Operator Good day, and welcome to the Spero Therapeutics Third Quarter 2020 Financial Results Conference Call. Today's conference is being recorded. At this time, I'd like to turn the call over to Sharon Klahre, Vice President of Investor Relations and Strategic Finance. Please go ahead, ma'am.

Great. Thank you, operator, and thank you all for participating in today's conference call. Earlier today, Spero Therapeutics released financial results and provided a pipeline update for the third quarter ended September 30, 2020. If you've not yet seen the press release, it's 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 this press release and on this conference call contain forward-looking statements based on current expectations, including statements about the initiation, timing and information to the FDA and NDA for tebipenem HBr and the potential approval of tebipenem HBr by the FDA. Future commercialization, the potential number of patients to be treated by tebipenem HBr and market demand for tebipenem HBr generative. Expected broad assets across payer channels for tebipenem HBr, the expected pricing of tebipenem HBr and the anticipated shift from interveners to oral administration. The design, initiation timing and progress and the results of the company's preclinical studies and clinical trials and its research and development programs. Management result of such preclinical study and clinical trials, the impact of COVID-19 pandemic and the company's business and operations, and the company's cash forecast and anticipated expenses and the sufficiency of its cash resources. So forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those contained in such statements. So the factors that could cause or contribute to such differences are described in detail in Spero Therapeutics filing with the SEC, including in the Risk Factors section of our quarterly report on Form 10-Q 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. With us in today's call from Spero are Dr. Ankit Mahadevia, Chief Executive Officer; Dr. David Melnick, Chief Medical Officer; Cristina Larkin, Chief Operating Officer; and Steve DiPalma, Interim Chief Financial Officer. And with that, I'd like to turn the call over to Dr. Ankit Mahadevia. Please go ahead, Ankit.

Thank you, Sharon, and good afternoon, everyone. This is a very exciting time for Spero, and I'm delighted to have the opportunity to review our progress with you today. First, I'd like to highlight our recent announcement indicating that the ADAPT-PO Phase 3 trial met its primary endpoint with data demonstrating that oral tebipenem HBr is non-inferior to IV or dependent for the treatment of complicated urinary tract infections and acute pyelonephritis. The positive results from this trial comparing oral tebipenem HBr to IV ertapenem in a representative population are quite noteworthy as they show that tebipenem HBr can provide the convenience of an oral therapy without making any compromises on clinical response, safety or tolerability. These results represent an important achievement not only for Spero, but also for the broader industry and our potential patients. ADAPT-PO was truly a landmark trial as it was the first head-to-head comparison of an all-oral regimen against an all IV regimen for the treatment of cUTI. The trial was designed to demonstrate robust clinical outcomes and give physicians the confidence to push oral tebipenem HBr. It's approved to the millions of cUTI and AP patients who otherwise would be at risk for needing IV therapy in hospitalization. If approved, tebipenem HBr will be the first new oral therapy for cUTI in 26 years, and the first oral carbapenem antibiotic approved for cUTI and AP. As previously discussed with FDA, positive results in the single, well-controlled pivotal trial could be sufficient to support the approval of a new drug application or NDA for tebipenem HBr. This trial, together with supported Phase 1 trials, will form the basis of our NDA submission for tebipenem HBr in the U.S. We continue to expect to make an NDA submission to the FDA in the second quarter of…

Thank you very much, Ankit, and good afternoon, everybody. We've continued to make significant progress on our pipeline programs through the third quarter, and I'm excited to review our clinical accomplishments today. I'll begin with our lead candidate, tebipenem HBr, an oral carbapenem that recently completed its successful Phase 3 clinical trial, ADAPT-PO, for the treatment of complicated urinary tract infections, including acute pyelonephritis. The trial met its primary endpoint, demonstrating that oral tebipenem HBr is non-inferior to IV ertapenem in the treatment of patients with complicated urinary tract infections and acute pyelonephritis. Primary endpoint was met with an overall with combined clinical and microbiological response rate of 58.8% for oral tebipenem HBr and 61.6% for IV ertapenem. This met the trial's pre-specified non-inferiority margin of 12.5% and is complemented by tebipenem's compelling safety and tolerability profile, which was similar to IV ertapenem. In October, we presented additional data from the ADAPT-PO trial as an oral late-breaker presentation at IDWeek 2020. You can find all 15 posters and presentations from IDWeek 2020 on the Spero Therapeutics website. Data from the ADAPT-PO trial demonstrated that both clinical cure and microbiological eradication rates, the current level between treatment groups at the end of treatment, the test of cure and at most tolerable features. Clinical cure rates, which are important to clinicians because they're a key determinant in the routine management of complicated UTI or acute pyelonephritis, were greater than 93% in both treatment groups at the primary outcome analysis of test of cure. The high clinical success rates was sustained through the late fall visits, demonstrating a durable clinical response with complicated UTI or acute pyelonephritis. Favorable microbiological eradication rates and test of cure were likewise comparable between treatment groups, and were sustained up through the late fall visit in both treatment…

