Q4 2021 Spero Therapeutics Inc Earnings Call

Good afternoon, and welcome to the Spiro Therapeutics fourth quarter and year end 2021 .

Operator: Good afternoon, and welcome to the Spero Therapeutics fourth quarter and year-end 2021 financial results conference call. At this time, all participants are in a listen-only mode.

<unk> financial results conference call.

At this time all participants are in a listen only mode.

Following the company's formal remarks, we will open the call up for questions.

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 todays announcements on the Spero therapeutics website at Www Dot Spero therapeutics Dot 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.

Operator: Following the company's formal remarks, we will open the call up for questions. 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.sperotherapeutics.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.

Ted Jenkins: Thank you, Operator, and thank you all for participating in today's conference. This afternoon, Spero Therapeutics released financial results and provided a pipeline update for the fourth quarter and full year of 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 contains forward-looking statements based on our current expectations, including statements about the potential approval of WMHBR by the FDA and the timing thereof.

Good afternoon, Spero Therapeutics released financial results and provided a pipeline update for the fourth quarter and full year 2021.

Ted Jenkins: The timing of the launch of tepipenem-HBR, future commercialization, the potential number of patients who could be treated by tepipenem-HBR, and market demand for tepipenem-HBR generally. Also, expected broad access across payer channels for tepipenem HVR, the expected pricing of tepipenem HVR, and the anticipated shift in treating patients from intravenous to oral administration. The Plans for the Company's Ongoing Development of SPR-720, Statements about the Future Development and Commercialization of SPR-206, and the Potential Receipt of Milestone Payments as well as Royalties on Possible Future Sales of SPR-206

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 <unk> by the FDA and the timing thereof, the timing of the launch of dependent H B R. Future commercialization the potential number of patients could be treated by <unk> and market demand for epipen them HDR generally.

Ted Jenkins: The Design, Initiation, Timing, Progress, and Results of the Company's Preclinical Studies and Clinical Trials and its Research Development Program, as well as 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 and the company's cash forecast and anticipated expenses. The sufficiency of its cash resources and the availability of additional non-dilutive funding from governmental agencies beyond any initially funded award. Such forward-looking statements are not guarantees of performance, and the company's actual results could differ materially from those contained in such statements.

Also expected broad access across payer channels, where type event of HCR, the expected pricing of <unk> dependent H B R and the anticipated shift in treating patients from intravenous to oral administration.

The plans for the Companys ongoing development of SPR 720 statements about the future development and commercialization of <unk> and the potential receipt of milestone payments as well as royalties on potential future sales of Spi two effects the design initiation timing progress and results of the company's preclinical studies.

In clinical trials and its research and development programs.

Management's assessment of the result of such preclinical studies and clinical trials the impact of the COVID-19 pandemic on the company's business and operations and the company's cash forecast and anticipated expenses. The sufficiency of its cash resources in the availability of additional non dilutive 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.

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.

Ted Jenkins: 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.

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 todays release and call.

Participating in today's calls are Dr. <unk> <unk>, Chief Executive Officer, Dr. David Melnick, Chief Medical Officer, Cristina Larkin, Chief operating officer, and SaaS <unk>, our Chief Financial Officer.

Ted Jenkins: Participating in today's calls are Dr. Amkit Mahadevia, Chief Executive Officer; Dr. David Melnick, Chief Medical Officer; Christina Larkin, Chief Operating Officer; and Sash Shukla, our Chief Financial Officer. With that, I'd like to turn the call over to Dr. Amkit Mahadevia. Please go ahead, Dr. Mahadevia.

With that I'd like to turn the call over to Dr. Rocket My idea. Please go ahead on kit.

Thank you Ted and thanks to all for joining us today to discuss our fourth quarter and full year 2021 financial results and corporate highlights.

Ankit Mahadevia: 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. In the beginning, we'll start with our first lead product candidate, Teddy Penham HBR. We received a notice from the FDA stating that as part of its ongoing review of our NDA, it has identified deficiencies 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.

Starting I'll start with our first lead product candidates <unk> HCR, we received a notice from the FDA, stating that as part of its ongoing review of our NDA I identified deficiencies 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 the Fda's ongoing review. We also note that this comes at the midpoint of the scheduled six month review period, which was the planned date to initiate discussions and proposed labeling and if necessary any post marketing requirements and our commitment requests there.

Ankit Mahadevia: We also note that this comes at the midpoint of the scheduled six-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 27th.

Our three months remaining before the applications to do FID date of June 27, we continue to have an active dialogue with FDA and we will continue to collaborate with them on the best path forward for Debbie kind of as quickly as we can if this can be done to the fda's satisfaction. We believe there will be sufficient time to progress labeling and PMC.

Ankit Mahadevia: We continue to have an active dialogue with FDA and will continue to collaborate with them on the best path forward for tebupenem as quickly as we can. If this can be done to the FDA's satisfaction, we believe there would be sufficient time to progress labeling and PMC-PMR discussions within the existing PDUFA timeframe, 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 know that there isn't any additional detail regarding the review of an NDA that we can share beyond what we've disclosed today.

Omar discussions within the existing producers timeframe 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 the NDA that we can share beyond what we disclosed today, we seek to understand any issues in greater depth and also since discussions with FDA are ongoing.

Ankit Mahadevia: 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 a reminder, the NDA package is seeking approval for tebipenem-HBR oral tablets for the treatment of complicated urinary tract infections, including pyelonephritis caused by certain microorganisms in adult patients with limited oral treatment options.

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 a reminder, the NDA package is seeking approval for <unk>, our oral tablets for the treatment of complicated urinary tract infections, including pyelonephritis caused by certain microorganisms in adult patients with limited oral treatment options.

We were pleased that FDA decided to grant this NDA a priority review designation.

Ankit Mahadevia: We were pleased that FDA decided to grant this NDA a priority review designation. Upon NDA acceptance, we were initially informed that FDA may hold an advisory committee as part of the review. However, as part of our ongoing discussions, FDA has informed us an advisory committee meeting is not.

<unk> NDA acceptance, we were initially informed the FDA made hold an advisory committee as part of the review as part of our ongoing discussions FBA as informed as an advisory Committee meeting is not it.

<unk> if approved has the potential to address a significant unmet need alleviate infections and help appropriate cotr patients avoid hospitalizations or transition home faster. After IV therapy. We continue to believe in the strength of our application. The foundation of that is our previously announced data.

Ankit Mahadevia: Tepipenem, if approved, has the potential to address a significant unmet need, alleviate infections, and help appropriate CUTI patients avoid hospitalizations or transition home faster after IV therapy. We continue to believe in the strength of our application. The foundation of that is our previously announced data from the Phase 3 ADAPT-PO trial. These data showed the trial meeting its primary endpoint as specified in the protocol by demonstrating that oral tepipenem-HBR was statistically non-inferior to intravenous vertepenem in the treatment of patients with complicated urinary tract infections, or CUTI, and patients with acute pyelonephritis, or ATI.

From the phase III adapt trial. These data showed the trial meeting its primary end point as specified in the protocol by demonstrating that oral <unk> was statistically non inferior to intravenous verdict that I'm in the treatment of patients with complicated urinary tract infections or CPI and patients with acute pilot.

