Robert Wallis, MD, is the chief scientific officer at the Aurum Institute and adjunct professor in the department of medicine at Vanderbilt University Medical Center.

Robert Wallis, MD

2026 American Thoracic Society (ATS) International Conference

 in Orlando, Florida, investigator Robert Wallis, MD, the chief science officer at the Aurum Institute & professor of medicine at Vanderbilt University, presented preliminary findings from the PanTB-HM phase 2c trial, which evaluated 3 novel 4-month pan-TB regimens, each containing the investigational oxazolidinone sutezolid, against standard 6-month HRZE therapy in 378 adults across South Africa, Tanzania, and Mozambique.

Among participants with impaired baseline lung function (FEV1 ≤62%), recipients of the S1600BPN regimen—sutezolid 1600 mg, bedaquiline, pretomanid, and N-acetylcysteine (NAC)—demonstrated markedly superior FEV1 recovery compared with controls, a 10.6 percentage point difference at day 14 that was largely maintained through day 168. No typical oxazolidinone adverse events were observed across any experimental arm.

 sat down with Wallis during the meeting to discuss what these results may mean for clinicians managing TB-associated lung disease and the evolving role of sutezolid and NAC in next-generation TB regimens.

 Pulmonologists know that structural lung damage from TB can be permanent. Is the FEV1 recovery you're seeing reflecting true functional restoration, or is some of this early resolution of inflammation and consolidation? How do you interpret that distinction clinically?

We need to do that study [further]. The longest we have followed patients is about a year and a half, and the numbers get small as we go out that far. Lung damage after TB does seem permanent [in most patients].

There was one study, [conducted in] South Africa by Paul Wilcox [and] published in 1989, that called 80 individuals back to the TB clinic after [they had been] discharged [as] cured, and their lung function was impaired—[in some cases] up to 17 years [later] in proportion to how bad their x-ray was at the time of TB diagnosis and even in proportion to how much sputum they were producing at the time.

You could plot a graph of FEV1 a decade later [against the] amount of [daily] sputum [volume] produced at the time of diagnosis, and they were very correlated. At a minimum, this is permanent damage, but we think it actually can be progressive in many patients because of impaired mucosal immunity and [recurrent] infections of many types: bacteria, fungal, and [viral].

 The lung function benefit appeared most pronounced in the S1600BPN arm—the one that includes NAC. How confident are you that NAC is doing meaningful work here?

I’m reasonably confident that the NAC was doing something. This is actually the second study that we have done [with NAC]. In the first study, it was added to standard TB treatment—HRZE—and we saw a similar benefit in terms of [FEV1] recovery. I think the majority of the [lung function] benefit…is probably attributable to NAC. I have to offer guarded advice to pulmonologists [about] how to use this information because of the findings [from] these two studies.

They are [small] phase 2 trials with some added long-term follow-up. In the first study that we did in Tanzania [n = 140; about 70 participants per arm], we had some indications that NAC might be interfering with the antimicrobial activity of the TB regimen. There were 2 [not statistically significant] relapses in the control arm and 5 relapses in the NAC arm. We saw a near-significant trend toward delayed culture conversion, [which had a hazard ratio of] 0.8, [but] the P-value was not less than .05—it was .08—[and] that’s a concern.

We also looked at the rate of change of [viable MTB] elimination of viable MTB [in] sputum [using] midget [time-to-positivity (TTP) in mycobacterial culture tubes]. This is an alternative way to measure colony counts. The clearance of colonies was slower [in the NAC arm], and this was highly statistically significant.

I say this because trying to understand the antimicrobial effects of NAC in TB is quite challenging. There have been a number of animal and in vitro studies that would suggest that NAC has direct antimicrobial activity against a wide range of organisms. [Studies] in guinea pigs and…mice that said colony counts in target organs go down, but when you start combining it with specific antimicrobial drugs, the picture gets very complicated. It seems to depend a lot on how you design the experiment, which drug you choose, how much of each drug you give, and what's the outcome measurement.

In some studies, it seemed like there might be a benefit. [In one study], the [NAC completely] took away the in vitro effect of isoniazid.

 Is there a broader message for pulmonologists about mucolytic or antioxidant adjuncts in TB treatment?

I am not an expert on this subject, but…the findings from these two studies…seem to indicate a detrimental effect when [NAC is combined with] standard TB treatment and [a possible] benefit when given with this new regimen. This difference needs to be explored further. Both [regimens] showed a benefit in lung function, but it's quite possible that only one of the regimens shows better antimicrobial activity.

 One of the concerns with oxazolidinones as a class is toxicity—myelosuppression, peripheral neuropathy. You saw no typical oxazolidinone SAEs here. How do you explain that?

[Across] the studies that I did at Pfizer and the [current studies], there are probably 5 or 6 clinical trials of sutezolid, and there are 3 in which the participants received doses in the range we're giving now—1200 or 1600 mg a day for more than a month, [in our case for] 4 months—[and we] saw none of the typical [lineazolid] adverse events. Those are peripheral neuropathy, anemia [or other] cytopenias, and an optic neuropathy.

We think that those [toxicities] occur due to off-target effects, [specifically] the inhibition of mitochondrial protein synthesis. It turns out that nerve cells and bone marrow cells are particularly sensitive to these unintended effects. We saw none of these [events] in 2 reasonably powered studies. [It is] very exciting to be able to advance a new oxazolidinone to be used worldwide for tuberculosis.

 How should clinicians think about sutezolid's safety profile relative to linezolid?

This problem with linezolid, [particularly its tendency to cause] anemia, is huge. Being able to put [rifampicin]-resistant TB patients on a BPAL [regimen] was a remarkable advance, but [linezolid] puts bedaquiline at risk because of the patients who end up having to have their treatment stopped, maybe a month or 2 months into treatment, because of severe anemia.

