Q4 2020 Spero Therapeutics Inc Earnings Call

Greetings and welcome to Spero Therapeutics fourth quarter, and full year, 2020 financial results call. At this time all participants are on a listen only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad as a reminder.

Operator: Greetings and welcome to Spero Therapeutics' fourth quarter and full year 2020 financial results call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone key.

Operator: As a reminder, this conference is being recorded. It is now my pleasure to introduce your host for today's call, Sharon Clary. Thank you. You may begin.

This conference is being recorded it is now my pleasure to introduce your host for todays call Sharon clarity. Thank you you may begin.

Great. Thank you operator, and thank you all for participating in today's conference call earlier today, Spero Therapeutics released financial results and provided of pipeline update for the fourth quarter and full year 2020.

Sharon Clary: Thank you, Operator, and thank you all for participating in today's conference call. Earlier today, Spero Therapeutics released financial results and provided a pipeline update for the fourth quarter and full year 2021. If you have not yet seen the press release, it's available on the investor page of the Spero Therapeutics website. Before I begin, I'd like to remind you that some of the information contained in the press release and on this conference call contains forward-looking statements based on our current expectations.

If you have not yet seen the press release, it's available on the Investor page of the sphere of Therapeutics website.

Before I begin and like to remind you and some of the information contained in the press release and on this conference call contain forward looking statements based on our current expectations and.

Sharon Clary: Including statements about the initiation, timing, and submission to the FDA of the NDA for tebupenem-HBR and the potential approval of tebupenem-HBR by the FDA, future commercialization, the potential number of patients who could be treated by tebupenem-HBR, and the market demand for tebupenem-HBR generally. Expected broad access across payer channels for WPEN and HBR, expected pricing for WPEN and HBR, and the anticipated shift from intravenous to oral administration. The Design, Initiation, Timing, Progress, and Results of the Company's Preclinical Studies and Clinical Trials in its Research and Development Programs

And at famous about the initiation timing and submission to the FDA of the NDA for Epipen of H B O S.

First of all of type of you've had of H B O S. T. A future commercialization of potential number of patients who could be treated by type of pet of H block and the market demand for Cathy Peng of age we are generally.

It brought access across their channels for kind of your kind of H B I D expected pricing for type of anyway and then.

Dissipates shifts from intravenous to oral administration of.

And the design initiation timing progress and result of the company's preclinical studies and clinical trials and research and development programs and managements assessment of the results of such of preclinical studies and clinical trials the impact of COVID-19 pandemic on the company's business and operations and it got many of cash forecasts anticipate of expenses and the sufficiency of it.

Sharon Clary: And 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 and the sufficiency of its cash resources. Such forward-looking statements are not guarantees 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.

And cash resources such forward looking statements are not a guarantee of performance and the company's actual results could differ materially from those contained in such statements.

Several factors that could cause or contribute to such differences are described in detail and spirit of theirs.

Sharon Clary: Spero Therapeutics filing 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.

Filing with the SEC, including and the risk factors section of our annual report on form 10-K today.

These forward looking statements speak only as of the day of this conference call and the company undertakes no obligation to publicly update any forward looking statements or supply and new information.

Sharon Clary: and the company undertakes no obligation to publicly update them any further.

Sharon Clary: Any foreseeing statements or supply new information regarding the company after the date of today's release and call.

Guarding the company after the day of today's release and call.

Participating on today's call from Spiro, our Doctor and get them on Dania Chief Executive Officer.

Sharon Clary: Participating entities

Sharon Clary: Dr. David Melnick. Gina Larkin, Chief Operating Officer.

Dr. David Melnick, Chief Medical Officer, Cristina Larkin, Chief operating officer, and Sastruga Chief Financial Officer.

Ankit Mahadevia: With that, I'd like to turn the call over to Dr. Ankit Mahadevia. Thank you, Sharon, and good evening, everyone. I'm very much looking forward to an exciting year ahead, and I'm pleased to have the opportunity today to review our progress and provide some updates. Our primary focus remains Tebipenem HBR's advancement towards commercialization following the positive ADAPT-PO Phase III trial results that we reported last September. These results showed that the trial met its primary endpoint with data demonstrating that an all-oral regimen of Tebipenem HBR is non-inferior to an all-IV regimen of ertapenem for the treatment of complicated urinary tract infections, or CUTI, and acute pyelonephritis, or AP.

With that I'd like to turn the call over to Doctor, Inc, and my data.

Go ahead of market.

Thank you Sharon and good evening, everyone and very much looking forward to and exciting year ahead, and I'm pleased to have the opportunity today to review our progress and provide some updates.

Our primary focus remains heavy panned on H b ours advancement towards commercialization following the positive adapt P. O phase III trial results that we reported losses.

These results showed that the trial met its primary endpoint with data demonstrating for the all oral regimen of turbine kind of H B R is non inferior to an all of IV regimen of <unk>.

<unk> for the treatment of complicated urinary tract infections or C T I and acute pyelonephritis for a P.

Ankit Mahadevia: We chose to design ADAPT-PO as the first head-to-head comparison of an all-oral and all-IV regimen in CUTI specifically to provide a robust result that would give physicians the confidence to prescribe tebupenem HBR to the millions of CUTI and AP patients who would otherwise receive IV therapy. We believe we have done just that, as our data show that tebupenem-HBR can provide the convenience of an oral therapy without making any compromises on clinical response, safety, or tolerability.

We chose the design of that P. O is the first head to head comparison of an all oral and all of IV regimen and cdti.

To provide a robust result that would give physicians the confidence of prescribers have you kind of and H B R. Tens of millions of C. UTI and a P patients who would otherwise receive IV therapy.

We believe we have done just that.

And as our data show that <unk> 10 of H B R can provide the convenience of and oral therapy without making any compromises on clinical response safety for Tolerability.

Ankit Mahadevia: Based on our previous FDA interactions and written communication, positive results from this single, well-controlled, pivotal trial could be sufficient to support the approval of a new drug application or NDA for tevipenem HBR. We continue to expect to make an NDA submission to FDA for tevipenem HBR for the treatment of CUTI and AP in the second half of 2021. We feel comfortable with this guidance, which we believe accounts for the possibility of COVID-19-related delays, given that the Phase III and all supported Phase I trials have been completed. If approved, tebupenem HPA would be the first new oral therapy for CUTI in 26 years and the first oral carbapenem antibiotic approved for CUTI and AP.

Just on our previous FDA interactions and written communication positive results from the single well controlled pivotal trial could be sufficient to support the approval of a new drug application or NDA for teddy's had on H B R. We.

Many of to expect to make an NDA submission to FDA for turbine pet and H B R. For the treatment of C. T I and AP and the second half of 2021, we feel comfortable with this guidance, which we believe accounts for the possibility of COVID-19 related delays given that the phase III and all support of phase one trials have been completed.

If approved <unk> kind of makes me that would be the first new oral therapy for C. T. I in 26 years and the first world corporate kind of of antibiotic approved for C. A T I D P.

Ankit Mahadevia: Tebipenem HBR, if approved, would be an important treatment option for the over two million patients in the U.S. alone each year with resistance to currently available oral therapy. Now, I'd like to provide some updates on the SPR 720 clinical program. As we previously announced, Spero initiated a Phase IIa clinical trial of 720 in patients with non-tuberculous mycobacterial disease, or NTM, in December of 2020. We initiated the trial based on positive data from the Phase I single-ascending and multiple-ascending dose trials, as well as non-clinical toxicology studies in non-human primates and rats.

Have you kind of of HDR, if approved would be and important treatment option for the over 2 million patients and the U S alone each year with resistance to currently available oral therapies.

I'd like to now provide some updates on the S. P. R of 720 <unk> clinical program.

And as we previously announced spero and initiated a phase Iia clinical trial of 720 and patients with non tuberculosis might go bacterial disease or N. P M and December of 2020, we initiated the trial based on positive data from phase one single ascending and multiple ascending dose trials as well as non clinical.

All of these studies in nonhuman primates and rats and.

Ankit Mahadevia: In parallel to conducting the phase two trial, we were also conducting additional non-human primate and rat studies looking at longer-term toxicology. In February of this year, we reported that we saw unexplained mortality in the non-human primate trial that required additional investigation.

In parallel to conducting a phase two trial. We were also conducting additional non human primate and rat studies looking at longer term and toxicology in February of this year, we reported that we saw unexplained mortality in the non human primate trial that required additional investigation and.