Friday's or <unk>, we are expecting the publication of the adapt trial results in a high impact peer review journal in early Q2.

Ankit Mahadevia: We are expecting the publication of the ADAPT-PO trial results in a high-impact peer-reviewed journal in early Q2. ADAPTEO was designed as the first head-to-head comparison of an oral versus IV regimen in CUTI. We believe it shows that tebupenem can provide the benefits of an oral therapy without making any compromises on clinical response, safety, or tolerability. We believe data from the trial not only supports our NDA, but if approved by the FDA, it will potentially provide physicians with the confidence needed to prescribe oral tebupenem HPR to appropriate patients in the place of IV therapy.

Adapt Po was designed as the first head to head comparison of an oral versus IV regimen and cdti. We believe it shows the turbine Panama can provide the benefits of an oral therapy without making any compromises on clinical response safety or Tolerability. We believe data from the trial not only supports our NDA.

But if approved by the FDA it will potentially provide physicians with the confidence needed to prescribe oral to IV pending HCR to appropriate patients in the place of IV therapy. This could be beneficial to patients healthcare providers and payers alike by shifting care to the outpatient setting.

Ankit Mahadevia: This could be beneficial to patients, healthcare providers, and payers alike by shifting care to the outpatient setting. This in turn would free up capacity for those patients with no viable alternatives to hospital treatment, a need that was underscored during the COVID-19 pandemic.

This in turn will free up capacity for those patients with no viable alternatives to hospital treatment and need that was underscored during the COVID-19 pandemic.

An approval for <unk> would make it the only oral cobre, Panama available for the treatment of cdti.

Ankit Mahadevia: And approval for tebupenem HBR would make it the only oral carbapenem available for the treatment of CUTI. We are encouraged by the responses we have received to date from physicians presented with tebupenem's value proposition and by feedback from payers who have expressed their willingness to cover tebupenem HDR, which would notably occur outside of the hospital diagnosis-related group. This bodes well for CUTI patients who could benefit from an oral carbapenem therapeutic. Now, let's turn our attention to SPR 720.

We are encouraged by the responses. We have received to date from physicians presented with turbine panama's value proposition and by feedback from payers, who have expressed their willingness to cover that we've done in <unk>, which would notably occur outside of the hospital diagnosis related group. This bodes well for the <unk> patients who could benefit from an oral carboplatin and therapeutic.

Now, let's turn our attention to Spi 2020, I'd like to now briefly recap the program's growing momentum.

Ankit Mahadevia: I'd like to now briefly recap the program's growing momentum. As you may recall, SPR720's Phase 2a clinical trial in patients with non-tuberculous mycobacterial disease, or NTM, was placed on hold by the FDA in February 2021, following review of data from a non-human primate toxicology study in which mortalities with inclusive causality to treatment were observed. At the start of 2022, we announced that the FDA lifted that clinical hold following the submission of a comprehensive study report with detailed analyses from the NHP toxicology study. These analyses supported our hypothesis that observed mortalities were not drug-related.

As you May recall SPR at 720 phase Iia clinical trial in patients with non tuberculosis mycobacteria lung disease or MTM was placed on hold by the FDA in February 2021. Following review of data from our nonhuman Primate toxicology study in which mortality with inclusive causality to treatment were observed at the start of 2022, we announced.

Is that the FDA lifted that clinical hold following the submission of a comprehensive study report with detailed analysis from the <unk> Toxicology study. These analysis supported our hypothesis that observed mortality were not drug related we are very pleased by the fda's decision to lift the hold and we've engaged with the agency to finalize the design and protocol.

Ankit Mahadevia: We are very pleased by the FDA's decision to lift the hold, and we've engaged with the agency to finalize the design and protocol of an upcoming Phase 2 trial, which we expect to begin in the second half of the year. David will speak more about the plans for this study shortly. SPR-206, our next-generation product candidate, also received significant milestones last year. We were pleased to engage with Pfizer, entering into a licensing agreement whereby Pfizer received the rights to develop, manufacture, and commercialize SPR-206 in ex-US and ex-Asia territories.

Of an upcoming phase II trial, which we expect to begin in the second half of the year.

David will speak more about the plans for this study shortly.

<unk> hundred six our next generation product candidate also received significant milestones last year, we were pleased to engage with Pfizer entering into a licensing agreement to which Pfizer received the license rights to develop manufacture and commercialize <unk> hundred six in ex U S ex Asia territories Intel.

Ankit Mahadevia: In tandem with the licensing agreement, Pfizer also made a $40 million equity investment in Spero as part of the Pfizer Breakthrough Growth Initiative. We also announced positive top-line results from SPR-206's Phase I Broncho-Alveolar Lavage Study. Finally, we completed our trial successfully of SPR-206 in regularly impaired patients.

And I'm with the licensing agreement Pfizer also made a $40 million equity investment Spiro as part of the Pfizer breakthrough gross initiatives.

We also announced a positive positive topline results from SPR 206, as phase one Bronchoalveolar Lavage study finally, we completed our trial successfully of ESCO to Asics in renal impaired patients.

With the ballad renal impairment data in hand, the program can move forward with ongoing FDA engagement and further clinical development.

Ankit Mahadevia: With the valid renal impairment data in hand, the program can move forward with ongoing FDA engagement and further clinical development. I would now like to highlight some recent appointments we've made to support the progress we're making in our pipeline. We're thrilled to welcome these individuals who are industry leaders with diverse and complementary skill sets. One of these industry leaders is David Musselman, who joined Sparrow as SVP of Sales and Market Access this past October.

I would now like to highlight some recent appointments we have made to support the progress we're making in our pipeline. We're thrilled to welcome. These individuals who are industry leaders with diverse and complementary skill sets. One of these industry leaders as David Musselman, who joined Spiro as SVP sales and market access. This past October David has over two decades of experience to the buyer.

Ankit Mahadevia: David has over two decades of experience in the biotech industry and was most recently responsible for building and executing Uravan's first product launch as their VP of Specialty Sales. We also recently brought on Jamie Brady as our Chief Human Resource Officer. Jamie has spent over 30 years working in senior human resource positions in the life science space. He's been deeply involved in guiding companies through their translation into commercial organizations.

The tech industry and was most recently responsible for building and executing your events versus product launches their VP of specialty sales were.

We also recently brought on Jamie Brady as our Chief Human Resource Officer, Jamie has spent over 30 years working in senior human resource positions of life science space. He's been deeply involved in guiding companies through their transition to commercial organization.

Alongside these additions to our leadership team. We also appointed Cerebellum Therapeutics, Chief Corporate Affairs Officer, Kathleen <unk> to our board of directors Kathleen has previous experience working incentive fee Biogen and as a professional staff number for the U S. Congress. We believe this experience together with her deep understanding of external engagement.

Ankit Mahadevia: Alongside these additions to our leadership team, we also appointed Cerebel Therapeutics Chief Corporate Affairs Officer Kathleen Tregonic to our board of directors. Kathleen has previous experience working for Sanofi, and Biogen and is a professional staff member for the U.S. Congress. We believe this experience, together with her deep understanding of external engagement strategies in a global global payer environment, will add important depth and a valuable perspective to our board. We're fortunate to have the support of high-quality investors and a strong financial foundation.

