Competitive Analysis of Duality Biologics' DB-1303 vs. Enhertu in Endometrial Cancer

Based on the collected information, I provide you with an in-depth analysis of the competitive landscape between Duality Biologics’ DB-1303 and Enhertu in the field of endometrial cancer.

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Category	DB-1303/BNT323	Enhertu (DS-8201)
Developer	Duality Biologics/BioNTech	Daiichi Sankyo/AstraZeneca
Target	HER2	HER2
Payload	Topoisomerase I Inhibitor (DITAC Platform)	Topoisomerase I Inhibitor (DXd)
Linker	Cleavable Linker	Cleavable Tetrapeptide Linker
Indication Phase	Phase III Clinical/Registration Filing Stage	Approved (Multiple Countries)
Endometrial Cancer Progress	Planned NDA submission in 2025	Approved, Multiple Lines of Therapy

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Based on Phase 1/2 clinical trial data presented by Duality Biologics/BioNTech at the 2023 ASCO and ESGO conferences:

• Objective Response Rate (ORR): 58.8%
  (Unconfirmed)
• Disease Control Rate (DCR): 94.1%
• Enrolled Patients: Heavily pretreated patients with advanced endometrial cancer
• Safety: Well-tolerated, with manageable safety profile

This data led to DB-1303 receiving

in January 2023[1].

Enhertu has been approved for endometrial cancer in multiple countries based on positive results from the DESTINY-PanTumor02 trial:

• Demonstrated efficacy in endometrial cancer patients with HER2 expression (IHC 3+, IHC 2+/ISH+, IHC 1+)
• Advancing DESTINY-Endometrial01 (first-line therapy) and DESTINY-Endometrial02 (adjuvant therapy) trials[2]

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Advantage Area	Analysis
Differentiated Positioning	Targets a broader patient population with HER2 expression (IHC 1+ and above), covering approximately 70-80% of endometrial cancer patients[0]
Breakthrough Therapy Designation	FDA Breakthrough Therapy Designation accelerates the approval pathway, with planned NDA submission in 2025[1]
Safety Profile	Clinical data shows manageable safety, which may become a key differentiator from Enhertu
China Market Rights	Duality Biologics retains rights in mainland China, Hong Kong, and Macau, and can leverage its advantages in the Chinese market[0]

Advantage Area	Analysis
First-Mover Advantage	Approved based on DESTINY-PanTumor02, becoming the first approved HER2 ADC in the endometrial cancer field[2]
Indication Coverage	Approved for multiple cancer types including breast cancer, gastric cancer, lung cancer, and endometrial cancer
Depth of Clinical Development	DESTINY-Endometrial01/02 are advancing to earlier lines of therapy, building a defensive line[2]
Mature Commercialization	2025 medical insurance price reduced to RMB 3,480 per vial, significantly improving accessibility

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Currently, there is no head-to-head clinical trial data between the two drugs, making direct efficacy comparison impossible. DB-1303’s 58.8% ORR is early-stage (unconfirmed) data, while Enhertu’s efficacy data is derived from larger-scale Phase 3 clinical trials.

Interstitial Lung Disease (ILD), a common adverse event of ADC drugs, is a key safety concern for Enhertu. If DB-1303 can demonstrate a superior safety profile, it will become an important differentiator.

• Enhertu
  : Has advanced from later lines to earlier lines of therapy (DESTINY-Endometrial01 for first-line therapy, DESTINY-Endometrial02 for adjuvant therapy)[2]
• DB-1303
  : Planned global Phase III confirmatory clinical trial targets second-line or subsequent therapy[0]

Endometrial cancer is a common gynecologic malignancy, with approximately 400,000 new cases worldwide each year. HER2-positive/expressing patients account for 20-30% of endometrial cancer patients, while HER2-low expressing (IHC 1+ or IHC 2+/ISH-) patients account for 50-60%. DB-1303 covers a broader range of HER2 expression levels, theoretically serving a larger patient population.

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1. Time Gap
   : Enhertu has established a first-mover advantage, and DB-1303 needs at least 2-3 years to catch up
2. Phase III Validation
   : Large-scale Phase III clinical trials are required to validate early-stage efficacy data
3. Production Capacity Pressure
   : Commercial production capacity needs to be expanded rapidly
4. Pricing Pressure
   : Enhertu has been included in medical insurance, posing challenges to DB-1303’s pricing strategy

1. Safety Competition
   : If DB-1303 has a superior safety profile, it may capture patient populations sensitive to toxicity
2. Price Competition
   : If DB-1303 is priced lower in the Chinese market, it may gain price-sensitive patients
3. Resistance Management
   : Later-line treatment options remain limited, and DB-1303 may become a treatment option for patients with Enhertu resistance

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• DB-1303 is expected to submit its NDA in 2025, with approval and launch anticipated in 2026-2027
• Initially, it will focus on patients previously treated with Enhertu or those unable to tolerate Enhertu
• The two drugs will form differentiated competition rather than direct substitution

• DB-1303 needs to demonstrate non-inferior efficacy to Enhertu through Phase III clinical trials
• Advancing to earlier lines of therapy is a key competitive battlefield
• Development of combination therapies may become a differentiated direction

, but it has the following growth potential:

1. Successful Differentiated Positioning
   : If it can establish advantages in HER2-low expressing populations or safety
2. Breakthrough in the Chinese Market
   : Leveraging Duality Biologics’ in-depth presence in the Chinese market to achieve differentiated competition
3. Innovation in Combination Therapies
   : Combination regimens with immunotherapy or targeted therapy may open up new opportunities

: DB-1303 needs to demonstrate competitive efficacy and safety data in its upcoming Phase III clinical trials, while establishing a differentiated clinical positioning, to gain a foothold in the endometrial cancer ADC market.

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[0] Duality Biologics Official Website - DB-1303/BNT323 Pipeline Information (https://www.dualitybiologics.com/17335757308177/newpath17336570213359/11.html)

[1] BioNTech - FDA Breakthrough Therapy Designation Announcement (https://investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-receive-fda-breakthrough-therapy)

[2] Daiichi Sankyo - DESTINY-Endometrial02 Phase 3 Trial Initiation (https://daiichisankyo.us/press-releases/-/article/destiny-endometrial02-phase-3-trial-of-enhertu-initiated-as-adjuvant-therapy-in-patients-with-her2-expressing-endometrial-cancer)