Q2 2021 Spero Therapeutics Inc Earnings Call

August 5, 2021

[music].

Operator: Good day, everyone, and thank you for standing by. Welcome to the Spero Therapeutics second quarter 2021 earnings call. Today's conference is being recorded. At this time, I'd like to turn the call over to Ted Jenkins, Vice President, Head of Investor Relations, at Spero Therapeutics. Mr. Jenkins, please go ahead, sir. Thank you.

Good day, everyone and thank you for standing by.

Welcome to the Spero Therapeutics second quarter 2021earnings call. Today's conference is being recorded at this time I'd like to turn the call over to Ted Jenkins, Vice President head of Investor Relations at Spero Therapeutics. Mr. Jenkins. Please go ahead Sir.

Thank you operator, and thank you all for participating on today's conference call.

Ted Jenkins: Thank you, Operator, and thank you all for participating in today's conference. Earlier today, Spero Therapeutics released financial results and provided a pipeline update for the second quarter of 2020. Our press release is available on the investors page of the Spero Therapeutics website. Before we begin, I'd like to remind you that some of the information contained in the newsrooms and on this conference call contains forward-looking statements based on our current expectations, including statements about the initiation, timing, and submission to the FDA of an NDA for tevipenem HBR and the potential approval of tevipenem HBR by the FDA.

Earlier today, Spero Therapeutics released financial results and provided a pipeline update from second quarter of 2021.

This release is available on the investors page of the startup therapeutics website before.

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 initiation timing and submission to the FDA of an NDA for <unk> have you paid on H B R.

Approval of <unk> by the debt.

Ted Jenkins: Future commercialization, the potential number of patients who could be treated by tebupenem-HBR and market demand for tebupenem-HBR generally. Expected broad access across payer channels for tebupenem-HBR. The expected pricing of tebupenem-HBR and the anticipated shift in treating patients from intravenous to oral administration. The plans for the company's ongoing development of SBR 720.

Future commercialization the potential number of patients who could be treated by COVID-19 dependent H b R and market demand for tip. Your hat on <unk> generally expected broad access across payer channels for type of your kind of H B R. The expected pricing after you've done on <unk> and the anticipated shift in treating patients for intravenous to oral administration.

Plans for the company's ongoing development of SBR 720 statements about the future development and commercialization of SPR, 2 O 6 and the potential receipt of milestone payments as well as royalties on potential future sales of SPR 2 assets.

Ted Jenkins: Statements about the future development and commercialization of SBR 206 and the potential receipt of milestone payments as well as royalties on potential future sales of SBR 206. The design, initiation, timing, progress, and results of the company's preclinical studies and clinical trials and its research and development programs. Management's assessment of the results of such preclinical studies and clinical trials and the impact of the COVID-19 pandemic on the company's business and operations. 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 initial 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.

The design initiation timing progress and result of the company's preclinical studies and clinical trials and its research and development programs Managements assessment of the results outside of preclinical studies and clinical trials the impact on the COVID-19 pandemic on the company's business and operations.

These cash forecast and anticipated expenses, the sufficiency of its cash resources in the availability of additional non dilutive funding from governmental agencies beyond any initial 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.

Ted Jenkins: Several factors that could cause or contribute to such differences are described in detail in Spero Therapeutics' filings with the FCC, included in the Risk Factors section of our quarterly report on 410Q 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.

Several factors that could cause or contribute to such differences are described in detail in spero therapeutics filings with the SEC included in the risk factors section of our quarterly report on form 10-Q filed 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 for supply new information regarding the company. After the date of todays release on call.

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

Participating on today's call are Dr. <unk>, <unk>, Chief Executive Officer, Dr. David Melnick, Chief Medical Officer, Cristina Larkin, Chief operating officer, and our Chief Financial Officer to go with that I'd like to turn the call over to Dr. Anthony <unk>. Please go ahead and get.

Ankit Mahadevia: Thank you, Ted. And thanks to all for joining us today to discuss our financial results and corporate highlights. As we continue to progress to the back half of 2021, we remain focused on preparing for the upcoming Tevipetam HBR NDA filing and executing on our corporate strategy as we work to transition to a commercial organization. I'm pleased to say that our efforts around these interrelated goals have continued to advance on track.

Thank you, Ken and thanks to all for joining us today to discuss our financial results and corporate highlights as.

As we continue to progress to the back half of 2021, we remain focused on preparing for the upcoming <unk> pet on H B, our NDA filing and executing on our corporate strategy as we work to transition to a commercial organization.

I'm pleased to say that our efforts around these interrelated goals have continued to advance on track.

On our last call we shared that we had accumulated all of the data necessary for our NDA submission for <unk> pent up.

Since then we had been performing all of the required analysis and drafting section for the NDA. Both at the study and summary levels. We've seen sustained progress on these fronts and we're confident that we will submit the NDA in the fourth quarter.

Ankit Mahadevia: On our last call, we shared that we had accumulated all of the data necessary for our NDA submission for Tepi Penum. Since then, we have been performing all of the required analyses and drafting sections of the NDA, both at the study and summary levels. We've seen sustained progress on these fronts, and we're confident that we'll submit the NDA in the fourth quarter. This is in line with the guidance provided on our last earnings call for an expected NDA submission during the second half of this year.

This is in line with the guidance provided on our last earnings call for an expected NDA submission during the second half of this year.

Our efforts around to be turned on H B are supported both by our strong clinical data and our positive regulatory interactions with FDA.

Positive phase III adapt trial results reported late last year showed that the trial's primary end primary endpoint was met with data demonstrating that an all oral regimen of COVID-19 depend on H B R is non inferior to an all IV regimen of are dependent for the treatment of complicated urinary tract infection or see UTI and acute pyelonephritis.

Ankit Mahadevia: Our efforts around Temepenem HPR are supported both by our strong clinical data and our positive regulatory interactions with FDA. The positive phase 3 ADAPT-PO trial results reported late last year showed that the trial's primary endpoint was met with data demonstrating that an all-oral regimen of tevipenem HBR is non-inferior to an all-IV regimen of ertapenem for the treatment of complicated urinary tract infection, or Now, our previous FDA interactions and written communication indicate that positive results from a single well-controlled pivotal trial, such as ADAPTO, could be sufficient to support the approval of an NDA for tebupenem HBR in the treatment of CUTI and AP.

Or <unk>.

Our previous FDA interactions and written communications indicate that positive results from a single well controlled pivotal trial, such as adapt Po could be sufficient to support the approval of an NDA for COVID-19 depend on <unk> in the treatment of CDI and <unk>. Additionally, through feedback we receive from our pre NDA meeting the FDA endorsed the.

Structure in form of our planned NDA submission and indicated that the dataset and CMC plan that we intend to submit in the NDA package meet their standards.

We are confident that our all our turbine kind of HDR program will continue to advance as planned as we move through the second half of 'twenty, 1 and into 2022 based on our positive clinical data and adapt Po is rigorous design, we believe that if approved to anytime on aged care will be an important physician treatment option for possibly over $2 million for UTI and AP.

Ankit Mahadevia: Additionally, through feedback we received from our pre-NDA meeting, the FDA endorsed the structure and form of our planned NDA submission and indicated that the data set and CMC plan that we intend to submit in the NDA package meet their standards. We are confident that our Tebupenem HPR program will continue to advance this plan as we move through the second half of 2019 and into 2022. Based on our positive clinical data and ADAPTPO's rigorous design, we believe that, if approved, Tebupenem HPR will be an important physician treatment option for possibly over 2 million CUTI and AP patients in the U.S. alone who are resistant to currently available oral therapy.

Patients in the U S alone who are resistant to currently available oral therapies adapt.

<unk> was designed as the first head to head comparison of an all oral versus an all IV regimen in C. U T. I specifically to provide a robust result that would give physicians confidence to prescribed heavily depend on <unk> C. UTI in 80 patients who would otherwise be required to receive IV therapy. We believe we have done just that as our <unk>.

Data show that <unk> been on H B R can provide the convenience of an oral therapy without any compromises on clinical response safety or tolerability.

If approved <unk> 10 on HBO would become the only oral carpet send them available for the treatment of UTI and AP.

Its ability to effectively replace IV therapy for these patients could prevent and shorten unnecessary hospitalizations delivering value to the patient and economics benefits to the health care providers and payers. This is let payors to express their willingness to cover AWP on an H B R, which bodes well as we live work towards potential launch.

Ankit Mahadevia: ADAPTL was designed as the first head-to-head comparison of an all-oral versus an all-IV regimen in CUTI specifically to provide a robust result that would give physicians confidence to prescribe tebupenem HBR to CUTI and AP patients who would otherwise be required to 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 any compromises on clinical response, safety, or tolerability.

I would now like to provide some updates on the SPR 720 clinical program.

As a reminder, Spi 720 advanced into a phase II clinical trial in patients with non tuberculosis mycobacteria lung disease or MTM at the end of last year.

Ankit Mahadevia: If approved, Tebucetam HBR would become the only oral carbacetam available for the treatment of CUTI and AP. Its ability to effectively replace IV therapy for these patients could prevent and shorten unnecessary hospitalizations, delivering value to the patient and economic benefits to the health care providers and payers. This has led payers to express their willingness to cover AWPEN and HBR, which bodes well as we work towards potential launch.

Initiation on this trial was supported by positive data from phase, 1 single and multiple ascending dose trials as well as non clinical toxicology studies in non human primates in rodents.

Within these studies multiple subjects.

Were dosed and no severe or serious adverse events were observed as the phase Iia trial is being conducted however, we also simultaneous engaged in additional longer term toxicology study in non human primates surprisingly and in contrast to the positive positive phase 1 sad mad human experience.

Unexplained and HP mortality for dessert whether were observed this led us to prudently pause the phase Iia clinical trial and promptly notified the FDA of this important dynamic. We then subsequently received the clinical hold letter in which the FDA requested additional information from the non human Primate studies, including a study report.

Ankit Mahadevia: I would now like to provide some updates on the SPR 720 clinical program. As a reminder, SPR-720 advanced into a Phase 2 clinical trial in patients with non-tuberculous mycobacterial disease, or NTM, at the end of last year. The initiation of this trial was supported by positive data from Phase 1 single and multiple ascending dose trials, as well as non-clinical toxicology studies in non-human primates and rodents. In these studies, multiple subjects were dosed, and no severe or serious adverse events were observed.

As we discussed on our last call we have since completed the non human Primate study and continue to analyze the data we expect to complete the requested study reported in the third quarter as planned with this information in hand, we will continue to engage the FDA on a full response to their clinical hold letter in early Q4.

We will give an update on these discussions following fda's written comment on direction as to our specific findings from the non human Primate study until then I will reiterate the data we've seen to date that support the hypothesis that the observed mortalities, where not drug related but rather dosing in specie specific this gives us confidence.

Ankit Mahadevia: As the Phase IIa trial was being conducted, however, we also simultaneously engaged in an additional, longer-term toxicology study in non-human primates. Surprisingly, and in contrast to the positive Phase 1 CADMAD human experience, unexplained NHP mortalities were observed. This led us to prudently pause the Phase 2a clinical trial and promptly notify the FDA of this important dynamic. We then received a clinical hold letter in which the FDA requested additional information from the non-human primate study, including a study report. As discussed in our last call, we have since completed the non-human primate study and continue to analyze the data. We expect to complete the requested study report in the third quarter, as planned.

But there is a path forward for the SPR <unk> clinical program, but of course, we must complete our interactions with FDA before a final determination can be made.

I would also now like to briefly highlight the recent exciting developments that occurred around the <unk> hundred 6 our next generation Polymyxin product candidate and then David can speak in more detail about the program.

We were thrilled to announce that we entered into a licensing agreement with Pfizer around this asset pursuant to which Pfizer received the rights to develop manufacturing commercial SPR <unk> in ex U S and ex Asia territories in exchange for these rights Spero is eligible to receive up to $80 million in development and sales milestones.

Ankit Mahadevia: With this information in hand, we will continue to engage the FDA on a full response to their clinical hold letter in early Q4. We will give an update on these discussions following FDA's written comment and direction as to our specific findings from the non-human primate study. Until then, I will reiterate the data we have seen to date that support the hypothesis that the observed mortalities were not drug-related but rather dosing and species-specific.

With high single digit to low double digit royalties on net sales.

In tandem with the licensing agreement Pfizer also made a $40 million equity investment in spero as part of the Pfizer breakthrough growth initiative a program focused on funding innovative science to meet patient needs. This investment which was made at a premium to market provides important capital, which we intend to use in preparation for the.

<unk> approval and launch for <unk> kind of HDR as well as to support ongoing clinical development of Spi 2020, and SPR 2 assets.

The equity investment in licensing agreement provides important external validation from an industry leader and support our broader corporate strategy and pipeline development of anti infectives for patients with unmet need.

Further the price of the transaction speaks to our ability to execute on our business development objectives. It is also representative of a recent uptick in interest and investment activity around product candidates with the potential to address the rising rate of antimicrobial resistance or EMR for.

For instance, Pfizer.

Along with more than 20, leading pharmaceutical companies contributed to the formation of the ALR action fund, which aims to invest over $1 billion.

Ankit Mahadevia: We were thrilled to announce that we entered into a licensing agreement with Pfizer around this asset, pursuant to which Pfizer receives the rights to develop, manufacture, and commercialize SPR-206 in ex-US and ex-Asia territories. In exchange for these rights, Spero is eligible to receive up to $80 million in development and sales milestones with high single-digit to low double-digit royalties on net sales. In tandem with the licensing agreement, Pfizer also made a $40 million equity investment in Spero as part of the Pfizer Breakthrough Growth Initiative, a program focused on funding innovative science to meet patient needs.

In antibiotic development by 2030, Pfizer is also already committed $100 million for this fund and recently acquired ample explore masuda goals and Ericsson pharmaceuticals, both of which have been focused on anti infectives.

This activity along with the efforts of other major pharmaceutical companies government agencies and Polish policymakers is increasing the dynamism on the antimicrobial development ecosystem Spero continues to remain active in the collaborative efforts of this ecosystem as shown by our recent deal with Pfizer our relationships with other corporate.

Partners on private foundations, and our partnerships with several government agencies, including BARDA. The U S Department of defense the defense threat reduction agency and the National Institutes of allergies infectious disease.

Ankit Mahadevia: This investment, which was made at a premium to market, provides important capital which we intend to use in preparation for the potential approval and launch of Tevipen on HPR, as well as to support ongoing clinical development of SPR720 and SPR206. The equity investment and licensing agreement provide important external validation from an industry leader and support our broader corporate strategy and pipeline development of anti-infectants for patients with unmet needs. Further, the price of the transaction speaks to our ability to execute on our business development objectives.

Before handing the call off to David I'd like to reiterate spero remains well equipped to continue executing on our objectives, even amongst the ever evolving circumstances of the COVID-19 pandemic, while our business has not been materially impacted by COVID-19 in 2021. The pandemic is highlighting the value of replacing IV therapies that are often administered in the hospital.

Setting with an at home oral option, we believe that <unk> signed on H B R. If approved could provide such an option and enable a shift in care for the outpatient setting this would provide value to patients health care providers and payers alike, because it would reduce patient exposure to COVID-19. Other secondary infections. Further hospital will also see a.

Ankit Mahadevia: It is also representative of a recent uptick in interest and investment activity around product candidates with the potential to address the rising rate of antimicrobial resistance. For instance, Pfizer, along with more than 20 leading pharmaceutical companies, contributed to the formation of the AMR Action Fund, which aims to invest over a billion dollars in antibiotic development by 2030. Pfizer has also already committed $100 million to this fund and recently acquired Amflix Pharmaceuticals and Erixa Pharmaceuticals, both of which are focused on anti-infectives.

Financial benefit and free up capacity for seriously ill patients with no viable alternatives the hospitalization.

I will now hand, it over to David to provide a more detailed update on our clinical progress in our pipeline.

Thank you on Kate and good afternoon, everybody, it's my pleasure to share our pipeline updates with you today.

