Annexon, Inc. Common Stock 2026 Q2 Earnings Call

Good morning and welcome, everyone. Earlier this morning, Annexon issued a press release announcing that we have expanded our ARCHER II phase III trial for vonaprument in geographic atrophy and a press release announcing key business updates and second-quarter financial results. Copies of these press releases are available on the company's website and through our SEC filings. On today's call, we will be making forward-looking statements, including statements relating to the existing clinical data and the therapeutic and commercial potential of our investigational drug candidates. Joining me today are Dr. Jamie Dannenberg, our EVP and Chief Medical Officer, and Dr. Lloyd Clark, SVP of Ophthalmology Strategy and Innovation, who will discuss our GBS and GA programs respectively.

I will then close before we open the call for questions, where we will be joined by Dr. Chad Jednák, EVP and Chief Innovation Officer, and Yajing Liu, our Chief Financial Officer. Before we turn to the updates, I'd like to briefly frame Annexon's broader opportunity and our excitement about building a leading, fully integrated biotech company driven by our mission to help millions of people live their best lives. Annexon was founded on discoveries from Stanford University to create a new class of targeted immunotherapies that stop C1q-mediated neuroinflammation at its source, with the goal of rapidly and meaningfully preserving and potentially improving function for patients with serious neuroinflammatory diseases of the body, the brain, and the eye.

Built on more than two decades of foundational C1q biology and a highly translational approach in the clinic, we have generated robust, compelling evidence supporting the potential of C1q inhibition across multiple diseases. Indeed, leveraging our pioneering science and our warrior spirit culture to tackle some of the most pressing diseases in our industry, Annexon is the first and only company to successfully conduct fully randomized placebo-controlled trials in GBS, a life-threatening and debilitating disease that is sudden and completely indiscriminate in who it strikes, robbing otherwise healthy people of their normal lives. Annexon is also the first and only company to demonstrate significant vision preservation in a fully randomized, sham-controlled study in geographic atrophy, a mass population disease of irreversible blindness that robs millions of people of their independence.

Lastly, Annexon is the first and only company to develop and clinically study an oral small molecule designed to selectively inhibit the classical pathway with the potential to offer those with serious complement-mediated autoimmune conditions a convenient and flexible oral dosing option. While disruptive science is not always quickly recognized, we are more energized than ever by the opportunity to create significant value with not just one, but with multiple potential blockbuster paradigm-shifting programs designed to bring hope and better outcomes to millions of people worldwide. Turning to our GBS program update, this program reflects the foundation of Annexon and our determination to take on challenges others have not. We are pleased to have generated the first positive placebo-controlled pivotal data in the 110 years since GBS was discovered.

tanruprubart is now under regulatory review in Europe, and we are on track to submit the U.S. BLA in the fourth quarter of this year. Last week, we reported clinical outcomes from the first cohort of patients enrolled in our FORWARD study across the United States and Europe, marking an important milestone for Annexon and for the GBS community. tanruprubart flat out works, and these data are more than the next step in our development program. They provide compelling evidence that the rapid, meaningful clinical improvements seen in our phase III study, where approximately 90% of treated patients responded by week one, are reproducible in Western patients. All 10 patients treated to date in FORWARD improved rapidly, with many showing outsized gains. These unprecedented outcomes, together with a well-tolerated safety profile, support a highly differentiated benefit risk profile for the roughly 150,000 people worldwide diagnosed with GBS each year.

We plan to include these data in our BLA submission in the fourth quarter. Turning next to our GA program, our second drug candidate, vonaprument, is advancing in the pivotal ARCHER II phase III trial for patients at risk of irreversible vision loss. Today, we announced a strategic expansion of the program by adding an independent month 24 dual primary endpoint alongside the existing month 15 primary endpoint. To be clear, we remain excited and confident about the month 15 readout expected in the fourth quarter of this year, supported by a powerful mechanism of action, robust preclinical package, compelling dose-dependent proof of concept data, and a well-powered, well-executed phase III study designed to replicate those results. With masked events tracking on plan, month 15 remains our base case for success. At the same time, adding the month 24 endpoint meaningfully strengthens the program in a potential $100 billion-plus franchise.

The endpoint is well-powered, requires no change to the conduct of the already masked 24-month trial, and gives vonaprument additional time to demonstrate the growing treatment effect observed in the proof of concept trial. Lloyd Clark will discuss this shortly, but in short, the ARCHER program is stronger with this enhancement. Related to the GA program, we were also pleased to announce initiation of the ARCHER II Open Label Extension, or OLE study. This allows all patients to enter the OLE after month 24 to receive vonaprument while enabling us to assess its longer-term safety and benefit profile. Shifting to corporate matters, as both the tanruprubart GBS and vonaprument GA programs advance toward registration, we also in the second quarter took a strategic step to further strengthen our financial position.

