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

To learn if KSQ-001EX is safe to give to participants with advanced forms of solid tumors.

Start Date31 Jan 2024

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

100 Clinical Results associated with KSQ-001

100 Translational Medicine associated with KSQ-001

100 Patents (Medical) associated with KSQ-001

Literatures (Medical) associated with KSQ-001

15 Dec 2023·Journal of Clinical Investigation

Rational design of a SOCS1-edited tumor-infiltrating lymphocyte therapy using CRISPR/Cas9 screens

Article

Author: Stegmeier, Frank ; Williams, Leila J. ; Wong, Karrie ; Tubo, Noah J. ; Cadzow, Louise ; Xu, Tianlei ; Thompson, Frank ; Shenker, Sol ; Wrocklage, Christopher ; Collester, Zachary R. ; Merkin, Jason J. ; Lin, Sharon ; Le Mercier, Isabelle ; Schlabach, Michael R. ; Kryukov, Gregory V. ; Sharp, Fiona A. ; Dunbar, Paul R. ; Benson, Micah J. ; Bullock, Caroline P. ; Gannon, Hugh S. ; Hohmann, Anja F. ; LaMothe, Robert A. ; Dugopolski, Caroline ; Calnan, Conor ; Sofjan, Katri ; Garrett, Tracy E. ; Keegan, Sean ; Colletti, Nicholas

Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the antitumor activity of T cell therapies, large-scale in vitro and in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, with the SOCS1 gene identified as a top T cell-enhancing target. In murine CD8+ T cell-therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of central memory T cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cells (Texprog) in tumors. A comprehensive CRISPR tiling screen of the SOCS1-coding region identified sgRNAs targeting the SH2 domain of SOCS1 as the most potent, with an sgRNA with minimal off-target cut sites used to manufacture KSQ-001, an engineered TIL therapy with SOCS1 inactivated by CRISPR/Cas9. 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.

News (Medical) associated with KSQ-001

28 Oct 2024

·www.prnewswire.com

Treg Cell-based Therapies Clinical Trial Pipeline Appears Robust With 51+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