I'll begin by speaking briefly about our lead candidate <unk>, an oral carpet 10 of them that is advancing toward an NDA filing expected for the fourth quarter.

To provide a recap of what has brought us to this point, we reported top line data showing that our phase III adapt trial met its primary endpoint in September we.

Ankit Mahadevia: This activity, along with the efforts of other major pharmaceutical companies, government agencies, and policymakers, is increasing the dynamism of the antimicrobial development ecosystem. Spero continues to remain active in the collaborative efforts of this ecosystem, as shown by our recent deal with Pfizer, our relationships with other corporate partners and private foundations, and our partnerships with several government agencies, including BARDA, the U.S. Department of Defense, the Defense Threat Reduction Agency, and the National Institutes of Allergies and Infectious Diseases.

We also continue to work to complete the backend activities for our suite of Phase 1 studies, which are designed to support the NDA. These activities included locking the steady databases analyzing these datasets and finalizing the.

Clinical study reports as we previously disclosed in December 2020. These phase 1 activities were delayed slightly due to the pandemic, but we were able to quickly adapt and have not seen any further delays during 2021.

We have since completed all of these activities and we are now focused on performing the required integrated analyses and drafting sections for the NDA submission given the straightforward nature of these activities. We are fully on track to submit the NDA in the fourth quarter.

Ankit Mahadevia: Before handing the call off to David, I'd like to reiterate that Spero remains well equipped to continue executing on our objectives, even in the ever-evolving circumstances of the COVID-19 pandemic. While our business has not been materially impacted by COVID-19 in 2021, the pandemic is highlighting the value of replacing IV therapies that are often administered in the hospital setting with an at-home oral option. We believe that tebufenam HBR, if approved, could provide such an option and enable a shift in care to the outpatient setting.

In parallel with our efforts regarding the NDA. We also continue to work with our partners to ramp up for CMC capabilities ahead of <unk> expected launch during 2022, I should remind everyone that 1 of our partners is major shakeup.

Experienced manufacturing a granule formulation of <unk>.

Over the past decade will be invaluable as we move toward commercialization.

Before I move on to speak about 720, and STR to 6 I'd like to take a moment to talk about our strong clinical data supporting <unk> 10 on HCR and what we believe it means from a physician's perspective.

Ankit Mahadevia: This would provide value to patients, healthcare providers, and payers alike as it would reduce patient exposure to COVID-19 and other secondary infections. Further, hospitals would also see a financial benefit and free up capacity for seriously ill patients with no viable alternatives to hospitalization. I will now hand it over to David to provide a more detailed update on our clinical progress and our pipeline. Thank you, Ankit. And good afternoon, everybody.

The increasing prevalence of resistance to existing oral therapies for complicated utis as well as safety concerns related to some of the existing oral therapies such as for floor loans. Currently leaves millions of patients with no choice, but to receive intravenous antibiotic therapy, which often requires hospital.

<unk> for IV access.

GAAP <unk> rigorous design allowed us to show that physicians treating C. UTI in AP patients could replace hospital IV therapies with oral <unk> without making any compromise on clinical response safety or tolerability.

David Melnick: It's my pleasure to share our pipeline updates with you today. I'll begin by speaking briefly about our lead candidate, Tebby Tenom HBR, an oral carbapenem that is advancing toward an NDA filing expected in the fourth quarter. To provide a recap of what has brought us to this point, we reported top-line data showing that our Phase III ADAPT-PO trial met its primary endpoint in September. We also continue to work to complete the back-end activities for our suite of Phase I studies, which are designed to support the NDA.

By doing this we believe we have positioned ourselves to see high uptake on Kevin kind of HDR after approval.

Beyond C. UTI the adapt Po data have also generated strong external interest from key opinion leaders on the use of <unk> to treat other infections, providing potential opportunities to explore new indications.

David Melnick: These activities included locking the study databases, analyzing these data sets, and finalizing the clinical study report. As we previously disclosed in December 2020, these phase one activities were delayed slightly due to the pandemic, though we were able to quickly adapt and have not seen any further delays during 2021. We have since completed all of these activities, and we are now focused on performing the required integrated analyses and drafting sections for the NDA submission. Given the straightforward nature of these activities, we are fully on track to submit the NDA in the fourth quarter.

1 example of this external interest is embodied by the Marina for trial that I mentioned at the time of our last call. This is being sponsored by the National Institute of allergy and infectious diseases and is being conducted by the antibiotic resistance leadership group.

As a reminder, Marino for is designed to compare the early transition to oral tablet from HDR with continuation of intravenous carpal tunnel therapy in patients with blood stream infections caused by ESPN positive bacteria.

In addition, we have completed data analysis from the BARDA funded phase 1 bronchoalveolar lavage trial, which assesses the lung penetration of turbine kind of H VR and we plan to present. These data at an upcoming medical meeting. This study will set the stage for subsequent BARDA funded.

David Melnick: In parallel with our efforts regarding the NDA, we also continue to work with our partners to ramp up our CMC capabilities ahead of Tebipenem's expected launch during 2022. I should remind everyone that one of our partners is Meiji Seika, whose experience manufacturing a granular formulation of Tebipenem over the past decade will be invaluable as we move toward commercialization. Before I move on to speak about 720 and SPR 206, I'd like to take a moment to talk about our strong clinical data supporting tepipenem HVR and what we believe it means from a physician's perspective.

Studies to evaluate the efficacy of orally administered <unk> HDR for mnemonic indications. This study has strong clinical rationale as the granular formulation of <unk> is approved in Japan for several respiratory indications, including the treatment of children with pneumonia.

Looking forward, we plan on continuing to educate the clinical community about <unk> 10 on <unk> through publication of a peer reviewed manuscript reporting the adapt trial results.

David Melnick: The increasing prevalence of resistance to existing oral therapies for complicated UTIs, as well as safety concerns related to some of the existing oral therapies, such as fluoroquinolones, currently leaves millions of patients with no choice but to receive intravenous antibiotic therapy, which often requires hospitalization for IV. AdaptPO's rigorous design allowed us to show that physicians treating CUTI and AP patients could replace hospital IV therapies with oral tebutinib- By doing this, we believe we have positioned ourselves to see high uptake of tebutinib-HBR after approval.

These results will happen.

<unk> been discussed at 5 infectious diseases, and urology conferences by the end of the year, including the upcoming <unk> meeting at these conferences, we intend to present additional adapt Po data as well as the in vitro surveillance data assessing the activity of <unk> kind of on HCR against the most important.

<unk> Gram negative pathogens.

I would now like to move on to speak briefly about 7.

Excuse me <unk> 720, our oral drug candidate that we're developing for the treatment of the MTM infection non tuberculosis mycobacteria lung infections on.

Get recap the events that led to the program's clinical hold during his portion of the call so rather than repeat what he said I'll just emphasize a few additional points.

David Melnick: Beyond CUTI, the ADAPTPO data have also generated strong external interest from key opinion leaders on the use of tebupenem HVR to treat other infections, providing potential opportunities to explore new indications. One example of this external interest is the Merino 4 trial that I mentioned at the time of our last call.

Most importantly, the more camera these observed in the non human Primate study that led to the whole did not correlate with either the dose nor with the duration of SPR 720 drug exposure.

Further adult non humans mechanics. The animals. In this study are known to be extremely challenging to dose, which adds a level of complexity to the analysis of the study.

David Melnick: This study is being sponsored by the National Institute of Allergy and Infectious Diseases and is being conducted by the Antibiotic Resistance Leadership Group. As a reminder, Moreno 4 is designed to compare the early transition to oral tebitinib HBR with continuation of intravenous carbapenem therapy in patients with bloodstream infections caused by ESBL-positive bacteria. In addition, we have completed data analysis from the BARDA-funded Phase I bronchoalveolar lobotomy trial, which assesses the lung penetration of tebupenem HBR, and we plan to present these data at an upcoming medical meeting.

Finally, the findings from this non human primates primates study are contrary to what we have seen in prior preclinical and clinical studies of SPR 720 is on Kate outlined earlier.

While we won't be sharing any specific findings from the non human primate study until the FDA has provided us with feedback on the data I'd like to again emphasize that based on the data we have seen to date, we remain confident that there is a path forward for the SPR 720 clinical program.

These data continue to support the hypothesis that the observed mortality where specific either to the oral gavage dosing method for to the species of monkeys and the study rather than related to an off target pharmacologic effect along these lines I also like to reiterate a point that we have made on that.

David Melnick: This study will set the stage for subsequent BARDA-funded studies to evaluate the efficacy of orally administered tebupenem HBR for pneumonic indications. This study has strong clinical rationale as the granular formulation of tebupenem is approved in Japan for several respiratory indications, including the treatment of children with pneumonia.

Our last 2 earnings calls, which is that our previously announced decision to discontinue the phase Iia clinical trial was not I repeat not indicative of our opinion regarding the ultimate success of the SPR 720 program rather it was a strategic decision.

David Melnick: Looking forward, we plan on continuing to educate the clinical community about tebupenem HBR through publication of a peer-reviewed manuscript reporting the ADAPT-PO trial results. These results will or have been discussed at five infectious diseases and urology conferences by the end of the year, including the upcoming AUA meeting. At these conferences, we intend to present additional ADAPT-PO data, as well as in vitro surveillance data assessing the activity of tebupenem HBR against the most important gram-negative pathogens.

That allowed us to avoid incurring costs from the trial, while it's on hold and that may facilitate potential future adjustments to the clinical trial design as required by FDA.

Looking ahead, we expect to complete the study report from the recently completed Primate study in the third quarter and to engage the FDA thereafter early in Q4. After we receive feedback from the agency regarding the review of these data and our full response to the clinical hold letter we will provide an update on our clinical development.

David Melnick: I'd now like to move on to speak briefly about seven, excuse me, SBR 720, our oral drug candidate that we're developing for the treatment of NTM infection, non-tuberculous mycobacterial infection. Ankit recapped the events that led to the program's clinical hold during his portion of the call, so rather than repeat what he said, I'll just emphasize a few additional points.

<unk> plans for $700.8 moving forward.

Switching gears now to discuss SPR <unk>, 6 which is on our intravenously administered next generation polymyxin product candidate.

Which is designed to act directly on Gram negative bacterial infections through the molecules interactions with the bacterial outer membrane.

David Melnick: Most importantly, the mortalities observed in the non-human primate study that led to the whole did not correlate with either the dose nor with the duration of SPR-720 drug exposure. Further, adult non-human macaques, the animals in this study, are known to be extremely challenging to dose, which adds a level of complexity to the analysis of the study. Finally, the findings from this non-human primate study are contrary to what we have seen in prior preclinical and clinical studies of SPR720, as Ankit outlined earlier.

<unk> has demonstrated potent broad spectrum activity against Gram negative bacteria, including the extensively drug resistant variants that have emerged as a major problem in both the hospital and community setting.

We believe that <unk> will offer a safer alternative for patients suffering from serious drug resistant infections, including drug resistant acinetobacter multi drug resistant pseudomonas and <unk>, producing enterobacteriaceae with us with the greatest unmet need currently exists.

David Melnick: While we won't be sharing any specific findings from the non-human primate study until the FDA has provided us with feedback on the data, I'd like to again emphasize that based on the data we have seen to date, we remain confident that there is a path forward for the SPR 720 clinical program. These data continue to support the hypothesis that the observed mortalities were specific either to the oral gavage dosing method or to the species of monkeys in the study rather than related to an off-target pharmacologic effect.

In the antibody formulary.

Today patients suffering from these infections are treated with a drug combination, which frequently includes a carpet panel work.

<unk> antibiotic usually in combination with polymyxin colistin treatment with these older Polymyxin is associated with neff for toxicity in many patients.

Clearly differentiates <unk> 6 compared to <unk> and the other polymyxin antibiotics use our phase 1 sad mad data showing a lack of nephrotoxicity at or above the predicted therapeutic dose. We thus believe SBR 2 of 6 could replace Colin.

David Melnick: Along these lines, I'd also like to reiterate a point that we have made on our last two earnings calls, which is that our previously announced decision to discontinue the Phase 2a clinical trial was not, I repeat, not, indicative of our opinion regarding the ultimate success of the SPR 720 program. Rather, it was a strategic decision that allowed us to avoid incurring costs from the trial while it's on hold and that may facilitate potential future adjustments to the clinical trial design as required by FDA.

And in Polymyxin B in the currently prescribed antibiotic combination regiments and providing an alternative option for patients.

Producing a significantly reduced risk of kidney injury. This would address a crucial unmet need is the <unk> 2019 antibiotic resistant.

On a threat report estimates 8500 drug resistant acinetobacter depth and 32600 drug resistant pseudomonas infections in the United States per year.

David Melnick: Looking ahead, we expect to complete the study report from the recently completed primate study in the third quarter and to engage the FDA thereafter early in Q4. After we receive feedback from the agency regarding their review of these data and our full response to the clinical hold letter, we will provide an update on our clinical development plans for 7-20 moving forward. Switching gears now to discuss SPR-206, which is our intravenously administered next-generation polymyxin product candidate, which is designed to act directly on major negative bacterial infections through the molecule's interactions with the bacterial outer membrane.

We saw significant progress on.

Around our <unk> program in the second quarter highlighted by 2 exciting collaborations that provide external validation for the potential <unk> offers for patients with serious Gram negative infections first is the investment in licensing licensing agreement with Pfizer that.

<unk> mentioned earlier, we believe sponsor and Everest medicines, who you may recall has rights to develop manufacture and commercialize <unk> in China and other select Asian countries are ideal partners to ensure patient access to <unk> globally when approved.

Additionally, their teams bring a wealth of expertise in antibacterial drug development and regional specific experience with foreign regulatory agencies and quality control standards that will be invaluable as we finalize a pivotal clinical development program for <unk>.

David Melnick: SBR 206 has demonstrated potent broad-spectrum activity against gram-negative bacteria, including the extensively drug-resistant variants that have emerged as a major problem in both the hospital and community setting. We believe that SPR-206 will offer a safer alternative for patients suffering from serious drug-resistant infections, including drug-resistant Acinetobacter, multi-drug-resistant Pseudomonas, and Carbapenemase-producing Today, patients suffering from these infections are treated with a drug combination that frequently includes a carbapenem or a BL-BLI antibiotic, usually in combination with polymyxin B or cholesterol.

We were also awarded up to $23 million by the National Institute of allergy and infectious diseases or <unk> to support the clinical development of <unk> in the second quarter.

Proximately $2.1 million is initially available from the award which provides funding for pharmacokinetic Pharmacodynamic studies to aid in dose selection.

Manufacturing process development clinical microbiology and support for our initial regulatory interactions if fully exercised we would receive an additional $21.3 million over 5 years, which will provide funding for a broad range of additional activities, including a phase 2 clinical proof of concept.

<unk> study in patients with the range of target pathogens and targeted indications.

David Melnick: Treatment with these older polymyxins is associated with nephrotoxicity in many patients. What clearly differentiates SPR206 compared to colistin and the other polymyxin antibiotics is our phase one SADMAD data showing a lack of nephrotoxicity at or above the predicted therapeutic dose. We thus believe SPR206 could replace colistin and polymyxin B in the currently prescribed antibiotic combination regimens and provide an alternative option for patients while producing a significantly reduced risk of kidney injury. This would address a crucial unmet need as the CDC's 2019 Antibiotic Resistant Threats Report estimates 8,500 drug-resistant acinetobacter deaths and 32,600 drug-resistant pseudomonas infections in the United States per year.

In addition to this funding the award provides yet another point of external validation for <unk> from a well regarded external entity.

Looking ahead, we continue to advance <unk> development with the support of our partners at the Department of Defense Everest medicines, and most recently Pfizer Nia I'd.

Participant dosing recently commenced in the phase 1 bronco alveolar lavage clinical trial assessing the penetration of <unk> into the pulmonary compartment with the data from the trial are expected by early next year.

Given that many of our target patients for STR to those 6 suffered from lung infections. We believe that these data could represent a key inflection point for our <unk> program.

