Iterum Therapeutics plc

Hello, everyone, and welcome to the ITARM Therapeutics fourth quarter and full year 2022 financial results and business update. My name is Charlie, and I'll be coordinating the call today. You'll have the opportunity to ask a question at the end of the presentation. If you'd like to register a question, please press star followed by one on your telephone keypads. I'll now hand over to our host, Louise Barrett, SVP Legal Affairs, to begin. Louise, please go ahead.

Thank you, Charlie. Good morning and welcome to interim therapeutics fourth quarter and full year 2022 financial results and business update conference call. A press release with our fourth quarter and full year 2022 results is issued early this morning and can be found on our website. We are joined this morning by Corey Fishman, CEO and Judy Matthews, CFO. Corey will provide some opening remarks, Judy will provide details on our financial results and then we'll open the line to some Q&A. Before I begin, I would like to remind you that this call will contain forward-looking statements concerning our plans, strategies, and prospects for our business, including the development, therapeutic, and market potential of Sulipenem, the timing, conduct, progress, and results of our ongoing Reassure clinical trial, the expected timing of resubmission of our NDA, the term and coverage provided by our patent and other intellectual property rights, and the sufficiency of our cash resources. Actual results may differ materially from those indicated by these forward-listing statements as a result of various important factors, including uncertainties inherent in the design, initiation, and conduct of clinical development, including the reassure clinical trials, the availability and timing of data from the reassure clinical trials, changes in regulatory requirements or decisions of regulatory authorities, the timing or likelihood of regulatory findings and approvals, including the potential resubmission of our NDA for oral sulipanim, Changes in public policy or legislation and commercialization plans and timelines before Sulapenem was approved. The actions of third party clinical research organizations, suppliers and manufacturers. The accuracy of our expectations regarding how Byron's future our cash in hand will fund our ongoing operations and other factors discussed under the caption risk factors in our annual report filed this morning. In addition, any forward-looking statements represent our views only as the date of this call and should not be relied on as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. We will also be referring to non-GAAP financial measures during the call. We have provided reconciliations of GAAP reported to non-GAAP adjusted information in the press release issued this morning. With that said, I'll turn it over now to Corey for some opening remarks.

Thanks, Louise. Welcome and thanks for joining us today. I want to share some highlights from 2022 and talk about our 2023 activities. We made significant progress in 2022 to move the clinical development of sulopenem forward. We worked with the FDA to align on a design for an additional phase three clinical trial for oral sulopenem to address certain deficiencies the FDA noted in their complete response letter we received in July 2021. We are conducting our new Phase III clinical trial under a special protocol assessment, SPA, agreement with the FDA. The SPA agreement provides that the design and planned analysis of the clinical trial, as set out in the protocol submitted to the FDA, adequately addresses the objectives necessary to support the potential resubmission of the company's new drug application for oral psilopentamide. As a brief reminder, our new phase three clinical trial, known as REASSURE, comparing oral sulopenem to oral augmentin for the treatment of uncomplicated urinary tract infections is currently enrolling subjects. The REASSURE study is designed as a non-inferiority trial comparing oral sulopenem and oral augmentin in the augmentin-susceptible population and is expected to enroll approximately 1,966 patients. In the reassured trial, patients will be randomized to receive either oral psilopennine twice daily for five days or oral Augmentin twice daily for five days. The primary endpoint is the overall response, clinical and microbiologic combined response at day 12 of the trial. We expect to complete enrollment in the first half of 2024, and if successful, we'll resubmit our NDA to the FDA in the second half of 2024. If the resubmission addresses all deficiencies in the complete response letter we received in July 2021 from FDA, then the FDA's review and action should occur six months from receipt of our resubmission. It's important to note that the need for new oral treatments in the uncomplicated urinary tract infection therapy area remains high. Although the market is quite large, with approximately 33 million prescriptions in the US annually, almost all currently available oral treatment options face safety and efficacy challenges, including increasing resistance. leaving community physicians seeking new and effective treatment options. We are very pleased to share that Iterum has been granted two U.S. patents, one directed to the composition of the bilayer tablet of oral sulopenin, which contains sulopenin exudroxil and probenicid in a single bilayer tablet, and one patent directed to the method of use of oral sulopenin in treating multiple diseases, including uncomplicated urinary tract infections. Both of these patents will provide protection into 2039, which allows for a substantial runway to protect the value of oral sulopenin in the U.S. Outside the U.S., we have pending patent applications, including in Europe, China, Japan, and parts of South America, which were submitted following receipt of the written opinion of the International Search Authority, indicating that several claims directed to the composition of the bilayer tablet of oral sulopenem are novel and inventive. Additionally, we continue to evaluate potential new areas where there is an unmet medical need and where sulopenem could be an important potential alternative in treating those patients. We will share additional details as and when this plan develops further. Our cash position remains solid with a balance of approximately $61 million as of year-end 2022. We expect that our current cash, cash equivalents, and short-term investments will be able to fund our operations into mid-2024. In summary, we are pleased to have aligned with the FDA and begun enrollment in our reassured clinical trial and are looking forward to potentially bringing the first new oral penum to the market in order to help address a serious medical need in the community. Now I'll turn the call over to Judy for additional details on our financial results. Thanks, Corey.

