This week’s respiratory update brings together recent clinical readouts, regulatory decisions, and strategic pivots across respiratory and inflammatory drug development, highlighting how safety, efficacy, and trial design are shaping the next wave of innovation.
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🧬 STAT3 in IPF: safety setback and strategic pivots [1] [US • 05 Dec 2025]
Context: Accendatech comments on a Phase 2 STAT3 inhibitor safety issue in IPF and surveys alternative approaches.
Key point: Company highlights toxicity risk with transcription-factor targets, and points to TNIK inhibition and ACT001 natural-compound strategy as contrasting paths (endpoints not specified).
Implication: Partnerships/BD. Signals pipeline investment and modality expansion.
💊 Glasmacinal first clinical data in COPD published 🫁 [2] [IS • 08 Dec 2025]
Context: Randomized, double-blind, placebo-controlled 12-week trial in stable COPD.
Key point: Well tolerated, reduced neutrophilic inflammation, no detectable microbiome impact; more patients achieved clinically meaningful SGRQ gains vs placebo.
Implication: Observational/RWE. Could inform practice and payer discussions, interpretation depends on study design and confounding control.
🧪 Kamada ends Phase 3 inhaled AAT in AATD after futility [3] [US/IL • 08 Dec 2025]
Context: DSMB interim analysis in InnovAATe indicated low likelihood of FEV1 benefit.
Key point: Trial discontinued for efficacy futility, not safety; company reiterates 2025 revenue and EBITDA guidance and ongoing GLASSIA supply.
Implication: Clinical topline/efficacy. May influence prescriber choice and payer reviews pending full data.
🧫 BiomX stops BX004 CF Phase 2b after AE signal and review [4] [IL • 08 Dec 2025]
Context: Internal analysis and DMC feedback after earlier safety review.
Key point: Discontinuation due to unexpectedly high AEs and resource constraints; shift toward BX011 in DFI and company-wide cost reductions.
Implication: Clinical topline/efficacy. May influence prescriber choice and payer reviews pending full data.
🌿 Deupirfenidone clears EOP2, heads to Phase 3 SURPASS-IPF [5] [US • 08 Dec 2025]
Context: FDA EOP2 supports a single pivotal, head-to-head trial vs pirfenidone, 505(b)(2) pathway.
Key point: Primary endpoint FVC change at Week 52, adults not on background therapy; ELEVATE-IPF Phase 2b data underpin program.
Implication: Clinical topline/efficacy. May influence prescriber choice and payer reviews pending full data.
🫀 FDA clears Phase IIb of CS1 in PAH (dose finding) [6] [08 Dec 2025]
https://cerenoscientific.com/press-single/?releaseIdentifier=008944355F62DA91
Context: Orphan and US Fast Track; multicenter, global, ~126 patients on background therapy.
Key point: 36-week primary period with PVR at Week 36 and 6MWD, then re-randomization to assess durability; FPI planned Q2 2026.
Implication: Clinical topline/efficacy. May influence prescriber choice and payer reviews pending full data.
🇨🇳 Nerandomilast first approval in PPF in China 🎉 [7] [CN • 10 Dec 2025]
Context: NMPA approval for JASCAYD in PPF, second CN indication after IPF.
Key point: FIBRONEER-ILD met primary endpoint of FVC change at Week 52; favorable safety without liver monitoring requirement.
Implication: Regulatory/generics. Introduces competition that may affect pricing and formulary access.
🌱 Enveda starts parallel Phase 2a in AD and asthma [8] [US • 09 Dec 2025]
Context: Move follows interim Phase 1b AD signal of robust efficacy and favorable safety.
Key point: First-in-class oral small molecule targeting a non-kinase inflammatory pathway, with Phase 2b planned in 2026.
Implication: Clinical topline/efficacy. May influence prescriber choice and payer reviews pending full data.
🧷 GRI-0621 Phase 2a topline positive in IPF [9] [US • 10 Dec 2025]
Context: 12-week randomized, placebo-controlled study, n=35.
Key point: Primary safety met, biomarker improvements suggest fibrosis resolution and basement-membrane repair; exploratory FVC increases reported.
Implication: Clinical topline/efficacy. May influence prescriber choice and payer reviews pending full data.
🧴 Quince highlights eDSP early studies in pulmonary and IBD [10] [US • 10 Dec 2025]
Context: Frontiers in Drug Delivery publication summarizing eight trials across COPD, CF, CD and UC.
Key point: Autologous RBC encapsulation enabled low-dose steroid delivery with persistence and reduced typical steroid toxicities, with signs of efficacy across indications.
Implication: Partnerships/BD. Signals pipeline investment and modality expansion.