Thank you, David, and good afternoon, everyone. In addition to working on advancing our clinical programs and the planning for the potential approval of tebipenem HBr, we've also been hard at work preparing for the much anticipated launch. And so today, I'm going to focus on a few key areas that – as we prepare our go-to-market strategy, including our conviction around the broad market opportunity, our focus on building advocacy and feedback from our customers, and lastly, how we're progressing in building our commercial infrastructure and capabilities. So let's start with the market opportunity. As Ankit mentioned, that it's been 26 years since the last oral drug has been approved in the United States for cUTI. And so we've been busy in analyzing multiple data sets to help us triangulate the size of the opportunity. First, we've done a bottoms-up claims analysis of the diagnosed UTI patients in the U.S., and the data points us to roughly 2.7 million prescriptions where tebipenem HBr could be a potential replacement. These are patients that are either receiving multiple rounds of oral antibiotics or receiving the second line IV therapy and could be a candidate for a new oral treatment. Next, we've reviewed the data on IV carbapenem use, and there's been more than 100% increase in carbapenem use over the last six years for cUTI, and a significant portion of that growth has been in the outpatient setting. All of this data combined with feedback from our customers, support the broad market opportunity for new oral carbapenem. In fact, we've engaged more than 200 healthcare providers, and they consistently reinforce the unmet need and their significant interest in tebipenem HBr. They've reinforced that patients with a prior failure to an oral antibiotic or patients with resistant bacteria are the right targets…

Thank you, Cristina, and good evening, everyone. I'll provide an overview of Spero's financial results for the quarter ended September 30, 2020. Total revenue for the third quarter of 2020 was $4 million compared with total revenue of $4.6 million in the third quarter of 2019. The decrease in the third quarter of 2020 was due to lower reimbursement under Spero's contract with the Biomedical Advanced Research and Development Authority or BARDA, or qualified tebipenem HBr expenses. As a reminder, we currently have total committed non-dilutive funding from BARDA of $44 million, inclusive of $10 million in funding from the Defense Threat Reduction Agency. We have received $20.1 million of committed funding from BARDA as of the end of September, and there's a second option of $12.7 million that remains exercisable by BARDA. Research and development expenses for the third quarter of 2020 were $17.7 million and were lower than this $18.5 million reported for the same period of 2019. This year-over-year decrease was due to lower expenses on the tebipenem HBr program following the completion of significant activities in the Phase 3 clinical trial. However, we do expect to incur some additional expenses related to tebipenem HBr as we finalized activities related to the Phase 3 clinical trial and advance the potential NDA filing for tebipenem HBr. General and administrative expenses for the third quarter of 2020 of $5.3 million were higher than $4.1 million reported in the same period of 2019, primarily due to increased headcount and professional fees to support pre-commercial activities and growth in the business. We continue to expect general and administrative expenses to increase to support tebipenem HBr through potential approval as well as historic other pipeline products. Spero reported net loss for the third quarter ended September 30, 2020 of $18.9 million or $0.86 per common share. Compared to a net loss of $17.7 million or $0.95 per common share reported for the same period in 2019. As of September 30, 2020, we had cash and cash equivalents of $127.2 million, including $74.7 million in net proceeds from the follow-on offering that closed on September 15, 2020. Subsequent to quarter end, we received an additional $11.2 million in net proceeds through the exercise of the over-allotment option for the underwriters, bringing the total net proceeds from this offering to $85.9 million. We believe that our existing cash, cash equivalents and marketable securities, together with our non-dilutive earning commitments, will be sufficient to fund operations into the first quarter of 2022 through the approval process for tebipenem HBr. For further details on our financials, including comparisons of the quarters ended September 30, 2020 and September 30, 2019, please refer to our 10-K[ph] filed with the SEC today. We'd now like to open the call for questions. Operator?

Thank you. [Operator Instructions] And we'll take our first question from Louise Chen with Cantor.

