Analysis of Hengrui Medicine's PD-L1/TGF-β Bispecific Antibody Approval and Clinical Design Controversies

Based on the collected information, I will provide you with an in-depth analysis report on Hengrui Medicine’s PD-L1/TGF-β bispecific antibody approval and clinical design controversies.

---

On January 7, 2026,

, independently developed by Hengrui Medicine, was officially approved for marketing by the National Medical Products Administration (NMPA) [1]. This product has the following key features:

• The world’s first approved anti-PD-L1/TGF-βRII bispecific antibody fusion protein
  [1][2]
• Indication
  : Combined with fluoropyrimidine and platinum-based drugs, for first-line treatment of locally advanced unresectable, recurrent or metastatic gastric and gastroesophageal junction adenocarcinoma with PD-L1-positive (CPS≥1) status confirmed by fully validated testing [1]
• R&D Entity
  : Suzhou Sundia Biopharmaceutical Co., Ltd., a subsidiary of Hengrui Medicine

Ruilafupu Alpha Injection adopts an innovative dual-target design:

Component	Mechanism of Action
Anti-PD-L1 IgG4 monoclonal antibody	Blocks PD-L1 signaling and releases the immune checkpoint
Extracellular domain of TGF-β receptor II (TGF-βRII)	Maintains high affinity for TGF-β and improves the immunosuppressive microenvironment

This unique structure achieves a dual mechanism of action:

[1][3].

---

The RELIGHT study (also known as SHR-1701-Ⅲ-307 study) is a

Phase III clinical trial, with Professor Shen Lin from Peking University Cancer Hospital serving as the principal investigator [1][4].

:

• Control Group
  : Placebo combined with chemotherapy (CAPOX regimen)
• Experimental Group
  : Ruilafupu Alpha Injection combined with chemotherapy
• Primary Endpoint
  : Overall Survival (OS)
• Study Scale
  : Participated by 43 hospitals in China

Based on the primary efficacy data reported at the 2024 ESMO Annual Congress (LBA60) [1][4][5]:

Population	Median OS (Experimental Group)	Median OS (Control Group)	Survival Improvement	Reduction in Mortality Risk (HR)
ITT Population	15.8 months	11.2 months	4.6 months	HR=0.66 (34%)
PD-L1 CPS≥1 Subgroup	16.7 months	10.3 months	6.4 months	HR=0.57 (43%)
Gastric Cancer with Liver Metastasis Subgroup	16.8 months	10.3 months	6.5 months	HR=0.46 (54%)

:

• Grade ≥3 treatment-related adverse events (TRAEs) showed no significant difference compared with the control group [4]
• Unique Advantage
  : The first immunotherapy drug observed in a Phase III study to improve chemotherapy-induced hematological toxicity (reduction in platelets, neutrophils, and white blood cells), with an approximately 10% reduction in hematological toxicity compared to the control group, demonstrating potential myeloprotective effects [4]

---

According to reports from professional medical media, the RELIGHT study has the following

[6]:

“The limitation of the study is that it did not conduct a head-to-head comparison with PD-1 inhibitor combined chemotherapy regimens.”

This indicates that the control group setting of the study has the following potential issues:

Comparison Dimension	Current Design	Ideal Design
Control Group Selection	Placebo + Chemotherapy	PD-1 Inhibitor + Chemotherapy (e.g., Pembrolizumab + Chemotherapy)
Direct Comparison	No	Yes
Clinical Guidance Value	Proves superiority over chemotherapy	Proves superiority over standard of care

:

1. Regulatory Approval
   : The study design has been recognized and approved for marketing by the NMPA, indicating that its scientific and ethical rationality has passed regulatory review [1]

2. Historical Control Significance
   : Before PD-1/PD-L1 inhibitors were approved for first-line gastric cancer treatment, chemotherapy was indeed the standard of care

3. Validation of Innovative Mechanism
   : This is the first time that the clinical value of a PD-L1/TGF-β bifunctional fusion protein has been demonstrated in a Phase III clinical trial [6]

:

1. Changes in Treatment Landscape
   : As PD-1 inhibitor combined chemotherapy regimens such as Pembrolizumab and Nivolumab have become the first-line standard of care for gastric cancer [7], the clinical guidance value of a chemotherapy-only control group has declined

2. Limitations of Indirect Comparison
   : Cannot directly prove whether SHR-1701 combined with chemotherapy is superior to existing PD-1 inhibitor combined chemotherapy regimens

3. Challenges in Medical Insurance Access
   : May face questions about the lack of head-to-head data during medical insurance negotiations

Professor Peng Zhi from Peking University Cancer Hospital pointed out: “There is still much to explore in terms of biomarkers. PD-L1 is an important biomarker, but how to better select patients who can benefit from Ruilafupu Alpha Injection (SHR-1701) treatment is a very important research topic.” [3]

---

[7]:

Product	Company	Target	Approval Status
Pembrolizumab	Merck & Co.	PD-1	Approved
Nivolumab	BMS	PD-1	Approved
Cadonilimab	Akeso Biopharma	PD-1/CTLA-4	Approved in September 2024
Aizeli®	Hengrui Medicine	PD-L1/TGF-β	Approved in January 2026

:

