Q2 2024 Spero Therapeutics Inc Earnings Call

August 5, 2024

Speaker Change: Good afternoon and welcome to the Spero Therapeutics Second Quarter 2024 Financial Results Conference Call. At this time, all participants are in listen-only mode. Following the company's formal remarks, we will open up the call for questions.

Operator: 24 Financial Results Conference Call At this time, all participants are in listen-only mode. Following the company's formal remarks, we will open up the call for questions. Please be advised that this call is being recorded and a replay will be available. You can find information on the replay and further information related to today's announcements on the Spero Therapeutics website at www.sperotherapeutics.com. At this time, I would like to turn the call over to Shai Biran, Senior Director, Investor Relations. Mr. Biran, please go ahead.

Speaker Change: Please be advised that this call is being recorded and a replay will be available. You can find information on the replay and further information related to today's announcements on the Spero Therapeutics website at www.spero-therapeutics.com.

Speaker Change: At this time, I would like to turn the call over to Shai Biran, Senior Director, Investor Relations. Mr. Biran, please go ahead.

Shai Biran: Thank you, Operator, and thank you all for participating in today's conference call. This afternoon, Spero Therapeutics released financial results and provided a business update for the second quarter of 2024. The press release is available on the investor page of the Spero Therapeutics website.

Shai Biran: The press release is available on the investor page of the Spero Therapeutics website.

Shai Biran: Before we begin, I would like to remind you that some of the information presented on this conference call contains forward-looking statements under the securities law. These forward-looking statements involve substantial risks and uncertainties that could cause our actual clinical problems. Future Results, Progress, Timing, Performance, or Achievements may differ materially from those expressed or implied by such forward-looking statements because of the risks and uncertainties associated with our business. And factors that could cause or contribute to such differences are described in detail in Spero Therapeutics' filing with the SEC, including in the Risk Factor section of its earnings report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC today.

Speaker Change: Before we begin, I would like to remind you that some of the information presented on this conference call contains forward-looking statements under the securities laws.

Speaker Change: These forward-looking statements involve substantial risks and uncertainties that could cause our actual clinical program, future results, progress, timing, performances, or achievements to differ materially from those expressed or implied by such forward-looking statements.

Speaker Change: These risks and uncertainties associated with our business.

Speaker Change: And factors that could...

Speaker Change: Spero Therapeutics filing with the SEC, including in the risk factor section of its earnings report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC today.

Shai Biran: We also ask that you reference the cautionary statement or forward-looking statement included with the slide presentation accompanying this conference call. Participating in today's call are Sat Shukla, Chief Executive Officer, and Esther Rajavelu, Chief Financial Officer and Chief Business Officer. Satya Shukla will begin the discussion. Please go ahead. Thank you.

Speaker Change: We also ask that you reference the cautionary statement or forward-looking statement included with the slide presentation accompanying this conference call.

Speaker Change: Participating in today's call are Sat Shukla, Chief Executive Officer, and Esther Rajavelu, Chief Financial Officer and Chief Business Officer.

Speaker Change: Satya Shukla will begin the discussion. Please go ahead, Satya. Thank you, Sai.

Sat Shukla: Good afternoon, everyone, and thank you for joining our conference call today. I am pleased to provide an update on the ongoing progress across our portfolio of clinical-stage assays. But before that, I would like to note a change in our executive leadership team with the departure of our chief medical officer, Dr. Kamal Hamed.

Sat Shukla: Good afternoon, everyone, and thank you for joining our conference call today. I am pleased to provide an update on the ongoing progress across our portfolio of clinical stage assets.

Speaker Change: Before that, I would like to note a change in our executive leadership team with the departure of our Chief Medical Officer, Dr. Kamal Hamed.

Sat Shukla: On behalf of the board, management, and all of our employees, we thank Dr. Hamed for his many contributions to Spero and wish him every success for the future. We are pleased to announce that Dr. John Portage, a distinguished industry veteran in our field and a member of Spero's board for the last six years, will help oversee and provide strategic guidance for our clinical programs during this transitionary period while we continue the search for our next chief medical officer.

Speaker Change: On behalf of the board, management, and all of our employees, we thank Dr. Hamed for his many contributions to Spero and wish him every success for the future.

Speaker Change: We are pleased to announce that Dr. John Portage

Speaker Change: A distinguished industry veteran in our field, and a member of Spero's board for the last six years, will help oversee and provide strategic guidance for our clinical programs during this transitionary period, while we continually search for our next chief medical officer.

Sat Shukla: Moving to our clinical pipeline, let me begin with SPR-720, which we are developing as a first-line oral agent for non-tuberculous mycobacterial pulmonary disease, or NTMPD, and TMPG has an estimated patient population of 245,000 patients in the US, EU, and Japan, with approximately 95,000 of those patients in the U.S. There is currently no approved first-line therapy for these patients. The current guidelines recommend off-label TB drugs that have a history of lack of efficacy, as well as serious tolerability issues.

Speaker Change: Moving to our clinical pipeline, let me begin with SPR-720, which we are developing as a first-line oral agent for non-tuberculous mycobacterial pulmonary disease, or NTMPD.

Speaker Change: NTMPG has an estimated patient population of 245,000 patients in the US, EU and Japan, with approximately 95,000 of those patients in the US.

Speaker Change: There is currently no approved first-line therapy for these patients.

Speaker Change: The current guidelines recommend off-label TB drugs, which have a history of lack of efficacy, as well as serious tolerability issues.

Sat Shukla: SPR 720 has a novel mechanism of action that is different from other standards of care agents, as well as those in development for NTMPG. Spero has conducted extensive in vitro and in vivo studies, which have shown no evidence of cross-resistance against marketed antibiotics as well as a low propensity for selection of resistance. Further, we have demonstrated SPR-720 to be potent against many more NTM pathways. Overall, we believe the preclinical data support SPR-720's potential for therapeutic benefits.

