Redasemtide Clears Ulcer Endpoint in Dystrophic EB but Misses Primary Endpoint in Global Phase 2 Acute Ischemic Stroke Trial
核心洞察
Shionogi and StemRIM (搜索) reported that redasemtide met the primary endpoint of refractory ulcer closure in 3 of 4 patients in an additional Phase 2 trial in dystrophic epidermolysis bullosa (搜索).
The global Phase 2b trial in acute ischemic stroke (搜索) did not achieve its primary endpoint, with no statistically significant improvement in 90-day modified Rankin Scale versus placebo.
Exploratory subgroup analysis suggested an mRS improvement trend in redasemtide-treated patients with higher stroke severity at onset who did not undergo endovascular recanalization therapy.
Shionogi & Co., Ltd. and StemRIM (搜索) Inc. reported topline results from two Phase 2 clinical trials of redasemtide (development code S-005151), a regeneration-inducing medicine® candidate in-licensed from StemRIM, delivering sharply contrasting outcomes across its two lead indications. In an additional Phase 2 trial in patients with dystrophic epidermolysis bullosa (搜索), the primary endpoint of closure of refractory ulcers was met in 3 of 4 patients. In the global Phase 2 trial in acute ischemic stroke (搜索), the drug failed to demonstrate a statistically significant improvement versus placebo on its primary endpoint.
Dystrophic Epidermolysis Bullosa: Ulcer Closure in Three of Four Patients
In the additional Phase 2 trial in dystrophic epidermolysis bullosa (搜索), favorable results were also observed in certain cases for clinical symptoms, including total body ulcer area. No new safety concerns were identified for redasemtide, and tolerability was confirmed to be favorable.
Dystrophic epidermolysis bullosa (搜索) is described by the companies as a serious rare disease with limited effective treatment options. The condition arises from mutations in genes encoding the structural proteins that mediate adhesion between the epidermis and dermis, so that even slight stimulation in daily life causes erosions and blisters on the skin and mucous membranes, significantly affecting daily life. Dystrophic epidermolysis bullosa is the most common form of epidermolysis bullosa, accounting for approximately 50% of all cases. In severe cases, the risk of digital fusion, esophageal stricture, iron-deficiency anemia, and the development of scar cancer also increases. The number of patients with epidermolysis bullosa in Japan is estimated at approximately 500 to 1,000, and there is currently no fundamental treatment.
Shionogi stated that, based on the results obtained in this trial, it will continue discussions with StemRIM (搜索) and relevant parties and will continue to consider its future development policy so that the drug can be delivered as soon as possible to the patients who need it. On StemRIM's fiscal year-end earnings call, President and CEO Masatsune Okajima said, "In some cases, we have obtained favorable results in clinical symptoms including total body ulcer area," and emphasized on safety and tolerability that "no concerns have been identified, and good tolerability has been confirmed." The indication received orphan drug designation in May 2023, and management explicitly stated its intention to file for regulatory approval.
Acute Ischemic Stroke: Primary Endpoint Missed, Signals in Subgroups
In the global Phase 2 trial, the efficacy and safety of redasemtide or placebo were evaluated in patients with acute ischemic stroke (搜索) within 25 hours of onset. In the cohort that did not undergo endovascular recanalization therapy, the primary endpoint was the modified Rankin Scale (mRS) at 90 days after the start of study drug administration, a measure of the degree of prognosis toward returning to social life. The redasemtide group did not show a statistically significant improvement compared with the placebo group, and the trial did not achieve its primary endpoint.
A trend toward improvement in mRS was observed in the redasemtide group in this Phase 2b study, similar to the previous Phase 2 trial conducted in Japan. In the Phase 2b study, an exploratory subgroup analysis suggested a trend toward improvement in mRS in the redasemtide group among patients with higher severity at onset within the cohort that did not undergo endovascular recanalization therapy. The incidence of adverse events was comparable between the redasemtide and placebo groups; no new safety concerns were identified and tolerability was confirmed to be favorable.
