Chimeric Antigen Receptor (CAR) T-cell therapies have revolutionized the treatment of B-cell Non-Hodgkin Lymphoma (NHL), demonstrating robust and durable responses even in heavily pretreated patients. However, while CD19-targeting CAR-T cell therapies have been approved for treatment in Diffuse Large B Cell Lymphoma (DLBC), follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), unmet medical needs remain, requiring ongoing development of novel therapies.[1]
SynKIR-310 is uniquely designed to prolong T-cell functional persistence and combat the challenges of disease relapse, offering a potentially life-saving option for these patients.
The first patient with follicular lymphoma, a slow-growing, B-cell type of non-Hodgkin lymphoma (NHL), making up about 20–30% of all NHL cases, has been treated in the CELESTIAL-301 Phase 1 clinical trial of SynKIR™-310, a CD19-targeting CAR T-cell therapy designed to enhance T-cell persistence in relapsed/refractory B-NHL. This milestone reflects Verismo’s commitment to addressing the urgent unmet medical need for patients with follicular lymphoma.
The CELESTIAL-301 study is a multicenter Phase 1 trial (NCT06544265) evaluating the safety, tolerability, and preliminary efficacy of SynKIR™-310 in patients with relapsed/refractory B-cell non-Hodgkin lymphomas (B-NHL), including FL.
The study is enrolling both patients who have relapsed after prior CAR T-cell therapy as well as those who have never received CAR T-treatment.
SynKIR™-310 combines Verismo’s proprietary KIR-CAR platform* with a new CD19 binder developed by the University of Pennsylvania (Penn) Perelman School of Medicine ** under a sponsored research agreement between Penn and Verismo, and exclusively licensed to Verismo, to target malignant B cells.
Preclinical studies indicate that the KIR-CAR technology may extend T cell persistence, potentially reducing relapse rates. The trial design includes 2 cohorts with dose escalation and an expansion cohort at the recommended Phase 2 dose.
In January 2025, Verismo announced a strategic investment from the Institute for Follicular Lymphoma Innovation (IFLI), a global, non-profit, private foundation dedicated to accelerating the development of innovative treatment options for patients with follicular lymphoma (FL). The investment of up to $4.05 million to support the SynKIR™-310 FL program, enabling expanded FL-focused clinical sites to increase FL patient enrollment.
“Treatment of the first follicular lymphoma patient in CELESTIAL-301 is an important milestone in the development of a CD19-directed KIR-CAR therapy and underscores the strength of our relationship with IFLI,” noted Bryan Kim, PhD., co-founder and Chief Executive Officer of Verismo Therapeutics.
“We appreciate IFLI’s commitment and expertise, which are helping us advance SynKIR™-310 for individuals in urgent need of new options,” Kim added.
“Treating the first follicular lymphoma patient in CELESTIAL-301 is an important step toward delivering next-generation cell therapies to this underserved patient population,” said Michel Azoulay, MD, MBA, Chief Medical Officer of IFLI.
“We are proud to work with Verismo to accelerate the development of SynKIR™-310 for follicular lymphoma.”
__
Note: * The KIR-CAR platform is a multi-chain CAR T cell therapy that has shown highly effective, prolonged solid tumor treatment in otherwise CAR-resistant preclinical animal models with challenging tumor microenvironments. Using NK cell-derived KIR and DAP12 split signaling provides a novel paired activation and co-stimulation separate from the usual T cell stimulation pathways. KIR-CAR enables sustained chimeric receptor expression with improved long-term CAR T cell function and decreased T cell exhaustion. This results in CAR T cell resistance to tumor immunosuppression, prolonged functional persistence, and improved tumor elimination. Together, this platform offers the potential to enhance CAR T treatment in both solid and hematologic tumors.
** The University of Pennsylvania (Penn) holds equity interests in Verismo’s parent company, Korea-based HLB Innovation, and has licensed certain Penn-owned intellectual property to Verismo. In addition, Penn’s Perelman School of Medicine receives funding for research and development of certain Verismo products. Penn may also receive future financial benefits related to the licensing of certain Penn intellectual property to Verismo.
Clinical Trials
SynKIR-310 for Relapsed/Refractory B-NHL – ClinicalTrials.gov ID NCT06544265
A Long-Term Follow-Up Basket Study for Participants Treated With SynKIR Chimeric Antigen Receptor (CAR) T Cell Product – ClinicalTrials.gov ID NCT06701201
Reference
[1] Tatake IJ, Arnason JE. CARs for lymphoma. Best Pract Res Clin Haematol. 2024 Dec;37(4):101601. doi: 10.1016/j.beha.2025.101601. Epub 2025 Feb 27. PMID: 40074511.
Featured image licensed under the Unsplash+ License and used with permission.
DOI