Treg Cell-based Therapies refer to therapeutic approaches that utilize regulatory T cells (Tregs) to modulate the immune system. Innovations in cell expansion and engineering techniques have greatly enhanced the ability to isolate, expand, and deliver functional Tregs. Ex vivo expansion technologies and genetic engineering (such as CAR-Tregs) have opened up new possibilities for enhancing the stability, specificity, and effectiveness of Treg therapies. LAS VEGAS, Oct. 28, 2024 /PRNewswire/ -- DelveInsight's ' Treg Cell-based Therapies Pipeline Insight 2024 ' report provides comprehensive global coverage of available, marketed, and pipeline Treg cell-based therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the Treg cell-based therapies pipeline domain. Key Takeaways from the Treg Cell-based Therapies Pipeline Report DelveInsight's Treg cell-based therapies pipeline report depicts a robust space with 50+ active players working to develop 55+ pipeline therapies for various indications. Key Treg cell-based therapies companies such as Orca Bio, Nektar Therapeutics, Quell Therapeutics, Cugene, Sangamo Therapeutics, Abata Therapeutics, HCW Biologics, GentiBio, Tr1X, PolTREG, Cellenkos, VT BIO, Miltenyi Biotec GmbH, KSQ Therapeutics, TeraImmune, Tract Therapeutics, and others are evaluating new Treg cell-based therapies to improve the treatment landscape. Promising Treg cell-based therapies in the pipeline in various stages of development include Orca-T, NKTR-358, QEL-001, CUG-252, TX200, ABA-101, HCW9302, GNTI-122, TRX-103, PTG-020, CK-0804, VT-301, TR-004, KSQ 001, TI-620, TRK 001, and others. In October 2024, Quell Therapeutics hired eXmoor Pharma to make supplies of its pipeline of novel immunosuppressive cell therapies—called CAR-Tregs—at its new cell and gene therapy facility. Quell recently teamed with fellow U.K.-based eXmoor in a strategic partnership that will see the contractor make its candidate autoimmune disease cell therapies for early-phase clinical studies. In September 2024, Abata Therapeutics announced that ABA-101, an autologous regulatory T-cell (Treg) therapy for the treatment of patients with progressive multiple sclerosis (MS), has received fast-track designation from the US FDA. In September 2024, PolTREG S.A. announced that China's National Intellectual Property Administration, PRC (CNIPA) had issued a notification to grant a patent for the intrathecal administration of the company's cellular therapies in patients with multiple sclerosis (MS). The intrathecal administration is an established method used to deliver therapy across the blood-brain barrier via injection into the subarachnoid space. In June 2024, Orca Bio announced that it had completed enrollment in the pivotal Precision-T Phase III clinical study. The primary endpoint of the Precision-T study is the rate of survival free from moderate-to-severe chronic graft versus host disease (GvHD). In March 2024, PolTREG announced that the company is planning to launch Phase II trials testing its Tregs therapy — the T-cell-based treatment PTG-007 in people with multiple sclerosis (MS). In February 2024, Cellenkos announced encouraging safety data from its innovative CK0803 neurotrophic T regulatory (Treg) cell therapy, being developed to help treat individuals with Amyotrophic Lateral Sclerosis (ALS). The company was given the green light to move ahead following a review of safety data by the Data Safety Monitoring Board (DSMB). In August 2023, BlueRock Therapeutics LP, a wholly owned, independently operated subsidiary of Bayer AG, and bit.bio, the company coding human cells for novel cures announced a collaboration and option agreement for the discovery and manufacture of iPSC-derived regulatory T cells (Tregs) for use in creating therapeutics. Request a sample and discover the recent advances in Treg cell-based therapies @ Treg Cell-based Therapies Pipeline Outlook The Treg cell-based therapies pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage Treg cell-based therapies, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the Treg cell-based therapies pipeline landscape. Treg Cell-based Therapies Overview Treg cell-based therapies represent a promising frontier in immunotherapy, focusing on harnessing regulatory T cells (Tregs) to modulate the immune response in various clinical settings. Tregs play a crucial role in maintaining immune homeostasis and preventing autoimmune reactions by suppressing excessive immune responses. In the context of autoimmune diseases, these therapies aim to restore balance by expanding or enhancing Tregs to dampen inappropriate immune activity. For instance, in diseases like type 1 diabetes or multiple sclerosis, Treg cell-based treatments seek to prevent or slow disease progression by reestablishing immune tolerance. Beyond autoimmune disorders, Treg cell-based therapies are also being explored in cancer treatment. Tumors often exploit Tregs to evade immune detection, and by manipulating these cells, it's possible to enhance the anti-tumor immune response. Strategies include expanding Tregs ex vivo and reinfusing them to boost their numbers or modifying them to more effectively target tumor-associated antigens. These approaches hold the potential to improve the efficacy of existing immunotherapies and offer new avenues for treating cancers that are currently resistant to conventional treatments. Find out more about Treg cell-based therapies @ Treg Cell-based Therapies in Development A snapshot of the Treg Cell-based Therapies Pipeline Drugs mentioned in the report: Learn more about the emerging Treg cell-based therapies @ Treg Cell-based Therapies Clinical Trials Treg Cell-based Therapies Therapeutics Assessment The Treg cell-based therapies pipeline report proffers an integral view of the emerging Treg cell-based therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Treg Cell-based Therapies Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intravenous, Subcutaneous, Oral, Intramuscular Therapeutics Assessment By Molecule Type: Monoclonal antibody, Small molecule, Peptide Therapeutics Assessment By Mechanism of Action: Immunologic cytotoxicity, T lymphocyte replacements, Interleukin 2 replacements, Cell replacements Key Treg Cell-based Therapies Companies: Orca Bio, Nektar Therapeutics, Quell Therapeutics, Cugene, Sangamo Therapeutics, Abata Therapeutics, HCW Biologics, GentiBio, Tr1X, PolTREG, Cellenkos, VT BIO, Miltenyi Biotec GmbH, KSQ Therapeutics, TeraImmune, Tract Therapeutics, and others. Key Treg Cell-based Therapies in Pipeline: Orca-T, NKTR-358, QEL-001, CUG-252, TX200, ABA-101, HCW9302, GNTI-122, TRX-103, PTG-020, CK-0804, VT-301, TR-004, KSQ 001, TI-620, TRK 001, and others. Dive deep into rich insights for Treg cell-based therapies assessment, visit @ Treg Cell-based Therapies Therapeutics Assessment Table of Contents For further information on the Treg cell-based therapies pipeline therapeutics, reach out @ Treg Cell-based Therapies Pipeline Landscape Related Reports Type 1 Diabetes Market Type 1 Diabetes Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key type 1 diabetes companies, including Histogen , Novo Nordisk, Prevention Bio, among others. 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Alzheimer's Disease Pipeline Alzheimer's Disease Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Alzheimer's Disease companies, including Biogen, AZTherapies, Cerecin, Neurotrope, Synaptogenix, INmune Bio, Cassava Sciences, EIP Pharma, Neuraly, AB Science, Cortexyme, Anavex Life Sciences, Athira Pharma, Time Therapeutics, Denali Therapeutics Inc., Alector Inc., Lexeo Therapeutics, TrueBinding, Inc., Vaccinex Inc., Annovis Bio Inc., Eisai Inc., Hoffmann-La Roche, Ionis Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Ltd., Cognition Therapeutics, Merck Sharp & Dohme LLC, ImmunoBrain Checkpoint, AbbVie, AriBio Co., Ltd., Oryzon Genomics S.A., Eli Lilly and Company, Neurokine Therapeutics, Excelsior, Seelos Therapeutics, Inc., Janssen Research & Development, LLC, Shanghai Hengrui Pharmaceutical Co., Ltd., reMYND, Alzinova AB, VTBIO Co. LTD, BioVie Inc., Prothena Corporation plc, Coya Therapeutics, Inc., among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ImmunotherapyCell TherapyFast TrackPhase 3