Use of the globe global payer environment will add important depth and a valuable perspective to our board.

We're fortunate to have the support of high quality investors in a strong financial Foundation. This is due in part to our two successful capital raises in 2021, both of which added cash to our balance sheet, while also providing external validation for our strategy and for our pipeline.

Ankit Mahadevia: This is due in part to our two successful capital raises in 2021, both of which added cash to our balance sheet while also providing external validation for our strategy and for our pipeline. The first of these raises was the $40 million equity investment from Pfizer, as previously mentioned, which was made at a premium and came alongside a licensing agreement for SPR-206. A couple of months after receiving this equity investment, we further strengthened our balance sheet by entering into a non-dilutive relevant interest financing agreement with healthcare royalty partners.

The first of these raises was the $40 million equity investment from Pfizer's previously mentioned, which was made at a premium and came alongside a licensing agreement press there two O six.

Couple of months after receiving this equity investment we further strengthened our balance sheet by entering into a non dilutive grant funding interest financing agreement with healthcare royalty partners. This agreement, which is worth up to $125 million.

Ankit Mahadevia: This agreement, which is worth up to $125 million, provides $50 million upfront, $50 million on approval of Tebipen and HPR and TTI, and $25 million upon the completion of pre-specified milestones and mutual agreement with healthcare royalty partners.

Provides 50 million upfront $50 million on approval of turbine kind of H B R and C. T R and 25 million upon the completion of pre specified milestones in mutual agreement with healthcare royalty partners with this transaction. We believe we preserve significant financial pressure flexibility and upside while securing revenue streams to support <unk> H B R.

Ankit Mahadevia: With this transaction, we believe we've preserved significant financial flexibility and upside, while securing revenue streams to support Tebipen and HPR, anticipated launch, and the advancement of the SPR 720 and SPR 206 programs. Lastly, I'd like to acknowledge our employees, partners, investigators, and importantly, the patients we serve, who've made considerable contributions to Spero in the midst of the ongoing COVID-19 pandemic. Despite the old crown wave that came and went during Q4, we continued to achieve significant milestones during the past number of months.

<unk> launch and the advancement of the SPR 720, and <unk> hundred six programs.

Lastly, I'd like to acknowledge our employees partners investigators and importantly, the patients we serve who've made contribute considerable contributions to sparrow in the midst of the ongoing COVID-19 pandemic. Despite the old Kron wave that came and went during Q4, we continued to achieve significant milestones during the past number of months.

With that I'll hand, it now over to David to provide a more detailed update on our clinical progress and on our pipeline.

Ankit Mahadevia: With that, I'll now hand it over to David to provide a more detailed update on our clinical progress and on our pipeline. 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, Tebby Penham HBR.

Yes.

Thank you Kate.

And good afternoon to all of you.

It's my pleasure to share our pipeline updates with all of those listening today I'll begin by speaking about our lead candidate tepid kind of H P. R and I would like to reiterate <unk> point that our near term focus will be working with the F. D. A to continue advancing our path forward towards approval.

David Melnick: 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 for the last decade. We believe that this manufacturing experience will be instrumental as we transition to a commercial organization.

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 major shakeup, who have extensive experience manufacturing a granular formulation of tami tenants over the.

The last decade, we believe that this manufacturing experience will be instrumental as we transitioned 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 diseases physicians and urologists so far.

David Melnick: 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 diseases physicians and urologists 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 Q2.

And a majority of them.

The major national and regional health plans and as <unk> noted earlier, we are also expecting and excited about the pending publication of the adapt trial results in a high impact peer reviewed journal.

Early in Q2.

Our efforts in this area together with the adapt Po results have produced strong external interest in <unk> 10 of them, including in ways in which we could broaden its potential therapeutic impact.

David Melnick: Our efforts in this area, together with the ADAPT-PO results, have produced strong external interest in tebupenem, including ways in which it could broaden its potential therapeutic impact. One recent example of this interest came in January when Spero was awarded up to $12.9 million by BARDA to support a clinical trial and related activities that are designed to advance orally administered tebupenem development as a treatment for pediatric patients with complicated UTI and acute pyelonephritis. This new funding was a result of BARDA adding and exercising an option to a contract originally awarded to Spero in 2018, which increased the total potential contract value to $59.7 million.

One recent example of this interest came in January when Spera was awarded up to an additional $12 $9 million by BARDA to support our clinical trial and related activities that are designed to advance orally administered turbine kind of boxes development as a treatment for pediatric patients with complicated.

<unk> and acute pyelonephritis.

This new funding was a result of BARDA, adding in exercising an option to contract originally awarded to Sparrow in 2018, which increased the total potential contract value to $59 $7 million. In addition to funding. We believe this new option provides important external validation.

David Melnick: In addition to funding, we believe this new option provides important external validation for the clinical utility of tebupenem, and it's a prime example of how we are building an umbrella of partnerships with thought leaders and government agencies. Another important example of these efforts is the Merino IV trial, which is being conducted by the Antibiotic Resistance Leadership Group and which is sponsored by the National Institute of Allergy and Infectious Diseases. This trial, which remains on track to begin dosing this year, is designed to compare early transition to oral tebupenem HBR to continued IV carbapenem therapy in patients with bloodstream infections caused by ESBL-positive gram-negative bacteria.

The clinical utility of <unk> 10 of them and its a primary Prime example of how we were building in Umbro up partnerships with thought leaders and government agencies. Another important example of these efforts is the Marina for trial, which is being conducted by the antibiotic resistance leadership group and which is sponsored by the national.

To the balance sheet and an infectious diseases. This trial, which remains on track to begin dosing. This year is designed to compare early transition to oral can be kind of H B R. Two continued IV carbon 10 am therapy in patients with blood stream infections caused by yes be all positive.

David Melnick: Additionally, we also successfully completed the BARDA-funded Phase I trial assessing the penetration of tebupenem HBR into the lung last year, and we anticipate presenting these data at an upcoming medical meeting later this year. I'll now transition on to speak about 720, our oral drug candidate in development for the treatment of non-tuberculous mycobacterial, or MTM, infection. Since Ankit already spoke about the lifting of FDA's clinical hold, I'd like to emphasize our eagerness and planning around getting SPR-720 back into the clinic and talk about our development plans and the unmet need we aim to address. Currently, there are no oral antibiotics specifically approved for use in pulmonary MTM disease.

Negative bacterium. Additionally, we also successfully completed the BARDA funded phase one trial assessing the penetration of can be kind of HDR into into the long last year and we anticipate presenting these data in an upcoming medical meeting later this year.

I'll now transition on to speak about 720.

Our oral drug candidate in development for the treatment of non tuberculosis mycobacteria or MTM infections. Since I'll get early spoke about the lift of Fda's clinical whole I'd like to emphasize our eagerness and planning around getting SPR 720 backing to enter the clinic and talk.

Our development plans and the unmet need we need we aim to address.

Currently there are no oral antibiotics, specifically approved for use in pulmonary MTM disease. This is a rare and devastating orphan indication that affects about 95000 people in the United States.