Speaker Change: SDR 720 has a novel mechanism of action that is different from other standards of care agents, as well as those in development for NTMPG.

Speaker Change: Spero has conducted extensive in vitro and in vivo studies which have shown no evidence of cross resistance against marketed antibiotics as well as a low propensity for selection of resistance.

Speaker Change: Further, we have demonstrated SPR-720 to be potent against multiple NTM pathogens.

Speaker Change: Overall, we believe the preclinical data supports SBR 720's potential for therapeutic benefit.

Sat Shukla: In Q4, we expect to share a comprehensive data set from our ongoing and recently completed clinical studies, which is expected to include data from the faith to a proof of concept study in treatment naive and treatment experienced non-refractory patients. We will also report data from two supportive Phase I studies in healthy volunteers. One of which assesses SPR720 exposure in the lung as monotherapy, and the second of which assesses exposure in plasma when co-administered with standard of care agents. Ezethromycin, Unknown Attendee. In phase 2, a clinical trial comprises two doses of SPR-720, 500 megs and 1000 megs. Administered as monotherapy versus placebo in patients with NTMPD due to M-abium complex or MAP.

Speaker Change: In Q4, we expect to share a comprehensive data set from our ongoing and recently completed clinical studies.

Speaker Change: This is anticipated to include data from the phase 2a proof-of-concept study in treatment-naive and treatment-experienced non-refractory patients.

Speaker Change: We will also report data from two supportive Phase I studies in healthy volunteers.

Speaker Change: One of which assesses FTR720 exposure in lung as monotherapy, and the second of which assesses exposure in plasma when co-administered with standard of care agents azithromycin and ethambutol.

Speaker Change: Phase 2, a clinical trial, compares two doses of SPR-720, 500 megs and 1000 megs, administered as monotherapy versus placebo, in patients with NTMPD due to M-abium complex, or MAC.

Sat Shukla: We have enrolled a total of 25 patients, including both treatment-naive and treatment-experienced patients who do not have treatment-refractory disease. It is our hope that the data from this study will indicate that SPR-720 as a monotherapy can decrease the NTM bacterial load over the treatment course of 50-60. To analyze this early bactericidal activity, we are measuring changes in bacterial load in patient's excretion, including the rate of change in log 10 colony forming units per milliliter, which is our primary endpoint in this study. We are also looking at the rate of change in time to positivity, which is a key secondary endpoint in this study.

Speaker Change: We have enrolled a total of 25 patients including both treatment naive and treatment experienced patients who do not have treatment refractory disease.

Speaker Change: It is our hope that the data from this study will indicate that SPR-720 as a monotherapy can decrease the NTM bacterial load over the treatment course of 56 days.

Speaker Change: To analyze this early bactericidal activity, we are measuring changes in bacterial loads in patient's excretion, including the rate of change in locked and colony-forming units per milliliter. For more information visit www.ISGlobal.org

Speaker Change: which is our primary endpoint in this study.

Speaker Change: We are also looking at the rate of change in time to positivity, which is a key secondary endpoint in the study.

Sat Shukla: A clear numerical difference in these measures between the treated arms and placebo could indicate that SPR-720 has a potential therapeutic effect in patients with NGMPD. We anticipate that success on these endpoints would also make SBR 720 the only oral agent in development that we are aware of to demonstrate early bactericidal activity in patients with NTMPD due to MAC and would enable us to move confidentially into late-stage development. Ultimately, we believe that SPR-720 could be used as part of combination treatment regimens, and, if the ongoing study confirms our expectations that the drug has monotherapy activity, we anticipate future registration-enabling studies to be designed to include standard of care agents.

Speaker Change: A clear numerical difference in these measures between the treated arms and placebo could indicate that SPR720 has a potential therapeutic effect in patients with NGMPD.

Speaker Change: We anticipate that success on these endpoints would also make SPR 720

Speaker Change: The only oral agent in development that we are aware of, to demonstrate early bactericidal activity in patients with NTMPD due to MAC, and would enable us to move confidentially into late stage development.

Speaker Change: If the ongoing study confirms our expectations that the drug has monotherapy activity, we anticipate the future registration-enabling study to be designed to include standard-of-care agents.

Sat Shukla: Complementing the Phase IIa data, as previously mentioned, we will also share data from two Phase I studies in healthy volunteers. The first study used bronchoalveolar lavage, or BAL, to examine intrapulmonary pharmacokinetics of SPR719, the active moiety of the prodrug SPR721.

Speaker Change: Complementing the Phase 2a data, as previously mentioned, we will also share data from two Phase 1 studies and healthy volunteers.

Speaker Change: The fourth study used a bronchoalveolar lavage, or BAL, to examine intrapulmonary pharmacokinetics of SPR719, the active moiety of the prodrug SPR720.

Sat Shukla: We expect to share PK measures showing the extent of exposures in the lungs, that is, the site of infection. The second study evaluates changes in plasma... And SPR 720 is co-administered with azithromycin and ethambutol. We anticipate this data to be informative when selecting doses in future combination studies. We recently completed an in-vitro resistance study of SPR719 in combination with standard of care agents and anticipate sharing these data at IG Week in October.

Speaker Change: We expect to share PK measures showing the extent of exposures in the lungs, that is, the site of infection.

Speaker Change: The second study evaluates changes in plasma PK when SPR720 is co-administered with azithromycin and ethambutol.

Speaker Change: We anticipate this data to be informative when selecting doses in future combination studies.

