Okay. Hi, everyone. Thank you for joining us this afternoon. My name is Nicole Martucci. I'm an associate here at TD Cowen, working under Senior Analyst Ritu Baral. Thank you for joining us. With us right now, we have Spero Therapeutics and Esther, who is the Interim Chief Executive Officer and also the Chief Financial Officer. She'll be giving a corporate presentation, and we'll follow up with some question-and-answer sessions. Please take it away.
Great. Thank you. Good afternoon, and thank you for your interest in Spero Therapeutics. Thank you to the Cowen team for hosting us at their conference. Here are the mandatory forward-looking statements, which always make for an exciting read. On slide three, Spero is a clinical stage company focused on areas of high unmet need in rare and multi-drug-resistant infectious diseases. We have a diversified portfolio of mid to late-stage clinical assets, including one in a phase III trial, which we are hopeful to have an inflection in this year. We typically focus on areas where there is an addressable patient population that's identified, and however, an unmet need exists, either because the current therapies are not well equipped to address the unmet need in the patient population, or if there is an opportunity to expand the addressable treatment options for physicians.
All our drugs have the Qualified Infectious Diseases Product designation , and where appropriate, we've also achieved Orphan and Fast Track designations. We have a strong global intellectual property portfolio with both formulation and/or composition of matter patents. Our runway is into mid-2026, and we are in a strong position to deliver on our key phase III inflection this year. In addition to our cash position, we have partnerships both with large pharma companies as well as collaborations with government agencies such as NIAID and BARDA that have provided non-dilutive capital for us to continue developing our pipeline. On this next slide, we lay out our pipeline, and you'll see that we are therapeutically diverse. Our lead asset, tebi HBr, is in a phase III trial for complicated urinary tract infection, and we've guided to completing enrollment in the second half of this year.
We also recently announced that we've completed over 60% enrollment in the trial over the course of 2024. We feel good about where we are with the enrollment. This asset is partnered with GSK for ex-Asia commercial rights, and Meiji holds the right for both development and commercialization in Asia. Our second asset, SPR-206, is a phase II ready asset for hospital-acquired and ventilator-acquired bacterial pneumonia. We hold the U.S. rights for this asset and outlicensed commercial rights to Pfizer for OUS regions and to Everest Medicines for Chinese rights for both development and commercialization. Lastly, our wholly owned asset is SPR-720, where we recently completed dosing in a phase IIa small proof of concept trial for non-refractory NTM-PD patients. We also announced late last year that following a planned interim analysis of about 16 patients, we saw activity in the drug.
However, there were dose-limiting toxicities as well. We suspended the oral program and are looking at completing the full data analysis and will determine next steps for that program later this year. I'll spend the majority of the time today talking about tebipenem , which is positioned to be the first oral carbapenem for complicated urinary tract infections. We'll cover the disease state and the competitive dynamics in that space, as well as why we believe an oral carbapenem remains a high unmet need and why tebi is best positioned to address that. On this next slide, on the right side of the image is the uncomplicated urinary tract infection. As many of you know, it is caused by bacterial infections and can be typically treated in an outpatient setting.
The complicated urinary tract infection patients typically have an abnormality of the urinary tract, or they have comorbidities such as kidney stones or kidney infections like pyelonephritis, or are typically hospitalized under catheterization. These patients are infected with resistant pathogens and have a much higher risk of recurrence and progression. The treatment landscape for cUTI, there are approved medications. However, patients that are progressive end up in a hospital or inpatient setting and have to undergo IV therapy. As you can imagine, hospitalized patients, there is a high burden of patient suffering as well as high costs of care when you have to spend 7-10 days in the hospital. Because these patients have resistant pathogens, there is a large patient, there is a large treat, there is a meaningful unmet need, and the estimated treatment episodes are about 3.4 million in the U.S.
On slide eight, we believe tebi is positioned to be the first oral carbapenem to reduce the treatment burden for cUTI patients. It is an orally bioavailable drug, and we are, as I mentioned before, we're enrolling the phase III trial, which is a large global trial, and we anticipate completing enrollment in the second half of this year. Our partnership with GSK has been a solid source of funding for us and has helped us push this program further in the clinic. The product has IP through 2041, and it has QIDP designation as well. This slide lays out the clinical trial design for the phase III trial. It is a global randomized double-blind, double-dummy, non-inferiority trial, and we're enrolling patients with both cUTI as well as acute pyelonephritis.
