Addressing
Immunosuppression
in the TME

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Addressing immunosuppression in the TME

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KVA12123
Anti-VISTA mAb

KVA12123 (formerly referred to as KVA12.1) is potentially a differentiated VISTA blocking immunotherapy to address the problem of immunosuppression in the tumor microenvironment (TME).

KVA12123 is a fully human engineered IgG1 monoclonal antibody that was designed to bind to VISTA through a unique epitope at physiologic and acidic pH levels. KVA12123 is being developed as an intravenous infusion.

In preclinical models, KVA12123 demonstrates single agent tumor growth inhibition in cold tumors and in combination with other checkpoint inhibitors (CPIs).  It is well-tolerated with no CRS-associated cytokine release (change IL6 and TNFα levels) or neurotoxicity seen in preclinical models.

Kineta opened a Phase 1 clinical study evaluating KVA12123 as a single agent and in combination with (pembrolizumab) in patients with advanced solid tumors.  The objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and anti-tumor responses of KVA12123 alone and in combination with KEYTRUDA® (pembrolizumab). 

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Target

VISTA is a key driver of immunosuppression in the TME resulting in blockade and down-regulation of the immune response which are the hallmarks of a ‘‘cold tumor.’’

VISTA is a negative  immune checkpoint that suppresses T cell function in a variety of solid tumors. High VISTA expression in tumor correlates with poor survival in cancer patients and has been associated with a lack of response to other CPIs.

Blocking VISTA drives an efficient polyfunctional immune response to address immunosuppression and turn cold tumors hot. VISTA is a novel immuno-oncology target due to its unique expression and activity. First, high VISTA expression on myeloid cells (monocytes and macrophages) is consistent across tumor types, making it a relevant target across multiple types of cancer. Re-programmed monocytes can drive tumor inflammation. Releasing suppression of myeloid cells by targeting VISTA can provide single agent tumor growth inhibition and also improve efficacy of T cell focused therapies like anti-PD(L)1 and anti-CTLA4.

Second, blocking VISTA induces activation of dendritic cells and ultimately proliferation and infiltration of T cells into the tumor. The combination of myeloid and T cell responses can reverse immunosuppression and drive anti-tumor activity. While many immuno-oncology targets address either T cell or myeloid functions, VISTA has indicated the potential to regulate both.

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Collaboration with Merck

Kineta entered into a clinical trial collaboration and supply agreement with Merck (known as MSD outside the U.S. and Canada).  Under this collaboration, Kineta will evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of KVA12123 (formerly KVA12.1), its novel anti-VISTA monoclonal antibody, alone and in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with advanced solid tumors.

Read the Press Release

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The Market

An estimated 19.3 M new cases of cancer were diagnosed with over 10 million deaths in 2020 worldwide.

Cancer is now the second leading cause of death in the United States, second only to heart disease, with over 600,000 deaths in 2020.  In 2021, roughly 1.9 million people will be diagnosed with cancer in the United States.  Breast, lung, and colorectal cancers account for 50% of all new diagnoses in women while prostate, lung, and colorectal cancers account for 46% new diagnoses in men.1

Based on the strong clinical rationale and commercial opportunity, Kineta has identified NSCLC, CRC and OC as potential initial indications for KVA12123. The projected new annual patients for each of these initial indications in 2027 totals 980,000 for Non-small cell lung cancer (NSCLC), 1.1 million for colorectal cancer (CRC) and 660,000 for ovarian cancer (OC), based on reports from GlobalData.2

In total, these three initial indications represent an estimated 2.7 million annual new patient opportunity for KVA12123.