We also recently began dosing patients in our renal impairment study of <unk>, which will guide dosing in the many patients with MTR gram negative infections that have reduced kidney function.

David Melnick: We saw significant progress around our SPR-206 program in the second quarter, highlighted by two exciting collaborations that provide external validation to the potential of SPR-206 for patients with serious gram-negative infections. First, there is the investment and licensing agreement with Pfizer that Ankit mentioned earlier. We believe Pfizer and Everest Medicines, who you may recall have rights to develop, manufacture, and commercialize SPR-206 in China and other select Asian countries, are ideal partners to ensure patient access to SPR-206 globally when approved.

Data from this study are also on track to be reported by early 2022.

With that I'll turn the call over to our Chief operating Officer, Cristina Larkin, who will provide you with a review of the market opportunity for our pipeline products and detail our strategy for the launch of <unk> 10 on HBO.

Yeah.

Thank you David and good afternoon, everyone.

We made closer to <unk> potential I pray for the work that we have done and continue to support this is especially true in March that will be.

We focused on urologists and Ids and that this strategy will allow us to still capture a significant portion of the approximately 2 million cdti patients for the U S debt. We believe are the right targets for <unk> if approved.

David Melnick: Additionally, their teams bring a wealth of expertise in antibacterial drug development and regional-specific experience with foreign regulatory agencies and quality control standards that will be invaluable as we finalize a pivotal clinical development program for SBR206. We were also awarded up to 23 million dollars by the National Institute of Allergy and Infectious Diseases, or NIAID, to support the clinical development of SPR-206 in the second quarter. Approximately 2.1 million dollars are initially available from the award, which provides funding for pharmacokinetic pharmacodynamic studies to aid in dose selection, Manufacturing Process Development, Clinical Microbiology, and Support for our Initial Regulatory Interactions.

And is the 2 million patients there was a great opportunity in both the community and the hospital discharge market by providing a great clinical and value story.

And in the community setting <unk> may prevent or reduce the frequency of hospitalization for patients who have failed previous oral therapies. So who are resistant to current oral cdti therapy.

And then the hospital discharge setting Kirby pennon HDR could give healthcare providers the ability to discharge cdti patient sundar, providing both the clinical and economic economic advantages to switching to oral therapy.

Christina Larkin: If fully exercised, we would receive an additional $21.3 million over five years, which will provide funding for a broad range of additional activities, including a Phase II clinical proof-of-concept study in patients with the range of target pathogens and target indications. In addition to this funding, the award provides yet another point of external validation for SPR-206 from a well-regarded external entity. Looking ahead, we continue to advance SPR-206's development with the support of our partners at the Department of Defense, Everest Medicines, and most recently, Pfizer and NIAID.

Now, whether it's the potential of keeping patients out of the hospital or getting them home sooner.

Perm HCR has the opportunity to deliver value to all of the relevant stakeholders, including patients health care providers and payers.

And this is the value that on all of our stakeholders continued share with us through our advisory boards market research and all of our industry interactions.

So let's pivot to discuss how we are preparing our go to market plans. We continue to take a phased approach to building out our launch teams.

Our marketing and our market access on our medical affairs teams have been in place for well over a year building and executing our go to market strategy.

Christina Larkin: Participant dosing recently commenced in the Phase I bronchoalveolar lavage clinical trial, assessing the penetration of SPR-206 into the pulmonary compartment, with data from the trial expected by early next year. Given that many of our target patients for SPR-206 suffer from lung infections, we believe that these data could represent a key inflection point for our SPR-206 program. We also recently began dosing patients in our renal impairment study of SBR 206, which will guide dosing in the many patients with MDR gram-negative infections that have reduced kidney function.

On my our medical liaison team has been out building from early key opinion on advocacy within the antibiotic and cdti space with a focused effort on infectious disease physicians and urologists.

We've also been engaging payers and building our health economic messaging and lastly, we've also launched our digital first strategy and this includes our customer engagement, which combines with personal and non personal interaction.

Our digital personal engagement has been launched VR MSL team and it has allowed us to utilize the hybrid approach to engage our customers and our non personal on branded digital efforts has launched earlier. This year and includes an unbranded website called C. UTI evolution Dot com.

Christina Larkin: Data from this study are also on track to be reported by early 2022. With that, I'll 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 the launch of Tebipenem HBR. Thanks.

Targeting hcp's or health care providers to educate them on the burden of cdti.

On the health care providers, the patients and the health care system overall, and the need for new oral outpatient therapy.

And finally as it relates to our plans on building our sales organization, we'll look to bring on our sales leadership on first.

Christina Larkin: Thank you, David, and good afternoon.

Christina Larkin: As we move closer to Tebby Pinham HBR's potential approval, the work that we have done continues to support that this is a

And then we will plan to wait until we're closer to total proved to our approval to build out our sales team.

Christina Larkin: Specialty-Driven Launch that will be focused on urologists and IDEs, and that the strategy

And as we look ahead, we will continue to plan for the potential approval on launch and we remain encouraged by the positive feedback from all of our stakeholders regarding heavy pennon and its overall value proposition and with that I'll turn the call over to SaaS, who will provide you with a financial update.

Christina Larkin: The strategy will allow us to still capture a significant portion of the approximately 2 million CTI patients in the U.S. that we believe are the right targets for tebupenem HBR if approved.

Christina Larkin: And of the 2 million patients, there is a great opportunity in both the community and the hospital.

Thank you Christina and good afternoon, everyone I'd now like to turn your attention to our overview of <unk> financial results for the quarter ended June 32021.

Christina Larkin: [inaudible]

Christina Larkin: And in the community setting, tedipenum HBR may prevent or reduce the frequency of hospitalizations for patients who have failed previous oral therapies or who are resistant to current oral CTI therapies. And in the hospital discharge setting, Tebipenem HBR could give health care providers the ability to discharge CTI patients sooner, providing both a clinical and a

Total revenue for the second quarter of 2021 were $5.1 million compared with revenues of $1.7 million in the second quarter of 2020.

The difference was primarily due to an increase in clients' revenue received from the Doj contract for it.

Christina Larkin: Clinical and Economic Advantages of Switching to Oral Therapy Now, whether it's the potential to keep patients out of the hospital or getting them home sooner, Tebby Penn MHBR has the opportunity to deliver value to all of the relevant stakeholders, including patients, health care providers, and payers. And this is the value that all of our stakeholders continue to share with us through our advisory boards, market research, and all of our industry interactions.

<unk> 6 and the BARDA contract, but have you been on HBO.

Collaboration revenue from our licensing agreements that fiber and Everest medicines.

Research and development expenses for the second quarter of 2021 was $14.5 million.

Compared with $15.7 million for the same period in 2020.

This year over year reduction was primarily due to a decrease in expense.

Christina Larkin: So let's pivot and discuss how we're preparing our go-to-market plans. We continue to take a phased approach to building out our launch teams. You know, our marketing, our market access, and our medical affairs teams have been in place for well over a year.

Given by completion of significant activities and phase III clinical trial for <unk> depend on HBO.

Partially offset by expenses from phase 1 clinical trials to support anticipated NDA filing for.

Christina Larkin: Building and Executing Our Go-To-Market Strategy. Our medical liaison team has been out building some early key opinion advocacy within the antibiotic and CUTI space with a focus

Tim depend on HBO and clinical costs incurred for phase 1 bolt on.

Clinical trials for <unk>.

We expect R&D expenses in 2021 to be consistent relative to 2020.

Christina Larkin: Infectious Disease Physicians and Neurologists. We've also been engaging payers and building our health economy. And lastly, we've also launched our digital first strategy. And this includes our customer engagement, which combines personal and non-personal interaction. Our digital personal engagement has been launched via our MSL team, and it has allowed us to utilize a hybrid approach to engage our customers. And our non-personal, unbranded digital efforts were launched earlier this year, and include an unbranded website called

Do you have a low debt some of the R&D expenses, we expect to incur this year Inc.

<unk> costs related to the expected to open them HP, our NDA submission and medical affair strategy as well as personnel related expense discipline on the pipeline.

General and administrative expenses for the second quarter of 2021 of $9.2 million were higher than the $4.5 million reported in the same period in 2020.

Primarily due to increased professional expenses and personnel costs to support the company's key commercial efforts.

Christina Larkin: cutievolution.com. Targeted

Christina Larkin: Targeting HCPs or healthcare providers to educate them on the burden of CUTI on the healthcare providers, the patients, and the healthcare system overall, and the need for new oral outpatient therapy.

We expect G&A expenses to increase in 2021 relative to 2020 as.

As he built commercial capabilities and infrastructure to support the expansion I hate to update potential kept depend on HB commercial launch in 2022.

Christina Larkin: And finally, as it relates to our plans for building our sales organization.

Christina Larkin: We'll look to bring in our SAIL leadership first.

Christina Larkin: And then we'll plan to wait until we're close to our approval to build out our sales plan. And as we look ahead, we'll continue to plan for the potential approval and launch, and we remain encouraged by the positive feedback from all of our stakeholders regarding Tevipenem and its overall value proposition. And with that, I'll turn the call over to Saf, who will provide you with a financial update. Thank you, Christina, and good afternoon, everyone.

Satyavrat Shukla: I'd now like to turn your attention to our overview of Spero's financial results for the quarter ended June 30, 2021. These are revenues for the second quarter of 2021, worth $5.1 million, compared with revenues of $1.7 million in the second quarter of 2020. The difference is primarily due to an increase in clients' revenue received from the DOD contract for SPR 206 and the BARDA contract for Chevy Penham HVR and collaboration revenue from our

Satyavrat Shukla: Research and Development Expert

Satyavrat Shukla: Research and Development Expenses for the second quarter of 2021 were $14.5 million, compared with $15.7 million for the same period in 2020. This year-over-year reduction was primarily due to a decrease in expense, driven by the completion of significant activity in a phase 3 clinical trial for jiripinam HVR. Partially offset by expenses from Phase 1 clinical trials to support an anticipated NTA filing for Tebepenem HVR and clinical costs incurred for Phase 1 valve and RIS clinical trials for SPR tools.

Function is turned off to allow your signal to reach our equipment.

Once again that it star 1 to ask a question and we'll pause for just a moment to allow everyone an opportunity to signal for questions.

And we'll go first to Reto borough with Cowan.

Hi, Thanks for taking my question. This is Leila on for me too and congrats on the progress and maybe just on a 720 program.

Ice on the complete it uhm nonhuman Primate study can you just remind US is there is any additional preclinical or talk with data that we're also requested as part of the data package to the F. D. A and what is the bill gating factor so to speak remaining for submitting this study reported thank you.

Oh, Hi, Lila Thanks for the question no. The primary focus point for the F. D. A discussion is the toxicology day that we've referenced in prior earnings calls and so the cadence hereafter as as we mentioned we are preparing analyzing the data on preparing to report for submission with.

Satyavrat Shukla: We expect R&D expenses in 2021 to be consistent relative to 2020, and I will note that some of the R&D expenses we expect to incur this year include costs related to the expected Tempenham HBR NDA submission and medical affairs strategy, as well as personnel-related spending. General and administrative expenses for the second quarter of 2021 were $9.2 million, higher than the $4.5 million reported for the same period in 2020, primarily due to increased professional expenses and personal costs.

With F D. A and you know really the cages. After that is to you know engage in the discussion with him have the discussion and then received the requisite minutes of the discussion and we plan to do that as expeditiously as possible.

Alright. Thank you and then just maybe just a quick follow up to your plan and you know what kind of a timeline for I know peanuts update for you announce to the street when you submit the data package or do you plan to just wait until you have maybe 10 minutes in hand. Thank you.

Okay. Thanks, Yeah as as David mentioned will plan to have the discussion and get the minutes. So we can give you all everybody the appropriate context, and so we'll wait until the minutes for back.

Alright, Thanks can help for color.

We'll go next to Luis Chen with Cantor.

Satyavrat Shukla: We reported a net loss for the second quarter ended June 30, 2021 of $18.6 million, or $0.63 per common share, compared to a net loss of $17.5 million, or $0.85 per common share, reported for the same period in 2020. As of June 30, 2021, we had cash, cash equivalents, and marketable securities of $99.2 million. This balance does not include the proceeds from the $40 million equity investment made by Pfizer, which were received subsequent to the quarters.

Satyavrat Shukla: Including this investment by Pfizer, we believe that our existing cash, cash equivalents, and marketable security, together with a non-dilutive funding commit, will be sufficient to fund operations into the fourth quarter of 2020. For further details on our financials, please refer to our 10-Q file with the SDC today. Would you now like to open the call for questions? Operator. Thank you.

Operator: Thank you. If you would like to ask a question, please signal by pressing the star followed by the number on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Once again, that is star number one to ask a question, and we'll pause for just a moment to allow everyone an opportunity to signal for questions. And we'll go first to Ritu Baral with Callan.

Set up the entire pipeline.

That's a good segue to Cristina who can talk more about why it would depend on will be successful in the current commercial environment and policy environment.

Lila: Hi, thanks for taking the question. This is Lila on behalf of Ritu, and congrats on the progress and, maybe just, on the 720 program. Aside from the completed non-human primate study, can you just remind us if there are any additional preclinical or toxic data that were also requested as part of the data package to the FDA? And what is the real gating factor, so to speak, remaining for submitting the study report? Thank you.

Yeah, Thanks on Kent, and I'll, just tack on to I think 1 of the comments that you had made and I think you you stated on the reimbursement side, which I think is a really important part if you remember.

To that many of the current launches that we've seen have been primarily based on the hospital environment and the DRG payment system is certainly 1 of the main reasons why many of these drugs have a cap to their success is because of the way that these drugs are reimbursed.

David Melnick: Hi Lila. Thanks for the question.

Tavy Pan on because of the benefit if we've seen both on the community and the hospital switch therapy market is that this drug will be primarily paid as a pharmacy benefit and not under the hospital DRG system and that's a that's a key differentiating.

David Melnick: The primary focus point for the FDA discussion is the toxicology data we've referenced in prior earnings calls. And so the cadence hereafter is, as we mentioned, we are preparing, analyzing the data, and preparing the report for submission to FDA. And really, the cadence after that is to engage in the discussion with them, have the discussion, and then receive the requisite approval.

Advantage that we see in the market I think that's 1 the second is is that you know would be looked at the landscape before <unk> will be best suited for is that you know what we see is we don't want to compete with generics and that becomes another key part of the value story when.

David Melnick: [inaudible]

David Melnick: And then maybe, just maybe, as a quick follow-up, do you plan, you know, what's the kind of timeline for announcing those updates? Will you announce it on the street when you submit the data package? Or do you plan to just wait until you have maybe the minutes in hand? Thank you.

When we talk about where to have your pen on will be best suited is that it's really and that's the way. We constructed the trial design was not to compete with generics and the rail alternative here is when physicians are having to turn to IV treatment and the fact that we've been able to demonstrate in our phase III trial equivalents to IV or non inferiority to <unk>.

David Melnick: Yeah, thanks. As David mentioned, we'll plan to have the discussion and get the minutes so we can give, you know, everybody the appropriate context. And so we'll wait until the minutes are back. Thanks for the helpful call.

IV or depend on is it a real advantage and that's what we've heard through our market research and through our data of the ability to deliver the convenience of an oral but being able to show non inferiority to Ah you know on IV product is 1 of the key advantages and to date, we're the only product that has ever been able to deliver that level of evidence.

Louise Alesandra Chen: We'll go next to Louise Chen with Kantor.

Ankit Mahadevia: Hi, thanks for taking my questions here. So my first question to you is, what gives you confidence in a strong launch and uptake for tebipen and HBR? I know you went through a lot of details on the call, but maybe you could address how you'll be different from some of the other companies that have launched antibiotics in the space. And then, secondly, what are your thoughts on the PASTURE Act and other initiatives to improve reimbursement for antibiotics?

Especially at launch if ever and so those are 2 real key Differentiators and then the last 1 I would mention is that you know.

For the for the primary audience that we're looking to go after as I mentioned is not only just infectious disease physicians, but urologist and that is another key differentiation I think in the type of position that we're looking to target at launch.