We aim to enroll about 2,650 patients in this trial, and it is a hospital treatment setting with about 7-10 days of inpatient dosing. The active comparator here is imipenem-cilastatin which is an IV standard of care for these patients, and we're dosing tebi orally. Our primary endpoint is overall response at the test of cure visit in the micro-ITT population, and we are looking for a 10% non-inferiority margin to meet thr primary endpoint. Moving on to the next slide, as you can see here, this lays out the competitive development landscape for complicated UTIs. And tebi is well positioned furthest along in the clinic, and we believe with good data could be the first oral carbapenem for these patients.
In addition, the bottom half of the slide lays out the potential therapies that have been recently approved for uncomplicated urinary tract infections, which is a different patient population. However, the number of oral candidates that are being developed for these patients is an indication of the high unmet need that remains in these patients for these patients. Lastly, I'll go through our deal terms with GSK, but I'll start off by saying that we have had a good collaboration with GSK, and they've been great partners to us in furthering the development of tebi. The partnership has also provided a solid financial foundation for Spero. To date, we've received about $200 million in funding and may be eligible to receive up to $400 million in regulatory and commercial milestones in addition to tiered royalties if the program continues to progress.
We are very excited about completing enrollment later this year and look forward to giving you an update on the next steps for this program and for the company. With that, I will open it up to questions.
Just on this GSK partnership, what about any other collaborations on when you might be looking for the next milestone?
Sure. The question was when we would be eligible for the next milestone under the GSK partnership. The committed milestones are, we still have about $47.5 million remaining to receive in the committed milestones to complete the phase II development, but the next real contingent milestone is the $25 million that we would qualify for when GSK submits the NDA, which they've guided to doing at the end of this year.
I think I saw another question over here.
Yeah, just staying on tebi, I know you mentioned around 6,000 patients enrolled in your last update. Do you plan on giving any other updates in terms of enrollment in your next quarterly earnings report? Do you have any further clarity on timing and the second half on data?
Sure. I'll just repeat the question. Are we planning to give additional updates on the tebi program on enrollment and when in the second half we would have data? We don't plan to give additional updates on enrollment. The 60% was a milestone that we hit, so we shared that update at the beginning of the year. The next real update on the program will be when we complete enrollment and have data to share. When in the second half, I think all I can say is the second half. You can do the math. If we've completed 60% enrollment in a year, it should give implications for where we could be.
For, oh, no, go ahead. Yeah.
I was going to say for 206, could you talk a little bit about the non-committed financing progress, kind of where it is? Any update on that in terms of when we can expect that trial to be going?
Sure. Yeah. The question was on 206 and non-dilutive financing sources and when we can expect that trial to get going. 206, we've made a commitment to continue funding that program through non-dilutive sources only, and NIAID has been a strong partner for that program for us in addition to our commercial partners. What I would say is we're continuing to look for funding for that program. We're working with NIAID again, and we also retain U.S. rights for that program, which could potentially be an additional source of financing. We're not going to start that trial until we're comfortable that we can get the financing and that there is a path forward.
Bringing it back to the tebi program, is there any potential for tebi to be developed in uncomplicated UTIs? What's kind of the overlap between treatments in those two spaces, and would it require an additional clinical trial, or what's the kind of pathway to that?
Yeah. Uncomplicated UTIs are a different patient pool than complicated. I think, honestly, it will be GSK's responsibility to continue developing it beyond the complicated urinary tract trial that we're running. Are there opportunities for label expansion? Absolutely, because it is a broad spectrum oral carbapenem. What I would say is, is uncomplicated UTI the first next indication that GSK may potentially pursue? I don't know, but there are definitely other indications that could be attractive for this.
When top line gets reported, will that be driven by GSK, or will that be something that you guys are responsible for doing and analyzing and kind of presenting that path forward?
