WATERTOWN, MA, USA I November 12, 2021 I Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD) to deliver novel small molecule protein degrader medicines, today presented new preclinical data from its STAT3 degrader program at the Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting, taking place from November 10 – 14, 2021 in Washington, D.C. and virtually.
The results reveal Kymera’s potent and selective STAT3 degraders exhibited anti-tumor activity in multiple preclinical animal models of solid and hematologic malignancies that respond poorly to immunotherapies. Administration of a tool STAT3 degrader, KTX-201, led to molecular and cellular changes in the tumor microenvironment that were predictive of favorable responses to checkpoint inhibition. Consistent with these findings, KTX-201 sensitized these tumors to anti-PD1 treatment when administered in combination, leading to durable anti-tumor responses and development of long-term immunological memory.
“These encouraging findings underscore the potential power of targeted protein degradation (TPD) to address a range of cancers driven by STAT3, an undruggable transcription factor with effects on both tumor cells and the tumor microenvironment,” said Jared Gollob, MD, Chief Medical Officer at Kymera Therapeutics. “We believe our novel data offer critical insights into the antitumor activity of Kymera’s STAT3 degraders, particularly their potential to synergize with immunotherapies such as checkpoint blockade – which only work in a small percentage of patients – thereby providing a rationale for selectively degrading STAT3 to sensitize cancers to immune checkpoint inhibition in the clinic.”
STAT3 is a transcription factor activated through a variety of different cytokine and growth factor receptors via Janus kinases (JAKs), as well as through oncogenic fusion proteins and mutations in STAT3 itself. Long considered an “undruggable” target, STAT3 hyperactivation is prominent in numerous liquid and solid tumors, including clinically aggressive lymphomas. Kymera is developing selective STAT3 degraders for the treatment of hematological malignancies and solid tumors, as well as autoimmune diseases and fibrosis. Kymera’s STAT3 degraders have previously demonstrated strong anti-tumor effects in mouse xenograft and syngeneic models of liquid and solid cancers.
“Research presented to date on Kymera’s STAT3 degraders has bolstered our knowledge of the mechanisms underlying the anti-tumor and immunomodulatory effects associated with STAT3 degradation,” said Nello Mainolfi, PhD, Co-Founder, President and CEO, Kymera Therapeutics. “We are eager to advance KT-333, a first-in-class selective STAT3 degrader for liquid and solid tumors into Phase 1 clinical trials by the end of 2021.”
Additional Research Highlights:
- Treatment of CT-26 (colorectal cancer) and A20 (B-cell lymphoma) tumor-bearing mice with a STAT3 degrader resulted in significant tumor growth inhibition compared to controls, with loss of STAT3 protein in both tumor cells and TME.
- Treatment of CT-26 and A20 tumor-bearing mice with a STAT3 degrader led to a decrease in M2 polarized macrophages and concomitant increases in M1 polarized macrophages and tumor infiltrating lymphocytes.
- Gene expression profiling of STAT3 degrader-treated CT-26 tumors showed marked increases in proinflammatory genes including T cell and M1 macrophage activation markers, compared to controls.
- Induction of an Ifnγ-responsive gene signature (Ifnγ, Stat1, Cxcl9, Cxcl10, Ido1) in CT-26 tumors showed that STAT3 degradation results in a T cell inflamed phenotype associated with responsiveness to immune checkpoint therapy.
- On-treatment tumors showed an upregulation of genes such as Pdl1, Ctla4, Lag3 which reflect T cell activation as well as counterregulatory mechanisms.
- STAT3 degradation in combination with anti-PD1 resulted in robust synergy in the CT-26 model with 60% complete responses and development of immunological memory as confirmed by tumor rechallenge studies.
- Studies are underway to ascertain the applicability of this combination therapy in different tumor immune contextures, and to elucidate the mechanistic basis of synergy.
Presentation at SITC Annual Meeting:
- Title: Targeted STAT3 Degradation Leads to Remodeling of an Immunosuppressive Tumor Microenvironment and Subsequent Sensitization to Immune Checkpoint Therapy
- Abstract Number: 603
- Session Time: 7:00 a.m. – 8:30 a.m. ET on Friday, Nov. 12, 2021
- Location: Poster Hall (Hall E), Walter E. Washington Convention Center, Washington, D.C.
- Presenter: Joyoti Dey, Associate Director, Translational Medicine, Kymera Therapeutics
About Kymera Therapeutics
Kymera Therapeutics (Nasdaq: KYMR) is a clinical-stage biopharmaceutical company founded with the mission to discover, develop, and commercialize transformative therapies while leading the evolution of targeted protein degradation, a transformative new approach to address previously intractable disease targets. Kymera’s Pegasus™ platform enables the discovery of novel small molecule degraders designed to harness the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on undrugged nodes in validated pathways currently inaccessible with conventional therapeutics. Kymera’s initial programs are IRAK4, IRAKIMiD, and STAT3, each of which addresses high impact targets within the IL-1R/TLR or JAK/STAT pathways, providing the opportunity to treat a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. Kymera’s goal is to be a fully integrated biopharmaceutical company at the forefront of this new class of protein degrader medicines, with a pipeline of novel degrader medicines targeting disease-causing proteins that were previously intractable.
Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” biotechnology company by FierceBiotech and has been recognized by the Boston Business Journal as one of Boston’s “Best Places to Work.” For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn.
