Clinical development of HMGB1 peptides for multiple indications

「An additional Phase II clinical trial began in July 2022, dosing of the first patient began in March 2023, patient enrolment was completed in July 2025, and the trial ended in September 2026. The trial achieved closure of refractory ulcers, its primary endpoint, in 3 of 4 patients.」

「Against this backdrop, research and development continued to progress toward the start of new clinical trials for redasemtide, a regenerative medicine product under development (a peptide drug created from HMGB1). Business development activities also continued to progress toward the preclinical development and out-licensing of TRIM3 and TRIM4, second-generation regenerative medicine products following redasemtide.」

「Research and development toward the start of a new clinical trial for the in vivo regenerative medicine candidate Redasemtide continues to progress, along with ongoing work」

「Enrollment of the final patient in the additional Phase 2 clinical trial in July 2025」

「Research and development continued to progress toward the start of new clinical trials for redasemtide, a regenerative medicine product under development (a peptide drug created from HMGB1). Business development activities also continued to progress toward the preclinical development and out-licensing of TRIM3 and TRIM4, second-generation regenerative medicine products following redasemtide.」

「During the cumulative third quarter of the fiscal year, research and development continued to progress for multiple clinical trials and preparations to begin new clinical trials involving redasemtide, a regenerative medicine product under development (a peptide drug created from HMGB1).」

「In March 2024, a Phase 2 investigator-initiated clinical trial began at multiple sites, led by Osaka University Hospital. The primary objective of the trial is to evaluate the efficacy and safety of ragasemtiv? (redasemtide) administered for 5 days to patients with ischemic cardiomyopathy who have undergone coronary artery bypass surgery, with 10 patients each receiving redasemtide or placebo. Among 5 patients who received redasemtide at 1.5 mg/kg body weight once weekly for 4 weeks, for a total of 4 doses, a trend toward improved liver stiffness, measured by MR elastography, was observed 78 and 162 days after treatment initiation. Average reductions from baseline were 12% and 8%, respectively.」

「The start of a Phase II investigator-initiated trial at multiple institutions, centered on Osaka University Hospital, is planned for the first half of 2024.」

「In addition to improvement in liver stiffness measured by MR elastography, multiple cases also showed a tendency toward improvement in other fibrosis indicators, including the fibrosis index, fibrosis markers and the modified HAI fibrosis stage. Based on a comprehensive assessment by the principal investigator incorporating the results of these efficacy measures, the investigator concluded that a tendency toward improvement in liver fibrosis was suggested in 3 of 5 patients (60%) who received retasemtiv at 1.5 mg/kg based on body weight once weekly for 4 weeks, for a total of 4 doses, and in 2 of 5 patients (40%) who received 4 consecutive days of dosing in Week 1 followed by once-weekly dosing in Weeks 2 to 4, for a total of 7 doses.」

「Regarding business results for the cumulative period of the first 3 quarters (1 August 2022 to 30 April 2023), R&D continued to progress toward the start of multiple clinical trials and new clinical trials for retasemtiv, a regenerative medicine drug candidate, a peptide drug created from HMGB1. In April 2023, a milestone related to the development of retasemtiv as a treatment for acute ischemic stroke was achieved, and a milestone payment of ¥2.35 billion was recognized as business revenue in the first 3 quarters.」

「For the development of PJ1-01, a treatment for dystrophic epidermolysis bullosa, an additional Phase II clinical trial began in July 2022, and dosing of the first patient began in March 2023.」

「Because efficacy was also confirmed at the post-study observation point, 52 weeks after the end of administration, following completion of the follow-up study conducted to evaluate maintenance of efficacy, the long-term persistence of the therapeutic effect of retasemtiv in dystrophic epidermolysis bullosa was also confirmed.」

「An additional Phase II clinical trial began in July 2022.」

「Since November 2020, an investigator-initiated Phase II clinical trial in patients with chronic liver disease has been conducted at Niigata University, and patient enrollment was completed in June 2022. Data analysis and evaluation are scheduled to follow a 6-month follow-up period.」

「Shionogi notified the company in December 2021 that the primary endpoint of the Phase II clinical trial had been achieved. The achievement was confirmed, establishing the efficacy of retasemtiv in patients with acute ischemic stroke. For the secondary safety endpoint, the incidence of adverse events was similar in the retasemtiv and placebo groups, confirming tolerability.」

「Because efficacy was also confirmed at the post-study observation point, 12 months after the end of administration, following completion of the follow-up study conducted to evaluate maintenance of efficacy, the long-term persistence of the therapeutic effect of retasemtiv in dystrophic epidermolysis bullosa was also confirmed.」

「A Phase II clinical trial conducted by Shionogi, the licensee of this drug, was under way. Patient enrollment and safety confirmation had progressed smoothly, and in July 2021 enrollment reached and was completed at the target of 150 patients.」

「In November 2020, a Phase II investigator-initiated trial in patients with chronic liver disease was started at Niigata University, and dosing of the first subject began in March 2021.」

「In November 2020, a Phase II investigator-initiated trial in patients with knee osteoarthritis was started at Hirosaki University, a national university corporation, and dosing of the first subject began in February 2021.」

「In November 2020, the company began a Phase II investigator-initiated trial at Hirosaki University, a national university corporation, in patients with knee osteoarthritis.」

「At present, clinical trials have been completed for 1 indication, are under way for 1 indication, and are being prepared for 3 indications.」

「In this clinical trial, the Phase II investigator-initiated trial, preliminary data analysis was published in January 2020. It was reported that the long-term persistence of the therapeutic effect of KOI2 in dystrophic epidermolysis bullosa had been confirmed and that no adverse events of concern were observed in the secondary safety assessment, confirming the safety of KOI2 administration in patients with dystrophic epidermolysis bullosa.」

「An analysis of all 9 patients with dystrophic epidermolysis bullosa who participated in this trial confirmed a statistically significant improvement in the primary endpoint, the rate of change from baseline in the total area of blisters, erosions and ulcers over the entire body, following administration of KOI2. At the final observation after completion of KOI2 administration, 6 months after the end of treatment, 7 of the 9 patients showed improvement below baseline, including 4 patients with marked improvement of 50% or more, confirming the long-term persistence of the therapeutic effect of KOI2 in dystrophic epidermolysis bullosa. In the secondary safety assessment, no adverse events of concern were observed, confirming the efficacy and safety of KOI2 administration in patients with dystrophic epidermolysis bullosa.」

「An investigator-initiated clinical trial (Phase II) was conducted at Osaka University to evaluate clinical efficacy in actual patients, and a follow-up study is currently under way.」

「Clinical trials are currently under way for 2 indications, and preparations for clinical research are under way for 1 indication.」