Aldeyra Therapeutics, Inc.

Ladies and gentlemen, this is the operator. Today's conference will begin in approximately two minutes. Until that time, your lines will again be placed on music hold. Thank you for your patience. Thank you. Thank you. Thank you. Thank you. Ladies and gentlemen, thank you for standing by and welcome to the Aldera Therapeutics Conference Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. I would now like to turn the conference over to your Chief Financial Officer, Joshua Reed. Please go ahead, sir.

Joshua Reed Good morning, everyone. With me is Dr. Todd Brady, President and Chief Executive Officer of Aldera. This morning we issued a news release reporting top line results from the Phase III Invigorate Clinical Trial of Reproxilab and Allergic Conjunctivitis. A copy of the news release is available on the Investors and Media section of our website, www.aldera.com. The news release should be read and considered in conjunction with the slides presented and prepared comments made on today's call. Please turn to slide two. This presentation and various remarks, which may be made during this presentation, contain forward-looking statements regarding Aldera and investigational drug candidate Raproxilab. Forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause Aldera's actual results performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. These statements reflect Aldera's current views with respect to future events and 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 results from clinical trials or portions of clinical trials may not accurately predict results of future trials for the same or different indications, and 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 may 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 the company's 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 the company's press release issued this morning and our filings with the FCC. Now, beginning with slide three, I will turn the call over to our President and Chief Executive Officer, Dr. Todd Brady.

Thank you, Joshua. I am excited to share with you all this morning the remarkable top line results from our phase three Invigorate trial in allergic conjunctivitis. in which statistically significant improvement over vehicle was observed for the primary endpoint of patient-reported ocular itching, the key secondary endpoint of investigator-assessed ocular redness, and the secondary endpoints of patient-reported ocular tearing, and of total ocular severity score. Invigorate is the second positive, large, well-controlled phase three trial for Reproxilab and allergic conjunctivitis, and the third positive trial of Reproxilab demonstrating improvement versus vehicle of signs and symptoms in a chamber model of anterior ocular inflammation, including allergic conjunctivitis and dry eye disease. We wish to thank the Invigorate investigators and the Aldera clinical staff that worked so hard on the Invigorate trial over the past two years, as well as the subjects that participated in an Invigorate. Most importantly, we are thrilled to provide new hope for the millions of patients and thousands of physicians that today are forced to rely on therapies that are often inadequate or cannot be used chronically due to serious side effects. Reproxilab represents true innovation in allergic conjunctivitis, a novel drug with a novel mechanism for the first time in decades. The results of Invigorate suggest substantial utility of Reproxilab in a disease that affects approximately one-third of the U.S. population and more than one billion people worldwide, as is described on slide four. With the rise in global temperatures and seasonal pollen counts, the prevalence of allergic conjunctivitis continues to increase. Current therapies are not effective in significant proportions of patients or cannot be used for chronic treatment due to serious side effects. And yet, new therapeutic mechanisms in allergic conjunctivitis are few and far between. As is illustrated on slide five, Reproxilab represents a potential new approach for the treatment of allergic conjunctivitis that is independent of histamine, which, after exposure to allergen, persists for only a limited time. The rapid elimination of histamine may explain why an estimated 30 million people in the United States alone are not adequately treated with topical antihistamines. And while topical corticosteroids may be used for the treatment of the persistent effects of ocular allergy, corticosteroids cannot be used for chronic therapy due to serious side effects, which may include the potential for elevations in intraocular pressure, cataract formation, ocular infection, corneal ulcers, and other potentially sight-threatening complications. In contrast to histamine, which is an acute and transient inflammatory mediator, RASP, the target of Reproxilab, lead to a chronic, self-perpetuating inflammation that results in persistent symptoms occurring over hours to days. Reproxilab covalently binds to and has been observed to irreversibly inhibit RASP, providing a potentially