Ankit Mahadevia: Following these findings, the FDA notified us verbally that a clinical hold was placed on our Phase 2a trial, and we have since then received written confirmation of this hold. FDA, in its notification, requested a study report from the non-human primate study. We continue to generate and analyze this data and advance our constructive dialogue with FDA as well as take steps to make the potential path forward for SPR-720 as efficient as possible.

Following these findings of the F D. A notified us verbally that of clinical hold was placed on a phase Iia trial and we have since then and received written confirmation of this whole F.

The FDA and its notification and requested of study report from the non human Primate study.

We continue to generate and analyze this data and advance our constructive dialogue with FDA as what was take steps to make the potential path forward for S. P ourselves and 'twenty as efficient as possible and we've worked to accelerate the readout of our toxicology studies and we've decided to discontinue the phase Iia clinical trial at this time.

Ankit Mahadevia: We've worked to accelerate the readout of our toxicology studies, and we've decided to discontinue the Phase 2a clinical trial at this time. We took the decision to discontinue the trial to facilitate potential adjustments to the Phase 2a SPR-720 clinical trial protocol that may be made in the future based on FDA feedback and avoid incurring costs associated with the clinical trial while it's on hold. Importantly, this is not a reflection of any findings from the primate study, nor does it reflect our thinking on the suitability of SPR-720 as a potential treatment for NTM, as we continue to believe there is a path forward for SPR-720 in this indication based on the data we have seen to date.

And we took the decision to discontinue the trials and facilitate potential adjustments for the phase Iia S. T. R. Seven and 20 clinical trial protocol that may be made and the future of based on FDA feedback and avoid incurring costs associated with the clinical trial, while it's on hold.

Importantly, this is not a reflection of any findings from the primate study nor does it reflect our thinking on the suitability of Spi of $7 20, as a potential treatment for N. P. M. As we continue to believe there is a path for trustee of seven and 20 in this indication based on the data we have seen to date.

Ankit Mahadevia: I will also note that the Phase IIa trial was in an early stage of enrollment at the time of the hold, so we do not believe that maintaining the trial in the pause phase would have been of benefit with regard to the trial and the data we could deliver. We continue to work with FDA to evaluate the findings and determine the best pathway for the continued development of the 720 clinical program.

I will also note that the phase Iia trial was and in early stage of enrollment at the time of the hold so we do not believe and maintaining the trial and the pause state would've been a benefit with regards to the trial and the data we could deliver.

We continue to work with FDA to evaluate the findings and determined the best pathway for the continued development of the sudden and 20 clinical program.

Before I hand, the call off the day, but to go into more detail on our pipeline I want to take a moment to discuss how we're executing on our strategy to efficiently manage our business during the COVID-19 pandemic.

Ankit Mahadevia: Before I hand the call off to David to go into more detail on our pipeline, I wanted to take a moment to discuss how we were executing on our strategy to efficiently manage our business during the COVID-19 pandemic. I'm very pleased to report that we have not seen any material impacts from the pandemic on our business this quarter. This is thanks to the talent and dedication of the Spero team and the investments we made in information technology early on that have enabled our fully remote workforce throughout the pandemic.

And I'm very pleased to report that we have not seen any material infection of the pandemic on our business. This quarter. This is thanks for the talent and the dedication of the spero team and the investments we made and information technology early on and that have enabled our fully remote work force throughout the pandemic.

Ankit Mahadevia: We have also been successful connecting digitally with physicians through our medical affairs efforts and in hiring new talent to support a potential launch for Tevipenem HBR. Looking forward, we will continue to monitor for potential impacts of COVID-19 on our business, and we'll continue to work diligently to stay ahead of them. Now, however, COVID-19 didn't materially impact our business last quarter.

We've also been successful connecting digitally with physicians through our medical affairs efforts and and hiring new talent to support the potential launch for <unk> kind of H B R.

Looking forward, we will continue to monitor for potential impacts of COVID-19 on our business and we'll continue to work diligently to stay ahead of them.

Now the COVID-19 didn't materially impact our business last quarter. It has changed the way that medicine is delivered by accelerating the trend of both physicians and patients seeking to prevent hospital admission and if possible.

Ankit Mahadevia: It has changed the way that medicine is delivered by accelerating the trend of both physicians and patients seeking to prevent hospital admissions if possible. While our conversations indicate that physicians would prefer to treat a complicated urinary tract infection outside of the hospital, this is not currently an option for millions of CUTI patients. This is due to the increasing prevalence of bacterial resistance to existing oral antibiotics, which often precipitates the need for IV therapy within the hospital.

While our conversations indicate that physicians would prefer to treat a complicated urinary tract infection outside of the hospital. This is not currently on option for millions of cdti patients. This is due to the increasing prevalence of bacterial resistance to existing oral antibiotics, which often precipitated the need for IV therapy within.

And the hospital.

Replacing these hospital IV therapies with an effective oral option would reduce patient exposure to COVID-19, and importantly also other secondary infections. It would offer of financial benefits of the hospital and free up capacity for seriously ill patients with no viable alternatives for hospitalization.

Ankit Mahadevia: Replacing these hospital IV therapies with an effective oral option would reduce patient exposure to COVID-19 and, importantly, also other secondary infections. It would offer a financial benefit to the hospital and free up capacity for seriously ill patients with no viable alternatives to hospitalization.

Dale ability of and oral medication that can enable of ship and care to the outpatient setting could best address critical unmet needs that have been exacerbated during these unprecedented times.

And then it gets also highlighted the need for a comprehensive approach to targeting current and future infectious threats. We are thrilled that policymakers and government agencies and major pharmaceutical companies have joined us in the biotech community and continue to develop innovative solutions to these threats that we face.

Ankit Mahadevia: The availability of an oral medication that can enable a shift in care to the outpatient setting could thus address critical unmet needs that have been exacerbated during these unprecedented times. The pandemic has also highlighted the need for a comprehensive approach to targeting current and future infectious threats. We're thrilled that policymakers, government agencies, and major pharmaceutical companies have joined us in the biotech community as we continue to develop innovative solutions to these threats that we face.

We remain active and these collaborative efforts and as shown by our partnerships with several government agencies, including BARDA. The U S Department of defense and Detroit as well as our relationships with corporate partners and private foundations and.

And with that I will hand, it over to David to review our of clinical progress and provide greater detail on our pipeline.

Thank you, Okay, I'm very happy to share our pipeline updates today.

Ankit Mahadevia: We remain active in these collaborative efforts, as shown by our partnerships with several government agencies, including BARDA, the U.S. Department of Defense, and DITRA, as well as our relationships with corporate partners and private foundations. And with that, I will hand it over to David to review our clinical progress and provide greater detail on our pipeline. Thank you, Ankit.

Let me begin with our lead candidates have you turned on each P. R and oral cadre of 10 of them for which we reported positive phase three data in September.

I used to preclinical trial entitled adapt Yo met its primary endpoint demonstrating that oral can be kind of H b R is non inferior to IV route of panel and the treatment of patients with complicated urinary tract infections, including acute Paolo enterprises and.

David Melnick: I'm very happy to share our pipeline updates today. Let me begin with our lead candidate, tebutenum HBR, and oral carbapenem, for which we reported positive phase 3 data in September. The phase 3 clinical trial, entitled ADAPT-PO, met its primary endpoint, demonstrating that oral tebutenum HBR is non-inferior to IV ertapenem in the treatment of patients with complicated urinary tract infections, including acute pyelonephritis. The primary endpoint was met with an overall, that is, a combined clinical and microbiologic response rate of 58.8% for oral tebupenem HBR and 61.6% for intravenous fertipenem, meeting the pre-specified non-inferiority margin of 12.5%.

Primary endpoint was met with and overall that is of combined clinical and microbiological response rate of 58, 8% for work type of kind of of H B R and 61 six per cent for intravenous route of kind of.

Meeting the pre specified non inferiority margin of 12 five per cent.

These and other GAAP P O data, which were presented and an oral late breaker presentation and I D week last October.

So that both of the clinical cure and microbiological eradication rates were comparable between the treatment groups at the end of treatment.

A test of cure and that's of late follow up visits.

Adapt deal also showed that have you kind of H b R and compelling.

David Melnick: These and other ADAPTPO data, which were presented in an oral late-break of presentation at ID Week last October, show that both the clinical cure and microbiologic eradication rates were comparable between the treatment groups at the end of treatment, at the test of cure, and at late follow-up. ADAPTEO also showed that Tebipenem HVR had a compelling safety and tolerability profile, which was similar to that of intravenously administered Both the type and frequency of adverse events were well balanced across the treatment groups, with treatment emergent adverse events reported in 26% of patients in both treatment arms.