Total operating expenses were $7.9 million and $30.4 million in the fourth quarter and full year 2022, compared to $6.8 million and $24.5 million in the fourth quarter and full year 2021. Operating expenses include research and development expenses and general and administrative expenses. R&D costs were $5.8 million for the fourth quarter and $17.6 million for the full year 2022, compared to $3.7 million and $10.7 million for the same period in 2021. The primary driver of the increase in R&D expense for the fourth quarter and full year was cost to support a reassure trial, which began enrollment in October 2022. gna costs were 2.1 million for the fourth quarter of 2022 which is 1 million dollars lower than gna costs of 3.1 million in the fourth quarter of 2021 due primarily to lower share based compensation expense full year gna costs were 12.8 million dollars in 2022 which is 1 million dollars lower than gna costs of 13.8 million dollars in 2021 primarily due to the cost of pre-commercialization activities carried out in 2021 prior to receipt of the CRL and a decrease in consultancies to support our general and administrative functions, partially offset by an increase in legal fees associated with the lawsuit filed in August 2021, which was dismissed with prejudice in January 2023, which means the case cannot be brought back to court. Our net loss on a U.S. GAAP basis was $5.1 million for the fourth quarter of 2022 and $44.4 million for the full year. Impacting the full year net loss was a non-cash charge of $17.4 million included in other income and expense in connection with the cancellation of share options. As we discussed last time, in July 2022, certain executives and employees agreed to the surrender and cancellation of previously granted share options in order to make available additional shares under the company's equity incentive plan, giving rise to this non-cash charge. There was no impact of this adjustment on cash or cash runway, which I will turn to in a moment. On a non-GAAP basis, which excludes certain non-cash adjustments, Our net loss of $6.4 million and $22.9 million in the fourth quarter and full year 2022 compared to our non-GAAP net loss of $3.3 million and $19.4 million in the fourth quarter and full year 2021. The $3.1 million and $3.5 million increase in our non-GAAP net loss for the fourth quarter and full year was primarily a result of higher R&D expenses related to our reassure trial. At the end of December, we had cash, cash equivalents, and short-term investments of $60.8 million, which, based on our current operating plan, will provide a cash runway until mid-2024. We expect to complete enrollment in the first half of 2024, and if the reassure trial is successful, we expect to resubmit to the FDA the NDA for the treatment of UTI in the second half of 2024. As of December 31st, 2022, we had approximately 12.6 million ordinary shares outstanding. Also, as of the end of December 2022, we had approximately $12.6 million of exchangeable notes outstanding, which can be exchanged at the option of the note holder for approximately 1.1 million shares. If the notes are not exchanged, we will pay the note holders $12.6 million plus accrued interest in January 2025. Now I will turn it back over to Corey for some closing comments.

Thanks, Judy. We'll open the line now to any questions.

Of course, thank you. If you'd like to ask your question, please press star followed by one on your telephone keypad now. We have a question from Ed Asa of HC Wainwright. Ed, your line is open. Please go ahead.

Hi, thank you so much for picking up our questions. This is Thomas here asking a couple questions for Ed. First, regarding Reassure, Can you tell us how many patients have been enrolled so far, and if not, approximately what percentage enrollment has been achieved so far?

Hey, Thomas. It's Corey. Thanks for the question. We're not going to disclose specifics around the study. We generally don't do that just in terms of, you know, trying not get people all riled up in good or bad ways. What I would tell you is I think the study is progressing very nicely. We've got a significant amount of sites open and we've had significant enrollment so far. So, you know, the piece that we will share and we have shared is that, you know, based on the current forecast of how that continues to go, we would expect to finish up enrollment in that first half of 24.

Got it.

And then perhaps a question regarding the interim analysis. What type of data can we expect after this analysis is finished? And is there any possible to adjust the trial based on the data?

Yeah, so the purpose of the interim analysis is really just to determine the patient size and make sure that the power remains where we had wanted it. And that's really the only information you get. It's generally done on a blinded basis. So you're really not looking at any of the data. And of course, you know, the company can never do that anyway. It's done by an outside data safety monitoring committee. So all they'll do is look at the blinded data and say, yeah, based on what we see right now, you're on track to maintain your power, or if you want to maintain this power, you need to add X patients if you're below where you expect it to be. So that's really the only piece of information you'll get when there's an interim analysis. It's really not about, you know, the efficacy in terms of, you know, we aren't going to know anything specific for SULO.

It's all going to be on a blinded basis. Got it. Thank you for the clarification.

Perhaps one last question. This one should be for Judy. A question about cash runway. You mentioned 2024. Just wondering, would this expect it to include top line data readout from Reassure?

Yeah.

You know, based, you know, we will definitely get through enrollment, as we said. in that first half of 2024, and, you know, we do expect to be able to fund up through data. So, you know, it's expected data is also expected, you know, shortly after, of course, within a few months of finishing enrollment.

Got it. Thank you so much, Corey and Julie, for taking our questions, and looking forward to anything . Thanks, Thomas.

Thank you. We currently have no further questions, so I'll hand back over to Corey for any final remarks.

Great. Thanks very much. So in conclusion, we want to thank you for joining us today. We continue to remain confident in the value of oral sulopenem to treat multidrug-resistant infections in the community. and we look forward to completing our ongoing clinical work and if successful resubmitting our nda to the fda for this important treatment option for physicians and patients ladies and gentlemen this concludes today's call thank you for joining you may now disconnect your lines