Periodic Reporting for period 3 - BERMES (A Novel BERberine derivative for Malignant MESothelioma)
Période du rapport: 2021-05-01 au 2021-10-31
Malignant Mesothelioma is a rare, aggressive and highly resistant tumour arising in the mesothelium, a thin tissue layer which covers important organs like the lungs, the peritoneal cavity organs, the heart and the testis. Despite being a rare cancer, its burden is increasing worldwide being recognized by the World Health Organization (WHO) as one of the top ten worldwide occupational cancers. This is due to the fact that mesothelioma is strongly associated with exposure to asbestos. The highest incidence rates are reported from the European Union countries where asbestos was definitively banned in January 2005. Knowing the long latency period for the disease, that takes 30-40 years to appear after asbestos exposure, an incidence peak is expected well beyond 2020. More alarming is the fact that there are still 190 countries mining and consuming asbestos. According to WHO, over 125 million persons remain daily exposed, of which 4-10% will develop eventually mesothelioma.
Current mesothelioma treatment includes the combination of surgery, chemotherapy and radiation. Unfortunately, most of the patients are diagnosed at advanced stage of the disease where chemotherapy remains the only option. The cisplatin and pemetrexed combination is considered the standard of care treatment although its efficacy is low: almost half of the patients are primary resistant and all finally develop resistance in less than 5 months. When therapy fails, there is no standard second-line chemotherapy treatment. Despite new targeted drugs and immunotherapy combinations are currently being evaluated in clinical trials, so far none has substantially improved the standard of care response rate or has been able to overcome the resistance phenotype.
Aware of the need, AROMICS develops a new class of antitumor agents (protected under granted patents) based on a pioneering mechanism of action: silencing an aberrantly expressed protein involved in the tumour progression and drug resistance. NAX035, is the first lead selected to advance up to clinics due to its great potency and appropriate pharmacology, toxicology and safety profile.
Activities inside BERMES has accomplished its main goals: the completion of the non-clinical regulatory package (proving its efficacy, pharmacology, toxicology and safety in relevant animal species) and the drug substance manufacture under GMP rules with the aim of obtaining the orphan drug designation as well as to accomplish all the regulatory requirements required by the European Medicine Agency to achieve the clinical trial authorization to proceed into human clinical trials (outlined in the project) right after the end of the project.
Current mesothelioma treatment includes the combination of surgery, chemotherapy and radiation. Unfortunately, most of the patients are diagnosed at advanced stage of the disease where chemotherapy remains the only option. The cisplatin and pemetrexed combination is considered the standard of care treatment although its efficacy is low: almost half of the patients are primary resistant and all finally develop resistance in less than 5 months. When therapy fails, there is no standard second-line chemotherapy treatment. Despite new targeted drugs and immunotherapy combinations are currently being evaluated in clinical trials, so far none has substantially improved the standard of care response rate or has been able to overcome the resistance phenotype.
Aware of the need, AROMICS develops a new class of antitumor agents (protected under granted patents) based on a pioneering mechanism of action: silencing an aberrantly expressed protein involved in the tumour progression and drug resistance. NAX035, is the first lead selected to advance up to clinics due to its great potency and appropriate pharmacology, toxicology and safety profile.
Activities inside BERMES has accomplished its main goals: the completion of the non-clinical regulatory package (proving its efficacy, pharmacology, toxicology and safety in relevant animal species) and the drug substance manufacture under GMP rules with the aim of obtaining the orphan drug designation as well as to accomplish all the regulatory requirements required by the European Medicine Agency to achieve the clinical trial authorization to proceed into human clinical trials (outlined in the project) right after the end of the project.
These are the main results achieved since the beginning of the project:
- The upscaling, piloting and production of NAX035 under GMP rules has been achieved. With process in hands, clinical batches manufacture can be undertaken.
- Evaluation of the in vivo antitumor efficacy of NAX035 as single agent or in combination with cisplatin in comparison with the standard of care. Selection of Intravenous route for future clinical indications according the data generated. The main processes responsible of drug effects, metabolism, the potential toxicity and safety concerns and information of in vivo biodistribution and kinetic analysis were completed in a relevant disease model.
- Toxicology and safety studies, including toxicokinetic profile, at repeated intravenous dose of NAX035 in relevant species has been completed according the regulatory guidelines for anticancer drugs, proving the safety of the compound in relevant in vivo models.
- All available data has been compiled and included in the different regulatory package documents (ODD and CTA package) and scientific discussions maintained with the regulatory agencies with the goal to achieve the indication approval.
-A solid communication plan including digital marketing plan was created and implemented. The project website (ongoing since early 2019) and the social network accounts have been maintained updated. The diverse promotional material for dissemination, communication and commercialization designed, have been used on different activities to report project results in scientific, business and investment events. Aware of the important social impact of the project, we have also actively participate in different community activities working with patients, victims’ and civil society to raise awareness on mesothelioma and other asbestos related diseases.
