2023 World Conference on Lung Cancer (Posters)-P1.12. LP-184, a Tumor Site Activated Small Molecule Acylfulvene, Is Effective Preclinically in Subsets of Lung Cancer

P1.12. LP-184, a Tumor Site Activated Small Molecule Acylfulvene, Is Effective Preclinically in Subsets of Lung Cancer - PDF(Abstract)

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Lantern Pharma is developing LP-184, a small molecule therapeutic, to target specific subsets of lung cancer. LP-184 is designed to activate at the tumor site and has shown effectiveness in preclinical studies. It induces DNA double strand breaks and forms adducts. LP-184 is a prodrug that depends on the expression of an oxidoreductase enzyme called PTGR1 for its anti-tumor cytotoxicity. Lung cancer cells with higher levels of PTGR1 are more sensitive to LP-184. Lung tumors with mutations in KEAP1, a co-regulator of NRF2, overexpress PTGR1, making them highly responsive to LP-184.<br /><br />The DNA damage induced by LP-184 is repaired primarily by nucleotide excision repair (NER) or homologous recombination (HR) pathways. LP-184 causes lethal double strand breaks that remain unrepaired in NER/HR deficient tumors, leading to tumor cell death. <br /><br />LP-184 has shown strong potency in patient-derived lung cancer models with homologous recombination deficiencies, such as those with ATM, BRCA1, or CHEK1 mutations. Its effectiveness was 12-350 times superior to that of Olaparib, a known therapeutic, in these models. LP-184 also demonstrated anti-tumor activity in a xenograft model of lung cancer with KEAP1/STK11 mutations.<br /><br />Based on these promising results, LP-184 is being considered for clinical development in small cell and non-small cell lung cancers. Preclinical toxicology studies have shown that LP-184 is well tolerated in rats and dogs. A Phase 1A trial is expected to enroll patients with advanced solid tumors, including lung cancers.

Asset Subtitle

Reginald Ewesuedo

Meta Tag

Speaker Reginald Ewesuedo

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

Lantern Pharma

LP-184

lung cancer

small molecule therapeutic

tumor site

preclinical studies

DNA double strand breaks

adducts

PTGR1

oxidoreductase enzyme