IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced that it has entered into an exclusive license agreement for SHR-4849, a novel DLL3-targeting Topo-I-payload ADC program with Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma, SHA: 600276), an innovative global pharmaceutical company headquartered in China focused on unmet clinical needs. Under the terms of the agreement, IDEAYA will develop and commercialize SHR-4849 worldwide outside of Greater China.    

"There is significant unmet medical need in DLL3-expressing solid tumors, and we are excited by the opportunity to develop SHR-4849, which has monotherapy potential in SCLC and NETs.  SHR-4849 is competitively well positioned with first-in-class potential in the DLL3 topo-I-payload ADC field, a therapeutic area that has demonstrated preliminary monotherapy clinical validation in SCLC," said Yujiro S. Hata, Chief Executive Officer and Founder, IDEAYA Biosciences. "In addition, SHR-4849 accelerates IDEAYA's strategic objective to develop rational clinical combinations of topo-payload based ADCs with our PARG inhibitor IDE161, where we observe enhanced preclinical combination efficacy versus evaluated topo-payload ADCs alone," said Daniel A. Simon, Chief Business Officer, IDEAYA Biosciences.

Frank Jiang, Chief Strategy Officer and Board Director, Hengrui Pharma, said "SHR-4849 is a novel DLL3 targeting ADC showing encouraging early clinical signals in small-cell lung cancer with a manageable safety profile. We are delighted to partner with IDEAYA to support the development of this ADC globally, which furthers our goal of delivering innovative medicines for the benefit of patients around the world."

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). In the ongoing Phase 1 dose escalation, SHR-4849 has reached therapeutic dose levels where multiple partial responses have been observed as of the data cut-off date of December 10, 2024. Among 11 evaluable small cell lung cancer (SCLC) subjects treated at therapeutic dose levels, 8 partial responses by RECIST 1.1 were observed, resulting in an overall response rate of ~73% (including both confirmed and unconfirmed responses, all unconfirmed responses were pending further evaluation).  As of the data cut-off date, treatment related adverse events (TRAEs) were predominantly Grade 1 or 2, and the Phase 1 dose escalation is ongoing with no reported drug-related discontinuations, and the maximum tolerated dose has not yet been reached.  The most common TRAEs observed were white blood cell count decreased, anemia, neutrophil count decreased, nausea and platelet count decreased. 

IDEAYA is targeting to file a US IND for SHR-4849 in the first half of 2025.

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.

Under the terms of the agreement, Hengrui Pharma is eligible to receive upfront and milestone payments totaling $1.045 billion, including a $75m upfront fee, up to $200m in development and regulatory milestone payments, plus commercial success-based milestones. Hengrui is also eligible to receive mid-single to low-double digit royalties on net sales outside of Greater China. The upfront and projected research and development costs, including potential milestone payments, does not change the earlier provided IDEAYA guided cash out runway of at least 2028.