And Tolerability profile, which was similar to that I think for me.

And asleep Ministry of Chemo.

Well the type and frequency of adverse events were well balanced across treatment groups with treatment emergent adverse events reported and 26% of patients in both treatment arms.

Most commonly observed treatment emergent adverse events were diarrhea, and headaches, which were of similar frequency in both arms. There were no cases of Clostridium difficile infection observed in the type of 10 of them H B R Group, which compares to three cases observed in the who depend on them for them of this study.

And Fortunately no deaths were reported across the treatment arms.

And I'd like to take a moment to reiterate and important point that we've made and the pass which is that we believe that these adapt po results means of positions.

David Melnick: The most commonly observed treatment-emerging adverse events were diarrhea and headaches, which were of similar frequency in both arms. There were no cases of Clostridium difficile infection observed in the cabipenem HBR group, which compares to three cases observed in the urtipenem arm of the study.

And an important advance and the treatment of patients with complicated UTI.

Continued emergence of antibiotic resistance and Gram negative bacteria has limited the utility of the currently available oral antibiotics for treatment options.

David Melnick: And fortunately, no deaths were reported across the treatment arms. Now I'd like to take a moment to reiterate an important point that we've made in the past, which is that we believe that these ADAPT-PO results mean to physicians an important advance in the treatment of patients with complicated UTI. The continued emergence of antibiotic resistance in gram-negative bacteria has limited the utility of the currently available oral antibiotic treatment options. As Ankit mentioned, ADAPTO was the first trial of its kind in complicated UTI as it was a straight head-to-head comparison of orally administered tevipenem HVR versus intravenously administered urtopenem. Specifically, it did not employ an IV lead-in in the cabipenem HPR arm nor an oral step-down in the IV urtipenem arm.

And I mentioned adapt P O.

The first trial of its kind of complicated UTI as it was the strength that's I had comparison of oil.

And the administered type of you kind of H B R versus intravenously administered route of panel specifically non point of IV reading them in the <unk> kind of makes the our arm more and oral step down in the IV route of Panama.

Thanks, and this robust trial design you have generated a strong data set that we believe provides physicians with the evidence they will need to feel confident prescribing or have you kind of instead of of IV route of pin them and pay for.

And that's with complicated urinary tract infections.

Looking for where we continue to anticipate completing the NDA submission for can be turned on H. We are in the second half of 2021 well.

All of the supporting Phase one studies has now been completed and all of the clinical data that will be included in the NDA package is currently in hand in parallel with these efforts regarding the M D. A.

David Melnick: Thanks to this robust trial design, we have generated a strong data set that we believe provides physicians with the evidence they will need to feel confident prescribing oral tebupenem instead of IV ertepenem to patients with complicated urinary tract infections. Looking forward, we continue to anticipate completing the NDA submission for Kebepen of HVR in the second half of 2021. All of the supporting Phase I studies have now been completed, and all of the clinical data that will be included in the NDA package is currently in hand.

We also continue to work with our partners to ramp up our CMC capabilities ahead of time dependent and expected launch in 2022.

Oh, it's been gratifying to see how much of strong external interest and there has been and the clinical utility of time, depending on each be or as an alternative for intravenous antibiotic therapy are.

And our medical affair strategy includes the initiation of several investigator sponsored studies that should increase our understanding of the function of <unk> have you kind of of H B R and different tissues. One study will assess the treatment of patients with Gram negative, yes P. L bacteremia comparing really.

David Melnick: In parallel with these efforts regarding the NDA, we also continue to work with our partners to ramp up our CMC capabilities ahead of Tebby Penham's expected launch in 2022. It's been gratifying to see how much strong external interest there has been in the clinical utility of tembutenib-HBR as an alternative to intravenous antibiotic therapy. Our medical affairs strategy includes the initiation of several investigator-sponsored studies that should increase our understanding of the function of tebutenum HBR in different tissues. One study will assess the treatment of patients with gram-negative ESBL bacteremia, comparing early transition to oral antibiotic therapy with tebutenum HBR to continued intravenous carbapenem therapy.

Transition for oral antibiotic therapy with turbine kind of of H B R. She continued intravenous carpet paint on therapy.

We also expect to report data from a phase one bronchial alveolar lavage trial assessing the longtime retrenching cutting and kind of H B R and the second half of this year.

This important trial, which commenced in December.

And to determine the pharmacokinetics of turbine Panama and lung tissue.

David Melnick: We also expect to report data from a Phase I bronchoalveolar lavage trial assessing the lung penetration of tebupenib-HBR in the second half of this year. This important trial, which commenced in December, is designed to determine the pharmacokinetics of tabipenem in lung tissue. Funded by BARDA, this study has a strong clinical rationale as a powdered form of tebupenem is currently approved in Japan for several respiratory indications, including the treatment of children with pneumonia.

Funded by BARDA. This study has a strong clinical rationale and such.

Powder form of heavy Panama is.

Currently approved in Japan, and several respiratory indications, including the treatment of children with pneumonia. In addition, we plan to have a presence and for infectious diseases and urology conferences. This year, where we will present additional adapt P O data as well as in vitro surveillance data sets.

David Melnick: In addition, we plan to have a presence at four infectious diseases and urology conferences this year where we will present additional ADAPT-PO data as well as in vitro surveillance data assessing the activity of tebupenem HBR against other gram-negative pathways. I'll now move on to discuss SPR-720, our oral drug candidate in development for the treatment of NTM infection. As Ankit mentioned, we initiated a Phase 2a clinical trial of 720 for the treatment of MTM patients in December.

And the activity of turbine Pan am H B R against other Gram negative pathogens.

I'll now move on to discuss as to your 720, our oral drug candidate and development for the treatment of MTM infection.

And as <unk> mentioned, we initiated a phase Iia clinical trial of seven and 20 for the treatment of MTM patients in December.

Last month, we announced that the FDA issued a verbal clinical hold for this trial.

David Melnick: Last month, we announced that the FDA issued a verbal clinical hold for this trial. This came after we had notified the agency of our internal decision to pause the trial based on unexplained mortality seen in a study of adult non-human primates in an ongoing toxicology study. I should note that the mortality did not correlate with the dose levels or duration of SPR-720 drug exposure. Furthermore, these adult non-human primates are historically known to be very challenging to dose, which adds a level of complexity to the analysis.

This came after we had notified of the agency of our internal decision to pause the trial based on unexplained mortality seen in a study of adult non human primates.

And in and ongoing toxicology study.

And I should note that for mortality did not correlate with the dose levels well duration of S. P. R seven and 20 drug exposure.

Further these adult non human primates, or historically known to be very challenging to dose, which adds a level of complexity to the analysis. We continue to evaluate the data in conjunction with FDA and better understand the cause of more mortality, mainly if it is related to the specifics.

David Melnick: We continue to evaluate the data in conjunction with FDA to better understand the cause of mortality, mainly if it is related to the specific species of monkey, the manner of administration, or if it is drug-related. In a recent written communication, the FDA asked for a study report from the Preclinical Toxicology Study, which we are currently working to complete. Before moving on to talk about SPR 206, I'd like to reiterate a point that Ankit touched on earlier.

She's a monkey the manner of administration or if it is of drug related attack.

And of recent written communication of the FDA asks for study report from the preclinical toxicology study, which we are currently working to complete.

Before moving on to talk about S. For your two O six I'd like to reiterate a point that you touched on earlier.

David Melnick: The events observed in this non-human primate toxicology study were a departure from what we had previously observed in preclinical and clinical studies with SBR 720. SPR 720 has previously been assessed in a series of non-clinical GLP toxicology and safety pharmacology studies, including IND-enabling 28-day and 31-day GLP toxicology studies in non-human primates and rats, respectively. There were no remarkable findings observed in these completed studies.

Events observed in this non human Primate toxicology study, where a departure from what we had previously observed in preclinical and clinical studies with SBR seven and 20 S.

S. T. R of 720 has previously been assessed in a series of non clinical G. L. P toxicology and safety Pharmacology studies, including I N D. Enabling 28 day, and 31 day G. L. P toxicology studies in nonhuman primates and rents respectively.

No remarkable findings observed and these completed studies. We are also currently conducting a four month toxicology study in rats that he has been on the dental.