Yeah. We are responsible for completing enrollment and delivering the data to GSK. We work in very close collaboration with them, and we have a JDC, so the data announcement would likely be a collaborative announcement, but we are ultimately responsible for completing the analysis and delivering the data.
Can you talk about what a successful clinical trial would look like for you guys? What is a clinically meaningful benefit? Kind of what are expectations as we are somewhat approaching enrollment completion?
Yeah. The primary endpoint for the trial is the 10% non-inferiority margin at the test of cure visit in the micro-ITT population. Ultimately, the goal is to get the patients out of the hospital sooner than they would if they were on an IV carbapenem. The trial is designed for the patients to stay in 7-10 days, but ultimately, in the commercial setting, it would be getting patients out of the hospital sooner and/or keeping them out of the hospital. From a trial standpoint, it is meeting that 10% non-inferiority margin. In a real-world setting, there would be additional benefits to patients.
Can you maybe, I know you mentioned it in the presentation, expand a little bit on the unmet need in these patient populations and what current therapies are lacking and how tebi can kind of improve upon that?
Yeah. Tebi is being developed for the patient population that is currently highly resistant to other oral therapies and have progressed to be in patients in a treatment center receiving IV therapies. That is a pretty high burden for both the patient to stay in the hospital for 7-10 days under an IV, and there is also a cost burden associated with it to the healthcare system at large. That is the unmet need that tebi is trying to fill, and it is the only oral carbapenem that's furthest along for complicated patients.
Great. I guess moving over to NTM and with some questions there. It was your prior main focus, and we've in the past touched upon the potential for you to kind of bypass the dose-limiting toxicities with a reformulation of the 720 asset. Can you kind of talk about that and what are next steps for that program and what would lead you guys down a path of reformulating it and potentially restarting the NTM program?
Sure. The first step would be to complete the data analysis of the full 25 patients that we have dosed and followed through the trial. What we've seen with the 16 patients is evidence of activity against MAC and also dose-limiting toxicities, which included Grade 3 liver enzyme elevations at the 1,000 milligram dose. Now, what's good about that, to the extent that there is anything good about that, is that once we stopped dosing, these patients did reverse back. There is evidence of reversion post-treatment period. That gives us confidence that if we can eliminate the systemic exposure, there could be a path forward with another formulation. We would consider inhaled formulations.
We have the scientific advisory boards that we've convened, and the additional work that we've done in the market suggests that the unmet need for this patient population is meaningful enough that another inhaled option would lead to better outcomes versus not exploring that at all. Again, it's a matter of completing the data analysis and looking at other steps, but we'll have additional updates later this year on that.
What exactly are you hoping to see from the further data analysis from the set?
We would be essentially looking to understand the, if you recall, the trial was a 56-day dosing duration. I think what we would be looking to understand is how the patients at each of those, with each of those sputum cultures, what the variability was in response. There was also a post-dose follow-up period. We would look to understand how patients trended post-dosing. I.e., if you're kind of seeing some level of response but not enough, but then you know that after dosing, you see the patients, the bacterial load increasing meaningfully, that theoretically demonstrates that the drug was doing something. Those are some of the signs that we would typically assess, but ultimately, the interim analysis was based on 16 patients.
Unless there is a huge amount of variability in the remaining patients, we would not expect to see anything meaningfully different with the oral dosing program.
Do you think that it's, I guess, a generally difficult, I guess, practice to do, converting it from an oral to an inhalation asset? Is that difficult to do? Do you think that if that was the path that you guys chose, that you would be able to kind of, what does, I guess, that process, what would that entail and kind of encompass?
Yeah. I mean, that would entail some formulation work, and it's one that many companies have pursued. If you look at the entire therapeutic landscape for NTM agents that are approved and in development, they're all reformulations of old oral drugs. The advantage we have here is that this is a new chemical entity, and it is a differential, it is a novel target for this indication and a differentiated mechanism of action. We would have to do some chemistry work. We'd have to understand dosing variability on oral versus an inhaled formulation. We'd have some homework to do before we can get confident.
Okay. Any last-minute questions or follow-ups from the audience? No? Okay. With that, thank you so much, Esther. It was a pleasure, and I hope everyone continues to enjoy the conference.
Thank you.