Aldeyra Therapeutics, Inc.

Ladies and gentlemen, thank you for standing by, and welcome to the Aldera Therapeutics Full Year 2021 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentations, there will be a question-and-answer session. I would now like to hand over the conference to the company's Chief Financial Officer, Mr. Joshua Reid. Please go ahead, sir.

Good morning, everyone. With me is Dr. Todd Brady, President and Chief Executive Officer of Aldera. This morning, we issued a press release reporting our financial results for the year end of December 31, 2021. A copy of the press release is available on the Investors and Media section of our website, www.aldera.com. Please note that this morning's conference call contains forward-looking statements regarding future events and the future performance of Aldera. Forward-looking statements include but are not limited to statements regarding submission of potential new drug applications, potential commercialization, the anticipated timing of results from our clinical trials, our projected cash runway, our possible or assumed future results of operations, expenses and financial position, and potential growth opportunities. These statements are based upon the information available to us today and reflect our current views concerning future events. They are based on assumptions and subject to risks and uncertainties, including the development, clinical, and regulatory plans or expectations for Aldera's product candidates and systems-based approaches. The risks that result from our clinical trials or portions of clinical trials may not accurately predict the results of future trials for the same or different indications in Aldera's continuing review and quality control analysis of clinical data. As a result of the COVID-19 pandemic, Clinical site availability, staffing, and patient recruitment have been negatively affected, and the timelines to complete our clinical trials may be delayed. Aldera assumes no obligation to update these statements as circumstances change. Future events and actual results could differ materially from those projected in our forward-looking statements, including the current and potential future impact of the COVID-19 pandemic on our business, results of operations, and financial position. Additional information concerning factors that could cause results to differ materially from our forward-looking statements are described in greater detail in our press release issued this morning and our filings with the SEC. I will now turn the call over to Dr. Brady.

