# ADC payload neutralisers

Source: https://onco.cc/technologies/adc-payload-neutralizer/  
OnCo record `adc-payload-neutralizer` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An ADC payload neutraliser is an antibody given alongside an ADC that mops up the poison once it leaks into the bloodstream, so the ADC can hit the tumour with fewer side effects.

## Summary

Free payload released from ADCs in circulation drives much of their toxicity (neuropathy, rash, hyperglycaemia with MMAE; neutropenia with SN-38). A neutralising antibody with high affinity for the free payload but not the conjugated form could widen the therapeutic index without changing the ADC. Generate Biomedicines' GB-4362, an AI-designed MMAE neutraliser, entered the clinic in 2026 with FDA Fast Track designation for enfortumab vedotin-induced toxicity in urothelial cancer.

## Fields

- Kind: Technology
- Status: phase-1
- Last checked: 2026-09-06
- Tags: frontier
- Principle: Antibody binds the released small-molecule payload in plasma, preventing uptake by normal tissue; conjugated payload on the ADC remains unaffected.
- Strengths: Adds to existing approved ADCs without reformulation; Could permit higher ADC doses
- Limitations: Early clinical stage; Payload-specific: one neutraliser per payload class; Risk of blunting bystander killing if payload diffuses into plasma from the tumour

## Sources

- Generate Biomedicines Q2 2026: https://www.biospace.com/press-releases/generate-biomedicines-inc-reports-second-quarter-2026-financial-results-and-provides-business-update

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/)
- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [De novo designed protein binders](https://onco.cc/technologies/de-novo-protein-design/)
- drugs: [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/)
- companies: [Generate:Biomedicines](https://onco.cc/companies/generate-biomedicines/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/)

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