Periodic Reporting for period 1 - PANC561 (LAM561 BEATS PANCREATIC CANCER)
Période du rapport: 2021-04-01 au 2023-03-31
LAM561 BEATS PANCREATIC CANCER proposal is a translational research project introducing an innovative therapeutic approach for fighting cancer that takes advantage of inter-sectoral industry-academia strengths and international cooperation. This is also an interdisciplinary project in which lipid chemistry, cell biology, molecular biology and medicinal chemistry, meet to improve the treatment of several cancers. The beneficiary (Laminar Pharmaceuticals SA) designs and develops synthetic bio-active lipids based on cutting edge technology, Membrane Lipid Therapy (MLT), which aims to regulate the membrane lipid composition and structure to control cell functions. The company has demonstrated that the compound LAM561 (2-hydroxyoleic acid, 2OHOA) which has been designated ‘orphan drug’ by the European Medicines Agency (EMA), it has obtained a "fast track designation" by the FDA to accelerate its development and review, it has a high efficacy in the treatment of malignant brain tumors (gliomas) and it is about to finish the clinical trial phase II/III which may allow to have the product in the market by 2024. The current proposal aims to initiate the pharmaceutical development of LAM561 in order to obtain the approval to a new indication: pancreatic cancer.
This project implies the challenges: 1st to extending the indications of LAM561 killer effect to pancreatic cancer and open the door to clinical trials in patients and 2nd to gain insights of LAM561 mechanism of action and promote the discovery of new MLT-based agents. Specifically, by the end of this translational project, I will have determined: Objective 1 the therapeutic potential and safety profile of LAM561 in cell models of pancreatic cancer, Objective 2 the antimigratory and antimetastatic activity in pancreatic cancer cell models, Objective 3 the antitumor safety and efficacy profile in different animal models of human and mouse pancreatic cancer and Objective 4 I will develop new MLT-based antitumor molecules against pancreatic cancer that broaden the Laminar Pharmaceuticals portfolio in oncology. LAM561 has demonstrated its efficacy against tumors like glioma, and this proposal intends to broaden the indications of this drug including data about its efficacy and safety in pancreatic cancer. The final objective of this work is to obtain the required data to advance in the development of a potential new therapy for pancreatic cancer disease. As this drug is already being developed in glioma, clinical development of the product in pancreatic cancer would be more rapid.
This project implies the challenges: 1st to extending the indications of LAM561 killer effect to pancreatic cancer and open the door to clinical trials in patients and 2nd to gain insights of LAM561 mechanism of action and promote the discovery of new MLT-based agents. Specifically, by the end of this translational project, I will have determined: Objective 1 the therapeutic potential and safety profile of LAM561 in cell models of pancreatic cancer, Objective 2 the antimigratory and antimetastatic activity in pancreatic cancer cell models, Objective 3 the antitumor safety and efficacy profile in different animal models of human and mouse pancreatic cancer and Objective 4 I will develop new MLT-based antitumor molecules against pancreatic cancer that broaden the Laminar Pharmaceuticals portfolio in oncology. LAM561 has demonstrated its efficacy against tumors like glioma, and this proposal intends to broaden the indications of this drug including data about its efficacy and safety in pancreatic cancer. The final objective of this work is to obtain the required data to advance in the development of a potential new therapy for pancreatic cancer disease. As this drug is already being developed in glioma, clinical development of the product in pancreatic cancer would be more rapid.
The work carried out in the PANC561 project has met its main objectives. The LAM561 has proved an antitumor effect on a panel of tumoral lines of pancreatic cancer. On one side, the research performed opens the way to extend the indications of LAM561 as antitumor drug for the treatment of pancreatic cancer. On the other hand, a body of cutting edge scientific data on the mechanism of action of LAM561 has been obtained, including the identification of a proferroptotic role for LAM561 and migration inhibitory activities in vitro. In addition, a new candidate drug of membrane lipid therapy (MLT) has been identified as glucosylceramide synthase (GCS) inhibitor that can be further developed broadening Laminar Pharma portfolio.
Overview of the dissemination & exploitation results: The dissemination of the results started with a participation in an EMBO conference on Ferroptosis as well as an inscription in a second EMBO workshop that will take place the next month of September. Next, a review article has been publisjed in a peer-reviewed journal (Biomedicines) and the writing of a paper draft based on the achieved results during the grant will be submitted in due course to a high impact factor journal (1st quartile). In addition, publications in the company newsletters, Laminar website, Spanish Asociation of Biotec Companies website (Asebio), Laminar Linkedin have been released and several seminars have been given by the researcher contributing to the dissemination plan.
Overview of the dissemination & exploitation results: The dissemination of the results started with a participation in an EMBO conference on Ferroptosis as well as an inscription in a second EMBO workshop that will take place the next month of September. Next, a review article has been publisjed in a peer-reviewed journal (Biomedicines) and the writing of a paper draft based on the achieved results during the grant will be submitted in due course to a high impact factor journal (1st quartile). In addition, publications in the company newsletters, Laminar website, Spanish Asociation of Biotec Companies website (Asebio), Laminar Linkedin have been released and several seminars have been given by the researcher contributing to the dissemination plan.
LAM561 BEATS PANCREATIC CANCER project is totally aligned with the impacts expected in the work program as it proposes the development of a new drug (LAM561) for patients living with pancreatic cancer. Pancreatic cancer is the fourth most fatal cancer. Pancreatic cancer is a deathly pathology that in 2020 affected approximately 1.8 in 10,000 people in the European Union (EU) in 2019. This was equivalent to a total of around 93,000 people, and is below the ceiling for orphan designation, which is 5 people in 10,000 (estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein). This represents a population of 518,400,000 (Eurostat 2019). Moreover, LAM561 acts through a novel and unique MoA, activating SGMS, a target never previously described for any other currently marketed anticancer drug. In pancreatic cancer innovative therapeutic approaches are demanded. Moreover, as results of this project are positive, the proposal will contribute to deliver a new non-toxic therapy for this rare disease, having a major impact on life expectancy and quality of life of patients with pancreatic cancer. Laminar Pharmaceuticals, in accordance with the ‘European Charter for Researchers’ confirms that the researcher will secure the benefits of the exploitation of R&D results through legal protection and through appropriate protection of IPR. Following the H2020 ‘Guidelines for your dissemination and exploitation activities’, and in order to ensure effective exploitation and dissemination of the project, WP0 includes the drafting of a realistic and achievable PEDR covering marketing strategy, dissemination and communication. Pivotal aspects such as market access strategy, pricing and reimbursement and a broad international health economics analysis will be developed during the project in order to define a clear policy to exploit the results of the LAM561 BEATS PANCREATIC CANCER project. Estimated number of newly diagnosed pancreatic cancer patients worldwide will reach almost 150.000 cases by 2018 and projected peak sales of LAM561 could exceed 750M€. This proposal will clearly contribute to strengthen the competitiveness and growth of all participant entities, and particularly that of Laminar Pharmaceuticals, who is currently a world leader in the field of lipid-modulation therapeutics and is well positioned to consolidate this innovative technology and develop new game-changing drugs to address urgent medical needs in serious diseases like cancer or Alzheimer's Disease. These treatments could have not only a remarkable economic impact, leading to important saving to the National Public Health Systems, but also an extraordinary social impact for millions of persons suffering from this condition worldwide.