David Melnick: This is a rare and devastating orphan indication that affects about 95,000 people in the United States. Treatment with the current standard of care requires prolonged therapy of up to 24 months with a combination of mostly unapproved drugs that are often associated with tolerability and or toxicity issues. Through SPR720's clinical development, we aim to show that we can improve the NTM treatment algorithm by providing patients with a convenient and well tolerated oral therapy.

<unk> with the current standard of care requires prolong therapy of up to 24 months with a combination of mostly unapproved drugs that are often associated with tolerability and toxicity issues.

SBR seven Twenty's clinical development, we aim to show that we can improve the MTM treatment algorithm by providing patients with a convenient and well tolerated oral therapy, we believe our phase one and preclinical data support this hypothesis as they demonstrate the favorable tolerability profile.

David Melnick: We believe our phase one and preclinical data support this hypothesis, as they demonstrate the favorable tolerability profile of SPR720 at doses where therapeutic activity against a range of NTM species has been demonstrated. Looking forward, we are currently preparing to initiate the SPR 720 Phase 2 trial in the second half of this year. We are working to get our CROs up and running and, in parallel, have engaged with the FDA regarding the specifics of the study design.

Of STR seven 'twenty at doses, where therapeutic activity against a range of MTM species has been demonstrated.

Looking forward. We are currently preparing to initiate the SPR seven phase two trial in the second half of this year, we are working to get our <unk> up and running and in parallel are engaged with the FDA regarding specifics of the study design, while it would be premature to provide specific.

David Melnick: While it would be premature to provide specific design elements now, what I can say is that we plan to utilize the design of the discontinued study as a guide, but we will also incorporate recent FDA guidance that could potentially streamline the path to approval. The key goal of the trial is to build upon our prior clinical results demonstrating SPR 720's favorable safety and pharmacokinetic profiles by showing a signal of efficacy in patients with NTM infection.

Design elements now what I can say is that we plan to utilize to the design of the discontinued study as a guide, but we will also incorporate recent FDA guidance that could potentially streamline the path to approval a key goal of the trial is to build upon our prior clinical results demonstrating.

<unk> seven <unk> favorable safety and pharmacokinetic profiles by showing a signal of efficacy in patients with MTM infection to accomplish this we intend to include endpoints that measure microbiological burden as well as clinical outcome measures of how patients feel and function.

David Melnick: To accomplish this, we intend to include endpoints that measure the microbiologic burden as well as clinical outcome measures of how patients feel and function. Turning now to SPR-206, our intravenously administered next-generation polymyxin cancer therapy. SBR2SX is designed to act directly on gram-negative bacterial infections through its interactions with the bacterial outer membrane, and it has demonstrated potent broad-spectrum activity against multidrug-resistant gram-negative bacteria in preclinical studies.

Turning now to S. P. R. Two a six our intravenously administered Dex generation Polymyxin candidate.

<unk> is designed to act directly on Gram negative bacterial infections through its interactions with the bacterial outer membrane.

And it has demonstrated potent broad spectrum activity against multi drug resistant gram negative bacteria.

In preclinical studies, we believe SPR to a six may offer a safer alternative for patients suffering from serious drug resistant infections caused by organisms, including drug resistant acinetobacter drug resistant pseudomonas and carpet <unk> producing <unk> as prior phase one results.

David Melnick: We believe SPR-206 may offer a safer alternative for patients suffering from serious drug-resistant infections caused by organisms including drug-resistant Acinetobacter, drug-resistant Pseudomonas, and Carbapenemase-producing Enterobacterialis, as prior Phase I results demonstrated a lack of nephrotoxicity at predicted therapeutic dose levels. In contrast, patients suffering from these infections are currently treated with drug combinations that often include older poly Through SPR-206's development, we intend to replace these older polymyxins in the treatment paradigm and fulfill the need for well-tolerated therapy with the potential for efficacy against carbapenem-resistant and other antibiotic-resistant pathogens.

<unk> demonstrated a lack of nephrotoxicity at predicted therapeutic dose levels. In contrast patients suffering from these pay these infections are currently treated with drug combinations that often include older polymyxin, they're associated with network toxicity in many patients through.

<unk> development, we intend to replace these older probably makes sense in the treatment paradigm and fulfill the need for well tolerated therapy with the potential for efficacy against Cobre, Panama resistant and other antibiotic resistant pathogens, such a therapy could have a wide ranging impact as the cdc's 'twenty.

David Melnick: Such a therapy could have a wide-ranging impact, as the CDC's 2019 Antibiotic Resistance Threats Report estimates 8,500 drug-resistant Acinetobacter cases and 32,600 drug-resistant Pseudomonas infections in the United States every year. This past February, we built upon SPR-206's prior clinical results with top-line findings from its Phase I bronchial alveolar lavage, or BAL, clinical A key objective of this trial was to assess the lung penetration of SPR-206 when administered three times daily at 100 milligrams.

19 antibiotic resistance threats report estimates 8500 drug resistant acinetobacter cases, and 30 to Samsung 600 drug resistant Pseudomonas infections in the United States every year.

This past February we built upon SPR two six's prior clinical results with top line findings from our phase one Bronco alveolar lavage will be a L. Clinical trial a key objective of this trial was to assess the lung penetration of SPR Jewish shifts when they administered three times daily.

<unk> at 100 milligrams. This is a critically important metric when you realize that approximately half of the patients infected with multi drug resistant gram negative bacteria suffer from lung infections.

David Melnick: This is a critically important metric when you realize that approximately half of the patients infected with multidrug-resistant gram-negative bacteria suffer from lung infection. Results from the trial showed that SPR206 was very well tolerated and achieved lung exposures above its minimum inhibitory concentration for the targeted gram-negative pathogens for the entire eight-hour dosing interval. We were very pleased with these findings, which support the advancement of SPR206 into clinical trials of patients with life-threatening pulmonary infections, such as hospital-acquired and ventilator-associated pneumonia.

Results from the trial showed that STR to a sixth was very well tolerated and achieved long exposures above its minimum inhibitory concentration for the targeted gram negative pathogens for the entire eight hour dosing interval. We were very pleased with these findings, which support the advancement of <unk> into.

Nicole trials for patients with life, threatening pulmonary infections, such as hospital acquired and ventilator associated pneumonia.

Also we recently completed SPR to six as phase one renal impairment study designed to inform our dosing strategy for patients with multi drug resistant infections and reduced kidney function. We are advancing the program forward, having gathered final safety and PK data final dosage recommendations, including <unk>.

David Melnick: Also, we recently completed SPR206's Phase I Renal Impairment Study, designed to inform our dosing strategy for patients with multidrug-resistant infections and reduced kidney function. We are advancing the program forward, having gathered final safety and PK data. Final dosage recommendations, including any adjustments for patients with renal impairment, will be developed after completion of ongoing non-clinical studies and detailed pharmacology analysis.

Any adjustments for patients with renal impairment.

We will be developed after completion of ongoing non clinical studies and detailed pharmacology analysis. The next step will be to engage with regulators to further our development plan for <unk> with that I will now turn the call over to our Chief operating officer Christina market.

Christina Larkin: The next step will be to engage with regulators to further our development plan for SPR206. With that, I will now turn the call over to our Chief Operating Officer, Christina Larkin, who will provide you with a review of the market opportunity for our pipeline products and detail our strategy for a potential launch of tebutenib-HBR. Christina, over to you.

