RP-1664 is a Potential First-in-Class, Selective, PLK4 Inhibitor
CAMBRIDGE, MA, USA & MONTREAL, Canada I February 15, 2024 I Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today announced the first patient has been dosed in the Company’s Phase 1 LIONS (PLK4 Inhibitor in Advanced Solid Tumors) clinical trial evaluating RP-1664, a potential first-in-class, highly selective, oral polo-like kinase 4 (PLK4) inhibitor, for the monotherapy treatment of adult and adolescent patients enriched for TRIM37-high solid tumors.
“RP-1664 exhibited deep tumor growth inhibition and regressions in multiple TRIM37-high solid tumor and neuroblastoma xenograft models, both internally and in collaboration with Children’s Hospital of Philadelphia. After evaluating safety in the LIONS clinical trial, we expect to move rapidly into a Phase 1/2 clinical trial in high risk, recurrent pediatric neuroblastoma, in which patients have a high prevalence of TRIM37-altered tumors and limited treatment options,” said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. “RP-1664 is Repare’s third internally-developed clinical therapeutic candidate, a testament to the productivity of our platform.”
The LIONS clinical trial (NCT06232408) is a first-in-human, multicenter, open-label Phase 1 study to investigate safety, pharmacokinetics, pharmacodynamics and the preliminary efficacy of RP-1664. The clinical trial is expected to enroll approximately 80 patients with molecularly selected advanced solid tumors, including those with gain or amplification of TRIM37, among other genetic alterations. The primary endpoints are to determine the safety, tolerability, dose and schedule of RP-1664 and assess any early antitumor activity.
About RP-1664
RP-1664 is a potential first-in-class, highly selective, oral PLK4 inhibitor designed to harness the synthetic lethal relationship with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for centriole biogenesis in S-phase of the cell cycle when TRIM37, an E3 ligase that reduces pericentriolar material, is high. Preclinical studies demonstrate that RP-1664 selectively inhibits PLK4 and drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors and in approximately 80% of all high-grade neuroblastomas. RP-1664 is the only selective PLK4 inhibitor known to be in the clinic.
About Repare Therapeutics’ SNIPRx® Platform
Repare’s SNIPRx® platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx® screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.
About Repare Therapeutics, Inc.
Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Company’s pipeline includes lunresertib (also known as RP-6306), a PKMYT1 inhibitor currently in Phase 1/2 clinical development; camonsertib (also known as RP-3500), a potential leading ATR inhibitor currently in Phase 1/2 clinical development; RP-1664, a Phase 1 PLK4 inhibitor; RP-3467, a preclinical Polθ ATPase inhibitor program; as well as additional, undisclosed preclinical programs. For more information, please visit reparerx.com and follow @Reparerx on X (formerly Twitter) and LinkedIn.
SOURCE: Repare Therapeutics
Post Views: 284
RP-1664 is a Potential First-in-Class, Selective, PLK4 Inhibitor
CAMBRIDGE, MA, USA & MONTREAL, Canada I February 15, 2024 I Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today announced the first patient has been dosed in the Company’s Phase 1 LIONS (PLK4 Inhibitor in Advanced Solid Tumors) clinical trial evaluating RP-1664, a potential first-in-class, highly selective, oral polo-like kinase 4 (PLK4) inhibitor, for the monotherapy treatment of adult and adolescent patients enriched for TRIM37-high solid tumors.
“RP-1664 exhibited deep tumor growth inhibition and regressions in multiple TRIM37-high solid tumor and neuroblastoma xenograft models, both internally and in collaboration with Children’s Hospital of Philadelphia. After evaluating safety in the LIONS clinical trial, we expect to move rapidly into a Phase 1/2 clinical trial in high risk, recurrent pediatric neuroblastoma, in which patients have a high prevalence of TRIM37-altered tumors and limited treatment options,” said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. “RP-1664 is Repare’s third internally-developed clinical therapeutic candidate, a testament to the productivity of our platform.”
The LIONS clinical trial (NCT06232408) is a first-in-human, multicenter, open-label Phase 1 study to investigate safety, pharmacokinetics, pharmacodynamics and the preliminary efficacy of RP-1664. The clinical trial is expected to enroll approximately 80 patients with molecularly selected advanced solid tumors, including those with gain or amplification of TRIM37, among other genetic alterations. The primary endpoints are to determine the safety, tolerability, dose and schedule of RP-1664 and assess any early antitumor activity.
About RP-1664
RP-1664 is a potential first-in-class, highly selective, oral PLK4 inhibitor designed to harness the synthetic lethal relationship with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for centriole biogenesis in S-phase of the cell cycle when TRIM37, an E3 ligase that reduces pericentriolar material, is high. Preclinical studies demonstrate that RP-1664 selectively inhibits PLK4 and drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors and in approximately 80% of all high-grade neuroblastomas. RP-1664 is the only selective PLK4 inhibitor known to be in the clinic.
About Repare Therapeutics’ SNIPRx® Platform
Repare’s SNIPRx® platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx® screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.
About Repare Therapeutics, Inc.
Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Company’s pipeline includes lunresertib (also known as RP-6306), a PKMYT1 inhibitor currently in Phase 1/2 clinical development; camonsertib (also known as RP-3500), a potential leading ATR inhibitor currently in Phase 1/2 clinical development; RP-1664, a Phase 1 PLK4 inhibitor; RP-3467, a preclinical Polθ ATPase inhibitor program; as well as additional, undisclosed preclinical programs. For more information, please visit reparerx.com and follow @Reparerx on X (formerly Twitter) and LinkedIn.
SOURCE: Repare Therapeutics
Post Views: 284
