Innovent Announces $1.08 Billion Global Licensing Deal with Roche for DLL3-Targeting ADC IBI3009

On January 2, Innovent Bio announced that it had reached a global exclusive cooperation and licensing agreement with Roche for a certain product.Global Exclusive Rights for Development, Manufacturing, and Commercialization of Next-Generation Antibody-Drug Conjugates (ADC) Targeting Delta-Like Ligand 3 (DLL3)Authorized to Roche.

According to the agreement, Innovent Bio will obtainAn upfront payment of 80 million USD and potential development and commercialization milestone payments of up to 1 billion USD, as well as future tiered royalties based on global annual net sales. The potential total amount reaches 1.08 billion US dollars (approximately 7.883 billion yuan).

The development of IBI3009 aims toAdvanced Small Cell Lung Cancer (SCLC)Providing patients with a new treatment option, it has received clinical trial application (IND) approval in Australia, China, and the United States, with the first patient dosing in the Phase I clinical study completed in December 2024. Both parties will jointly oversee the early development of this ADC candidate drug, while subsequent clinical development will be led by Roche.

Just four days ago, Hengrui Medicine and IDEAYA Biosciences also announced a global (excluding Greater China) collaboration and licensing agreement for the DLL3-targeted ADC pipeline SHR-4849. The latter will pay an upfront payment of 75 million US dollars, with subsequent milestone payments not exceeding 970 million US dollars, and a potential total amount exceeding 1 billion US dollars.

In 2025, China's ADC shopping spree has reached the blue ocean target market that has yet to be developed into drugs.

Currently, no DLL3 ADC products have been approved for marketing globally.

DLL3 is a single-pass transmembrane protein attached to the cell surface and belongs to the Notch ligand family. It can bind to Notch receptors 1-4 to activate the Notch signaling pathway. The Notch pathway is a highly conserved cellular signaling pathway associated with malignant transformation, cell proliferation, cell cycle arrest and apoptosis, epithelial-mesenchymal transition, and inhibition of neuroendocrine differentiation. It also plays a role in the development and chemoresistance of SCLC. DLL3 is rarely expressed in normal tissues but shows high specific expression in SCLC tissues and other neuroendocrine tumors.

The primary reason for the boiling of the blue ocean market lies in the first-line indication—small cell lung cancer (SCLC) market.

As the leading cause of cancer-related deaths globally, there were 2.17 million new cases of lung cancer in 2020, of which 250,000 were SCLC, accounting for approximately 14% of all lung cancers. SCLC is an aggressive, high-grade neuroendocrine carcinoma with a very poor prognosis, a 5-year survival rate of less than 7%, and characteristics of early metastasis. Clinical treatments often involve chemotherapy, combined immunotherapy with PD-L1 inhibitors, and the use of second-line treatment drugs such as topotecan. However, drug resistance and recurrence are almost inevitable, making long-term disease control unattainable for most patients through current therapeutic approaches.

The tumor specificity of the DLL3 target has long attracted attention in the new drug development community: In April 2016, AbbVie spent $5.8 billion to acquire Stemcentrx, obtaining its ADC Rova-T for the treatment of SCLC. Preclinical research results showed that it had excellent anti-tumor effects in CDX and PDX models with high DLL3 expression. However, the development of Rova-T stumbled, with later clinical data showing an overall response rate of only 18% for SCLC, and a median OS of just 5.8 months—only one month longer than the standard treatment regimen for SCLC. As a result, AbbVie abandoned the development of Rova-T in 2019. Despite this initial setback, the evidence from Rova-T was sufficient to establish DLL3 as a key target for SCLC.

Secondly, DLL3 ushers in its first bispecific antibody to reach the market — Tarlatamab, demonstrating remarkable efficacy as a significant boost.

In May 2024, Amgen's DLL3/CD3 bispecific antibody Tarlatamab (Imdelltra) received accelerated FDA approval for the treatment of extensive-stage small cell lung cancer (ES-SCLC) that progressed after platinum-based chemotherapy, becoming the world’s first approved DLL3-targeted drug. BeiGene holds the commercial rights in China and has already initiated a Phase 3 clinical trial domestically.

Tarlatamab is a bispecific T-cell engager (BiTE) targeting DLL3 and CD3. The phase 2 clinical trial data showed that, among patients evaluable for antitumor activity and survival, the objective response rate (ORR) reached 32% in the 100mg group and 40% in the 10mg group, compared to only 15% ORR in patients previously treated with standard therapies upon recurrence; the median progression-free survival (PFS) was 4.9 months in the 10mg group and 3.9 months in the 100mg group; at 9 months of treatment, the estimated overall survival rates were 68% and 66%, respectively.