Who will provide you with a review of the market opportunity for our pipeline products and detail our strategy for a potential launch of <unk> kind of H B R. Cristina over to you.

Thank you so much David and it's a pleasure to be with you. This evening to discuss the progress of this have you kind of H B R.

Christina Larkin: Thank you so much, David. And it's a pleasure to be with you this evening to discuss the progress of Teddy Penham's HBR. Our preparation for launch is focused on building a best-in-class commercial organization and creating a launch readiness plan that we believe will be a transformative treatment for CETI. We continue building our launch plans as we work with the FDA to move forward on the ongoing review process of tebupenem HVR for the treatment of CETI.

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 cdti.

We continue building our launch plans as we work with the SBA can move forward on the ongoing review process with <unk> for the treatment of CPI.

There are an estimated 3 million patients annually in the U S that could benefit from a new effective and safe oral treatment for cdti.

Christina Larkin: 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, increase 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 healthcare providers who, in attempts to avoid hospitalization for their patients, are often cycling most patients through multiple These challenges have made treatment for CUTI in the outpatient setting one of the most common and problematic infectious disease conditions help care providers face today.

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 and most common bacteria for cdti increased threefold.

We now face a significant health crisis with more than one out of every three for UTI 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 are an attempt to avoid hospitalization for their patients.

And frankly, most patients through multiple rounds, and effective or unapproved medications for cdti.

These challenges have made the treatment for cdti in the outpatient setting one of the most common and problematic infectious disease condition health care provider space today.

As we prepare for launch we are focused on three distinct components, one ensuring we drive early health care practitioner awareness and trial without a neurologist infectious disease physicians and hospitalist.

Christina Larkin: 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 hospitalists. Two, building advocacy and support with key thought leaders and ensuring appropriate use as we look to bring the first oral carpependum to market. And three, ensuring patient access and affordability. With respect to our healthcare practitioners, we have engaged over 32,000 healthcare providers in the community and hospital setting through our Disease State Education Campaign to raise awareness of the unmet need.

Christina Larkin: We've also completed our profiling and targeting work and confirmed that with our planned sales force of approximately 135 representatives, we can reach hospitals accounting for 50% of carbapenem use in the US and 60 to 70% of fluoroquinolone CTI use in the community setting. This concentrated market of urologists, IDs, and targeted hospitals allows us to have reach and frequency in both the community and the hospital.

Two building advocacy and support with key thought leaders and ensuring appropriate use as we look to bring the first oral carpet paint them to market and three ensuring patient access and affordability.

With respect to the health care practitioners, we have engaged over 32000 health care providers in the community and hospital setting through our disease State education campaign to raise awareness of the unmet need. We've also completed our profiling and targeting work and confirmed that with our planned sales force of approximately 135.

<unk> we.

We can reach hospitals accounting for 50% of Cobre, Panama use in the U S.

60% to 70% of Fluoroquinolones C T I used in the community setting.

This concentrated market of urologist I D and targeted hospital allows us to have a reach and frequency in both the community and the hospital. We believe that we have the right resources, including innovative digital approaches and a talented and experienced sales leadership to drive early adoption. These key specialists well I'm sure.

Christina Larkin: We believe that we have the right resources, including innovative digital approaches and talented and experienced sales leadership, to drive early adoption of these key specialties while ensuring a competitive share of voice with less capital investment. Now, we're often asked about our commercial resilience as access to health care providers still has not completely returned to pre-COVID-19 numbers and could play a potential factor in current and future engagement with HCPs. We are building a nimble infrastructure so that our teams can quickly react to customer dynamics in real time.

A competitive share of voice with less capital investment.

Now, we're often asked about our commercial resilience as access to health care providers still has not completely return to pre COVID-19 numbers.

And could play a potential factor in current and future engagement with at HCP.

We are building a nimble infrastructure so that our teams can quickly react to customer dynamics real time.

We are also ensuring we allow for flexibility for.

These types of engage with our customers to enable our field team to provide continuity of this support to our clinicians and their office staff.

Christina Larkin: We are also ensuring we allow for the flexibility for these types of engagements with our customers to enable our field team to provide continuity of this support to our clinicians and their office staff. Now, moving on to the second component of our launch readiness, building our KOL advocacy and demonstrating our commitment to responsible and rational use of TeddiePenhamHBR. We have relied very heavily on our key opinion leaders to hear their perspective on balancing unmet needs with the responsible use of introducing the first oral carbapenem to market in the U.S. We have focused significant efforts to responsibly bring an oral carbapenem to the healthcare sector in a manner that directly supports strong antimicrobial stewardship.

Now moving onto the second component of our launch readiness of building, our kols advocacy and demonstrating our commitment to responsible and rational use of cat dependent H BR.

We have relied very heavily on our key opinion leaders to hear their perspective on balance sheet unmet needs with the responsible use of introducing the first squirrel carpet paint them to market in the U S.

We have focused significant efforts to responsibly brain and oral cobre panam to the health care sector in a manner that directly support strong antimicrobial stewardship.

Kathy pediments, well aligned with health care.

Christina Larkin: Kevi Penham is well-aligned with public health stewardship principles by potentially reducing suboptimal clinical outcomes and unnecessary hospitalizations resulting from inappropriate oral therapy and CUTI. Spero's investment in tebupenem's rational use includes numerous preclinical and clinical studies demonstrating that tebupenem has a low potential for the development of resistance, extensive PK and PD work supporting optimal dose selection, and a gut microbiome study.

With public health stewardship principles by potentially reducing sub optimal clinical outcomes and unnecessary hospitalization, resulting from inappropriate oral therapy in CCI.

<unk> investment in <unk> rationale use includes numerous preclinical and clinical studies demonstrating that <unk> has a low potential for the development of resistance.

Extensive PK PD work supporting optimal dose selection and it got microbiome study.

In addition, we have plant expansion stewardship and appropriate use of educational programs.

Christina Larkin: In addition, we have planned expansive stewardship and appropriate youth educational programs. Inclusive of that are patient education tools and identification tools, Surveillance Tracking to monitor resistance to Tebupenem and other antibiotics, A Concentrated Deployment to Specialists with a High Unmet Need for Patients, And finally, patient and healthcare provider educational materials on appropriate antibiotic use and stewardship principles in both the community and the hospital setting.

Inclusive of that or patient education tools and identification tool.

Surveillance tracking to monitor at resistance Covid, Panama. Another antibiotics are concentrated deployment to specialist with a high unmet need for patients.

And finally patient and health care provider educational materials on the appropriate antibiotic use and stewardship principles in both the community and hospital settings.

All of these efforts are focused on ensuring the responsible use of all antibiotics, including a new oral cobre Panama.

Christina Larkin: All of these efforts are focused on ensuring the responsible use of all antibiotics, including a new oral Prabhupada. The third and final component of our strategy has been ensuring access and affordability. We continue to make progress engaging with our payers through our pre-approval information exchange. Our field account team now has the opportunity to meet with more than 85% of targeted large national and regional payers. These meetings are encouraging and allow us to better understand the information needed to make coverage decisions for novel products like Tevipenna.

The third and final component of our strategy has been ensuring access and affordability.

