AlloCAR T™
THERAPY

ALLOGENEIC CAR T THERAPY—
THE NEXT REVOLUTION IN CELL THERAPY

Allogene is working to overcome the limitations of AutoCAR T™ therapies by creating allogeneic CAR T cell therapies, or AlloCAR T™ therapies. Unlike autologous cell therapy, AlloCAR T™ therapy uses T cells from healthy donors.

These cells are isolated in a manufacturing facility, engineered to express CARs to recognize and destroy cancer cells, and modified via gene editing to limit autoimmune response when given to a patient. These therapies are then stored for off-the-shelf use on demand. We believe that, at scale, a single manufacturing run has the potential to yield treatment for 100+ patients.

WHY ALLOGENEIC CELL THERAPY
HAS THE POTENTIAL TO LEAD THE REVOLUTION

ACCESS

  • Potential to treat all eligible patients
  • Repeat dosing, if needed
  • No need for complex logistics

COST

  • Scalable and efficient manufacturing
  • Potential to treat 100+ patients from a single manufacturing run
  • Lower ancillary costs

SPEED/ RELIABILITY

  • Off-the-shelf for on-demand treatment
  • Less product variability, made from healthy T cells

INNOVATION

  • Multiplex gene-engineering and gene-editing capabilities
  • Opportunity for product optimization

THE DIFFERENCE STARTS WITH HEALTHY DONORS

AlloCAR T TM therapy as developed by Allogene Therapeutics

THE DIFFERENCE STARTS WITH HEALTHY DONORS

APPLYING INNOVATIVE TECHNOLOGY TO DEVELOP AlloCARSTM

Diagram showing Allogene’s development process of AlloCARs™ therapy

APPLYING INNOVATIVE TECHNOLOGY TO DEVELOP AlloCARSTM


The process for manufacturing our investigational off-the-shelf AlloCAR TTM therapy begins by harvesting healthy, selected, screened and tested T cells from healthy donors. The benefit of starting with healthy donors is that a larger portion of eligible patients, including those who are critically ill and lack a robust supply of T cells for harvest and expansion, can potentially receive treatment.

Additionally, with our platform no patient needs to undergo leukapheresis (a laboratory procedure in which a patient’s white blood cells are separated and the remaining blood cells and plasma are returned to the patient).

Next, the T cells are engineered to express CARs, which recognize certain cell-surface proteins that are expressed in hematologic or solid tumors. ALLO-501/501A and UCART19, two of our investigational therapies, recognize CD19, a cell-surface protein expressed on B-cells, including cancerous B-cells; they are just the first in a line of AlloCAR TTM therapies we plan to develop. The next step in the process involves gene editing to reduce the risk of graft-vs-host disease (GVHD) and allogeneic rejection. A T cell receptor gene is knocked out to avoid GVHD. The CD52 gene is knocked out to render the CAR T product resistant to anti-CD52 antibody treatment. ALLO-647, our proprietary investigational anti-CD52 monoclonal antibody, is designed to suppress the host immune system and allow the AlloCAR TTM therapy to stay engrafted in order to achieve full therapeutic impact.

The engineered T cells then undergo a purification step and are ultimately cryopreserved in vials for delivery to patients.

ALLOGENE IS CREATING THE AlloCAR T™ PLATFORM FOR TOMORROW

INDUCED PLURIPOTENT STEM CELLS (iPSCs)*
  • Renewable starting-cell source
  • Master cell bank of engineered iPSCs
  • Proprietary T cell differentiation technology

LEARN ABOUT iPSCs ››
IMPROVING T CELL FITNESS
  • TurboCARs™
  • Manufacturing improvement
  • Site-specific integration

LEARN ABOUT TurboCARs™ ››
PREVENTING GRAFT REJECTION
  • Enhanced lymphodepletion
  • Immune evasion

SEE HOW WE'RE ADDRESSING GVHD ››

SEE HOW WE’RE DELAYING GRAFT REJECTION ››
EXPANDING TARGET REPERTOIRE
  • Target selection/validation
  • CAR optimization
  • Multitargeting CARs
INDUCED PLURIPOTENT STEM CELLS (iPSCs)*
  • Renewable starting-cell source
  • Master cell bank of engineered
    iPSCs
  • Proprietary T cell differentiation
    technology

LEARN ABOUT iPSCs ››
PREVENTING GRAFT REJECTION
  • Enhanced lymphodepletion
  • Immune evasion

SEE HOW WE'RE ADDRESSING GVHD ››

SEE HOW WE’RE DELAYING GRAFT REJECTION ››
IMPROVING T CELL FITNESS
  • TurboCARs™
  • Manufacturing improvement
  • Site-specific integration

LEARN ABOUT TurboCARs™ ››
EXPANDING TARGET REPERTOIRE
  • Target selection/validation
  • CAR optimization
  • Multitargeting CARs
*In collaboration with Notch Therapeutics.

iPSCs: THE ROAD TO A RENEWABLE CELL SOURCE

  • Notch Therapeutics' proprietary platform supports scalable, feeder cell-free manufacturing of mature T cells and CAR T engineered cells
  • Induced pluripotent stem cells (iPSCs) can be engineered at the stem-cell stage, enabling banking of clonal cells
  • Exclusive worldwide licensing agreement to develop iPSC AlloCAR™ products for initial application in non-Hodgkin lymphoma, leukemia, and multiple myeloma
  • Notch Therapeutics is a recognized leader in the differentiation of iPSCs into T cells

TurboCAR™: TURBOCHARGING CAR T CELLS

Diagram of the turbocharging of Car T cells (TurboCAR™)
  • Cytokine stimulation can increase the potency and durability of engineered T cells
  • TurboCAR™ is designed to recapitulate cytokine signaling selectively in CAR T cells and may have potential benefits, subject to investigation
    – Minimizes systemic toxicity
    – Does not stimulate host immune cells which could reject CAR
    – Delivers survival benefit selectively to CAR T cells
  • Opportunities for development include
    – Improving the efficacy of CAR T cells
    – Reducing CAR T cell dose requirement
    – Overcoming exhaustion to enable CAR T therapies to be used for solid tumors

ELIMINATION OF TCR IN DONOR T CELLS MAY CONTROL GvHD

Diagram showing the elimination of TCR in donor T Cells
Diagram showing the elimination of TCR in donor T Cells

ALLO-647: SELECTIVE LYMPHODEPLETION MAY DELAY GRAFT REJECTION

Host T Cell Recovery Delayed by Addition of Anti-CD52
Diagram showing ALLO-647
STATE-OF-THE-ART, IN-HOUSE MANUFACTURING FOR ON-DEMAND AlloCAR T™ AVAILABILITY
Allogene’s in-house manufacturing center
Building state-of-the-art, world-class manufacturing capabilities is at the core of our strategy to deliver readily available cell therapy faster, more reliably, and at greater scale. Our new manufacturing facility, located in Newark, California, in the eastern region of the San Francisco Bay Area, is being designed to provide in-house quality assurance and quality control, per good manufacturing practices (GMPs), to ensure a reliable supply of AlloCARs™ for our clinical programs and commercial products, pending regulatory approval.

AlloCAR T™ therapies for Allogene's clinical trials are manufactured in a dedicated, purpose-built GMP suite by a contract manufacturing organization (CMO), which is expected to remain a component of our manufacturing strategy.
©2020 ALLOGENE THERAPEUTICS