Speaker Change: Lastly, we recently completed an in-vitro resistance study of SPR 719 in combination with standard of care agents and anticipate sharing these data at IG Week in October .

Sat Shukla: The team is excited about this upcoming data readout in Q4. These studies are expected to provide us with a robust data set that we will use to determine the registrational path for SPR720 as first-line oral treatment for NTMP2. Turning now to tebupenem HVR, which we are developing as the first potential oral carbapenem antibiotic for the treatment of complicated urinary tract infections, or CUTI. And don't forget that our ongoing Phase 3 global PIVX-PO clinical trial is on track. And we are pleased with the progress made since the beginning of the year. Our goal remains to complete enrollment in the second half of 2020.

Speaker Change: The team is excited about this upcoming data readout in Q4. These studies are expected to provide us with a robust data set that we will use to determine the registrational path for SPR720 as first-line oral treatment for NTMPG.

Speaker Change: Turning now to tebupenem HVR, which we are developing as the first potential oral carbapenem antibiotic for the treatment of complicated urinary tract infections, or CUTI.

Speaker Change: Enrollment in our ongoing Phase 3 Global PIVX PO Clinical Trial is on track, and we are pleased with the progress made since the beginning of the year. Our goal remains to complete enrollment in the second half of 2025.

Sat Shukla: Patients are randomized one-to-one in this Pivotal Phase III clinical trial to receive terapenem HVR 600mg orally every six hours or in a pen and filstation 500 megs intravenously every six hours for a total of 7 to 10 days. Target enrollment is approximately 2,648 patients. The primary efficacy endpoint is overall response, which is a composite of clinical and microbiological response and the test of cure rate. The primary analysis for the trial will be an assessment of non-inferiority in the microbiological intent-to-treat population based on a 10% non-inferiority model. As a reminder, Telepanel and HVR are partnered with GSK.

Speaker Change: Patients are randomized one-to-one in this pivotal phase 3 clinical trial to receive teripenem HVR 600 megs orally every six hours.

Speaker Change: or Independent Philostatin 500mg intravenously every 6 hours for a total of 7-10 days.

Speaker Change: Target enrollment is approximately 2,648 patients.

Speaker Change: The primary efficacy endpoint is overall response, which is a composite of clinical and microbiological response and the test of cure visit.

Speaker Change: The primary analysis for the trial will be an assessment of non-inferiority in the microbiological intent-to-treat population based on a 10% non-inferiority margin.

Speaker Change: As a reminder, Character Dynamics VR is partnered with GSK.

Sat Shukla: We are responsible for the execution of the ongoing Phase II trial, and GSK is responsible for outside-U.S. development and worldwide commercialization, excluding certain rights in Asian territories held by another partner, Mekong State. QTR infections are a leading cause of hospitalization in the U.S. The incidence is estimated to be over 3 million cases per year, which translates into a significant burden on the healthcare system. Chalpenam HVR is, to our knowledge, the only oral calvapenem in Germany.

Speaker Change: We are responsible for the execution of the ongoing Phase 2 trial, and GSK is responsible for ex-U.S. development and worldwide commercialization, excluding certain rights in Asian territories held by another partner, Meiji Seika.

Speaker Change: QTR infections are a leading cause of hospitalization in the U.S. The incidence is estimated to be over 3 million cases per year, which translates into a significant burden on the healthcare system.

Ted Panam: Chalpenam HVR is, to our knowledge, the only oral chalwapenam in development.

Sat Shukla: If approved, it could address the need for an oral carbapenem in patients with complicated urinary tract infections caused by multidrug-resistant uropathogens, potentially eliminating the need for hospitalization or reducing length of stay with transitions from intravenous to oral carbapenem. Finally, wrap up with SPR 2.0. SPR-206 is an innovative, investigational, intravenously administered direct-reacting polymixin partnered with Pfizer for the European market. We announced that in the first quarter of this year, the FDA cleared the ING to advance SPR-206 into a Phase II clinical trial in patients with hospital-acquired or ventilator-associated bacterial pneumonia, and that the FDA also awarded SPR-206 a fast-tracking signal. As a reminder, we plan to initiate a phase 2 study contingent on the availability of non-dialysis. With that, I turn the call over to Esther to review our quarterly financial results.

Ted Panam: It could address the need for an oral carbapenem in patients with complicated urinary tract infections caused by multidrug-resistant uropathogens, potentially eliminating the need for hospitalization or reducing length of stay with transition from intravenous to oral carbapenem therapy.

Speaker Change: Finally, wrapping up with SPR 206.

Ted Panam: SPR-206 is an innovative, investigational, intravenously-administered, direct-reacting polymixin partnered with Pfizer for European markets.

Ted Panam: We announced that in the first quarter of this year, the FDA cleared the ING to advance SPR-206 into a Phase II clinical trial in patients with hospital-acquired or ventilator-associated bacterial pneumonia.

Ted Panam: and that the FDA also awarded SPR-206 fast-track designation.

Ted Panam: As a reminder, we plan to initiate a phase 2 study contingent on availability of non-value-just funding.

Ted Panam: With that, I turn the call over to Esther to review our quarterly financial results.

Esther Rajavelu: Thank you, Sal. And good afternoon to all of you joining us on the call.

Esther Rajavelu: Thank you, Saf, and good afternoon to all of you joining us on the call. I'll begin with our cash guidance first and then summarize our GAAP financial s.

Esther Rajavelu: I'll begin with our cash guidance first and then summarize our GAAP financials. Spero ended the second quarter with $63.5 million in cash and cash equivalents. In addition to the cash on our balance sheet, we anticipate three remaining tranches of development milestone payments from GSK in the approximate amount of $24 million every six months. As a reminder, upon initiation of the Phase III PIVOT-PO clinical trial, Spero qualified for $95 million in development milestone payments from GSK, which are payable in four equal installments over two years.

