By John Vandermosten, CFA

NASDAQ:LTRN

READ THE FULL LTRN RESEARCH REPORT

Lantern Pharma, Inc (NASDAQ:LTRN) continues to enroll its HARMONIC trial for LP-300 at sites around the globe with the most recent focus on Taiwan and Japan, where the prevalence of never-smoker non-small cell lung cancer (NSCLC) is from two to three times higher than in the United States. Lantern’s RADR (Response Algorithm for Drug Positioning & Rescue) platform continues to break ground with new capabilities in predicting blood brain barrier (BBB) permeability of drug candidates and improving the development of antibody drug conjugate (ADC) design. Lantern’s LP-184 gains another Fast Track designation for triple negative breast cancer (TNBC) following the receipt of the same designation for glioblastoma last October. The company also angled a spotlight towards its STAR-001 (LP-184) program at the Society for Neuro-Oncology (SNO) 2024 conference. The associated poster provided support for the combination of spironolactone with the next-generation acylfulvene in glioblastoma multiforme (GBM) and clarified the path forward for STAR-001 with the candidate’s trial design. GBM also made an appearance in a recent transaction where Jazz Pharmaceuticals (NASDAQ:JAZZ) made a bid to acquire Chimerix (NASDAQ:CMRX) for its brain cancer drug for almost $1 billion. The deal should provide an additional framework for determining the value of Lantern’s STAR-001 asset in GBM.

AI-Model Activity

Patent Application

Lantern’s Patent Cooperation Treaty (PCT) patent application entitled Machine Learning System and Method for Predicting Blood Brain Barrier Permeability was published by the World Intellectual Property Organization (WIPO) as reported in a February 19^th press release. The PCT application enables Lantern to pursue patent protection in major markets worldwide, with potential coverage extending 20 years from the filing date. The application describes a machine learning system and method for predicting blood-brain barrier permeability. It obtains samples of data associated with molecules from various data sources, converts the samples into structural representations, and generates features from the structural representations. Tests are conducted to determine blood-brain barrier permeability dependency. The system analyzes the ratio of permeable to non-permeable samples in the data and augments them with synthetic data to create a balanced dataset if an imbalance between the types of samples is detected. The system reduces the features utilized for training the machine learning utilizing a technique to create a selected set of features for the balanced dataset. The system trains a machine learning model using the balanced dataset, utilizing the machine learning model to predict blood-brain barrier permeability for the candidate molecule.

Lantern writes that the algorithm has performed well, processing up to 100,000 molecules per hour with notable accuracy. The technology can potentially accelerate drug development by identifying treatments that can enter the brain and central nervous system (CNS) thereby avoiding molecules that do not have this critical feature. The company plans to use the model to collaborate with pharmaceutical partners and biotechnology-driven companies to help them accelerate the advancement of their pipeline.

RADR Use in Identifying ADC Candidates

Lantern has also been developing an AI-powered module to improve the precision, cost and time to develop antibody drug conjugates (ADCs) for cancer. In late January the company announced that it had developed an AI-driven approach to identify ADC targets and target-indication combinations with a high degree of accuracy. 22 of the targets identified by the RADR platform have been validated in clinical or preclinical settings. Lantern has identified 60 additional targets that have potential for development. The company asserts that the AI-driven optimization capability could enhance the selective targeting and therapeutic window of the ADC payload candidates as well as reduce the time and cost of drug development. The team sees potential for partnership opportunities. The work was memorialized in a research article published in PLOS One entitled Expanding the repertoire of Antibody Drug Conjugate (ADC) targets with improved tumor selectivity and range of potent payloads through in-silico analysis.

Triple Negative Breast Cancer Target

LP-184 Receives Fast Track Designation

The FDA granted Lantern’s LP-184 a Fast Track designation in triple negative breast cancer (TNBC) late last year. This is the second such designation that the FDA has granted LP-184 in 2024. In October 2024, LP-184 was awarded Fast Track for a glioblastoma indication. Fast Track is granted to drug candidates that address serious or life-threatening conditions and an unmet medical need. The designation enables more frequent communication with the FDA, eligibility for rolling review and potential qualification for accelerated approval or priority review.

LP-184 is being evaluated in a Phase Ia clinical trial in patients with advanced solid tumors (NCT05933265) including TNBC. The trial is also enrolling patients diagnosed with glioblastoma multiforme (GBM), which was also granted a Fast Track designation last October.

TNBC Poster

Several authors on behalf of Lantern presented a poster entitled LP-184, a Novel Acylfulvene, Sensitizes Immuno-refractory Triple Negative Breast Cancers (TNBCs) to Anti-PD1 Therapy by Affecting the Tumor Microenvironment at the AACR Immuno-Oncology Conference in February. The poster summarized LP-184 work examining synergistic anti-tumor efficacy in a mouse TNBC model, gene expression at the single cell level as well as antigen presentation and interferon signaling in tumor cells among other preclinical studies in TNBC.

