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Relating Drugs to Genotypes to Transform Precision Cancer Therapeutics with Tuba-seq - a Novel, Highly Scalable and Quantitative Preclinical Experimental Oncology Platform

Award Number: R44CA250672
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/08/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2022

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Relating Drugs to Genotypes to Transform Precision Cancer Therapeutics with Tuba-seq - a Novel, Highly Scalable and Quantitative Preclinical Experimental Oncology Platform - PROJECT SUMMARY D2G Oncology, Inc. proposes to develop a novel preclinical experimental platform that will effectively relate cancer drugs to genotypes (“D2G”) to predict pharmacogenomic interactions. D2G Oncology's innovative approach dramatically improves on established autochthonous mouse models of human cancer. These proven models allow controlled genomic alterations to initiate tumors in vivo in an appropriate immune-competent microenvironment and faithfully recapitulate progression of human cancer. D2G's innovative methods for the first time enable these animal models to become truly scalable and rigorously quantitative, and hence prac- tical to support drug discovery. D2G's approach can efficiently interrogate a large matrix of tumor genotypes to predict differential patient responses to therapies. Pharmaceutical companies are eager to obtain this infor- mation. D2G will significantly advance the state of the art in precision cancer therapy by helping pharma to rationally select candidate compounds to advance and better match them to patients. D2G's oncology platform will increase the success rate of clinical trials and lead to more effective personalized cancer treatments. The key innovation is a novel tumor barcoding and sequencing (Tuba-seq) pipeline. Every clonal tumor is uniquely barcoded, so the identity and number of cancer cells in each tumor can be readily quantified from bulk tumor-bearing tissues. Combined with lentiviral-mediated CRISPR/Cas9 somatic genome editing, tumor barcoding allows many predefined tumor genotypes to be generated all at once in individual animals and tracked separately. Tuba-seq enables many tens of experiments (which would each ordinarily require separate cohorts of mice) to be multiplexed into a single mouse. Compared with conventional genetically engineered mouse models, this approach enormously enhances scalability, introduces rigorous quantification, and reduces sources of variation. The overall goal of the proposed Direct Phase 2 SBIR project is to transform the Tuba-seq pipeline into a robust platform that can be marketed as a commercial service to pharmaceutical companies. Specific aims are to (1) expand the panel of tumor suppressor genes that the platform interrogates and carefully calibrate their effect sizes and (2) rigorously validate the ability of the platform to resolve small but clinically meaningful differences in tumor suppressor gene-drug effect sizes with high statistical confidence, relying only on small cohorts of ani- mals. D2G will create the first practical and scalable preclinical experimental modeling approach that can assess how candidate drugs interact with diverse, precisely-engineered cancer genotypes to predict differential patient responses to therapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	D2G ONCOLOGY, INC.	353 LOWELL AVE	PALO ALTO	CA	94301	SANTA CLARA	USA	Cancer Treatment Research	000	2	10/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $865,070 )
2021	2021	D2G ONCOLOGY, INC.	353 LOWELL AVE	PALO ALTO	CA	94301	SANTA CLARA	USA	Cancer Treatment Research	000	2	8/26/2021	NON-COMPETING CONTINUATION	$865,070
														Subtotal = $865,070

Issue Date FY: 2020 ( Subtotal = $1,134,487 )
2020	2020	D2G ONCOLOGY, INC.	353 LOWELL AVE	PALO ALTO	CA	94301	SANTA CLARA	USA	Cancer Treatment Research	000	1	9/8/2020	NEW	$1,134,487
														Subtotal = $1,134,487

Grand Total All Awards = $1,999,557

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Relating Drugs to Genotypes to Transform Precision Cancer Therapeutics with Tuba-seq - a Novel, Highly Scalable and Quantitative Preclinical Experimental Oncology Platform

Award Number: R44CA250672

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/08/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2022

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