CDK12 Inhibitor Demonstrates Strong Anti-Tumor Activity as Single Agent and in Combination with a DNA Damaging Agent and a PARP Inhibitor in Models of Breast, Lung, and Ovarian Cancer
On Track to Nominate CDK12 Inhibitor as Next Development Candidate in 2H 2022
CAMBRIDGE, MA, USA I April 8, 2022 I Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, today announced new preclinical data from our CDK12 inhibitor program, demonstrating robust anti-tumor activity of our oral, selective CDK12 inhibitors in models of breast, lung, and ovarian cancer, including in a PARP inhibitor resistant model. The data support the advancement of a development candidate from Syros’ CDK12 inhibitor program towards clinical development. These findings were presented in an e-poster as part of the American Association for Cancer Research (AACR) Annual Meeting 2022.
“CDK12 is an attractive cancer target due to its role in transcription and DNA damage repair regulation. Leveraging our selective CDK inhibition expertise, we discovered potent, selective, and oral CDK12 inhibitors, which affect the expression of genes involved in DNA damage response to drive anti-tumor activity,” said Eric R. Olson, Ph.D., Chief Scientific Officer of Syros. “Based on the promising new data presented at AACR, in which CDK12 inhibition induced strong tumor growth inhibition and demonstrated synergies in combination with existing standard of care approaches, we believe a CDK12 inhibitor has the potential to play a key role in breast, lung, and ovarian cancer treatment. We look forward to nominating our next development candidate from our CDK12 program in the second half of this year, as we aim to address a significant unmet need for patients, including those who are resistant to DNA damaging agents or PARP inhibitors.”
Preclinical Data from Oral CDK12 Inhibitor Program
Syros designed a series of CDK12 inhibitors that were profiled in biochemical and cellular assays. The data presented at AACR detail for the first time the potency, selectivity, and anti-tumor activity from a representative member of the class, which exhibited low nanomolar potency and selectivity over CDK2, CDK7, and CDK9 of 46-, 27-, and 9-fold, respectively.
As a single agent in cancer cell models, this CDK12 inhibitor induced DNA damage, cell cycle dysregulation and genomic instability leading to growth inhibition and apoptosis. Additionally, as a single agent in in vivo cancer models this CDK12 inhibitor demonstrated tumor regressions in small cell lung cancer and breast cancer models, at well tolerated doses.
In combination in vitro, this CDK12 inhibitor showed synergistic or additive antiproliferative effects in combination with the DNA damaging agent, lurbinectedin, and the PARP inhibitor, olaparib, with increases in DNA damage and impaired DNA damage repair. In vivo, CDK12 inhibition in combination with lurbinectedin showed enhanced anti-tumor activity in a cell line derived model of small cell lung cancer, and in combination with olaparib showed enhanced anti-tumor activity in a PARP inhibitor resistant patient-derived model (PDX) of ovarian cancer.
The poster is now available on the Publications and Abstracts section of the Syros website at www.syros.com.
About Syros Pharmaceuticals
Syros is redefining the power of small molecules to control the expression of genes. Based on its unique ability to elucidate regulatory regions of the genome, Syros aims to develop medicines that provide a profound benefit for patients with diseases that have eluded other genomics-based approaches. Syros is advancing a robust clinical-stage pipeline, including: tamibarotene, a first-in-class oral selective RARα agonist in RARA-positive patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia; SY-2101, a novel oral form of arsenic trioxide in patients with acute promyelocytic leukemia; and SY-5609, a highly selective and potent oral CDK7 inhibitor in patients with select solid tumors and blood cancers. Syros also has multiple preclinical and discovery programs in oncology and monogenic diseases. For more information, visit www.syros.com and follow us on Twitter (@SyrosPharma) and LinkedIn.
SOURCE: Syros Pharmaceuticals
Post Views: 38
CDK12 Inhibitor Demonstrates Strong Anti-Tumor Activity as Single Agent and in Combination with a DNA Damaging Agent and a PARP Inhibitor in Models of Breast, Lung, and Ovarian Cancer
On Track to Nominate CDK12 Inhibitor as Next Development Candidate in 2H 2022
CAMBRIDGE, MA, USA I April 8, 2022 I Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, today announced new preclinical data from our CDK12 inhibitor program, demonstrating robust anti-tumor activity of our oral, selective CDK12 inhibitors in models of breast, lung, and ovarian cancer, including in a PARP inhibitor resistant model. The data support the advancement of a development candidate from Syros’ CDK12 inhibitor program towards clinical development. These findings were presented in an e-poster as part of the American Association for Cancer Research (AACR) Annual Meeting 2022.
“CDK12 is an attractive cancer target due to its role in transcription and DNA damage repair regulation. Leveraging our selective CDK inhibition expertise, we discovered potent, selective, and oral CDK12 inhibitors, which affect the expression of genes involved in DNA damage response to drive anti-tumor activity,” said Eric R. Olson, Ph.D., Chief Scientific Officer of Syros. “Based on the promising new data presented at AACR, in which CDK12 inhibition induced strong tumor growth inhibition and demonstrated synergies in combination with existing standard of care approaches, we believe a CDK12 inhibitor has the potential to play a key role in breast, lung, and ovarian cancer treatment. We look forward to nominating our next development candidate from our CDK12 program in the second half of this year, as we aim to address a significant unmet need for patients, including those who are resistant to DNA damaging agents or PARP inhibitors.”
Preclinical Data from Oral CDK12 Inhibitor Program
Syros designed a series of CDK12 inhibitors that were profiled in biochemical and cellular assays. The data presented at AACR detail for the first time the potency, selectivity, and anti-tumor activity from a representative member of the class, which exhibited low nanomolar potency and selectivity over CDK2, CDK7, and CDK9 of 46-, 27-, and 9-fold, respectively.
As a single agent in cancer cell models, this CDK12 inhibitor induced DNA damage, cell cycle dysregulation and genomic instability leading to growth inhibition and apoptosis. Additionally, as a single agent in in vivo cancer models this CDK12 inhibitor demonstrated tumor regressions in small cell lung cancer and breast cancer models, at well tolerated doses.
In combination in vitro, this CDK12 inhibitor showed synergistic or additive antiproliferative effects in combination with the DNA damaging agent, lurbinectedin, and the PARP inhibitor, olaparib, with increases in DNA damage and impaired DNA damage repair. In vivo, CDK12 inhibition in combination with lurbinectedin showed enhanced anti-tumor activity in a cell line derived model of small cell lung cancer, and in combination with olaparib showed enhanced anti-tumor activity in a PARP inhibitor resistant patient-derived model (PDX) of ovarian cancer.
The poster is now available on the Publications and Abstracts section of the Syros website at www.syros.com.
About Syros Pharmaceuticals
Syros is redefining the power of small molecules to control the expression of genes. Based on its unique ability to elucidate regulatory regions of the genome, Syros aims to develop medicines that provide a profound benefit for patients with diseases that have eluded other genomics-based approaches. Syros is advancing a robust clinical-stage pipeline, including: tamibarotene, a first-in-class oral selective RARα agonist in RARA-positive patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia; SY-2101, a novel oral form of arsenic trioxide in patients with acute promyelocytic leukemia; and SY-5609, a highly selective and potent oral CDK7 inhibitor in patients with select solid tumors and blood cancers. Syros also has multiple preclinical and discovery programs in oncology and monogenic diseases. For more information, visit www.syros.com and follow us on Twitter (@SyrosPharma) and LinkedIn.
SOURCE: Syros Pharmaceuticals
Post Views: 38