Why it matters
Approvals and late-stage readouts in fibrosing lung disease are accelerating, with nerandomilast setting a new benchmark in PPF access in China [7].
Program discontinuations in AATD and CF underscore safety and efficacy hurdles in respiratory innovation and the value of robust interim governance [3][4].
Diverse modalities, from deuterated antifibrotics to epigenetic modulators and autologous RBC carriers, broaden options for IPF, PAH and inflammatory comorbidities [5][6][10].
Oral, non-biologic anti-inflammatory strategies could shift adherence and access dynamics in COPD, AD and asthma if signals hold in larger studies [2][8].
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FAQ
What is deupirfenidone’s Phase 3 design in IPF?
A global, randomized, double-blind, head-to-head trial vs pirfenidone, primary endpoint FVC change at Week 52. FDA feedback supports a 505(b)(2) path and a single pivotal if successful [5].
Why did Kamada stop its inhaled AAT Phase 3?
A DSMB futility analysis indicated low probability of FEV1 primary endpoint success. The decision was not driven by safety; commercial guidance was reiterated [3].
What ended BiomX’s BX004 CF trial?
Unexpectedly high adverse events and resource constraints following DMC input led to discontinuation. BiomX will prioritize BX011 for S. aureus in DFI and reduce costs [4].
What did EpiEndo’s EP395 COPD trial show?
In a 12-week RCT, glasmacinal reduced neutrophilic inflammation, was well tolerated, and did not perturb the lung microbiome. More patients improved on SGRQ vs placebo [2].
What is CS1 aiming to show in PAH?
A Phase IIb dose-finding study will assess PVR at Week 36 and 6MWD, on top of standard therapies, to inform Phase 3 dose and potential disease-modifying activity [6].
What exactly was approved for PPF in China?
JASCAYD, nerandomilast, a preferential PDE4B inhibitor, based on FIBRONEER-ILD meeting its FVC primary endpoint and showing favorable safety. Additional reviews are ongoing globally [7].
Entities / Keywords
Accendatech; STAT3; NF-κB; TNIK; ACT001 • EpiEndo Pharmaceuticals; glasmacinal; EP395; COPD; neutrophilic inflammation; SGRQ • Kamada; InnovAATe; inhaled AAT; AATD; FEV1 • BiomX; BX004; cystic fibrosis; Pseudomonas aeruginosa; BX011; DFI • PureTech Health; Celea Therapeutics; deupirfenidone; LYT-100; IPF; SURPASS-IPF; 505(b)(2) • Cereno Scientific; CS1; HDAC inhibitor; PAH; PVR; 6MWD • Boehringer Ingelheim; JASCAYD; nerandomilast; PPF; FIBRONEER-ILD; NMPA • Enveda; ENV-294; atopic dermatitis; asthma; oral anti-inflammatory • GRI Bio; GRI-0621; IPF; biomarkers; FVC • Quince Therapeutics; eDSP; dexamethasone sodium phosphate; autologous erythrocytes; COPD; CF; IBD.
References
- https://www.globenewswire.com/news-release/2025/12/05/3200737/0/en/Accendatech-US-comments-on-the-recent-setback-in-phase-2-study-to-evaluate-STAT3-as-therapeutic-target-and-other-drug-development-strategies-such-as-AI-and-precision-medicine-to-tr.html
- https://www.epiendo.com/en/news-events/erj-open-research-article-reports-first-clinical-trial-of-glasmacinal-ep395-in-copd-patients
- https://www.kamada.com/news/kamada-announces-discontinuation-of-its-phase-3-inhaled-aat-clinical-trial-reiterates-2025-full-year-guidance-and-projects-double-digit-growth-in-revenues-and-profitability-in-2026/
- https://ir.biomx.com/news-releases/news-release-details/biomx-announces-discontinuation-phase-2b-bx004-trial-following
- https://www.businesswire.com/news/home/20251207891734/en/PureTech-Announces-Successful-End-of-Phase-2-Meeting-with-FDA-for-Deupirfenidone-LYT-100-in-Idiopathic-Pulmonary-Fibrosis
- https://cerenoscientific.com/press-single/?releaseIdentifier=008944355F62DA91
- https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/jascayd-nerandomilast-first-regulatory-approval-ppf-china
- https://www.businesswire.com/news/home/20251209287981/en/Enveda-Initiates-Phase-2-Clinical-Trials-of-ENV-294-a-First-in-Class-Oral-Therapy-in-Atopic-Dermatitis-and-Asthma
- https://gribio.com/gri-bio-announces-positive-topline-data-from-its-phase-2a-study-in-idiopathic-pulmonary-fibrosis-ipf/
- https://ir.quincetx.com/news-releases/news-release-details/quince-therapeutics-announces-publication-use-edsp-early-stage