14 Jun 2024

·www.globenewswire.com

KSQ Therapeutics Announces First Patient Dosed in Clinical Development Program for KSQ-001EX, a CRISPR/Cas9 Engineered Tumor Infiltrating Lymphocyte (eTIL®) Therapy

June 12, 2024 -- KSQ Therapeutics, Inc. (KSQ), a clinical-stage biotechnology company developing treatments for solid tumors, today 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. KSQ's CRISPRomics® platform identified SOCS1 as a key gene inhibiting T cell growth, survival, and differentiation by negatively regulating cytokine signaling in the tumor microenvironment. "TIL have emerged as a powerful new treatment modality, and we believe both of our eTIL® programs, KSQ-001EX and KSQ-004EX, have the potential to significantly advance the field by improving the potency of TIL therapy for the treatment of a variety of solid tumor types. In preclinical studies, KSQ-001EX demonstrated enhanced anti-tumor activity, polyclonality, persistence, and memory formation in multiple solid tumor models compared to unmodified TIL. We also saw robust anti-tumor activity in models insensitive to PD-1 inhibition,” said Qasim Rizvi, Chief Executive Officer of KSQ. “We look forward to evaluating KSQ-001EX in patients with difficult-to-treat solid tumors, including melanoma, head and neck squamous cell carcinoma, and non-small cell lung cancer.” The first patient treated with KSQ-001EX was enrolled by Rodabe Amaria, M.D., professor of Melanoma Medical Oncology and principal investigator of the study at The University of Texas MD Anderson Cancer Center. 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. In the safety lead-in portion, a cohort of patients will be initially dosed without IL-2. The primary objective of Phase 2 is to evaluate antitumor activity in indication-specific cohorts. KSQ’s lead eTIL® cell therapy program, KSQ-001EX, in which TIL are edited to inactivate the SOCS1 gene, has the potential to revolutionize the treatment of solid tumors. In preclinical studies, KSQ-001EX demonstrated enhanced anti-tumor function in solid tumor models refractory to PD-1 inhibition, as well as enhanced persistence and memory formation. KSQ Therapeutics is advancing a pipeline of novel drug candidates to treat cancer across multiple drug modalities, including targeted therapies, adoptive cell therapies, and immunotherapies. KSQ's proprietary CRISPRomics® discovery engine enables genome-scale insights driving novel therapeutic discovery. For more information, please visit the company's website at www.ksqtx.com. The content above comes from the network. if any infringement, please contact us to modify.

