Redefining ADCs with Novel Mechanisms of Action

The future of Antibody-Drug Conjugates requires moving beyond traditional payload mechanisms of topoisomerase and tubulin inhibitors. Hexagon’s proprietary ADC discovery platform has identified orthogonal ADC payloads that are essential to cancer cell survival.

Our lead programs focus on Protein Translation Inhibitors (PTIs), exploiting a critical vulnerability in cancer cells that rely on continuous proteome remodeling. By targeting this vulnerability, Hexagon’s PTI payloads offer first-in-class potential to deliver deep, durable responses.

Hexagon’s discovery engine is also identifying other new payload mechanisms beyond PTIs, building a pipeline of mono-payload and dual-payload ADCs.

See Our Pipeline

Lead Program: HEX-360

Why new ADC payloads? Addressing major unmet needs in cancer

Overcoming Acquired Resistance: Tumors evolve resistance to the limited classes of standard ADC payloads, such as topoisomerase 1 (topo) and tubulin inhibitors. Novel payloads are needed to bypass these entrenched resistance pathways.
Expanding Treatable Indications: Many intractable solid tumors do not respond to traditional ADC mechanisms. Discovering payloads in untapped chemical space allows therapies to target a broader spectrum of cancers that are currently unaddressable by ADCs.
Widening the Therapeutic Window: Current payloads are often restricted by dose-limiting toxicities. Next-generation payloads, with orthogonal mechanisms, are needed to minimize effects on healthy tissue.
Exploiting New Cellular Vulnerabilities: Novel payloads can target different biological dependencies, such as protein translation, shutting down cancer cell survival mechanisms from a completely new angle.

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.

See Our Pipeline

Hexagon’s ADC payload discovery engine

All FDA-approved ADC payloads are natural product-derived: topo inhibitors are derived from plants, and tubulin inhibitors are derived from microbes. These molecules evolved over millions of years as potent cytotoxins, and scientists now use them as valuable ADC payloads. Advances in genomics and metabolomics, combined with AI, have changed the landscape of natural product discovery, allowing a deeper understanding of these small molecules. Hexagon leverages these advances to unlock next-generation ADC payload mechanisms.

Drug-Target Prediction

AI-enabled platform predicts small molecules that inhibit cancer-related proteins.

Genomic + Metabolomic database

We built the world’s largest database of microbial genomes and metabolites via LCMS

Compound Production

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

Hexagon's AI-enabled ADC discovery engine

Hexagon’s ADC platform has identified novel payload mechanisms of action spanning pathways such as cell cycle, transcription, translation, cytoskeleton, and more.

Our AI-enabled microbial genome database is the world’s largest, with over 100,000 strains banked and over 80,000 genomes sequenced.

Our discovery engine predicts ~400 potential mechanisms of action, including DNA/RNA-associated pathways, energy production, protein-associated pathways, fat/lipid synthesis, and other cancer-related pathways.

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. This creates broad opportunities to discover and develop new approaches to treating patients with intractable cancers.

See Our Pipeline

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).

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.

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.

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

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

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

An antifungal with a novel mechanism of action discovered via resistance gene-guided genome mining

Bruno Perlatti, Sandeep Vellanki, Yalong Zhang, Yi-Ming Chiang, Yingxia Hu, Mengdi Yuan, Kyle Dunbar, Abigail Fine, Michelle F Grau, Sheena Li, Timothy O’Donnell, Rajani Shenoy, Hongtao Li, Hui Shi, Xia Xu, Zeyu Chen, Tara Arvedson, Yi Tang, Robert A Cramer, Victor Cee, Colin JB Harvey

Resistance Gene-Guided Genome Mining Reveals RPL10 as the Target of Ligustrone A

Journal of the American Chemical Society

Danielle A. Yee, Ross D. Overacker, Michelle F. Grau, Amber Cornelius, Adrianne Pigula, Daniel Mummau, Thomas Pavey, Cynthia Bailey, Clarence Hue Lok Yeung, Lawrence S. Hon, Joseph E. Spraker, Sheena Li, Bruno Perlatti, Samuel K. Oteng-Pabi, Henry H. Le, Colin J. B. Harvey

Resistance gene–guided genome mining reveals the roseopurpurins as inhibitors of cyclin-dependent kinases

Proceedings of the National Academy of Sciences

Kyle L. Dunbar, Bruno Perlatti, Nicholas Liu, Amber Cornelius, Daniel Mummau, Yi-Ming Chiang, Lawrence Hon, Monika Nimavat, Jason Pallas, Sina Kordes, Ho Leung Ng, Colin J. B. Harvey

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

Redefining ADCs with Novel Mechanisms of Action

The future of Antibody-Drug Conjugates requires moving beyond traditional payload mechanisms of topoisomerase and tubulin inhibitors. Hexagon’s proprietary ADC discovery platform has identified orthogonal ADC payloads that are essential to cancer cell survival.

Our lead programs focus on Protein Translation Inhibitors (PTIs), exploiting a critical vulnerability in cancer cells that rely on continuous proteome remodeling. By targeting this vulnerability, Hexagon’s PTI payloads offer first-in-class potential to deliver deep, durable responses.

Hexagon’s discovery engine is also identifying other new payload mechanisms beyond PTIs, building a pipeline of mono-payload and dual-payload ADCs.

Lead Program: HEX-360

Why new ADC payloads? Addressing major unmet needs in cancer

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.

Hexagon’s ADC payload discovery engine

Drug-Target Prediction

Genomic + Metabolomic database

Compound Production

Hexagon's AI-enabled ADC discovery engine

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

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