Iterum Therapeutics plc (ITRMF) Earnings Call Transcript & Summary

Hello, everybody, and welcome to the Iterum Therapeutics, P3 REASSURE Clinical Trial Results. [Operator Instructions] It is now my pleasure to turn the conference over to Louise Barrett, Senior Vice President, Legal Affairs.

Thank you, Drew. Good morning, and welcome to the Iterum Therapeutics Phase III REASSURE Clinical Trial Results conference call. A press release with our top line results was issued earlier this morning and can be found on our website. The press release also has a link to the webcast and if you're not using the webcast, the slides we'll be referencing are available on our website, www.iterumtx.com, under the heading Investors and Events and Presentations and also filed as an exhibit to our current report on Form 8-K filed this morning with the SEC. We are joined this morning by our Chief Executive Officer, Corey Fishman; our Chief Medical Officer, Dr. Sailaja Puttagunta; and our Chief Financial Officer, Judy Matthews. Corey will provide some opening remarks. Sailaja will provide some more data on the results of our study, and then we will open our lines for Q&A. Before we begin, I would like to remind you that some of the information presented on this conference call will contain forward-looking statements concerning our plans, strategies and prospects for our business, including the development, therapeutic and market potential of oral sulopenem, our ability to address inefficiency set out in the complete response letter received from the FDA in July 2021, the expected timing of resubmission of our NDA, the expected timing of review of the NDA by the FDA, and the company's strategic process to sell, license or otherwise dispose of its right to sulopenem to maximize stakeholder value. Actual results may differ materially from those indicated by these forward-looking statements as a result of various factors outside of our control, including uncertainties inherent in the design initiation and conduct of clinical and nonclinical development, changes in the regulatory requirements or decisions of extra authorities, the timing or likelihood of regulatory filings and approvals, including the potential resubmission of our NDA for oral sulopenem, changes in public policy or legislation, the accuracy of our expectations regarding how far into the future our cash in hand will fund our ongoing operations, our ability to maintain our listing on the NASDAQ Capital Market, risks and uncertainties concerning the outcome, impact, effects and results of Iterum's pursuit of strategic alternatives, including returns, timing, structure, value benefits and cost of any strategic process and our ability to complete one at all, and the other factors discussed under the caption Risk Factors in our quarterly report on Form 10-Q filed with the SEC on November 14, 2023. In addition, any forward-looking statements represent our views only as of the date of this call and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that all said, now I'll turn you over to Corey for your opening remarks.

Thanks, Louise. Welcome, and thanks for joining us today. First and foremost, I want to share some very exciting news. We are very pleased to announce positive data from our confirmatory Phase III clinical trial in uncomplicated urinary tract infections, which was conducted under Special Protocol Assessment agreement with the FDA. Results demonstrate that oral sulopenem was noninferior to Augmentin with respect to the trial's primary endpoint, which was overall response which is the combined clinical cure plus microbiologic eradication at the test-of-cure visit in the microbiological modified intent-to-treat susceptible population. Very importantly, I'd like to thank all of the patients and physicians that participated in the REASSURE trial. And now I'll turn the call over to Dr. Sailaja Puttagunta, our Chief Medical Officer, for a bit more data on the results of our study.

Thanks, Corey, and good morning, everyone. On Slide 3, you'll see that REASSURE is a randomized, multicenter, double-blind, at the control study that randomized 2,222 adult women with uncomplicated UTI in a 1:1 manner to receive either oral sulopenem or oral Augmentin twice daily for 5 days. At the end-of-treatment visit occurred on day 5, the primary end point of overall response was measured on day 12 at the test-of-cure visit. The final study visit occurred on day 28. Slide 4 shows that the primary endpoint for this study was overall response, which was combined clinical success as well as microbiologic eradication. Clinical success in this study was defined as resolution of all baseline uUTI symptoms and the absence of any new uUTI symptoms. Microbiologic eradication was defined as a urine culture with less than 10 to the 3 colony-forming units per ml of the baseline uropathogen. The primary objective of this study was to establish noninferiority of sulopenem compared to Augmentin in the Augmentin susceptible population at the test-of-cure visit on day 12. Slide 5 highlights the results for the primary end point of overall response at the test-of-cure visit in the micro MITTS or Augmentin susceptible population. 61.7% of patients who received oral sulopenem achieved overall success compared to 55% of those that received Augmentin. The difference in success rates between the 2 treatment groups was 6.7%. And the lower bound with a 95% confidence interval around the treatment difference was 0.3. Noninferiority of oral sulopenem of Augmentin was established as the lower bound of the 95% CI was above minus 10%, and superiority was concluded as the 95% confidence interval did not include 0 and the ad hoc p-value was 0.02. Slide 6 shows that oral sulopenem also demonstrated consistent efficacy for all key secondary endpoints at the test-of-cure visit. Similar proportions of patients in each treatment group achieved clinical success, about 77%, while the higher proportion of patients in the sulopenem treatment group attained microbiologic success, 75%, relative to the 67% observed in the Augmentin treatment group. Slide 7 highlights that sulopenem demonstrated a consistent safety profile in this study relative to previous sulopenem Phase III studies and similar to other beta-lactam antibiotics. Both oral sulopenem and Augmentin were well tolerated in this study with less than 1% of patients discontinuing treatment due to adverse events. Overall, 19% of patients in the sulopenem arm and 12% in the Augmentin arm reported an adverse event. Drug-related adverse events were reported by 14% of patients in the sulopenem group relative to 8% in the Augmentin group. There were no serious adverse events in the sulopenem treatment group, while 5 patients in the Augmentin group reported serious adverse events. [ Both sulopenem ] were thought to be translated. There were no deaths in either treatment group in this study. The most common adverse events reported were diarrhea, nausea and headache, similar to those reported in the previous Phase III uUTI study. In conclusion, sulopenem was well tolerated with an adverse event profile consistent with beta-lactam antibiotics and no new safety signals were identified for oral sulopenem in this study. I'll stop here now and turn the call back to Corey.

Thanks, Sailaja. On Slide 8, you'll see that as Sailaja covered, we achieved our primary endpoint in this study by demonstrating that sulopenem was noninferior to Augmentin in the overall response at the test of cure in the Augmentin susceptible population. Additionally, in this population, sulopenem also demonstrated statistical superiority. Oral sulopenem also showed consistent efficacy in secondary and additional endpoints. Lastly, sulopenem demonstrated a very solid safety profile. In terms of next steps, we expect to resubmit our new drug application for oral sulopenem in Q2 of this year and provided that the resubmitted NDA addresses all of the deficiencies identified in the complete response letter we received from the FDA in July of 2021, we expect the FDA will complete its review and take action in the fourth quarter of this year, which would be 6 months from the date the FDA receives the resubmitted new drug application. Let's spend just a minute and talk about market dynamics. The uncomplicated urinary tract market is quite large, estimated at over 30 million infections annually. There is a significant need for new efficacious and safe oral products to treat uncomplicated urinary tract infections as the existing older oral products are experiencing high and increasing resistant rates as well as exhibiting subpar safety profiles. If approved, sulopenem would be the first oral penem approved in the United States and one of the first new branded treatments approved in the U.S. for uncomplicated urinary tract infections since the turn of the century. With positive data now in hand, we will be focusing on a strategic process to sell, license or otherwise dispose of our rights to sulopenem with the goal of maximizing value for our stakeholders. We're excited about potentially having sulopenem in the hands of patients and physicians in the underserved uncomplicated urinary tract infection market. We'll now open the lines for Q&A.

[Operator Instructions] Our first question today comes from Jason McCarthy from Maxim Group.

Congratulations on the data. Corey, can you talk a little bit about the outcome ending up being also superior on the primary endpoint? And if that's related to issues with resistance to Augmentin already, which is one of the standard therapies for UTIs and how sulopenem can really impact clinical outcomes if it gets approved or when it gets approved?

Sure. Actually, it's kind of interesting, Jason. Thanks for the question, first of all, because sulopenem hit the noninferiority as we talked about, in the susceptible population and was statistically superior, but that was in the susceptible population. So it's actually even a little bit different than, I would say, a little bit more favorable because we're not talking about the resistance population. Those are patients that had a bug that was susceptible to Augmentin. And in that population, we were both noninferior and statistically superior in that population.

Will the full data set be stratified by a resistant population as well as it had been in the prior study? Or is it because they are in the same class as lactams that you don't need to do that?

Yes. The resistant population in the study ended up being very, very small. And I believe we only had something on the order of 67 patients that were resistant and therefore, no conclusions can be drawn from a sample size that small. So we may look at that, but I don't think there's any conclusions that can be drawn just because of the sample size is as small as it is.

Got it. Last question. In terms of your commercial readiness, can you talk just a little bit about a lot of that readiness and kind of leg work that was done prior with expectations of approval in 2021, and what you'll need to do to kind of ramp that up should sulopenem get approved later this year?

Yes. I think the commercial side, as you said, had quite a bit of work done previously. And I think the real -- the opportunity for doing some more on the commercial is really just an update or a refresh of the data that was done, the research that was done and talking with payers, just confirming what we had already found out previously. And clearly, that -- all of that information is valuable in any scenario that we would take forward, be that in a potential transaction, be that on your own, all of that is always going to be important for getting the product ready to hit the market and have a very good solid uptake.

Congrats on the data.

[Operator Instructions] We have no further questions at this time. So I will hand back over for any closing remarks.

Great. Thanks very much. We appreciate you joining us today on this call. We are very excited by the results that oral sulopenem has demonstrated in our REASSURE trial, and we're looking forward to resubmitting our new drug application and working with the FDA during the review period with an eye toward potentially having this important treatment in the hands of patients and physicians in the underserved market of uncomplicated urinary tract infections. Have a great day.

That concludes today's call. You may now disconnect your lines.