PACT Pharma
Our Platform

Approach

Each person’s cancer is driven by a unique set of mutations that can code for cancer-specific proteins that are displayed on the tumor cells called “neoantigens.” Selected peptides that are both derived from neoantigens binding to the patient’s HLA and recognized by autologous T cells are called neoepitopes (neoE). These neoEs are designed to be highly specific to each person’s cancer with less than one percent of these peptide-HLA targets shared among individuals with solid cancer. T cells capable of targeting neoepitopes from tumor-specific mutations hold the potential to recognize and kill tumor cells.

PACT has developed a high-throughput technology called imPACT Isolation Technology®. This technology allows us to identify and capture neoE-specific T cells from peripheral blood. Following manufacturing of these specific T cells, the PACT platform directs a patient’s own immune system to trigger a response directly against their specific tumor mutations:

  • Our proprietary functional verification and characterization process allows us to choose the T cells for potential therapeutic benefit to the patient, from which we extract the T cell receptor (TCR) sequences to develop a polyclonal product.
  • Using non-viral precision genome engineering, the neoE-targeted TCR sequences replace the endogenous TCR of fresh CD8 and CD4 T cells collected by apheresis from that same patient’s peripheral blood (autologous neoE TCR engineered into autologous fresh T cells).
  • The engineered cells are expanded in culture and subsequently reinfused into the patient.

A Personalized Therapy for Every Patient

Tumor immunogenicity is not only patient specific but inherently exclusive to the individual tumor itself. Tumor-specific mutations are presented to T cells on Human Leukocyte Antigens (HLA) molecules. These neo-epitope-HLA protein targets are different for each cancer patient. Less than 1% of neo-epitope specific HLA (neoE-HLA) targets are the same among individuals with solid cancer.

PACT’s technology platform enables us to build a designer library of neoE-HLA snares for each patient regardless of ethnicity. These neoE-HLA snares are then assembled into barcoded “snare libraries” for the interrogation of matched peripheral blood mononuclear cells (PBMCs) from that patient for CD8 T cells that specifically bind the neoE-HLA tumor targets.

Following imPACT Isolation Technology®, our bioinformatics algorithms define the most therapeutically relevant neoantigens present in each patient's tumor, from which we extract the T cell receptor (TCR) sequences for PACT product development. Using non-viral precision genome engineering, the neoTCR replaces the endogenous TCR of fresh CD8 and CD4 T cells collected from that same patient’s peripheral blood by leukapheresis (autologous neoE TCR engineered into autologous fresh T cells) for re-infusion into the patient.

The PACT Difference

Our platform is designed to enable engineered T cells to address key challenges for solid cancer treatment: target specificity and validation, broad applicability and precise non-viral genome engineering for exclusive on-tumor targeting.

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Target Specificity: Personalized neoantigens in blood are not only predicted but also verified using our proprietary imPACT Isolation Technology®

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Broad applicability across all solid cancers & all patient ethnicities: Patient's own tumor-specific neoTCRs guide PACT to engineer neoTCR T cells for that patient

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Precision non-viral genome engineering:  Produces  functionally natural neoTCR T cells of a younger phenotype which are known to persist longer inside a patient after infusion

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Scalable manufacturing: Proprietary TrifeCtaRModular in-house GMP manufacturing

Our Approach to Developing Personalized T-Cell Therapies

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Personalized NeoTCR Discovery & Validation Process

Predict and prioritize targets from tumor mutation sequencing

  • PACT receives patient tumor biopsy and peripheral blood samples

  • PACT deep sequences patient tumor biopsy specimen to derive sequence information

  • PACT’s proprietary bioinformatic algorithms effectively predict and prioritize a list of potential neoE-HLA targets that are most likely to mount an immune response

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