We continue to make progress engaging with our payers to our preapproval information exchange.

Our field account team now has the opportunity has had the opportunity to meet with more than 85% of targeted large national and regional payers.

The meetings are encouraging and allow us to better understand the information needed to make coverage decisions for novel products like heavy panel.

The dialogue with these formulary decision makers has been consistent with what we have previously heard in market research.

Christina Larkin: The dialogue with these formulary decision-makers has been consistent with what we have previously heard in market research. They understand the unmet need for an oral carbapenem and CUTI as it would give B.E.A.R. members the opportunity to avoid IV treatment, hospitalization, and Cycling Through Ineffective Oral Therapy. An oral choice also allows for treatment in the community at home, which is at a lower cost and potentially safer setting of care for these appropriate patients.

Stan the unmet need for an oral carpet pediments UTI.

It would give their members the opportunity to avoid IV treatment hospitalization.

In cycling through an effective oral therapies.

And oral choice also allows for treatment in the community at home, which is at a lower cost and potentially safer setting of care for these appropriate patients.

Further payers understand that patients with serious infections likes the U T I need access to their prescribed medication quickly.

Christina Larkin: Further, payers understand that patients with serious infections like CUTI need access to their prescribed medication quickly. So as we prepare for our launch, our commercial team has plans in place to ensure that patients can access Pevipenem easily with a focus on services for timely dispense and patient affordability. In conclusion, we are building out a best-in-class commercial organization and finalizing our launch tactics, and we look forward to transforming the way that we treat CUTI so that avoiding unnecessary IV therapy and hospitalizations or ineffective oral therapies can be a thing of the past. With that, I'll now turn the call over to Saf, who will provide you with a financial update. Thank you, Christina. And good afternoon, everyone.

So as we prepare for our launch our commercial team have plans in place to ensure that patients can access have you kind of easily with a focus on services for timely dispense and patient affordability.

In conclusion, we are building out a best in class commercial organization and finalizing our launch tactics and we look forward to transforming the way that we treat UTI, so that avoiding unnecessary IV therapies and hospitalization or in effect of oral therapies can be a thing of the past.

With that I'll now turn the call over to SaaS, who will provide you with a financial update SaaS.

Thank you Christina and good afternoon, everyone I'd now like to turn your attention to our overview of <unk> financial results for the fourth quarter and full year ended December 31 2021.

Sash Shukla: I'd now like to turn your attention to our overview of Spero's financial results for the fourth quarter and for the year ended December 31, 2021. Total revenues for the fourth quarter of 2021 were 2.7 million compared to revenues of 1.9 million for the fourth quarter of 2021. The revenue mix was composed of reimbursement for pipeline candidates and their collaboration agreements with third parties, and Grants from various governments. [inaudible] Social revenue for the year ended December 31, 2021 was $18.3 million compared to $9.3 million for the 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 our collaboration agreements with third parties.

And clients 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 do.

Sash Shukla: Total revenue for the full year 2021 was higher than the same period in 2020 due to increased grant revenue received from Spero's contracts with DoD relating to SPR207, BARDA relating to Tevipenem HVR, and collaboration revenue from the company's license agreements with Pfizer and AstraZeneca. Research and development expenses for the fourth quarter of 2021 were 17.2 million, compared to 13.2 million for the same period in 2012. This year-over-year increase was primarily due to increased direct costs related to SPR206 and an increase in research and development.

Due to increased revenue received from <unk> contracts with Dod relating to Spi two of six <unk>.

Relating to <unk> H b.

In collaboration revenue from the company's license agreements at Pfizer and Everest 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 SPR towards six.

And on the increase in research and development headcount.

Research and development expenses for the year ended December 31, 2021 was $64 5 million compared to 67 million for the year ended December 31 2020.

Sash Shukla: 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 a Phase III clinical trial for teripenem HVR, although offset by increased direct costs related to SPR 206 and an increase in research and development. Looking forward, we expect research and development expenses to remain relatively flat in 2022 relative to 2021, as we continue to support our pipeline. General and administrative expenses for the fourth quarter of 2021 were higher than the 7.5 million reported for the same period in 2020.

With the decrease in expenses due to the completion of significant activities and related costs, a phase III clinical trial for <unk>.

Offset by increased startup costs related to Spi, two a six 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.

We continue to support our pipeline candidates.

General and administrative expenses for the fourth quarter of 2021 after Hurricane Maria were higher than the $7 5 million reported in the same period in 2020.

Primarily due to increased head count and professional fees to support pre commercial activities and growth of the business.

Sash Shukla: Primarily due to increased headcount and professional fees to support pre-commercial activities and the growth of the business. General and Administrative Expenses for the full year ended December 31, 2021 were 41.7 million compared to 21.4 million for the year ended December 31, 2020, with increased expenses in 2021 compared to 2020, again due to increased headcount and professional fees to support pre-commercial activities and the growth of the business. Looking forward, we expect that general and administrative expenses will increase in 2022 relative to 2021.

General and administrative expenses for the full year ended December 31 2021.

<unk> $41 7 million compared with 21 4 million for the year ended December 31 2020.

With increased expenses in 2021 compared to 2020 again due to increased head count and professional fees to support pre commercial activities and the growth of the business.

Looking forward, we expect that general and administrative expenses will increase in 2022 relative to 2021.

As we continue to build our commercial capabilities and expand our infrastructure.

Sash Shukla: As we continue to build our commercial capabilities and expand our infrastructure ahead of a potential Terrapenem HVR commercial launch in 2020, we reported a net loss for the fourth quarter and year ended December 31, 2021 of 29.2 million and 89.8 million, which are 90 cents and two dollars and 91 cents for a share, respectively. Net losses for the same period in 2020 were $18.6 million and $78.8 million, or $0.68 and $3.52 per common share, respectively.

Potentially JV Panam H B R commercial launch in 2022.

We reported a net loss for the fourth quarter and year ended December 31, 2021 of $29 2 million and $89 8 million or 90 and $2 91.

Well sure per common share respectively.

Net loss for the same periods in 2020 was $18 6 million and $78 8 million.

Our 68 cents and $3 five $2 per common share respectively.

As of December 31, 2021, we had cash cash equivalents and marketable securities of $146 4 million.

Sash Shukla: As of December 31, 2021, we had cash, cash from, and marketable securities of 146.4 million, based on current projects. Spero believes that its existing cash, cash equivalents, and marketable securities are sufficient. Together with committed funding from its border contract and other non-diluted funding commitments, it will be sufficient to fund its operating expenses and capital expenditure requirements into the second half of 2020. This forecast includes the $50 million in upfront proceeds received under the Revenue Interest Financing Agreement with Healthcare Royalty Partners and the addition of 15 million milestone fabled under such financing agreement upon approval of Tevipanam HBR in 2012. If the upfront proceeds from healthcare royalty partners and the additional 50 million milestone payments payable under such a financing agreement are excluded, Spero should have sufficient funding into the fourth quarter of 2020.

Based on current projections.

Believes that its existing cash cash equivalents and marketable securities.

With committed funding from BARDA contract and other non diluted funding commitments.

There'll be sufficient to fund its operating expenses and capital expenditure requirements into the second half of 2023.

This forecast includes the 15 million in upfront proceeds.