David Melnick: We are also currently conducting a four-month toxicology study in rats that has been uneventful. In addition, in the prior single and multiple ascending dose phase one clinical trial evaluating the safety, tolerability, and pharmacokinetics of orally administered SBR 720, no serious adverse events were reported, and all human volunteers completed the trial. Based on the data we have seen to date, we continue to believe that there is a path forward for SPR 720 for the treatment of MTM pulmonary disease. To better facilitate potential adjustments to the Phase IIa clinical trial protocol, we have decided to discontinue the Phase IIa clinical trial at this time.

In addition in the prior single and multiple ascending dose phase one clinical trial evaluating the safety Tolerability and pharmacokinetics of orally administered SPR seven and 20, no serious adverse events were reported and all human volunteers completed the trial.

Based on the data we've seen to date, we continue to believe that there is a path forward for S. P. R $7 20 for the treatment of MTN pulmonary disease.

Better facilitate potential adjustments to the phase Iia clinical trial protocol, we have decided to discontinue the phase Iia clinical trial at this time I should reiterate a point that aren't get made earlier and say that discontinuing. The trial is not and I repeat not indicative of any decision that we've made on.

David Melnick: I should reiterate a point that Ankit made earlier and say that discontinuing the trial is not, and I repeat, not indicative of any decision that we've made on the program or any drug-related findings. The clinical trial was at an early stage of enrollment at the time of this whole. Thus, we believe maintaining the trial in the paused state would not have been of any benefit with regard to the trial and data that we could deliver.

And the program, whereas any drug related findings the clinical trial was set and early stage of enrollment at the time of the whole. Thus we believe maintaining of the trial in the POS state we've not been of any benefit with regards to the trial and data that we could deliver we continue to work with FDA to evaluate the for.

David Melnick: We continue to work with FDA to evaluate the findings and determine the best pathway for the continued clinical development of SPR720. Switching gears now to discuss SPR-206, our next generation IV polymixing agent that was developed as part of our potentiator platform. We continue to advance this compound with support from our partners at the Department of Defense and Everest Medicine. SBR-206 is a potent drug candidate that has shown activity against extensively drug-resistant bacterial strains, including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenemase-producing Enterobacter ales, all of which are on the World Health Organization priority pathogen list.

Findings and determined the best pathway for the continued clinical development of S. P of our 720.

Switching gears now to discuss S. P. R. Two of six our next generation IV Polymyxin agent that was developed as part of our potentiate or platform.

We continue to advance this compound with support from our partners at the Department of Defense and Everest medicines SBR two of our six is a potent drug candidate that has shown activity against extensively drug resistant bacterial strains, including multi drug resistant Pseudomonas aeruginosa asked you need of back.

Oh man Yang and cadre of pyramid, producing and Rebecca Ralph's all of which are on the World Health organization priority pathogen list.

David Melnick: The need for good medicines to fight bacterial infections in hospitals is further emphasized by the COVID-19 pandemic. In particular, patients with severe COVID-19 often require intubation and mechanical ventilation, rendering them vulnerable to ventilator-associated bacterial pneumonia. In fact, mortality in COVID-19 is frequently associated with these secondary bacterial infections, which are, in turn, often caused by antibiotic-resistant pathogens.

The need for good medicines to fight bacterial infections and the hospital is further emphasized by the COVID-19 pandemic.

Particular patients with severe COVID-19, often require intubation and mechanical ventilation and rendering them vulnerable to ventilator associated bacterial pneumonia in fact mortality and COVID-19 is frequently associated with these secondary bacterial infections, which art and turn often caused by <unk>.

Antibiotic resistant pathogens, we remain on track to initiate our phase one bronchoalveolar lavage clinical trial in the first half of 2021 in order to evaluate the penetration of SBR two of six into the lung compartment, where we're also on track to initiate a renal impairment study.

David Melnick: We remain on track to initiate our Phase I bronchoalveolar lavage clinical trial in the first half of 2021 in order to evaluate the penetration of SBR-206 into the lung compartment. We are also on track to initiate a renal impairment study this year. We are advancing SPR-206 into these additional trials based on the encouraging phase one data in healthy volunteers that we announced last year. In this study, healthy volunteers were given doses of SPR-206 up to 300 milligrams daily for 14 consecutive days, and there were no severe or serious adverse events reported.

This year.

We are advancing S. P. R. Two of six each of these additional crowds based on the encouraging phase one data in healthy volunteers that we announced last year and.

And this study healthy volunteers were given doses of S. For your two or six up to 300 milligrams daily for 14 consecutive days and there were no severe or serious adverse events reported importantly, there was no evidence of nephrotoxicity were clinically significant challenges and laboratory tests.

David Melnick: Importantly, there was no evidence of nephrotoxicity or clinically significant changes in laboratory tests, which clearly differentiates 206 from the earlier generation polymix. I will now turn the call over to Christina Larkin, our Chief Operating Officer, who will provide you with a review of the market opportunity for our pipeline products and detail our strategy for the potential launch of Tebupenem HBR.

Which clearly differentiates two of six from the earlier generation probably makes sense.

I will now turn the call over to Cristina Larkin, our Chief operating officer, who will provide you with a review of the market opportunity for our pipeline products and detail our strategy could the potential launch of <unk> Pan of H B R. Christina.

Thank you, Dave is and I'm happy to detail some of the great work on a commercial market access and medical affairs teams, arguing cause of pair for the petty kind of nature of our much anticipated launch.

Christina Larkin: Thank you, David, and I'm happy to detail some of the great work our commercial market access and medical affairs teams are doing to prepare for the much anticipated launch of Tebby Pinnum HVR. First, let me begin by saying that our conviction around the large opportunity for Tebby Penham HBR remains strong, and it is supported by two separate data analytic projects. First, we conducted a claim study of diagnosed CTI patients in the U.S., which indicated there were roughly 2.7 million prescriptions written annually for which tebupenem HBR could be a potential replacement.

First let me begin by saying that our conviction around the large opportunity for to be kind of on H B R remains strong and is supported by two separate data analytic projects.

First we conducted of claims study of diagnose C. P I patients and Iraq, which indicated there of roughly 2.7 million prescriptions written annually for heavy pen of H B R could be of potential replacement.

Christina Larkin: These patients are either receiving multiple rounds of oral therapy or receiving a second-line IV therapy, such as a carbapenem or zosyn, and thus could be a candidate for a new oral treatment option. You know, I think it's important that the market opportunity is also similarly split between the community and the hospital discharge market. Second, we examined data on current IV carbapenemuses. The data show more than 100% increase in IV carbapenem use over the last six years for CUTI.

And now these patients are either receiving multiple rounds of oral therapies are receiving of second line IV therapy, such as of Cobre, Panama, our Soc and and thus could be a candidate for a new oral treatment option.

And I think it's important that the market opportunity. It's also similarly split between the community and the hospital discharge market.

Second we examined data on current IV Cobre, Panama, yes.

The data show more than 100% increase and IV cobre, Panama views over the last six years for UTI and a significant portion of that growth is from the outpatient setting.

Christina Larkin: And a significant portion of that growth is from the outpatient setting. Now these data support the need for and the broad opportunity for new oral parvipenems. And we also continue to gather more information regarding our targeted prescribers. In the community setting, urologists are the largest treaters of these second-line CTI patients.

Now these data support the need for and the broad opportunity for new oral Cobre Panama.

And we also continued to gather and more information regarding our targeted prescribers.

And and the community setting urologists are the largest treaters that'd be second line for UTI patients and and the hospital setting ibs at the largest treaters.

Christina Larkin: And in the hospital setting, IDs are the largest treaters, and this data further reinforces our prior findings. This is going to be a specially driven launch with a focus on urology and ID. We've also engaged more than 200 healthcare providers and payers that cover 85% of payer lives. Together, they discussed their thoughts on how Pevipen and HVR will fit into the CETI treatment paradigm. These conversations consistently confirmed that there is a substantial unmet need for and significant interest in tebupenem HBR as a treatment for CETI.

And the state of further reinforces our prior findings this is gonna be especially driven launch for the focus on neurology and I D.

We've also engaged more than 200 health care providers and payers that cover 85 per cent of the Payor lives together their thoughts and how petty kind of H B R will fit into the ctr treatment paradigm.

And these conversations have consistently confirmed that there was a span of substantial unmet need for and significant interest and can be pinned on H b ours of treatment for cdti.

Christina Larkin: The payers have indicated that they see potential for value-based pricing and expressed their willingness to cover Kevipenem HBR if it's approved. They said this is because Tevipenum HVR has strong Phase III evidence and is addressing an unmet need by potentially replacing an IV.