ImmunotherapyGene TherapyCell Therapy

29 Nov 2023

·www.globenewswire.com

KSQ Therapeutics Announces FDA Clearance of IND Application for KSQ-001EX, a CRISPR/Cas9 Engineered Tumor Infiltrating Lymphocyte (eTIL®) Therapy

Phase 1/2 clinical study will evaluate the safety, pharmacokinetics, and preliminary efficacy of KSQ-001EX in melanoma, head and neck squamous cell carcinoma, and non-small cell lung cancerLEXINGTON, Mass., Nov. 29, 2023 (GLOBE NEWSWIRE) -- KSQ Therapeutics, Inc. (KSQ), a clinical-stage biotechnology company developing novel treatments for solid tumors, in collaboration with The University of Texas MD Anderson Cancer Center and the Cell Therapy Manufacturing Center (CTMC), today 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. KSQ-001EX consists of TILs in which the SOCS1 gene is inactivated by CRISPR/Cas9 gene editing. KSQ's CRISPRomics® platform identified SOCS1 as a key gene regulating the anti-tumor potency and persistence of TIL and provides KSQ-001EX with best-in-class potential in the treatment of solid tumors. "Our team has made great progress advancing our KSQ-001EX and KSQ-004EX eTIL® programs. Through our platform insights, we've identified how to enhance the effectiveness of T cells in the treatment of solid tumors. We believe our eTIL® cell therapies have tremendous potential to benefit patients with cancer who have limited treatment options. We look forward to working closely with the clinical experts at MD Anderson, where the study will be initiated,” said Qasim Rizvi, Chief Executive Officer of KSQ. “Our partnership with CTMC has yielded a robust manufacturing process for our eTIL® cell therapy that is derived from patient tumor samples, including core biopsies. The collaborative effort allowed the IND to be submitted in an accelerated timeframe.” “New treatment options are urgently needed in melanoma and other solid tumors, and the potential to improve outcomes and patient experience is very exciting. KSQ-001EX exhibited considerable efficacy in preclinical studies,” said Rodabe Amaria, M.D., professor of Melanoma Medical Oncology at MD Anderson and principal investigator of the KSQ-001EX study. “We look forward to working closely with KSQ as we advance this program.” Phase 1/2 Trial Design 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 safety and tolerability of KSQ-001EX. In the safety lead-in portion, a cohort of patients will be initially dosed without IL-2. The primary objective of Phase 2 is to evaluate antitumor activity in indication-specific cohorts. About KSQ-001EX KSQ’s lead eTIL® cell therapy program, KSQ-001EX, in which TILs are edited to inactivate the SOCS1 gene, has the potential to revolutionize the treatment of solid tumors. In preclinical studies, KSQ-001EX demonstrated enhanced anti-tumor function in solid tumor models refractory to PD-1 inhibition, as well as enhanced persistence, and memory formation. About KSQ Therapeutics KSQ Therapeutics is advancing a pipeline of novel drug candidates to treat cancer across multiple drug modalities, including targeted therapies, adoptive cell therapies, and immunotherapies. KSQ's proprietary CRISPRomics® discovery engine enables genome-scale insights driving novel therapeutic discovery. For more information, please visit the company's website at www.ksqtx.com. KSQ Media Contact: Cory Trombleecory@scientpr.com

Cell TherapyINDPhase 2ImmunotherapyPhase 1

100 Deals associated with KSQ-001

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	US	KSQ Therapeutics, Inc.Startup	31 Jan 2024
Head and Neck Neoplasms	Phase 2	US	KSQ Therapeutics, Inc.Startup	31 Jan 2024
Lung Cancer	Phase 2	US	KSQ Therapeutics, Inc.Startup	31 Jan 2024
Melanoma	Phase 2	US	KSQ Therapeutics, Inc.Startup	31 Jan 2024
Non-Small Cell Lung Cancer	IND Approval	US	KSQ Therapeutics, Inc.Startup	29 Nov 2023
Squamous Cell Carcinoma of Head and Neck	IND Approval	US	KSQ Therapeutics, Inc.Startup	29 Nov 2023
Solid tumor	Preclinical	US	Takeda Pharmaceutical Co., Ltd.	-

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SITC2022	Not Applicable	SOCS1 gene	11	KSQ-001	ltmbtlsynv(ubqpycwwia) = KSQ-001 manufactured using ExRPESS exhibited heightened anti-tumor function when compared to un-engineered TIL cwzuvngmld (jfozasigxp )	Positive	07 Nov 2022
SITC2022	Not Applicable	Squamous Cell Carcinoma of Head and Neck	8	KSQ-001	ffjlnekmxn(ezurdiddkg) = enhanced against 3D tumor spheroids in vitro lnyiwqbyyy (mqmjyidzgi ) View more	Positive	07 Nov 2022
SITC2021	Not Applicable	Solid tumor	-	KSQ-001	upkxsobjte(bywcffbwyr) = exhibited a hypersensitivity to IL-12 signaling pgtkwrzzny (bsjdhoqjwm ) View more	-	10 Nov 2021

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