• The world’s first approved PD-L1/TGF-β bispecific antibody fusion protein [1]
• Dual-target synergistic effect, showing significant benefits in refractory populations such as gastric cancer with liver metastasis (HR=0.46) [4]

:

• Meta-analysis showed a superior OS benefit trend in advanced gastric cancer patients with PD-L1 CPS≥1 [4]
• Unique safety profile (myeloprotective effects) [4]

:

• As a first-in-class product, it may receive policy support in medical insurance negotiations and hospital access

Challenge Type	Specific Content	Impact Level
Clinical Evidence	Lack of head-to-head comparison with PD-1 inhibitor combined chemotherapy	Medium-High
Medical Insurance Access	Need to demonstrate incremental value compared to existing standard of care	Medium
Competitive Pressure	Akeso’s Cadonilimab has been approved and included in guidelines	Medium
Commercialization Capability	Need to build a new commercial team to promote the bispecific antibody product	Medium-Low

(as of January 9, 2026) [8]:

Indicator	Value
Current Price	$63.78
Market Capitalization	$406.85B
Price-to-Earnings Ratio (P/E)	56.40x
1-Year Growth	+48.05%
5-Day Growth After Approval	+6.19%

[8]:

• Net Profit Margin: 24.10%
• Return on Equity (ROE): 14.19%
• Current Ratio: 6.55 (sound financial condition)

---

:

1. Restricted Academic Promotion
   : May face questions such as “Why not compare with standard of care” during academic promotion
2. Disadvantage in Medical Insurance Negotiations
   : Lack of head-to-head data may affect pricing power in medical insurance negotiations
3. Guideline Recommendation Priority
   : Guidelines such as CSCO and NCCN may prioritize regimens with head-to-head evidence

:

1. Regulatory Endorsement
   : NMPA approval has confirmed its clinical value
2. Differentiated Positioning
   : Dual-target mechanism provides differentiated competitive advantages
3. Liver Metastasis Subgroup Data
   : Shows outstanding efficacy in refractory populations (HR=0.46), which can be used as a core promotion point

:

• Initiate a head-to-head Phase III study with PD-1 inhibitor combined chemotherapy
• Expected Timeline: 2-3 years

:

• Conduct post-marketing real-world studies
• Collect clinical practice data in refractory populations such as those with liver metastasis

:

• Emphasize the unique value of the dual-target mechanism
• Highlight significant benefits in populations with liver metastasis
• Emphasize the safety advantage of myeloprotection

:

• Combined therapy with ADC drugs
• Explore earlier application scenarios such as neoadjuvant therapy

---

Evaluation Dimension	Conclusion
Product Value	Has first-in-class innovative value with solid clinical data
Clinical Design Controversy	Has certain limitations but has obtained regulatory approval
Commercial Prospects	Opportunities and challenges coexist; differentiated positioning is the key
Short-term Impact	Stock price has already reflected some positive news; need to pay attention to medical insurance negotiation progress
Long-term Value	Depends on head-to-head study results and medical insurance access status

1. Risk of innovative drug R&D falling short of expectations
2. Risk of policy changes in the pharmaceutical industry (medical insurance negotiations, volume-based procurement)
3. Impact of macroeconomic fluctuations on the pharmaceutical industry
4. Competitive pressure from accelerated launch of competing products

Taking into account:

• Hengrui Medicine’s platform advantages as a leading domestic innovative drug enterprise
• The first-in-class value of the PD-L1/TGF-β bispecific antibody
• A rich R&D pipeline (over 100 independently developed innovative products in clinical development) [1]

It is recommended to

the progress of medical insurance negotiations for this product and the release of subsequent commercial data.

---

[1] Hengrui Medicine - Hengrui’s Innovative Drug Aizeli® Approved for Advanced Gastric Cancer, the World’s First Marketed Anti-PD-L1/TGF-βRII Bispecific Antibody Fusion Protein (https://www.hengrui.com/media/detail-901.html)

[2] Pharmcube - World’s First! NMPA Approves PD-L1/TGF-βRⅡ Bispecific Antibody Fusion Protein (https://bydrug.pharmcube.com/news/detail/7fe0d54799d4e3819be3c714cf1d9b68)

[3] Liangyihui Oncology News - Professor Peng Zhi: China’s Original PD-L1/TGF-β Bifunctional Fusion Protein SHR-1701 Shines Again on the International Stage (https://bydrug.pharmcube.com/news/detail/6d4ba04782edcf5bfd2e61183984e89b)

[4] Shen L, et al. 2024 ESMO LBA60 - Primary Efficacy Data of the RELIGHT Study

[5] Peng Z, et al. 2025 ESMO Asia Poster 298P - Analysis Results of the PD-L1 CPS≥1 Subgroup

[6] Yisheng - Current Status and Problems of Advanced Gastric Cancer Treatment in 2024 (https://apps.medtrib.cn/media/phone/post/app/2523973/)

[7] 2025 CSCO Guidelines for the Diagnosis and Treatment of Gastric Cancer and NCCN Guidelines Version 3.2025 Gastric Cancer

[8] Jinling AI - Hengrui Medicine Company Fundamental Data (600276.SS)

---

: January 10, 2026

: This report is for reference only and does not constitute investment advice. Investors should make investment decisions based on their own risk tolerance.