And that the payers have indicated that they see potential for value based pricing and expressed their willingness to cover Kelly Pan of H B R. If it's approved.

They've indicated that this is because can be panamax VR has strong phase III evidence and this is addressing an unmet need of potentially replacing and IV and this has value to the payers and the patients for which they are servicing.

Christina Larkin: And this has value to the payers and the patients for which they're servicing. Now, armed with this information regarding our target customers and market size, we are continuing to build out our commercial market access and medical affairs infrastructure and capability. These individuals have deep expertise in launching new products and antibiotics and have strong relationships with these key specialties and payers, and are essential for our short-term and long-term success. And we've made investments in several digital tools to engage the healthcare provider community.

Now armed with this information regarding our target customers and market size, we are continuing to build out of our commercial market access and medical affairs infrastructure and capabilities.

These individuals have deep expertise and launching new products and antibiotics and they have strong relationships with these key specialties and payors and our central for our short term and long term success.

And we've made investments and several digital tools to engage the health care provider community.

And all of a small size of our team has allowed us to remain nimble and productive as we manage our day to day activities and we continue to leverage technology, where appropriate to prepare for a launch, especially during these COVID-19 times.

Christina Larkin: Now, the small size of our team has allowed us to remain nimble and productive as we manage our day-to-day activities, and we continue to leverage technology where appropriate to prepare for our launch, especially during these COVID times. And with that, I'm going to now turn the call over to Saf, who's going to provide you with a financial update. Good evening, everyone.

And with that and then and I'll turn the call over to SaaS who's going to provide you with a financial update.

Thank you Christina and good evening, everyone and we'll provide an overview of payroll and financial results for the QUADRA and and full year of ended December towards you went 20 of trenching and but.

Satyavrat Shukla: I will provide an overview of Spero's financial results for the quarter and fully-arranged December 31, 2020. But first, as this is my first Spero call, I would take a moment to introduce myself. I joined Spero in January 2021 as Chief Financial Officer, and most recently, I was the Chief Financial Officer at Ziopharm Oncology, another NASDAQ-created biotech, And prior to that, I was at Vertex Pharmaceuticals, where over a seven year period, I served as their head of commercial forecasting and analytics, and then their vice president and global head of corporate, I'm excited to have joined Spero's management team at this juncture in the company's trajectory, and I'm pleased to meet you all today.

First as that this is my first day I recall other take a moment to introduce myself.

I joined Spero and January 'twenty, 'twenty, one as Chief Financial Officer, and most recently I was the Chief financial Officer, and Biopharma oncology, another NASDAQ traded biotech company.

And prior to that I was at vertex pharmaceuticals, they're already 70 of periods I served as their head of commercial forecasting and analytics and then there of vice President and global head of corporate finance.

And I'm excited to have joined spirit of his management team at this juncture and the company's trajectory and I'm pleased to meet you on today.

Satyavrat Shukla: Tuning now to our financial update. Total revenue for the 4th Quarter of 2020, of $1.9 million, was lower than the $3.6 million for the same period in 2019. Total revenue for the full year ended December 31, 2020 was $9.3 million compared to $18.1 million for the full quarter ended December 31, 2019. Total revenue for the fourth quarter and for the year 2020 was lower than the same period in 2019 due to lower reimbursement under Spero's contract with the Biomedical Advanced Research and Development Authority, BARGA, for qualified tebupenem HVR expenses, as well as lower collaboration. As a reminder, we currently have total committed non-dilutive funding from BARDA of approximately $44 million.

Turning now to our financial update.

Total revenue for the fourth quarter 2021, 9 million was lower than the $3 6 million for the same PVH and 2019.

Total revenue per day full year ended December 31, and 2020 was $9 3 million compared to $18, one money and for the full quarter of ended December 31 2019.

Total revenue for the fourth quarter and full year, 2020 was lower than the St. Petersburg, and 2019 due to lower reimbursement and just payroll contract with the biomedical advanced research and development of a part of cheap bargained for.

Well qualified and can be found on H b, our expenses as well as lower collaboration revenue.

As a reminder, we currently have total committed non dilutive funding from BARDA of approximately 44 million inclusive of 10 million and funding from the defense threat reduction agency debt.

Satyavrat Shukla: Inclusive of $10 million in funding from the Defense Threats Reduction Agency, we have accounted for $21.4 million of committed funding from BARJA as of the end of December 31st. And beyond the current commitment, there is a second option of $12.7 million that remains exercisable by by-law.

We have accounted for $21 4 million of committed funding from BARDA as of the end of December 31st.

And beyond the current commitment that as of second option of $12 7 million debt.

Exercisable by Bajaj.

Research and jumbo pinch of expenses for the first quarter 2020 of $13 2 million were lower than the $25 7 million for the same PTH and 2019, primarily due to lower spend on the adapt appeal phase III trial. Following the receipt of top line data in September 2020.

Satyavrat Shukla: Research and Development Experts, for the fourth quarter of 2020, of $13.3 million, were lower than the $25.7 million for the same period in 2019, primarily due to lower spend on the ADAPT-PO Phase III trial following the receipt of top-line data in September 2020. R&G expenses for the full year ended December 31, 2020, were $67 million compared to 65.8 million for the full year ended December 31, 2019. R&D expenses were modestly higher year-over-year due to greater personnel-related spending.

R&D expenses for the full year of ended December 31, 2020 were 67 million compared to 65 point each volume for the full year of ended December 31 and 2019.

R&D expenses of modestly higher year over year due to greater personnel related spend.

For the pipeline candidates, partially offset by lower spend on the turbine for them H B R and S. T R. Two of six programs.

And we expect that's out of R&D expenses will decrease in 2021 relative to 2020 due to lower debt expense on the clinical trial costs and the launch that's some of the research and develop expenses, we expect to encourage 2021 and.

Satyavrat Shukla: Support the Pipeline candidates, partially offset by lower spend on the Tebipenem, HVR, and STR206 programs. We expect that our R&D expenses will decrease in 2021 relative to 2020 due to lower direct spend on clinical trial costs. I will note that some of the research and development expenses we expect to incur in 2021 include costs related to the expected Teri Panem HVR NDA submission and medical affairs strategy, as well as personnel-related spend

Include costs related to the expected kept depend on H b, our NDA submission and medical affair strategy as well as personal religious spent just a point of the pipeline.

General and administrative expenses for the fourth quarter 2020 of $7 5 million were higher than the $3 8 million and for the same period and 2019.

Satyavrat Shukla: General and administrative expenses for the fourth quarter of 2020 of $7.5 million were higher than the $3.8 million for the same period in 2019. GNA expenses for the full year ended December 31, 2020, were $21.4 million compared to $15.6 million for the full year ended December 31, 2019. Increased G.N.A.

G&A expenses for the full year and it's just.

But for Q1 2021.

For $21 4 million compared to $15 6 million for the full year ended December 31 2019.

Increased G&A expenses, and the fourth quarter and full year end of 2020.

Most of these same periods and then 2019 were due to increased headcount and professional fees to support.

Satyavrat Shukla: expenses in the fourth quarter and fully-arrended 2020 versus the same period in 2019 were due to increased headcount and professional fees to support Pre-Commercial Activities and our Expanding Business. We expect G&A expenses to increase in 2021 relative to 2020.

<unk> pre commercial activities and on expanding business.

We expect G&A expenses to increase and 'twenty, 'twenty, one and relative to 2020 and.

That's a bunch of commercial capabilities and the infrastructure to support the expansion of hedge of pay per day search of depend on H B, our commercial launch in 2020 two.

We reported a net loss for the fourth quarter and year ended December 31 and 2020.

Satyavrat Shukla: As we build commercial capabilities and the infrastructure to support the expansion ahead of a potential HBR commercial launch in 2021, we reported a net loss for the fourth quarter and year ended December 31, 2020, of $18.6 million and $78.8 million, or $0.68 and $3.52 per common share, respectively. This compares to a net loss for the fourth quarter and full year ended December 31, 2019, of $25 million and $60.9 million, respectively, of $1.31 and $3.35 per common share. As of December 31, 2020, We had cash and cash equivalents of $126.9 million.

Of $18 6 million and $78 8 million or 60 of spend and $3 five $2 per common share respectively.

This compares to a net loss for the fourth quarter and full year ended December 31 2019.

Of 25 million and $60 9 million of.

And 131 and.

And $3 $35 per common share respectively.

As of December took you on 2020, we had cash and cash equivalents of $126 9 million tonnes.

Do you believe that's out of existing cash cash equivalence and marketable securities.

