A pipeline-swap in oncology: Kelun-Biotech and Crescent Biopharma forge up to $1.38B strategic partnership

On December 4, Kelun-Biotech and Crescent jointly announced the establishment of a strategic partnership to co-develop and commercialize oncology therapeutics, including novel combination therapies. The collaboration involves Kelun-Biotech's ADC product SKB105 and Crescent's PD-1 x VEGF bispecific antibody CR-001. These two candidate drugs are being developed for the treatment of solid tumors, with Phase 1/2 monotherapy clinical trials expected to commence in the first quarter of 2026.

Under the terms of the agreement, Kelun-Biotech will receive an upfront payment of $80 million from Crescent and is eligible to receive up to $1.25 billion in milestone payments (for a total of $1.33 billion), along with tiered royalties based on the net sales of SKB105. Crescent will receive an upfront payment of $20 million from Kelun-Biotech and is eligible to receive up to $30 million in milestone payments (for a total of $50 million), along with tiered royalties based on the net sales of CR-001. The total potential deal value for the collaboration between Kelun-Biotech and Crescent regarding SKB105 and CR-001 is up to $1.38 billion.

SKB105 is a differentiated ADC targeting ITGB6, with a topoisomerase I inhibitor payload. ITGB6 is highly expressed in multiple solid tumors but shows low or no expression in most normal tissues, offering the potential to reduce systemic toxicity and off-target risks. Preclinical studies have demonstrated favorable efficacy, safety, and pharmacokinetic (PK) profiles for SKB105. A Phase 1/2 clinical trial of SKB105 in patients with solid tumors is expected to initiate in the first quarter of 2026.

CR-001 is a PD-1 x VEGF bispecific antibody currently in development for the treatment of solid tumors. In preclinical studies, CR-001 demonstrated cooperative pharmacology, potentially enhancing PD-1 binding and signal blockade through its VEGF blockade activity, along with potent antitumor activity. CR-001's anti-VEGF activity may also normalize the vasculature at the tumor site, potentially improving the localization and effectiveness of combination therapies, such as those pairing CR-001 with ADCs. A global Phase 1/2 trial of CR-001 in patients with solid tumors is expected to initiate in the first quarter of 2026.

Under the terms of the agreement, Kelun-Biotech has granted Crescent exclusive rights to research, develop, manufacture, and commercialize SKB105 in the United States, Europe, and all markets outside of Greater China. In turn, Crescent has granted Kelun-Biotech exclusive rights to research, develop, manufacture, and commercialize CR-001 in Greater China. The collaboration includes the development of both candidates as monotherapies and the evaluation of CR-001 in combination with SKB105. Both parties retain the right to independently develop CR-001 in additional combination regimens, including combinations with their respective proprietary ADC pipeline assets.

Unlike traditional one-way out-licensing or in-licensing deals, this collaboration represents a pipeline swap transaction: Kelun-Biotech has in-licensed Crescent's bispecific antibody CR-001, while Crescent has in-licensed Kelun-Biotech's ADC SKB105. This transaction achieves complementarity in geographic rights, synergy in target indications and clinical timelines—both programs target solid tumors and are expected to initiate global Phase 1/2 trials in the first quarter of 2026. More importantly, both parties retain the right to develop each therapy independently or in combination, fully exploring the potential for "1+1>2" clinical value behind the ADC plus bispecific antibody strategy.

Kelun-Biotech stated that this innovative global collaboration model effectively integrates the strengths and resources of both parties to explore novel monotherapy and combination strategies for SKB105 and CR-001 in oncology. Leveraging China's rich clinical resources and efficient execution capabilities, Kelun-Biotech will accelerate clinical development while adhering to the highest international standards. The powerful synergies released through this collaboration will maximize the therapeutic potential of these two candidates in both the Chinese and global markets.

To support subsequent development, in a separate but concurrent announcement, Crescent disclosed a $185 million private placement, expected to close on or about December 8, 2025. This financing includes participation from both new and existing investors, including leading healthcare investment firms such as Forbion, Fairmount, Vestal Point Capital, BVF Partners, ADAR1, Balyasny Asset Management, and Venrock Healthcare Capital Partners. Combined with the upfront payment from this collaboration and existing funds, Crescent's cash reserves are expected to support operations into 2028.

The development of bispecific antibody (bispecific) + antibody-drug conjugate (ADC) combination therapies has become a major focus in the innovative drug sector.

Several Chinese companies have already established collaborations in this field. For example, 3SBio and Biokin Pharmaceutical have partnered to jointly advance the combination of the PD-1/VEGF bispecific SSGJ-707 with the HER3/EGFR bispecific ADC BL-B01D1 for the treatment of solid tumors in China. Summit Therapeutics, the international development partner for Akesobio's Ivonescimab (a PD-1/VEGF bispecific), has entered into a clinical trial collaboration with Pfizer to jointly advance the application of Ivonescimab in combination with several of Pfizer's ADCs across various solid tumors.

Globally, BNT47, a PD-1/VEGF bispecific jointly developed by Bristol Myers Squibb and BioNTech, has been explicitly positioned as a platform asset capable of forming combination regimens with multiple ADCs and bispecific products. Roche, with its extensive experience in anti-VEGF therapy and immuno-oncology combinations, is also advancing several "immunotherapy + ADC" combination development programs.

Why are both multinational corporations (MNCs) and biotechnology companies (Biotechs) strategically investing in this niche area? Combination therapies involving ADCs and bispecifics hold the potential to overcome the limitations of single-agent treatments and provide more effective therapeutic options for cancer patients through mechanisms such as precise targeting, synergistic effects, and immune activation.

First, regarding targeting, ADCs precisely recognize specific targets on the surface of tumor cells, while bispecifics can simultaneously target two different antigens or two epitopes on the same antigen. Their combined use can broaden the scope of target coverage, address multiple tumor antigens or signaling pathways, enhance the specificity of tumor cell recognition, and reduce off-target effects.

Second, in terms of overcoming resistance, tumor cells often develop resistance to single agents through mechanisms like target mutations or compensatory signaling pathways. The combination of ADCs and bispecifics can inhibit multiple targets or pathways simultaneously, blocking tumor escape mechanisms, delaying or reversing the onset of resistance, and prolonging therapeutic efficacy.

Third, concerning immune activation and tumor microenvironment modulation, immune checkpoint bispecifics (e.g., PD-1/PD-L1 bispecifics) can alleviate immune suppression and activate immune cells such as T cells. Antigens released during ADC-mediated tumor cell killing can serve as immunogens, further stimulating the immune system. The combination can enhance the body's anti-tumor immune response, improve the tumor microenvironment, and promote immune cell recognition and clearance of tumor cells.

Fourth, regarding safety, combination therapies achieve therapeutic effects at lower drug doses through multi-target synergy, potentially reducing the toxicity associated with high doses of single agents. Additionally, structural optimizations in bispecifics (e.g., Fc domain modifications) and careful selection of ADC linkers and payloads can help mitigate immune-related adverse reactions and off-target toxicity.

Furthermore, since ADCs and bispecifics target different tumor antigens and indications, their combination can expand the range of treatable cancers, including those resistant to conventional therapies or lacking effective treatment options, thereby providing patients with more therapeutic choices.

However, despite the numerous theoretical advantages of bispecific + ADC combination therapies, no such combinations have yet reached the commercial application stage. Currently, companies including Roche, BioNTech, Akesobio, Pfizer, Biokin Pharmaceutical, and 3SBio have reported promising clinical-stage data. Through industry-wide collaboration, it is hoped that bispecific + ADC combination therapies will successfully reach the market, bringing new breakthroughs in cancer treatment.