Spero Therapeutics, Inc.

We're about to begin. Good day and welcome to the Sparrow 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 Clary, Vice President of Investor Relations and Strategic Finance. Please go ahead, Nan.

Great. Thank you, Operator, and thank you all for participating in today's conference call. Earlier today, Spiro Therapeutics released financial results and provided a pipeline update for the third quarter end of September 30th, 2020. If you've not yet seen the press release, it's available on the investor page of the Spiro 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 our current expectations, including statements about the initiation, timing, and submission to the FDA and the NDA for W-BEN and HBR, and the potential approval of Tevipen and HBR by the FDA. Future commercialization, the potential number of patients to be treated by Tevipen and HBR, and the market demand for Tevipen and HBR genomics. Expected broad access across payer channels for Tevipen and HBR, the expected pricing of Tevipen and HBR, and the anticipated shift from intravenous to oral administration. The design, initiation, time, and progress, and the results of the company's preclinical studies and clinical trials, and its research and development programs. management assessment of the results of such preclinical studies and clinical trials, the impact of COVID-19 pandemic on the company's business and operations, and the company's cash forecast and the anticipated expenses and the sufficiency of its cash resources. Before-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 Spiro Therapeutics' policy with the SEC, including in the risk factors section. of our quarterly report on Form 1025 today. These forward-looking statements speak only as of the date of this conference call, and the company only takes 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 from Spiro are Dr. Ankit Mahavidya, Chief Executive Officer, Dr. David Melnick, Chief Medical Officer, Christina Larkin, Chief Operating Officer, with Steve DePalma, interim chief financial officer. With that, I'd like to turn the call over to Dr. Ankit Mahadeva. Please go ahead, Ankit.