<unk> under the revenue interest financing agreement with healthcare royalty partners.

And the additional $15 million milestone payment payable under such financing agreement upon approval of <unk> in 2022.

If the upfront proceeds from healthcare royalty partners and the additional $50 million milestone payments payable in just such financing we went to exclude yet Spanish.

Spanish should have sufficient funding into the fourth quarter of 2022.

For further details on our financials. Please refer to our 10-K filed with the SEC today.

Sash Shukla: For further details on our financials, please refer to our 10-K-5, the DSP. Would you now like to open the call for questions? At this time, we will now begin the question and answer session. If you would like to ask a question, please press star then 1 on your touchtone phone. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue.

I'd now like to open the call for questions operator.

Okay.

At this time, we will now begin the question and answer session.

If you would like to ask a question. Please press Star then one on your Touchtone phone.

A confirmation tone will indicate your line is in the question queue.

You May press star two if he would like to remove your question from the queue.

For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Operator: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the start button. One moment, please, while we poll for questions. The first question today comes from Louise Chen, who has cancer. Please go ahead.

One moment, please while we poll for questions.

Yeah.

The first question today comes from Louise Chen with Cantor. Please go ahead.

Hi, Thanks for taking my questions here. So I had a few questions on the FDA update I'm, just curious what kind of deficiencies in general I know you can't talk about specifics could preclude discussions of labeling and post marketing requirements secondly, how much interaction.

Louise Chen: Hi, thanks for taking my questions here. I had a few questions on the FDA update. I'm just curious what kind of deficiencies, in general, I know you can't talk about specifics, could preclude discussions of labeling and post-marketing requirements?

Ankit Mahadevia: Secondly, how much interaction have you had with the FDA since your, and the third question is, what are the most likely potential outcomes when you get your update on or before May 2021? Louise, thanks so much for the question. We completely understand and empathize with the interest in going deeper into the substance of the review. However, 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.

Have you had with the FDA. Since you received this notice and is there. A question is what are the most likely potential outcomes. When you get your update on or before May 2022. Thank you.

Okay.

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 or in front of us.

Ankit Mahadevia: 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 the ongoing FDA discussions. What our commitment will be is as those discussions happen, and we highlighted a 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-night. The next question comes from Ritu Baral with Cowan. Please go ahead. Good afternoon, guys.

And secondly, we do want to protect the integrity of ongoing FDA discussions.

What our commitment will be is as those discussions happened 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.

Okay. Thank you.

Okay.

The next question comes from Ritu <unk> with Cowen. Please go ahead.

Good afternoon, guys. Thanks for taking the question okay.

Ritu Baral: Thanks for taking the question. Ankit, is it fair to say that you know what the topics of the deficient are based on the FDA communication to date, you know, 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? Unknown Speaker Attendee, and then I have a couple follow-ups.

It's fair to say that you you know what the topics.

Of the deficiencies.

Sure.

Based on the FDA communication to date.

And if so how.

How much clarity do you think that you have right now or how much understanding of those topics do you have like you said 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, Yeah, 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 FBA. It's one of the benefits of priority review.

Ankit Mahadevia: Yeah, thanks, Ritu, for the question. You know, I would say, and we've said this in prior earnings calls, that we continue to have frequent and active interaction with our colleagues at FDA. It's one of the benefits of priority review.

Ankit Mahadevia: I would say that, you know, 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, you know, as we do have substantive dialogue with FDA; we address and discuss with them in real time. But again, you know, 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.

I would say that we continue to engage with them on a variety of subjects within the the NDA application as the process has gone on one of the reasons why we will 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 you need for them over the following weeks to even start addressing the deficiency like you can't start in April essentially is that fair.

Ankit Mahadevia: 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? Now, I would say that, like I said, that we have engagement with the agency on a variety of topics, we engage 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.

No I would say that like I said that we have engagement with the agency on a variety of topics, we engage 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.

Ankit Mahadevia: Further, you know, as we build that understanding, again, we want to be respectful of the ongoing dialogue we have with the agency. So, you know, rest assured, we're working on the problem, and as soon as we can say more and have a fuller picture, we will tell you more.

While we have with the agency so rest assured we're working the problem and as soon as we can say more and have a fulsome picture we will.

We will tell you more.

Got it.

Ankit Mahadevia: Um, like the last one, 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, you know, 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.

The last couple of months have you submitted any new any data or any requested analysis.

You know was that was the full safety update recently submitted.

I mean, thanks for that question as well like I said, you know we've had a very productive and collaborative engagement with FDA, where we 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 the minute mechanics of the <unk>.

The back and forth at the same time.

Ankit Mahadevia: 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 go in the coming weeks.

As you have 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 go in the coming weeks.

Got it and in the meantime, I guess are.

Ankit Mahadevia: And in the meantime, I guess, are you planning any change in commercial commercial prep spend for Q2 in the meantime? Well, I think you heard from Christina and from me, we're continuing to invest to prepare for the pre-commercial activities that we're undertaking and thinking about launch should Teddy Penham be approved. But but has the rate of that changed at all or, or certain certain, I guess aspects of the preparation, have they been sort of postponed or anything like that?

Are you planning any change in commercial.

Commercial prep spend mm four for Q2 in the meantime.

Well I think you heard from from from Cristina <unk> from me, we're continuing to invest to prepare for the.

The pre commercial activities that we're undertaking and thinking about launch until we kind of be approved.

But has the has the rate of that changed at all or or certain a certain I guess.

Aspects of the prep has had they've been sort of postponed or anything like that.

I mean, we've laid out the key priorities for preparing for launch and that is educating our clinician colleagues about.

Ankit Mahadevia: We've laid out the key priorities for preparing for launch, and that is educating clinician colleagues about the unmet need that Tevipenem can solve, preparing to engage with our payers, as well as mapping out how best to deliver Tevipenem to clinicians if approved. All of those activities are ongoing, and we continue to invest in them. Okay, thanks so much. The next question comes from Esther Hong in Thirenburg. Please go ahead. Hi, thanks for taking my questions. So the first question is, what typically occurs during a late cycle review?

The unmet need post the turbine Panama can solve preparing to engage with our payers as well as mapping out how best to deliver tami tenants. The clinicians if approved all of those activities are ongoing and we continue to invest in them.

Okay. Thanks, so much.

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

Hi, Thanks for taking my questions.

Esther Rajavelu: Just generally, and then is that where, you know, at some point, and how would that shift in terms of where your discussions are with? Yeah, 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. So 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 first question is what typically occurs during a late cycle review I'm just generally and then is that where you know 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 Youre alluding to is that our Paducah date is in late June and we're sitting here in late March we are about halfway through the plan 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 <unk>.

Aging with them on during the review period.

What I want to emphasize from our prior remarks is that we are in a deliberative and collaborative phase with our colleagues in 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.

Esther Rajavelu: So, you know, what I want to emphasize from our prior remarks is that, you know, 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. Okay.

Okay got it that's helpful. You answered most of my questions. Thanks.

Ankit Mahadevia: That's helpful. Yeah, answered both my questions. Thanks. As a reminder, if you would like to ask a question, please press star then 1 to join the question queue. The next question comes from Raghuram Selvaraju with HCE Wainwright. Please go ahead.