unique and durable approach for the treatment of ocular allergy. Given Reproxilab's safety profile and clinical results observed now across 14 clinical trials, we believe that Reproxilab, if approved, could represent an ideal complement to antihistamines and a replacement for corticosteroids. Slide 6 summarizes the Invigorate trial, which was conducted in an allergen chamber. as part of an FDA-approved trial design. The allergen chamber model is an innovative and demanding method we believe is optimal for testing allergic conjunctivitis drug activity because it combines the real-world exposure of a field trial with the controlled pollen exposure of directly administering allergen to the eye. In addition, the allergen chamber allows for the assessment of prophylactic and treatment effect of drug. To our knowledge, Reproxilab is the first late-stage investigational therapeutic that has been rigorously tested in an allergen chamber. Slide 7 outlines the two-way crossover design of the randomized vehicle-controlled double-masked Invigorate trial. Allergic conjunctivitis patients were exposed continuously to controlled amounts of ragweed pollen over approximately three and a half hours. Subject-reported ocular itching and tearing scores, as well as investigator-assessed ocular redness scores, were recorded approximately every 10 minutes. Droger vehicle was administered just prior to allergen exposure and at 90 minutes when peak symptoms typically occur. The administration schedule allowed for the assessment of the activity of Reproxilab in preventing the development of allergy symptoms and signs. as well as drug activity in treating the disease at near-peak symptomatology. As shown on the right of the slide, the primary endpoint for invigorate was statistical significance in ocular itching at a majority of 11 time points between 110 and 210 minutes in the allergen chamber. The key secondary endpoint was change from baseline in ocular redness. The trial also evaluated patient-reported ocular tearing score and the ocular severity score, an 11-point composite of itching, tearing, and redness scores in the allergen chamber. The key secondary and secondary endpoints were assessed using a mixed-effect model of repeated measures, or NNRM analysis, over the duration of the chamber. Remarkably, Invigorate achieved the primary endpoint of improvement over vehicle and patient reported ocular itching score at all 11 pre-specified time points, each with a p-value of less than 0.0001, as is summarized on slide 8. Over the duration of the allergen chamber, improvement over vehicle for the key secondary endpoint of ocular redness was achieved. as were the secondary endpoints of patient-reported ocular tiering score and the total ocular severity score. Consistent with the primary endpoint, p-values for all secondary endpoints were less than 0.0001, indicating definitive superiority of roproxilab over vehicle across symptoms and signs of allergic conjunctivitis in a setting of continuously moderate to high pollen exposure. Importantly, we are not aware that any other investigational drug has demonstrated similar activity in a late-stage allergen chamber trial. Invigorate enrolled 95 subjects, 89 of whom completed both treatments. Consistent with prior clinical experience, there were no observed safety or tolerability concerns in the trial and no discontinuations due to adverse events. Slide 9 illustrates the results of the primary endpoint of patient-reported ocular itching. Per FDA recommendations, the primary endpoint required that a majority of time points between 110 and 210 minutes after chamber entry were statistically significant in favor of drug. As is indicated on the chart, all pre-specified time points were statistically significant. and the p-value for each time point was less than 0.0001. Both prophylactic and treatment effects of drug were demonstrated. In particular, the slope of the itching score curve between the first and the second doses of drug was lower than that of the vehicle curve, and the increase in ocular itching from baseline for each time point over the entire chamber was less in Reproxilab-treated patients. After the second dose, progression of ocular itching was halted and trended slightly lower in drug-treated patients versus slightly higher in vehicle-treated patients. Similarly, the key secondary endpoint of ocular redness on slide 10 was observed to be statistically significant over the entire chamber. Unlike with ocular itching scores, baseline redness was slightly higher in drug-treated patients However, the increase in redness from baseline for every time point over the entire chamber was less in reproxilab-treated patients than in vehicle-treated patients. The redness scores were remarkably consistent across patients. Standard errors were approximately 0.03 units for each arm and 0.01 units for the contrast across arms. Importantly, Any noticeable change in redness, which is by definition what the redness scale measures, is clinically relevant. As we discussed with the release of the top-line results