WS635, a small molecule innovative drug for the treatment of postoperative delirium, was approved by the FDA for phase Ib/II clinical trials

On January 11, 2023, Eastern Time, Sino-American Huashitong Biomedical Technology (Wuhan) Co., Ltd. (hereinafter referred to as "Huashiton") received an email from the FDA approving its Phase 1 new drug WS635 tablets with completely independent intellectual property rights to carry out a Phase Ib/II clinical study for postoperative delirium (POD).

About postoperative delirium

Postoperative delirium (POD) is one of the most serious complications of anesthesia plus surgery, occurring in 15 to 50 percent [1], and in the intensive care care population as high as 70 to 80 percent throughout hospitalization [2]. POD is a state in which patients experience acute fluctuations in consciousness, orientation, memory, perception, and behavior, which may lead to longer hospital stays, doubling mortality, and permanent but subtle memory loss and cognitive deficits in daily life, especially in older populations [3].

There is currently no effective drug treatment for POD and is a clinically urgent drug development area [4]. Commonly used preventive measures include identifying high-risk patients and developing an individualized intraoperative anesthesia management plan for older patients (e.g., avoiding large fluctuations in blood pressure, maintaining normal temperature, ensuring adequate analgesia, and monitoring depth of anesthesia); In terms of drug management, there are limited efficacy data for clinical use, and they are often treated with antipsychotics, particularly haloperidol and atypical antipsychotics (olanzapine, quetiapine, risperidone), and to date, no drugs have been approved by the FDA for the prevention and treatment of postoperative delirium.

About WS635

WS635 is a high-affinity non-immunosuppressive inhibitor of cyclophilin A and D and a functional enhancer of mitochondria. WS635 is uniquely designed to completely remove derivatives of immunosuppressive signaling pathways by double substitution at positions 3 and 4 of CsA (cyclosporine A), and its activity on peptidyl proline cis- trans-isomerase A and D is similar to CsA, both highly active PPIase enzyme inhibitors. In vitro studies have shown that WS635 rapidly regulates the ATP metabolism level of mPTP in mitochondria by inhibiting the activity of cyclin D (CypD). In vivo pharmacodynamic collaboration with the Department of Anesthesiology at Harvard Medical School and the POD group at Massachusetts General Hospital has shown that WS635 can significantly improve anesthesia/surgery-induced delirium-like or amnesia and cognitive impairment behavior in elderly and young mice, and its mechanism of action may be related to enhancing ATP concentration and synaptic marker (PSD-95) levels in brain tissue. Huaston owns the global rights to WS635 and has an extensive patent layout for compound crystal forms and new indications. WS635 has completed 5 clinical trials (4 phase I clinical studies and 1 phase IIa clinical study) in the early stage of liver disease indications, which proves the safety of the drug. With the FDA's clinical approval, the Company will conduct a Phase II/III POD clinical study following the Phase Ib bridging trial in healthy older adults.