During the quarter, we entered a credit facility with Oxford Finance that provides access up to $200 million in non-dilutive capital, extending our cash runway into 2028. This facility enhances our financial and operational flexibility as we prepare for global commercialization, while further diversifying our capital structure, strengthening our balance sheet, and supporting both near and longer-term growth strategies. With that overview, I will now turn the call over to Jamie to review the recent data for our GBS program. Following that, Lloyd will then discuss our vonaprument program updates in more detail. Jamie, over to you. Thanks, Doug.

Before reviewing the FORWARD data, I'd like to briefly highlight the significant unmet need in GBS. As Doug mentioned, GBS is an indiscriminate, life-threatening neuromuscular emergency with a rapid, devastating onset, compounded by long-term, life-altering consequences. GBS can strike anyone, anywhere, causing paralysis, respiratory failure, and even death. Without immediate intervention, patients face continued neuroinflammation and peripheral nerve damage caused by GBS that leads to muscle weakness and paralysis, with lifelong residual deficits impacting their health and quality of life. Approximately 22,000 patients each year across the U.S. and Europe are afflicted with GBS, and it carries an estimated annual healthcare burden of more than $20 billion in the U.S. alone. Despite more than 110 years since GBS was first described, there are still no approved targeted therapies that meaningfully alter the course of the disease.

Current standard of care, intravenous immunoglobulin, or IVIG, is not FDA approved for GBS and provides incomplete benefit for many patients. Despite treatment, one-year mortality remains as high as 10% overall and approaches 25% in patients over the age of 65. Many patients continue to deteriorate during or shortly after five-day IVIG treatment, requiring mechanical ventilation, prolonged ICU stays, and experiencing months or even years of disability and persistent physical limitations. These challenges underscore the urgent need for therapies that can rapidly stop the underlying disease process and improve patient outcomes. Turning now to the FORWARD study, we are very encouraged by the initial results from the first cohort of 10 patients treated with a single 30 milligram per kilogram infusion of tanruprubart. Across this initial cohort, every patient demonstrated rapid, clinically meaningful improvement in muscle strength within four days of treatment.

Importantly, four patients who were bed-bound early in the course of their disease regained the ability to walk with or without assistance between days two and eight. We also observed outsized improvements in some of the most severely affected patients. The one patient who required mechanical ventilation early in the disease course was successfully weaned from the ventilator within four days. Five additional patients experienced marked functional improvement within 48 hours of treatment. Bear in mind that these outcomes with tanruprubart occurred well short of the five-day span that is typically required to deliver a full course of IVIG. From a safety perspective, tanruprubart was generally well-tolerated. The most significant adverse events were related to GBS itself and expected complications of the disease and were consistent with the safety profile observed in our phase III study.

It's also worth noting that this initial cohort represented a broad cross-section of GBS patients, including both males and females, ranging from 12 to 78 years of age, and spanning moderate to severe disease. Importantly, these findings are consistent with the outcomes we observed in our phase III study, where approximately 90% of patients demonstrated rapid, clinically meaningful improvement by day 8. Taken together, we believe these results provide further evidence that targeted inhibition of C1q with tanruprubart has the potential to fundamentally change the treatment paradigm for patients with GBS by delivering rapid and meaningful clinical benefit after a single infusion. Finally, I'd like to briefly touch on where we are from a regulatory and clinical development perspective. Our marketing authorisation application is currently on track and under review by the European Medicines Agency and is supported by a comprehensive data package.

This includes robust placebo-controlled studies demonstrating rapid improvement in function and disability, as well as real-world evidence showing favorable outcomes compared with current standard of care, including IVIG and plasma exchange. At the same time, we continue to advance the FORWARD study across the U.S. and Europe. This study is designed to expand our experience with tanruprubart in Western patients, including pediatric patients, while further characterizing its pharmacokinetic and pharmacodynamic profile, early effects on function and biomarkers, and overall safety. Importantly, the FORWARD data are expected to support our planned Biologics License Application, or BLA, submission to the FDA in the fourth quarter of this year. Together with our ongoing EMA review, these data are intended to further support the generalizability of tanruprubart's rapid clinical benefit across diverse populations and geographies and reinforce the broad treatment label we are seeking for patients with GBS.