IPF pipeline heats up: Boehringer preps NDA, Refoxy raises $9.58M

Refoxy Pharma has raised €9.1 million ($9.58 million) to push a preclinical FOXO3-targeting candidate into the clinic by 2027, part of a wider wave of idiopathic pulmonary fibrosis (IPF) programs now moving through funding rounds and late-stage trials.

The Cologne-based biotech's round, led by the Boehringer Ingelheim Venture Fund, will accelerate development of RP-01, designed to activate FOXO3 — what CEO and co-founder Victor Bustos calls a "pivotal master regulator of healthy aging." Refoxy identified the candidate with its proprietary F.act Finder platform, which integrates cellular, biochemical and bioinformatics assays.

The stakes are high. The FDA has approved only two IPF drugs — nintedanib (Boehringer's Ofev) and pirfenidone (Roche's Esbriet) — and neither reverses or halts disease progression, Bustos noted. Existing therapies also carry side effects that drive high discontinuation rates. According to the National Institutes of Health, FOXO3 plays a key role in fibrogenesis, the tissue-repair mechanism that turns pathological under prolonged injury.

"While it is still early in development, our data suggest we are on the right track, and underscores a potentially novel angle to tackle IPF," Bustos said.

Which candidate is closest to market?

Boehringer Ingelheim plans to submit an NDA for nerandomilast, an oral phosphodiesterase 4B inhibitor, with the FDA and other regulators after the drug hit the primary endpoint of a phase 3 trial in September — absolute change from baseline in Forced Vital Capacity (FVC) at week 52 versus placebo. Approval would put it in competition with the incumbent Ofev and Esbriet.

The field is littered with prior failures: pamrevlumab (FibroGen), ziritaxestat (Galapagos/Gilead) and GB0139 (Galecto) were all scrapped in late-stage trials, and Novartis and Amgen recently dropped mid-stage programs for LTP001 and fipaxalparant, respectively.

What does the phase 2 data show?

Several biotechas report positive mid-stage results:

• Insilico Medicine's ISM001-055, an AI-discovered TNIK inhibitor, showed dose-dependent FVC improvement after 12 weeks in a phase 2a study in China enrolling 71 patients, per Fierce Biotech.
• Endeavor BioMedicines' ENV-101, a hedgehog pathway inhibitor, produced a 1.9% mean FVC improvement from baseline versus a 1.3% decline on placebo, and reversed quantitative lung fibrosis (QLF) and QILD measures. A $132.5 million series C in May funds further development.
• Vicore's buloxibutid, which targets the renin-angiotensin system, hit both primary and secondary FVC endpoints in phase 2a. The Swedish biotech raised SEK 782 million ($71.20 million) in October and licensed Japan rights to Nippon Shinyaku for $10 million upfront and up to $275 million in milestones.
• Bristol Myers Squibb's BMS-986278, an LPA1 antagonist, reduced the FVC decline rate by 69% versus placebo over 26 weeks at 60 mg twice daily in phase 2, earning the first FDA Breakthrough Therapy Designation of its kind. Phase 3 is ongoing.
• Pliant Therapeutics' bexotegrast, a dual αvβ6/αvβ1 integrin inhibitor that blocks TGF-β activation, decreased total lung collagen on PET imaging versus an increase on placebo after 12 weeks in phase 2a, and alleviated chronic cough. It holds FDA Orphan Drug and Fast Track designations plus EMA Orphan Drug status.

Where is the money going?

Funding continues to flow across modalities. Surrozen and The Column Group's TCGFB signed a $6 million deal to discover TGF-β-targeting antibodies. "We look forward to working with TCGFB to discover antibodies targeting TGF-β as a potential novel, first-in-class therapeutic approach," CEO Craig Parker said.

Arda Therapeutics raised $43 million last month from Eli Lilly and other investors to test antibody-drug conjugates in fibrosis. "Arda is taking the 'oncology toolbox' outside of oncology," said Andreessen Horowitz general partner Vineeta Agarwala. Founder and CEO Adam Freund argued that targeting cells rather than pathways "offers a transformative shift in how chronic diseases are treated."

Contineum Therapeutics, which IPO'd in April for $108 million, will advance its LPA1R antagonist into a phase 1b study.

With IPF affecting roughly 3 million people worldwide and the two approved drugs unable to stop disease progression, the next test for this pipeline is whether nerandomilast's approval — and the phase 3 readouts behind it — can finally convert a decade of target diversity into sustained clinical benefit.