# Development of Deep Mutational Scanning with Duplex Sequencing (DMS-DS) for anti-cancer drug evaluation and administration

> **NIH NIH R42** · ATLAS BIOLOGICS, LLC · 2024 · $400,000

## Abstract

Cancer remains a leading cause of death worldwide. Targeted agents have dramatically improved the
prognosis of over 30 cancer types, but are fundamentally limited by the evolution of resistance. Currently,
next generation targeted therapies are retrospectively designed to cover the liabilities of clinically
available targeted therapies. Unfortunately, every investigational compound will have resistance
mutations that prevent complete and durable response. Deep mutational scanning (DMS) has emerged
as a powerful tool for evaluating the mutational landscape of target proteins. DMS screens have recently
been used by academic labs to characterize the resistance landscape of targeted anticancer compounds,
but employ standard next generation sequencing (NGS) techniques to measure a highly complex mutant
pool. NGS has a high error rate that prohibits accurate measurements of complex mutational pools.
Duplex Sequencing (DS) is an error correction method that enables the precise measurement of
mutations down to a frequency of 1 in 300,000 in a pooled cell-based library. The Pritchard lab has
developed Deep Mutational Scanning with Duplex Sequencing (DMS-DS) and propose to refine this
technology into a commercially viable service for anticancer pharmaceutical development. In Phase I of
this Small Business Transition Grant, we will harden and scale our DMS-DS technology into an industry-
viable screening platform. In Phase II we will screen all approved BCR-ABL inhibitors, design and build
DMS-DS screens for two lung cancer drug targets, and harden our BCR-ABL DMS-DS platform into a
commercialized end-to-end service. The final product of this SBTG project will be a robust, powerful, and
marketable new research tool ready for use by anticancer pharmaceutical developers. Our company will
leverage this tool (DMS-DS) to expedite lead candidate prioritization and optimize next generation drug
design.
Targeted therapies have revolutionized clinical outcomes for numerous cancers, but acquired resistance
critically limits their long-term utility. Having a commercially available screening platform that can
accurately predict the mutational landscape of next generation therapies will lead to more successful
clinical trials, better targeted therapies, and more effective treatment plans for cancer patients. We firmly
believe our technology will accelerate effective anticancer drug development and that our team is an
unparalleled position to succeed at the commercialization of this product.

## Key facts

- **NIH application ID:** 10912139
- **Project number:** 1R42CA290940-01
- **Recipient organization:** ATLAS BIOLOGICS, LLC
- **Principal Investigator:** Joshua Reynolds
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2024-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912139

## Citation

> US National Institutes of Health, RePORTER application 10912139, Development of Deep Mutational Scanning with Duplex Sequencing (DMS-DS) for anti-cancer drug evaluation and administration (1R42CA290940-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10912139. Licensed CC0.

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