The other of it on non diluted funding commitments there'll be sufficient to fund operations and to the second quarter of 2022.

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

And would now like to open the call for questions.

Satyavrat Shukla: We believe that our existing cash, cash equivalents, and marketable security, together with our non-dilutive funding commitments will be sufficient to fund operations into the second quarter of 2020. For further details on our, please refer to our 10-K files for the essay. We would now like to open the call for questions. Operator? Thank you. At this time, we'll be conducting a question and answer session. If you'd like to ask a question, please press star 1. Confirmation to indicate your line is in the, Press Star 2. It may be necessary to pick up your handset before.

Thank you.

At this time, we'll be conducting a question and answer session. If you'd like to ask a question. Please press star one on your telephone keypad.

And confirmation tone will indicate your line is and the question queue and May Press star two if you'd like to remove your question from the queue for.

And for participants using speaker equipment, and it may be necessary to pick up of your handset before pressing the star keys, one moment. Please while we poll for questions.

Our first question comes from or to borrow with Cowen and company. Please proceed with your question.

Hi, guys. Thank you for taking the question and thanks for the update this is lot of Ontario to and you just really quickly.

Operator: One moment, please. Our first question comes from Ritu Baral of Cowan and Company. Please proceed.

And do you estimate you'll be able to submit for study report for the preclinical tox.

Lila Anfur: Hi guys. Thank you for taking the question and thanks for the update. This is Lila Anfur, Ritu.

For <unk>, seven and 20 program for the F. D. A and then maybe as a quick follow up since you're discontinuing of phase two eight study does that mean you become on blinded to the data and are you planning to potentially of at least any of that early data to the public. Thank you.

Lila Anfur: Maybe just really quickly, when do you estimate you'll be able to submit the study report for the preclinical tox data for the 720 program to the FDA? And then, maybe as a quick follow-up, since you're discontinuing the Phase 2A study, does that mean you become unblinded to the data, and are you planning to potentially release any of that early data to the public? Thank you.

Oh, good evening library, and and thanks for the question and the first question was was it and the potential timing of <unk>.

Our discussions with FDA, so we're going to take a step wise process and so as we've noted we'll submit.

Submit the study and report to FDA and we'll have that additional dialogue what we've done in the meantime, as we've taken steps to expedite the process and that includes looking to accelerate data collection and delivery of wherever possible from these from these toxicology studies and we and stopping the current phase II study will facilitate that restart trend downstream.

Ankit Mahadevia: Good evening, Lila, and thanks for the question. And the first question was the potential timing of our discussions with FDA. So we're going to take a step-wise process, and as we've noted, we'll submit the study report to FDA, and we'll have that additional dialogue. But what we've done in the meantime is we've taken steps to expedite the process, and that includes looking to accelerate data collection and delivery wherever possible from these toxicology studies, and stopping the current Phase II study will facilitate that restart trend downstream.

In terms of the timing.

Just because these are dependent on ongoing discussions with FDA I can't provide details at this time, but as those details become clear and we will communicate that to the street.

And then but thank you for the question.

And you also maybe just on the unwinding of the phase III do you have access to debt.

Sort of continuing.

Yes. Thank you for that question and that is something that we're going to further assess as we look at the data and and collaborate with FDA and certainly as we learn more and and we put the pieces together, we'll be communicating that and of public for them at a later time.

Ankit Mahadevia: In terms of the timing, just because these are dependent on ongoing discussions with FDA, I can't provide details at this time, but as those details become clear, we will communicate that to the street. But thank you for the question.

That's helpful. Thank you very helpful.

Our next question comes from Louise Chen with Cantor Fitzgerald. Please proceed with your question.

Hi, Thank you for taking my questions here. So first question I had for you is how do you think about the pricing for Tibet Panam H B I know you talked about value based pricing, but I guess, what would the cost of the patient be and then how accessible while this drug would be upon launch and.

Ankit Mahadevia: Also, maybe just on the unblinding of phase 2a; do you have access to that data since you're discontinuing it?

Ankit Mahadevia: Thank you for that question. That is something that we're going to further assess as we look at the data and collaborate with FDA. And certainly, as we learn more and we put the pieces together, we'll be communicating that in a public forum at a later time.

And then can you give more color on your launch preparations when you'll be building out the sales force marketing and all of that and then last question is just more color on this SG&A increase year over year, just curious what the magnitude could be and if you can't say and number maybe that could dovetail on the launch preparation for type of your Pan am and you know what your bill.

Ankit Mahadevia: Thank you, very helpful.

Louise Alesandra Chen: Our next question comes from Louise Chen with Cantor. Hi, thank you for taking my questions here. So the first question I have for you is, how do you think about the pricing for tebepenem HBR? I know you talked about value-based pricing, but I guess what the cost to the patient would be and then how accessible will this drug be upon launch?

And there thank you.

Thanks, Louise for the questions I'll direct the first two questions on pricing and access and launch prep to Christina and then I'll direct the final question on SG&A build to stop on that.

Louise Alesandra Chen: And then, can you give more color on your launch preparations when you'll be building out the sales force, marketing, and all of that? And then, last question, just more color on this SG&A increase year over year. Just curious what the magnitude could be, and if you can't say a number, maybe that could dovetail with the launch preparations for Tebipenem and, you know, what you're building there. Thanks, Louise, for the questions.

First of all Christy and I'll hand, those first two questions for you.

Yeah, I think for me.

And as it relates to pricing and we really havent guided to our exact price yet and what we've said is that we expect a range between that 350 to 500 per day of their reasonable assumption I think we'll guide more as we learn more information I think that guide to the next point that you made which is what's the patient out of pocket expense.

Louise Alesandra Chen: I'll direct the first two questions on pricing and access and launch prep to Christina, and then I'll direct the final question on SG&A build to Sat. But first, Christina, I'll hand those first two questions to you. Yeah, thanks, Louise.

I think certainly as we understand more about the pricing that will guide our exactly what that number will be I think through that payer engagement. As we had indicated I think that early information that we've gotten is that we have gotten certainly really strong acceptance of our knowledge from our payer and we do expect.

Christina Larkin: As it relates to pricing, we really haven't guided to our exact price yet. What we've said is that we expect a range between $350 to $500 per day to be a reasonable assumption. I think we'll guide more as we learn more information. I think that leads to the next point that you made, which is what is the patient's out-of-pocket expense.

That the early read that we've gotten is that day.

And believe that we're gonna get broad coverage for the compound. They believe this is because we have strong phase III evidence and it is addressing this unmet need and this is giving value to payers and so that's you know the best evidence that we have today on the second question you ask about is when we're looking to build out of our sales force and the rest of day.

Christina Larkin: I think certainly as we understand more about the pricing, that will guide exactly what that number will be. I think through that payer engagement, as we had indicated, I think the early information that we've gotten is that we have gotten certainly really strong acceptance or knowledge from our payers. We do expect that the early read that we've gotten is that they believe that we're going to get broad coverage for the compound. The rest of the organization, as we are looking, and right now, we have a medical affairs market access person in our marketing team.

And the organization right now our plan around the field forces that we would book to build.

Build out the sales team at the time of approval.

But the rest of the organization as we are.

And looking and right now we have of medical affairs.

Market access and our marketing team those leadership roles, we believe that building out that loose capabilities first is how we're deploying we do have of medical liaison team that is out speaking to customers and they say, but we do have of market access team that has been deployed.

Christina Larkin: Those leadership roles, we believe that building out those capabilities first is how we're deploying them. We do have a medical liaison team that is out speaking to customers. In the same way, we do have a market access team that has been deployed. And on that last question, Luis, this is Sat.

And on that last question Luisa for that I can just say that the idea of G&A expenses ran bus such as it will be will indeed be tied to exactly the prioritized spent for our enabling a strong launch.

Satyavrat Shukla: I can just say that the GHG and AX spend ramp, such as it will be, will indeed be tied to exactly the prioritized spend for enabling a strong launch. Beyond that, we will continue to be very mindful, as you can imagine, on the G&A side of spend. And then overall spend, as you heard us say, for our gas runway into 2Q2022, if you back into the numbers, you'll see that we are essentially forecasting a relatively flat spend compared to recent run rates. So while G&A spend is expected to go up somewhat. We expect that the decline in R&D spend will make our total spend relatively flat.

Beyond that we will continue to be very mindful of as you can imagine on the G&A and so I just spent.

On the and overall spend as you heard us say for our cash Sunday into <unk>, 2020 to.

