ACT-001(Accendatech)

BOSTON, Dec. 05, 2025 (GLOBE NEWSWIRE) -- A recent setback due to unexpected safety concern from a phase 2 study to evaluate a STAT3 inhibitor in IPF patients refreshed an old debate regarding the feasibility to develop therapeutics targeting tricky transcriptional factors such as STAT3 and NF-kB that are involved in numerous aspects of physiologic and pathological processes. Toxicity is one of major bottlenecks in this area due to the elusive therapeutic windows for this class of therapeutic agents based on comment from Accendatech US Corporated Company, the source of current press release. In the era of LLM-assisted drug development, a new approach was adopted to tackle the same disease such as IPF as shown in the fast pace of target validation and assessment of a TNIK inhibitor by Insilico Medicine which exhibited an impressive safety profile and short-term efficacy signal. Another approach is to focus on the natural structures that have interesting pharmacological properties that may not be easily identified in totally synthesized compounds. For instance, ACT001 was developed based on a natural compound called parthenolide and evaluated for its therapeutic potential in patients with IPF and Fibrosing-ILD (F-ILD). The proposed MoA is its simultaneous inhibition of STAT3 and NF-κB pathways which are involved in pathological processes of IPF and ILD degenerative. Robust enrollment was noted partially due to its good tolerability either as a single agent or in combination with anti-fibrotic agents. On the efficacy side, 38% or 11 out of 29 evaluable IPF patients exhibited non-progression disease after taking ACT001 for 12 months as defined by at least 0 or positive FVC% Pred (the ratio increased to 45% if an FVC% Pred decline of 1 is considered as a stable disease indicator as proposed recently). Although the subject size of ILD cohort is smaller for the same study (7 evaluable patients in total), the non-progression rate is even higher: 5 out of 7 F-ILD patients exhibited stable disease as defined the same way as in patients with IPF. Furthermore, ACT001 was also evaluated in a phase 2b trial in SCLC patients with brain metastasis which revealed encouraging intracranial tumor response and overall survival signal. The trial has entered phase 3 stage since September,2025. The data further support the robustness of nature product-based strategy for drug development to treat complicated diseases involving multiple pathways. A more recent development in IPF space is the announcement of a major support from NIH and Three Lakes Foundation for a phase 3 PRECISIONS study to confirm the sensitivity of IPF patient with TOLLIP rs3750920 TT genotype to NAC treatment based on the assumption that these patients are more sensitive to ROS and inflammation intervention, and thus likely become the first precision medicine in degenerative disease6. Interestingly, ACT001 belongs to a class of natural drugs that were shown to activate Nrf2 pathways leading to reduced ROS production. It was proposed that the tissue damage repair during ACT001 treatment is likely due to its impact on ROS production. Contact: Doug Cai info@accendatech.com