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Novel ADC Payloads for Cancer

Hexagon Bio is developing novel ADC payload mechanisms to overcome resistance to today’s payloads and expand the indication space for ADCs.

 

 

Next-generation payloads to address major unmet needs in cancer

All FDA-approved ADC payloads were discovered as natural products:   topoisomerase-1 inhibitors are derived from plants, and tubulin inhibitors are derived from microbes. These molecules evolved over millions of years to be potent cytotoxins; scientists put them to use as valuable ADC payloads.

Advances in genomics, metabolomics, and medicinal chemistry have changed the landscape of cytotoxic natural products, allowing a deeper understanding of these small molecules and how to deploy them as ADC payloads.  Hexagon leverages these advances to unlock next-generation of ADC payload mechanisms, beyond topo and tubulin inhibitors.

Today we’re solving for resistance to existing treatments in cancer. Tomorrow, we’ll unlock the full potential of targeted cytotoxic therapy for cancer, aiming to deliver deep, durable responses and potential cures.

Our ADC payload discovery engine

Advances over the last decade in genomics, metabolomics, and medicinal chemistry have changed the landscape of natural product discovery. Hexagon leverages natural products from plant and microbial sources and deploys them as ADC payloads for cancer.

Drug-Target Prediction

Our genomic platform computationally predicts cytotoxic small molecules that inhibit cancer-related proteins.

Genomic + Metabolomic database

We are building the world’s largest database of microbial genomes and metabolites, giving us access to diverse, cytotoxic natural products

Compound Production

Our in-house production platform uses advances in medicinal chemistry and fermentation, safely producing potent compounds at scale

Solving for cancer

Many of the compounds produced by the earth’s biodiversity target core pathways implicated in cancer. These compounds went on to form the basis of antibody-drug conjugates.

For ADCs to be effective, they need to carry potent, cytotoxic payloads. All currently approved ADC payloads are derived from cytotoxic natural products, which evolved over millions of years in microbes and plants:

Tubulin inhibitors

  • Monomethylauristatins: MMAE, MMAF (marine mollusk Dolabella auricularia)
  • Maytansine derivatives: DM1, DM4 (Ethiopian shrub Maytenus serrata)

DNA damage
(Break or Alkylation)

  • Calicheamicin (bacterium Micromonospora echinospora)
  • PBD (bacterium Streptomyces erythraeus)
  • Duocarmycins (bacterium Streptomyces sp)

DNA damage
(Topoisomerase-1 inhibition)

  • Camptothecin derivatives (Chinese tree Camptotheca acuminata)
Antibody Drug Conjugates in Oncology

Humans, microbes, and plants all share ancient, growth-related pathways, including some that are implicated in cancer. These pathways include tubulin, topoisomerase, and DNA replication, which are the targets of existing antibody drug conjugate (ADC) payloads today. All of these are based on natural products. Hexagon’s platform has identified other mechanisms of action, representing next-generation ADC payloads, spanning pathways such as cell cycle, transcription, translation, cytoskeleton, and more. This creates broad opportunities to discover and develop new small molecule approaches to treating patients with intractable cancers.

Our proprietary genome database is expanding, with over 100,000 organismal strains banked and over 80,000 genomes sequenced.

Our discovery engine predicts ~400 hundred potential ADC payload mechanisms of action, including DNA/RNA-associated pathways, energy production, protein-associated pathways, fat/lipid synthesis, and other cancer-related pathways. We have identified the most promising among these, using our proprietary tools.

Hexagon’s compound production systems can safely manufacture highly potent, toxic natural products at production scale.

Hexagon’s ADC payloads bring an opportunity to improve therapeutic response and overcome resistance observed to other payload classes. These payloads will also bring treatment options to tumor types that do not respond to topo- or tubulin-based ADCs in the first place.

1% of the world’s microbial and plant genomes have been sequenced. Many existing blockbuster drugs were discovered here.

99% of microbial and plant
genomes have yet to
be sequenced

Vast troves of new medicines are waiting to be surfaced.

Publications & Presentations

HER2-Translation Inhibitor ADC: A Development Candidate ADC Featuring a Novel Translation Inhibitor Payload With Broad Efficacy and a Favorable Non Human Primate Safety Profile

AACR Annual Meeting 2026

Tara Arvedson, Madhura Deshpande, Kyle Dunbar, Amandeep Gakhal, Christopher Kimberlin, Corey Reeves, Edres Babacarkhial, Cynthia Bailey, Nolan Carney, Yi-Ming Chiang, Amber Cornelius, Natalie Duong,
Colin Harvey, Yingxia Hu, Dimitri Khrakovsky, Jose Leighton Jr, Yu (Dennis) Liu, Luca Lizzadro, Wadie Mahauad-Fernandez, Octovia Monteiro, Samuel Oteng-Pabi, Bruno Perlatti, Samantha Saiki, Jennifer Schmidt, Rajani Marthappa
Shenoy, Joseph Spraker, Mélanie Uguen, Jakub Vaith, Sandeep Venkataram, Kendra Wheeler, Shiyan Xu, Danielle Yee, Clarence Hue Lok Yeung, Bo (Eva) Yuan, Victor Cee, Natacha Le Moan (nlemoan@hexagonbio.com).