Ankit Mahadevia: Do these only help hospital drugs, or could they be a benefit to you as well? And then just last question here on OPEX for the third and fourth quarter versus what you spend in the second quarter. Just trying to get a sense of how OPEX will look throughout the remainder of the year. Thanks, Luis, for the questions.

Thank you.

Yeah.

And Louise I can answer your question on the ramp for Opex for the remainder of the year.

Thank God.

Showed earlier for R&D.

Which we expect to be roughly even with 1 H.

1 of the age R&D once you on engie numbers on a little higher than <unk>, but on average I think thats. What you can expect at least for the remainder of the year sort of trending in that the overall for the trials.

Ankit Mahadevia: I will start with your question on Pasteur, then I'll hand it to Christina to talk about how our launch will be differentiated based on the differentiation of Tevipenem, and then I'll hand it to Saf to talk about OPEX. So as it relates to Pasteur, as we mentioned, the antimicrobial ecosystem has really started to percolate in a very interesting way, both with partnering activity, including with us, as well as activity on the policy front, as well as on the public financing front, including with us.

And then for G&A and commercial.

Ankit Mahadevia: As we look holistically at the field, we believe that our pipeline, because we've chosen it in a way that treats the maximal patient unmet need and also gives us the maximal chance at commercial viability, we do not need incentives to be able to be successful with medicines like tebipenem. However, we think that acts like Pasteur, which would provide a very large nine-figure payment to companies developing drugs that treat unmet needs in AMR, is great for the field.

Ankit Mahadevia: We think it would be a shot in the arm for the ecosystem, and we think it's beginning to gain some momentum on the Hill. So, we're very big fans of it, think it's good for the ecosystem, think it's very good for patients, and it could be additive and beneficial to tebipenem. However, we don't need it in order to be successful, and that's how we've set up the entire pipeline. I think that's a good segue to Christina, who can talk more about why tebipenem will be successful in the current commercial environment and policy environment.

Okay on the room on the parents studies. These expectation you have to go into a trade new setting and uhm as we think about yeah I've seen it back for market positioning you got some sponsors.

Christina Larkin: Yeah, thanks, Ankit. And I'll just tag on to, I think, one of the comments that you had made, and I think you stated,

<unk> looked at sort of a refractory on it.

Cindy colors send population would you also have to go.

And impatient set yeah has failed those therapies over yep going a bit earlier in in the treatment landscape make more sense for care 6 you have given them for the price for awhile.

Christina Larkin: On the reimbursement side, which I think is a really important part, if you remember, you know, two of the

Christina Larkin: System is certainly one of the main reasons why many of these drugs have a cap on their success is because of the way that these drugs are used.

Hi, Kevin Thanks, very much for the question.

Your your senses correct that after we've received data from the balance on Reno impairment studies will begin planning for both in collaboration with NAIAD, Pfizer and Everest advancing 2 O 6 into phase 2 study in patients you also write that given the broad utility of 2.

Christina Larkin: Ankit Mahadevia, Kamal Hamed, Satyavrat Shukla, Ankit Mahadevia, Kamal Hamed, Spero Therapeutics It's really, and that's the way we constructed the trial design, was not to compete with generics. And the real alternative here is when physicians are having to turn to IV treatment. And the fact that we've been able to demonstrate in our Phase 3 trial equivalents to IV or non-inferiority to IV or to Pentum is a real advantage. And that's what we've heard through our market research and through our data, about the ability to deliver the convenience of an oral. But being

2 O 6 for patients with resistant infections and do have several options in front of us in terms of how we trial what 2 O 6 can do.

That is a discussion debt we want to continue to progress spoke with our partners, but also as we continue to have discussions with both key opinion leaders, we'd collaborate with and ultimately the regulators. So so more on that as we get closer to that event, but I think your point is worth emphasizing that 2 O 6 has utility.

Christina Larkin: [inaudible]

Christina Larkin: And that is another key differentiation, I think, in the type of physician that we're looking to target at launch.

Satyavrat Shukla: Okay, and Luis, if I can answer your question.

Not just didn't ask you need it back for for those patients for that limited options, but also in Pseudomonas, which has a larger population of patients that need as well as enterobacter Alice patients who have resistance to existing therapeutic options. Further I'll note that in typical clinical practice poly mix and are often used in combination.

Satyavrat Shukla: on the ramp for OPEX for the remainder of the year.

Satyavrat Shukla: As I mentioned earlier, for R&D, you know, 2H we expect to be roughly even between.

Satyavrat Shukla: and OneQ R&G numbers are a little higher than 2Q, but on average, I think that's what you can expect, at least for the remainder of the year, sort of trending in the overall first half. And then for DNA and commercial, we'll certainly continue to, as Christina mentioned, take a phased approach to continue to build out our capabilities.

<unk> with other standard of care therapy, because these patients are really in dire Straits and need as many options as they can get so we do have options in terms of the clinical usage of 2 O 6 and we will make those choices as we get closer to that.

Satyavrat Shukla: So you'll see a bit of a ramp; our disclosed cash runway is now at two-fold.

Great and then maybe just as a follow up question or a separate question.

Satyavrat Shukla: for 4Q2022.

Have you had on them and as we think about you know the progression of medical education over the next 12 months or so apart lodge for if you think about y'all relative emphasis on.

Satyavrat Shukla: If you just did a burn rate from the last couple of quarters, you could tell that the cash flow may be a quarter or so longer than that, and the reason for the 4Q 2022 is

D weekend critics on with S disease conferences are you on he called out with her parents for you know expectation with regard to your presentation.

Satyavrat Shukla: and Spero Therapeutics Inc. Thank you. Thank you. Thank you.

Satyavrat Shukla: Which, for your estimation purposes, you could probably assume will be somewhat linear, maybe a little slower at the start and then building more into the first half of 2022. So, for the cash runway guidance and burn rates, you can see the trend in what we expect our public to be.

And while you're on D is that correct meetings, just kind of where do you think an early adoption uhm.

Complicated you most pacman hassle on that occasion.

Yeah, absolutely Kevin we have a very robust medical affairs for medical education strategy and you know it it's point worth emphasizing that we are targeting those clinicians we aimed to partner with them. So as David mentioned is we think about it there are really 3.3 things that were hoping to you know amplify in the.

Kevin DeGeneres: We'll go next to Kevin DeGeneres with Oppenheimer.

Kevin DeGeneres: Hey, thanks for taking my question. Maybe I'm one on 206. Can you just clarify?

David Melnick: So we're following the completion of the bowel and renal impairment studies, and there's expectation to go into a treatment setting. As we think about acetobacter market positioning, some sponsors have looked at a sort of refractory polymyxin D, and colistin population. We do also look to go... and in patients that have failed those therapies or were going a bit earlier in the treatment landscape, which makes more sense for 206, you know, given the product. Hi Kevin.

In the medical discourse on number 1 is the therapeutic opportunity an unmet need and we are doing that both with our infectious disease colleagues, but also at meetings like the American Urological Association, because it's Christina mentioned, we will be partnering with both types of clinicians as we get that'd be kind of patients secondly, both in the.

Medical education realm, and otherwise square day.

Eloping data and publishing it that speaks to the value that can depend on brings to the health care system and that is spelled for the clinicians who are very sensitive to these economics as well as our colleagues in the Payor community and then finally, we will find the right venues to continue to David mentioned generate and share data on the utility.

David Melnick: Thanks very much for the question. Your sense is correct that after we've received data from the bowel and the renal impairment studies, we will begin planning for, both in collaboration with NIAID, Pfizer, and Everest, advancing 206 into phase two studies in patients. You're also right that given the broad utility of 206 for patients with resistant infections, we do have several options in front of us in terms of how we test what 206 can do.

Tubby Pena mattress and C T I, but another other setting so the marine Oh for setting that David had mentioned as 1 example, so we're taking a holistic approach we're both interacting with a girl neurology colleagues as well as our I D colleagues and also keeping an eye for the value arguments that are really resident as we talk to pay us.

David Melnick: That is a discussion that, you know, we want to continue to progress both with our partners but also as we continue to have discussions with both key opinion leaders we collaborate with and ultimately with the regulators. So, more on that as we get closer to that event, but I think your point is worth emphasizing that 206 has utility not just in Acinetobacter for those patients that have limited options but also in Pseudomonas, which is a larger population of patients in need, as well as Enterobacterial patients who have resistance to existing therapeutic options.

[noise], thanks for taking my questions.

Thank you Kevin.

We'll go next to ask for your home with Fahrenheit.

Hi, Thanks for taking my question. So regarding the can check spansion opportunities tabby pennant H 9 specifically pneumonia can you discuss what's meant sir twin granular tabby Pennan Uhm, which is approved in Japan for pneumonia in children. Thanks.

Yeah. Thanks after for the question and if we first of all persons zoom out to 100000 feet as we think about our day to generation activities clinically for for can be kind of them. They come in 2 flavors. The first flavor is we've had a groundswell of interest from the clinician community to trial Tubby pet in <unk>.

David Melnick: Further, I'll note that in typical clinical practice, polymixins are often used in combination with other standard of care therapies because these patients are really in dire straits and need as many options as they can get. So, you know, we do have options in terms of the clinical usage of 206, and we'll make those choices as we get closer. Great, and then maybe just as a follow-up question or a separate question on, you know, have you had, I mean, as we think about, you know, the progression of medical education over, you know, the next 12 months or so prior to launch, should we think about, you know, a relative emphasis on, you know, ID week and, you know, traditional infectious disease?

Patient populations that matter to them Marino for is a good example, where the K welcoming it became to US and said that you have to try this a doctor imitation send and we're working with them. The second aspect is on a more formal indication basis, we're taking a step wise strategy. So to your question. We are we are undertaking the the Bronx.

The order number artwork as the first step to understanding how <unk> can work in patients with lung infection to your point the B granules that were approved by our partner majors taken Japan 10 years ago have extensive experience in respiratory indicated an indication spelled upper respiratory as well as it pneumonia.

David Melnick: Ankit Mahadevia, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc. Yeah, absolutely. Kevin, we have a very robust pipeline.

And we've seen that that that data suggest that heavy pen on can be affected and as well as cheaps lung penetration and so it will be in in coming medical meetings will be excited to share what our topic on them tablets can do with the prescriber community.

David Melnick: Yeah, absolutely, Kevin. We have a very robust medical affairs and medical education strategy. And, you know, it's a point worth emphasizing that we are targeting those clinicians we aim to partner with. And so, as David mentioned, as we think about it, there are really three things that we're hoping to amplify in the medical discourse. Number one is the therapeutic opportunity and unmet need.

Got it thanks.

Oh, we'll go next to her on some argue with H C. Wainwright.

Thanks, very much for taking my questions. Firstly I was wondering if we could circle back to the utility of <unk> and bloodstream infections and if you could just comment on whether the usage paradigm the dosing regimen the length of treatment and that specific context might be meeting.

David Melnick: And we are doing that both with our infectious disease colleagues but also at meetings like the American Urological Association. Because, as Christina mentioned, we will be partnering with both types of clinicians as we get Tevipenem to patients. Secondly, both in the medical education realm and otherwise, we're developing data and publishing it that speaks to the value that Tevipenem brings to the health care system. And that is for both clinicians who are very sensitive to these economics, as well as our colleagues in the payer community.

For the different from the lead labeled indication that you're seeking approval for.

David Melnick: And then finally, we will find the right venues to continue to, as David mentioned, generate and share data on the utility of Tevipenem, not just in CTI but in other settings. So, the Merino 4 setting that David had mentioned is one example.

David Melnick: So, we're taking a holistic approach. We're both interacting with our urology colleagues, as well as our ID colleagues, and also keeping an eye on the value arguments that are really relevant as we talk to payers.

Esther P. Rajavelu: We'll go next to Esther Hong with Berenberg. Hi, thanks for taking my question.

David Melnick: So regarding the potential expansion opportunities of Kevipenem AIDS,

David Melnick: Can you discuss what's been observed with granular tebupenem, which is approved in Japan from the Yeah, thanks, Esther, for the question. If we first, I'll first zoom out to 100,000 feet, as we think about our data generation activities clinically for tebupenem, they come in two flavors. The first flavor is that we've had a groundswell of interest from the clinician community to trial tebupenem in patient populations that matter to them. Moreno 4 is a good example where the KOL community came to us and said that you have to try this with bacteremic patients, and we're working with them. The second aspect is, on a more formal indication basis, we're taking a stepwise strategy.

It has a lot of gram negative activity and that's really the realm and which we think about it is that for you know for example in <unk> AP patients that otherwise are required to take carpet kind of on like <unk> have heavy as an oral option and really that's the frame that we'll think about as we go into studies in patients in other indications.

David Melnick: So, to your question, we are, you know, we are undertaking the bronchoalveolar lavage work as the first step to understanding how tevipenem can work in patients with lung infection. To your point, the granules that were approved by our partner Meiji Seika in Japan 10 years ago have extensive experience in respiratory indications, both upper respiratory as well as in pneumonia. And we've seen that that data suggests that tevipenem can be effective and, as well as, achieve lung penetration. And so we'll be excited to share what our tevipenem tablets can do with the prescriber community.

Okay, Great and then jump out.

So I had 1 set for possible surplus for and does not active against ESPN producing organisms and therefore would not work in Marina for.

Well understood. Thank you.

Couple of quick questions on the 206 market opportunity.

Can you frame for us what you think the likely market opportunity is in terms of the total addressable market size in the Pfizer territories. Please.

Unknown Attendee: And we'll go next to Ram Selvaraju with H.C. Wainwright.

I'll pass that question over to Christina.

Yeah, I think what we see without giving the exact numbers, but what we do see in terms of resistance rates to the common pathogens for <unk> 6 and David I think shared the specter of activity, which 2.6 is quite broad in terms of activity against Acinetobacter <unk>.

David Melnick: Thank you for taking my questions. Firstly, I was wondering if we could circle back to the utility of tebupenem in bloodstream infections, and if you could just comment on whether the usage paradigm, the dosing regimen, and the length of treatment in that specific context might be meaningfully different from the lead label indication that you're seeking approval for.

For pennon resistant.

David Melnick: Thanks, Ram, for the question. I'll pass that question to David, who can address it.

And her Baxter HCA and Pseudomonas and I think that's what makes this compound very unique is its ability to have coverage against you know the 3 big bugs in terms of the largest problems that we see across.

David Melnick: address the utility of tevipenem in bacteremic patients. Yeah

David Melnick: Yeah, the short answer to that question is no. The dosing regimen that we plan to run in Merino 4 will be identical to that in ADAPTO. And there are two lines of evidence to support that. First of all, there was a substantial subpopulation of patients with bacteremia included in the ADAPTO study population, and those patients did quite well on tebupenem. And remember, this was initial therapy with tebupenem. There was no need for IV therapy.

Institution, not only here in the United States, but that that exist in Europe, and the rest of world and so without giving you exact numbers on what I would say that those are the 3 biggest bugs in the 3 biggest problems that we see in institutions today.

Thanks, and then just 1 last point of clarification.

David Melnick: So that gives us confidence. The second line of evidence is the PKPD. You know, as we've discussed with you in the past, we have chosen a dosing regimen that provides extremely robust coverage and has pharmacodynamic equivalence to intravenously administered carbapenem. So for those two reasons, we don't plan any change in the dosing regimen. Okay, and can you just comment on whether you believe that in that specific indication, tebupenem would compete against ceftobiprol, which is currently in late stage clinical development, or if you think that, effectively, since these are clearly two different classes of antibiotics that

David Melnick: Biotics that they would essentially complement one another. Yeah, Ram.

David Melnick: Yeah, Ram, thank you for the question. Yeah, so thanks for the question, Ron.

David Melnick: You know, in a sense, tebipenem, we think of the utility of tebipenem as following the utility of other carbapenems, like an ertapenem, for example, which was our comparator in the trial. And carbapenem has a unique spectrum, has a lot of gram-negative activity. And that's really the realm in which we think about it, because for, for example, in CUTI and AT, patients that otherwise would be required to take carbapenems like ERTA have TEVI as an oral option. And really, that's the framework that we'll think about as we go into studies in patients and other indications.