Hi, good afternoon. This is Carvey in for Louise today. Thank you for the color on COVID. Just want to dig deeper. How much COVID-19 impacted the treatment landscape for bacterial infections that require IV administrations? Have patients been switched to other types or other classes of treatment? Has COVID-19 impact clinical trial speed in the infectious space? Secondly, what are the biggest competitors to oral tebipenem HBr, which drugs would take the most shares from, given the discussed pricing range about $300 to $500 a day for a 10-day course? Thank you so much.

Well, thanks very much for the questions. I will take the first one in terms of the impact of COVID-19, and I'll pass the competitive landscape on to Cristina. So in terms of the impact of COVID-19, really, the ethos generally in infectious disease has been to treat patients outside of the hospital whenever possible. And certainly, in the setting of COVID-19, given the increased risk that a patient has as an inpatient in getting COVID-19 as well as the capacity issues that are unnecessary hospitalization can pose to the hospital, there has been a continued push to try to treat our patients in the outpatient setting wherever possible. And as Cristina mentioned, we cannot do so for patients with complicated urinary tract infections and acute pyelonephritis is that there isn't an oral agent that can treat those types of resistant infections. And so really, tebipenem is positioned well to be a part of the toolkit to help treat patients where they should be whenever possible, which is outside of the hospital. That was true prior to the advent of COVID-19, and it's especially true now. In terms of your question on clinical trials, certainly, just throughout the ecosystem, COVID-19 has had, and I think continues to have, an impact on the enrollment and follow-up of patients with clinical trials. Fortunately, for us we have been able to, with an excellent clinical operations team, manage that well and we're able to deliver ADAPT-PO on time with high-quality data, number one. And number two, also the Phase 1 studies that were outstanding for the filing of the NDA. Further, we've accounted for that in our operational timelines for our pipeline. And so the team demonstrated their ability to navigate this and deliver and we've certainly accounted for that. Cristina, I'll pass the question about the competitive landscape in the marketplace to you.

Thanks, Ankit. And there are two parts to it. I think you asked also about where we're going to take share from, which I think also plays into the competitive landscape a bit. And as we've seen the patient journey is that patients are often having to go to the emergency room or ultimately getting hospitalized because of the lack of oral treatment options, not because they're sick and require this. And so we do see a significant portion of the business in deflecting that or catching them on the other side of the hospitalization. So it's very telling to see that maybe ertapenem and the other carbapenems, much of the growth that we've seen, as I shared today, where we would take share from in addition to drugs such as Hiperson[ph] and [indiscernible], which is also a drug that is often used for ESBL and [indiscernible] strain. The reason why I don't point you to any oral agents is because there aren't any available oral agents that fit this criteria that will meet the resistance patterns that we're seeing today. There's nothing today in the marketplace, either branded or generic, that will meet that on the oral side, and there's nothing in the near-term pipeline either. I think that's why this needs a pretty broad and open market opportunity for us.

Got it. That was super helpful. Thank you so much.

[Operator Instructions] And we'll take our next question from Ritu Baral with Cowen.

Hi. This is on Vishal on for Ritu. A few questions regarding the upcoming NDA launch. Are there any remaining required items for the NDA in terms of kind of finishing up Phase 1 studies? Any preemptive data left to be generated? And a quick follow-up, if the pre-NDA meeting have been scheduled yet for the FDA or it's not happened yet? Thanks guys.

Yes. Thanks so much, Dushyanth, for the question. So the three parts to filing the NDA, number one, is the Phase 3 data, of course. Secondly is the supportive nonclinical and Phase 1 studies. And then third is documentation around our CMC. And I would say that all three of those elements are on track as it relates to our overall timeline for NDA. Relative to our last earnings call, we have completed enrollment for the Phase 1 study that were outstanding. And again, that's been accounted for in our timelines.

Okay. Perfect. And any color on whether the pre-NDA meeting has occurred and if it has been set yet?

The pre-NDA meeting has not occurred, but we would expect that in 2021.

Okay. Perfect. Thanks guys.

Thank you and next, we'll hear from Stephen Willey with Stifel.

Hi. This is Ellen on for Steve. Thank you for taking the question. So can you provide any updates with regards to potential partnership discussions for ex-U.S. commercialization of tebipenem? Or maybe where those commercialization stand as they've started and how you're thinking about that opportunity?

Thanks so much for the question. I would maybe zoom out to 100,000 feet, and we have a variety of opportunities to continue to build our balance sheet as well as our wherewithal to advance our medicines, and these include partnerships around the pipeline as well as partnerships around different regions of tebipenem along with ability to collaborate with public agencies to complement what we're doing. And finally, just given the low royalty burden on tebipenem, the ability to collaborate around the product itself. And so really, the status of those discussions, certainly, with the quality of data we've had, we continue to have dialogues about the best way to both build our balance sheet as well as continue to think about the best way to deploy tebipenem and our other pipeline medicines to patients. We really won't comment further than that in terms of our public dialogue. Those conversations continue to go on. And certainly, the quality data we have around our pipeline has facilitated those.

