NEW YORK – Lantern Pharma received clearance from the US Food and Drug Administration to begin a Phase Ib/II trial for LP-184, a small molecule drug for triple-negative breast cancer that was developed using artificial intelligence.
LP-184 is a small molecule that targets the enzyme prostaglandin reductase 1. Dallas-based Lantern said it used in silico AI modeling to determine LP-184 is synthetically lethal in cancer cells with alterations in genes involved in DNA damage repair (DDR). Further in vivo models showed its efficacy in PARP-resistant TNBC due to weakened homologous recombination repair pathways in those tumors, and LP-184's ability to penetrate the blood-brain barrier in advanced TNBC patients with brain metastasis.
Lantern's pipeline is AI-driven in that the company uses its machine-learning platform, RADR, to identify potential biomarkers to target, predict patient responses to treatment, and home in on combination therapies. Other biopharmaceutical firms have collaborated with Lantern to use RADR to advance their therapeutic pipelines, including Actuate Therapeutics, which has used the platform to identify combination treatment strategies that can overcome resistance to checkpoint inhibitors.
AI-developed drugs are still a relatively recent phenomenon, with very few having advanced beyond Phase II trials yet.
"This IND clearance for LP-184 in a Phase Ib/II study represents a pivotal advancement in our mission to bring precisely targeted, AI-developed medicines to patients with aggressive cancers and limited treatment options," Lantern CEO and President Panna Sharma said in a statement. "The strategic design of our clinical program reflects both the compelling mechanistic rationale and the encouraging data supporting LP-184's potential in TNBC."
The Phase Ib/II trial will be conducted at sites across the US, as well as at select academic institutions in India and Nigeria, which have high rates of TNBC comprising up to 40 percent of all breast cancer diagnoses. The monotherapy portion will involve 30 patients with advanced TNBC. In another arm, researchers are administering LP-184 with AstraZeneca and Merck's PARP inhibitor Lynparza (olaparib) as a second-line treatment to breast cancer patients with BRCA1 or BRCA2 mutations.
Patients with tumor types that are likely to have DDR genetic alterations or PTGR1 overexpression may be preferentially enrolled in the Phase Ia portion of the trial. In order to partake in the study, patients must provide archival biological samples for assessment of DDR genetic alterations, PTGR1 expression, and other genomic alterations if they achieve a partial or complete response to treatment they receive in the study.
Lantern said LP-184 has shown promise in other cancers with DNA damage repair gene mutations, including lung, bladder, pancreatic, and ovarian cancers, and it is planning further clinical trials to assess the drug in these settings.