Genmab’s ProfoundBio Bet: Navigating the Risky World of ADC Development
Genmab is pressing forward with GEN1106, an antibody-drug conjugate (ADC) acquired through its $1.8 billion takeover of ProfoundBio, despite a wave of recent ADC project discontinuations within the acquired portfolio. This move signals the company’s continued commitment to leveraging the ProfoundBio assets, even as the path forward proves challenging.
The Allure and Risk of SLITRK6 Targeting
GEN1106 uniquely targets SLITRK6, a protein involved in neural development. This represents a relatively unexplored area in oncology, with Astellas’s previously discontinued ASG-15E being the only other known industry project to attempt a similar approach. The failure of ASG-15E, attributed to dose-limiting toxicities despite initial response rates in bladder cancer, highlights the inherent risks in targeting this pathway.
However, Genmab appears optimistic. GEN1106 differs structurally from ASG-15E, utilizing a topoisomerase 1 inhibitor payload – likely the same as that used in ProfoundBio’s rinatabart sesutecan – while ASG-15E employed an MMAE payload. This structural difference could potentially mitigate the toxicity issues encountered with the earlier compound.
ADC Pipeline Pruning: A Common Trend
Genmab’s experience reflects a broader trend in the ADC space. The company has recently discontinued several other ProfoundBio-originated ADCs targeting EGFR x cMet, CD70, and PTK7. GEN1160, a Phase I/II ADC for blood cancers and solid tumors, was shelved due to slow enrollment, and GEN1107 was discontinued due to an unfavorable benefit-risk profile. This pruning aligns with a “portfolio prioritization strategy” aimed at focusing resources on the most promising candidates.
Rinatabart Sesutecan Remains a Key Asset
Despite the setbacks, rinatabart sesutecan (Rina-S), an anti-FRα ADC, remains a central focus for Genmab. It is currently in late-stage development for platinum-resistant ovarian and endometrial cancer. However, competition from companies like Lilly and AstraZeneca could pose a challenge to its success.
Beyond Genmab: Emerging Trends in ADC Development
The clinical trial landscape reveals several other noteworthy developments in ADC research. Boundless Bio, after facing setbacks with CHK1 inhibition, has shifted its focus to BBI-940, an oral kinesin degrader. This illustrates a willingness to pivot and explore novel targets within the oncology space.
New Targets and Mechanisms of Action
Several companies are pursuing new targets, including FGFR2b (Humanwell’s HWS116) and PI3Kα (GeneScience’s GenSci145). The PI3Kα inhibition field is evolving towards more selective inhibitors, including mutation-specific options like Cogent’s CGT6297, aiming to overcome the limitations of earlier-generation PI3Kα inhibitors.
Did you understand? The development of ADCs is a complex process, requiring careful selection of both the antibody target and the cytotoxic payload to maximize efficacy and minimize toxicity.
The Importance of Payload Technology
The choice of payload is critical. While MMAE (used in ASG-15E) has been a common choice, topoisomerase 1 inhibitors (like that used in GEN1106 and rinatabart sesutecan) are gaining traction. The structural differences in payloads can significantly impact the overall safety and efficacy profile of an ADC.
Frequently Asked Questions (FAQ)
Q: What is an ADC?
A: An antibody-drug conjugate is a targeted therapy that combines the specificity of an antibody with the potency of a cytotoxic drug.
Q: Why are ADCs often discontinued during development?
A: ADCs can be discontinued due to various reasons, including toxicity, lack of efficacy, or slow enrollment in clinical trials.
Q: What is SLITRK6?
A: SLITRK6 is a protein involved in neural development that is being explored as a potential target in cancer therapy.
Q: What is the significance of the ProfoundBio acquisition for Genmab?
A: The acquisition aimed to expand Genmab’s ADC pipeline, but the company is now carefully prioritizing its ADC projects.
Pro Tip: Keep an eye on clinicaltrials.gov for the latest updates on ADC development programs. This is a valuable resource for tracking progress and identifying emerging trends.
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