First-in-Class AT2R Antagonist TRD205 Enters Phase II

Beijing Tide Pharmaceutical Co., Ltd., a division under Sino Biopharmaceutical Limited, has reached a significant milestone in medical innovation with the successful initial dosing of a patient in their Phase II clinical trial for TRD205, a groundbreaking analgesic drug. TRD205 is a highly selective antagonist of the angiotensin II type 2 receptor (AT2R), which presents a novel approach to treating chronic post-surgical neuropathic pain (CPSP). This achievement marks it as the first drug of its kind globally to progress to this advanced stage of clinical development.

The medical community faces substantial challenges in managing CPSP, which affects roughly 10% of individuals who undergo surgery worldwide, equating to over 30 million new cases annually. Traditional treatments, such as opioids, are only effective for a quarter of these patients and come with significant risks, including addiction and depression. Non-opioid options, like NSAIDs and antidepressants, often fall short in effectively managing neuropathic pain. TRD205's innovation addresses these shortcomings by specifically targeting the AT2R pathway. Normally, when this receptor is abnormally activated following nerve injury, it prompts macrophages to release reactive oxygen and nitrogen species, increasing calcium influx in dorsal root ganglion sensory neurons and heightening pain sensitivity. TRD205 precisely blocks this pathway, reducing pain at its origin without involving the central nervous system, thus steering clear of the traditional risks associated with opioids, such as addiction and respiratory issues.

Both the U.S. FDA and China's NMPA have approved TRD205 for clinical trials, and initial Phase I trials in healthy Chinese volunteers have demonstrated a promising safety and pharmacokinetic profile.

CPSP is a public health concern characterized by pain persisting for more than three months post-surgery. It is particularly common following certain surgeries, such as limb amputations, thoracotomies, breast surgeries, and hernia repairs, with prevalence rates varying significantly. Beyond the physical pain, CPSP can lead to anxiety, depression, and other psychological symptoms. Currently available treatments meet less than 30% of clinical needs in this area, highlighting the necessity for innovative treatments like TRD205 that do not rely on opioids. The ongoing Phase II study aims to enroll 184 CPSP patients to assess improvements in pain scores over a six-week period across various dosage groups.

The market potential for TRD205 is significant, as the global development of AT2R-targeted drugs is still in its infancy, with few competitors like Lilly's CFTX-1554 currently in Phase I trials. Approval of TRD205 would mark it as the first AT2R therapy available for CPSP, with promising expansion possibilities into other conditions such as diabetic neuropathy and postherpetic neuralgia. These combined markets represent a substantial opportunity, exceeding $10 billion.

The initiation of TRD205’s Phase II trials signifies a critical shift from reliance on opioid-based pain management to more precise molecular targeting. If clinical validation is successful, this drug could revolutionize treatment options for millions of patients worldwide, establishing a new standard in non-opioid analgesic therapies.