Opus Genetics, Inc. Common Stock Study result

Please go ahead. Good morning, and thank you for joining us on today's call to discuss top-line results from cohort 1 of Opus Genetics' BEST1 phase I/II clinical trial.

Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements. Various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of the company's annual report on Form 10-K for the year ended December 31, 2025, quarterly reports on Form 10-Q, and our other SEC filings available on the Opus website. In addition, any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date.

While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change. Presenters from the Opus management team on today's call are Dr. George Magrath, Chief Executive Officer, Dr. Sally Tucker, Chief Medical Officer, Dr. Ash Jayagopal, Chief Scientific and Development Officer, Dr. Ben Yerxa, President, and Rob Gagnon, Chief Financial Officer, are also on the call and will participate in the Q&A session. In addition, following the prepared remarks, Dr. Mark Pennesi, Chief Medical Officer and Director of Ophthalmic Genetics at the Retina Foundation and Principal Investigator for the phase I/II study, will offer his insights on the results and be available for Q&A. The remarks on today's call will be accompanied by a slide presentation, which is available in the Events section of Opus Genetics' Investor Relations website at opusgtx.com.

A recording of this call will be available on the website later today. I would now like to turn the call over to Dr. Magrath.

Thank you, Jenny, and thank you all for joining us this morning. We are excited to share the current results from cohort 1 in our BEST1 phase I/II clinical trial, known as BIRD-1, which exceeded our expectations from this first in human cohort. At a high level, we have several key takeaways. Most importantly, OPGX-BEST1 demonstrated a well-tolerated safety profile with no serious adverse events, no dose-limiting toxicities, and no intraocular inflammation at any of the visits. Our gene therapy has been well-tolerated in this first cohort out to 3 months. Additionally, we saw evidence of biologic activity. When we began the trial, we thought we would see changes in subretinal fluid, but surprisingly, we saw a reduction in vitelliform material, the hallmark of Best vitelliform macular dystrophy. Further, we ended up seeing functional improvements in all 5 patients.

That functional improvement was directly paired with structural improvements at just the 3-month time point in 4 of the 5 participants. The combined functional and structural improvement on the same location in the retina, which we are defining as co-localization, gives us confidence as we continue advancing the development program. In August, we held a positive Type C meeting with the FDA regarding phase I/II data, the phase III clinical development program, and our commercial manufacturing plans. We also discussed the potential pivotal trial endpoint in that meeting, and we aligned with the agency that a 3-decibel or greater improvement in microperimetry could be acceptable as a potential primary endpoint for a phase III program. Because OPGX-BEST1 produced localized functional improvement in the treated viable retina, the FDA agreed that the same measure, in conjunction with a patient-reported outcome, may support a future pivotal trial.

Our phase III and commercial drug supply should be ready for use in early 2027. Until then, we have enrolled cohort 2, the high-dose cohort. Initially, cohort 2 was planned for 5 participants. We currently have enrolled 8 participants. The first has been dosed and is doing well. We expect dosing to be complete in Q4 of this year. Further, recent epidemiology research found that the number of BEST1 patients in the U.S. likely numbers around 23,600, while the global patient population is expected to number approximately 45,400 patients. The updated estimates are based on a survey of 150 retina specialists, general ophthalmologists, and optometrists, and account for evidence that a majority of patients with Best disease stay with their local retina physician, are not genotyped, and are not counted in a lot of the databases.

More information on this research is provided in the appendix of today's presentation. Today, I will provide an overview of Opus and the BEST1 pathophysiology. Dr. Sally Tucker will describe our trial design and top-line results. Then Dr. Ash Jayagopal will review individual participant case studies, and I will close with a program summary and our next steps. We have a deep pipeline built on a durable platform that is well-funded into 2029 to advance these clinical programs. LCA5 is our most advanced program. This phase III trial is fully enrolled, and we expect results next year. If the results are positive, we would move quickly towards a BLA filing. BEST1 is what we are going to talk about today. We also have RDH12, MERTK, and RHO all entering the clinic in the near future. It is an exciting time here at Opus.

As you look across our pipeline, there is one consistent theme. There are no approved products to treat any of these inherited retinal diseases. These also represent diseases where we think we may see rapid evidence of target engagement and use a similar manufacturing platform. Importantly, we own global rights to all our gene therapy programs, and we believe each one has the potential to qualify for a priority review voucher. We are breaking new ground in each of these indications, and we are proud of the string-of-pearls pipeline we are advancing. Today, we are going to talk about BEST1 disease. As I mentioned earlier, BEST1 is a disease that affects 23,600 U.S. patients, and a majority of these have Best vitelliform macular dystrophy, or BVMD.

BVMD is a type of autosomal dominant Best disease that presents with this vitelliform material in the center of the macula that ophthalmologists refer to as an egg yolk lesion. This disrupts the vision, and over time, leads to macular atrophy. BEST1 typically begins when patients are in their 20s or 30s, and they begin to have distorted vision. That distorted vision then turns into geographic atrophy and a permanent scotoma, or blind spot, over time. Our objective is to intervene when the disease is still in the partially affected stage and before it becomes atrophic. In cohort 1 of our trial, the participants are all pretty close to atrophic because this is a first-in-human subretinal delivery of a novel gene therapy. Therefore, we selected patients that already had significant vision loss.

As we gained experience, we were able to begin to enroll earlier stage patients, and you will see an example of that with our last participant enrolled. There is also a recessive version of the disease known as autosomal recessive bestrophinopathy, or ARB, that is much less common and presents earlier in life. ARB patients have a more severe and diffuse phenotype, where instead of one vitelliform lesion, they have many lesions spread throughout the macula. This is represented in 2 of our participants today. The BEST1 gene encodes for a protein in the RPE that creates a transmembrane calcium-activated chloride channel. This channel opens and moves chloride ions through the basolateral side of the RPE, creating an electric gradient across the RPE cells, which normally pulls this vitelliform material into the choroidal circulatory system for disposal.

These vitelliform lesions or deposits are most likely lipofuscin and waste products of the photoreceptors that normally are trafficked out of the eye. But in Best disease, they are not transported out of the eye, and they accumulate under the retina. As the patient develops a backup of these waste products, the photoreceptors begin to atrophy. As the photoreceptors atrophy, the patient enters the later stages of disease and develops fluid over the lesion, which presents as what we call a pseudohypopyon, or subretinal fluid with a vitelliform material dispersed within it. As the photoreceptors further atrophy, the patient gets less and less of this vitelliform material being created because there is less metabolic activity. The material starts to fragment and then eventually goes away and leaves an atrophic spot, similar to what happens in geographic atrophy.

As a first-in-human trial, cohort 1 primarily enrolled participants in the later stage of disease where the vitelliform material is fragmented. As you will see in our data, OPGX-BEST1 had a meaningful impact in reduction of the vitelliform material in 2 of the BVMD participants. With that disease overview, I would like to now turn it over to Dr. Sally Tucker, our Chief Medical Officer, to walk through the BIRD-1 clinical trial design and top-line results.