The agenda, if you back into the numbers, you'll see that we are essentially for gas staying relatively flat spend compared to recent run rates. So I, while G&A expense is expected to go up so much.

We expect that the the.

The decline and R&D spends will make our total spend relatively flat.

Kevin: Thank you very much. Our next question comes from Kevin. Please proceed with your question. Hey guys, thanks for taking my questions. Maybe two to start on 720.

Okay. Thank you very much.

Our next question comes from Kevin Day Jeter.

With Oppenheimer. Please proceed with your question.

Hey, guys. Thanks for taking my questions maybe for you to start on sovereign 20, I'm first of I heard you correctly on kit, you mentioned potentially accelerating certain findings for certain work on toxicology too broad of a little more granularity on.

Kevin: First, if I heard you correctly, Ankit, you mentioned potentially accelerating certain findings or certain work on toxicology to provide a little more granularity on what steps, if any, you can take to accelerate the learning and the exchange with FDA. In terms of next steps on 720, assuming a constructive resolution with FDA, should we expect the next clinical trial experience to be in healthy volunteers or continuing on? you know, and you know, patients with NPM. Good evening, Kevin.

And on what steps if any.

Here, you can take to accelerate the learning and the exchange with FDA and and terms of next steps on seven and 'twenty, assuming a constructive resolution with FDA and should we expect the next clinical trial experience to be and healthy volunteers are continuing on.

And yeah.

<unk> with MTN.

Good evening, Kevin. Thank you for the questions to your first question in terms of how we're trying to expedite our time to resolution of all of our dialogue on the hold.

Ankit Mahadevia: Thank you for the questions. To your first question, in terms of how we're trying to expedite our time to resolution of our dialogue on the whole, we are working on multiple fronts, as we've mentioned. I think number one is it relates to data generation.

And are working on multiple fronts as we've mentioned I think number one as it relates to the data generation, we're working closely with our <unk> to make sure that the study itself is conducted and as efficient a manner as possible as well as debt reporting of that data comes to the team and real time and that we can continue our.

Ankit Mahadevia: We're working closely with our CRO to make sure that the study itself is conducted in as efficient a manner as possible, as well as that reporting of that data comes to the team in real time, and that we can continue our discussions with FDA on an ongoing basis. And so, you know, we've had a certainly a good collaborative relationship both with the group running the study and with our colleagues at FDA in terms of the pace of having these conversations.

Discussions with FDA on a on an ongoing basis and so we've had to make a good of collaborative relationship both with the group running this study as well as with our colleagues at FDA and in terms of the cadence of having these dialogues and they will continue to expedite as best as we can.

Ankit Mahadevia: And we'll continue to expedite as best we can. To your second point on what future clinical work may look like, we are in the process right now of assembling and analyzing ongoing data from this study, and a lot of that will depend on the nature of the dialogue that we ultimately continue to have with FDA. So we do not have the full picture or the full data yet, but as we do, we will communicate that publicly. Great.

To your to your second point on what future clinical work May look like we are in the process right now of of assembling and analyzing ongoing data from the study and a lot of that will depend on the nature of the dialogue that we ultimately continue to have with FDA. So we do not.

Have the.

For the full picture of the full data yet there, but as we do we will communicate that publicly.

Great and then my follow up question is on other type of you've had on them and.

Christina Larkin: And then my follow-up question is on Tabipanam and, And specifically, you highlighted the importance of the IEDs in the hospital and urologist in the community setting. And I'm wondering, you know, what the best analog for a recent launch in this space is in terms of that interplay between ID and urologist. I think we're kind of more accustomed to seeing an interplay between ID and maybe, you know, GP in the outpatient community setting.

And specifically you highlighted the importance of the Ids and hospital, and then urologists and the community setting and I'm wondering what the best you know at all on for our recent launch and this space is in terms of that interplay between Heidi and urologists I think we're kind of more accustomed to seeing and now.

And between Oh, you're doing and maybe your GP and the and.

The outpatient community setting you know just how do we think about it.

Christina Larkin: You know, just how do we think about, you know, the importance of ID and sort of informing attitudes in urology? Thank you for the question. I will pass that one to Christina. Thanks, Kevin. You know, I think there's two parts here.

The importance of the Ied and sort of informing attitudes and neurology community.

Thank you for the question I will pass that one day Christina.

[laughter] Thanks, Kevin.

I think there's two parts here I think it depends on the setting of care you know what we do know is that of ideas play a really important role and the hospital and what we certainly know is that there are key influencer and that hospital arena and the community setting.

Christina Larkin: I think it depends on the setting of care. You know, what we do know is that IVs play a really important role in the hospital, and what we certainly know is that they're a key influencer in that hospital setting. In the community setting, from, you know, looking at the influence that the urologist has on these second-line treaters, they are showing up in our claims data, in addition to our research, as experts in treating urinary tract infections.

From you know looking at the influence of the Urologists has and the second line treaters, they are showing up and our and our claims data and addition to on research as experts and treating urinary tract infections.

Christina Larkin: You know, I wouldn't consider them antibiotic experts, but they are important treaters within the urinary tract. And I think, you know, they've expressed great interest in utilizing pevipenem, which I think gives us great confidence that they'll be an important early advocate for the compound, which I think is great news for us. Is there an analog I can point you to, to the exact launch that we're about to embark on? Not where there's an interplay between urology and IC, except if I were going to go back to the fluoroquinolones, you know, more than two decades ago?

And you know I wouldn't consider them antibiotic experts and are they are important and treaters within the urinary track and I think you know they have expressed great interest in and utilizing PV 10 of them, which I think gives us great confidence that they'll be and important.

Early advocate for the compound, which is I think is great news for US is there and analog I can point you to to the exact launch that we're about to embark on [laughter], not where there's an interplay between urology and IC, except if I was gonna go back for the Fluoroquinolones and you know more for two decades ago.

Okay.

No completely fair and I appreciate you taking my questions. Thanks, so much.

Kevin: No, completely fair. And I appreciate you taking my questions. Thanks. Our next question comes from Esther Hong, who says, Please proceed with your question.

Our next question comes from Esther Hong with Aaron Berg. Please proceed with your question.

Hi, so thanks for taking my question as we get closer to NDA submission for <unk> on an H B R and.

Esther P. Rajavelu: Hi, so thanks for taking my question. As we get closer to the NDA submission for tebipenem HBR and potential approval next year, I wanted to know if you could remind us of the precedent for FDA approvals based on a single well-controlled study. I think it's more common than realized, but wanted to get your thoughts.

And potential approval next year wanted to know if you could remind us of the cash.

Resident of FDA approvals based on a single well controlled study and I think it's more common than realized that and wanted to get your thoughts. Thanks.

Esther P. Rajavelu: Thank you, Esther, for the question. I'll pass that one to David.

Oh, Thank you and aster for the question I'll I'll pass that one to David.

David Melnick: Yeah, there's a well-defined pathway which is laid out in FDA guidance regarding the development of drugs for urgent unmet needs, and that clearly allows for a single trial approval. There, you know, perhaps, from my experience, a good example is the development of ceftazidime abibatam, which was initially approved based on phase two data, pending phase three results. Some of the additional BLI studies have been approved based on a single indication-based trial, sometimes with supporting resistant pathogen data.

Yeah, there, there's a well defined pathway, which is laid out in the F. D. A guidance regarding the development of drugs for urgent unmet need net like clearly allows for a single trial approval.

There you know perhaps for my experience are a good example is the development of Ceftazidime net backed him which was initially approved based on phase II data are pending phase three results.

Some of the additional.

P. L. P. L. I studies have been approved based on a single indication based trial, sometimes with supporting resistant pathogen data.

David Melnick: There is no analog in the oral antibiotic space because no one has successfully developed a gram-negative oral antibiotic in recent years. There are five different compounds that have actually had the single pivotal trial pathway, as David mentioned. Phytrosia, Recarbio, Zemdry, Vapomir, and Avicaz. All were single pivotal trials that went through that single pathway based on that unmet need.

There.

Is no analog in the oral antibiotics space because no one has successfully developed for Gram negative.

And oral antibiotic in recent years.

After you know there are five different compounds that I've actually had the single pivotal trial pathway as David had mentioned Patricia for Carpio with century, they've been here and how the cash all where single trial pivotal trials that went through that single pathway based on the unmet need.

Very helpful. Thank you.

David Melnick: Very helpful. Thank you.

Our next question is from Roms of ours, you with H C. Wainwright. Please proceed with your question.