[music].

David Melnick: Okay, great. Thank you. Go ahead, go ahead. Septobitomol is a cephalosporin that's not active against ESBL-producing organisms and therefore would not work in Merino 4.

David Melnick: Well, I have a couple of quick questions on the 206 market opportunity. Can you frame for us what you think the likely market opportunity is in terms of a total addressable market size in the Pfizer territories? I'll pass that question over to Chris.

Christina Larkin: Yeah, I think, you know, what we see without giving the exact numbers, but what we do see in terms of resistance rates to common pathogens for what 206, and David, I think, shared the spectrum of activity, which 206 is quite broad in terms of activity against Acinetobacter, you know, carbapenem-resistant Enterobacteraceae, and Pseudomonas. And I think that's what makes this compound very unique is its ability to have coverage against, you know, the three big bugs in terms of the largest problems that we see.

Christina Larkin: And so these are the three largest problems that we see across institutions not only here in the United States but that exist in Europe and the rest of the world. And so, without giving you exact numbers, I would say that those are the three biggest bugs in the three biggest problems that we see in institutions today.

Christina Larkin: Thanks. And then I just want to make one last point of clarification. What do you anticipate the FDA to classify with respect to the tebupenem NDA at this juncture with regard to the assignation of a review period? Ram, just to make sure I clarify the thinking, are you asking what we expect the review period to be once submitted? That's correct. Yeah, so Teddy Penham has received fast track designation, and fast track provides for an overall eight month review period, which is a six month review plus two month validation.

Operator: And that concludes today's question and answer session. I'd like to turn the conference back over to today's presenters for any additional or closing remarks.

Ankit Mahadevia: Thank you, operator. And I appreciate everyone for joining us today. We look forward to the continued advancement of our pipeline, and we'll keep everyone updated along the way. Thanks again. And that concludes.

Operator: That concludes today's conference. Thank you for your participation. You may now disconnect.

Operator: ... Copyright © 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. [inaudible] Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ??...

[music].

Ted Jenkins: Thank you, Operator, and thank you all for participating in today's conference. Earlier today, Spero Therapeutics released financial results and provided a pipeline update for the second quarter of 2020. Our press release is available on the investors 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 initiation, timing, and submission to the FDA of an NDA for tevipenem HBR and the potential approval of tevipenem HBR by the FDA.

Ted Jenkins: Statements about the future development and commercialization of SBR 206 and the potential receipt of milestone payments as well as royalties on potential future sales of SBR 206. The design, initiation, timing, progress, and result of the company's preclinical studies and clinical trials and its research and development program. Management's assessment of the results of such preclinical studies and clinical trials and the impact of the COVID-19 pandemic on the company's business and operations. 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 initial 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.

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

Second quarter 2021 earnings call. Today's conference is being recorded at this time I'd like to turn the call over to Ted Jenkins, Vice President head of Investor Relations at Spiro Therapeutics. Mr. Jenkins. Please go ahead Sir.

Ankit Mahadevia: Thank you, Ted. And thanks to all for joining us today to discuss our financial results and corporate highlights. As we continue to progress to the back half of 2021, we remain focused on preparing for the upcoming Tepipenem HBR NDA filing and executing on our corporate strategy as we work to transition to a commercial organization. I'm pleased to say that our efforts around these interrelated goals have continued to advance on track. On our last call, we shared that we had accumulated all of the data necessary for our NDA submission for TEPI-PENM.

Thank you operator, and thank you all for participating on today's conference call earlier today, Spero Therapeutics released financial results and provided a pipeline update for the second quarter of 2021.

Our press release is available on the investors page I'll just start with therapeutics website.

Ankit Mahadevia: Since then, we have been performing all of the required analyses and drafting sections of the NDA, both at the study and summary levels. We've seen sustained progress on these fronts, and we're confident that we'll submit the NDA in the fourth quarter. This is in line with the guidance provided on our last earnings call for an expected NDA submission during the second half of this year. Our efforts around Tevipenem HPR are supported both by our strong clinical data and our positive regulatory interactions with FDA.

Future commercialization the potential number of patients who could be treated by COVID-19 dependent <unk> and market demand for tip. Your hat on <unk> generally expected broad access across payer channels for type of your kind of HDR.

<unk> pricing on <unk> and the anticipated shift in treating patients from intravenous to oral administration of the <unk>.

<unk> for the company's ongoing development of <unk> 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 SPR 2 assets.

The design initiation timing progress and result of the company's preclinical studies and clinical trials and its research and development programs Managements assessment of the results on such a preclinical studies and clinical trials the impact on the COVID-19 pandemic on the company's business and operations.

Ankit Mahadevia: The positive Phase 3 ADAPT-PO trial results reported late last year showed that the trial's primary endpoint was met, with data demonstrating that an all-oral regimen of tevipenem-HBR is non-inferior to an all-IV regimen of ertepenem for the treatment of complicated urinary tract infection, or CUTI, and acute pyelonephritis, or AP. Now, our previous FDA interactions and written communication indicate that positive results from a single well-controlled pivotal trial, such as ADAPTEO, could be sufficient to support the approval of an NDA for teb-dependent HPR in the treatment of CUTI and AP.

These cash forecast and anticipated expenses, the sufficiency of its cash resources in the availability of additional non dilutive funding from governmental agencies beyond any initial 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.

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 new information regarding the company. After the date of todays release and call.

Participating on today's call are Dr. <unk>, <unk>, Chief Executive Officer, Dr. David Melnick, Chief Medical Officer, Cristina Larkin, Chief operating officer, and our Chief Financial Officer, Chico with that I'd like to turn the call over to Dr. Anthony <unk>. Please go ahead and get.

Thank you Ted and thanks to all for joining us today to discuss our financial results and corporate highlights as.

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

As we continue to progress to the back half of 2021, we remain focused on preparing for the upcoming heavy kind of H b, our NDA filing and executing on our corporate strategy as we work to transition to a commercial organization.

I'm pleased to say that our efforts around these interrelated goals have continued to advance on track.

On our last call we shared that we had accumulated all of the data necessary for our NDA submission for <unk> kind of.

Ankit Mahadevia: If approved, tebupenib-HBi would become the only oral carbapenem available for the treatment of CUTI and AP. Its ability to effectively replace IV therapy for these patients could prevent and shorten unnecessary hospitalizations, delivering value to the patient and economic benefits to the health care providers and payers. This has led payers to express their willingness to cover HMEPhenam HVR, which bodes well as we work towards potential launch.

Since then we have been performing all of the required analysis and drafting section for the NDA. Both at the study and summary levels. We've seen sustained progress on these fronts and we're confident that we will submit the NDA in the fourth quarter.

This is in line with the guidance provided on our last earnings call for an expected NDA submission during the second half of this year.

Our efforts around to be turned on HBO are supported both by our strong clinical data and our positive regulatory interactions with FDA.

Positive phase III adapt trial results reported late last year showed that the trial's primary end primary.

Ankit Mahadevia: I would now like to provide some updates on the SPR-720 clinical program. As a reminder, SPR-720 advanced into a Phase II clinical trial in patients with non-tuberculous mycobacterial disease, or NTM, at the end of last year. The initiation of this trial was supported by positive data from Phase I single and multiple ascending dose trials, as well as non-clinical toxicology studies in non-human primates and rodents. In these studies, multiple subjects were dosed, and no severe or serious adverse events were observed.

Primary endpoint was met with data demonstrating that an all oral regimen of COVID-19 depend on H B R is non inferior to an all IV regimen of are dependent for the treatment of complicated urinary tract infection or see UTI and acute pyelonephritis or AP.

Our previous FDA interactions and written communications indicate that positive results from a single well controlled pivotal trial, such as adapt Po could be sufficient to support the approval of an NDA for <unk> depend on <unk> in the treatment of CDI and <unk>. Additionally, through a feedback we receive from our pre NDA meeting the FDA endorsed the <unk>.

Structure in form of our planned NDA submission and indicated that the dataset and CMC plan that we intend to submit in the NDA package meet their standards.

We are confident that our all our turbine kind of on HBO program will continue to advance as planned as we move through the second half of 'twenty, 1 and into 2022 based on our positive clinical data and adapt Po is rigorous design. We believe that if approved to anytime on HCR will be an important physician treatment option for possibly over $2 million for UTI and AP.

Patients in the U S alone who are resistant to currently available oral therapies.

<unk> was designed as the first head to head comparison of an all oral versus an all IV regimen in <unk>, specifically to provide a robust result that would give physicians confidence to prescribe that depend on <unk> in 80 patients who would otherwise be required to receive IV therapy.

Ankit Mahadevia: With this information in hand, we will continue to engage the FDA on a full response to their clinical letter in early Q4. We will give an update on these discussions following FDA's written comment and direction as to our specific findings from the non-human primate study. Until then, I will reiterate the data we have seen to date that support the hypothesis that the observed mortalities were not drug-related, but rather dosing and species-specific.

We believe we have done just that as our data show that <unk> can provide the convenience of an oral therapy without any compromises on clinical response safety or tolerability.

If approved <unk> 10 on HBO would become the only oral carpet send them available for the treatment of UTI and AP.

Its ability to effectively replace IV therapy for these patients could prevent and shorten unnecessary hospitalizations delivering value to the patient and economics benefits to the health care providers and payers. This is led payers to expressed their willingness to cover HIV pennant H B R, which bodes well as we live work towards potential launch.

Ankit Mahadevia: This gives us confidence that there is a path forward for the SPR 720 clinical program, but, of course, we must complete our interactions with FDA before a final determination can be made. I would also now like to briefly highlight the recent exciting developments that have occurred around SPR-206, our next-generation polymyxin product candidate, and then David can speak in more detail about the program. We were thrilled to announce that we entered into a licensing agreement with Pfizer around this asset, pursuant to which Pfizer receives the rights to develop, manufacture, and commercialize SPR-206 in ex-U.S. and ex-Asia territories. In exchange for these rights, Spero is eligible to receive up to $80 million in development and sales milestones, with high single-digit to low double-digit royalties on net sales.

Okay.

I would now like to provide some updates on the SPR 720 clinical program.

As a reminder, Spi 720 advanced into a phase II clinical trial in patients with non tuberculous mycobacteria lung disease or MTM at the end of last year.

Initiation on this trial was supported by positive data from phase, 1 single and multiple ascending dose trials as well as non clinical toxicology studies in non human primates and roads.

Within these studies multiple subjects.

Our dose and no severe or serious adverse events were observed as the phase Iia trial is being conducted however, we also simultaneous engaged in additional longer term toxicology study in non human primates surprisingly and in contrast to the positive positive phase 1 sad mad human experience unexpected.

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, a program focused on funding innovative science to meet patient needs. This investment, which was made at a premium to market, provides important capital which we intend to use in preparation for the potential approval and launch of Tevipen and HPR, as well as to support ongoing clinical development of SPR720 and SPR207.

Explain and HP mortality for dessert.

Observed this led us to prudently pause the phase Iia clinical trial and promptly notified the FDA of this important dynamic. We then subsequently received the clinical hold letter in which the FDA requested additional information from the non human Primate studies, including a study report.

As we discussed on our last call we have since completed the non human Primate study and continue to analyze the data we expect to complete the requested study report on the third quarter as planned with this information in hand, we will continue to engage the FDA on a full response to their clinical hold letter in early Q4.

Ankit Mahadevia: The Equity Investment and Licensing Agreement provide important external validation from an industry leader and support our broader corporate strategy and pipeline development of anti-infectives for patients with unmet needs. Further, the value of the transaction speaks to our ability to execute on our business development objectives.

Port the hypothesis, that's been observed with <unk>, we're not drug related but rather dosing and species specific this gives us confidence that there's a path forward for the Spi 2020 clinical program, but of course, we must complete our interactions with FDA before a final determination can be made.

Ankit Mahadevia: It is also representative of a recent uptick in interest and investment activity around product candidates with the potential to address the rising rate of antimicrobial resistance or AMR. For instance, Pfizer, along with more than 20 leading pharmaceutical companies, contributed to the formation of the AMR Action Fund, which aims to invest over a billion dollars in antibiotic development by 2030. Pfizer has also already committed 100 million dollars to this fund and recently acquired Amplix Pharmaceuticals and Erixa Pharmaceuticals, both of which are focused on anti-infectives.

Eligible to receive up to $80 million in development and sales milestones with high single digit to low double digit royalties on net sales in.

In tandem with the licensing agreement Pfizer also made a $40 million equity investment in spero as part of the Pfizer breakthrough growth initiative, a program focused on funding innovative science to meet patient needs.

This investment which was made at a premium to market provides important capital, which we intend to use in preparation for the potential approval and launch for turbine pet on H B R. As well as to support ongoing clinical development of Spi 2020, and SPR to upset the.

Ankit Mahadevia: Before handing the call off to David, I'd like to reiterate Spero remains well equipped to continue executing on our objectives, even amongst the ever-evolving circumstances of the COVID-19 pandemic. While our business has not been materially impacted by COVID-19 in 2021, the pandemic is highlighting the value of replacing IV therapies that are often administered in the hospital setting with an at-home oral option. We believe that Tevifenom HBR, if approved, could provide such an option and enable a shift in care to the outpatient setting.

For instance, Pfizer.

Along with more than 20, leading pharmaceutical companies contributed to the formation of the Anr action fund, which aims to invest over $1 billion.

In antibiotic development by 2030.

Pfizer has also already committed $100 million for this fund and recently acquired ample expire on masuda goals and Eric's of pharmaceuticals, both of which have been focused on anti infectives.

This activity along with the efforts of other major pharmaceutical companies government agencies, and Polish policymakers is increasing the dynamism on the antimicrobial development ecosystem.

Ankit Mahadevia: This would provide value to patients, healthcare providers, and payers alike as it would reduce patient exposure to COVID-19 and other secondary infections. Further, hospitals will also see a financial benefit and free up capacity for seriously ill patients with no viable alternatives to hospitalization. I will now hand it over to David to provide a more detailed update on our clinical progress and our pipeline. Thank you, Ankit, and good afternoon everybody.

<unk> continues to remain active in the collaborative efforts of this ecosystem as shown by our recent deal with Pfizer our relationships with other corporate partners and private foundations and our partnerships with several government agencies, including BARDA. The U S Department of defense the defense threat reduction agency and the National Institutes of allergy is infectious.

Disease.

David Melnick: It's my pleasure to share our pipeline updates with you today. I'll begin by speaking briefly about our lead candidate, Tebutenum HBR, an oral carbapenem that is advancing toward an NDA filing expected in the fourth quarter. To provide a recap of what has brought us to this point, we reported top-line data showing that our Phase III ADAPT-PO trial met its primary endpoint in September. We also continue to work to complete the back-end activities for our suite of Phase I studies, which are designed to support the NDA.

Betty with an at home oral option.

We believe that <unk> signed on H B R. If approved could provide such an option and enable us shifting care for the outpatient setting this would provide value to patients health care providers and payers alike, because it would reduce patient exposure to COVID-19, and other secondary infections. Further hospital will also see a financial benefit and free up capacity for <unk>.

Seriously ill patients with no viable alternatives for hospitalization.

I will now hand, it over to David to provide a more detailed update on our clinical progress in our pipeline.

Thank you on kit and good afternoon, everybody, it's my pleasure to share our pipeline updates with you today.

I'll begin by speaking briefly about our lead candidate <unk>, an oral card for 10 of them that is advancing toward an NDA filing expected for the fourth quarter.

To provide a recap of what has brought us to this point, we reported top line data showing that our phase III adapt trial met its primary endpoint in September we.

We also continued to work to complete the backend activities for our suite of Phase 1 studies, which are designed to support the NDA. These activities included locking the steady databases analyzing these datasets and finalizing the.

