LP-284

P1, N=110, Recruiting, Lantern Pharma Inc. | Not yet recruiting --> Recruiting | Initiation date: Nov 2023 --> Jan 2023

In preclinical pharmacology studies, the mantle cell lymphoma (MCL) xenograft tumor mouse model derived from JeKo-1, which has mutated TP53 and checkpoint kinase 2 (CHEK2), an HRD score of 46, and was refractory to ibrutinib and bortezomib, showed near complete response after LP-284 treatment. Overall, based on its impressive preclinical anti-tumor efficacy profile, low drug-drug interaction liability, and findings from toxicological studies, a Phase 1 study is currently planned with LP-284 to assess its safety, tolerability, pharmacokinetics, and clinical activity in patients with relapsed or refractory B-cell lymphoma. Clinical development will be informed by an emphasis on patient selection strategy based on DDR/HR biomarkers.

P1, N=110, Not yet recruiting, Lantern Pharma Inc.

As a monotherapy, LP-284 (2 mg/ kg) treatment resulted in 57% TGI, whereas combination treatment with LP-284 (2 mg/kg) and rituximab (10 mg/kg) resulted in 93% TGI. Taken together, our data support further characterization of HRDs in B-NHLs and the development of LP-284 as a targeted B-NHL therapy.

In addition, LP-284 is capable of inhibiting tumor growth of JeKo-1 xenografts that are refractory to bortezomib or ibrutinib. We further showed that LP-284 is particularly lethal in cells with deficient DNA damage response and repair, a targetable vulnerability in NHL.

LP-184, a small-molecule DNA-damaging agent, is known to be synthetically lethal in tumors with DNA-repair deficiencies, including tumors with ATM mutations...These MCL cell lines included cell lines resistant to ibrutinib, zanubrutinib, venetoclax, and bortezomib...Because ATM orchestrates the activities of the NER and HR pathways, MCL patients with ATM deficiencies are likely to have better responses to LP-284 treatment. Collectively, these data indicate that LP-284 is a promising preclinical DNA-damaging agent that possesses nanomolar-range anti-tumor activities in multiple and diverse MCL cell lines, with the potential to treat MCL patients who are resistant to other therapies.