Conclusions from the poster found a synergistic anti-tumor response for LP-184 in combination with anti-PD-1 compared to monotherapies in mouse TNBC tumors that are non-hypermutated and IO agent resistant. LP-184 treatment appeared to reshape the tumor microenvironment by decreasing M2 macrophages, increasing T cell infiltration and enhancing individual T cell function when combined with immune checkpoint blockade therapy.

Transactions

A recent acquisition announcement in the oncology space between Jazz Pharmaceuticals (NASDAQ:JAZZ) and its target, Chimerix (NASDAQ:CMRX), valued the latter at $8.55 per share or $935 million for its lead clinical asset dordaviprone alongside other interests. Dordaviprone is an imipridone, a molecule discovered as a p53-independent inducer of TNF-related apoptosis-inducing ligand (TRAIL) gene transcription. It is in clinical-stage development for H3-K27M mutant diffuse glioma as its lead indication. Chimerix’ candidate has been submitted to the FDA in a new drug application (NDA) and has been granted priority review with a target action date of August 18^th, 2025.

H3 K27M-Mutant Diffuse Glioma

H3 K27M-mutant diffuse glioma is a significant and aggressive form of brain tumor Its genetic signature is the H3 K27M mutation which occurs in the histone H3 protein, which plays a crucial role in regulating gene expression.

This mutation leads to changes in how genes are expressed, contributing to the uncontrolled growth of tumor cells. The cancer is highly malignant and the tumors typically arise in the midline structures of the brain, such as the pons (leading to diffuse intrinsic pontine glioma or DIPG), the thalamus, spinal cord and other locations of the brain.

The estimated incidence of H3-K27 mutated gliomas is from 2,000 to 2,200 patients in the United States,^[1] which is markedly smaller than the estimated addressable market of 12,000 to 15,000 patients for STAR-001. Our research found a source that identified the H3-K27 mutation in 15% of cases.^[2] The disease is more common in children and is highly malignant.^[3]

Acquisition activity is an important driver for valuations, especially for earlier stage companies such as Lantern Pharma. This deal is particularly relevant as Chimerix is pursuing a subset of brain cancer that is hard to treat and has no FDA approved therapies. With an addressable market of several thousand patients per year and a course of therapy priced at $300 to $500 thousand, global revenues could easily surpass $1 billion for dordaviprone.

While it is in an earlier stage of development and must still demonstrate efficacy in GBM, Lantern’s STAR-101 may address a larger market in this indication. To place the two assets in context relative to their development stage, we generally apply a 10% probability of success to Phase I assets such as STAR-001 and up to a 90% probability of success for candidates that have been accepted for review by the FDA such as dordaviprone.

Expansion of Harmonic Trial to Asia

An April 22^nd, 2024 press release informed investors that the Harmonic trial for non-small cell lung cancer (NSCLC) in never smokers will expand into Japan and Taiwan. A statistic from UCSF’s cancer center found that over 50% of Asian American females diagnosed with lung cancer did not smoke. In Chinese females, the proportion went as high as 80%.^[4] The susceptibility to lung adenocarcinomas from never-smoker females can be in part attributable to oncogenic mutations.^[5] Lantern identified a source that finds one-third of all lung cancer patients in East Asia are non-smokers. Asia is an important market for LP-300 and clinical work in this region will provide the data necessary for regulatory approval in areas that require additional studies conducted in target ethnic populations. Success in these populations would be an important tailwind for LP-300 as there is a material unmet need. Expansion into Asia may also increase Lantern’s attractiveness with global biopharma companies. Management has activated ten sites in the region and as of mid-November enrolled its first patient in Japan and by early December, enrolled its first patient in Taiwan. All sites are continuing to actively screen patients.

SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR. 

DISCLOSURE: Zacks SCR has received compensation from the issuer directly, from an investment manager, or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks SCR provides and Zacks SCR receives quarterly payments totaling a maximum fee of up to $40,000 annually for these services provided to or regarding the issuer. Full Disclaimer HERE.

________________________

^{[1] Incidence provided by Lantern Pharma.}

^{[2] Schreck, K.C., et al. Incidence and clinicopathologic features of H3 K27M mutations in adults with radiographically-determined midline gliomas. Journal of Neurooncology. March 2019.}

^{[3] Zheng, L., et al. Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children. American Journal of Surgical Pathology. April 2022.}

^{[4]Addressing High Lung Cancer Rates Among Female Asian Non-Smokers. Karen Gehrman. January 13, 2022.}

^{[5] Ha, S. et al. Lung cancer in never-smoker Asian females is driven by oncogenic mutations most often involving EGFR. Oncotarget. March 2015.}