Okay.

As a reminder, if you would like to ask a question. Please press Star then one to join the question queue.

The next question comes from Robert Baird, you with H.

Wainwright. Please go ahead.

Hello, This is representing <unk> H C. Wainwright, thanks for taking my questions.

Raghuram Selvaraju: Hello, this is Maz representing Varan at AC Wainwright. Thanks for taking our questions. We were wondering what new market research, if any, might be presented to the investment community prior to the Teddy Penn and HBR PDUFA dates later this year.

We were wondering what new market research, if any might be presented to the investment community prior to the <unk> date later this year.

Yeah.

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

Christina Larkin: No, thanks for the question. I will pass that to my colleague, Christina Larkin, who can best answer that. Yeah, thanks for the question, Ron. 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 and, and trial usage market research where we can understand readiness to prescribe tevipenem when it's available.

Yeah. Thanks for the question, Rob, 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 the and advocating that end and.

And trial usage market research, where we can understand readiness to prescribed heavy tenant when its available and all of that data.

Christina Larkin: And all of that data continues to reinforce, I think, for us, one, the high unmet need that we are starting to see and their interest in utilizing tevipenem for the appropriate patients. The full access to all of that data as we get closer to launch. I think our plan is to 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, in the near term, involving elements of the pipeline? Can you refresh us on, you know, the current activities Pfizer is undertaking with SPR tools? Great question.

Denise to reinforce I think for US one of the high unmet need that we start to see in their interest in utilizing PV panels.

Appropriate for the appropriate patients.

Full access of all of that data as we get closer to launch I think our plan is would be able to share more of our commercialization plans as we get closer to the Paducah date.

Okay, great and are there likely to be any other regional partnerships signed near term involving elements of the pipeline.

Can you refresh us on the current activities Pfizer is undertaking with S. P O to O six thank you.

Okay.

Great question. So on the first point strategically as we've mentioned in prior calls we are committed to.

Ankit Mahadevia: So on the first point, strategically, you know, as we've mentioned in prior calls, we are committed to, you know, focusing on preparing for a Tevipenem launch in the US. We are continuing to, you know, think about the right partners to help us commercialize Tevipenem in the US, and as for the rest of the pipeline, as you rightly note, SPR-206, we're delighted to have two great partners in Pfizer and Everest, and we'll opportunistically look for the right partners. for SPR-720.

Second preparing for Covid kind of launch in the U S. We are continuing to think.

Think about the right partners to help us commercialize <unk> kind of ex U S and as for the rest of the pipeline as you rightly note SCR two O. Six we have we're delighted to have two great partners, and Pfizer and Everest and we'll Opportunistically look for the right partners for STR of 720.

Ankit Mahadevia: You know, as it relates to the activities that Pfizer is collaborating with us on, you know, firstly, as we, as Sathya mentioned, they've made a equity investment in the company that supports our overall activities. Secondly, they've provided very thoughtful, you know, collaborative efforts on the ongoing development of SPR-206, and certainly their investment in the ongoing milestones help us support the ongoing development of Tevipenem. 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 SPR-206 on non-diluted financing, including a phase two study. Thanks for taking our questions. You're welcome. The next question comes from Tevin D. Dieter with Oppenheimer.

As it relates to the activities.

Pfizer is collaborating with us on.

Firstly as we saw.

Stop attention they've made our equity investment in the company that supports our overall activities secondly, they've provided very thoughtful and collaborative efforts on the ongoing development of <unk> 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 gives us the opportunity to advance a variety of activities for STR 206 on non dilutive financing, including a phase II study.

Great. Thanks for taking my questions.

Tevin D. Dieter: Please go ahead. Hey, guys. Yeah, thanks for taking our questions. Maybe one on 720.

Welcome.

The next question comes from Kevin <unk> with Oppenheimer. Please go ahead.

Hey, guys, yeah, Thanks for taking my questions.

David Melnick: Appreciate the update and David's comments with regard to, you know, the study kickoff in the second half of 2022 being based, first of all, on the prior 720 study design, but, you know, plus some feed, you know, incorporation of recent FDA guidance. So I'm wondering whether you could expand on the specific aspects of that FDA guidance that you will be looking to capture in the upcoming phase two 720 program. Thanks Kevin for the question. David, I'll pass the question to you.

Maybe one on 720 I appreciate the update and David's comments with regard to you know.

What was the starting to kick off in the second half of 2022 being base first of all off of the prior 700000 study design, but.

Plus some feed.

Incorporation of recent FDA guidance I'm wondering whether you could expand on specific aspects of that FDA guidance that you will be looking to capture in the upcoming.

That's coming.

Two seven pointing program.

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

David Melnick: Yeah, we're, you know, as I said, we're very excited about getting back into patients with 720. We worked hard with FDA in collaboration to lift the clinical hold, and in the end, the project got a clean bill of health. So we're moving forward. I think if you want hints about the structure of that study, I'd refer you to the ClinTrials listing for the prior trial. It will look somewhat similar in design.

As I said, we're very excited about getting back into patients was 720.

No.

We worked hard with FDA and in collaboration to lift the clinical hold in and in the end.

The project got a clean bill of health, So where we're moving forward I think if you want hints about the structure of that study I'd refer you to the clinic trials.

This thing for the.

<unk> prior trial, it will look somewhat similar in design.

David Melnick: 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. In particular, 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. Thanks for that. It's really helpful.

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 micro biologic end points, but FDA has become extremely interested in clinical outcome measures as endpoints for N. P. M studies and the phase II study that we've planned will assess a number of different approaches to that problem.

Great Thanks for that.

Sash Shukla: And then with regard to the next $50 million, potential draw under the, you know, royalty financing structure. Can you remind us whether Ted Bupenim, HBR Needs Approval by a specific time to exercise that next $50 million grant or under different timelines for approval scenarios, there's access to that blockchain? Yeah, thanks for the question, Kevin. This is that. Kevin Penham requires approval by the end of the year to qualify for that additional 50 million tranche.

Really helpful and then with regard to the next 50 million dollar.

Potential draw under the.

You know royalty financing structure can you remind us whether.

Toby Pan Am H B R needs approval by.

A specific time to exercise that next $50 million tranche or under under different timeline to approval scenarios.

You know does access to that backdrop.

Bedrock change.

Yes. Thanks for the question Kevin This is that I.

Sash Shukla: And I think that's what's been disclosed. And that's, that's what I would do. Great. Thanks for taking our questions. This concludes our question and answer session. I would like to turn the conference back over to Dr. Maha Divya 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.

Kevin.

Requires approval by the end of the year to qualify for that additional 50 million tranche.

And.

Got it that's that's been disclosed and that's.

That's a what I would say.

Great. Thanks for taking our questions.

This concludes our question and answer session I would like to turn the conference back over to Dr. <unk> 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.

Yeah.

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Ankit Mahadevia: Copyright © 2020 Mooji Media Ltd. All Rights Reserved. Copyright © 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. © BF-WATCH TV 2021, [inaudible] [music] © BF-WATCH TV 2021 [inaudible] Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc [inaudible] Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeuts, Inc Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeuts, Inc Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeuts, Inc, Copyright © 2021 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. © BF-WATCH TV 2021

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