Okay. Great. Thank you for the color. And then maybe just one more from me. So for SPR206, you partnered with Everest Medicine, I'm just wondering if you could remind us, to what extent going forward future Phase 2 registrational trial design and clinical development planning will Everest involve in those decisions, is more of a collaboration effort between partners? Or is it more Spero-centric? Thanks.

Well, yes, and this speaks perhaps to our philosophy in terms of partners. And so along with Everest, we collaborate with both pharmaceutical companies and private foundations and public agencies throughout our pipeline. And as always, we do see all of these partnerships as true partnerships and the opportunity to seek input from these partners who would have thoughtful and well informed ideas about drug development is something we enjoy and welcome. And so certainly, we welcome all of our partners, including Everest input in the plan. And ultimately, we'll drive forward on 206 certainly what's right for patients here in the U.S. and Europe, but also in the rest of the world.

That is great. Thank you.

Thank you and next from Oppenheimer, we hear from Kevin DeGeeter.

Hi. This is Susan calling on behalf of Kevin. I had a couple of questions on SPR720 program that I wanted to follow-up on. When can we expect to get the complete design for Phase 2 study? And I mean the clinical part Phase 2b?

Yes. Thanks for the question. Just to be clear, the subsequent studies after the Phase 2a that we expect to begin dosing this year are something that we continue to contemplate and collaborate with both the NTM physician community, but also our colleagues at FDA. And so I don't have a set time on to when we will start to have that dialogue. But a few parameters that the team has already commented on publicly, which is number one, the Phase 2a that we are embarking on is a crucial step ahead of subsequent clinical studies because what it does is it enables us to show that oral 720 can drive resolution of disease on its own. And we really set it up well downstream for combining with other agents in the downstream Phase 2b. We've also said that there's an opportunity for those studies to go faster and be more attuned to the way the care of NTM patients evolving by having a clinical endpoint. And in terms of further details, we're going to continue to collaborate with the physician community as well as our colleagues among the regulatory agencies to deliver more in the future date.

So just kind of a follow-up on that. What was your view and maybe the clinician community's view of the omadacycline data for NTM? Because I know that they can be a little bit different by using a clinical composite score?

Yes, and I'll have to say that we won't comment specifically on the Paratek, I would say that 100,000 feet that they are focused on mycobacterium abscessus, which is a smaller but also important indication. And I think that the limited data that we've seen to-date suggest that it could be a potential option, but we certainly look forward to more details on what measure they'll use in a more fulsome trial that can provide a more fulsome and statistically based platform for us to better understand the role of [indiscernible] in abscessus. And so certainly, much likely we will look for the details, and perhaps that will be helpful for the community as we go forward as well.

Okay, great. Those are all the questions.

And next, we'll have a follow-up from Ritu Baral.

Hi. This is Vishal again. Thank you for taking my follow up question. I just wanted to also ask about the NTM study with SPR720 entering for the Phase 2a, if any information can be given on how and when do you assume placebo effect? And if you are expecting dose response from the two doses? Thank you.

I'll pass that to David. David, over to you to talk about the two issues.

Yes. In terms of a dose response, the two doses that have been chosen for Phase 2a were derived from, that combination of data that was actually presented at IDWeek. We are bracketing our predictive therapeutic exposure with the two doses that we're using will depend on the pharmacodynamics in men, I think both doses are likely to be active. Will we see a dose response? Not sure yet. And the first part of your question?

Okay. Thanks. Yes, regarding whether how we are aiming for this study? And what is the assumed placebo effect for the Phase 2a?

Yes. For the Phase IIa study, the role of the placebo effect is – or the role of the placebo is created baseline against which we can assess the microbiologic activity of the active compounds. So the response assessment will be based on demonstrating a change in the slope of the camp overturn compared to placebo.

Okay. Perfect. Very helpful. Thank you very much.

Thank you. I am showing no further questions in the queue. I will now turn the call back over to Dr. Mahadevia for additional comments.

Thank you, operator, and I appreciate everyone's time for joining us today. I invite everyone to join us at our next webcast presentation at the Stifel Nicolaus Healthcare Conference on November 18. Thank you very much, everyone, and have a great evening.

That concludes today’s conference call. We thank you for joining. You may now disconnect.