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Launching twoXAR’s PDAC program with SBIR Grant support from the National Cancer Institute of the National Institutes of Health

by: Tim Heuer, PhD
Senior Director Translational Science,
Principal Investigator, SBIR Grant Award Number R43 CA236164–01

Pancreatic cancer is a terrible disease. The most common form, pancreatic ductal adenocarcinoma (PDAC), has a grim prognosis and the efficacy of existing and experimental treatments leaves much to be desired.

  • Poor Prognosis — PDAC is projected to be the 2nd leading cause of cancer-related deaths in the U.S. by 2030 at 63,000 annual deaths.[1][2] Survival rates for PDAC patients are very low (5-year overall survival is 8%), in part from late diagnosis, early metastasis, low immunogenicity, & poor response to cytotoxic agents.[3][4]
  • Limited Treatment Landscape — Standard of care therapies are cytotoxic chemotherapy agents, gemcitabine and nab-paclitaxel, which have a median overall survival of 6–11 months.[1] Immune-based therapies have not shown significant activity to date in PDAC.[1][5]
  • Limited Targets/Ideas — Mutation of the KRAS oncogene, which presents a very difficult drug target, is a primary driver of PDAC oncogenesis and progression.[6][7][8]

Because of these factors, there is a strong need for anti-cancer agents that are effective in the PDAC tumor setting that act on differentiated mechanisms. With advances in software and a significant amount of real-world PDAC data, there is the opportunity to leverage technology to model the disease more holistically and identify better potential treatments for patients.

As the promise of artificial intelligence continues to permeate many facets of our daily life, at twoXAR we are proponents of practical applications of predictive algorithms, especially in the field of drug discovery and development. We’ve applied our drug discovery technology to many indications across therapeutic areas including oncology, immunology, and ophthalmology. We are honored to announce that the National Institutes of Health (NIH) recognizes this opportunity and has awarded the twoXAR team a Small Business Innovation Research (SBIR) grant to development targeted, safe, and effective drugs against PDAC by leveraging our computational drug discovery approach. With support from the NIH’s SBIR grant, we have launched our PDAC program into preclinical studies.

As Senior Director of Translational Science, I focus on steering our programs on the best path to the clinic. This often involves bringing expertise and resources to the table to increase the probability of a twoXAR-discovered drug benefiting patients, and NIH funding is a key ally in our drug development network. As with any drug development program in the challenging field of medicine, there are no guarantees, but we’re working to bring technology-driven approaches to PDAC drug development.

The content of this blog post is solely the responsibility of twoXAR, Inc. and does not necessarily represent the official views of the National Institutes of Health. This blog post discusses a project that will be supported by National Cancer Institute (NCI) of the National Institutes of Health under award number R43 CA236164–01.

[1] Chiaravalli M, Reni M, O’Reilly EM. Pancreatic ductal adenocarcinoma: State-of-the-art 2017 and new therapeutic strategies. Cancer Treatment Reviews. 2017;60:32–43. DOI: 10.1016/j.ctrv.2017.08.007

[2] Rahib L, Smith BD, […] Matrisian LM. Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913–21.

[3] Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2006;20(10):1218–49. PMID: 16702400. DOI: 10.1101/gad.1415606.

[4] Luchini C, Capelli P, Scarpa A. Pancreatic Ductal Adenocarcinoma and Its Variants. Surg Pathol Clin. 2016;9(4):547–60. PMID: 27926359. DOI: 10.1016/j.path.2016.05.003

[5] Wartenberg M, Cibin S, […]Karamitopoulou E. Integrated Genomic and Immunophenotypic Classification of Pancreatic Cancer Reveals Three Distinct Subtypes with Prognostic/ Predictive Significance. 2018; Clin Cancer Res; 24(18).

[6] Mueller S, Engleitner T, […]Rad R. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. Nature 2018: 554(7690):62–68.

[7] The Cancer Genome Atlas Research Network. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell 2017; 32, 185–203.

[8] Bailey P, Chang DK, […] Grimmond SM. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47–52.

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