Esther Rajavelu: Spero ended the second quarter with $63.5 million in cash and cash equivalents.

Esther Rajavelu: In addition to the cash on our balance sheet, we anticipate three remaining tranches of development milestone payments from GSK in the approximate amount of $24 million every six months.

Esther Rajavelu: As a reminder, upon initiation of the Phase III PIVOT-PO clinical trial, Spero qualified for $95 million in development milestones from GSK, which are payable in four equal installments over two years.

Esther Rajavelu: The second tranche of approximately $24 million is payable in the third quarter of this year. We estimate that our cash and cash equivalents, together with other non-dilutive funding commitments, will be sufficient to fund our operating expenses and capital expenditure requirements into late 2025.

Esther Rajavelu: The second tranche of approximately $24 million is payable in the third quarter of this year.

Esther Rajavelu: We estimate that our cash and cash equivalents, together with other non-dilutive funding commitments, will be sufficient to fund our operating expenses and capital expenditure requirements into late 2025.

Esther Rajavelu: Now, moving on to summarize our GAP financials. Total revenue for the second quarter of 2024 was $10.2 million compared with total revenue of $2.7 million for the second quarter of 2023. The revenue increase for the second quarter of 24 was primarily due to an increase in collaboration revenue related to our agreement with GSK and an increase in grant revenue related to our BARDA contract, both for Tabupetam-HDR. These were partially offset by a decrease under our NIAID agreement relating to FPR-206 and collaboration revenue related to our agreement with Pfizer for FPR-206.

Esther Rajavelu: Now, moving on to summarize our GAAP financial s.

Esther Rajavelu: Research and development expenses for the second quarter of 2024 were $23.7 million, compared to $9.5 million for the same period in 2023. The increase in research and development expenses year over year was primarily due to higher direct costs related to the Pivotal Phase III trial for tebupenem-HVR and the Phase IIa clinical trial for SPR-720, partially offset by lower direct costs related to SPR-206. G&A expenses for the second quarter of 2024 were $5.5 million compared to $6.1 million for the same period in 2023. This year-over-year decrease was primarily due to a decrease in GNA personnel-related costs, partially offset by increases in professional and consulting.

Esther Rajavelu: Total revenue for the second quarter of 2024 was $10.2 million compared with total revenue of $2.7 million for the second quarter of 2023.

Esther Rajavelu: The revenue increase for the second quarter of 2024 was primarily due to an increase in collaboration revenue related to our agreement with GSK and an increase in grant revenue related to our BARDA contract, both for Tabupetam-HDR.

Esther Rajavelu: These were partially offset by a decrease under our NIAID agreement relating to SPR-206 and collaboration revenue related to our agreement with Pfizer for SPR-206.

Esther Rajavelu: Research and development expenses for the second quarter of 2024 were $23.7 million compared to $9.5 million for the same period in 2023.

Esther Rajavelu: The increase in research and development expenses year-over-year was primarily due to higher direct costs related to the Pivotal Phase III trial for tebupenem-HBR, and the Phase IIa clinical trial for SPR-720.

Esther Rajavelu: partially offset by lower direct costs related to SPR 206.

Esther Rajavelu: G&A expenses for the second quarter of 2024 were $5.5 million compared to $6.1 million for the same period in 2023.

Esther Rajavelu: This year-over-year decrease was primarily due to a decrease in GNA personnel-related costs, partially offset by increases in professional and consulting fees.

Esther Rajavelu: Spero reported a net loss of $17.9 million, or $0.33 per share of common stock, basic and diluted for the second quarter and this June 30, 2024. This compares to a net loss of $11.9 million, or $0.23 per share of common stock for the comparable period in 2020. For further details on our financials, please refer to our 10-Q filed with the SEC today. Operator?

Sarah: Spero reported a net loss of $17.9 million, or $0.33 per share of common stock.

Speaker Change: Basic and Diluted for the second quarter and this June 30th, 2024.

Speaker Change: This compares to the net loss of $11.9 million or $0.23 per share of common stock for the comparable period in 2023.

Speaker Change: For further details on our financials, please refer to our 10-Q files with the SEC today.

Speaker Change: We will now open the call for questions. Operator?

Operator: Ladies and gentlemen, we will now be conducting a question and answer session. If you would like to ask a question, please press star and 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star and 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Ladies and gentlemen, we will wait for a moment while we poll you for questions. Our first question comes from the line of Luis Chen with Cantor Fitzgerald. Please go ahead.

Speaker Change: Thank you.

Speaker Change: Ladies and gentlemen, we will now be conducting a question and answer session.

Speaker Change: If you would like to ask a question, please press star and 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue.

Speaker Change: You may press star and 2 if you would like to remove your question from the queue.

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

Speaker Change: Ladies and gentlemen, we will wait for a moment while we poll for questions.

Luis Chen: Hi, congratulations on all the progress and thanks for taking my questions here. So I have two quick questions for you. The first one I wanted to ask you was the significance of the ID week data that you're going to present and what we think we should learn from all of this. And the second question is just about Kamal's departure. He didn't give a lot of details here, but obviously, ahead of the data, people are wondering what happened here, so any color you can give would be great. Thank you. Hey Luis, thanks for the question.

Speaker Change: Our first question comes from the line of Luis Chen with Cantor Fitzgerald. Please go ahead.

Sat Shukla: Hey, Luis. Thanks for the questions and great to hear from you. I'll answer your questions in reverse order.

Speaker Change: Hi, congratulations on all the progress and thanks for taking my questions here. So I have two quick questions for you. First one I wanted to ask you was the significance of the ID week data that you're going to present and what we think we should learn from all of this.

