Respiratory Today—November 14, 2025

LucidQuest

4 days ago

Explore this week’s respiratory highlights, including Phase 3 starts, Phase 2b expansions, protocol filings, and early signals across TB, PAH, IPF, and NTM.

In Today’s Newsletter

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🧪 Otsuka starts dosing in QUANTUM-TB Phase 3 for MDR-TB [1] [PH • 06 Nov 2025]

https://www.otsuka.co.jp/en/company/newsreleases/2025/20251106_1.html
Context: Randomized study in adults and adolescents ≥14 years across >30 sites globally, including Japan; ClinicalTrials.gov NCT07209761.
Key point: First participants enrolled and dosed in Phase 3 comparing quabodepistat-based regimens vs WHO standards in MDR-TB, including FQ-sensitive (17 weeks) and FQ-resistant (26 weeks) cohorts.
Implication: May influence prescriber choice and payer reviews pending full data.

🫁 Rein’s LTI-03 preprint shows biomarker reductions and AT2 cell preservation in IPF [2] [US • 06 Nov 2025]

https://ir.reintx.com/news-releases/news-release-details/rein-therapeutics-announces-new-scientific-publication
Context: Clinical and translational findings posted on medRxiv for IPF; supports ongoing global Phase 2 RENEW trial.
Key point: Inhaled, dose-escalation study reported LTI-03 was generally well tolerated with reductions in fibrosis-associated biomarkers and preservation of AT2 progenitor cells (endpoint specifics not stated).
Implication: May influence prescriber choice and payer reviews pending full data.

🤝 AN2 Therapeutics collaborates with GSK on boron-based LeuRS inhibitors for TB [3] [US • 10 Nov 2025]

https://investor.an2therapeutics.com/news-releases/news-release-details/an2-therapeutics-announces-research-collaboration-gsk-advance
Context: LeuRS target underpins epetraborole, ganfeborole and tavaborole; partnership leverages AN2’s boron chemistry platform.
Key point: Collaboration to advance LeuRS-targeting compounds for TB, with Gates Foundation providing a third year of funding support.
Implication: Partnerships/BD. Signals pipeline investment and modality expansion.

📝 Cereno submits CS1 Phase IIb PAH protocol to FDA [4] [US • 10 Nov 2025]

https://cerenoscientific.com/press-single/?releaseIdentifier=2900BB5F3B0832FF
Context: Builds on Phase IIa signals for reverse vascular remodeling and right heart function; ODD in US/EU and US Fast Track in Aug 2025.
Key point: FDA submission for global, multicenter, placebo-controlled Phase IIb of oral HDAC inhibitor CS1 in PAH; design aligned with recent Type C feedback.
Implication: May influence prescriber choice and payer reviews pending full data.

🧫 BioVersys BV100 Phase 2b to run via ADVANCE-ID network funded by Wellcome [5] [EU • 10 Nov 2025]

https://ir.bioversys.com/news/bioversys-bv100-phase-2b-to-be-conducted-via-wellcome-funded-trial-network/399f93ee-c099-4eda-a194-506deff83447
Context: Non-dilutive support from Wellcome; sites across Southeast Asia; combinations include BV100 with ceftazidime/avibactam or cefiderocol vs best available therapy.
Key point: ADVANCE-ID/NUS will conduct an open-label randomized Phase 2b in CRAB infections, expanding Part A to 90 evaluable patients with 3 arms; interim readout planned H2 2026.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.

🇰🇷 GSK Korea marks Nucala autoinjector launch with internal event [6] [KR • 06 Nov 2025]

http://www.bokuennews.com/news/article.html?no=268562
Context: Highlights device ease of use and patient-preference themes; cites high self-administration success rate (numerics not restated here).
Key point: Company event commemorated availability of mepolizumab autoinjector for SEA, EGPA and HES, emphasizing self-administration convenience.
Implication: DTC/telehealth. Could streamline initiation and adherence via remote prescribing and logistics.

