On March 28, 2024 Larkspur Biosciences, a company pioneering a new wave in cancer therapy by targeting cancer-intrinsic drivers of immune evasion, reported that it will present positive preclinical efficacy data for LRK-A, Larkspur’s novel, lead investigational therapy targeting the lipid kinase PIP4K2C, in primary human tumor samples and an in vivo model of colorectal cancer (CRC) (Press release, Larkspur Biosciences, MAR 28, 2024, View Source [SID1234641568]). The data will be featured in a poster presentation at the 115th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2024) in San Diego, CA.
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"Larkspur Biosciences pursues novel targets inside the cancer, like PIP4K2C, that prevent the immune system from seeing and attacking it. Our data at AACR (Free AACR Whitepaper) 2024 demonstrate the potential of targeted PIP4K2C degradation to uncloak the tumor and support the advancement of our PIP4K2C degrader program as a monotherapy to treat CRC and other solid tumors," said Catherine Sabatos-Peyton, PhD, CEO of Larkspur Biosciences. "Using LarkXCRC, our proprietary bioinformatics platform, Larkspur developed a patient biomarker strategy to select the patients most likely to respond to LRK-A. This strategy enables the design of clinical trials that are smaller, faster, and have a higher probability of success."
CRC is the second leading cause of cancer-related deaths in the U.S.; in people under the age of 50, CRC is the top cause of cancer mortality in men and second cause in women 1. Larkspur aims to shift the treatment paradigm – which hasn’t meaningfully changed in decades – by effectively activating the immune system against tumors by targeting PIP4K2C.
"PIP4K2C is part of the ‘dark kinome’ – the approximately 25% of kinases with unknown or poorly understood functions," said Nathanael Gray, PhD, professor of chemical and systems biology at Stanford University and co-founder of Larkspur. "My co-founders and I jointly discovered that PIP4K2C acts in both cancer cells and immune cells to get tumor antigens presented to the right immune cells. Lew Cantley discovered that uniquely among the family of PI5P4K isoforms, mice that were germline knockouts of PIP4K2C broke tolerance, a hallmark of key targets that drive cancer immune evasion. Larkspur’s AACR (Free AACR Whitepaper) 2024 presentation sheds further light on PIP4K2C by offering key evidence for its role as a cancer-intrinsic driver of immune evasion in both tumor and immune cells, and demonstrating the therapeutic promise of degrading the target in CRC and other solid tumors."
Presentation details:
Published Abstract Number: 5574
Title: "Degradation of PIP4K2C by novel bivalent functional degrader LRK-A induces tumor regression in CRC"
Session Category / Session Title: Tumor Biology / Tumor-Immune System Cross-Talk
Session Date and Time: Tuesday, April 9, 1:30-5:30 pm PDT
Location / Poster Board Number: Poster Section 12 / Number 30
Presenter: Eva d’Hennezel, PhD, Director of Immunology, Larkspur Biosciences