Speaker Change: And the second question is just on Kamal's departure. He didn't give a lot of details here, but obviously ahead of the data, people are wondering what happened here. So any colors you give would be great. Thank you.

Sat Shukla: Kamal's departure, obviously, is an event for the company, but it has nothing to do with the data or the programs that we can share with you. Like the rest of you, we are looking forward to the unblinding and reporting of the top-line data for SBIR 720 and 4Q. And then, of course, for Chabipanam next year, where our enrollment continues on track and is expected to be completed in the second half of next year.

Speaker Change: Hey Luis, thanks for the questions and great to hear from you.

Speaker Change: I'll answer your questions in reverse order. Kamal's departure, obviously, is an event for the company, but it has nothing to do with the data or the programs.

Speaker Change: That we can share with you. Like the rest of you, we are looking forward to the unblinding and reporting of the top-line data for SPR 720 in 4Q.

Speaker Change: And then, of course, for Chabibanam next year, where our enrollment continues on track and is expected to be completed in the second half of next year.

Sat Shukla: Moving to your first question, for IG Week, we are particularly excited about presenting resistance data. So, one of the value propositions for SPR 720, as you know, is that with that novel MOA, the data we have seen to date has shown a low propensity for resistance and no evidence of crossing. So for IG Week in particular, that will be a data set we will build.

Speaker Change: Moving to your first question, for ID week, we are particularly excited about presenting

Speaker Change: Resistance data. So one of the value propositions for SPR 720, as you know, is that with that novel MOA, the data we have seen to date has shown a low propensity for resistance and no evidence of cross-resistance.

Speaker Change: So, for IG Week in particular, that will be a data set we will build on.

Speaker Change: Thank you.

Gavin Clark: Our next question comes from the line of Gavin Clark Gardner with Evercore ISI; please go ahead.

Speaker Change: Thank you.

Speaker Change: Our next question comes from the line of Gavin Clark Gartner with Evercore ISI. Please go ahead.

Gavin Clark: Hey, guys. Thanks for taking the question. I just had one. So I appreciate that you're doing the PK sub-study, which includes BALs, but for both of the doses that you're testing in your Phase 2a, over a given day, roughly what duration of MIK-90 coverage do you believe that 720 has at both of the doses and specifically at the site of infection? Thanks.

Speaker Change: Hey guys, thanks for taking the question. I just had one. So I appreciate that you're doing the PK sub-study which includes bowels, but for both of the doses that you're testing in your phase 2a, over a given day

Speaker Change: Roughly what duration of MIK-90 coverage do you believe that 720 has at both of the doses and specifically at the site of infection? Thanks.

Sat Shukla: Thanks for the question, Gavin. I'll have to look back on what we have disclosed on that question and perhaps come back to you, but I do not believe that we have disclosed that data just yet. Obviously, that data will be part of what we report out, but for today, I'm not sure I can elaborate on it to the degree you asked. Great. We'll look forward to seeing you.

Speaker Change: Thanks for the question, Gavin. I'll have to look back on what we have disclosed on that question and perhaps come back to you, but I do not believe that we have disclosed that data just yet.

Speaker Change: Obviously, that data will be part of what we report out, but for today, I'm not sure I can elaborate on it to the degree you ask.

Gavin Clark: Great. We'll look forward to seeing more. Thanks.

Gavin: Great. We'll look forward to seeing more. Thanks.

Ritu Baral: Our next question comes from the line of Ritu Baral with T.D. Cowan. Please go ahead.

Gavin: Thanks again.

Gavin: Thank you.

Speaker Change: Our next question comes from the line of Ritu Baral with TD Cowan. Please go ahead.

Ritu Baral: Good afternoon, everyone. Thanks for taking the questions. I wanted to make sure that I heard you correctly. You said that the 25 patients enrolled were I'm sorry if I put this wrong, but the 25 patients were all treatment-naive, or did you have treatment-experienced patients in there, and, well, I'll let you answer that first.

Speaker Change: I'm sorry if I put this wrong, but the 25 patients were all treatment naive or did you have treatment experienced patients in there and Well, I'll let you answer that before I follow up

Sat Shukla: Sure, so we've always said that this trial would have treatment naive and non-refractory treatment experience patients. And that is the expectation for those 25 patients.

Speaker Change: Sure, so we've always said that this trial would have treatment naïve and non-refractory treatment experience patients, Ritu.

Ritu Baral: Did that answer your question? Got it. Yeah. Can you speak to the mix that you ended up with final enrollment and how it might impact both the primary and secondary end-point expectations, and then I have a follow-up. Unfortunately, right now, we can't Ritu because most of those data are blinded to us, so even the mix of treatment naive and treatment experienced patients is not something we have disposed of just yet.

Speaker Change: And that is the expectation for those 25 patients.

Speaker Change: Can you speak to the mix that you ended up with final enrollment and how it might impact both the primary and secondary end-point expectations, and then I have a follow-up.

Speaker Change: Unfortunately, right now we can't Ritu, because most of those data are blinded to us, so even the mix of treatment naive and treatment experienced patients is not something we have disposed just yet.

Ritu Baral: Got it. I wanted to also ask about the secondary endpoint of time to positivity. Can you elaborate on that? I think previous previous drugs have discussed sort of time to sputum negativity. Can you go into a little detail on what time to positivity is and what sort of a meaningful time point is in that endpoint? Yeah, so I think for context.

Speaker Change: Got it.

Speaker Change: I wanted to also ask about the secondary endpoint of time to positivity. Can you elaborate on that? I think previous previous drugs have

Speaker Change: have discussed sort of time to spew to negativity. Can you go into a little detail on what time to positivity is and and what sort of a meaningful time point in that end point?