David Melnick: In parallel with our efforts regarding the NDA, we also continue to work with our partners to ramp up our CMC capabilities ahead of Tebipenem's expected launch during 2022. I should remind everyone that one of our partners is Meiji Seika, whose experience manufacturing a granular formulation of Tebipenem over the past decade will be invaluable as we move toward commercialization. Before I move on to speak about 720 and SPR 206, I'd like to take a moment to talk about our strong clinical data supporting tepipenem HBR and what we believe it means from a physician's perspective.

We have since completed all of these activities and we are now focused on performing the required integrated analyses and grafting sections for the NDA submission given the straightforward nature of these activities. We are fully on track to submit the NDA in the fourth quarter.

Experienced manufacturing a granule formulation of <unk>.

Over the past decade will be invaluable as we move toward commercialization.

Before I move on to speak about 720, and STR to a 6 I'd like to take a moment to talk about our strong clinical data supporting <unk> 10 on HCR and what we believe it means from a physician's perspective.

David Melnick: A DAPTO's rigorous design allowed us to show that physicians treating CUTI and AP patients could replace hospital IV therapies with oral Tebutanib-HBR without making any compromise on clinical response, safety, or tolerability. By doing this, we believe we have positioned ourselves to see high uptake of Tebutanib-HBR after approval. Beyond CUTI, the ADAPTPO data have also generated strong external interest from key opinion leaders on the use of cabipenem HVR to treat other infections, providing potential opportunities to explore new indications. One example of this external interest is the Merino 4 trial that I mentioned at the time of our last call.

The increasing prevalence of resistance to existing oral therapies for complicated utis as well as safety concerns related to some of the existing oral therapies such as for floor plan loans. Currently leaves millions of patients with no choice, but to receive intravenous antibiotic therapy, which often requires.

Organization for IV access at GAAP <unk> rigorous design allowed us to show that physicians treating C. UTI on AP patients could where price hospital IV therapies with oral <unk> without making any compromise on clinical response safety or tolerability.

Doing this we believe we have positioned ourselves to see high uptake on <unk> kind of HCR after approval.

David Melnick: This study is being sponsored by the National Institute of Allergy and Infectious Diseases and is being conducted by the Antibiotic Resistance Leadership Group. As a reminder, Merino 4 is designed to compare the early transition to oral tebitinib-HBR with continuation of intravenous parvipenem therapy in patients with bloodstream infections caused by ESBL-positive bacteria. In addition, we have completed data analysis from the BARDA-funded Phase I bronchoalveolar lavage trial, which assesses the lung penetration of tebupenem HBR, and we plan to present these data at an upcoming medical meeting.

1 example of this external interest is embodied by them Marino for trial that I mentioned at the time of our last call. This is being sponsored by the National Institute of allergy and infectious diseases and is being conducted by the antibiotic resistance leadership group.

As a reminder, Marino for is designed to compare the early transition to oral <unk> with continuation of intravenous <unk> therapy in patients with blood stream infections caused by ESPN positive bacteria.

In addition, we have completed data analysis from the BARDA funded phase 1 bronchoalveolar lavage trial, which assesses the lung penetration of turbine kind of H B R and we plan to present these data at an upcoming medical meeting. This study will set the stage for subsequent BARDA funded.

David Melnick: Looking forward, we plan on continuing to educate the clinical community about tebutanin HBR through publication of a peer-reviewed manuscript reporting the ADAPT-PO trial results. These results will or have been discussed at five infectious diseases and urology conferences by the end of the year, including the upcoming AUA meeting. At these conferences, we intend to present additional ADAPT-PO data, as well as in vitro surveillance data assessing the activity of tebutanin HBR against the most important gram-negative pathogens.

Studies to evaluate the efficacy of orally administered <unk> HDR for Pneumonic indications. This study has strong clinical rationale as the granular formulation of <unk> is approved in Japan for several respiratory indications, including the treatment of children with pneumonia.

Looking forward, we plan on continuing to educate the clinical community about <unk> 10 on HBO through publication of a peer reviewed manuscript reporting the adapt trial results.

These results will or have been discussed at 5 infectious diseases and urology conferences by the end of the year, including the upcoming <unk> meeting at these conferences, we intend to present additional adapt Po data as well as the in vitro surveillance data assessing the activity of <unk> kind of on HCR.

Against the most important gram negative pathogens.

I'd now like to move on to speak briefly about 7.

SBR 720, our oral drug candidate that we're developing for the treatment of the MTM infection non tuberculosis mycobacteria lung infections on kit.

David Melnick: Most importantly, the mortalities observed in the non-human primate study that led to the hole did not correlate with either the dose nor with the duration of SPR-720 drug exposure. Further, adult non-human macaques, the animals in this study, are known to be extremely challenging to dose, which adds a level of complexity to the analysis of the study. Finally, the findings from this nonhuman primate study are contrary to what we have seen in prior preclinical and clinical studies of SPR720, as Ankit outlined earlier.

Recap the events that led to the program's clinical hold during his portion of the call so rather than repeat what he said I'll just emphasize a few additional points.

Most importantly, the more camera these observed in the non human Primate study that led to the whole did not correlate with either the dose nor with the duration of SPR 7.8 drug exposure for.

<unk>.

Non human mechanics, the animals. In this study are known to be extremely challenging to dose, which adds a level of complexity to the analysis of the study.

Finally, the findings from this non human primates primates study are contrary to what we have seen in prior preclinical and clinical studies of SPR 720 is on Kate outlined earlier.

David Melnick: Along these lines, I'd also like to reiterate a point that we have made on our last two earnings calls, which is that our previously announced decision to discontinue the Phase IIa clinical trial was not, I repeat, not indicative of our opinion regarding the ultimate success of the SPR 720 program. Rather, it was a strategic decision that allowed us to avoid incurring costs from the trial while it's on hold and that may facilitate potential future adjustments to the clinical trial design as required by FDA.

These data continue to support the hypothesis that the observed mortality where specific either to the oral gavage dosing method for to the species from monkeys and the study rather than related to an off target pharmacologic effect along these lines I also like to reiterate a point that we have made on there.

Last 2 earning calls which is that our previously announced decision to discontinue the phase Iia clinical trial was not I repeat not indicative of our opinion regarding the ultimate success of the <unk> 720 program rather it was a strategic decision.

David Melnick: Looking ahead, we expect to complete the study report from the recently completed primate study in the third quarter and to engage the FDA thereafter early in Q4. After we receive feedback from the agency regarding their review of these data and our full response to the clinical hold letter, we will provide an update on our clinical development plans for 7-20 moving forward. Switching gears now to discuss SPR-206, which is our intravenously administered next-generation polymyxin product candidate, which is designed to act directly on gram-negative bacterial infections through the molecule's interactions with the bacterial outer membrane.

That allowed us to avoid incurring costs from the trial, while it's on hold and that may facilitate potential future adjustments to the clinical trial design as required by FDA.

<unk> plans for <unk> moving forward.

Switching gears now to discuss <unk>, which is on our intravenously administered next generation polymyxin product candidate.

David Melnick: SPR206 has demonstrated potent broad-spectrum activity against gram-negative bacteria, including the extensively drug-resistant variants that have emerged as a major problem in both the hospital and community settings. We believe that SPR-206 will offer a safer alternative for patients suffering from serious drug-resistant infections, including drug-resistant Acinetobacter, multi-drug-resistant Pseudomonas, and Carbapenemase-producing Enter Today, patients suffering from these infections are treated with a drug combination that frequently includes a carbapenem or a BL-BLI antibiotic, usually in combination with polymyxin B or cholesterol. However, treatment with these older polymyxins is associated with nephrotoxicity in many patients.

Which is designed to act directly on Gram negative bacterial infections through the molecules interactions with the bacterial outer membrane.

We believe the SPR <unk> will offer a safer alternative for patients suffering from serious drug resistant infections, including drug resistant acinetobacter multi drug resistant pseudomonas and <unk> producing enterobacteriaceae with the greatest unmet need currently exists.

In the antibiotic formula.

Today patients suffering from these infections are treated with a drug combination, which frequently includes a carbo panel work.

David Melnick: What clearly differentiates SPR206 compared to colistin and the other polymyxin antibiotics is our phase one SADMAD data showing a lack of nephrotoxicity at or above the predicted therapeutic dose. We thus believe SPR206 could replace colistin and polymyxin B in the currently prescribed antibiotic combination regimens and provide an alternative option for patients while producing a significantly reduced risk of kidney injury. This would address a crucial unmet need, as the CDC's 2019 Antibiotic Resistant Threats Report estimates 8,500 drug-resistant acinetobacter deaths and 32,600 drug-resistant pseudomonas infections in the United States per year.

BLI antibiotic usually in combination with polymyxin colistin.

Treatment with these older Polymyxin is associated with nephrotoxicity in many patients.

We're clearly differentiates <unk> 6 compared to Clifton and the other polymyxin antibiotics use our phase 1 sad mad data showing a lack of network toxicity at or above the predicted therapeutic dose with us believe SPR <unk> could replace <unk>.

<unk> and polymyxin B in the currently prescribed antibiotic combination regiments and providing an alternative option for patients.

Producing a significantly reduced risk of kidney injury. This would address a crucial unmet need is the <unk> 2019 antibiotic resistant threat.

David Melnick: We saw significant progress around our SPR-206 program in the second quarter, highlighted by two exciting collaborations that provide external validation for the potential of SPR-206 for patients with serious gram-negative infections. First, there is the investment and licensing agreement with Pfizer that Ankit mentioned earlier. We believe Pfizer and Everest Medicines, who you may recall have rights to develop, manufacture, and commercialize SPR-206 in China and other select Asian countries, are ideal partners to ensure patient access to SPR-206 globally when approved.

Threats report estimates 8500.

<unk> resistant acinetobacter debt and 32600 drug resistant pseudomonas infections in the United States per year.

We saw significant progress around our <unk> hundred 6 program in the second quarter highlighted by 2 exciting collaborations that provide external validation for the potential <unk> offers for patients with serious gram negative infections first is the investment in license.

Licensing agreement with Pfizer that <unk> mentioned earlier, we believe sponsor and Everest medicines, who you may recall has rights to develop manufacture and commercialize <unk> in China and other select Asian countries are ideal partners to ensure patient access.

David Melnick: Additionally, their teams bring a wealth of expertise in antibacterial drug development and regional specific experience with foreign regulatory agencies and quality control standards that will be invaluable as we finalize a pivotal clinical development program for SBR 206. We were also awarded up to $23 million by the National Institute of Allergy and Infectious Diseases, or NIAID, to support the clinical development of SPR-206 in the second quarter. Approximately $2.1 million is initially available from the award, which provides funding for pharmacokinetic pharmacodynamic studies to aid in dose selection, Manufacturing Process Development, Clinical Microbiology, and Support for our Initial Regulatory Interactions.

To STR 206 globally when approved <unk>.

Additionally, their teams bring a wealth of expertise and antibacterial drug development and regional specific experience with foreign regulatory agencies and quality control standards that will be invaluable as we finalize a pivotal clinical development program for <unk>.

We were also awarded up to $23 million by the National Institute of allergy and infectious diseases or <unk> to support the clinical development of STR <unk> 6 in the second quarter approximately $2.1 million is initially available from the award which provides funding for pharmacokinetics.

<unk> Pharmacodynamic studies to aid in dose selection.

David Melnick: If fully exercised, we would receive an additional $21.3 million over five years, which will provide funding for a broad range of additional activities, including a Phase II clinical proof-of-concept study in patients with the range of target pathogens and target indications. In addition to this funding, the award provides yet another point of external validation for SPR-2SX from a well-regarded external entity. Looking ahead, we continue to advance SPR-206's development with the support of our partners at the Department of Defense, Everest Medicines, and most recently, Pfizer and NIAID.

<unk> study in patients.

With the range of target pathogens and targeted indications in.

In addition to this funding the award provides yet another point of external validation for <unk> from a well regarded external entity.

Looking ahead, we continue to advance <unk> development with the support of our partners at the Department of Defense Everest medicines, and most recently Pfizer and NIH.

David Melnick: Participant dosing recently commenced in the Phase I bronchoalveolar lavage clinical trial, assessing the penetration of SPR-206 into the pulmonary compartment, with data from the trial expected by early next year. Given that many of our target patients for SPR-206 suffer from lung infections, we believe that these data could represent a key inflection point for our SPR-206 program. We also recently began dosing patients in our renal impairment study of SBR 206, which will guide dosing in the many patients with MDR gram-negative infections that have reduced kidney function.

Participants dosing recently commenced in the phase 1 bronco alveolar lavage clinical trial assessing the penetration of <unk> into the pulmonary compartment with the data from the trial expected by early next year.

Given that many of our target patients for STR to those 6 suffer from lung infections. We believe that these data could represent a key inflection point for our <unk> program.

We also recently began dosing patients in our renal impairment study of <unk>, which will guide dosing in the many patients with MTR gram negative infections that have reduced kidney function.

David Melnick: Data from this study are also on track to be reported by early 2022. With that, I'll 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 the launch of Tebipenem HBR. Thanks.

Data from this study are also on track to be reported by early 2022.

Christina Larkin: Thank you, David, and good afternoon, everyone.

Yeah.

Thank you David and good afternoon, everyone.

Christina Larkin: As we move closer to Tebby Penham HBR's potential approval, the work that we have done continues to support that this is a specialty-driven launch.

We made closer to Kirby pet on H B Rs potential appraisal work that we have done and continue to support that this is especially true in March that will be focused on urologists and Ids and that this strategy will allow us to still capture a significant portion of the approximately 2 million UTI patients for the U S.

Christina Larkin: That'll be focused on urologists and IDEs.

Christina Larkin: And that the strategy will allow us to still capture a significant portion of the approximately 2 million CTI patients in the U.S. that we believe are the right targets for tebupenem HBR, if approved. And of these 2 million patients, there is a great opportunity in both the community and the hospital discharge market by providing a great clinical and value story. And in the community setting, tedipenum HBR may prevent or reduce the frequency of hospitalizations for patients who have failed previous oral therapies or who are resistant to current oral CTI therapies. And in the hospital discharge setting, Tebby Pitt.

That we believe at the right targets for <unk> if approved.

And at the 2 million patients there is a great opportunity in both the community and the hospital discharge market by providing a great clinical and value story.

And in the community setting Kenny Panama, HDR may prevent or reduce the frequency of hospitalization for patients who have failed previous oral therapies.

So who are resistant to current oral cdti therapy.

And then the hospital discharge setting Kirby pennon, HDR could give healthcare providers the ability to discharge cdti patients sooner.

Christina Larkin: HVR could give health care providers the ability to discharge CTI patients sooner.

Christina Larkin: for providing both clinical and economic advantages to switching to oral therapy. Now, whether it's the potential to keep patients out of the hospital or getting them home sooner, Tebby Penham HBR has the opportunity to deliver value to all of the relevant stakeholders, including patients, health care providers, and payers. And this is the value that all of our stakeholders continue to share with us through our advisory boards, market research, and all of our industry interactions. Now, let's pivot and discuss how we're preparing.

Riding both the clinical and economic economic advantages to switching to oral therapy now.

Now, whether it's the potential of keeping patients out of the hospital or getting them home sooner.

Pam HCR has the opportunity to deliver value to all of the relevant stakeholders, including patients health care providers and payers.

And this is the value that on all of our stakeholders continued share with us through our advisory boards market research and all of our industry interactions.

So let's pivot to discuss how we are preparing our go to market plans. We continue to take a phased approach to building out our launch teams.

Christina Larkin: Sharing Our Go-To-Market Plans

Christina Larkin: We continue to take a phased approach to building out our launch team. You know, our marketing, our market access, and our medical affairs teams have been in place for well over a year building and executing our go-to-market strategy.

And on market, our marketing and our market access and our medical affairs teams have been in place for well over a year building and executing our go to market strategy.

Christina Larkin: Our medical liaison team has been out building some early key opinion advocacy within the antibiotic and CUTI space with a focus on

On our medical liaison team has been out building from early key opinion advocacy within the antibiotic and for UTI space with a focused effort on infectious disease physicians and urologists.

