ADC Target Selection Summit Meeting 2024

December 10 – 12, 2024

San Diego, CA

Dowdy Jackson, Ph.D.

Jackson Consulting Group

This year’s ADC Target Selection Summit had several great presentations. I like the fact that this is a smaller meeting where audience participation is welcomed and encouraged. The audience was very engaged and it was great to have such an interactive meeting where we had great discussions and exchanges of ideas and experiences. Thanks to the Hanson-Wade team for organizing this meeting.

The meeting was focused on how we can identify new ADC targets and move away from developing ADCs against crowded ADC targets, such as HER2, TROP2 and Claudin 18.2. The presentations and discussions also focused on how we can diversify the ADC target landscape.

Several presentations, including my presentation, focused on the use of computational and machine learning methods to aid in target identification and prioritization. While the targets identified using these methods may not be novel targets, since we are commonly using data from known public databases, these methods can be used to focus on lesser-known targets, which have promising tumor expression profiles.

Other presentations focused on using the tumor’s biology to identify new ADC targets. Dr. Hans Wandall from GO Therapeutics gave an interesting presentation on how they have identified antibodies that bind to selective glyco-epitopes on tumor cell surface receptors, which aren’t expressed on normal human cells. This essentially is a multi-specific ADC because the ADC can bind to multiple receptors that have the same or similar glyco-epitopes. Since you can target multiple receptors with a single ADC, this could be one way to address the heterogeneous tumor expression problem that many ADC targets face.

Dr. Neil Cashman from Epifold Bio, gave an interesting presentation about novel misfolded epitopes found on some cell surface tumor receptors that could potentially be used as novel ADC targets. One example is the antibody, AMF-1c-120, which recognizes a misfolded prion protein that is expressed by ovarian and lung cancer cells and is not expressed by normal human cells.

Matthew Metzger from Oxford BioTherapeutics gave a presentation about how they are using mass spectrometry to identify ADC targets. This approach utilizes human patient tumors that have been enriched for plasma membranes, undergo mass spectrometry and data analysis which results in the identification of cell surface receptors that are selectively expressed by patient tumors. This approach focuses on identifying cell surface proteins expressed by patient tumors and avoids the disconnect often seen between mRNA expression and protein expression.

According to their website, their technology platform, OGAP®, is the world's largest, cancer specific, membrane protein library, directly measuring plasma membrane protein expression in patient tumors.

They are also incorporating immunohistochemistry (IHC) into their target validation strategy.

 OGAP® platform

Dr. Mark Wappett from Almac Discovery introduced their platform, OmniaScapeTM to identify bispecific targets. This platform was used to identify their ROR1 x EGFR bispecific ADC, ALM-401. ALM-401 consists of the ROR1 arm being a Variable New Antigen Receptor (VNAR), the EGFR arm is a VHH domain with a lower affinity to EGFR and an Fc fusion with engineered cysteines for site specific conjugation to vc-MMAE resulting in a homogenous DAR of 4. The smaller antibody format provides better tumor penetration than the traditional IgG.

OmniaScape description

ALM-401 (ROR1 x EGFGR) ADC:

This meeting provided some good insights into the methods used to identify the next generation of ADC targets. I am looking forward to next year’s meeting.

I’d like to thank Charlotte Taylor-Brooks from Hanson-Wade and her team for organizing a great meeting. I’d also like to thank Drs. Rakesh Dixit and Robert Lawrence for chairing the meeting. Lastly, I’d like to thank all of the meeting attendees for their active participation in the discussions.