Nuformix plc (LON:NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, has provided a further update on NXP002, the Company’s lead programme and a potential novel inhaled treatment for Idiopathic Pulmonary Fibrosis (IPF), Progressive Pulmonary Fibrosis (PPF) and other progressive fibrosing interstitial lung diseases (ILDs).
Highlights
- Further positive results from NXP002’s pilot inhaled target engagement study, demonstrating statistically significant modulation of TGF-β/SMAD signalling, a clinically relevant pathway central to pulmonary fibrosis progression.
- Pronounced suppression of pSMAD/SMAD observed at the lowest dose studied, with statistically significant reductions at multiple timepoints across three dose levels, strengthening evidence of fibrosis-relevant pathway engagement following inhalation of NXP002.
- New findings complement previously reported positive α-SMA results, providing a second, distinct biological readout and further supporting the relationship between inhaled dose, pulmonary exposure and fibrosis-relevant biological activity.
- Combined results strengthen the development rationale for NXP002 and help define dose ranges for subsequent studies as the programme progresses towards IND-enabling studies.
- An expert advisory board is being convened to provide strategic guidance for the next phase of development.
- Prospective partnering discussions continue following meetings at the European Respiratory Society Congress, with the Company sufficiently capitalised to complete its currently planned development programme.
As previously announced, the Company is undertaking a focused programme of preclinical studies to advance NXP002 towards subsequent development stages and address specific questions arising from discussions and due diligence with prospective development and licensing partners.
The Company is pleased to report further positive results from its pilot inhaled target engagement study, designed to assess the relationship between inhaled dose, pulmonary and systemic exposure and engagement of fibrosis-relevant biology in vivo.
Initial results demonstrated substantial pulmonary exposure to NXP002 and attenuation of bleomycin-induced expression of alpha-smooth muscle actin (“α-SMA”), a biomarker associated with activated myofibroblasts and the fibrotic lung phenotype.
Further analysis has now assessed phosphorylated SMAD2/3 relative to total SMAD2/3 (“pSMAD/SMAD”), a well-established mechanistic readout of canonical transforming growth factor beta (“TGF-β”) signalling. Pulmonary pSMAD has previously been used in human clinical studies as a pharmacodynamic measure of TGF-β pathway engagement and represents a validated endpoint, predictive of clinical efficacy.
TGF-β is recognised as a central driver of fibrosis, with pathway modulation considered an important component of therapeutic strategies targeting fibrotic disease. Clinical-stage therapeutics targeting TGF-β activation have demonstrated effects on lung-function decline in patients with IPF, although safety concerns have also led to discontinuation of development. This highlights both the clinical relevance of the pathway and the importance of balancing efficacy and safety.
The new results demonstrate that:
- bleomycin challenge produced a substantial increase in the pSMAD/SMAD ratio, consistent with activation of pro-fibrotic TGF-β/SMAD signalling and the observed increase in α-SMA expression;
- inhaled NXP002 produced statistically significant reductions in the pSMAD/SMAD ratio at multiple timepoints across the three dose levels studied;
- a pronounced response was observed at the lowest dose, providing important information to guide dose selection for subsequent development studies; and
- the pSMAD/SMAD findings provide a second, complementary line of evidence that inhaled NXP002 modulates fibrosis-relevant biology in vivo.
These readouts reflect different levels of fibrosis biology: pSMAD/SMAD measures TGF-β pathway signalling, while α-SMA reflects the downstream activated myofibroblast phenotype associated with fibrotic tissue remodelling. Their consistent responses strengthen the Company’s evidence of pathway engagement following inhaled NXP002 administration.
The new findings also provide mechanistic support for the Company’s broader evidence base indicating that NXP002 may act across multiple processes involved in fibrotic disease. Previous studies have identified effects associated with other fibrosis-relevant pathways, including WNT/β-catenin and NLRP3. The Company believes this broader pharmacological profile may offer important differentiation from approaches focused on individual fibrosis pathways.
NXP002 is being developed as an inhaled form of tranilast, a drug with an extensive history of oral clinical use and evidence of anti-fibrotic activity across multiple organ systems. Historical clinical data include evidence consistent with fibrosis resolution and restoration of tissue function. The inhaled approach aims to exploit this pharmacology through direct lung delivery while addressing the pharmacokinetic, tolerability and physicochemical limitations associated with chronic oral administration.
Combined with previously generated pulmonary and systemic exposure data, the results are helping define biologically rational dose ranges, inform further development and support ongoing discussions with potential development partners.
The Company is convening an expert advisory board to review the emerging NXP002 data package and advise on the design and prioritisation of future activities, with a view to progressing towards IND-enabling studies.
In parallel, work has commenced using an innovative target discovery platform to probe for further specific molecular targets underlying NXP002’s anti-fibrotic activity. Updates will be provided as appropriate.
The Company held meetings with prospective development and licensing partners at the recent European Respiratory Society Congress in Barcelona. Discussions continue to progress, supported by the latest results.
Commenting, Dr Dan Gooding, Executive Director of Nuformix, said:
“We are extremely pleased with these results. Modulation of TGF-β/SMAD signalling is precisely the mechanistic evidence we wanted this pilot study to generate, and it is particularly encouraging to see a pronounced, statistically significant response even at the lowest dose studied.
“The significance extends beyond another positive biomarker response. TGF-β signalling is central to fibrotic disease progression, and previous therapies targeting this pathway have demonstrated clinical efficacy signals in IPF. However, they have also highlighted the challenge of achieving an acceptable benefit-risk profile.
“We believe NXP002 offers an attractive opportunity in this respect, combining tranilast’s well-characterised history of safe oral clinical use and substantial anti-fibrotic evidence base with an inhaled approach designed to achieve pharmacologically active lung concentrations while limiting systemic exposure. Its potential multi-pathway influence on fibrosis biology could offer further differentiation as a future therapy.
“Importantly, we are now connecting critical elements of the NXP002 development story: activity demonstrated in human IPF lung tissue, therapeutically relevant pulmonary exposures following inhalation, and consistent modulation of both pathway-level signalling and downstream fibrosis-relevant biology in vivo. This strengthens our confidence in NXP002’s development potential and provides a rational basis for dose selection — a key question from prospective partners — and subsequent studies.
“We look forward to progressing into the next phase of development, guided by our expert advisory board, and further target discovery work. Our discussions with prospective partners following ERS in Barcelona have also been encouraging, with these latest results strengthening the supporting data package.
“With the Company sufficiently capitalised to complete its currently planned programme of work, I look forward to reporting further progress as we advance NXP002.”