Christina Larkin: on Infectious Disease Physicians and Neurologists. We've also been engaging payers and building our health economic messages. And lastly, we've also launched our digital first strategy, which includes our customer engagement, which combines with personal

Also for engaging payers and building our health economic messaging.

And lastly, we've also launched our digital for our strategy and this includes our customer engagement, which combines with personal and non personal interaction.

Christina Larkin: of Personal and Non-Personal Interaction

Christina Larkin: Our digital personal engagement has been launched via our MSL team, and it has allowed us to utilize the hybrid approach to engage our customers, and our non-personal, unbranded digital efforts launched earlier this year. They include an unbranded website called CUTIEvolution.com targeting HCPs or healthcare providers to educate them on the burden of CUTI on the healthcare providers, the patients, and the healthcare system overall, and the need for new oral outpatient therapy.

Our digital personal engagement has been launched VR MSL team and has allowed us to utilize the hybrid approach to engage our customers and our non personal on branded digital efforts has launched earlier. This year and includes an unbranded website called C. UTI evolution Dot com.

Targeting hcp's or health care providers to educate them on the burden of cdti.

On the health care providers, the patients and the health care system overall, and the need for new oral outpatient therapy.

Christina Larkin: And finally, as it relates to our plans for building our sales organization, we'll look to bring on our sales leadership arm first, and then we'll plan to wait until we're close to our approval to build out our sales organization. And as we look ahead, we'll continue to plan for the potential approval and launch, and we remain encouraged by the positive feedback from all of our stakeholders regarding tebupenem and its overall value proposition.

And finally as it relates to our plans on building our sales organization, we will look to bring on our sales leadership on first.

And then we'll plan to wait until we're closer to total proved to our approval to build out our sales team.

And as we look ahead, we'll continue to plan for the potential approval on launch and we remain encouraged by the positive feedback from all of our stakeholders regarding <unk> and its overall value proposition and with that I'll turn the call over to SaaS, who will provide you with a financial update.

Satyavrat Shukla: And with that, I'll turn the call over to Saf, who'll provide you with a financial update.

Satyavrat Shukla: Thank you, Christina, and good afternoon, everyone. I'd now like to turn your attention to our over.

Thank you Christina and good afternoon, everyone.

Satyavrat Shukla: I'd now like to turn your attention to our overview of Spero's financial results for the quarter ended June 30, 2021. Social revenues for the Second Quarter of 2021 were $5.1 million, compared with revenues of $1.7 million in the second quarter of 2020.

I'd now like to turn your attention to our overview of <unk> financial results for the quarter ended June 32021.

Total revenue for the second quarter of 2021 were $5.1 million.

Compared with revenues of $1.7 million in the second quarter of 2020.

Satyavrat Shukla: The difference was primarily due to an increase in clients' revenue received from the DoD contract for SPR 206 and the BARDA contract for Chevipenem HVR and collaboration revenue from our licensing agreements with Pfizer and Everest Medicine. Research and Development Expenses for the second quarter of 2021 were $14.5 million, compared with $15.7 million for the same period in 2020. This year-over-year reduction was primarily due to a decrease in expense, driven by completion of significant activity, in phase 3 clinical trials for terapenem HVR, although partially offset by expenses from Phase 1 clinical trials to support an anticipated NTA filing for Tebephenem HVR and clinical costs incurred for Phase I valve and RIS clinical trials for SPR tools.

The difference was primarily due to an increase in client revenue received from the Doj contract for S. P.

<unk> 6 and the BARDA contract, but have you been on HB and collaboration revenue from our licensing agreements that fiber and Everest medicines.

Research and development expenses for the second quarter of 2021 were $14.5 million.

Compared with $15.7 million for the same period in 2020.

This year over year reduction was primarily due to a decrease in expense driven by completion of significant activities and phase III clinical trial for Jerry for them each be on.

Partially offset by expenses from phase 1 clinical trials to support the anticipated NDA filing for.

So it can depend on HBO and clinical costs and coach for phase 1 bolt on I clinical trials for <unk>.

Satyavrat Shukla: We expect R&D expenses in 2021 to be consistent relative to 2020, and I will note that some of the R&D expenses we expect to incur this year include costs related to the expected telefinem HBR NDA submission and medical affairs strategy, as well as personnel-related spending. General and administrative expenses for the second quarter of 2021 were $9.2 million, higher than the $4.5 million reported for the same period in 2020, primarily due to increased professional expenses and personal costs.

<unk>.

We expect R&D expenses in 2021 cubic consistent relative to 2020.

And to have a low debt some of the R&D expenses, we expect to incur this year include costs related to the expected to open them HP, our NDA submission and medical affair strategy as the last question on it related expense discipline on the pipeline.

General and administrative expenses for the second quarter of 2021 of $9.2 million were higher than the $4.5 million reported in the same period in 2020.

Primarily due to increased professional expenses and personnel costs to support the company's key commercial efforts.

Satyavrat Shukla: Support the company's pre-commercial efforts. We expect G&A expenses to increase in 2021 relative to 2020 as we build commercial capabilities and the infrastructure to support the expansion ahead of the potential Tebepenem HBR commercial launch in 2022. We reported a net loss for the second quarter ended June 30, 2021 of $18.6 million, or $0.63 per common share, compared to a net loss of $17.5 million, or $0.85 per common share, reported for the same period in 2020.

We expect G&A expenses to increase in 2021 relative to 2020 as he built commercial capabilities and the infrastructure to support the expansion I hate to update potential can depend on HB commercial launch in 2022.

We reported a net loss for the second quarter ended June 32021 of.

$18.6 million or <unk> 63 per common share.

Compared to a net loss of $17.5 million on 85 cents per common share reported for the same period in 2020.

Satyavrat Shukla: As of June 30, 2021, we had cash, cash equivalents, and marketable security of 99.2 million jobs. This balance does not include the proceeds from the $40 million equity investment made by Pfizer, which were received subsequently to the quarters. Including this investment by Pfizer, we believe that our existing cash, cash equivalents, and marketable security, together with a non-dilutive funding committee, will be sufficient to fund operations into the fourth quarter of 2021. For further details on the financials, please refer to our 10-2 file with the SDC today. We would now like to open the call for questions. Operator? Thank you.

As of June 32.

2021.

We had cash cash equivalents and marketable securities of $99.2 million.

This balance does not include the proceeds from the $40 million equity investment made by Pfizer.

Were received subsequently to the quarter cent Inc.

Including this investment by Pfizer.

We believe that our existing cash cash equivalents in marketable securities.

Together with our non diluted funding commitments will be sufficient to fund operations into the fourth quarter of 2022.

For further details on our financials.

Please refer to our 10-Q filed with the SEC to date.

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

Operations.

Thank you if he would like to ask a question. Please signal by pressing star followed by the 1 on your telephone keypad.

You are using a speaker phone. Please make sure your mute function is turned off to allow your signal to reach our equipment.

Once again that is star 1 to ask a question and we will pause for just a moment to allow everyone an opportunity to signal for questions.

Okay.

Yeah.

And we'll go first to Ritu <unk> with Cowen.

Hi, Thanks for taking the question I think while on for me Kevin Congrats on the progress and maybe just on a 700000 program.

<unk> completed on non human Primate study can you just remind us for Paris.

Any additional preclinical tox data that were also requested as part of a data package to the FDA and what is the milk gain.

Sachin Inc. Remaining price for many months study reported thank you.

Hi, <unk> thanks for the question.

David Melnick: Hi Lila, thanks for the question. The primary focus point for the FDA discussion is the toxicology data we've referenced in prior earnings calls. And so the cadence hereafter is, as we mentioned, we are preparing, analyzing the data, and preparing the report for submission to FDA. And really, the cadence after that is to engage in the discussion with them, have the discussion, and then receive the requisite approval.

The primary focus point for the updated discussion is the toxicology data that we've referenced in prior earnings calls and so the cadence hereafter as as we mentioned we are preparing analyzing the data on preparing the report for submission with.

With FDA.

And really the cadence after that is to engage in that discussion with them have the discussion and then received the requisite minutes of the discussion.

David Melnick: Transcripts provided by Transcription Outsourcing, LLC.

And we plan to do that as expeditiously as possible.

David Melnick: Got it, thank you. And then, just maybe, as a quick follow-up, do you plan, you know, what's the kind of timeline for announcing those updates? Will you announce it on the street when you submit the data package? Or do you plan to just wait until you have maybe the minutes in hand? Thank you.

Alright. Thank you and then just maybe as a quick follow up do you plan on you know what's kind of a timeline for announcing those updates will you announce to the street. When you submit the data package or do you plan to just wait until you have maybe 10 minutes on hand. Thank you.

Got it thanks.

As David mentioned, we'll plan to have the discussion and get the minutes. So we can give.

Everybody in the appropriate context, and so we'll wait until the day minutes you're back.

David Melnick: Thanks for the helpful call.

Thanks for calling.

Louise Alesandra Chen: We'll go next to Louise Chen with Cantor.

We will go next to Louise Chen with Cantor.

Louise Alesandra Chen: Hi, thanks for taking my questions here. So my first question to you is, what gives you confidence in a strong launch and uptake for Tebby Penn MHBR? I know you went through a lot of details on the call, but maybe if you could address how you'll be different from

Hi, Thanks for taking my questions here. So my first question to you is what gives you confidence and a strong launch and uptake for Toby Panama H B I know you went through a lot of details on the call, but maybe if you could address how youll be different from some of the other companies that have launched antibiotics for the space.

Louise Alesandra Chen: Unknown Speaker from some of the other companies that have launched antibiotics into space. And then, secondly, what are your thoughts on this?

And then secondly, what are your thoughts on the pasture and other initiatives to improve reimbursement for antibiotics do these only help hospital drugs or could they be a benefit to you as well and then just last question here on Opex for third and fourth quarter versus what you spend on second quarter, just trying to get defensive how opex will look throughout the remainder of the year.

Louise Alesandra Chen: What are your thoughts on the PASTURE Act and other initiatives to improve reimbursement for antibiotics? Do these only help hospital drugs or could they be a benefit to you as well? And then, just last question here on OpEx. [inaudible] Thanks, Luis, for the questions.

Thank you.

Thanks Louise for the questions I will start with your question on past sure then I'll hand, it to Christina to talk about how our launch will be differentiated based on the differentiation of <unk> and then I'll hand, this off to talk about Opex.

Ankit Mahadevia: I will start with your question on Pasteur, then I'll hand it to Christina to talk about how our launch will be differentiated based on the differentiation of Tevipenem, and then I'll hand it to Saf to talk about OPEX. So as it relates to Pasteur, you know, as we mentioned, the antimicrobial ecosystem has really started to percolate in a very interesting way, both with partnering activity, including with us, as well as activity on the policy front, as well as on the public financing front, including with us.

So as it relates to past sure as we mentioned the anti microbial.

The ecosystem has really started to percolate in a very interesting way, both with partnering activity, including with us.

As well as activity on the policy front as well as on the public financing front, including with us.

Ankit Mahadevia: We are, you know, as we look holistically at the field, we believe that our pipeline, because we've chosen it in a way that treats the maximal patient unmet need and also gives us the maximal chance at commercial viability, we do not need incentives to be able to be successful with medicines like tebipenem. However, we think that acts like Pasteur, which would provide a very large nine-figure payment to companies developing drugs that treat unmet needs in AMR, is great for the field.

We are.

As we look holistically at the field, we believe that our pipeline because we've chosen it in a way that.

Treats the maximal patient unmet need and also gives us the maximal chance at commercial viability, we do not need.

Incentives to be able to be successful with medicines like <unk> pen on however, we think that acts like patch store, which would provide a very large 9 figure payment.

2 companies developing drugs that treat unmet needs of EMR, we think that's great for the field and we think it would be a shop me on for the ecosystem and we think it's beginning to gain some momentum on the hill. So very big fans of it think it's good for the ecosystem that gets very good for patients and it couldnt be additive and beneficial to <unk>.

Ankit Mahadevia: We think it'd be a shot in the arm for the ecosystem, and we think it's beginning to gain some momentum on the Hill. So, very big fans of it, think it's good for the ecosystem, think it's very good for patients, and it could be additive and beneficial to tebipenem. However, we don't need it in order to be successful, and that's how we've set up the entire pipeline. I think that's a good segue to Christina, who can talk more about why tebipenem will be successful in the current commercial environment and policy environment.

Ever we don't need it in order to be successful and that's how we've set up the entire pipeline I think thats a good segue to Cristina who can talk more about why it would depend on will be successful in the current commercial environment and policy environment.

Christina Larkin: Yeah, thanks, Ankit. And I'll just tag on to, I think, one of the comments that you had made, and I think you stated on the reimbursement.

Yeah, Thanks on Kent, and I'll, just tack on to I think 1 of the comments that you made and I think you stated on the reimbursement side, which I think is a really important part if you remember.

Christina Larkin: https://www.youtube.com

Christina Larkin: The current launches that we've seen have been primarily based in the hospital environment, and the DRG payment system is

To that many of the current launches that we've seen have been primarily based on the hospital environment and the DRG payment system is certainly 1 of the main reasons why many of these drugs have a cap their success is because the way that these drugs are reimbursed.

Christina Larkin: One of the main reasons why many of these drugs have a cap on their success is because of the way that these drugs are reimbursed. Tevipenem, because of the benefit we've seen both in the community and the hospital switch therapy market, will be primarily paid as a pharmacy benefit and not under the hospital DRG system. And that's a key differentiating advantage that we see in the market. I think that's an important one.

Teddy panel because if the benefit if we've seen both in the community and the hospital switched therapy market is that this drug will be primarily paid as a pharmacy benefit and not under the hospital DRG system and that's a that's a key differentiating.

Advantage that we see in the market I think thats..1. The second is is that you know would be looked at the landscape of where <unk> will be best suited for is that what we see is we don't want to compete with generics and that becomes another key part of the value story.

Christina Larkin: The second is that, you know, when we looked at the landscape of where Tevipenem would be best suited, what we saw was we don't want to compete with generics. And that becomes another key part of the value story. When we talk about where Tevipenem will be best suited, it's really, and that's the way we constructed the trial design, not to compete with generics. And the real alternative here is when physicians are having to turn to IV treatment.

We talk about where to heavy Panama be best suited is that it's really and that's the way. We constructed the trial design was not to compete with generics and the rail alternative here is when physicians are having to turn to IV treatment and the fact that we've been able to demonstrate in our phase III trial equivalents to IV or non inferiority to <unk>.

Christina Larkin: The fact that we've been able to demonstrate in our phase three trial equivalence to IV or non-inferiority to IV or Tevipenem is a real advantage, and that's what we've heard through our market research and through our data about the ability to deliver the convenience of an oral but being able to show non-inferiority to, you know, an IV product is one of the key advantages. And to date, we're the only product that has ever been able to deliver that level of evidence, especially at launch, if ever.

Or depend on is it a real advantage and that's what we've heard through our market research and through our data of the debt.

The ability to deliver the convenience of an oral but being able to show non inferiority too you know on.

On the IV product is 1 of the key advantages and to date, we're the only product that has ever been able to deliver that level of evidence, especially at launch if ever and so those are 2 real key differentiators and then the last 1 I would mention is that you know.

You know for the for the primary audience that we're looking to go after as I mentioned is not only just infectious disease physicians that urologists and that is another key differentiation I think in the type of position that we're looking to target at launch.

Christina Larkin: And so those are two real key differentiators. And then the last one I would mention is that, you know, for the primary audience that we're looking to go after, as I mentioned, it is not only just infectious diseases.

Thank you.

Okay.

If I can answer your question on the ramp for Opex for the remainder of the year Inc.

I mentioned earlier for R&D.

Christina Larkin: [inaudible]

Satyavrat Shukla: And Louis, if I can answer your question on the ramp for OPEX for the remainder of the year, I think, as I mentioned earlier, for R&D, which we expect to be roughly even with.

We expect to be roughly even with 1 H.

1 of the age of R&D <unk> numbers were a little higher than <unk>, but on average I think thats, what Jay you can expect at least for the remainder of the year sort of trailing EBITDA. The overall first half.

