Two recent announcements have put Delta-like ligand 3 (DLL3), a high-potential target, into the spotlight. Both Hengrui Pharma and Innovent's ADC innovative drugs were licensed out for more than US$1 billion.
DLL3
Antibody–drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells.
DLL3 has been reported to be expressed in multiple solid tumor types, including in SCLC and Neuroendocrine Tumors at approximately 85% and 20-40%, respectively, based on the Human Protein Atlas database. DLL3 has limited extracellular expression in normal tissues, making it a promising therapeutic target in these tumor types, for which there remains significant unmet medical need.
As far as we know, no DLL3 ADC products have been approved for marketing worldwide.
Hengrui Pharma Partners with IDEAYA
On 29 December 2024, Jiangsu Hengrui Pharmaceuticals Co., Ltd ("Hengrui Pharma") announced a licensing agreement with IDEAYA Biosciences, Inc.("IDEAYA") for SHR-4849, a novel DLL3-targeting Topo-I-payload ADC program.
Under the terms of the agreement, IDEAYA will develop and commercialize SHR-4849 worldwide outside of Greater China. Meanwhile, Hengrui Pharma is eligible to receive upfront and milestone payments totaling US$1.045 billion, including a US$75 million upfront fee, up to US$200 million in development and regulatory milestone payments, plus commercial success-based milestones. Hengrui Pharma is also eligible to receive mid-single to low-double digit royalties on net sales outside of Greater China.
According to IDEAYA, SHR-4849 has shown promising antitumor activity in preclinical studies, including tumor regression as a monotherapy in multiple models. This drug is currently being evaluated in a Phase 1 clinical trial for advanced solid tumors in China (NCT06443489). IDEAYA is targeting to file a US IND for SHR-4849 in the first half of 2025.
Innovent Joins Hands with Roche
On 2 January, Innovent Biologics, Inc. ("Innovent") announced a collaboration and exclusive license agreement with Roche to advance the development of IBI3009.
IBI3009 is another leading and potentially best-in-class DLL3-targeting ADC, which has shown encouraging anti-tumor activity in multiple tumor-bearing mouse models, particularly in chemo-resistant tumor types, and has demonstrated a favorable safety profile. It is hoped to bring innovative treatment options to patients with advanced small cell lung cancer. IBI3009 has already obtained IND approvals in Australia, China, and the U.S., with the first patient for the Phase 1 study dosed in December 2024.
Under the agreement, Innovent has granted Roche exclusive global rights to develop, manufacture and commercialize IBI3009. The two parties will jointly focus on the early-stage development of this ADC candidate, after which Roche will take over full development. Innovent will receive an upfront payment of US$80 million and is eligible to receive up to US$1 billion in development and commercial milestone payments, along with tiered royalties on net sales.
Chinese Innovative ADC Drugs Shine on the Global Stage
According to Frost & Sullivan's data, the global ADC drug market size has always maintained a high growth rate, soaring from US$ 2 billion in 2018 to US$ 10.4 billion in 2023, with a CAGR of 39.1%. It is expected that the market will continue to boost and reach US$ 66.2 billion in 2030.
With the rapid growth of China's innovative drug industry, new achievements are emerging in the field of ADCs. According to the statistics from Insight database, as of May 2024, a total of 519 new drugs have been developed for ADCs in China, accounting for 43.8% of the global total, making the country a core participant in global R&D of ADCs. A total of 155 domestic ADCs have entered clinical trials, accounting for 41.1% of the global total.
Since Chinese pharmaceutical companies started to develop innovative ADC drugs, a number of companies, including CSPC Pharmaceutical Group Co., Ltd. and Sichuan Kelun Pharmaceutical Co., ltd., have licensed out their ADC-related products at sky-high prices.
The future is promising; the competition is fierce.
During the challenging times of a capital winter, license-out is presently one of the primary ways for Chinese drug companies to increase profits. Potential target or product often faces competition from multiple companies. Teams that have sufficient innovation and R&D capability to independently develop innovative drugs with international competitiveness are more likely to seize commercial opportunities.
Source: Nature
Source: Company Materials, SPDB International
Translation: China IP Today