Thank you, Joshua, and good morning, everyone. 2022 promises to be an exciting year for Aldera as we enter a catalyst-rich period It will highlight not only what we hope will be the successful completion of clinical development for reproxilap and dry eye disease, but also the emergence of our RAS modulator platform for the treatment of systemic autoimmune and inflammatory diseases and late stage regulatory milestones for ADX2191 for the treatment of certain rare retinal diseases. We believe that our systemic and retinal platforms are broadly underappreciated and underexposed. And we therefore intend to aggressively build awareness of these platforms throughout 2022 and beyond. Our plan to increase recognition of our systemic immune modulating platform is indeed near term. The Aldera Therapeutics R&D Day will occur on March 29th. during which we plan to announce top line data from our phase two proof of concept trials of ADX629, our first in class oral RASP modulator in psoriasis, asthma, and COVID-19. The goals of the ADX629 proof of concept trials are threefold. First, to demonstrate an acceptable safety and tolerability profile for what represents The first time a RAS modulator has been orally administered to humans. Second, to indicate pharmacodynamic activity of ADX629 across a variety of biomarkers related to inflammation. And third, to elucidate signals with clinical activity consistent with what might be expected from small trials with varying levels of doses, durations of therapy, trial designs, and disease states. ADX629 and related molecules from our RAS modulator platform have the potential to be transformative for Aldera, creating a broad range of new commercial opportunities in systemic disease and complementing our late stage retinal and topical ocular programs. In addition to describing the initial Phase II outcomes for ADX629 and potential future clinical indications, we're particularly excited to welcome Dr. Jeffrey Thiele as the featured speaker for R&D Day. Dr. Thiele is the Umbach Professor of Internal Medicine in the Division of Rheumatology at the University of Nebraska Medical Center. He is a leader in the research of malondialdehyde, acetaldehyde, and other RASP as potentiators of the inflammatory response. Dr. Thiele brings a unique understanding of the science behind our RASP programs. We look forward to his perspectives on ADX629 and the potential for RASP modulation broadly as a novel approach for the treatment of inflammatory diseases. Our next set of catalysts relate to Reproxilab, a first-in-class RAS modulator for the treatment of dry eye disease and what we believe has the potential to be the next novel entrant in the dry eye disease marketplace. Results from the Phase III Tranquility II trial of Reproxilab in dry eye disease are expected during the middle of this year. Pending the outcome of Tranquility II and enrollment in the 12-month safety trial of Reproxilab in dry disease patients, we plan to submit an NDA for Reproxilab in dry disease after the completion of Tranquility II. The endpoint of the Tranquility II trial will be met if either Shermer test or ocular redness demonstrates statistical significance in favor of Reproxilab over vehicle. We've also initiated two additional trials, a crossover dry eye disease chamber trial and a one-day Shermer test trial, either of which could serve as pivotal trials in support of an NDA submission. In recent months, we've met with a number of ophthalmologists and optometrists across the United States to learn more about the substantial unmet medical need associated with treating dry eye disease. which we estimate affects 39 million or more adults in the United States. Nearly 20 years since the approval of the first prescription drug for dry eye disease, the market remains significantly underserved, a point supported by the millions of patients who report that first-line therapies are ineffective. Many of the dry eye disease professionals express a keen interest in a rapid and durable treatment that can be used chronically and enables improved patient outcomes compared with the current standard of care. We believe Roproxilab has the potential to be that treatment. The clinical benefits of Reproxilab are supported by a growing body of scientific research. In January, we reported the results of a Phase II dry eye chamber trial comparing patient-reported ocular discomfort and ocular itching symptom scores of Reproxilab versus Zydra, an approved drug for the treatment of dry eye disease. For both endpoints, Reproxilab demonstrated statistically significant symptom improvement compared to Zydra. And a separate study published last year in Clinical Ophthalmology, the Reproxilab eye drop experience, including a broad assessment of ocular sensations, over one hour following administration, was superior to that of Zydra. In allergic conjunctivitis, the Phase III Invigorate II allergen chamber trial was initiated in the first quarter of this year. Invigorate II was a randomized, double-masked, crossover trial. The trial design is substantially similar to that of the Phase III invigorate trial, the results of which were announced in April 2021. The invigorate trial demonstrated statistically significant superiority of roproxilab over vehicle in reducing ocular itching and redness, the key symptom and sign of allergic conjunctivitis, respectively. To avoid the confounding effects of pollen in the environment, allergen chamber trials are conducted exclusively in winter and often require two winter seasons to enroll sufficient numbers of patients, as was the case with the Invigorate trial. Therefore, we expect results from Invigorate 2 in 2023. In addition to Aldera's advancement to systemic disease, we are committed to a significant development effort in retinal diseases. Many of these diseases lead to loss of sight and are poorly treated today, especially retinal diseases that are rare. Along those lines, I am pleased to report the initiation of the phase two trial of ADX2191 in retinitis pigmentosa, an incurable, potentially blinding disease with no approved therapy. This single center, open label trial will evaluate the safety and tolerability of ADX2191 and patients diagnosed with retinitis pigmentosa due to specific genetic mutations, animal models of which responded to methotrexate treatment. The trial, which will be conducted at Duke University Medical Center, is expected to enroll eight patients, four patients receiving monthly and four patients receiving twice monthly intravitreal injections of ADX2191 over a period of three months. Results are expected during the second half of this year. In January, we announced the completion of enrollment in part one of the phase three GARD trial of ADX2191 in patients with proliferative vitreoretinopathy, or PVR. Another rare retinal disease that can lead to loss of vision yet has no approved therapy. PVR is the leading cause of primary retinal detachment after surgical failure occurring in an estimated 5 to 10 percent of retinal detachments. Results from Part 1 of GARD are expected in the second half of this year. To our knowledge, ADX2191 is the first methotrexate formulation specifically designed to be compatible with the vitreous, the fluid in the back of the eye. Thus, ADX2191 represents a unique commercial opportunity. For example, off-label methotrexate injections are standard of care for the treatment of ocular lymphoma. Together with retinitis pigmentosa and PVR, the current indications for our ADX2191 platform span three rare retinal diseases. In each indication, ADX2191 has received the U.S. FDA's orphan drug designation. Now I'll turn the call back over to Joshua for the financial review, after which I will summarize our recent clinical progress and our future potential in developing novel platforms for the treatment of immune-mediated disease.