Satyavrat Shukla: And then for DNA and commercial, you'll certainly continue to, as Christina mentioned, take a phased approach to continue to build out that capability. So you'll see a bit of a ramp.

And then for G&A and commercial.

We'll certainly continue to ESCO C&I with could take a phased approach to continue to build agile capabilities. So you'll see a beta for ramp.

Satyavrat Shukla: Our disclosed cash runway now is into 4Q2022. If you just did a burn rate from the last couple of quarters, you could tell that the cash runway might be a quarter or so longer than that. And the reason for 4Q2022 is that sort of phase ramp on the commercial and GNA OPEX, which for your estimation purposes.

Disclosed cash runway now is into for 2022.

If you just did a.

Born rates from the last couple of quarters, you could tell that the cash on there might be a quarter or so longer than that.

And the reason for the <unk> 'twenty 'twenty 2 is that sort of.

Phased ramp on the commercial and G&A.

Opex.

Satyavrat Shukla: For your estimation purposes, you could probably assume it will be somewhat linear, maybe a little slower at the start and then building more into the first half of 2022. So for the cash runway guidance and burn rates, you can see the trend in what we expect from our Black Studio.

Yes for your estimation purposes, you could probably assume there'll be somewhat linear maybe.

Maybe a little slower on the storage often in building more into the flow of staff off for 2022.

For the cash on the guidance and up on rates.

You can see the trend.

And what we expect our Opex Judy.

Kevin DeGeneres: We'll go next to Kevin DeGeneres with Oppenheimer.

Okay. Thank you.

Kevin DeGeneres: Hey, thanks for taking my question. Maybe I'm 102 or 106.

We will go next to Kevin <unk> with Oppenheimer.

Hey, Thanks for taking my questions, maybe 1 on pure Samsung can you just clarify.

Kevin DeGeneres: Can you just clarify? Following the completion of the Bowen and Rehmann impairment studies, these expectations were to go into a treatment setting. And as we think about Acina-Bacter market positioning, some sponsors have looked at sort of a refractory polymyxin B colistin population. We do also look at patients that have failed those therapies or were going a bit earlier. In the treatment landscape, it makes more sense for 206, have given the product. Hi, Kevin.

Following the completion of the bag.

On the re enrollment parents studies these expectation.

Go into a.

Treatment setting in.

As we think about Athena back their market positioning some sponsors.

Looked at sort of on a refractory on mix can be cornerstone population would you also have to go.

And patients that have failed other therapies.

Going a bit earlier.

And the treatment landscape, Mike Morris for aerospace.

Given the product profile.

Hi, Kevin Thanks.

Thanks very much for the question.

Your sense is correct that after we've received data from the balance of renal impairment studies, we will begin planning for both in collaboration with <unk> advisor.

Pfizer and address advancing <unk> into phase III study in patients.

Youre also right that given the broad utility of 206 for patients with resistant infections and do have several options in front of us in terms of how we trial what <unk> can do.

That is a discussion that we want to continue to progress both with our partners, but also as we continue to have discussions with both key opinion leaders, who can collaborate with and ultimately the regulators so more on that as we get closer to that for back but I think your point.

It's worth emphasizing that 206 has utility not just didnt acinetobacter for those patients that have limited options, but also on Pseudomonas, which is a larger population of patients that need as well as <unk> patients who have resistance to existing therapeutic options. Further I'll note that in typical clinical pre.

Actis poly.

Polymyxin are often used in combination with other standard of care therapies. Because these patients are really in dire Straits and need as many options as they can get so we do have options in terms of the clinical usage of <unk> and we'll make those choices as we get closer to that.

Great and then maybe just as a follow up question or a separate question on.

Have you had them on as we think about.

On the progression on medical education over the next 12 months of sales prior to launch should we think about relative emphasis on.

David Melnick: Unknown Speaker You have a heavy hand. I mean, as we think

I'd week in non traditional infectious disease conferences are called out in the prepared script.

David Melnick: , , , , , , , , , , , , , ,

David Melnick: [inaudible]

David Melnick: Unknown Speaker 05.01.23 Yeah, absolutely. Kevin, we have a very robust system.

On your expectation with regard to your presentation.

And while urology soundtracks.

Meetings, just kind of where do you think an early adoption.

David Melnick: Yeah, absolutely, Kevin. We have a very robust medical affairs and medical education strategy, and, you know, it's a point worth emphasizing that we are targeting those clinicians we aim to partner with. And so, as David mentioned, as we think about it, there are really three things that we're hoping to, you know, amplify in the medical discourse. Number one is the therapeutic opportunity and unmet need, and we are doing that both with our infectious disease colleagues but also at meetings like the American Urological Association, because, as Christina mentioned, we will be partnering with both types of clinicians as we get tebupenem to patients.

The opportunity for most impactful on medical education.

Yes, absolutely Kevin we have a very robust medical affairs medical education strategy, and it's a point worth emphasizing that we are targeting those clinicians we aim to partner with them. So as David mentioned.

As we think about it there are really 3.3 things that we're hoping to.

Amplify in the in the medical discourse on number 1 is the therapeutic opportunity and unmet need and we are doing that both with our infectious disease colleagues, but also at meetings like the American Urological Association, because as Kristina mentioned, we will be partnering with both types of clinicians as we get <unk> to patients.

David Melnick: Secondly, both in the medical education realm and otherwise, we're, you know, developing data and publishing it that speaks to the value that tebupenem brings to the health care system, and that is both for clinicians who are very sensitive to these economics, as well as for our colleagues in the payer community. And then, finally, we will find the right venues to continue to, as David mentioned, generate and share data on the utility of tebupenem, not just in CUTI but in other settings; the Merino 4 setting that David had mentioned is one example. So we're taking a holistic approach. We're both interacting with our urology colleagues, as well as our ID colleagues, and also keeping an eye on the value arguments that are really relevant as we talk to payers.

Secondly, both in the medical education realm, and otherwise we are developing data and publishing it that speaks to the value that can depend on brings to the health care system and that is both for the clinicians who are very sensitive to these economics as well as our colleagues on the payer community and then finally, we will find the right venues to.

2 as David mentioned.

Generate and share data on the utility of <unk> not just in cdti, but another other settings that marino for setting debt.

David had mentioned as 1 example, so we're taking a holistic approach where both interacting with our neurology colleagues as well as our colleagues and also keeping an eye for the value arguments that are really resonate as we talk to payers.

Esther P. Rajavelu: We'll go next to Esther Honk with Berenberg. Hi, thanks for taking my question. So regarding potential

Thanks for taking my questions.

Thank you Kevin.

We'll go next to Esther Hong with Bahrenburg.

Hi, Thanks for taking my question, so regarding potential expansion opportunities of heavy Panama, HDR and specifically pneumonia can you discuss what's been observed with granular tab depend on them, which is approved in Japan for pneumonia.

Esther P. Rajavelu: Regarding potential expansion opportunities of tebupenem HDR, and specifically pneumonia, can you discuss what's been observed with granular tebupenem, which is approved in Japan for pneumonia in children? Yeah, thanks, Esther, for the question.

David Melnick: Yeah, thanks, Esther, for the question. If we first, I'll first zoom out to 100,000 feet, as we think about our data generation activities clinically for tebupenem, they come in two flavors. The first flavor is that we've had a groundswell of interest from the clinician community to trial tebupenem in patient populations that matter to them. Moreno 4 is a good example where the KOL community came to us and said that you have to try this with bacteremic patients, and we're working with them. The second aspect is on a more formal indication basis; we're taking a stepwise strategy.

Children.

Yeah. Thanks, Oscar for the question, if we personnel persons zoom out to 100000 feet as we think about our data generation activities clinically for.

For <unk> they come in 2 flavors. The first flavor is we've had a ground swell of interest from the clinician community to trials have been put on in patient populations that matter to them Marino for is a good example, where the K welcoming it became for US and said that you have to try this and factoring that patients and we're working with them.

The second aspect is on a more formal indication basis, we're taking a stepwise strategy. So to your question.

David Melnick: So to your question, we are, you know, we are undertaking the bronchoalveolar lavage work as the first step to understanding how tevipenem can work in patients with lung infection. To your point, the granules that were approved by our partner Meiji Seika in Japan 10 years ago have extensive experience in respiratory indications, both upper respiratory as well as in pneumonia. And we've seen that that data suggests that tevipenem can be effective and achieve lung penetration. And so we'll be at coming medical meetings; we'll be excited to share what our tevipenem tablets can do, what the prescriber can do.

We are undertaking the bronchoalveolar lavage work as the first step to understanding how to heavy Panama can work in patients with lung infection to your point.

The granules that were approved by our partner of AG sake on Japan 10 years ago.

<unk> experience in respiratory, indicating indications, both upper respiratory as well as in pneumonia and we've seen that that that data suggests that <unk> can be effective and as well as achieves lung.

Lung penetration and so we will be in <unk>.

Coming medical meetings will be excited to share what our <unk> depend on tablets can do with the prescriber community.

Unknown Attendee: And we'll go next to Ram Selvaraju with H.C. Wainwright.

Got it thanks.

And we will go next to Rob <unk> with H C Wainwright.

Unknown Attendee: My questions. Firstly, I was wondering if we could circle back to the utility of tebupenem in bloodstream infections, and if you could just comment on whether the usage paradigm, the dosing regimen, and the length of treatment in that specific context might be meaningfully different from the lead label indication that you're seeking approval for. Thanks, Ram, for the question. I'll pass that question to David, who can address the utility of tevipenem in bacterial inhibition.

Thanks, very much for taking my questions.

Firstly I was wondering if we could circle back to the utility of <unk> and bloodstream infections and if you could just comment on whether the usage paradigm the dosing regimen the length of treatment in that specific context.

Be meaningfully different from the lead labeled indication that you are seeking approval for.

Thanks, Rob for the question.

Ask that question to David can address the utility of <unk>, Panama and battery mutations.

Unknown Attendee: Yeah, the short answer to that question is no. The dosing regimen that we plan to run in Merino 4 will be identical to that in ADAPTO. And there are two lines of evidence to support that. First of all, there was a substantial subpopulation of patients with bacteremia included in the ADAPTO study population, and those patients did quite well on tebupenem. And remember, this was initial therapy with tebupenem. There was no need for IV therapy. So that gives us confidence. The second line of evidence is the PKPD.

Yes, the short answer to that question is no the dosing regimen that we plan to run in Marino for will be identical to that and adapt Po and there are 2 lines of evidence to support that first of all there was a substantial subpopulation of patients with bacteremia included in the adapt study population and those patients did.

Quite well.

On on TV panel and remember this was initial therapy, which can be kind of on there was no need in IV therapy. So that gives us confidence second line of evidence is the PK PD.

David Melnick: As we've discussed with you in the past, we have chosen a dosing regimen that provides extremely robust coverage and has pharmacodynamic equivalence to intravenously administered carbapenem. So for those two reasons, we don't plan any change in the dosing regimen. Okay, and can you just comment on whether you believe that in that specific indication, tebupenem would compete against ceftobiprol, which is currently in late stage clinical development? Or if you think that, effectively, since these are clearly two different classes of antibiotics,

As we've discussed with with you in the past we have chosen a dosing regimen that provides extremely robust coverage.

And has pharmacodynamic equivalents equivalents to intravenously administered carver pin them. So.

For those 2 reasons, we don't plan any changes in the dosing regimen.

Okay and can you just comment on whether you believe that in that specific indication.

David Tennant would compete against sexual byproduct, which is currently in late stage clinical development or if you think that effectively since these are clearly 2 different classes of antibiotics that they would essentially complement 1 another.

David Melnick: of Antibiotics that they would essentially complement one another. Yeah, Ram.

David Melnick: Yeah, Ram, thank you for the question. Yes, thanks for the question, Ram.

Yeah Ross Thank you for about for Western.

Yeah. So thanks for the question Rob.

David Melnick: You know, in a sense, tevipenem, we think of the utility of tevipenem as following the utility of other carbapenems, like an ertapenem, for example, which was our comparator in the trial. And carbapenem has a unique spectrum, has a lot of gram-negative activity. And that's really the realm in which we think about it is that, for example, in CUTI and AP, patients that otherwise are required to take carbapenems like ERTA have tevi as an oral option.

In a sense.

<unk> panel, we think of the utility of <unk> panel is following the utility of other carbo pounds like on Earth. Pat on for example, which was our comparator in the trial Cobre, Panama has a unique spectrum.

There's a lot of gram negative activity and Thats really the realm, and which we think about it is debt for for example in <unk> AP patients that otherwise are required to take carpet down on like Arda have heavy as an oral option and really that's the frame that we'll think about as we go into studies in patients in other indications.

David Melnick: And really, that's the framework that we'll think about as we go into studies in patients and other indications. Okay, great. And I just add that... Go ahead, go ahead. Septibodipole is a cephalosporin that's not active against ESBL-producing organisms and therefore would not work in Merino 4.

Okay, Great and then jump out.

So I had 1 set of possible surplus for and it's not active against DSP on producing organisms and therefore would not work in Marina for.

Well understood. Thank you.

Couple of quick questions on the <unk> market opportunity.

Can you frame for us what you think the likely market opportunity is in terms of the total addressable market size in the Pfizer territories. Please.

I'll pass that question over to Christina.

Yeah, I think what we see without giving the exact numbers, but what we do see in terms of persistence rates to the common pathogens for <unk> 6 and David I think shared the spectrum of activity, which 2.6 is quite broad in terms of activity against Acinetobacter <unk>.

Christina Larkin: Yeah, I think you know what we see without.

Christina Larkin: Unknown Speaker We do see resistance rates to common pathogens for what 206 and David shared the spectrum of activity, which 206 is quite broad in terms of activity.

Opinion resistant.

<unk> interpreter, HCA and Pseudomonas and I think that's what makes this compound very unique is its ability to have coverage again, you know the 3 big buckets in terms of the largest problems that we see across Inc.

Christina Larkin: [inaudible]

Christina Larkin: So these are the three big bugs in terms of the largest.

Christina Larkin: The largest problems that we see across institutions, not only here in the United States but that exist in Europe and the rest of the world. And so, without giving you exact numbers, I would say that those are the three biggest bugs and the three biggest problems that we see in institutions today.

Institutions, not only here on the United States, but that that exist in Europe, and the rest of world and so without giving you exact numbers, but I would say that those are the 3 biggest bugs in the 3 biggest problems that we see an institution today.

Christina Larkin: Thanks. And then I just want to make one last point of clarification. What do you anticipate the SBA to classify with respect to the tebupenem NDA at this juncture with regard to the assignation of a review period? Ram, just to make sure I clarify the thinking, are you asking what we expect the review period to be once submitted? That's correct. Yeah, so Teddy Penham has received fast track designation, and fast track provides for an overall eight month review period, which is a six month review plus two month validation.

Thanks, and then just 1 last point of clarification.

What do you anticipate the SBA to classify with respect to the <unk> 10 am NBA at this juncture with regard to the assignation of a review period.

Rob just to make sure I clarify the thinking or are you asking what we expect the review period to be once submitted.

That's correct.

Yes. So <unk> has received fast track designation and fast track provides for an overall 8 month review period, which is a 6 months review plus 2 months validation.

Operator: And that concludes today's question and answer session. I'd like to turn the conference back over to today's presenters for any additional or closing remarks.

Thank you very much.

Thank you Rob.

And that concludes today's question and answer session I would like to turn the conference back over to today's presenters for any additional or closing remarks.

Ankit Mahadevia: Thank you, Operator, and I appreciate everyone for joining us today. We look forward to the continued advancement of our pipeline, and we'll keep everyone updated along the way. Thanks again.

Thank you operator, and I appreciate everyone for joining US today, we look forward to the continued advancement of our pipeline that we will keep everyone updated along the way. Thanks again.

Operator: That concludes today's conference. Thank you for your participation. You may now disconnect.

Yeah.

And that concludes today's conference. Thank you for your participation you may now disconnect.

Q2 2021 Spero Therapeutics Inc Earnings Call

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