In prostate cancer mouse xenograft studies, LP-100 demonstrated synergistic potency when used in combination with the FDA-approved PARP inhibitor Olaparib.
LP-100 also demonstrated synergy with the FDA-approved PARP inhibitors Olaparib, Rucaparib, and Niraparib in ovarian cancer cell line studies.
The observations from these studies are further supported by in-silico evaluation of LP-100 in combination with PARP inhibitors using Lantern's AI platform, RADR.
LP-100 and PARP inhibitors act by complementary mechanisms. LP-100 acts by a synthetically lethal mechanism of action that preferentially damages DNA in cancer cells lacking nucleotide excision repair capabilities.
Sensitivity to LP-100 is also higher in tumors with homologous recombination repair deficiency, suggesting that this pathway is also involved in the repair of DNA damage from LP-100.
PARP inhibitors have been shown to be effective in the treatment of tumors with HRR deficiencies.
Lantern said it believes the simultaneous exploitation of both these mechanisms will enhance the development opportunities for LP-100, while also expanding potential market opportunities for existing PARP inhibitors.
LP-100 has previously been in a genomic signature guided Phase 2 clinical trial in Denmark where the drug candidate was used without PARP inhibitors for patients with metastatic castration-resistant prostate cancer (mCRPC).
In this trial 9 patients (out of a targeted enrollment of 27) were treated and had a median overall survival of approximately 12.5 months, which is an improvement over other similar fourth-line treatment regimens for mCRPC.
In conjunction with its evaluation work on LP-100 with PARP inhibitors, Lantern has been collaborating with the Danish Cancer Society Research Center (DCSRC) to explore the future clinical potential of LP-100 across 9 different solid tumor types that have known deficiencies in DNA repair pathway mechanisms.
This work has included an examination of the role of NER deficiency in breast, ovarian, prostate, lung, kidney, bladder, stomach, pancreatic, and esophageal cancers, with the aim of identifying the most promising patient populations for future LP-100 therapy.
Lantern expects to present additional details on the results of its collaboration with DCSRC later this year.
Based on Lantern's evaluation of the synergies of LP-100 with PARP inhibitors, and the industry's development of entirely new classes of radio-ligand based therapy for mCRPC, the decision has been made to close the Phase 2 clinical trial in Denmark, to allow the focus of LP-100-directed resources on positioning the molecule for development in earlier lines of therapy with potentially larger market opportunities.
Earlier line treatment indications where Lantern believes LP-100 in combination with PARPi could have potential future treatment benefits include prostate cancer indications such as HRR gene-mutated metastatic castration-resistant prostate cancer, ovarian cancer indications such as first line platinum-responsive advanced ovarian cancer, and breast cancer indications such as germline BRCA-mutated metastatic breast cancer.
The total US market size of these and other potential target development indications for the LP-100 and PARPi combination is estimated at between USD 700m and USD 2bn.
Lantern Pharma (NASDAQ: LTRN) is a clinical-stage oncology-focused biopharmaceutical company leveraging its proprietary RADR AI and machine learning platform to discover biomarker signatures that identify patients most likely to respond to its pipeline of genomically-targeted therapeutics.
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