We have worked on the management and securement of the IPR generated. We have worked on different commercialization aspects of the technology with the goal of establishing strategic alliances and potential collaborations with the pharma industry, secure further investment and advance into next stage, the implementation of clinical studies to prove safety and efficacy in humans.
The different dissemination and communication activities allowed both, the company and the project to gain visibility and traction, being selected to be part of different European accelerator programs designed to facilitate the access to funding for selected deep tech companies in EU.
- The upscaling, piloting and production of NAX035 under GMP rules has been achieved. With process in hands, clinical batches manufacture can be undertaken.
- Evaluation of the in vivo antitumor efficacy of NAX035 as single agent or in combination with cisplatin in comparison with the standard of care. Selection of Intravenous route for future clinical indications according the data generated. The main processes responsible of drug effects, metabolism, the potential toxicity and safety concerns and information of in vivo biodistribution and kinetic analysis were completed in a relevant disease model.
- Toxicology and safety studies, including toxicokinetic profile, at repeated intravenous dose of NAX035 in relevant species has been completed according the regulatory guidelines for anticancer drugs, proving the safety of the compound in relevant in vivo models.
- All available data has been compiled and included in the different regulatory package documents (ODD and CTA package) and scientific discussions maintained with the regulatory agencies with the goal to achieve the indication approval.
-A solid communication plan including digital marketing plan was created and implemented. The project website (ongoing since early 2019) and the social network accounts have been maintained updated. The diverse promotional material for dissemination, communication and commercialization designed, have been used on different activities to report project results in scientific, business and investment events. Aware of the important social impact of the project, we have also actively participate in different community activities working with patients, victims’ and civil society to raise awareness on mesothelioma and other asbestos related diseases.
We have worked on the management and securement of the IPR generated. We have worked on different commercialization aspects of the technology with the goal of establishing strategic alliances and potential collaborations with the pharma industry, secure further investment and advance into next stage, the implementation of clinical studies to prove safety and efficacy in humans.
The different dissemination and communication activities allowed both, the company and the project to gain visibility and traction, being selected to be part of different European accelerator programs designed to facilitate the access to funding for selected deep tech companies in EU.
BERMES represents a clear progress beyond the state of the art according to three major aspects: (A) It targets an aggressive cancer with high social impact, raising worldwide incidence and in clear demand of efficient therapies; (B) The uniqueness of the product relaying on an innovative mechanism of action: binding RNA and silencing the expression of a protein involved in tumour progression and drug resistance; and (C) the product aims to cover all relevant market aspects to attract the larger pharmaceutical industry including a niche market opportunity, a strong intellectual property, a clear route to manufacture and the potential scalability to other larger indications.
Regarding expected results, the project achieved a relevant valuable point: completing the manufacture and non-clinical package according regulatory guidelines with the aim to achieve a first indication status to perform clinical trials. The preclinical package contains all relevant data on manufacturing, efficacy, toxicology, pharmacology and safety and devise the optimal clinical development for the compound. Data achieved will also attract industry collaborations and investors in order to secure the financial requirements for further clinical trials, setting up the for bases for future collaborations with the pharma industry.
The indication selected, mesothelioma is an incurable disease with high socioeconomic impact. Despite rare, mesothelioma is among the top ten occupational cancers in the world as per its link to asbestos exposure. Thus, the impact for healthcare systems and society as a whole of an improved therapy, able to improve the course of the disease and the quality of life of the patients will generate an obvious socioeconomic impact. The project has already received the support of society, asbestos victims and associations and the support of public funds and private investors. Specific dissemination actions have been addressed during the project to them, to raise aware on the disease and the results achieved.
Regarding expected results, the project achieved a relevant valuable point: completing the manufacture and non-clinical package according regulatory guidelines with the aim to achieve a first indication status to perform clinical trials. The preclinical package contains all relevant data on manufacturing, efficacy, toxicology, pharmacology and safety and devise the optimal clinical development for the compound. Data achieved will also attract industry collaborations and investors in order to secure the financial requirements for further clinical trials, setting up the for bases for future collaborations with the pharma industry.
The indication selected, mesothelioma is an incurable disease with high socioeconomic impact. Despite rare, mesothelioma is among the top ten occupational cancers in the world as per its link to asbestos exposure. Thus, the impact for healthcare systems and society as a whole of an improved therapy, able to improve the course of the disease and the quality of life of the patients will generate an obvious socioeconomic impact. The project has already received the support of society, asbestos victims and associations and the support of public funds and private investors. Specific dissemination actions have been addressed during the project to them, to raise aware on the disease and the results achieved.