Chinese clinical-stage biotech company Kelun-Biotech*,  a subsidiary of Sichuan Kelun Pharmaceutical, has signed an exclusive license agreement with Merck & Co/MSD to develop an investigational antibody-drug conjugate (ADC) for the treatment of solid tumors.

Under the terms of the agreement, Kelun-Biotech has the exclusive rights to develop, manufacture, and commercialize an investigational ADC. The companies will also collaborate on the early clinical development of the investigational ADC. In return, Kelun-Biotech will receive an upfront payment of US $ 35 million and is eligible to receive future development, approval, and commercial milestone payments totaling up to US $ 901 million, plus tiered royalties on net sales.

Eric H. Rubin, M.D., senior vice president, oncology early development, Merck & Co/MSD Research Laboratories. Photo courtesy: © 2016 – 2022 Merck & Co/MSD. used with permission.

SKB-264
This latest transaction follows Merck & Co/MSD’s decision earlier this year to exercise an option for worldwide rights, except for the Greater China region (including Mainland China, Hong Kong, Macau, and Taiwan), to SKB-264, an investigational drug composed of an antibody targeting the trophoblast cell-surface antigen 2 (TROP2), which is overexpressed in many types of solid tumors, coupled to moderate cytotoxic belotecan-derivative (Camtobell®; CKD602), a novel camptothecin derivative antitumor agent, through a novel linker which was designed to balance the extracellular stability and intracellular rupture. [1]

Elevated expression of TROP2 is often associated with invasion/aggression, progression, and metastasis of many different tumor types, and efficacies of a variety of anti-TROP2 ADCs have been demonstrated both pre-clinically and in the clinical trials.

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Kelun-Biotech’s SKB264 is being optimized as a TROP2-targeting ADC with a proprietary cytotoxic, belotecan-derived payload and novel stable conjugation chemistry to achieve an average drug-to-antibody ratio (DAR) of 7.4.[2]

In extensive preclinical studies, SKB264 demonstrated in vitro antitumor activity in xenograft and patient-derived xenograft (PDX) animal models. In addition, safety studies also demonstrated a good safety profile, leading to SKB264 being studied in the clinic.

Results presented during the European Society for Medical Oncology (ESMO) in September 2021 of a phase 1/2 trials including paged ≥18 with unresectable solid tumors refractory to/relapsed from standard treatment with measurable disease per RECIST 1.1 who received SKB264 Q2W every 4 weeks as monotherapy, demonstrated encouraging safety and antitumor activity.[1]

SKB264 is currently being evaluated in a phase 3 clinical trial for the treatment of metastatic triple-negative breast cancer and in phase 2 trials for non-small cell lung cancer and advanced solid tumors.

Collaboration
Kelun-Biotech and Merck & Co/MSD will collaborate on certain early clinical development plans, including evaluating the potential of SKB-264 as a monotherapy and in combination with pembrolizumab (Keytruda®; Merck & Co/MSD) for the treatment of patients diagnosed with advanced solid tumors.

“These collaborations with Merck & Co/MSD underscore the sophistication and capabilities of Kelun-Biotech’s ADC platform and the potential of our ADC therapeutics,” noted Junyou Ge, MD, Chief Executive Officer of Kelun-Biotech.

“Incorporating Merck & Co/MSD’s deep and broad global expertise with Kelun-Biotech’s innovation power has the potential to generate great development synergy, significantly accelerating the development and commercialization of the collaboration programs. These collaborations will also strengthen our strategic position in building a global, innovative, fully-integrated biopharmaceutical company.”

“The collaboration with Kelun-Biotech strengthens and diversifies Merck & Co/MSD’s oncology pipeline as we seek to further the potential of ADCs to provide more treatment options and improve outcomes for people with cancer,” noted Eric H. Rubin, M.D., senior vice president, oncology early development, Merck & Co/MSD Research Laboratories.

“We look forward to advancing this collaboration with the Kelun-Biotech team,” Rubin concluded.

Note: * KLUS Pharma is the US subsidiary of Kelun-Biotech.

Clinical trials
SKB264 +/- KL-A167 in Recurrent or Metastatic Triple-negative Breast Cancer – NCT05445908
SKB264 Injection vs Investigator Selected Regimens to Treat Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer – NCT05347134
A Phase Ⅱ Clinical Study of Combination Therapy of SKB264 in Patients With Advanced or Metastatic Non-small Cell Lung Cancer – NCT05351788
Phase I-II, FIH, TROP2 ADC, Advanced Unresectable/Metastatic Solid Tumors, Refractory to Standard Therapies (A264) – NCT04152499

Highlights of Prescribing information
Pembrolizumab (Keytruda®; Merck & Co/MSD) [Prescribing Information]

Reference
[1] Rodon J, Li J, Xue J, Diao Y, Xu Y, Liu G, Rao C, Fan B, Cheng Y, Wang J. An open-label, global, first-in-human study of SKB264 in patients with locally advanced or metastatic solid tumors. Annals of Oncology (2021) 32 (suppl_5): S583-S620. 10.1016/annonc/annonc699
[2] Liu Y, Lian W, Zhao X, Diao Y, Xu J, Xiao L, Qing Y, Xue T, Wang J SKB264 ADC: A first-in-human study of SKB264 in patients with locally advanced unresectable/metastatic solid tumors who are refractory to available standard therapies. DOI: 10.1200/JCO.2020.38.15_suppl.TPS3659 Journal of Clinical Oncology 38, no. 15_suppl/Published online May 25, 2020.

Featured image: Merck & Co. Booth. image courtesy: 2016 – 2022 Sunvalley Communication/Evan Wendt. Used with permission.

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