Although significant advances have been made in the use of targeted and biomarker-based therapies in cancer, pancreatic cancer remains an area that has not experienced significant improvement in patient outcomes.

Today, the overall five-year survival rate for pancreatic cancer across all stages remains at only 10.0% in the US and 8.2% globally. Prostate cancer is the 2nd leading cause of cancer death in the USA in behind lung cancer according to data from the National Cancer Institute’s SEER Database.[1]

Using a proprietary platform technology to improve drug discovery & development and identify patients who will benefit from its targeted oncology therapeutics, Lantern Pharma confirmed a collaboration and research agreement with Fox Chase Cancer Center for the further development of Lantern’s LP-184 in pancreatic cancer.

Machine learning
Taking advantage of developments in machine learning and genomics, Lantern has developed a proprietary artificial intelligence (AI) platform called RADR® to repurpose, revitalize, and develop precision therapeutics in oncology.

According to the company’s scientists, machine learning, genomics, and computational methods can help accelerate the revitalization, refocusing, and development of small molecule-based therapies.

Scientists at the company use the company’s proprietary RADR® platform to discover biomarker signatures that help identify patients more likely to respond to the company’s pipeline of cancer therapeutics.

Igor Astsaturov, M.D., Ph.D., Associate Professor, Department of Hematology/Oncology, Co-Director, Marvin & Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center. Photo courtesy: ©2020 Temple University Health System/Fox Chase Cancer Center. Used with permission.

Collaboration
The Fox Chase collaboration focuses on advancing the targeted use of LP-184 in molecularly-defined sub-types of pancreatic cancer.

The goal of the collaboration is to create a more biologically relevant and robust gene signature in preparation for future clinical trials, enabling pancreatic cancer patients to potentially benefit from more effective and personalized cancer therapy.

“Collaborations with world-leading cancer centers are an essential part of our strategy to rapidly advance the insights driving our therapeutic programs and grow our RADR® A.I. platform by adding millions of new, unique, and proprietary data points,” said Panna Sharma, Chief Executive Officer of Lantern Pharma.

“This relationship with Fox Chase will allow us to use state-of-the-art models and biological methods to add more physiologically relevant data and insights into the mechanisms of LP-184, and will further shape our algorithms for how certain compounds interact with specific tumor types,” Sharma added.

“The unique insights we gain will equip Lantern with critical advantages in our aim of accelerating LP-184’s path to clinical trials and ultimately commercialization while saving millions of dollars in development costs. This data-enabled and biomarker-based approach has the potential to meaningfully bend the cost curve of cancer drug development and help bring personalized cancer therapies to patients with reduced economic burden, and greater efficacy,” he concluded.

The research will be led by Igor Astsaturov, MD, Ph.D., Associate Professor, Department of Hematology/Oncology at Fox Chase.

Astsaturov, an internationally-recognized researcher in gastrointestinal cancers at the Molecular Therapeutics Program at Fox Chase specializes in investigating signaling pathways that inform the choice of biomarkers and innovative therapy combinations in clinical trials. He is known for his research in a number of cancer indications spanning pancreatic, stomach, liver, and several others, as well as his belief that each individual cancer patient will soon be defined by the molecular makeup of their cancer cells.

Translational research
LP-184 or hydroxyureamethyl-acylfulvene, is a DNA-damaging small molecule drug candidate currently in preclinical development for certain genomically defined solid tumors, including pancreatic cancer. As a next-generation alkylating agent that preferentially damages DNA in cancer cells that overexpress certain biomarkers, LP-184 has the potential to be used as both monotherapies as well as a synergistic agent in combination with other drugs.

The investigational drug is a promising member of a new generation of acylfulvenes, a family of naturally-derived anti-cancer drug candidates. In preclinical studies, LP-184 has shown significantly enhanced anti-tumor activity and substantially reduced toxicity as compared to earlier generations of acylfulvenes.

Mechanism of action of LP-184, or hydroxyureamethyl-acylfulvene, a small molecule drug candidate currently in preclinical development. It is a next-generation alkylating agent that preferentially damages DNA in cancer cells that overexpress certain biomarkers and is from the fulvene class of compounds. Image courtesy: © 2020 Lantern Pharma.

Scientists at Lantern have used the company’s RADR™ platform technology together with the work of collaborators, to develop a patient-specific biomarker test predictive of LP-184’s efficacy.

“We are very pleased to partner with Lantern Pharma in establishing a collaboration that will play an important role in our research,” Astsaturov, MD, Ph.D.,

“Our advanced research approach using patient-derived cancer models will provide us with critical insights into the efficacy of LP-184 in pancreatic cancers. We look forward to sharing these results with the broader scientific community and hopefully bringing this drug to cancer patients that can best benefit from this compound.”

The research program is at the forefront of translational cancer medicine and will use patient-derived cancers that are grown in the lab and transformed into physiologically relevant 3D organoids and PDx models.

Understanding the biology
This innovative approach allows researchers to more precisely understand the biology of what actually happens inside the cancer tumor, which will more accurately establish the precise biomarker signatures and help provide data-driven insight into additional mechanisms that can be leveraged in the fight against pancreatic cancer.

Among several objectives, the research will determine whether the overexpression of the gene PTGR1, a biomarker that has been linked to cancer cell proliferation, will indicate heightened sensitivity to LP-184 and a more favorable response rate and efficacy as compared to standard of care agents.

References
[1] Cancer Stat Facts: Pancreatic Cancer. National Cancer Institute. Online. Last Accessed on September 22, 2020.

Featured image: Fox Chase Cancer Center. Photo courtesy: ©2014 – 2020 Temple University Health System/Fox Chase Cancer Center. Used with permission.

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