Sat Shukla: Yeah, so I think for context, for both the primary end point, which is the reduction in the log 10 CFU per milliliter, as well as time for positive. These are metrics that are well established and covered in TB, for example, but in NTM, of course, this being a relatively new therapeutic space, there is a limited academic and medical literature that creates cutoffs, for example, but the way time to positivity works is that it's basically the daily prolongation of time to positivity.

Speaker Change: Yeah, so I think for context, for both the primary endpoint, which is the reduction in the log 10 CFU per milliliter, as well as time for positivity.

Speaker Change: These are metrics that are well-established and covered in TB, for example, but in NTM, of course, this being a relatively new therapeutic space,

Speaker Change: There is limited academic and medical literature that creates cut-offs, for example. But the way time to positivity works is that it's basically the daily prolongation of time to positivity. So it measures the time growth.

Sat Shukla: So it measures time. In this process, the liquid media are inoculated with a sputum sample, and then when that reaches a predefined signal for the evidence of bacterial growth, that can indicate the efficacy of the treatment in question.

Speaker Change: In this process, the liquid media are inoculated with a sputum sample, and then when that reaches a predefined signal,

Speaker Change: For the evidence of bacterial growth, that can indicate the efficacy of the treatment in question. So really, the longer that time to positivity, the better it is.

Sat Shukla: So really, the longer that time to positivity, the better it is. In TB, this measure is well established. For us, it's always been a key secondary endpoint, but within TB, there is usually a high degree of correlation between what we have characterized as a primary endpoint, the log reduction, and the time to positivity. So, what we hope is that as we report both of these out, they will show the activity of the drug on a monthly basis.

Speaker Change: In TB, this measure is well established, for us it's always been a key secondary end point, but within TB there's usually a high degree of correlation.

Speaker Change: between what we have characterized as a primary endpoint, the log reduction, and the time to positivity. So what we hope is that as we report both of these out,

Speaker Change: They will show an activity of the drug on microbial reduction.

Ram Selvaraju: Ritu Baral, Esther Rajavelu, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc. Our next question comes from the line of Ram Selvaraju with HC Wainwright. Please go ahead.

Speaker Change: Got it. Thanks for sharing the questions.

Speaker Change: Thank you.

Speaker Change: Our next question comes from the line of Ram Selvaraju with HC Wainwright. Please go ahead.

Ram Selvaraju: Hi, thanks very much for taking my questions and congrats on all the progress. I wanted to ask about the Tebepenem Phase 3 program and if you could give us more granularity regarding the total number of clinical sites that are currently involved and what factors you expect to impact enrollment either positively or negatively with respect to being able to get to that enrollment completion timeline target that you disclosed in today's press release.

Ram Selvaraju: Hi, thanks very much for taking my questions and congrats on all the progress.

Ram Selvaraju: I wanted to ask about the Tebepenem Phase III program and if you could give us an additional granularity regarding the total number of clinical sites that are currently involved and what factors you expect.

Speaker Change: to impact enrollment either positively or negatively with respect to being able to get to that enrollment completion timeline target that you disclosed in today's press release. Thank you.

Sat Shukla: Thanks, Ram, for the question. We haven't given a precise number yet, but if you were to assume, you know, somewhere in the triple digits in – it's a global study, so multiple countries, you know, you would be in the ballpark. So larger trial than the last one, as you know, and as you mentioned on the call, on track for enrollment. To date, we have not seen headwinds like the one we saw for ADAPT, where COVID, among other features, was a restricting factor for us.

Speaker Change: Thanks, Tom, for the question. We haven't given a precise number yet, but if you were to assume, you know, somewhere in the triple digits, it's a global study, so multiple countries,

Speaker Change: You would be in the ballpark, so a larger trial than the last one, as you know, and as you mentioned on the call on track for enrollment.

Speaker Change: Unknown Attendee, Boobalan Pachaiyappan, Kamal Have not seen a headwinds like the ones we saw for adapt where Corvette of among other features was a restricting factor for us.

Sat Shukla: So at this moment in time, we continue to hold to our expectation of that completion of enrollment in the second half of next year. And as you know, our partners at GSK are also setting out their timelines for a NTA submission that is also congruent with that timeframe. So the bottom line for CHEBI is on track, and we are excited to see it.

Speaker Change: So, at this moment in time, we continue to hold to our expectation of that completion of enrollment.

Speaker Change: in the second half of next year, and as you know, our partners at GSK are also setting out their timelines for a NGA submission that is also congruent with that timeframe. So the bottom line for Chevy is on track, and we are excited to see the data.

Ram Selvaraju: Okay, and then just two technical questions regarding 720. First, can you just give us a brief description of the manner in which the pro-drug 720 is converted into the active moiety 719? And secondly, if you can comment on what additional combinations or permutations, if any, you might want to look at in terms of variability in plasma PK beyond azithromycin and etambutol in the context of the use of 720.

Speaker Change: Okay, and then just two technical questions regarding 720.

Speaker Change: First is, can you just...

Speaker Change: Please give us a brief description of the manner in which the prodrug 720 is converted into the active moiety 719. And secondly, if you can comment on what additional combinations or permutations.

Speaker Change: Transcript by Transcription Outsourcing, www.transcriptionoutsourcing.com

Sat Shukla: Sure. For the first question, Ram, we'll dig into the publications we have and send them to you. What we have stated in calls is that 720 has a very rapid conversion to its active moiety. But on the granularity, we'll just have to forward to you what we have published, so we can ensure that after the call.

Sat Shukla: Thank you. Sure. For the first question, we'll...

