KRAS is the most common driver oncogene in human malignancies. Mutations in KRAS act as oncogenic drivers in multiple diverse cancer types
pancreatic
adenocarcinoma
94%
KRAS is the most common driver oncogene in human malignancies. Mutations in KRAS act as oncogenic drivers in multiple diverse cancer types
lung
adenocarcinoma
26%
KRAS is the most common driver oncogene in human malignancies. Mutations in KRAS act as oncogenic drivers in multiple diverse cancer types
colorectal
adenocarcinoma
30-40%
KRAS is the most common driver oncogene in human malignancies. Mutations in KRAS act as oncogenic drivers in multiple diverse cancer types
multiple
myeloma
30%
Among cancers where KRAS mutations are most common, nearly 90% of all mutations occur at the Glycine at position 12, and most often substitute a valine or aspartic acid (G12V or G12D). Affini-T targets mutations with engineered T cells expressing TCRs with high affinity and specificity for mutant KRAS that are identified through our precise, high throughput platform.
Our Platform
Discovery
Evaluate millions of T Cells from the natural repertoires of many donors with Affini-T’s high-throughput platform to identify unusually effective TCRs with very high affinity and specificity for common KRAS mutations. For each KRAS mutation, Many candidate TCRs are synthesized and evaluated through in-depth functional analysis to identify the most effective receptors for use in patients.
T Cell Engineering
Affini-T genetically reprograms patient T cells, empowering them to recognize the target KRAS mutation, and also maintaining and enhancing pathways that make the cells function better than T cells normally present, with the goal of creating cells that can cure malignancy.
Expansion
Multiply the engineered, high- affinity T cells to create an army of cells that express the highly effective, cloned TCRs through an in vitro expansion process that maintains T cell function. A few to many concept.
Delivery
In vivo delivery of safe, high affinity T cells that express the cloned TCR’s that can function and persist after infusion into cancer patients.
Driver mutations are often single amino acid substitutions in key regulatory genes that spur uncontrollable cell proliferation. Within the extraordinary diversity of any individual’s T cell repertoire, there may only be a handful of T cells that express a TCR capable of recognizing this subtle molecular change.
We evaluate the most effective mutation- specific TCRs from many repertoires, to identify rare TCRs that confer unusually potent recognition of the target mutation. These high affinity TCRs exhibit a low risk of off-target toxicity, since they are identified from the peripheral blood of healthy individuals.
We use NGS-based technologies to analyze antigen-specific T cells from multiple donors. Our unique approach allows us to identify and characterize a comprehensive set of antigen- specific T cell clonotypes present in each donor repertoire. For each clonotype we assess peptide/MHC binding, T cell phenotype and transcriptional profile to predict TCR affinity and functional avidity.
Individual clonotypes can exhibit substantial variability in phenotype and function that is independent of the TCR, but which can influence apparent TCR affinity and antigen responsiveness. We have devised a unique screening platform that accounts for these differences to identify a more comprehensive set of candidate TCRs from each donor repertoire, including high affinity/avidity TCRs that would likely be missed by alternative approaches.
Leadership
Phil Greenburg, MD
Dr. Greenberg is the Rona Jaffe Foundation Endowed Chair and Head of the Program in Immunology at the Fred Hutchinson Cancer Research Center, Professor of Medicine & Immunology at the University of Washington, and Investigator of the Parker Institute for Cancer Immunotherapy.
Jak Knowles, MD
Dr. Jak Knowles joined Leaps by Bayer as Vice President of Venture Investments in 2018. Prior to joining
Bayer Jak served as CEO of CytoSen Therapeutics,
Inc. a cancer immunotherapy company focused on developing Natural Killer cell therapies for oncology indications. In 2016, Jak co-founded and launched Exonics Therapeutics, a CRISPR gene-editing company focused on delivering therapies for Duchenne muscular dystrophy, and served as President and interim CEO. Jak has a medical degree from Stanford University where he graduated with honors in biomedical research, and has had a career in healthcare investing spanning over a decade. Jak has previously served on the Board of Directors for the pharma biotech
Aude Chapuis, MD
Dr Chapuis is an Associate Member of the Clinical Research Division and an Associate Professor in the Department of Medicine She is also an attending physician in immunotherapy and bone marrow transplant, and the John C and Karyl Kay Hughes Endowed Chair.
Tom Schmitt, MD
