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KSQ Therapeutics Announces First Patient Dosed in Combination Portion of the Ongoing Phase 1 Study of KSQ-4279, A First-In-Class USP1 Inhibitor, In Patients with Advanced Solid Tumors

Lexington, Mass., December 7, 2022- KSQ Therapeutics, a clinical-stage biotechnology company developing therapies to treat cancer and autoimmune diseases using its proprietary, integrated discovery CRISPRomics® platform, today announced the initiation of dosing in the combination therapy portion of Study KSQ-4279-1101, a Phase 1 clinical study of KSQ-4279 in patients with advanced solid tumors. This stage of the clinical study will investigate KSQ-4279 across multiple indications, both in combination with a PARP inhibitor and in combination with chemotherapy.

“The initiation of the combination therapy portion of the study is a significant milestone for KSQ. We are excited by the strong combination activity that we observed across multiple preclinical models in both BRCA mutant ovarian and triple-negative breast cancers, including models from patients that relapsed after multiple rounds of chemotherapy and treatment with PARP inhibitors,” said Andrew Wylie, Ph.D., Senior Vice President, Head of Oncology at KSQ. “We continue to see strong evidence of the promise and potential of our CRISPRomics® platform and believe we are just beginning to realize the tremendous opportunities to develop therapies with true curative potential for a wide range of cancers, in particular solid tumors, as well as autoimmune diseases.”

“The preclinical data suggests there is a broad opportunity to combine KSQ-4279 with PARP inhibitors and with chemotherapy,” said Qasim Rizvi, Chief Executive Officer of KSQ. “The safety profile was favorable in preclinical studies, and KSQ-4279 has been well-tolerated in the ongoing Phase 1 clinical trial. No dose-limiting toxicities have been reported to date in the monotherapy dose escalation portion of the clinical trial. In addition, KSQ-4279 has demonstrated tumor growth inhibition as a single agent and led to deep and durable tumor regressions when administered in combination with a PARP inhibitor in multiple preclinical tumor models.”

KSQ-4279 preclinical data highlights:

  • KSQ-4279 is active as a monotherapy in BRCA1-mutant ovarian PDX models, with tumor regressions observed at doses well below its maximum tolerated dose.
  • KSQ-4279 activity is seen in cancers that harbor defects in homologous recombination (HR), a genetic driver event prevalent in several solid tumor types.
  • In patient-derived TNBC xenograft models resistant to PARP inhibitor treatment, combining KSQ-4279 with a PARP inhibitor led to durable tumor regressions.
  • Data presented at the recent ENA 2022 conference described the activity of KSQ-4279 in ovarian tumor ascites models derived from patient tumors that had relapsed after multiple rounds of chemotherapy, including, in some cases, PARP inhibitor therapy.
  • Four of the ovarian models tested had BRCA1 mutations but were resistant to PARP inhibitor therapy, yet all four were sensitive to KSQ-4279 when used in combination with a PARP inhibitor.

KSQ utilized its proprietary CRISPRomics platform to identify the deubiquitinating enzyme USP1 as an attractive cancer target with established roles in DNA damage repair processes that are distinct from PARP inhibitors and other approaches currently being tested in the clinic. Potent and highly selective inhibitors of USP1 were developed, and profiling of the clinical development candidate KSQ-4279 across a large collection of tumor models confirmed an enriched response rate in cancers with genetic alterations in BRCA1/2 or other HRD lesions.

Study KSQ-4279-1101 is a Phase 1 clinical trial expected to enroll approximately 140 patients with advanced solid tumors. It is a dose-escalation and expansion trial of KSQ-4279 as a monotherapy and in combination. 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 will also explore potential predictive biomarkers and other genetic factors and their correlation with clinical outcomes.


KSQ-4279 is a first-in-class small molecule targeting USP1, a protein regulating DNA damage response (DDR). USP1 was identified by KSQ’s CRISPRomics platform as a novel synthetic lethal target in cancers with certain types of genomic instability. KSQ-4279 is currently being evaluated in a Phase 1 study in patients with advanced solid tumors.

About KSQ Therapeutics

KSQ Therapeutics is advancing a pipeline of tumor- and immune-focused drug candidates to treat cancer and autoimmune disease across multiple drug modalities, including targeted therapies, adoptive cell therapies, and immunotherapies. KSQ’s proprietary CRISPRomics® discovery engine enables genome-scale, in vivo validated, unbiased drug discovery across broad therapeutic areas. For more information, please visit the company’s website at and follow @ksq_tx on Twitter.

Media Contact:
Cory Tromblee
Tel: 617-571-7220

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