Great. Thanks, Dan. So a pleasure to be here today to discuss the Spero story. A reminder that today's session will include forward-looking statements. So as Spero enters our second decade, the company is a leader in developing therapies for rare and multi-drug resistant infectious diseases. The company has a diversified clinical-stage portfolio, a late-stage development pipeline that's focused on indications with high unmet need in addressable patient populations. In development, we focus on oral small molecule drugs, and these assets have strong IP and orphan drug and/or QIDP designations. Today, we'll spend most of our time covering SPR720, our lead asset, which is positioned for near-term inflection.
This is potentially a novel oral first-line treatment for Nontuberculous Mycobacterial disease, which is NTM-PD, a rare disease with approximately 245,000 patients in developed markets, approximately 100,000 of whom are in the United States. In NTM-PD, there are currently no first-line approved therapies. SPR720 is positioned for a proof of concept data readout in the fourth quarter of 2024, so coming up very soon indeed. Development of SPR720 and development of our other assets is usually supported by world-class partnerships. Milestones from these partnerships, along with our cash and cash equivalents, provide Spero with a cash runway into late 2025, during which time we expect to have several clinical outcomes. But this is a snapshot of the portfolio as it stands today.
We talked about SPR720, our wholly owned lead asset, with a data readout anticipated in the fourth quarter. Moving to our other assets, Tebipenem HBr is potentially the first oral carbapenem for treatment of complicated urinary tract infections. This asset is currently enrolling in a phase III trial, with a target completion of enrollment in the second half of 2025 . This asset is partnered with GSK, who own worldwide commercial rights, ex- Asia. They're also the leading investors in Spero, and to date have invested approximately $200 million in equity or milestones in progressing Tebi, with potentially another $400 million plus royalties to come, should the phase III data be positive. Finally, SPR206 is our next-generation polymyxin.
This is for treatment of multi-drug resistant Gram-negative pathogens, and it has recently received IND clearance from the FDA earlier this year to initiate a phase II HAP/VAP study. This is partnered with Everest Medicines in China and with Pfizer, ex-U.S., ex-China. Pfizer are also leading shareholders in Spero. Spero retains rights for the U.S. for SPR206. Given the time that we have today, as we have clinical outcomes on the first two assets coming out over the next couple of years, we'll spend our talking time talking about SPR720 and Tebipenem for the most part. Moving on to SPR720. So the NTM-PD landscape is pretty challenging for patients. It's a chronic, debilitating disease. Most of us inhaled NTM pathogens probably today in shower water and elsewhere, but for most of us, our systems clear it.
For a subset of patients with existing lung damage or pre-existing conditions, if exposed to NTM species such as M. avium complex, which drives 80%-85% of these infections, or M. abscessus, which drives another 5%-10% of these infections, many patients develop the signs and symptoms listed on the right side of the slide, ranging from fatigue to shortness of breath, to fever, to weight loss. In addition to these, life-altering signs and symptoms, these patients also start incurring lung damage. Right now, after diagnosis, the first-line treatment options include a combination of antibiotics, including a macrolide, for 6-12 months. We'll talk about that SOC in just a moment. But the bottom line for many of these patients is that drug resistance and/or exacerbations lead to a five-year all-cause mortality of 35%.
So with that said, just building on that landscape, we talked about the unmet need. The current SOC treatments have severe limitations, so poor outcomes driven by emergence of resistance. Since nothing is approved for first-line treatment, the agents used to treat first-line patients have all been around for a while, and therefore, bacteria have over time developed resistance to many of these agents that have been around for decades. As these are currently not easy to tolerate for patients, there's a high rate of treatment drop-offs, and from the patients who actually begin therapy on non-approved, guideline-based SOC, there is a 50% chance of infection recurrence. So again, a condition requiring long-term treatment. The first-line treatment off-label is usually azithromycin or clarithromycin macrolides, followed by, or supported by ethambutol and rifampin, usually for resistance concerns.
