Sino Bio scores first BTD for an AT2R antagonist in China for neuropathic pain

Sino Biopharmaceutical Limited (HKEX: 01177) announced that TRD205, a peripherally-restricted, highly selective angiotensin II type 2 receptor (AT2R) antagonist developed by its subsidiary Beijing Tide Pharmaceutical Co., Ltd., has received Breakthrough Therapy Designation from China’s National Medical Products Administration Centre for Drug Evaluation (CDE). The BTD relates to the molecule’s potential use in treating chronic post-surgical neuropathic pain (CPSNP). The designation follows completion of a Phase II trial in CPSNP and positions TRD205 as the only AT2R-targeted therapy to reach this regulatory milestone in this indication.

CPSNP — defined as pain persisting three months or more after surgery — affects an estimated 10% of the approximately 320 million patients who undergo surgery globally each year. No approved therapy is specifically indicated for the condition. Existing options, including calcium channel modulators such as gabapentinoids, NSAIDs, and antidepressants, carry meaningful tolerability limitations or demonstrate limited efficacy against neuropathic pain mechanisms.

TRD205 acts selectively on peripheral AT2R receptors through a dual mechanism: it inhibits macrophage migration to injury sites, reducing expression of neurotransmitters, reactive oxygen species, and inflammatory factors, thereby attenuating peripheral sensitization; and, in animal models, it suppresses expression of pain-related ion channels Nav1.8 and TRPV1 in dorsal root ganglia, blocking neural excitation transmission. Because the drug acts exclusively at the peripheral level, it is designed to avoid the CNS-related adverse effects — somnolence, dizziness, and addiction risk — associated with opioids and gabapentinoids.

The CDE Breakthrough Therapy Designation, analogous in intent to the US FDA’s Breakthrough Therapy Designation, is granted when preliminary clinical evidence indicates that a drug may offer substantial improvement over existing therapies on at least one clinically meaningful endpoint. The designation is intended to expedite development and review, including more intensive CDE guidance during the clinical program.

The Phase II basis for the designation was a multi-center, randomized, double-blind, placebo-controlled, parallel-group, dose-exploratory trial enrolling 184 patients with CPSNP, with Numerical Rating Scale (NRS) pain score improvement across dose groups versus placebo over six weeks as the primary endpoint. Sino Bio described the results as positive but has not released specific efficacy numerics in any public filing to date. The Phase II trial was initiated in May 2025, when the first patient was dosed.

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The AT2R antagonist class has no approved members in any major jurisdiction. The closest historical comparator, Novartis’s olodanrigan (EMA401), a selective AT2R antagonist developed for peripheral neuropathic pain, did not advance beyond Phase II and was discontinued. The May 2025 Phase II initiation announcement identified CFTX-1554, co-developed by Confo Therapeutics and Eli Lilly, as a Phase I-stage competitor in AT2R-targeted analgesia, though that program targets a different stage of development and no efficacy data are publicly available for it either.

For Sino Biopharmaceutical, the designation supports the strategic rationale for its AI-driven drug discovery platform. TRD205 was generated using a target-driven de novo molecular generation approach that used only the three-dimensional geometric and physicochemical properties of the AT2R binding pocket as input, without reference to known ligand structures. The company has positioned TRD205 as a validation of that platform’s translational utility.

The company has indicated it will advance TRD205 into subsequent clinical development and intends to explore additional chronic pain indications, specifically diabetic peripheral neuropathic pain (DPNP). Both the US FDA and China’s NMPA have previously cleared Investigational New Drug (IND) applications for TRD205, and Phase I trials in healthy volunteers confirmed a safety and pharmacokinetic profile the company described as favorable. The next meaningful public milestones will be disclosure of the Phase II efficacy and safety data and announcement of Phase III design and timeline.


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