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The Development Path of a HER2-Targeted Translation Inhibitor ADC: A Novel Payload and ADC to Address a Growing Clinical Need

5th ADC Analytical Development Summit

Christopher Kimberlin, Madhura Deshpande, Kyle Dunbar, Amandeep Gakhal, Corey Reeves, Edres Babacarkhial, Cynthia Bailey, Nolan Carney, Yi-Ming Chiang, Amber Cornelius, Natalie Duong, Colin Harvey,
Yingxia Hu, Dimitri Khrakovsky, Jose Leighton Jr, Yu (Dennis) Liu, Luca Lizzadro, Wadie Mahauad-Fernandez, Octovia Monteiro, Samuel Oteng-Pabi, Bruno Perlatti, Samantha Saiki, Jennifer Schmidt, Rajani Marthappa Shenoy, Joseph Spraker,
Mélanie Uguen, Jakub Vaith, Sandeep Venkataram, Kendra Wheeler, Shiyan Xu, Danielle Yee, Clarence Hue Lok Yeung, Bo (Eva) Yuan, Natacha Le Moan, Victor Cee, Tara Arvedson.

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Protein Translation Inhibitors (PTIs) Enable Next-Generation Antibody Drug Conjugates

2026 WADC London

Victor Cee, Madhura Deshpande, Kyle Dunbar, Amandeep Gakhal, Christopher Kimberlin, Corey Reeves, Edres Babacarkhial, Cynthia Bailey, Nolan Carney, Xufeng Cao, Yi-Ming Chiang, Amber Cornelius, Natalie
Duong, Colin Harvey, Yingxia Hu, Dimitri Khrakovsky, Jose Leighton Jr, Yu (Dennis) Liu, Luca Lizzadro, Wadie Mahauad-Fernandez, Octovia Monteiro, Samuel Oteng-Pabi, Bruno Perlatti, Jennifer Schmidt, Rajani Marthappa Shenoy,
Joseph Spraker, Mélanie Uguen, Jakub Vaith, Sandeep Venkataram, Kylie Wells, Kendra Wheeler, Shiyan Xu, Danielle Yee, Clarence Hue Lok Yeung, Bo (Eva) Yuan, Natacha Le Moan, Tara Arvedson.

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Antibody Drug Conjugates With Novel Translation Inhibitor Payloads Exhibit Tumor Growth Inhibition in Solid Tumor Models

16th World ADC San Diego Conference

Corey Reeves, Edres Babacarkhial, Cynthia Bailey, Nolan Carney, Xufeng Cao, Yi-Ming Chiang, Amber Cornelius, Madhura Deshpande, Kyle Dunbar, Natalie Duong, Amandeep Gakhal, Colin Harvey, Yingxia
Hu, Dimitri Khrakovsky, Christopher Kimberlin, Jose Leighton Jr, Yu (Dennis) Liu, Luca Lizzadro, Octovia Monteiro, Samuel Oteng-Pabi, Bruno Perlatti, Rajani Marthappa Shenoy, Joseph Spraker, Mélanie Uguen, Jakub Vaith, Sandeep Venkataram, Kylie Wells, Kendra Wheeler, Shiyan Xu, Danielle Yee, Clarence Hue Lok Yeung, Bo (Eva) Yuan, Natacha Le Moan, Victor Cee, Tara Arvedson

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Characterization of First-In-Class Translation Inhibitor ADCs to Overcome SOC Payload Resistance

16th World ADC San Diego Conference

Amandeep K. Gakhal, Cynthia Bailey, Edres Babacarkhial, Nolan Carney, Xufeng Cao, Yi-Ming Chiang, Amber Cornelius, Madhura Deshpande, Kyle Dunbar, Natalie Duong, Colin Harvey, Yingxia Hu, Dimitri Khrakovsky, Christopher Kimberlin, Jose Leighton Jr, Yu (Dennis) Liu, Luca Lizzardo, Octovia Monteiro, Ryan Mun, Samuel Oteng-Pabi, Bruno Perlatti, Corey Reeves, Rajani Marthappa Shenoy, Joseph Spraker, Mélanie Uguen, Jakub Vaith, Sandeep Venkataram, Kylie Wells, Kendra Wheeler, Shiyan Xu, Danielle Yee, Clarence Hue Lok Yeung, Bo (Eva) Yuan, Victor Cee, Natacha Le Moan, Tara Arvedson

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Inhibiting Protein Translation: A Novel ADC Payload With Strong Antitumor Activity in Mono- and Dual-Payload Formats

AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

Tara Arvedson, Edres Babacarkhial, Cynthia Bailey, Nolan Carney, Xufeng Cao, Yi-Ming Chiang, Amber Cornelius, Madhura Deshpande, Kyle Dunbar, Natalie Duong, Amandeep Gakhal, Colin Harvey, Yingxia Hu, Dimitri Khrakovsky, Christopher Kimberlin, Jose Leighton Jr, Yu (Dennis) Liu, Luca Lizzadro, Octovia Monteiro, Samuel Oteng-Pabi, Bruno Perlatti, Corey Reeves, Rajani Marthappa Shenoy, Joseph Spraker, Mélanie Uguen, Jakub Vaith, Sandeep Venkataram, Kylie Wells, Kendra Wheeler, Shiyan Xu, Danielle Yee, Clarence Hue Lok Yeung, Bo (Eva) Yuan, Victor Cee, Natacha Le Moan

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Inducible mismatch repair streamlines forward genetic approaches to target identification of cytotoxic small molecules

Cell Chemical Biology

Thu P. Nguyen, Min Fang, Jiwoong Kim, Baiyun Wang, Elisa Lin, Vishal Khivansara, Neha Barrows, Giomar Rivera-Cancel, Maria Goralski, Christopher L. Cervantes, Shanhai Xie, Johann M. Peterson, Juan Manuel Povedano, Monika I. Antczak, Bruce A. Posner, Colin J.B. Harvey, Brian T. Naughton, David G. McFadden, Joseph M. Ready, Jef K. De Brabander, Deepak Nijhawan

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