Inhaled amikacin is in a phase three trial in first-line NTM right now, but no other oral agents are in clinical development at this time. Where would SPR720 fit in? It's an oral small molecule gyrase B inhibitor to develop the unmet need. It has shown in vitro and in vivo potency against multiple NTM pathogens, especially against M. avium complex, which drives the majority of such infections. It has a novel MOA for NTM PD that is not exploited by current antibiotics, and the implications of that are that it has shown no evidence of cross-resistance against marketed antibiotics, and also a low propensity for selection of resistance, which in this space are really key drivers. The data to date support a potential for efficacy, lung macrophage penetration, and safety and tolerability.
It can be administered with or without food, and the IP and other designations give it a lengthy LOE. On the right side of the slide, it shows SPR720, the phosphate ester prodrug that converts rapidly to SPR719, the active moiety, and over the subsequent slides, I cover both. Very briefly on the novel mechanism of action. So SPR720 or SPR719, it targets DNA gyrase, which thereby inhibits DNA replication. That's the box on the top left. The current SOC agents, azithromycin and ethambutol. Azithromycin disrupts ribosomal activity, and ethambutol attacks the cell membrane. So if you look at the bacteria, the addition of SPR720 is an incremental approach to disrupting bacterial activity beyond azithromycin and ethambutol.
That novel target and differentiated MOA potentially position SPR720 to improve current SOC regimen, and if the data are positive, to potentially be the first oral approved therapy in this space. To the stage of development, we have brought SPR720 to today, we based it on what we have seen in vitro and in vivo data and in safety studies. In vitro data showed that you needed a less degree of SPR720 than the other agents that are used to treat or have the potential to treat NTM. So this chart shows a MIC90 measure, the degree of drug required to reduce bacterial burden by 90%. You can see SPR719, the active moiety, compared to amikacin, the foundation for Arikayce, clarithromycin, which is the macrolide, and other agents.
Across this spectrum, for these species that are most responsible for these infections, SPR719 showed a high degree of potency. In vivo data supported our view of that potency. This is a standard murine mouse model. The chart is in log terms, so a move from six to four shows a 90%+ reduction in bacterial burden, and the bar, the black bar, is untreated subjects. The blue bars are SPR720 as monotherapy, and the green bars are SOC or combination with 720. As shown in the blue bars, 720 as monotherapy led to a two-log drop, even at relatively lower doses in that bacterial burden, and a very low dose in combination with clarithromycin and ethambutol, shown on the very right, led to a four-log drop.
These in vivo data were supportive of our assumption of potency for SPR720. A healthy volunteer study with 96 subjects also showed no SAEs, generally well-tolerated at doses up to 1,000 mgs, and a dose-dependent increase in plasma exposure. Only one discontinuation, well above predicted therapeutic levels, was a grade two pancreatic enzyme elevation that was asymptomatic, monitorable, and reversible. These charts show, again, the chart on the left, the plasma concentration increase with dose escalation, and on the right, it shows a comparison of fasted versus fed patients. So this basically, again, reinforced that this was a drug that could be taken with or without food. I'll scroll quickly through this slide.
So the therapeutic landscape challenges we talked about earlier, no approved oral therapies, no approved therapies right now in first line, no oral therapies in clinical development. The intolerability by many SOC agents, emergence of resistance, and limited efficacy, seven twenty has the potential to be the only oral agent. The dosing to date showed a tolerable profile, and the in vitro data showed both potency and the low evidence of emergence of resistance. These are the areas for 720 clinical development we focused on for this year. We wanted to see efficacy as monotherapy. We had seen that it kills bugs in vitro, in vivo. We had seen it well tolerated by healthy volunteers, and now we want to see, does it, in isolation, working by itself, kill bugs in patients? We also wanted to get data on exposure and PK.
So either as by itself in a hollow-fiber study or in co-administration studies with hollow-fiber work, does it get to where it needs to get to, either in isolation or, again, with current SOC? And then finally, what's the resistance profile when it's used with SOC agents? This is the key data that we expect to read out later this year. So it's 25 patients enrolled and dosed, 56 days of dosing. We are expecting these data to read out for the endpoints that are listed on the right. The primary endpoint for this study would be the reduction in colony-forming units per milliliter.
