouse model (Neuroscience 2023) - P2a | "A Phase 2 study of ANX005, an anti-C1q therapy, in ALS patients is ongoing (ClinicalTrials. gov: NCT04569435)."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders