Good afternoon, and welcome to the Spero Therapeutics Fourth Quarter and Year-End 2021 Financial Results Conference Call. [Operator Instructions] Please be advised that this call is being recorded, and a replay will be available. You can find information on the replay and further information related to today's announcement on the Spero Therapeutics website at www.serotherapeutics.com. At this time, I would like to turn the call over to Ted Jenkins, Vice President, Investor Relations at Spero Therapeutics. Mr. Jenkins, please go ahead.

Thank you, operator, and thank you all for participating in today's conference call. This afternoon, Spero Therapeutics released financial results and provided a pipeline update for the fourth quarter and full year 2021. Our press release is available on the Investor page of the Spero Therapeutics website. Before we begin, I'd like to remind you that some of the information contained in the news release and on this conference call contain forward-looking statements based on our current expectations, including statements about the potential approval of tebipenem HBr by the FDA and the timing thereof. The timing of the launch of tebipenem HBr, future commercialization, the potential number of patients could be treated by tebipenem HBr and market demand for tebipenem HBr generally. Also expected broad access across payer channels for tebipenem HBr, the expected pricing of tebipenem HBr and the anticipated shift in treating patients from intravenous to oral administration. The plans for the company's ongoing development of SPR720 statements about the future development and commercialization of SPR206 and the potential receipt of milestone payments as well as royalties on potential future sales of SPR206, the design, initiation, timing, progress and results of the company's preclinical studies, and clinical trials and its research development programs. management's assessment of the results of such preclinical studies and clinical trials; the impact of the COVID-19 pandemic on the company's business and operations in the company's cash forecast and anticipated expenses. The sufficiency of its cash resources and the availability of additional nondilutive funding from governmental agencies beyond any initially funded awards. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those contained in such statements. Several factors that could cause or contribute to such differences are described in detail in Spero Therapeutics' filings with the SEC, including in the Risk Factors section of our annual report on Form 10-K filed today. These forward-looking statements speak only as of the date of this conference call, and the company undertakes no obligation to publicly update any forward-looking statements or supply new information regarding the company after the date of today's release and call. Participating in today's call are Dr. Ankit Mahadevia, Chief Executive Officer; Dr. David Melnick, Chief Medical Officer; Cristina Larkin, Chief Operating Officer; and Sat Shukla, our Chief Financial Officer. With that, I'd like to turn the call over to Dr. Ankit Mahadevia. Please go ahead, Ankit.

Thank you, Ted, and thanks to all for joining us today to discuss our fourth quarter and full year 2021 financial results and corporate hotlines. Starting -- we'll start with our first lead product candidate, tebipenem HBr. We received a notice from the FDA stating that as part of its ongoing review of our NDA has identified efficiencies that preclude the discussion of labeling and post-marketing commitments at this time. This notice is clear that it does not reflect a final decision on FDA's ongoing review. We also note that this comes at the midpoint of the scheduled 6-month review period, which was the planned date to initiate discussions on proposed labeling and if necessary, any post-marketing requirements and/or commitment requests. There are three months remaining before the application's PDUFA date of June 27. We continue to have an active dialogue with FDA, and we'll continue to collaborate with them on the best path forward for tebipenem as quickly as we can. If this can be done to the FDA satisfaction, we believe there would be sufficient time to progress labeling anti-PMC PMR discussions within the existing PDUFA time frame, given how early in the review period, those discussions were originally scheduled to occur. We expect a late cycle review meeting to occur in the coming weeks, where we will have the opportunity for these continued discussions. Please note that there isn't additional detail regarding the review of India that we can share beyond what we've disclosed today. We seek to understand any issues in greater depth and also since discussions with FDA are ongoing. Given the timing of our ongoing discussions with the FDA, we will provide an update on or before our next earnings call, and we look forward to doing that as soon as we're able. As…

Thank you, Ankit, and good afternoon to all of you. It's my pleasure to share our pipeline updates with all those listening today. I'll begin by speaking about our lead candidate, tebipenem HBr. And I would like to reiterate Ankit's point that our near-term focus will be working with the FDA to continue advancing a path forward towards approval. In parallel with our regulatory efforts and in preparation for potential commercialization, we continue to work to ramp up our CMC capabilities. As part of these efforts, we are working with partners such as Meiji Seika, who have extensive experience manufacturing a granular formulation of tebipenem over the last decade. We believe that this manufacturing experience will be instrumental as we transition to a commercial organization. We are also continuing our work to refine our understanding of the needs of the clinical community and to forge partnerships with external clinicians. We are taking a multifaceted approach here as our medical affairs team has interacted with over 700 infectious disease physicians and neurologists so far, and a majority of the major national and regional health plans. And as Ankit noted earlier, we are also expecting and excited about the pending publication of the ADAPT-PO trial results in a high-impact peer-reviewed journal very early in I2. Our efforts in this area, together with the ADAPT-PO results have produced strong external interest in tebipenem, including in ways in which we could broaden its potential therapeutic impact. One recent example of this interest came in January when Spire was awarded up to an additional $12.9 million by BARDA to support a clinical trial and related activities that are designed to advance orderly administered tebipenem [indiscernible] development as a treatment for pediatric patients with complicated UTI and acute cinetobacter. This new funding was a result of…

Thank you so much, David, and it's a pleasure to be with you this evening to discuss the progress of tebipenem HBr. Our preparation for launch is focused on building a best-in-class commercial organization and creating a launch readiness plan that we believe to be a transformative treatment for cUTI. We continue building our launch plans as we work with the FDA to move forward on the ongoing review process of tebipenem HBr for the treatment of cUTI. There are an estimated 3 million patients annually in the U.S. that could benefit from a new, effective and safe oral treatment for cUTI. It's been 25 years since we've had a new approved oral therapy to treat these infections. And during the last 10 years, we have seen resistance to E.coli, the most common bacteria for cUTI increased threefold. We now face a significant health crisis with more than one out of every three cUTI patients in the hospital and one out of every five patients in the community that have limited or no oral options. And this is leading to challenging times for health care providers, who in attempts to avoid hospitalization for their patients are often cycling most patients through multiple rounds of ineffective or unapproved medications for cUTI. These challenges have made the treatment for cUTI in the outpatient setting, one of the most common and problematic infectious disease conditions health care providers face today. As we prepare for launch, we are focused on three distinct components: one, ensuring we drive early health care practitioner awareness and trial with our urologist, infectious disease physicians and hospitalist; two, building advocacy and support with key thought leaders and ensuring appropriate use as we look to bring the first oral carbapenem to market; and three, ensuring patient access and affordability. With…

Thank you, Cristina, and good afternoon, everyone. I'd now like to turn your attention to our overview of Spero's financial results for the fourth quarter and full year ended December 31, 2021. Total revenues for the fourth quarter of 2021 were $2.7 million compared with revenues of $1.9 million for the fourth quarter of 2020. The revenue mix was composed of reimbursement for pipeline candidates under collaboration agreements with third parties, the grants from various government agencies. Total revenue for the year ended December 31, 2021, was $18.3 million compared to $9.3 million for the year ended December 31, 2020. Total revenue for the full year 2021 was higher than the same period in 2020 due to increased client revenue received from Spero's contracts with DoD relating to SPR206. BARDA relating to tebipenem HBr and collaboration revenue from the company's license agreements at Pfizer and Epris Medicines. Research and development expenses for the fourth quarter of 2021 was $17.2 million compared to $13.2 million for the same period in 2020. This year-over-year increase was primarily due to increased direct costs related to SPR206 and an increase in research and development headcount. Research and development expenses for the year ended December 31, 2021, were $64.5 million compared to $67 million for the year ended December 31, 2020, with the decreased expenses due to the completion of significant activities and related costs of Phase 3 clinical trial for tebipenem HBr, offset by increased start-up costs related to SPR206 and an increase in research and development headcount. Looking forward, we expect research and development expenses to remain relatively flat in 2022 relative to 2021 and as we continue to support our pipeline candidates. General and administrative expenses for the fourth quarter of 2021 of $13 million were higher than the $7.5 million reported…

[Operator Instructions] The first question today comes from Louise Chen with Cantor. Please go ahead.

So I had a few questions on the FDA update. Just curious what kind of deficiencies in general? I know you can't talk about specifics, could preclude discussion of labeling and post-marketing requirements Secondly, how much interaction have you had with the FDA since you received this notice? And the third question is, what are the most likely potential outcomes when you get your update on or before May 2022?

Louise, thanks so much for the question. We completely understand and empathize with the interest in going deeper into the substance of the review. As we mentioned on the call, right now, we're not going to be able to go much deeper into those questions for two main reasons. One is that our ongoing dialogue with FDA will give us an opportunity to seek to understand better what the topics at hand are in front of us. And secondly, we do want to protect the integrity of ongoing FDA discussions. What our commitment will be is as those discussions happen and we highlighted late cycle review meeting in the coming weeks, we will commit to providing a deeper update no later than the next earnings call, which should be in mid-May.

The next question comes from Ritu Baral with Cowen. Please go ahead.

One, is it fair to say that you know what the topics of the deficiencies are based on the FDA communication to date? And if so, how much clarity do you think that you have right now or how much understanding of those topics do you have -- like is it enough to start addressing the deficiencies now? Or do you really, really need a lot more from FDA before you know even how to start addressing the deficiencies. And then I have a couple of follow-ups.

Yes. Thanks, Ritu, for the question. I would say, and we've said this in prior earnings calls that we continue to have a frequent and active interaction with our colleagues at FDA. It's one of the benefits of priority review. I would say that we continue to engage with them on a variety of subjects within the NDA application as the process has gone on. One of the reasons why we'll commit to the coming weeks to provide a deeper update is that we do need to seek a deeper understanding as we do have substantive dialogue with FDA. We do address and discuss with them in real time. But again, we won't be able to go much deeper here because we do want to seek to understand more deeply one. And second, because this is the subject of ongoing dialogue, we want to respect that process and then come back and give you updates at the appropriate time.

Got it. So it sounds like you need more over the following weeks to even start addressing the deficiency like you can't start in April, essentially, is that fair?

No. I would say that -- like I said, that we have engagement with the agency on a variety of topics. We engaged with them real time. We do need more information for me to give all of you a more comprehensive picture of where we are and what the next steps are. Further, as we build that understanding, again, we want to be respectful of the ongoing dialogue we have with the agency. So rest assured, we're working a problem. And as soon as we can say more and have a fulsome picture, we will tell you more.

Got it. In like the last couple of months, have you submitted any new data or any requested analysis? Was the full safety update recently submitted?

I mean, thanks for that question as well. Like I said, we've had a very productive and collaborative engagement with FDA, where we continue to correspond with them on the basis of the data that we've submitted. We won't go much deeper into kind of the minute mechanics of the back and forth. At the same time. As you've noted, we are having that collaborative discussion. We are working the problem. We will have more clarity to give you a comprehensive picture as we've done in the coming weeks.

Got it. And in the meantime, I guess, are you planning any change in commercial prep spend for Q2 in the meantime?

Well, I think you heard from Cristina and from me, we're continuing to invest to prepare for the precommercial activities that we're undertaking and thinking about launch should tebipenem be approved.

But has the rate of that changed at all or certain, I guess, aspects of the prep. Have they been sort of postponed or anything like that?

We're -- I mean, we've laid out the key priorities for preparing for launch, and that is educating clinician colleagues about the unmet need post the tebipenem CONSOL, preparing to engage with our payers as well as mapping out how best to deliver tebipenem, the clinicians have approved. All of those activities are ongoing, and we continue to invest in them.

The next question comes from Esther Hong with Berenberg. Please go ahead.

So first question is what typically occurs during a late-cycle review just generally? And then is that where at some point? And how would that shift in terms of where your discussions are with the FDA?

Yes, that's a great question. Thanks for asking it, Esther. I think one point that you're alluding to is that our PDUFA date is in late June, and we're sitting here in late March. We are about halfway through the planned review period. And you make an important point that that late cycle review meeting is another opportunity for us to engage with the agency on the topics that we've continued to be engaging with them on during the review period. So what I want to emphasize from our prior remarks is that we are in a deliberative and collaborative phase with our colleagues and agencies, not in a decisional phase and that continued dialogue including the late cycle visit gives us an opportunity to continue to work with them collaboratively to find the right path forward.

[Operator Instructions] The next question comes from Ram Selvaraju with H.C. Wainwright. Please go ahead.

This is [Matt] representing Ram at H.C. Wainwright. We were wondering what new market research, if any, might be presented to the investment community prior to the tebipenem HBr PDUFA date later this year.

Thanks for the question. I will pass that to my colleague, Cristina Larkin, who can best answer that.

Yes. Thanks for the question, Ram. We've actually done quite a bit of market research as it relates to the product, some of which is related to our targeting and understanding more about so that we can do some great behavioral mapping from our clinicians. And the second part is what you have, which is a an attitude and trial usage market research where we can understand readiness to prescribe tebipenem when it's available. And all of that data continues to reinforce, I think, for us, one, the high unmet need that we start to see and their interest in utilizing tebipenem and an appropriate -- for the appropriate patients. The full access of all of that data as we get closer to launch, I think our plan is we'd be able to share more of our commercialization plans as we get closer to the PDUFA date.

Okay. Great. And are there likely to be any other regional partnerships signed near-term involving elements of the pipeline? And can you refresh us on the current activities Pfizer is undertaking with SPR206?

Great question. So on the first point, strategically, as we've mentioned in prior calls, we are committed to focusing on preparing for tebipenem launch in the U.S. we are continuing to think about the right partners to help us commercialize tebipenem ex U.S., and as for the rest of the pipeline. As you rightly know, SPR206, we have -- we're delighted to have great partners in Pfizer and Everest and will opportunistically look for the right partners for SPR720. As it relates to the activities that Pfizer is collaborating with us on. Firstly, as we -- as Satya mentioned, they've made an equity investment in the company that supports our overall activities. Secondly, they've provided a very thoughtful, collaborative efforts on the ongoing development of SPR206 and certainly, their investment in the ongoing milestones help us support the ongoing activities as well as our colleagues at NIH and the Department of Defense, which give us the opportunity to advance a variety of activities for SPR206 on nonwood financing, including a Phase 2 study.

The next question comes from Kevin DeGeeter with Oppenheimer. Please go ahead.

Maybe one on 720. I appreciate the update and David's comments with regard to the study to kick off in the second half of 2022 being base, first of all, off of the probable 720 design. But plus some fee incorporation of recent FDA guidance on wondering whether you could expand on specific aspects of that FDA guidance that you will be looking to capture in the upcoming Phase 2 720 program.

Thanks, Kevin, for the question. David, I'll pass the question to you.

Yes. We're -- as I said, we're very excited about getting back into patients with -- we worked hard with FDA in collaboration to lift the clinical hold and in the end, the project at a clean bill of health. So we're moving forward. I think if you won't hint about the structure of that study, I'd refer you to the clinic trials listing for the prior trial, it will look somewhat similar in design. We will potentially take advantage of the fact that we now have a longer duration of toxicology coverage to extend the duration of that study. I think importantly, it gives us an opportunity to not only look at microbiologic endpoints, but FDA has become extremely interested in clinical outcome measures as endpoints for NTM studies and the Phase 2 study that we plan will assess a number of different approaches to that problem.

Great. Really helpful. And then with regard to the next $50 million potential draw under the royalty financing structure. Can you remind us whether tebipenem HBr needs approval by a specific time to exercise that next $50 million tranche or under different time line to approval scenarios, does access to that drug change?

Yes. Thanks for the question, Kevin. This is Sath. Tebipenem requires approval by the end of the year to qualify for that additional $50 million tranche. And I think that's been disclosed and that's what I would say.

This concludes our question-and-answer session. I would like to turn the conference back over to Dr. Mahadevia for any closing remarks.

Thank you, operator, and thanks to all that have joined us today. We look forward to the continued advancement of our pipeline, and we'll keep everyone updated as we go.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.