SOURCE: Kymera Therapeutics
Post Views: 78
WATERTOWN, MA, USA I November 12, 2021 I Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD) to deliver novel small molecule protein degrader medicines, today presented new preclinical data from its STAT3 degrader program at the Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting, taking place from November 10 – 14, 2021 in Washington, D.C. and virtually.
The results reveal Kymera’s potent and selective STAT3 degraders exhibited anti-tumor activity in multiple preclinical animal models of solid and hematologic malignancies that respond poorly to immunotherapies. Administration of a tool STAT3 degrader, KTX-201, led to molecular and cellular changes in the tumor microenvironment that were predictive of favorable responses to checkpoint inhibition. Consistent with these findings, KTX-201 sensitized these tumors to anti-PD1 treatment when administered in combination, leading to durable anti-tumor responses and development of long-term immunological memory.
“These encouraging findings underscore the potential power of targeted protein degradation (TPD) to address a range of cancers driven by STAT3, an undruggable transcription factor with effects on both tumor cells and the tumor microenvironment,” said Jared Gollob, MD, Chief Medical Officer at Kymera Therapeutics. “We believe our novel data offer critical insights into the antitumor activity of Kymera’s STAT3 degraders, particularly their potential to synergize with immunotherapies such as checkpoint blockade – which only work in a small percentage of patients – thereby providing a rationale for selectively degrading STAT3 to sensitize cancers to immune checkpoint inhibition in the clinic.”
STAT3 is a transcription factor activated through a variety of different cytokine and growth factor receptors via Janus kinases (JAKs), as well as through oncogenic fusion proteins and mutations in STAT3 itself. Long considered an “undruggable” target, STAT3 hyperactivation is prominent in numerous liquid and solid tumors, including clinically aggressive lymphomas. Kymera is developing selective STAT3 degraders for the treatment of hematological malignancies and solid tumors, as well as autoimmune diseases and fibrosis. Kymera’s STAT3 degraders have previously demonstrated strong anti-tumor effects in mouse xenograft and syngeneic models of liquid and solid cancers.
“Research presented to date on Kymera’s STAT3 degraders has bolstered our knowledge of the mechanisms underlying the anti-tumor and immunomodulatory effects associated with STAT3 degradation,” said Nello Mainolfi, PhD, Co-Founder, President and CEO, Kymera Therapeutics. “We are eager to advance KT-333, a first-in-class selective STAT3 degrader for liquid and solid tumors into Phase 1 clinical trials by the end of 2021.”
Additional Research Highlights:
- Treatment of CT-26 (colorectal cancer) and A20 (B-cell lymphoma) tumor-bearing mice with a STAT3 degrader resulted in significant tumor growth inhibition compared to controls, with loss of STAT3 protein in both tumor cells and TME.
- Treatment of CT-26 and A20 tumor-bearing mice with a STAT3 degrader led to a decrease in M2 polarized macrophages and concomitant increases in M1 polarized macrophages and tumor infiltrating lymphocytes.
- Gene expression profiling of STAT3 degrader-treated CT-26 tumors showed marked increases in proinflammatory genes including T cell and M1 macrophage activation markers, compared to controls.
- Induction of an Ifnγ-responsive gene signature (Ifnγ, Stat1, Cxcl9, Cxcl10, Ido1) in CT-26 tumors showed that STAT3 degradation results in a T cell inflamed phenotype associated with responsiveness to immune checkpoint therapy.
- On-treatment tumors showed an upregulation of genes such as Pdl1, Ctla4, Lag3 which reflect T cell activation as well as counterregulatory mechanisms.
- STAT3 degradation in combination with anti-PD1 resulted in robust synergy in the CT-26 model with 60% complete responses and development of immunological memory as confirmed by tumor rechallenge studies.
- Studies are underway to ascertain the applicability of this combination therapy in different tumor immune contextures, and to elucidate the mechanistic basis of synergy.
Presentation at SITC Annual Meeting:
- Title: Targeted STAT3 Degradation Leads to Remodeling of an Immunosuppressive Tumor Microenvironment and Subsequent Sensitization to Immune Checkpoint Therapy
- Abstract Number: 603
- Session Time: 7:00 a.m. – 8:30 a.m. ET on Friday, Nov. 12, 2021
- Location: Poster Hall (Hall E), Walter E. Washington Convention Center, Washington, D.C.
- Presenter: Joyoti Dey, Associate Director, Translational Medicine, Kymera Therapeutics
About Kymera Therapeutics
Kymera Therapeutics (Nasdaq: KYMR) is a clinical-stage biopharmaceutical company founded with the mission to discover, develop, and commercialize transformative therapies while leading the evolution of targeted protein degradation, a transformative new approach to address previously intractable disease targets. Kymera’s Pegasus™ platform enables the discovery of novel small molecule degraders designed to harness the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on undrugged nodes in validated pathways currently inaccessible with conventional therapeutics. Kymera’s initial programs are IRAK4, IRAKIMiD, and STAT3, each of which addresses high impact targets within the IL-1R/TLR or JAK/STAT pathways, providing the opportunity to treat a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. Kymera’s goal is to be a fully integrated biopharmaceutical company at the forefront of this new class of protein degrader medicines, with a pipeline of novel degrader medicines targeting disease-causing proteins that were previously intractable.
Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” biotechnology company by FierceBiotech and has been recognized by the Boston Business Journal as one of Boston’s “Best Places to Work.” For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn.
SOURCE: Kymera Therapeutics
Post Views: 78