🛑 MannKind stops Phase 3 ICoN-1 for nebulized clofazimine in refractory NTM [7] [US • 10 Nov 2025]

https://investors.mannkindcorp.com/news-releases/news-release-details/mannkind-provides-update-phase-3-icon-1-trial-nebulized
Context: Multi-national, randomized, double-blind study in MAC-NTM on top of guideline therapy; DPI clofazimine MNKD-102 remains under consideration.
Key point: Trial discontinued for futility after no sputum culture conversions among first 46 completers; DSMB noted no safety concerns.
Implication: May influence prescriber choice and payer reviews pending full data.

🧠 CalciMedica preclinical data support CRAC/Orai1 inhibitor CM5480 in PAH [8] [US • 12 Nov 2025]

https://ir.calcimedica.com/news-releases/news-release-details/calcimedica-announces-publication-jci-insight-preclinical-data
Context: JCI Insight paper co-authored with Inserm and Université Paris-Saclay investigators; mechanism aligns with Auxora platform.
Key point: In MCT-rat PAH, CM5480 improved RVSP, PVR, RV hypertrophy and remodeling; combos with ambrisentan or sildenafil outperformed monotherapy.
Implication: May influence prescriber choice and payer reviews pending full data.

Why it matters

MDR-TB programs are advancing with both novel regimens and target-specific small molecules, spanning industry partnerships and late-stage trials [1][3][5].
Self-administration and device options continue to expand in eosinophilic diseases, potentially improving adherence and access [6].
Setbacks in NTM underscore modality and formulation differentiation, informing future inhaled anti-infective strategies [7].
PAH innovation is diversifying from hemodynamics-focused SOC to epigenetic and calcium-signaling approaches with combo potential [4][8].

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FAQ

What is quabodepistat and what is QUANTUM-TB testing?

Quabodepistat is an investigational MDR-TB agent. QUANTUM-TB is a randomized Phase 3 comparing shorter quabodepistat-based regimens vs WHO standards in FQ-sensitive and FQ-resistant MDR-TB across global sites, with first patients dosed in the Philippines [1].

What did Rein’s LTI-03 study show in IPF?

A medRxiv preprint reports LTI-03 was generally well tolerated, with reductions in fibrosis-associated biomarkers and signals of AT2 cell preservation, supporting the ongoing Phase 2 RENEW study (endpoint specifics not stated) [2].

How are AN2 and GSK collaborating in TB?

They will advance boron-based LeuRS inhibitors for TB within a collaboration supported by a third year of Gates Foundation funding, building on prior boron-chemistry programs that validate LeuRS as a target [3].

What is Cereno’s CS1 and where is it in development?

CS1 is an oral HDAC inhibitor for PAH. Cereno submitted a global Phase IIb protocol to the FDA, aligned to Type C feedback, following Phase IIa signals in remodeling and right heart function; it holds ODD in US/EU and US Fast Track [4].

Why was MannKind’s ICoN-1 stopped?

A futility assessment found no sputum culture conversions among the first 46 completers. The DSMB agreed with discontinuation and noted no safety issues. The DPI clofazimine program MNKD-102 remains under consideration [7].

What does CalciMedica’s CM5480 paper add in PAH?

In an animal PAH model, selective Orai1/CRAC inhibition improved pulmonary vascular remodeling and RV function, and enhanced effects in combination with ambrisentan or sildenafil, supporting a potential new mechanism in PAH [8].

Entities / Keywords

Otsuka; quabodepistat; QUANTUM-TB; MDR-TB • Rein Therapeutics; LTI-03; Caveolin-1; IPF; RENEW • AN2 Therapeutics; GSK; boron chemistry; LeuRS; tuberculosis • Cereno Scientific; CS1; HDAC inhibitor; PAH; FDA Type C • BioVersys; BV100; rifabutin formulation; CRAB; ADVANCE-ID; Wellcome; NUS • GSK Korea; Nucala; mepolizumab; autoinjector; SEA; EGPA; HES • MannKind; MNKD-101; MNKD-102; ICoN-1; NTM; MAC • CalciMedica; CM5480; Orai1; CRAC channel; Auxora; JCI Insight; PAH.