Toby Maher, MD, PhD

From Slowing Decline to Restoring Function: Taladegib’s Promise in IPF, With Toby Maher, MD, PhD

Idiopathic pulmonary fibrosis (IPF) remains one of the most challenging and devastating chronic lung diseases, marked by progressive scarring that relentlessly limits lung function and quality of life. For years, standard of care treatment with antifibrotic therapies like pirfenidone and nintedanib has focused on slowing but not halting the decline in lung capacity. Promising new data on taladegib (ENV-101), a hedgehog (Hh) inhibitor, show potential to disrupt that standard.

In a small phase 2a proof-of-concept trial recently published in 

 and presented at the 2025 ERS International Congress, taladegib demonstrated an ability to improve rather than merely slow decline in lung function. Patients receiving the investigational therapy experienced measurable gains in forced vital capacity (FVC) and total lung capacity over 12 weeks, alongside reductions in CT-measured fibrosis. While the data are early and short term, they are an encouraging signal in a field where slowing disease progression has long been the most attainable goal. The phase 2a data support continued development in the ongoing phase 2b WHISTLE-PF trial, designed to confirm efficacy and long-term safety in a larger, global population.

spoke with Toby Maher, MD, PhD, Professor of Medicine and Director of Interstitial Lung Disease at the Keck School of Medicine, University of Southern California, to learn more about the new data and about taladegib as the potenital first in a new class of therapy for IPF. 

Maher gave some background on Hh signaling and other investigations into the pathway for IPF and other indications, including cancers. While earlier Hh inhibitors were limited by tolerability concerns, taladegib's more selective targeting yielded a favorable safety profile in the trial, supporting its use. 

Maher shared his anticipation for further data that will come out of the WHISTLE-PF trial that he hopes will validate the initial findings. He also emphasized the importance of further research into the biology of IPF and earlier screening and detection of IPF to maximize therapeutic benefit.

"It's a small trial," Maher cautioned. "We never want to get too excited about small trials, but nonetheless, to actually see some improvement over [3 months] suggests that the efficacy of the drug is better than we've seen with other molecules in the past."

Maher's disclosures include Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, FibroGen, Genentech, GSK, Merck, PureTech Health, Sanofi, Trevi Therapeutics, and United Therapeutics.

Johnson V. Taladegib Shows Potential to Improve FVC in Idiopathic Pulmonary Fibrosis. Article. HCPLive. October 9, 2025. https://www.hcplive.com/view/taladegib-shows-potential-improve-fvc-idiopathic-pulmonary-fibrosis

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Maher discussed taladegib's potential to improve FVC, rather than slow decline, in people with idiopathic pulmonary fibrosis.

Nerandomilast Approval Breaks Decade-Long Dry Spell for IPF, With Toby Maher, MD, PhD

The United States Food and Drug Administration (FDA) approval of nerandomilast (Jascayd; Boehringer Ingelheim) in October 2025 marks a major milestone in the treatment of idiopathic pulmonary fibrosis (IPF)—the first new therapy for the progressive and often fatal lung disease in more than a decade.

 IPF, a chronic and irreversible fibrotic condition characterized by scarring of lung tissue, has long been a field of unmet medical need, with limited treatment options since nintedanib and pirfenidone were approved in 2014.

 Now, with the FDA’s authorization of nerandomilast in both 9 mg and 18 mg tablet doses, clinicians have a new tool to help slow lung function decline and potentially improve patient outcomes, especially in patients with limited tolerance to existing drugs.

Nerandomilast, a selective phosphodiesterase 4B (PDE4B) inhibitor, represents a novel mechanism of action among antifibrotic therapies. Results from the phase 3 FIBRONEER-IPF trial demonstrated that patients on nerandomilast experienced a significantly smaller decline in forced vital capacity (FVC) compared with placebo—an adjusted mean decline of –106 mL in the 18 mg arm and –122 mL in the 9 mg arm, versus –170 mL for placebo. The drug also showed a favorable safety profile, with fewer discontinuations due to adverse events compared with previously approved antifibrotic agents.

 spoke with Toby Maher, MD, PhD, professor of clinical medicine at the Keck School of Medicine of USC and an investigator in the FIBRONEER-IPF study, to discuss the clinical significance of nerandomilast’s approval and what it means for future treatment strategies. He reflects on how the new therapy fits into the evolving IPF landscape, the potential for combination and sequencing approaches, and how the new approval represents a step in the right direction for the IPF field.

"There's still scope for for better efficacy, but I think having more treatment options available means we're going to be able to offer a benefit to more patients. So I think it's really important. I think it's a step in the right direction, and hopefully it won't be another decade before the next drug is approved," Maher said.

Johnson V. Nerandomilast Nets First New FDA Approval for Idiopathic Pulmonary Fibrosis in Over 10 Years. Article. HCPLive. October 7, 2025. https://www.hcplive.com/view/nerandomilast-first-new-fda-approval-idiopathic-pulmonary-fibrosis-over-10-years

Dempsey TM, Payne S, Sangaralingham L, Yao X, Shah ND, Limper AH. Adoption of the Antifibrotic Medications Pirfenidone and Nintedanib for Patients with Idiopathic Pulmonary Fibrosis. 

. 2021;18(7):1121-1128. doi:10.1513/AnnalsATS.202007-901OC

Global phase III trials demonstrate that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo. Boehringer Ingelheim. May 19, 2025. Accessed May 19, 2025. https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/phase-3-trials-nerandomilast-slowed-lung-function-decline-ipf-and-ppf.


Maher discussed the new FDA approved drug, marketed as Jascayd, and its impact for idiopathic pulmonary fibrosis.