from the run-in cohort of the Tranquility Trial in Dry Eye Disease, ocular redness represents possibly the only objective sign of ocular inflammation that is of importance to patients. In allergic conjunctivitis in particular, ocular redness represents the key sign of the disease, hence the designation of redness as the key secondary endpoint. As with ocular itching scores, both prophylactic and treatment effects of drug were demonstrated. The slope of the redness curve was lower in drug-treated patients between the first and second doses, and after the second dose, progression of redness was halted and trended slightly lower in drug-treated patients versus slightly higher in vehicle-treated patients. Similar statistically significant results were achieved for the secondary endpoints of patient reported ocular tearing score, illustrated on slide 11, and the composite ocular severity score, which includes itching, redness, and tearing, illustrated on slide 12. Ocular tearing is another disturbing and persistent symptom that diminishes quality of life for allergic conjunctivitis patients. and represents the second most bothersome symptom besides itching. The activity of Reproxilab versus vehicle, as assessed by the total ocular severity score, an omnibus measure of the signs and symptoms of allergic conjunctivitis, indicates the near-definitive overall utility of Reproxilab for the treatment of the disease. Slide 13 summarizes the safety profile for Invigorate. There were no discontinuations due to adverse events, and there were no observed safety or tolerability concerns. Reproxilab has now been administered to more than 1,200 patients across 14 clinical trials with no observed clinically significant findings on safety assessments, including visual acuity, intraocular pressure, slit lamp biomicroscopy, and dilated fundoscopy. Turning to slide 14, in aggregate, Riproxilab has demonstrated success across a robust development program of allergic conjunctivitis trials across two different allergen challenge models. In combination with Alleviate, the Invigorate trial represents the second large, well-controlled trial to achieve statistical significance for the primary endpoint of ocular itching. including the run-in cohort of the Tranquility Trial and Dry Eye Disease, Invigorate also represents the third chamber trial in which Reproxilab was statistically superior to vehicle for symptoms and ocular redness. To our knowledge, no investigational allergic conjunctivitis compound has demonstrated comparable activity across symptoms and signs in a large, well-controlled allergen chamber trial, and in addition, to our knowledge, No recent investigational allergic conjunctivitis treatment filing has encompassed a comparable breadth of data across multiple models. The profound interrelationship between allergic conjunctivitis and dry eye disease, summarized on slide 15, is well described in the scientific literature. About half the patients that complain of ocular dryness also complain of ocular itching and vice versa. The three common culprits of ocular surface disease, pollen pollutants and parched environments, make the etiologies of dry eye disease and allergic conjunctivitis difficult to untangle for healthcare providers, necessitating novel therapies for chronic use that can treat both conditions. The potential importance of the relationship of Reproxilab to the overlap of allergic conjunctivitis and dry eye disease is illustrated on slide 16, which demonstrates the consistency of improvement in itching and dryness, two hallmark symptoms of ocular surface disease, across different challenge models featuring pollen and dry air irritants, and across patients with allergic conjunctivitis and patients with dry eye disease. The striking consistency for improvement over vehicle and reduction of ocular redness is illustrated on slide 17. As mentioned previously, ocular redness may represent the only objective sign of anterior ocular inflammation that is of importance to patients and, by extension, to healthcare providers. Looking at our upcoming milestones on slide 18, now having completed Invigorate, we remain on track to report top line results from Tranquility and Tranquility 2 in the second half of this year. And we look forward to discussing our NDA filing in allergic conjunctivitis with the US Food and Drug Administration shortly. Slide 19 summarizes the potential commercial advantages of Reproxilab in allergic conjunctivitis and dry eye disease. Reproxilab appears to improve symptoms and signs within minutes, and the symptomatic activity of Reproxilab appears to be broad. In sum, Reproxilab represents a new paradigm for the treatment of anterior ocular inflammation, a single drug, with broad applicability in inflammatory diseases that affect the front of the eye. In conclusion, I reiterate my gratitude to the staff and patients involved in Invigorate and join the patient and healthcare community in welcoming a potential new approach for the treatment of allergic conjunctivitis. With that, operator, we'd be happy to take questions.