Otonomy, Inc.

Ladies and gentlemen, thank you for standing by and welcome to the Q4 2021 Autonomy, Inc. Earnings Conference Call. At this time, all participants are in listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during this time, you will need to press star 1 on your telephone keypad. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Mr. Robert Uhl. Thank you. Please go ahead.

Good afternoon, and welcome to Autonomy's fourth quarter and full year 2021 financial results and business update conference call. Joining me on the call from Autonomy are Dr. David Weber, President and Chief Executive Officer, and Paul Kerr, Chief Financial and Business Officer. Before I turn the call over to Dr. Weber, I would like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Autonomy's filings with the SEC, which are available from the SEC or on the Autonomy website, for information concerning the risk factors that could affect the company. Autonomy specifically disclaims any obligation to update any forward-looking statements except as required by law. I will now turn the call over to Dave Weber, President and CEO of Autonomy.

Thank you, Robert. Good afternoon, everyone, and thank you for joining us on this call to discuss Autonomy's recent business updates as well as our financial results for the fourth quarter and full year. We have continued to execute well against our development goals, which has set up 2022 to be a year of multiple clinical readouts for two of the largest market opportunities in neuro-otology, each with significant unmet medical need. Key takeaways from this update are as follows. As we announced last week, we have completed patient enrollment in the OTO 313 Phase II trial in tinnitus ahead of schedule. with top-line results for all time points expected in mid-2022. We also fully enrolled the OTO 413 Phase 2A cohort in hearing loss earlier than planned and moved up the timing for top-line results to early in the second quarter of 2022. Additionally, we have initiated clinical evaluation of higher dosing for OTO 413 and are initiating safety evaluation of higher and bilateral dosing for OTO 313. The data from this expanded set of clinical studies will support and inform our next steps for both programs. We believe these include initiating a full dose ranging phase two efficacy trial for OTO 413 by the end of this year and initiating the phase three program for OTO 313 in the first half of 2023. Regarding our OTO 825 gene therapy program, We continue to make good progress with ongoing IND enabling activities and still expect to file an IND in the first half of 2023. We're also continuing to progress our two other preclinical programs, OTO 510 for OTO protection and OTO 6XX for severe hearing loss. Finally, our balance sheet remains strong and we continue to expect that our current cash will fund the company through these multiple clinical readouts and into the second half of 2023. During this call, I'll provide a brief update on our programs, including plans for an investor R&D event in March, and then ask Paul to summarize the financial results. We can then open up the line for any questions. Beginning with OTO 313, we have completed enrollment in the Phase II trial ahead of schedule. We randomized 153 patients with persistent unilateral tinnitus of at least moderate severity, which is above our target enrollment of 140 patients. Patients were randomized one-to-one to a single intratempanic injection of 0.32 mg O313 or placebo and are being followed for four months. The primary endpoint is the same as reported for the successful Phase I-II trial. a responder analysis based on the proportion of patients who report a clinically meaningful improvement in the tinnitus functional index, or TFI, from baseline to months one and two following treatment. To assess durability of the OTO313 treatment effect, we extended the follow-up period out to four months. Compliance for completion of the TFI and daily symptom diary remains high, and we look forward to announcing top-line results for all time points in mid-2022. Additionally, we are close to initiating safety evaluations for bilateral as well as higher dosing of OTO313. This effort is important for the program since bilateral patients comprise approximately 50% of the tinnitus population. Furthermore, the higher dose we're evaluating is 0.64 milligrams. twice the dose used in the successful Phase 1-2 trial and ongoing Phase 2. We expect results from this one-month safety evaluation in the second half of 2022. This data, together with the Phase 2 results, are expected to support an end of Phase 2 meeting with the FDA and inform the design of the Phase 3 clinical program planned to start in the first half of 2023. Our next clinical stage program is OTO 413 for hearing loss. Following a successful ascending-dose Phase 1-2 trial, we initiated a Phase 2a cohort that enrolled a total of 33 patients with speech and noise hearing loss, the most common reason that patients seek treatment for hearing loss. This is a randomized, double-blind, placebo-controlled study that randomized patients two to one for a single intratempanic injection of 0.3 milligram Oto413 or placebo. Patients are being followed for three months and evaluated using the same three clinically validated speech and noise hearing tests used in the prior cohorts. The Digits and Noise, Words and Noise, and American English Matrix Phrase Test. Enrollment of the Phase IIa was completed ahead of schedule, and we expect top-line results early in the second quarter of 2022. In addition to the Phase IIa, we have also initiated clinical evaluation of higher dosing for OTO413. We expect to enroll approximately 12 hearing loss patients randomized 2 to 1 to OTO413 or placebo in at least one higher dose safety cohort, beginning with 0.75 milligrams. This is more than twice the dose used in the successful Phase 1-2 trial, which is an important expansion of the clinical data set to support next steps for this program. Based on results from the Phase 2a and higher dose evaluation, we expect to initiate a full dose-ranging Phase 2 efficacy trial in hearing loss patients by the end of 2022. Our third development program is OTO825, a gene therapy targeting GJB2, which is the most common cause of congenital hearing loss. Patients born with this mutation can have severe to profound deafness in both ears that is identified in screening tests now performed routinely in newborns. Preclinical proof-of-concept results for OTO825 demonstrate that a single administration of OTO825 rescues hearing loss and cochlear damage in two preclinical models representing a range of hearing loss severity caused by GJB2 deficiency. We have completed a pre-IND meeting with the FDA that provided guidance regarding non-clinical study design, manufacturing requirements, and clinical trial considerations, and have incorporated this feedback into our IND enabling programs. These activities are ongoing, and we expect to file an I&D in the first half of 2023. Our remaining two programs are OTO 510, an otoprotectant for patients at risk for cisplatin-induced hearing loss, and OTO 6XX, which targets hair cell repair or regeneration for patients with severe hearing loss. Preclinical development continues on both programs. In summary, we are making good progress in advancing our multiple programs for treating hearing loss and tinnitus, which represent large untapped markets with significant unmet medical need. In fact, we believe that the early completion of enrollment for both the OTO 313 Phase II and OTO 413 Phase II-A trials demonstrate the interest in new therapeutic options for these conditions. To help prepare investors for our upcoming clinical readouts, we will be hosting an investor R&D event on March 22nd. This event will include presentations by multiple key opinion leaders who will provide background information on tinnitus and hearing loss and review the Phase 1-2 trial results for OTO 313 and OTO 413. Additionally, members of our senior management team will provide an update on the ongoing trials and outline next steps for these programs. We hope that you are able to join us for this informative session, which is open for registration via the events page on our website. With that, I'll turn the call over to Paul Kerr, our Chief Financial and Business Officer, who will provide a summary of our financial results and plan.