American Thoracic Society (ATS) International Conference

, discussing the phase 3 FIBRONEER-IPF and FIBRONEER-ILD studies, Toby Maher, MD, PhD, described nerandomilast’s success in achieving its primary endpoint in both trials on patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

After discussing some of the most notable findings in these late-breaking data on the investigational oral phosphodiesterase 4B (PDE4B) inhibitor, the FIBRONEER trial investigator and professor of Clinical Medicine at USC’s Keck School of Medicine spoke with 

 about nerandomilast’s safety findings in the analyses.

Safety Findings on Nerandomilast for Pulmonary Fibrosis, with Toby Maher, MD, PhD

In addition to nerandomilast’s efficacy demonstrated by the reduction of forced vital capacity (FVC) in those with IPF and PPF over 52 weeks of medication use, discontinuation rates due to adverse events were also noted as having been comparable between nerandomilast and placebo cohorts in both of trials.

“I think it is an important observation that the discontinuation rates are similar across all 3 arms, including the placebo arm,” Maher said. “We know that IPF trials are difficult for patients. They're committing to over a year of being in the study. Life events come up, and disease related events come up. So we always expect some patients to discontinue. In the past, when we've used difficult to tolerate drugs, we've seen a very clear increase in discontinuations in the active treatment arm. The fact that we're not seeing that in this study, to me, reinforces the idea that nerandomilast is a much easier drug for patients to tolerate. I'm hoping that that is going to make life a lot easier in clinical practice.”

Maher was also asked about the future of nerandomilast for IPF and PPF, given the positive findings in the FIBRONEER trial program presented at ATS.

“Hopefully the regulatory bodies, the FDA, will look very favorably upon this data,” Maher said. “I'm very optimistic that the drug will hopefully be approved in the near future for use in clinical practice. You know, this trial was designed to test the effect of nerandomilast in an environment where we have anti-fibrotic drugs. We know that it slows disease progression, and we know that it can be used safely in combination with existing treatments.”

Maher added that what is not yet present is evidence on is whether clinicians should be thinking about upfront combinations of drugs.

“I think that is something that we need to look at in the future,” Maher said. “Similarly, we don't have data on when it is a new drug should be added on, so I think there are things for us to still tease out and understand about the position of nerandomilast within treatment and how we now think about treating IPF and PPF when we have drugs that can be used in combination.”

To find out any additional information on recent data presented at ATS, view our 

The quotes used in this summary were edited for the purposes of clarity.

Maher previously reported receiving personal fees from Boehringer Ingelheim, Galapagos, Roche/Genentech, Pfizer, BMS, GSK, Sanofi-Aventis, Pliant, Trevi, Galecto, Merck, Astra Zeneca, CSL Behring, Vicore, Scleroderma Research Foundation, Qureight, and Veracyte.

Global phase III trials demonstrate that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo. Boehringer Ingelheim. May 19, 2025. Accessed May 23, 2025. 

https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/phase-3-trials-nerandomilast-slowed-lung-function-decline-ipf-and-ppf.

In this interview, nerandomilast’s safety profile in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) is highlighted.

, drawn from the FIBRONEER-IPF and FIBRONEER-ILD studies, indicated that nerandomilast met its primary endpoint in both studies assessing patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

The late-breaking data on nerandomilast, an investigational oral and preferential inhibitor of phosphodiesterase 4B (PDE4B), were 

. The findings were discussed by trial investigator and professor of Clinical Medicine at USC’s Keck School of Medicine, Toby Maher, MD, PhD, who spoke with the 

 editorial team about the data’s significance for patients with IPF and PPF.

Significance of New Nerandomilast Findings for Pulmonary Fibrosis, with Toby Maher, MD, PhD

“The two FIBRONEER trials were very similar in design, with both studies looking at a primary endpoint of change in [forced vital capacity] over 52 weeks,” Maher explained. “Both studies compared 2 active doses of nerandomilast to placebo, so 18 milligrams and 9 milligrams. Both studies continue to follow patients beyond 52 weeks…The key finding in both trials, both doses of nerandomilast slowed the rate of FVC decline compared to placebo. The reason why we think that is important is that FVC is essentially a surrogate for survival. So we think that means that patients treated long term will live longer.”

Nerandomilast showed significant efficacy in the reduction of forced vital capacity (FVC) decline in those with IPF and PPF over 52 weeks of use. Rates of drug discontinuation due to adverse events were also found to be comparable between nerandomilast and placebo cohorts in both of the studies.

“With the [FVC] reduction across the 2 studies, there's just 1 little wrinkle to be aware of,” Maher said. “Which is that there was an unexpected drug interaction with the pirfenidone in the IPF study, resulting in patients essentially getting a lower dose of nerandomilast than anticipated. That has led to a slight underestimate, I think, of the treatment effect. But that notwithstanding, in the IPF study, we saw about a 35 to 38% reduction in the rate of FVC decline. In the PPF study, we were seeing around a 40 to 45% reduction in FVC…What I anticipate that means for patients is that they should be able to live longer with their disease, and that not only hopefully, will they live longer, but it will also delay important events like respiratory failure, the need for oxygen, etc.”

For additional information on late-breaking data presented at ATS, view the 

The quotes in this interview summary were edited for clarity.

Maher has previously reported receiving personal fees from Boehringer Ingelheim, Galapagos, Roche/Genentech, Pfizer, BMS, GSK, Sanofi-Aventis, Pliant, Trevi, Galecto, Merck, Astra Zeneca, CSL Behring, Vicore, Scleroderma Research Foundation, Qureight, and Veracyte.

https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/phase-3-trials-nerandomilast-slowed-lung-function-decline-ipf-and-pp

This interview highlights phase 3 trial data on nerandomilast’s use in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

Toby Maher, MD, PhD

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