Innovent Bio's IBI3009, which specifically targets DLL3 and is authorized to Roche this time, was designed and developed based on Innovent Bio's proprietary novel topoisomerase I inhibitor (TOPO1i) platform. Currently, IBI3009 has demonstrated encouraging anti-tumor activity in multiple tumor-bearing mouse models (especially in chemotherapy-resistant tumor types) and exhibits a favorable safety profile.

Meanwhile, globally, the development and transactions of innovative drugs targeting DLL3 are flourishing.In April 2023, Zai Lab partnered with Yilian Biotech to acquire the global development and commercialization rights to its DLL3 ADC drug YL212, which has already initiated Phase 1 clinical trials in the United States. In November, Novartis secured Legend Biotech's DLL3 CAR-T LB2102 in a deal worth $1.11 billion. Additionally, the world's first targeted DLL3 radiopharmaceutical ABD-147 received IND approval in 2024.

As a global leading innovative oncology pharmaceutical company, Roche is also one of the earliest companies to successfully commercialize ADCs.

In 2013, Roche's Kadcyla was approved by the FDA for marketing, becoming the world’s first HER2 ADC and the third ADC to be marketed globally. By filling the critical gap in second-line treatment for HER2-positive breast cancer, Kadcyla achieved global sales exceeding $1 billion in 2018, making it a blockbuster drug that became a pillar of Roche's performance. In 2023, when the ADC market size surpassed $10 billion for the first time, Kadcyla ranked second with $2.22 billion in sales.

In 2019, Roche's second ADC product, Polivy, was approved for marketing to treat patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had received at least two prior therapies. In April 2023, Polivy was further approved for use in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) as a first-line treatment for patients with diffuse large B-cell lymphoma (DLBCL). This marks the first new first-line therapy for DLBCL approved by the FDA in nearly 20 years. In 2023, Polivy ranked sixth globally in sales, reaching approximately $950 million.

Notably, both ADCs had technical collaborations during their development—Kadcyla was developed by Genentech based on ImmunoGen's ADC platform, while Polivy was developed by Roche using Seagen's ADC technology.

After achieving tremendous commercial success with Kadcyla and Polivy, Roche's ADC sector fell silent for several years, with no significant developments in its self-developed pipeline or collaboration deals. During this period, the next-generation HER2 ADC Enhertu claimed the top spot as the best-selling ADC. Coupled with the relentless pursuit of biosimilars from India, Roche stated at the 2024 JPM Conference, "plans to engage in more transactions within the ADC field."

This restart is based on early R&D and technology collaboration in the ADC field, with the partner now being a Chinese Biotech company.

On January 2, 2024, Roche and Yilian Biotech reached an agreement to co-develop the ADC candidate product YL211 targeting Mesenchymal Epithelial Transition Factor (c-MET) for the treatment of solid tumors. Roche will pay 50 million US dollars as an upfront payment and near-term milestone payments, nearly 1 billion US dollars in potential milestone payments, and future tiered royalties.

Overall, Roche's recent two ADC acquisitions have followed a similar strategy——In the IND and Phase I clinical stages, take over global clinical development and commercialization.IBI3009 has received multi-country IND approval and completed the first dosing in Phase I clinical trials; YL211, a collaboration between Innovent Bio and Roche China Innovation Center (CICoR), submitted an IND in China after the deal was announced and has also secured FDA IND approval, rapidly advancing into Phase I clinical trials.

In terms of targets and markets, Roche has chosen popular solid tumor targets for which ADC drugs have not yet been developed at this stage., or hope to recreate another Kadcyla era: IBI3009 targeting DLL3, YL211 targeting c-MET.

However, the competition in the MNC ADC market is no longer the same as it was in 2013. More competitors who have been building their capabilities for a long time are starting to enter the arena:In September 2024, AbbVie welcomed its first self-developed ADC product, telisotuzumab vedotin (Teliso-V, ABBV-399), for which a Biologics License Application (BLA) has been submitted. This is also the first c-Met ADC product to have a BLA submitted, intended for the treatment of adult patients with previously treated c-Met protein overexpression, epidermal growth factor receptor (EGFR) wild-type advanced/metastatic non-squamous non-small cell lung cancer (NSCLC).

References:

Chinese Journal of Cancer Biotherapy "Research Progress in Targeting DLL3 for the Treatment of Small Cell Lung Cancer"

VCBeat "7.6 Billion! Overseas Star Biotech Buys Another Chinese ADC"

VCBeat "ADC Drug Market Explosion: Annual Sales Break Through 10 Billion, 5 Drugs Enter the Billion-Dollar Club"