SBP GROUP - VOLUNTARY ANNOUNCEMENT - TRD205 "AT2R ANTAGONIST" GRANTED THE CDE'S BREAKTHROUGH THERAPY DESIGNATION

(Incorporated in the Cayman Islands with limited liability) Website: www.sbpgroup.com (Stock code: 1177)

VOLUNTARY ANNOUNCEMENT TRD205 "AT2R ANTAGONIST" GRANTED THE CDE'S

BREAKTHROUGH THERAPY DESIGNATION

The board of directors (the "Board") of Sino Biopharmaceutical Limited (the "Company", together with its subsidiaries, the "Group") announces that TRD205 "AT2R antagonist", a National Category 1 innovative drug independently developed by Beijing Tide Pharmaceutical Co., Ltd. ("Beijing Tide"), a subsidiary of the Group, has completed a Phase II clinical trial for chronic post-surgical neuropathic

pain (CPSNP). Based on the positive results of this trial, TRD205 has been granted the Breakthrough Therapy Designation by the Centre for Drug Evaluation (CDE) of China's National Medical Products Administration.

TRD205 is a highly selective AT2R antagonist developed through the Group's second-generation artificial intelligence (AI)-driven drug discovery platform. During the molecular design phase, this platform employs a "target-driven de novo generation" strategy, which does not rely on any known

ligand structures. Instead, it uses only the three-dimensional geometric features and physicochemical properties of the AT2R target pocket as input, enabling the AI to directly generate entirely new molecules from a vast chemical space. Following generation, the platform applies a multi-layered computational screening cascade to evaluate candidate molecules based on spatial complementarity,

electronic profiles, and core physicochemical attributes. This approach effectively eliminates, prior to chemical synthesis, a substantial number of molecules that fail to meet the target-binding criteria or fall outside the predefined property boundaries.

The core innovation of TRD205 lies in its highly selective action on peripheral AT2R receptors, achieving multi-modal analgesia through a dual mechanism. On one hand, by inhibiting the migration of macrophages to the site of injury, which is the key to pain, it downregulates the expression of neurotransmitters, reactive oxygen species and inflammatory factors, thereby effectively reducing peripheral sensitization. On the other hand, in animal models, it inhibits the expression of pain-related

ion channels (such as Nav1.8 and TRPV1) in the dorsal root ganglion (DRG), thereby blocking the transmission of neural excitation. As this drug acts solely at the peripheral level, it avoids the central

nervous system-related adverse effects commonly associated with other analgesics, such as somnolence and dizziness. This profile significantly improves the clinical challenge of poor long-term tolerability in

patients with chronic pain, filling a gap in existing treatment options.

CPSNP refers to pain persisting for three months or more following surgery. Among approximately 320 million patients undergoing surgery worldwide each year, around 10% of patients suffer from this condition[1,2]. It is particularly prevalent following procedures such as amputation (50%–85%), open-

chest surgery (30%–50%), breast surgery (25%–50%) and hernia repair (5%–35%)[3]. Currently, there are no specific therapeutic drugs for CPSNP in clinical use, and all of the existing treatment regimens have significant limitations: calcium channel modulators are prone to causing central nervous system adverse reactions such as dizziness and drowsiness, whilst non-steroidal anti-inflammatory drugs (NSAIDs)

and antidepressants/anxiolytics have very limited efficacy against neuropathic pain[4]. Exploring novel mechanism-based approaches to the prevention and management of chronic post-operative pain is of great significance for improving patient outcomes.

TRD205's inclusion in the breakthrough therapy designation is primarily based on a multi-center,

randomized, double-blind, placebo-controlled, parallel-group and dose-exploratory Phase II clinical trial designed to evaluate its efficacy and safety in the treatment of chronic post-operative neuropathic pain. As one of the flagship achievements resulting from translational achievement of the Group's second- generation AI drug discovery platform, TRD205 further validates the practical value of AI technology

in molecular structure generation and candidate screening. The Group will continue to advance the subsequent clinical development of TRD205 and expand its exploration into other chronic pain indications, such as diabetic peripheral neuropathic pain (DPNP), to provide innovative solutions for the treatment of chronic neuropathic pain.

Sources:

[1] Macrae WA, Davies HTO. Chronic postsurgical pain. Epidemiology of pain. Seattle: IASP Press, 1999, 125-142.

[2] Glare P, Aubrey KR, Myles PS. Transition from acute to chronic pain after surgery[J]. Lancet, 2019, 393(10180):1537- 1546.

[3] Badiola IJ. Can chronic pain be prevented? Anesthesiology Clin, 2016，34(2):303-315.

[4] Dinges HC, Otto S, Stay DK, et al. Side effect rates of opioids in equianalgesic doses via intravenous patient-controlled analgesia: a systematic review and network meta-analysis [J]. Anesth Analg. 2019;129(4):1153-1162.

By order of the Board Sino Biopharmaceutical Limited Tse, Theresa Y Y

Chairwoman

Hong Kong, 14 July 2026