Speaker Change: For the first question, we'll dig into the publications we have and send them to you. What we have stated in calls is that 720 has a very rapid conversion to its active moiety.

Speaker Change: But on the granularity, we'll just have to forward to you what we have published so we can ensure that after the call.

Sat Shukla: For your second question right now, so, you know, azithromycin serves as a macrolide. And so with a macrolide under discussion, we feel that that is an appropriate measure to evaluate co-administration with Tambutol. But as the landscape for NTM evolves, obviously, we will be open to evaluation of what makes sense as we enter later stage development. For today, as an oral therapy, right now, the only one in development, as you know, in the first line, those are the oral therapies that make the most sense to us. But certainly, after we see the data and in discussions with the FDA, we will be evaluating all the optionalities that would make sense in progressing the app.

Speaker Change: For your second question right now, so, you know, azithromycin serves as a macrolide. And so with a macrolide under discussion, we feel that that is

Speaker Change: a appropriate measure to evaluate co-administration with, along with the TAMU talks.

Speaker Change: Which as the landscape for NTM evolves, obviously we will be open to evaluation of what makes sense as we enter later stage development.

Speaker Change: Transcribed by https://otter.ai

Speaker Change: And in discussions with the FDA, we will be evaluating all the optionality that would make sense in progressing the asset.

Speaker Change: Thank you very much.

Sat Shukla: Ladies and gentlemen, this concludes our question and answer session. I would now hand the conference over to Sat Shukla for his closing comments.

Speaker Change: Thank you.

Speaker Change: Ladies and gentlemen, this concludes our question and answer session. I would now hand the conference over to Sat Shukla for his closing comments.

Sat Shukla: Thank you everyone for joining in. We look forward to updating you as we progress with our pipeline.

Sat Shukla: Thank you everyone for dialing in. We look forward to updating you as we progress our pipeline. Have a great day.

Operator: Have a great day. Thank you. The conference of Spero Therapeutics has now concluded. Thank you for your participation. You may now disconnect your lines.

Speaker Change: Thank you. The conference of Spero Therapeutics has now concluded. Thank you for your participation. You may now disconnect your lines.

Operator: ?? ?? ?? Copyright © 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. Copyright © 2020 Mooji Media Ltd. All Rights Reserved. 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, Ritu Baral, Esther Rajavelu, Stephen DiPalma, Unknown Executive, Unknown Attendee, Boobalan Pachaiyappan, Gavin Clark, Raghuram Selvaraju, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc

Speaker Change: Ritu Baral, Esther Rajavelu, Stephen DiPalma, Unknown Attendee, Boobalan Pachaiyappan, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc Ritu Baral, Esther Rajavelu, Stephen DiPalma, Unknown Attendee, Boobalan Pachaiyappan, Kamal Hamed, Satyavrat Shukla, Ted Jenkins, Spero Therapeutics Inc

Speaker Change: [inaudible]

Operator: Good afternoon, and welcome to the Spero Therapeutics second quarter 2024 financial results conference call. At this time, all participants are in listen-only mode.

Speaker Change: Good afternoon and welcome to the Spero Therapeutics Second Quarter 2024 Financial Results Conference Call. At this time, all participants are in listen-only mode.

Shai Biran: Following the company's formal remarks, we will open up the call for questions. Please be advised that this call is being recorded, and a replay will be available. You can find information on the replay and further information related to today's announcements on the Spero Therapeutics website at www.spero-therapeutics.com. At this time, I would like to turn the call over to Shai Biran, Senior Director, Investor Relations. Mr. Bilan, please go ahead.

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

Speaker Change: At this time, I would like to turn the call over to Shai Biran, Senior Director, Investor Relations.

Shai Biran: Mr. Biran, please go ahead.

Shai Biran: The press release is available on the investor page of the Spero Therapeutics website.

Shai Biran: Before we begin, I would like to remind you that some of the information presented on this conference call contains forward-looking statements under the securities law. These forward-looking statements involve substantial risks and uncertainties that could affect our actual clinical progress. Future Results, Progress, Timing, Performance, or Achievements may differ materially from those expressed or implied by such for the King State due to these risks and uncertainties associated with our business. Spero Therapeutics filing with the SEC, including in the risk factor section of the earnings report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC today. We also ask that you reference the cautionary statement or forward-looking statement included with the slide presentation accompanying this conference call.

Speaker Change: Before we begin, I would like to remind you that some of the information presented on this conference call contains forward-looking statements under the security laws.

Speaker Change: These risks and uncertainties associated with our business.

Speaker Change: Factors that could contribute to such differences are described in detail in Spero Therapeutics filing with the SEC, including in the Risk Factors section of its earnings report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC today.

Speaker Change: We also ask that you reference the cautionary statement or forward-looking statement included with the slide presentation accompanying this conference call.

Sat Shukla: Participating in today's call are Sat Shukla, Chief Executive Officer, and Esther Rajavelu, Chief Financial Officer and Chief Business Officer. Satyavrat Shukla will begin the discussion. Please go ahead, Satyavrat.

Speaker Change: Participating in today's call are Sat Shukla, Chief Executive Officer, and Esther Rajavelu, Chief Financial Officer and Chief Business Officer.

Speaker Change: Satya Shukla will begin the discussion. Please go ahead, Satya.

Sat Shukla: Good afternoon, everyone, and thank you for joining our conference call today. I am pleased to provide an update on the ongoing progress across our portfolio of clinical-stage assets. Before that, I would like to note a change in our executive leadership team with the departure of our chief medical officer, Dr. Kamal Hamed.

Saab Shukla: Thank you. Bye.

Saab Shukla: Good afternoon, everyone, and thank you for joining our conference call today.

