Lantern Pharma (LTRN) Status Update summary

Clinical trial results and safety profile

• Phase I-A trial of LP-184 completed with favorable safety and tolerability, showing mostly manageable Grade 1 and 2 adverse events and no significant cumulative toxicity, even with long-term dosing.

• Maximum tolerated dose established at dose level 11, with dose level 10 recommended for Phase II; dose-limiting toxicities were reversible and manageable.

• Drug achieved therapeutic concentrations from dose level 7 upwards, supporting both monotherapy and combination regimens.

• No significant hepatic or ocular toxicities observed, differentiating LP-184 from predecessors in its class.

• Patients with advanced, heavily pretreated solid tumors, including those with DNA damage repair deficiencies, showed durable stable disease, with some on treatment for over a year.

Mechanism of action and biomarker strategy

• LP-184 is a synthetic molecule inspired by illudin, designed for synthetic lethality in tumors with DNA damage repair deficiencies.

• Efficacy is highly dependent on PTGR1 expression; tumors with high PTGR1 and DNA repair pathway mutations are most sensitive.

• Developed an RT-qPCR assay for PTGR1 to enable precision medicine and tumor stratification.

• LP-184 induces double-strand DNA breaks, with selectivity for tumor cells due to low PTGR1 in normal cells.

• Combination with agents like Spironolactone and PARP inhibitors shows synergistic effects, expanding therapeutic potential.

Preclinical and clinical efficacy highlights

• Demonstrated superior or comparable efficacy to PARP inhibitors in HR-deficient tumors, including triple-negative breast cancer and pancreatic cancer.

• LP-184 effective in PARP inhibitor-resistant models and in combination regimens, showing complete tumor regression in preclinical studies.

• High potency observed in pancreatic cancer models, with 20x-400x greater efficacy than standard agents.

• Durable disease control observed in patients with DDR alterations, with some maintaining benefit for over a year.

• High prevalence of PTGR1 expression in trial patients supports the biomarker-driven approach.