In most poor countries, what happens is they're given an iron supplement or they're given something else, and they're monitored, and finally the treatment is stopped, and then finally they're admitted to a hospital for transfusion, because in very few of these areas are there capabilities to do transfusions as outpatients—it can take a month [or] 2 months before patients can get back on to treatment. The problem is that the treatment is not really stopped because they have already received a month or 2 of bedaquiline.

Their tissues are saturated with bedaquiline, and so effectively they are continued on bedaquiline monotherapy during this [period], while the anemia due to linezolid is being sorted out. At least in my opinion, this is the key reason why there has been [such rapid] emergence of bedaquiline resistance as quickly as we have seen it.

Editor’s note: A relevant disclosure for Wallis includes Otsuka Pharmaceutical Development & Commercialization.

Wallis R, Mudzengi D, Mashatole S, et al. (

) Novel 4-month Pan-TB Regimens Promoting Recovery of Lung Function: Preliminary Findings of the PanTB-HM Phase 2c Trial. Poster presented at ATS 2026 on May 17.

Wallis R. Novel 4-Month Pan-TB Regimens Show Promise for Lung Function Recovery. HCPLive May 18, 2026. Accessed June 8, 2026. 

https://www.hcplive.com/view/4-month-pan-tb-regimens-promise-lung-function-recovery

Articles

At ATS 2026, Robert Wallis, MD, discussed PanTB-HM findings on FEV1 recovery and NAC antimicrobial interactions.

Sutezolid Shows Promise as Safer Oxazolidinone in Novel 4-Month TB Regimen

Novel 4-Month Pan-TB Regimens Show Promise for Lung Function Recovery

 regimen containing the investigational oxazolidinone sutezolid and N-acetylcysteine (NAC) demonstrated encouraging lung function recovery and fewer adverse events than standard therapy in preliminary phase 2c findings presented at the 

In an interview at ATS 2026, Robert Wallis, MD, the chief science officer at
the Aurum Institute & professor of medicine at Vanderbilt University, discussed how the PanTB-HM trial was designed to address 2 major unmet needs in global TB care: the need for a “pan-TB” regimen that can be used without rifampin susceptibility testing and the long-term pulmonary damage that persists after microbiologic cure.

“We hope to tackle 2 problems with this strategy,” Wallis said. “One of them is the pan-TB angle, and the other is the lung function recovery angle.”

The phase 2c PanTB-HM trial evaluated 3 investigational 4-month regimens against standard 6-month HRZE therapy in adults with culture-confirmed rifampin-susceptible pulmonary TB. Experimental regimens combined sutezolid, bedaquiline, and pretomanid, with 1 arm additionally receiving NAC 1800 mg twice daily.

Among 378 participants, the mean baseline forced expiratory volume in 1 second (FEV1) was 72% predicted. Investigators reported 334 adverse events in the HRZE control arm compared with 212 to 221 adverse events across the experimental groups. Serious adverse events potentially attributable to treatment occurred more frequently in the control arm than in investigational arms, and investigators noted no typical oxazolidinone-associated serious adverse events.

The most notable findings involved lung function recovery in participants with impaired baseline pulmonary function, defined as FEV1 ≤ 62% predicted. Linear mixed-effects modeling demonstrated superior FEV1 recovery during the first 14 days among participants receiving the S1600BPN regimen containing NAC compared with HRZE (

 =.004). Investigators observed a 10.6-point difference in FEV1 at day 14 versus standard therapy (

 =.003), with the improvement largely maintained through day 168.

Wallis said the pulmonary recovery signal may have substantial implications, given growing recognition that many patients discharged as “cured” continue to experience chronic respiratory morbidity.

“Only within the past several years has it come to everyone’s realization that when we discharge someone from the TB clinic and say they’re cured, they’re not,” Wallis said. “At least half have bronchiectasis or fibrosis or cavities.”

He explained that post-TB lung disease contributes to recurrent infections, progressive airway damage, and shortened survival. According to Wallis, observational analyses suggest mortality risk after TB remains approximately 3-fold greater than expected, with reduced FEV1 appearing closely associated with long-term outcomes.

The rationale for NAC centers on oxidative lung injury. Wallis described how reactive oxygen species generated during pulmonary infection may damage mammalian airways and lung tissue despite limited effectiveness against 

. NAC serves as a precursor to glutathione, a sulfur-containing antioxidant molecule depleted during prolonged TB infection and malnutrition.

“Our objective is that if glutathione is going to protect the lung in TB, then getting cysteine to help support glutathione synthesis is really critical,” Wallis said. “The easy way to do that is with NAC and acetylcysteine.”

He noted NAC is inexpensive, widely available, and already used clinically to prevent acetaminophen-induced liver injury, making it an appealing adjunctive therapy candidate in resource-limited settings.

Wallis also suggested sutezolid itself may contribute to pulmonary recovery through anti-inflammatory effects. Experimental arms containing sutezolid but not NAC showed intermediate improvements in lung function, raising the possibility that the agent modulates phagocytic cell inflammatory responses in addition to antimicrobial activity.

Although relapse data remain preliminary, as of January 2026, investigators reported 5 relapses in the S1200BP arm, 11 in the S1600BP arm, 6 in the S1600BPN arm, and 6 in the HRZE arm.

Investigators concluded the novel 4-month regimens “appear poised to meet WHO target regimen profiles for a pan-TB indication and to provide the additional benefit of superior recovery of lung function.”

Videos

At ATS 2026, Robert Wallis, MD, shared preliminary phase 2c data showing a novel 4-month pan-TB regimen containing sutezolid and N-acetylcysteine improved lung function recovery.