Unknown Attendee: Our next question is from Ram Selvaraju with HG Wainwright. Hi, thanks very much for taking my questions. I'll start with just one on Tebupenem. I was wondering if you could comment on your thinking regarding, assuming Tebupenem gets approved, what kinds of post-marketing, post-approval studies or real-world data collection you could effectively undertake to bring in? so as to enhance the value of the property. [inaudible] Ram, good evening, and thanks for that great question.

Hi, Thanks, very much for taking my questions I'll start with just one on top of 10 of them I was wondering if you could comment on your thinking regarding assuming to be kind of gets approved what kind of post marketing post approval studies or a real world data collection and could you effectively undertake.

To bring in.

It has to enhance the value proposition of type of kind of still further and broaden its reach.

ROM.

Good evening, and thanks for that and Great question and it is something that for.

Ankit Mahadevia: It is something that's a focus of ours. You know, we are focused on maximizing the value of tebipenem and CUTI. We do believe this is the largest unmet need in infectious disease today. Beyond that, in terms of how we create value, we see several avenues in terms of how we continue to build the data story for tebipenem. First, we are contemplating larger and more formal trials in different infections in the future, and we'll guide them to that when we have a more solid plan.

Focus of ours.

We are focused on maximizing the value for <unk>, Panama and C. T. I. We do believe this is the largest unmet need in infectious disease today.

And on that in terms of how we create value we see several avenues in terms of of how we continue to build the data story for Turkey, Panama for.

First we are contemplating larger and more formal trials and different infections and the future and we'll guide to that when we have more of a solid plan.

Beyond the phase III adapt P O study, which is quite powerful and its own right. We're building the case for a utility and heavy pen and in two ways as we continue our work in 2021 for.

Ankit Mahadevia: Beyond the Phase III ADAPT-PO study, which is quite powerful in its own right, we're building the case for the utility of tebipenem in two ways as we continue our work in 2021. First, we're laying the groundwork for possible future studies through our clinical plan. As an example, as David mentioned, we're conducting a Phase I bronchoalveolar lavage trial to assess the lung penetration of tebipenem, which would be important should we advance tebipenem and pneumonia.

First we're laying the groundwork for possible future studies for our clinical plan as an example, as David mentioned, we're conducting a phase one bronchoalveolar lavage trial to assess the lung penetration of turbine and of.

Which would be important should we advanced heavy and pneumonia and second we just given the profile of Epipen and we've had significant interest from investigators to initiate studies with Tami tenants and we would expect several investigator sponsored studies to initiate a debt will give clinicians more information on <unk> and on H B R.

Ankit Mahadevia: And secondly, just given the profile of tebipenem, we've had significant interest from investigators to initiate studies with tebipenem, and we'll expect several investigator-sponsored studies to start that will give clinicians more information on tebipenem HVR and its utility. And as David mentioned, you should expect us to be active at the medical meetings communicating that story. Very helpful.

And its utility and as David mentioned, you'll you'll you should expect us to be active at the medical meetings and communicating that story.

Yeah.

Very helpful. And then on 722 points of clarification, So firstly, I think and and the press release, there was some language relating to.

Unknown Attendee: And then on 720, just two points of clarification. So firstly, I think in the press release, there was some language relating to the possibility that Unknown Attendee, Boobalan Pachaiyappan, Gavin Clark, Ankit Mahadevia, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc., would be employed in whatever the next clinical trial. As and when clinical development, could be different from the dosing regimen that you originally intended to employ. Can you just kind of drill down on that?

And the possibility of that.

Yeah.

Based on findings or you know FDA recommendations, the dosing regimen and employed and whatever the next clinical trial is.

As and when critical development resumes could be different from the dosing regimen that you. Originally intended to employees can you just kind of drill down on that and give me a sense of how.

The new dosing regimen might differ from the original dosing regimen in order to take account of you know whatever recommendations of the FDA might and do I understand that speculation at this point, but just give me some scenarios.

Unknown Attendee: [inaudible] Yeah, thanks, Ron, for the question. As you rightly note, the specifics of what will be next for SPR 720 are dependent on the data we continue to generate and the dialogue that we will have with FDA. We do not have those specifics today, and when we do, we'll certainly communicate that in the right public forum. Just as a matter of historical precedent, what we mean when we say that we might see adjustments to the trial, just historically when agents have come off hold, sometimes you will see adjustments to elements of the protocol, such as inclusion or exclusion criteria, monitoring, or potentially something about the dose.

Yeah. Thanks, Thanks, Rob for the question as you rightly note. This specifics of what will be next for SPR seven and 20 are dependent on the data we continue to generate and the dialogue that we will have with FDA and we do not have those specifics today and when we do and we'll certainly communicate that and the right pubs.

Look for them just as a matter of historical precedent and what we mean, when we say that we might see adjustments to the trial. Just historically went when agents have come off of old sometimes you will see adjustments to elements of the protocols, such as inclusion or exclusion criteria monitoring of potentially something about the dose.

Unknown Attendee: In terms of what's specifically in store for 720, we have more work to do as well as more conversations to have with our colleagues at FDA to figure that out. And when we do, we'll be communicating that.

In terms of of what specifically and store for seven and 'twenty, we have more work to do as well as more conversation to have with our colleagues at F. D. A to bottom that out and when we do we will be communicating that.

Just to add one of family.

Ankit Mahadevia: Just to add one more thing. Just to add one point, that the dosing in the toxicology study of the adult primates is being done by oral gavage dosing, that is, the medication is administered through a tube that's introduced into the esophagus, it's completely unrelated to the way that dosing is done in human beings, so that the concern, you know, may be that it is this dosing procedure that is the problem in the toxicology study, and that would not imply any change in dosing or dose regimen in humans.

I'm sorry go ahead.

And just to add one point that the dosing in the toxicology study of the adult primates is being done by oral gavage dosing that is.

The medication is administered through a tube that's introduced into the esophagus, it's completely unrelated to the way the dosing is done and human beings so that.

The concern you know may be that it is this dosing procedure that is the problem and the toxicology study and that would not imply any change in dosing or dose regimen in humans.

And just to clarify and all of the evidence you have seen to date. There is no direct indication that there is any issue with the dosing regimen that you originally promulgated for use in humans first of all there's there's still no overt indication relative to what.

Ankit Mahadevia: And just to clarify, in all of the evidence you have seen to date, there's no direct indication with the dosing regimen that you originally promulgated for use in humans. First of all, there's still no overt indication relative to when you originally made the announcement of the FDA clinical hold notification and versus where we are now. There's still no overt indication that we can definitively point to a drug-related effect. Is that correct

And you originally made the announcement of the FDA clinical hold notification and.

And versus where we are now there is still no overt indication that we can definitively 0.2 of drug related effect is that correct.

Ankit Mahadevia: Yeah, Rob, let me review the evidence that we have. You know, I think that, as we've noted before, we have prior rat primate studies, as well as normal healthy volunteer studies up to 14 days, as well as an ongoing rat chronic toxicology study that suggests the same things that we felt when we opened up the phase two study. What we know to date is consistent with the fact that there could be dosing-related, species-specific, or drug-related hypotheses.

Yeah, Rob Let me review of the evidence that we have it.

I think that and as we've noted before we have prior rat primate studies as well as normal healthy volunteer studies up to 14 days as well as an ongoing rat chronic toxicology studies that suggest.

You know the same things that we felt when we opened up the phase II study.

What we know to date is consistent with the fact that there could be dosing related species specific or drug related hypotheses. The data to date continues to suggest that those hypotheses are relevant and as we get more data, we'll continue to confirm that with FDA. So.

Ankit Mahadevia: The data to date continues to suggest that those hypotheses are relevant, and, you know, as we get more data, we'll continue to confirm that with FDA. So, you see, the data that we have continues to support the viability of those hypotheses.

The data that we have continues to support the viability of those hypothesis.

Operator: Thank you. We have reached the end of the question and answer session. At this time, I, Thank you, Operator, and I appreciate everyone's time for joining us today. I invite everyone to join us for our next webcast presentation at the Oppenheimer Healthcare Conference on March 16th, 2021. Have a great evening. This concludes today's conference. You may disconnect your lines.

Thank you.

We have reached the end of the question and answer session. At this time I'd like to turn the call back over to management for closing comments.

Okay.

Thank you operator and I appreciate everyone.

Tom for joining us today I invite everyone to join US at our next webcast presentation at the Oppenheimer Healthcare Conference on March 16, 2021 have a great evening.

This concludes today's conference you may disconnect your lines at this time and we thank you for your participation.

Okay.