On March 9, 2023 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical-stage biopharmaceutical company using its proprietary RADR artificial intelligence ("AI") and machine learning ("ML") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported new data for its product candidate LP-100 supporting the development of LP-100 in combination with the class of anticancer agents known as PARP inhibitors (PARPi) (Press release, Lantern Pharma, MAR 9, 2023, View Source [SID1234628483]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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.
"The combined anti-tumor potency of LP-100 in combination with PARP inhibitors, strongly supports the pursuit of this development pathway for LP-100," stated Panna Sharma, Lantern’s President and CEO. "We also believe this development focus will enhance the potential to position LP-100 in earlier lines of therapy, while also opening the door to pursue treatment indications with larger market sizes," continued Sharma. "Exposure to LP-100 results in double-strand DNA breaks and PARP inhibitors prevent the repair of these types of breaks. We believe this mechanistic combination provides a potent and highly synergistic method to eradicate tumors."
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 (NER) capabilities. Sensitivity to LP-100 is also higher in tumors with homologous recombination repair (HRR) 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 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 (OS) of approximately 12.5 months, which is an improvement over other similar fourth-line treatment regimens for mCRPC.
"Based on these results, the synergies of LP-100 with PARPi, along with the increasingly narrow field of patients in mCRPC due to the emergence of radio-ligand based therapies, we believe that the positioning of LP-100 in an earlier and more genomically defined setting is the best use of our resources and can lead to improved patient outcomes," continued Sharma.
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 U.S. market size of these and other potential target development indications for the LP-100 and PARPi combination is estimated at between $700 million and $2 billion.