IDEAYA Biosciences Enters Exclusive License with Hengrui Pharma for SHR-4849, a Novel Phase 1 DLL3 Topo-I-Payload ADC Targeting SCLC and NET Solid Tumors

Rhea-AI Summary

IDEAYA Biosciences (NASDAQ: IDYA) has secured an exclusive global license outside Greater China for SHR-4849, a Phase 1 DLL3-targeting antibody drug conjugate (ADC) from Hengrui Pharma. The drug targets Small Cell Lung Cancer (SCLC) and Neuroendocrine Tumors (NETs), showing promising early clinical results with a ~73% response rate in SCLC patients at therapeutic doses. The deal includes a $75M upfront payment and potential milestone payments totaling $1.045B, plus royalties.

In the ongoing Phase 1 trial, SHR-4849 demonstrated 8 partial responses among 11 evaluable SCLC subjects, with manageable safety profile primarily showing Grade 1 or 2 adverse events. IDEAYA plans to file a US IND in H1 2025. The agreement maintains IDEAYA's guided cash runway through at least 2028.

Positive

• Strong early clinical efficacy with ~73% response rate in SCLC patients
• Favorable safety profile with primarily Grade 1-2 adverse events
• Large market opportunity with DLL3 expression in 85% of SCLC and 20-40% of NET cases
• Deal structure preserves cash runway through 2028
• Potential for $1.045B in total milestone payments

Negative

• Significant upfront cash payment of $75M required
• Phase 1 trial still ongoing with maximum tolerated dose not yet determined
• US IND filing not expected until H1 2025

Insights

Biotechnology Research Analyst

The exclusive licensing deal for SHR-4849 represents a strategic expansion into the high-potential ADC market. The preliminary Phase 1 data showing a 73% response rate in SCLC is remarkably promising, significantly outperforming current standard treatments. The safety profile appears manageable with predominantly Grade 1-2 adverse events and no drug-related discontinuations, suggesting a potentially favorable therapeutic window.

The $1.045 billion deal structure, including $75 million upfront, is well-structured with milestone-based payments that align with development success. The maintained cash runway through 2028 indicates prudent financial management despite the substantial upfront payment.

Think of this deal as acquiring a precision-guided missile for cancer treatment - DLL3's high expression in SCLC (85%) and presence in normal tissues makes it an ideal target, similar to having a lock-and-key mechanism that primarily affects cancer cells.

Oncology Specialist

The clinical data for SHR-4849 is particularly compelling in the SCLC setting, where treatment options are The 73% response rate among 11 evaluable patients, even including unconfirmed responses, suggests potentially superior efficacy compared to existing treatments. The manageable safety profile, with predominantly hematological adverse events, aligns with expectations for ADC therapeutics.

The combination potential with PARG inhibitor IDE161 could address resistance mechanisms in DNA damage repair pathways, potentially enhancing therapeutic outcomes. For perspective, imagine combining a precision tool that targets cancer cells (SHR-4849) with a mechanism that prevents cancer cells from repairing themselves (IDE161) - it's like cutting the brake lines while simultaneously accelerating.

Financial Analyst

The deal terms reflect significant value potential while maintaining fiscal responsibility. The $75 million upfront payment represents only 7.2% of the total potential deal value of $1.045 billion, with the majority tied to success-based milestones. This structure effectively shares development risk with Hengrui while preserving IDEAYA's cash position.

The maintenance of cash runway through 2028 despite this acquisition demonstrates strong financial planning. The mid-single to low-double digit royalty structure provides meaningful long-term revenue potential if SHR-4849 achieves commercial success. For context, in the rapidly growing ADC market, successful products can achieve blockbuster status (>$1 billion annual sales), making the milestone payments and royalty structure potentially highly lucrative.

• Exclusive global license outside of Greater China for SHR-4849, a Phase 1 DLL3-targeting Topo-I-payload antibody drug conjugate (ADC)
• DLL3 highly expressed in Small Cell Lung Cancer (SCLC) and Neuroendocrine Tumors (NETs), respectively 85% and 20-40%
• Rational combination opportunities with IDEAYA's DNA Damage Repair (DDR) clinical pipeline, including Phase 1 PARG inhibitor IDE161
• Targeting US IND filing for SHR-4849 in H1 2025

SOUTH SAN FRANCISCO, Calif. and SHANGHAI, Dec. 29, 2024 /PRNewswire/ -- 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.

About IDEAYA Biosciences

IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its early research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets. 

About Hengrui Pharma

Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) is an innovative global pharmaceutical company focused on unmet clinical needs, with a strong track record of scientific and technological innovation. Since its first innovative drug approval in 2011, Hengrui Pharma has invested more than $5.4 billion in R&D and set up 14 R&D centers in Lianyungang, Shanghai, the U.S., and Europe. It has 9 major manufacturing sites and a global R&D team of more than 5,000 professionals. Hengrui Pharma has independently established a number of leading technology platforms such as its ADC platform, proteolysis targeting chimera (PROTAC), molecular gels, bi/multi-specific antibodies, and AI molecular design, which provide a strong foundation for innovative R&D. Hengrui strives for continued innovation and collaboration with global partners to serve a healthy China and benefit patients around the world.

Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to (i) the timing of a potential IND filing, (ii) potential development strategies, (iii) the estimated potential addressable market and (iv) the potential therapeutic benefits of IDEAYA therapeutics. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Annual Report on Form 10-K dated February 20, 2024 and any current and periodic reports filed with the U.S. Securities and Exchange Commission.

Investor and Media Contact
IDEAYA Biosciences
Andres Ruiz Briseno
SVP, Head of Finance and Investor Relations
investor@ideayabio.com 

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FAQ

What are the clinical results of SHR-4849 in SCLC patients?

In Phase 1 trials, SHR-4849 showed 8 partial responses among 11 evaluable SCLC subjects, achieving a ~73% overall response rate at therapeutic dose levels.

How much is IDEAYA paying for the SHR-4849 license agreement?

IDEAYA is paying $75M upfront, with potential milestone payments totaling $1.045B, plus mid-single to low-double digit royalties on net sales outside Greater China.

What is the target population for SHR-4849?

SHR-4849 targets tumors expressing DLL3, which is present in approximately 85% of SCLC cases and 20-40% of Neuroendocrine Tumors.

When will IDEAYA file the US IND for SHR-4849?

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

What are the main side effects of SHR-4849 in clinical trials?

The most common treatment-related adverse events were decreased white blood cell count, anemia, decreased neutrophil count, nausea, and decreased platelet count, mostly Grade 1 or 2.