Recently, another innovative biopharmaceutical company officially submitted its IPO application to the Hong Kong Stock Exchange. According to disclosures, Zhejiang Shima Pharmaceutical Co., Ltd.-B (Shima Pharma) has filed its main board listing prospectus, with Huatai International acting as the sole sponsor. Prior to this, Shima Pharma successfully completed a CNY 330 million Series C financing in 2022, achieving a post-investment valuation of CNY 2.23 billion, with participation from notable institutions including Beta Pharma, BeiJia Investment, Wens Group, Hangzhou High-Tech Financial Investment, Zhejiang Securities, and MabPlex.
Founded in 2017, Shima Pharma is a pioneer and global leader in next-generation T-cell engager (TCE) therapies, leveraging the human immune system to combat cancer. The company has developed a next-generation masked TCE therapy that can be selectively activated in tumors for treating solid tumors.
Shima Pharma’s capital market debut coincides with the rapid global expansion of the TCE sector. Since the second half of 2024, transaction activity in this field has surged, with international giants intensifying their investments. Against this backdrop, Shima Pharma, with its focus on solid tumor TCE therapies and multiple globally leading clinical pipelines, has naturally drawn significant attention.
**TCE Therapy Pipeline: Four Innovative Drugs in Clinical Stages** Shima Pharma remains in the clinical R&D phase with no commercialized products. Financial data shows other income and gains of CNY 14.649 million, CNY 6.618 million, and CNY 2.278 million in 2023, 2024, and H1 2025, respectively. The company’s financial assets, primarily structured deposits, stood at CNY 216 million, CNY 164 million, and CNY 66.637 million at the end of each period.
Net losses narrowed to CNY 74.943 million, CNY 59.899 million, and CNY 25.42 million over the same periods, while R&D expenses totaled CNY 76.109 million, CNY 53.382 million, and CNY 22.389 million, respectively. Employee costs were the second-largest R&D expense, reaching CNY 2.595 million in H1 2025, with 31 R&D staff averaging a monthly salary of ~CNY 14,000.
Shima Pharma’s pipeline includes four self-developed clinical-stage candidates and two preclinical next-gen multifunctional/logic-gated TCE candidates (CMDE101 and CMDE102), targeting FOLR1×PD-L1×CD3 and PSMA×PD-L1×CD3, respectively.
- **DNV3**: A potential best-in-class LAG3-targeting T-cell modulator (TCM), Shima Pharma’s most advanced candidate, comparable to Bristol Myers Squibb’s approved LAG-3 antibody therapy Opdualag. Opdualag, FDA-approved in 2022, achieved USD 928 million in 2024 sales (+48% YoY), highlighting LAG-3’s commercial potential. Preclinical and clinical data suggest DNV3 may reverse PD-1/PD-L1 inhibitor resistance, with superior T/B-cell binding (20% and 10x higher, respectively) versus existing therapies. In trials, DNV3 combined with anti-PD-1 and chemotherapy showed a 44.4% ORR in PD-(L)1-resistant mucosal melanoma (3x higher than benchmarks) and 66.7% in cutaneous melanoma (5x higher). A Phase II trial for unresectable/metastatic melanoma is ongoing. DNV3 ranks second globally and in China for LAG-3 antibody development.
- **SMET12**: A potential first-in-class intravenous EGFR×CD3 TCE for EGFR+ solid tumors, leading global and Chinese pipelines. It has FDA IND clearance and is in Phase IIa trials.
- **CMD011**: A best-in-class GPC3×CD3 TCE, and **CMDE005**: a first-in-class EGFR×CD3 masked TCE, both with FDA IND approval and in Phase I. CMD011 ranks top-two globally, while CMDE005 is China’s first and global top-two masked-peptide TCE.
Shima Pharma’s candidates are developed via proprietary platforms (multi-channel antibody discovery, H-BiTE, Pro-BiTE, and multifunctional/logic-gated TCE), forming its core competitive edge.
**The Billion-Dollar TCE Blue Ocean Heats Up** TCEs, which bind tumor antigens and CD3 to activate T-cells, offer high specificity, accessibility, and safety. Unlike CAR-T’s high-cost customization or ADCs’ cytotoxic risks, TCEs are emerging as a next-gen immuno-oncology direction.
Global TCE interest has surged, with 2024 transactions exceeding USD 8.5 billion, involving Amgen, Johnson & Johnson, AbbVie, Merck, and Roche. Amgen’s CD19×CD3 bispecific Blincyto became the first TCE to surpass USD 1 billion annually (USD 1.2 billion in 2024). The TCE market grew from USD 400 million in 2020 to USD 3 billion in 2024 (67.6% CAGR), projected to reach USD 47.5 billion by 2030 and USD 120 billion by 2035.
However, TCE development is uneven, with blood cancers (10% of cancer cases) dominating, while solid tumors (90%) face challenges like target safety and lymphocyte scarcity. Amgen’s tarlatamab, FDA-approved in May 2024 for small-cell lung cancer, marked the first solid-tumor TCE, boosting sector interest.
Shima Pharma’s prospectus notes only two approved solid-tumor TCEs globally, creating structural opportunities. Three of its four clinical candidates target solid tumors (SMET12, CMD011, CMDE005), differentiating its pipeline.
In China, over 150 TCE pipelines exist, mostly early-stage and blood-cancer-focused. Solid-tumor competitors include Zenshine Pharma (ZG006 trispecific), KeyMed Biosciences (out-licensed TCEs), and Leads Biolabs (LBL-033, the second global MUC16×CD3 TCE in trials for gynecologic tumors).
Autoimmune diseases are TCE’s next frontier, offering better CRS control and subcutaneous dosing advantages. Over 20 TCEs are in autoimmune trials (e.g., CD3×CD19, CD3×CD20). Merck’s USD 1.3 billion acquisition of Tongrun Biosciences’ CN201 (CD3×CD19) underscores big pharma’s confidence.
**Investment Outlook** Shima Pharma, with its solid-tumor focus and globally competitive pipeline, presents long-term commercial potential. However, its candidates are in early-to-mid clinical stages, requiring further validation and sustained R&D investment, posing cash flow and financing challenges. For investors eyeing the TCE sector’s early-mover potential, Shima Pharma is a noteworthy candidate.
Comments