Pipeline

Transformational
medicines

our goals

maximize patient responses

Develop CRISPRomics-enabled medicines with the promise to drive patient cures

impact every patient

Deliver on the promise of CRISPRomics to bring transformational medicines with curative potential to as many patients as possible

“

By overcoming many of the biological challenges facing the treatment of cancer, we believe eTIL therapies could represent transformative medicine in the treatment of solid tumors.”

Qasim rizvi, mb.Chb.
Chief executive officer

our pipeline

KSQ-001EX is an investigational eTIL therapy manufactured using our ExPRESS™ process in which the SOCS1 gene is inactivated by CRISPR/Cas9 gene editing.
KSQ’s Immune CRISPRomics^® platform identified SOCS1 as a top target, constraining TIL anti-tumor function, engraftment, and persistence.
The U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for a Phase 1/2 clinical study of KSQ-001EX.

Phase 1/2 clinical trial (NCT06237881):
- The Phase 1/2 clinical trial is designed as an open-label, safety lead-in study for people 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-004EX, a dual-edit eTIL investigational therapy in which both the Regnase-1 and SOCS1 genes are inactivated by CRISPR/Cas9 gene editing, is also manufactured using our ExPRESS process.
Using our in vivo CRISPR^2TMscreening approach, we identified Regnase-1 and SOCS1 as the genome’s top dual-edit combination driving best-in-biology anti-tumor potential.
We are currently conducting IND-enabling studies to advance KSQ-004EX into clinical development.

KSQ-4279 is a first-in-class, potent, and selective small-molecule inhibitor of USP1, a protein that regulates DNA damage response (DDR).
In July 2023, we entered into a worldwide license and collaboration agreement with Roche for the development and commercialization of KSQ-4279; under the collaboration, Roche has assumed all development responsibilities for KSQ-4279 (as RO7623066).
KSQ-4279/RO7623066 is currently being studied in a Phase 1 clinical trial in patients with a variety of advanced solid tumors:

Phase 1 clinical trial (NCT05240898):
- Expected enrollment is approximately 140 patients and is a dose-escalation and expansion trial of KSQ-4279 as a monotherapy and in combination with a PARP inhibitor or with chemotherapy.
- The study’s primary endpoint is to assess the safety of KSQ-4279 both alone and in combination, determine the maximum tolerated dose, and establish a recommended Phase 2 dose.
- Secondary endpoints include characterizing the pharmacokinetics of KSQ-4279 and evaluating its preliminary antitumor activity alone and in combination. The trial is also exploring potential predictive biomarkers and other genetic outcomes.

EXPANDED ACCESS POLICY

Read our EAP.

PUBLICATIONS

2024

Development of a gene editing platform for the manufacture of CRISPR/Cas9 engineered TIL (eTIL)
Poster presented at SITC, November 9, 2024

KSQ-004EX: A SOCS1/Regnase-1 Dual-Edited eTIL Therapy Demonstrating Enhanced Anti-Tumor Activity
Poster presented at SITC, November 8, 2024

Dual inactivation of SOCS1 and Regnase-1 in T cell therapies demonstrated enhanced anti-tumor activity by expanding discrete cell states in pre-clinical syngeneic mouse models
Poster presented at SITC, November 8, 2024

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
Poster presented at SITC, November 7, 2024

Pan-cancer Analysis of Homologous Recombination Deficiency in Cell Lines
Cancer Res Commun. 2024 Nov 1

KSQ-001EX, an Engineered TIL Therapy, Manufactured from a Clinical-Scale, Feeder-Free Process for the Treatment of Solid Tumor Indications
Poster presented at AACR, April 2024

2023

KSQ-4279, a first-in-class USP1 inhibitor, shows strong combination activity with multiple PARP inhibitors in BRCA mutant cancers
Poster presented at AACR, April 2023

KSQ-4279-mediated USP1 inhibition induces replication-associated DNA gaps that contribute to cell death
Poster presented at AACR, April 2023

Rational design of a SOCS1-edited tumor-infiltrating lymphocyte therapy using CRISPR/Cas9 screens.
J Clin Invest. 2023 December

2022

ExPRESS™: An accelerated process for the manufacture of KSQ-001, a CRISPR/Cas9-edited eTIL® product

Poster presented at SITC 2022

Manufacture of KSQ-001, a CRISPR/Cas9-engineered TIL (eTIL®) therapy, for the treatment of Head and Neck Squamous Cell Carcinoma
Poster presented at SITC 2022

KSQ-4279, a first-in-class USP1 inhibitor shows strong combination activity in BRCA mutant cancers with intrinsic or acquired resistance to PARP inhibitors
Poster presented at EORTC-NIC-AACR, October 2022

“KSQ-4279: A first-in-class USP1 inhibitor for the treatment of cancers with homologous recombination deficiency”
Presentation, AACR 2022

2021

KSQ-004: Unbiased pair-wise discovery of SOCS1 and Regnase-1 as the top CRISPR/Cas9 dual-edit combination enhancing in vivo TIL potency against solid tumors

Poster presented at SITC 2021

Development of KSQ-001, An Engineered TIL (eTIL®) Therapy For Solid Tumors Through CRISPR/Cas9-Mediated Inactivation Of SOCS1

Poster presented at SITC 2021

2020

Development of KSQ-4279 as a First-in-Class USP1 Inhibitor for the Treatment of BRCA-Deficient Cancers

Poster presented at ENA 2020

Plenary Slide Deck presented at ENA 2020

KSQ-001: A CRISPR/Cas9-Engineered Tumor Infiltrating Lymphocyte (eTIL®) Therapy For Solid Tumors

Poster presented at AACR 2020

Systematic Identification Of Potent Guide RNAs With Minimal Off-Target Activity For The CRISPR/Cas9 Engineering Of KSQ-001, And Engineered Tumor Infiltrating Lymphocyte (eTIL®)

Poster presented at ASGCT 2020

Genome-scale in vivo CRISPR/Cas9 T cell screen unveils targets enabling rational design of engineered Tumor Infiltrating Lymphocyte (eTIL®) therapies for solid tumors
Keystone Synopsis, Engineering the Genome, February 2020

2019

An Immune-CRISPRomics platform enabling genome-scale and pair-wise combination in vivo T-cell function screens enables comprehensive identification of novel therapeutic targets

Poster presented at SITC 2019