Thank you, Sharon, and good afternoon, everyone. This is a very exciting time for Sparrow, 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 III trial met its primary endpoint with data demonstrating that oral tebupenem HVR is non-inferior to IV ertapenem for the treatment of complicated urinary tract infections and acute pyelonephritis. The positive results from this trial comparing oral tebupenem HVR to IV ertapenem in a representative population are quite noteworthy, as they show that tebupenem HVR 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 Sparrow, but also for the broader industry and our potential patients. ADAPT-TL was truly a landmark trial, as it was the first head-to-head comparison of an all oral regimen against an all IG regimen for the treatment of CVTI. The trial was designed to demonstrate robust clinical outcomes and give physicians the confidence to prescribe oral to become an HPR. It's approved to the millions of CUTI and AP patients who otherwise would be at risk for needing IV therapy and hospitalization. If approved, 10-E-Pen and HPI 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 tebupenem-HVR. This trial, together with supporting phase one trials, will form the basis of our NDA submission for tebupenem-HVR in the U.S. We continue to expect to make an NDA submission to the FDA in the second quarter of 2021. We have also made progress on our other clinical programs, which like tebupenem, are designed to treat important unmet needs in infectious disease. We were excited to announce in August that the FDA accepted the INV4-SPR720, our orally administered agent, being developed for non-tuberculous microbacterial, or NTM, infections. We remain on track to initiate dosing in a Phase IIa NTM trial by year end. Before handing off the call to David to go into more detail on the pipeline, I'd like to provide a few comments on how we're managing our business during the COVID-19 pandemic and the impact it's having on the practice of medicine. We continue to monitor for potential impacts of COVID-19 on our business and our ability to conduct our operations. In this pandemic environment, the Sparrow team is diligently trying to stay ahead of any potential impacts from COVID-19. And I'm pleased to report that at the current time, we do not see material impacts on our operations. We continue to benefit from the investments we made in informational technology early on that enable a fully remote workforce as the pandemic continues. We should also note that COVID-19 has changed the way medicine is delivered, with physicians and patients seeking to prevent hospital admissions whenever possible. What we are hearing from physicians is that they would prefer to treat a complicated urinary tract infection outside of the hospital, but at the current time, with the increasing prevalence of bacterial resistance among the existing oral antibiotics, millions of CUTI patients just don't have that option. Physicians are looking for ways to streamline patient care and expand access in the outpatient setting. Further, outpatient treatment could reduce exposure to secondary infection, including COVID banking, offer financial benefit to the hospital, and free up capacity for the seriously ill patients who have no viable alternatives to hospitalization. The availability of an oral medication that could enable a shift in care to the outpatient setting could thus address critical unmet needs that have been made worse during these unprecedented times. The pandemic also highlights the need for a comprehensive approach to developing medicine to address current and future infectious threats. Policymakers, government agencies, and major pharmaceutical companies are joining us in in supporting the development of critical solutions to these threats. We're thrilled to collaborate with the ecosystem in these efforts, highlighted by our partnerships with several government agencies, including BARDA, the U.S. Department of Defense, and DTRA, as well as our relationships with corporate partners and private foundations. Finally, before handing it off to David, I want to mention our success on the financial front. During the third quarter, we completed an equity financing for net proceeds of $85.9 million, including the exercise of the over-allotment option. We have sufficient cash, cash equivalents, and marketable securities together with our non-believer financing commitments to fund the company into the first quarter of 2022 through the approval process for TBI. And with that, I will hand it over to David to review our clinical progress and provide greater detail on our pipeline. 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, Kevipenem HBR, an oral carbapenem that recently completed its successful phase three clinical trial, ADAPT-DO, for the treatment of complicated urinary tract infections including acute pyelonephritis. The trial met its primary endpoint, demonstrating that oral tebupenem, HBR, is non-inferior to IV urtepenem in the treatment of patients with complicated urinary tract infections and acute pyelonephritis. The primary endpoint was met with an overall or combined clinical and microbiological response rate of 58.8%, with oral tebupenem HVR and 61.6% for IV ertapenem. This met the trial's pre-specified non-inferiority margin of 12.5% and was complemented by tebupenem's compelling safety and tolerability profile, which was similar to IV ertapenem. In October, we presented additional data from the ADAPT-PA trial as an oral late-break of presentation at ID Week 2020. You can find all 15 posters and presentations from ID Week 2020 on the Sparrow Therapeutics website. Data from the ADAPT-DO trial demonstrated that both the clinical cure and microbiological eradication rates were comparable between treatment groups at the end of treatment, the test of cure, and at the late follow-up visits. Clinical cure rates which are important to clinicians because they are 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 were sustained through the late follow-up visits, demonstrating a durable clinical response with the complicated UTI or acute pyelonephritis. Favorable microbiological eradication rates and tests of cure were likewise comparable between treatment groups and were sustained up through the late formal visit in both treatment groups. There were no statistically significant differences in response rates across key subgroups of interest, including age, baseline diagnosis, and presence of bacteria at baseline. The pathogen microbiological response rates were generally balanced across the treatment groups for the predominant neuro pathogens. The safety and tolerability profile for oral TEP-dependent HPR was also similar to intravenously administered adipinem. Both the type and frequency of adverse events were well balanced across treatment groups, with treatment emerging adverse events reported being 26% of treated patients in both arms. The most commonly observed TEAEs were diarrhea and headaches, which were similar in frequency in both arms. There were no cases of clostridium diphtheria infection observed in the cabipenem HBR group, which compares to three cases observed in the IV adipenem arm. And fortunately, there were no deaths reported in this study. I want to take just a moment now to emphasize the highly demanding design of ADAPT-PO. This head-to-head comparison of an all-oral versus all-IV antibiotic treatment regimen was the first of its kind in complicated urinary tract infection. Specifically, we did not include an IV lead-in in the oral tebupenum HBR arm, nor an oral step-in in the IV ertapenum arm. because we wanted to provide physicians with direct evidence that they needed to feel confident in prescribing tebupenem HVR in place of IV carbapenem therapy. Treatment options for complicated UTI have become increasingly limited by antibiotic resistance, as well as safety concerns around existing oral antibiotics. Tebupenem HVR, if approved, could once again provide physicians with the opportunity to treat eligible patients with an oral agent outside of the hospital setting. All of the required Phase I clinical trials for NDA submission have now completed enrollment, and looking forward, we anticipate completing the NDA submission for TepiPam and HBR in the second quarter of 2021. I'll now move on to discuss SPR 720. our oral drug candidate for the treatment of non-tuberculous mycobacterial, or NTM, infections. In October, we presented data on SDR720 at IDE from the Phase I single and multiple ascending dose clinical trial, as well as pharmacokinetic and pharmacodynamic analyses based on data from our preclinical NTM infection models. These data and analyses indicated that the predicted therapeutic exposures could be attained with a 500 to 1,000 milligram dose administered once daily and have informed the design of our Phase IIa study. The IND application for SPR720 was accepted by the FDA in August 2020. and we were awarded Fast-Track designation for the treatment of adult patients with MGM pulmonary disease by the FDA in September. The next important milestone for this program will be the initiation of dosing in the Phase 2A clinical trial, which is expected before year end. This innovative trial is designed as a 28-day dose-ranging, placebo-controlled clinical trial evaluating SPR720 as monotherapy in 90 treatment inexperienced patients with NPM pulmonary disease caused by mycobacterium avian complex. The goal of the trial is not only to assess safety, tolerability, and the pharmacokinetics of SPR720, but also to assess early microbiologic response to the drug candidate and outcome that, if positive, will highlight the activity of SPR-720 as a single agent versus placebo. Regarding SPR-206, our next-generation IV polymixing agent that was developed as part of our potentiator platform, we continue to advance the compound with support from our partners at the Department of Defense and Everest Medicines. We remain on track to initiate our phase one bronchoalveolar levon or BAL clinical trial in the first half of 2021 and to initiate a renal impairment study next year. The phase one data in healthy volunteers announced earlier this year were encouraging. In the phase one SADMAD trial, healthy volunteers were given doses of SPR206 up to 300 milligrams daily of split doses for 14 consecutive days. There were no severe or serious adverse events reported in these volunteers. Furthermore, there was no evidence of nephrotoxicity or clinically significant changes in laboratory tests, which differentiates SPR206 from earlier generation polymixins. I will now turn the call over to Christina Larkin, our COO, who will provide you with a review of the market opportunity for our pipeline products and detail some of the preparations in-day for Pebucon and HBR's potential approval and commercial launch.