Saab Shukla: I am pleased to provide an update on the ongoing progress across our portfolio of clinical stage assets.

Speaker Change: Before that, I would like to note a change in our executive leadership team with the departure of our Chief Medical Officer, Dr. Kamal Hamed.

Sat Shukla: On behalf of the board, management, and all of our employees, we thank Dr. Hamed for his many contributions to Spero and wish him every success for the future. Let me announce that Dr. John Portage, a distinguished industry veteran in our field and a member of Spero's board for the last six years, will help oversee and provide strategic guidance for our clinical programs during this transitionary period while we continually search for our next chief medical officer.

Speaker Change: On behalf of the board, management, and all of our employees, we thank Dr. Hamed for his many contributions to Spero and wish him every success for the future.

Speaker Change: We are pleased to announce that Dr. John Portage

Speaker Change: Moving through our clinical pipeline, let me begin with SPR-720, which we are developing as a first-line oral agent for non-tuberculous mycobacterial pulmonary disease, or NTMPD.

Speaker Change: NTMPG has an estimated patient population of 245,000 patients in the U.S., EU, and Japan, with approximately 95,000 of those patients in the U.S.

Speaker Change: There is currently no approved first-line therapy for these patients.

Speaker Change: The current guidelines recommend off-label TB drugs, which have a history of lack of efficacy, as well as serious tolerability issues.

Sat Shukla: SDR 720 has a novel mechanism of action that is different from other standards of care agents, as well as those in development for NTMP2. Spero has conducted extensive in vitro and in vivo studies, which have shown no evidence of cross-resistance against marketed antibiotics as well as a low propensity for selection of resistance. Furthermore, we have demonstrated SPR-720 to be potent against multiple NTM patterns.

Speaker Change: SPR 720 has a novel mechanism of action that is different from other standard of care agents as well as those in development for NTMPG.

Speaker Change: Spero has conducted extensive in-vitro and in-vivo studies.

Speaker Change: which have shown no evidence of cross-resistance against marketed antibiotics, as well as a low propensity for selection of resistance.

Speaker Change: Further, we have demonstrated SPR-720 to be potent against multiple NTM pathogens.

Sat Shukla: Overall, we believe the preclinical data supports SBR 720's potential for therapeutic benefits. In Q4, we expect to share a comprehensive data set from our ongoing and recently completed clinical study. This is anticipated to include data from the phase 2A proof-of-concept study in treatment-naive and treatment-experienced non-refractory patients. We will also report data from two supportive Phase I studies in healthy volunteers. One of which assesses SPR720 exposure in the lung as monotherapy, and the second of which assesses exposure in plasma when co-administered with standard of care agents.

Speaker Change: Overall, we believe the preclinical data supports SBR 720's potential for therapeutic benefit.

Speaker Change: In Q4, we expect to share a comprehensive data set from our ongoing and recently completed clinical studies.

Speaker Change: This is anticipated to include data from the PHASE II-A proof-of-concept study in treatment-naive and treatment-experienced non-refractory patients.

Speaker Change: We will also report data from two supportive Phase I studies in healthy volunteers.

Speaker Change: One of which assesses SPR720 exposure in lung as monotherapy, and the second of which assesses exposure in plasma when co-administered with standard of care agents azithromycin and ethambutol.

Sat Shukla: Ezethromycin, Unknown Attendee, In Phase 2, a clinical trial compares two doses of SPR-720, 500 mg and 1,000 mg, administered as monotherapy versus placebo in patients with NTMPD due to M-abium complex or MAP. We have enrolled a total of 25 patients.

Speaker Change: The Phase 2A clinical trial compares two doses of SPR-720, 500mg and 1000mg.

Speaker Change: Administered as monotherapy versus placebo in patients with NTMPD due to M-abium complex or MAC.

Sat Shukla: Including both treatment-naive and treatment-experienced patients who do not have treatment-refractory disease. It is our hope that the data from this study will indicate that SPR-720 as a monotherapy can decrease the NTM bacterial load over the treatment course of 50-60. To analyze this early bactericidal activity, we are measuring changes in bacterial load in patient's excretion, including the rate of change in locked and colony-forming units per milliliter, which is our primary endpoint in this study. We are also looking at the rate of change in time to positivity, which is a key secondary endpoint in this study.

Speaker Change: We have enrolled a total of 25 patients.

Speaker Change: Including both treatment-naive and treatment-experienced patients who do not have treatment-refractory disease.

Speaker Change: It is our hope that the data from this study will indicate that SPR-720 as a monotherapy can decrease the NTM bacterial load over the treatment course of 56 days.

Speaker Change: To analyze this early bactericidal activity, we are measuring changes in bacterial loads in patient's excretion, including the rate of change in log10 colony forming units per milliliter.

Speaker Change: which is our primary endpoint in this study.

Speaker Change: We are also looking at the rate of change in time to positivity, which is a key secondary endpoint in the study.

Sat Shukla: A clear numerical difference in these measures between the treated arms and placebo could indicate that SPR-720 has a potential therapeutic effect in patients with NGMPD. We anticipate that success on these endpoints would also make SPR-720 the only oral agent in development that we are aware of to demonstrate early bactericidal activity in patients with NTN-PD due to MAC and would enable us to move confidently into late-stage development. We believe that SPR-720 could be used as part of the COVID-19 vaccine.

Speaker Change: A clear numerical difference in these measures between the treated arms and placebo could indicate that SPR720 has a potential therapeutic effect in patients with NTMPD.

Speaker Change: We anticipate that success on these endpoints would also make SPR 720

Speaker Change: The only oral agent in development that we are aware of to demonstrate early bactericidal activity in patients with NTMPD due to MAC and which enable us to move confidently into late-stage development.

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