What we would like to see is for the patients on drug, 500 milligrams and 1,000 milligrams, compared to placebo, whether the reduction in their lung burden compared to placebo is meaningful at 56 days. As we mentioned before, the treatment duration for NTM for culture conversion often takes a year or longer. If we see a divergence from placebo over only 56 days, we would consider that really promising data. The secondary endpoint is a time to positivity. This basically would evaluate, after treatment, how long does it take for patients' sputum to become positive again? The longer the time, the better the reduction was to start with. Both CFUs and time to positivity are well-established measures in an adjacent therapeutic space in TB. We were the first to apply that in NTM to see if it translates, hopefully, into culture conversion for longer trials.
Along with that, we expect to see secondary endpoints on safety and tolerability and plasma PK. This chart just visually lays out what we just covered. The top is the CFU analysis. Over time, we expect to see a lowering burden for CFUs. On the time to positivity, the same sputum inoculated in liquid medium, the longer the time before that becomes positive, the stronger the efficacy trend. So what we hope to see for SPR720, on the left are the questions we had posed and the studies we are running right now. But pretty soon, we hope to see the bars on the right. Numerical differences in the key quantitative bacterial burden metrics and a well tolerated regimen.
We want to see if the drug gets to the lung macrophages, where it needs to get to, and whether it is consistent in its exposure as a monotherapy versus combo, and finally, a resistance profile. If we see these data, we would find this to be a promising asset to progress to potentially pivotal trials going forward, so a very comprehensive data set that is coming up in the fourth quarter of this year, and we are very excited to see it. Moving on to Tebipenem. In contrast to SPR720, we had talked about a diversified clinical stage portfolio. Tebipenem is an area with a very large patient population. Right now, complicated urinary tract infections in the United States are north of three million every year.
For many of these patients, carbapenems are an agent of choice for addressing those infections. Currently, all carbapenems are IV. For the large subset of those CUTI patients who are going on carbapenems today, your choices are unfortunately the ones listed on the left. Most of these involve staying in a hospital bed for seven to 10 days, which lends itself to a very high burden, not only for patients, but also for hospitals. Tebipenem HBr has the potential to reduce that burden because it is the only oral carbapenem in development that we know of. Beyond the prescriber base that it has really looked at the ID space here historically, Tebipenem HBr has the potential to expand that base.
It could potentially keep people out of the hospital, or if you're in the hospital, it would enable you to go home sooner. Patients could be treated in community centers. This is therefore potentially a transformative therapy, and given the degree of incidence, three million cases every year, one does not need aggressive assumptions for pricing or market penetration to see how this could be a very successful drug. The phase III is currently enrolling, and the global commercial partnership with GSK was established on the promise of that commercial performance. This is the trial that's enrolling right now. It's a very large trial. Up to 2,648 patients, two treatment arms, randomized and blinded, the oral tebipenem and dummy IV infusions, compared to imipenem/cilastatin and dummy tablets.
The primary endpoints will be the overall response at the test of cure sites, and the measure will be a non-inferiority measure at a 10% NI margin. Further de-risking this program is a special protocol assessment agreement we entered into with the FDA that laid out clear measures for success, and the FDA's indication that this study, along with previously indicated studies, could be sufficient to support approval for Tebipenem HBr for a limited use indication within those 3 million patients. Just to close off, I believe I'm at time. This lays out the financial structure for tebipenem. As I mentioned at the outset, Spero has received up or qualified for $200 million, either as equity investments or milestones to date, and is eligible to receive another $400 million in potential regulatory, commercial, and sales milestones, plus royalties.
More specifically, if we see positive data and if GSK file that NDA, the company gets $25 million right upon the filing of that NDA. On first sale, the company receives up to $150 million on that first sale. We say up to because there's a U.S. and an EU component to it, and this will be the U.S. first sale of the phase three data. In addition to being a compelling asset on its own right, the financial upside for Tebi also gives us great flexibility for progressing SPR720 and the portfolio. Stop there on the formal part and be happy to take questions.