On April 26, 2021 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") platform to transform oncology drug discovery and development, reported a manuscript describing the efficacy profile of LP-184 in a variety of non-small cell lung cancer models was published in Oncotarget (Press release, Lantern Pharma, APR 26, 2021, View Source [SID1234578495]). The manuscript is titled ‘The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations’. LP-184 is being developed by Lantern for the potential treatment of non-small cell lung cancer (NSCLC) among several other targeted indications in solid tumors including pancreatic and CNS cancers.
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The unmet clinical need where LP-184-based therapy could potentially be valuable is for those non-small cell lung cancer patients that are ineligible for targeted therapy options or have developed resistance to other forms of therapy. Existing targeted therapies, such as EGFR or ALK inhibitors, only work in specific, genetically defined patient subsets. There’s a sizable fraction of lung cancers — 30 to 40 percent — that do not have those targetable alterations, or have developed resistance to the current standard of care therapies which can often leave lung cancer patients without additional therapeutic options. According to Panna Sharma, CEO of Lantern Pharma, "More people continue to die of lung cancer every year than any other type of cancer, and significant improvements have been made in the era of targeted and combination therapies; however, many lung cancers rapidly evolve and form resistance to both targeted agents and chemotherapy combinations, and there is a major clinical need for new options and potentially extending patient lives further." Mr. Sharma continued, "With this additional indication for our DNA-damaging agent, LP-184, we continue to invest in the development of therapeutic options for increasing the personalization of therapy for lung cancer patients."
This publication in Oncotarget highlights LP-184’s nanomolar in vitro potency in primary and metastatic NSCLC models. It also demonstrates that LP-184 is generally more potent in vitro than commonly prescribed platin and taxane based chemotherapeutics. Based on the research conducted, the activity profile of LP-184 is not influenced by the presence of mutations in key oncogenes such as KRAS or KEAP1 and tumor suppressors such as TP53 and STK11, that otherwise underlie resistance to other drugs. LP-184 is believed to be a promising drug candidate that can address the treatment of KEAP1 mutant NSCLC, because the mutations up-regulate expression of PTGR1, and increased PTGR1 in turn makes tumor cells increasingly sensitive to LP-184.
Additionally, LP-184 showed tumor growth inhibition in a mouse xenograft model of KRAS/KEAP1 mutant lung cancer. Co-occurring KRAS and KEAP1 mutations occur in about 17 percent of lung adenocarcinoma cases and are believed to represent an aggressive form of lung cancer that is believed to be "undruggable". Lantern Pharma has developed a genomic signature that is believed to predict response in tumors that will be responsive to LP-184. This correlation and pinpointing of clinical need were supported by further TCGA analysis of 517 lung adenocarcinoma patients, out of which 35% showed elevated PTGR1, and 40% of those further displayed statistically significant co-occurrence of KEAP1 mutations. Considering an overlap between LP-184-specific response biomarkers and NSCLC-related genomic groups, we believe that the clinical data analyses reveal patient subgroups with distinct molecular backgrounds that are likely to be responders to LP-184 and benefit from this drug candidate.
According to Mr. Sharma, "Using our data-driven approach we have shown that not only can we find unique biomarkers that link to drug response and mechanism, but we can also rapidly uncover clinically meaningful patient subgroups that can benefit from our portfolio of therapies." Mr. Sharma continued, "By understanding the genomic and biomarker characteristics driving a compound’s activity in various sub types of cancer, we can rapidly develop new meaningful indications that have the potential to deliver life changing therapy options for cancer patients — and we can do this faster and with better insights as a result or our RADR platform. We will continue to invest into increasing the data, scope and functionality of the A.I. platform and expect that it will be able to play a wider role in cancer therapy development.
Lantern is continuing to validate LP-184 sensitivity in advanced lung tumor models both as monotherapy and in combination with drugs prioritized by Lantern’s RADR models, to increase the potential future benefit to patients with tumors that are or have become otherwise "undruggable" or non-responsive to existing approved therapies.