Vicore Pharma Holding AB (publ) announced an updated interim analysis of its AIR phase 2a trial with C21 in idiopathic pulmonary fibrosis (IPF). With 51 patients enrolled, the data demonstrates that C21 has the potential to transform the treatment of IPF and restore lung function. The disease is currently considered to be incurable and inevitably progressive.

C21 continues to be safe and well tolerated with no treatment-related serious adverse events C21 continues to demonstrate long-term efficacy, at 36 weeks the average FVC had increased to +350 mL over baseline, which is +530 mL over the expected trajectory of untreated patients (n= 19; p=0.001). The data will be orally presented at the American Thoracic Society (ATS) international congress on May 21st and during a webcast on May 26th, including a Q&A session. Vicore plans to progress clinical development of C21 through initiation of a phase 2b trial (ANDAS) and will conclude recruitment to the AIR trial.

The AIR trial, a multi-center, open label, single arm 24-week trial with a 12-week extension studying the safety and efficacy of the angiotensin II type 2 receptor agonist (ATRAG) C21 in patients with IPF, has now enrolled 51 patients. At the time of analysis, 27 patients had completed 24 weeks of treatment with an average increase in FVC of +50mL and a 3-visit average increase of +110 mL (p=0.007 versus the expected trajectory of untreated patients), and 19 patients had completed 36 weeks of treatment with an average increase in FVC of +350 mL and a 3-visit average increase of +220 mL (p=0.001 versus the expected trajectory of untreated patients). Out of the 19 patients that had completed 36 weeks of treatment, 17 presented an FVC value that was better than what would have been expected of an untreated population.

The new dataset shows a stabilization of lung capacity already at week 6 and, in line with previous interim analysis, a subsequent increase of FVC from week 16 to 36. Now, with twice the number of patients versus the interim analysis announced in November 2022, the previously reported early stabilization followed by an increase in lung function is confirmed, suggesting that C21 has the potential to transform the treatment of IPF. C21 continued to be safe and well tolerated with no treatment-related serious adverse events; there was a low rate of disease progression or worsening of cough and no gastrointestinal tolerability issues.

94% and 96% of patients at week 12 and 24, respectively, showed a positive benefit/risk, according to a joint benefit/risk assessment by the patients and principal investigator. Recruitment to the AIR trial will be concluded to fully focus on the next step of development, the phase 2b ANDAS trial. Vicore has engaged world leading experts and patient advocacy organizations in its advisory committee to aid in the design and successful conduct of the trial.

Biomarkers further validate C21 results: The clinical findings with FVC have been confirmed with relevant biomarkers, thereby increasing the confidence in C21. FVC correlated strongly with lung volume (p=0.001) as measured in 3D reconstructions of CT scans, reinforcing the accuracy of the FVC measurements. Furthermore, patients with early IPF disease showed significantly less end-terminal fibrosis in the scans (p<0.02) and a higher degree of FVC increase after 36 weeks of treatment compared to patients with established IPF.

This is in line with the C21 mechanism of action, promoting alveolar repair. The biomarker TGFb1 was reduced from baseline by 57% at 24 weeks (n=18), suggesting a reduced fibrosis drive. TGFb1 is a key mediator of fibrosis and its reduction has consistently been seen in cell cultures, animal models as well as in slices of human IPF lung tissue exposed to C21.