Internal Development Programs
|Program||Indication||Preclinical||Phase 1||Phase 2||Phase 3||Next Catalyst|
|XCART Platform™||B-Cell Non-Hodgkin Lymphoma||
Preclinical Phase in progress
Phase 1 Phase not started
Phase 2 Phase not started
Phase 3 Phase not started
|Meet with regulatory authorities to discuss development plan|
We plan to apply the XCART technology platform to develop cell-based therapeutics targeting the unique B-cell receptor on the surface of an individual patient’s malignant tumor cells for the treatment of B-cell lymphomas, an area of significant unmet medical need. Non-Hodgkin lymphoma (NHL) is a cancer that originates in the lymphatic system, with approximately 75,000 new cases each year, and represents a $5 billion market opportunity.1
XCART: Initial Market Opportunity in NHL
XCART: Proof of Mechanism in B-cell Lymphoma2
Utilizing XCART, two CAR T cell lines were generated which can differentiate between the B-cell Receptors (BCRs) derived from two individual Follicular Lymphoma (FL) patients.
In vitro target selectivity and in vivo efficacy have been demonstrated and are illustrated below:
XCART-Designed CAR T Cells Selectively Kill Raji Cell Lines Expressing Patient- Specific Target BCRs
In vitro cytotoxicity assay illustrating that XCART can generate CD8+ CAR T cells capable of targeting and lysing B cells in a BCR-specific manner. In this example, unique individual BCRs are derived from the tumors of two follicular lymphoma (FL) patients.
Left: FL1-CART and CD19-CART are both cytotoxic to Raji cells expressing the BCR from FL Patient #1.
However, FL1-CART does not target Raji cells expressing the BCR from FL Patient #3.
Right: Conversely, FL3-CART and CD19-CART are both cytotoxic to Raji cells expressing the BCR from FL Patient #3.
However, FL3-CART does not target Raji cells expressing the BCR from FL Patient #1.
XCART-Designed CAR T Cells Are Effective and Persistent in an In Vivo Mouse Tumor Model
NOD SCID mice were engrafted on Day 0 with a Raji-BCR#1 tumor line (expressing the BCR from FL Patient #1).
CD19-CART, myc-CART, or FL1-CART (targeting BCR#1) CAR T cells were infused on Day 17.
Left: CD19-CART (Black) and FL1-CART (Red) treatments have similar effect on survival.
Right: CD19-CART and FL1-CART have similar effects on tumor growth.
(Inset: Relative persistence of CD19-CART and FL1-CART, 21 days post-infusion).
- https://seer.cancer.gov/; 2: Crump, M et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood 2017 Aug 3; 3: Market Reports World. GLOBAL NON-HODGKIN LYMPHOMA THERAPEUTICS MARKET - SEGMENTED BY TYPE OF TREATMENT - GROWTH, TRENDS AND FORECASTS (2018 - 2023); BioPharm Insight Surveillance, Epidemiology, and End Results (SEER) 9 registries, National Cancer Institute, 2017
- Stepanov A, et al. 14 November 2018. Autocrine-based selection of ligands for personalized CAR-T therapy of lymphoma. Sci Adv. 4(11):eaau4580