KSQ-001EX / KSQ Therapeutics - LARVOL DELTA

Recent Advances in Tumor-Infiltrating Lymphocyte Therapy for Melanoma. (PubMed, Curr Treat Options Oncol) - "We then review current clinical evidence for conventional TIL products, including lifileucel, TM001, LM103, HS-IT101, and GC101, highlighting their efficacy and safety profiles...In addition, advances in genetically engineered TILs, such as OBX-115, KSQ-001EX, and IOV-4001, are reviewed...Challenges and future directions of TIL therapy in melanoma are also discussed. Overall, TIL therapy constitutes a rapidly evolving and clinically potent treatment modality for melanoma."

Biomarker • IO biomarker • Journal • Review • Tumor-infiltrating lymphocyte • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • IL2

Anti-tumor function and long-term persistence of KSQ-001EX, a SOCS1-edited eTIL® therapy, independent of IL-2 co-administration (AACR 2026) - P1/2 | "Based on these collective data, we confirm the functional enhancement introduced by SOCS1 deletion. Further investigation of eTIL in the absence of IL-2 and higher DP doses is warranted."

IO biomarker • Melanoma • Oncology • Solid Tumor • CD27 • CD8 • IL2 • SOCS1

Results of first-in-human, Phase 1 study of KSQ-001EX, an autologous tumor infiltrating lymphocyte therapy engineered to inactivate the SOCS1 gene, in patients with select advanced solid tumors (AACR 2026) - P1/2 | "Patients received lymphodepleting chemotherapy (LDC) with cyclophosphamide and fludarabine followed by a single infusion of KSQ-001EX. Consistent with the biology of SOCS1 edited TIL, elevated serum IFNγ levels (median peak 276 pg/mL [range 69-1530]) were observed in most patients independent of IL-2 dosing. Data from the phase 1 portion of the study demonstrates that KSQ-001EX has a manageable safety profile regardless of IL-2 administration, favorable kinetics and encouraging preliminary anti-tumor activity even at low cell doses (<10e9 cells)."

Clinical • First-in-human • Metastases • P1 data • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • SOCS1

Characterizing the impact of SOCS1 and Regnase-1 inactivation on tumor reactive T cells present in CRISPR/Cas9-engineered TIL (eTIL®) therapies derived from melanoma and NSCLC tumors through functional and single cell analyses (AACR 2025) - "Seeking to improve the clinical activity of TIL therapy, we developed KSQ-001EX and KSQ-004EX, two CRISPR/Cas9-engineered TIL (eTIL®) therapies wherein the genes encoding SOCS1 or SOCS1 in combination with Regnase-1 are inactivated, respectively. The majority of predTRT clones were also detected in DPs, where they preferentially aligned to effector memory and proliferating states. Further demonstrating the impact of SOCS1 and Regnase-1 edits on predTRT clones, we observed enrichment of an activated interferon-stimulated gene signature in eTIL DPs, with predTRT clones in dual-edited KSQ-004EX uniquely enriched for heightened expression of a Regnase-1 transcriptional signature.To conclude, we observe that eTIL possess reactivity against tumor through retention of TRT clones, with SOCS1 and Regnase-1 inactivation enhancing the anti-tumor functionality of TRT clones within eTIL DP."

IO biomarker • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD69 • CD8 • CXCL13 • GZMB • IFNG • IL2RA • IL7R • ISG20 • SOCS1 • TNFRSF9

KSQ-001EX: An engineered TIL therapy manufactured from a clinical-scale, feeder-free process for the treatment of solid tumor indications (AACR 2024) - "KSQ-001EX exhibits heightened anti-tumor activity in preclinical models, with therapeutic benefit to be evaluated in a planned clinical trial in patients with treatment-refractory melanoma, NSCLC, and HNSCC. [SM1]Spell out these at first instance?"