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Publications

Shawn Iadonato, Yulia Ovechkina, Kurt Lustig, Jessica Cross, Nathan Eyde, Emily Frazier, Neda Kabi, Chen Katz, Remington Lance, David Peckham, Shaarwari Sridhar, Carla Talbaux, Isabelle Tihista, Mei Xu, Thierry Guillaudeux* Frontiers in Immunology | December 12, 2023

Thierry Guillaudeux, Shaarwari Sridhar, Emily Frazier, Yulia Ovechkina, Shawn Iadonato Blood - American Society of Hematology | November 28, 2023

Thierry Guillaudeux, Phd, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 2023 | November 3, 2023

Randolph J. Noelle, J. Louise Lines, Lionel D. Lewis, Robert E. Martell, Thierry Guillaudeux, Sam W. Lee, Kathleen M. Mahoney, Matthew D. Vesely, Jerome Boyd-Kirkup, Dhanya K. Nambiar and Andrew M. Scott
Frontiers in Oncology | September 15, 2023

Thierry Guillaudeux, PhD, Chief Scientific Officer
American Association for Cancer Research (AACR) Annual Meeting 2023 | April 16, 2023

Thierry Guillaudeux, PhD, Chief Scientific Officer
Antibody Engineering & Therapeutics Conference | December 7, 2022

Thierry Guillaudeux, PhD, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 2022 | November, 2022

Shaarwari Sridhar, Scientist at Kineta
Tumor Myeloid-Directed Therapies Summit 2022 | June 14, 2022

Thierry Guillaudeux, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 2021 | November, 2021

Thierry Guillaudeux, PhD, Chief Scientific Officer
American Association for Cancer Research (AACR) Annual Meeting 2021 | April, 2021

Thierry Guillaudeux, PhD, Chief Scientific Officer
European Society for Medical Oncology (ESMO) Virtual Congress 2020 | December 9, 2020

Thierry Guillaudeux, PhD, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting | November 12, 2020

Thierry Guillaudeux, PhD, Chief Scientific Officer
American Association for Cancer Research (AACR) Virtual Special Conference: Tumor Immunology and Immunotherapy | October 19-20, 2020

Shawn Iadonato, Yulia Ovechkina, Kurt Lustig, Jessica Cross, Nathan Eyde, Emily Frazier, Neda Kabi, Chen Katz, Remington Lance, David Peckham, Shaarwari Sridhar, Carla Talbaux, Isabelle Tihista, Mei Xu, Thierry Guillaudeux* Frontiers in Immunology | December 12, 2023

Thierry Guillaudeux, Shaarwari Sridhar, Emily Frazier, Yulia Ovechkina, Shawn Iadonato Blood - American Society of Hematology | November 28, 2023

Thierry Guillaudeux, Phd, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 2023 | November 3, 2023

Randolph J. Noelle, J. Louise Lines, Lionel D. Lewis, Robert E. Martell, Thierry Guillaudeux, Sam W. Lee, Kathleen M. Mahoney, Matthew D. Vesely, Jerome Boyd-Kirkup, Dhanya K. Nambiar and Andrew M. Scott
Frontiers in Oncology | September 15, 2023

Thierry Guillaudeux, PhD, Chief Scientific Officer
American Association for Cancer Research (AACR) Annual Meeting 2023 | April 16, 2023

Thierry Guillaudeux, PhD, Chief Scientific Officer
Antibody Engineering & Therapeutics Conference | December 7, 2022

Thierry Guillaudeux, PhD, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 2022 | November, 2022

Shaarwari Sridhar, Scientist at Kineta
Tumor Myeloid-Directed Therapies Summit 2022 | June 14, 2022

Thierry Guillaudeux, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 2021 | November, 2021

Thierry Guillaudeux, PhD, Chief Scientific Officer
American Association for Cancer Research (AACR) Annual Meeting 2021 | April, 2021

Thierry Guillaudeux, PhD, Chief Scientific Officer
European Society for Medical Oncology (ESMO) Virtual Congress 2020 | December 9, 2020

Thierry Guillaudeux, PhD, Chief Scientific Officer
Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting | November 12, 2020

Thierry Guillaudeux, PhD, Chief Scientific Officer
American Association for Cancer Research (AACR) Virtual Special Conference: Tumor Immunology and Immunotherapy | October 19-20, 2020

References:
1. Rebecca L. Siegel et al.; Cancer statistics, 2020; ACS Journals; First published: 08 January 2020 https://doi.org/10.3322/caac.21660
2. GlobalData epidemiology forecasts for NSCLC, CRC, OC