Okajima acknowledged the outcome candidly, saying, "Unfortunately, the results showed no statistically significant difference versus the placebo group," while noting that "an mRS improvement trend in the redasemtide group was confirmed, consistent with the Japanese domestic Phase II trial." The low-dose group (0.75 mg/kg) received a discontinuation recommendation at interim analysis, and final evaluation was conducted only in the high-dose group (1.5 mg/kg). Shionogi said it will continue to consider its future policy for acute ischemic stroke (搜索) after conducting a detailed analysis of the results.
Acute ischemic stroke (搜索) occurs when cerebral blood flow decreases due to occlusion or stenosis of a cerebral blood vessel. Treatments include endovascular recanalization therapies such as intravenous thrombolytic therapy using tissue plasminogen activator (t-PA), intra-arterial thrombolytic therapy, and thrombectomy. However, the patients eligible for these treatments are limited, and even when applied, the effect is limited in some patients, so the development of new treatments is anticipated. Thrombolytic therapy is selected within 4.5 hours of onset, and mechanical thrombectomy within 8 hours (within 24 hours if various conditions are met).
Mechanism and Broader Development Program
Redasemtide is a peptide drug created from HMGB1 (搜索), a nuclear protein that recruits mesenchymal stem cells in the body to the affected area. It is a regeneration-inducing medicine® candidate designed to regenerate tissue damaged by injury or disease through drug administration, without using living cells. Leveraging these characteristics, redasemtide is in development in chronic liver disease (搜索), osteoarthritis (搜索), and cardiomyopathy (搜索), in addition to dystrophic epidermolysis bullosa (搜索) and acute ischemic stroke (搜索).
StemRIM (搜索) is a drug-discovery R&D-type biotech company originating from Osaka University, established in 2006 to develop as a pharmaceutical the bone-marrow-derived pluripotent stem cell mobilization factor identified by Professor Katsuto Tamai and colleagues at the Graduate School of Medicine, Osaka University.
Pipeline, Finances, and Organizational Changes
On the earnings call for the fiscal year ended July 2026, StemRIM (搜索) reported business revenue of zero for the second consecutive year, with no milestone revenue or upfront payments recorded. R&D expenses rose 7.5% year on year to ¥1.49939 billion (approximately $9.7 million), a record high, while SG&A expenses declined 13.4% to ¥499.46 million (approximately $3.2 million) due to a decrease in stock-based compensation. Operating loss widened slightly to ¥1.99886 billion, while ordinary loss narrowed to ¥1.87989 billion and net loss narrowed to ¥1.8515 billion. Net loss per share improved to ¥29.63 from ¥31.16.
Cash and cash equivalents at fiscal year-end stood at ¥2.17703 billion (approximately $14.1 million), down ¥4.81756 billion from the prior year-end, though total cash and deposits were ¥5.3 billion (approximately $34.3 million) as of end-July. Okajima said annual cash outflow has remained at approximately ¥1.5 billion (approximately $9.7 million) over the past several years, adding, "We have conservatively stated funding through 2028, but if you do the math, we hold more than three years of cash." The equity ratio declined from 78.0% to 70.4%.
For next-generation candidates, StemRIM (搜索) said it is advancing out-licensing activities with multiple companies in Japan and overseas for the systemically administered novel peptides TRIM3 (搜索) and TRIM4 (搜索), and is expanding disease model animal data for the locally administered TRIM5 (搜索). For the stem cell gene therapy SR-GT1 (搜索), the company reported that technical challenges in large-scale culture have been overcome, with a clinical trial planned for 2028. During the fiscal year, patents related to regenerative medicine were granted in multiple countries, including for redasemtide in Canada, Australia, and Mexico for cartilage diseases; Canada for cardiomyopathy (搜索) and chronic heart failure; Japan and Russia for fatty liver/NASH; and the United States for liver indications. For SR-GT1, multiple patents were granted in Japan and South Korea.
Effective September 9, founder Professor Tamai was promoted from Director and Chief Scientific Officer to Representative Director Chairman and CSO. Okajima explained the rationale: "Given the results of the additional Phase II trial, Professor Tamai's commitment is critically important in delivering an EB treatment to patients as soon as possible." In August, the company also established its purpose — "Empower Life, Regeneration" — along with ten values, and it currently has 70 employees, including 48 full-time and 22 temporary staff.