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IFNG • IL12A • SOCS1

Evolving therapeutic pipeline for tumor-infiltrating lymphocytes in metastatic melanoma - a review. (PubMed, Front Immunol) - "The recent U.S. FDA approval of lifileucel, a non-engineered, autologous tumor-infiltrating lymphocyte (TIL) therapy, for unresectable or metastatic melanoma represents a major milestone for cellular therapies in solid tumors...OBX-115, designed with regulatable membrane-bound IL-15 expression, eliminates the need for IL-2 infusion and has shown early clinical activity. KSQ-001EX uses CRISPR/Cas9 to inactivate SOCS1, while KSQ-004EX additionally targets Regnase-1 to enhance TIL function...TIL therapy remains among the most promising strategies in melanoma and solid tumors after immunotherapy failure. Ongoing research aims to optimize cell dose, phenotype, tumor procurement, treatment sequencing, and rational combinations to improve durable benefit."

IO biomarker • Journal • Review • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • IL15 • SOCS1

A Phase 1/2 Study of KSQ-001EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate the SOCS1 Gene, in Patients With Select Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=15 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | N=72 ➔ 15

Enrollment change • Enrollment closed • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A phase 1/2 study of KSQ-001EX: an autologous tumor-infiltrating lymphocyte therapy engineered to inactivate the SOCS1 gene in patients with select advanced solid tumors (SITC 2024) - "Patients receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) prior to KSQ-001EX infusion. The primary objective of phase 1 is to evaluate the safety and tolerability of KSQ-001EX in adult patients with melanoma, HNSCC, and NSCLC.In phase 2, patients with melanoma, HNSCC, and NSCLC will be enrolled in indication-specific cohorts. The objective of phase 2 is to assess the anti-tumor activity of KSQ-001EX in patients with advanced malignant solid tumors by ORR per RECIST v1.1.This is currently a single-institution study that is actively enrolling/recruiting patients."

Clinical • Metastases • P1/2 data • Tumor-infiltrating lymphocyte • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IFNG • IL2 • SOCS1

Development of a gene editing platform for the manufacture of CRISPR/Cas9 engineered TIL (eTIL) (SITC 2024) - "Background To improve the clinical activity of Tumor Infiltrating Lymphocyte (TIL) therapy, we developed engineered TIL (eTIL®) using CRISPR/Cas9 gene editing: KSQ-001EX is a single-edit eTIL product with SOCS1 inactivated; KSQ-004EX is a dual-edit eTIL product with inactivation of both SOCS1 and Regnase-1. Robust eTIL editing efficiency was achieved while maintaining consistently high cell viability, in vitro functionality, and other process attributes. Conclusions With the goal of simplifying the manufacture of eTIL and improving sterility assurance, we report the development of a robust, scalable gene editing platform that accounts for tumor variability in the manufacture of eTIL using a next generation ExPRESS manufacturing process."

Oncology • Solid Tumor • SOCS1

A phase 1/2 study of KSQ-001EX: an autologous tumor-infiltrating lymphocyte therapy engineered to inactivate the SOCS1 gene in patients with select advanced solid tumors (SITC 2024) - "Patients receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) prior to KSQ-001EX infusion. The primary objective of phase 1 is to evaluate the safety and tolerability of KSQ-001EX in adult patients with melanoma, HNSCC, and NSCLC.In phase 2, patients with melanoma, HNSCC, and NSCLC will be enrolled in indication-specific cohorts. The objective of phase 2 is to assess the anti-tumor activity of KSQ-001EX in patients with advanced malignant solid tumors by ORR per RECIST v1.1.This is currently a single-institution study that is actively enrolling/recruiting patients."

