UCD19 CAR T Cells / University of Colorado - LARVOL DELTA

UCD19 CAR-T cell therapy for adults with B-cell acute lymphoblastic leukemia in first complete remission with MRD positivity: Preliminary Results of A phase I/ib clincal trial (ASH 2025) - "All three patients with NGS-MRD recurrence became NGS-MRD negative after one cycle of blinatumomab and were subsequently consolidated with allogeneic stemcell transplant. Low disease burden relapses (detected by NGS-MRD)occurred in some patients who had loss of BCA within 6 months of infusion. Enrollment in the phase 1bdose expansion at DL2 is ongoing."

CAR T-Cell Therapy • Clinical • IO biomarker • Minimal residual disease • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • CRLF2 • EBF1 • KMT2A • PDGFRB • TP53

Use of CD19 CAR-T Cells in Adult B-Cell Acute Lymphoblastic Leukemia (B-ALL) with Minimal Residual Disease (MRD) Positivity at First Complete Remission: Preliminary Outcomes from a Phase I Clinical Trial (ASH 2024) - "Incorporation of blinatumomab and/or inotuzumab in CR1 may mitigate the negative prognostic significance of MRD, however it is unclear if intensity of standard post-remission therapy can be safely reduced without compromising outcomes...We designed a phase I clinical trial to determine safety and tolerability of UCD19 CAR-T cell therapy for adults with B-ALL in MRD+ CR1 who are at high risk for relapse.Methods : Eligible patients include adults (≥18yo) with B-ALL in CR1 after induction therapy, with MRD positivity by either flow cytometry or NGS (Clonoseq)...Longer follow-up is needed to determine if remissions remain durable, and to determine the relationship between functional persistence (as measured by B-cell aplasia) and remission durability. Enrollment is ongoing at DL2."

CAR T-Cell Therapy • Clinical • Minimal residual disease • P1 data • Residual disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Septic Shock • Thrombocytopenia • CXCL8 • IFNG • IL6 • TNFA

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: University of Colorado, Denver | Active, not recruiting ➔ Completed

Trial completion • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

UCD19 CAR T Therapy in Adults With B-ALL and MRD Positivity in CR1 (clinicaltrials.gov) - P1 | N=29 | Recruiting | Sponsor: University of Colorado, Denver | N=14 ➔ 29 | Trial completion date: Jul 2027 ➔ Jun 2030 | Trial primary completion date: Jul 2025 ➔ Jun 2027

Enrollment change • Minimal residual disease • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: University of Colorado, Denver

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • CD19

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: University of Colorado, Denver | Trial primary completion date: Dec 2023 ➔ Mar 2023

Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

UCD19 CAR T Therapy in Adults With B-ALL and MRD Positivity in CR1 (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: University of Colorado, Denver | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2026 ➔ Jul 2027 | Initiation date: Dec 2023 ➔ Jul 2023 | Trial primary completion date: Apr 2025 ➔ Jul 2025

CAR T-Cell Therapy • Enrollment open • Minimal residual disease • Trial completion date • Trial initiation date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: University of Colorado, Denver | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

UCD19 CAR T Therapy in Adults With B-ALL and MRD Positivity in CR1 (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: University of Colorado, Denver | Initiation date: Dec 2022 ➔ Dec 2023

CAR T-Cell Therapy • Minimal residual disease • Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • CD19

UCD19 CAR T Therapy in Adults With B-ALL and MRD Positivity in CR1 (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: University of Colorado, Denver

CAR T-Cell Therapy • Minimal residual disease • New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • CD19

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: University of Colorado, Denver | Recruiting ➔ Active, not recruiting | N=20 ➔ 11

Enrollment change • Enrollment closed • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL (clinicaltrials.gov) - P1/2; N=50; Recruiting; Sponsor: University of Colorado, Denver; Trial completion date: Jul 2021 ➔ Jul 2026; Trial primary completion date: Jun 2021 ➔ Jun 2026

CAR T-Cell Therapy • Clinical • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • CD19

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: University of Colorado, Denver; Trial completion date: Mar 2024 ➔ Dec 2022; Trial primary completion date: Mar 2024 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL (clinicaltrials.gov) - P1/2; N=50; Recruiting; Sponsor: University of Colorado, Denver; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • CD19

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: University of Colorado, Denver; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1; N=20; Not yet recruiting; Sponsor: University of Colorado, Denver; Initiation date: Mar 2020 ➔ Sep 2020

Clinical • Trial initiation date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL) (clinicaltrials.gov) - P1; N=20; Not yet recruiting; Sponsor: University of Colorado, Denver

Clinical • New P1 trial