IDEAYA Biosciences has entered into an exclusive license agreement with Jiangsu Hengrui Pharmaceuticals for SHR-4849, a novel DLL3-targeting Topo-I-payload antibody-drug conjugate (ADC). The deal, potentially worth up to $1.045 billion, grants IDEAYA the rights to develop and commercialize SHR-4849 worldwide, excluding Greater China. This strategic move aims to address the unmet medical needs in DLL3-expressing solid tumors, particularly small cell lung cancer (SCLC) and neuroendocrine tumors (NETs).
Clinical Potential of SHR-4849
SHR-4849 is currently being evaluated in a Phase 1 clinical trial in China (NCT06443489) for advanced solid tumors. Preliminary data from the dose-escalation study, with a data cut-off date of December 10, 2024, showed encouraging signs of efficacy and a manageable safety profile. Among 11 evaluable SCLC subjects treated at therapeutic dose levels, 8 partial responses were observed based on RECIST 1.1 criteria, resulting in an overall response rate of approximately 73% (including both confirmed and unconfirmed responses).
The treatment-related adverse events (TRAEs) were predominantly Grade 1 or 2, with no reported drug-related discontinuations, and the maximum tolerated dose had not yet been reached. The most common TRAEs included decreased white blood cell count, anemia, decreased neutrophil count, nausea, and decreased platelet count.
Strategic Rationale for the Deal
IDEAYA Biosciences plans to leverage SHR-4849's potential as a monotherapy and in combination with its existing pipeline, including the PARG inhibitor IDE161. Daniel A. Simon, Chief Business Officer of IDEAYA Biosciences, noted the enhanced preclinical combination efficacy observed with topo-payload ADCs and IDE161.
Yujiro S. Hata, Chief Executive Officer and Founder of IDEAYA Biosciences, emphasized the significant unmet medical need in DLL3-expressing solid tumors and the first-in-class potential of SHR-4849 in the DLL3 topo-I-payload ADC field.
Financial Terms and Future Plans
Under the agreement, Hengrui Pharma will receive a $75 million upfront fee and is eligible for up to $200 million in development and regulatory milestone payments, as well as commercial success-based milestones. Additionally, Hengrui will receive mid-single to low-double-digit royalties on net sales outside of Greater China.
IDEAYA is targeting to file a US IND for SHR-4849 in the first half of 2025. This aligns with IDEAYA's strategic objective to develop rational clinical combinations of topo-payload-based ADCs with their PARG inhibitor IDE161.
DLL3 as a Therapeutic Target
DLL3 (Delta-like ligand 3) is a protein highly expressed in SCLC (approximately 85%) and neuroendocrine tumors (20-40%), with limited expression in normal tissues, according to the Human Protein Atlas database. This makes it a promising therapeutic target for these tumor types, where significant unmet medical needs persist.