Clinical • Metastases • P1/2 data • Tumor-infiltrating lymphocyte • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IFNG • IL2 • SOCS1

KSQ Therapeutics Announces First Patient Dosed in Clinical Development Program for KSQ-001EX, a CRISPR/Cas9 Engineered Tumor Infiltrating Lymphocyte (eTIL) Therapy (GlobeNewswire) - "KSQ Therapeutics...announced the first patient dosed in the Phase 1/2 clinical study of KSQ-001EX, a novel edited TIL therapy. KSQ-001EX consists of TIL in which the SOCS1 gene is inactivated by CRISPR/Cas9 gene editing, giving it the potential to be a best-in-class treatment for a variety of solid tumor indications....The Phase 1/2 clinical trial is an open-label, safety lead-in study for patients with melanoma, head and neck squamous cell carcinoma (HNSCC), and non-small cell lung cancer (NSCLC). The primary objective of the Phase 1 portion of the trial is to evaluate the safety and tolerability of KSQ-001EX."

Trial status • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

A Phase 1/2 Study of KSQ-001EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate the SOCS1 Gene, in Patients With Select Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=72 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Phase 1/2 Study of KSQ-001EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate the SOCS1 Gene, in Patients With Select Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=72 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1/2 trial • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Rational design of a SOCS1-edited tumor-infiltrating lymphocyte therapy using CRISPR/Cas9 screens. (PubMed, J Clin Invest) - "KSQ-001 possessed increased responsiveness to cytokine signals and enhanced in vivo antitumor function in mouse models. These data demonstrate the use of CRISPR/Cas9 screens in the rational design of T cell therapies."

Journal • Tumor-infiltrating lymphocyte • Gene Therapies • Oncology • Solid Tumor • CD8 • SOCS1

KSQ Therapeutics Announces FDA Clearance of IND Application for KSQ-001EX, a CRISPR/Cas9 Engineered Tumor Infiltrating Lymphocyte (eTIL) Therapy (GlobeNewswire) - "KSQ Therapeutics, Inc...announced the Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for a Phase 1/2 clinical study of KSQ-001EX, KSQ’s lead engineered tumor-infiltrating lymphocyte (eTIL^®) program....The Phase 1/2 clinical trial is an open-label, safety lead-in study for patients with melanoma, head and neck squamous cell carcinoma (HNSCC), and non-small cell lung cancer (NSCLC)."

IND • New P1/2 trial • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

KSQ Therapeutics and CTMC Announce Strategic Collaboration to Accelerate the Development of Novel Engineered Tumor Infiltrating Lymphocyte (eTIL) Therapies for the Treatment of Solid Tumors (Businesswire) - "KSQ Therapeutics, Inc...and MD Anderson Cancer Center, announced today a strategic collaboration to expedite the development of KSQ's two lead engineered tumor-infiltrating lymphocyte (eTIL^®) programs, KSQ-001EX and KSQ-004EX, both of which are advancing toward clinical studies for the treatment of solid tumors."

Licensing / partnership • Oncology • Solid Tumor

Manufacture of KSQ-001, a CRISPR/Cas9-engineered TIL (eTIL) therapy, for the treatment of Head and Neck Squamous Cell Carcinoma (SITC 2022) - "KSQ-001 from HNSCC tumors consistently displayed enhanced functional potency while retaining a highly diverse TCR repertoire. These data provide a compelling rationale for evaluating KSQ-001 as a therapeutic strategy for patients with HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IFNG • IL12A • IL2 • SOCS1

ExPRESSTM: An accelerated process for the manufacture of KSQ-001, a CRISPR/Cas9-edited eTILTM product (SITC 2022) - "KSQ-001 can be manufactured at clinically relevant doses in 21 days or less and displays enhanced functional potency. These data support evaluating KSQ-001 manufactured by the ExPRESS process in the treatment of patients with metastatic treatment-refractory solid tumors."

Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNG • SOCS1

Development of KSQ-001, an engineered TIL (eTIL) therapy for solid tumors through CRISPR/Cas9-mediated editing of SOCS1 (SITC 2021) - "Conclusions Based on insights from our Immune-CRISPRomics® platform and demonstrated efficacy across multiple preclinical tumor models, we have developed KSQ-001, a novel eTIL therapy. These preclinical data support clinical testing of KSQ-001 in a variety of solid tumor indications."

Oncology • Solid Tumor • IL12A • PD-1 • SOCS1