Periodic Reporting for period 2 - ProM (The ProM platform: New ways to drug the undruggable)
Okres sprawozdawczy: 2023-04-01 do 2025-03-31
The development of innovative therapeutics is crucial in modern medicine, especially for combating complex diseases such as cancer, neurodegenerative diseases, and chronic immune and metabolic disorders. Existing pharmaceutical methods can only target a small subset of all disease-relevant proteins (<15%) in the human proteome. Given this limitation, pharmaceutical companies are running out of options to develop effective drugs to tackle hard-to-treat diseases and require new therapeutic modalities that can address previously unexplored mechanisms. A promising solution is provided by the patented ProM technology from PROSION. This platform technology combines the advantages of small molecules and biologics to address a specific class of yet undruggable proteins linked to hard-to-treat-diseases. —an ability that no other therapeutic modality currently offers in the same way. These proteins play a key-role in pathologies such as cancer, Alzheimer’s, cardiovascular diseases and immune mediated disorders., which is why ProM-based therapeutics have the potential to treat a wide range of diseases.
Through this EIC Accelerator program, PROSION preclinically validated a first ProM-based drug candidate against a fundamental and so far undruggable driver of tumor progression. PROSION was able to design a specific inhibitor able to bind to this protein and prevent it’s activity in cancer cells, which translated to anti-tumor efficacy in vivo. Furthermore, PROSION has demonstrated the upscaled manufacturing of ProMs, further mined the proteome and identified a large set of disease-driving proteins that are amenable to the ProM-technology. Based on these promising results, PROSION aims to build its own internal pipeline of ProM-based drugs for the treatment of cancer and other indications.
Through this EIC Accelerator program, PROSION preclinically validated a first ProM-based drug candidate against a fundamental and so far undruggable driver of tumor progression. PROSION was able to design a specific inhibitor able to bind to this protein and prevent it’s activity in cancer cells, which translated to anti-tumor efficacy in vivo. Furthermore, PROSION has demonstrated the upscaled manufacturing of ProMs, further mined the proteome and identified a large set of disease-driving proteins that are amenable to the ProM-technology. Based on these promising results, PROSION aims to build its own internal pipeline of ProM-based drugs for the treatment of cancer and other indications.
PROSION's EIC Accelerator project was designed to advance our proprietary ProM technology and strategically position the company for future growth. Our approach was structured around six work packages, with three interconnected science-focused packages being critical to enhancing the innovation of our ProM technology. The following provides a detailed overview of the work conducted within these packages.
At the heart of this project was Work Package 4, which focused on optimizing the ProM-synthesis process, enabling the upscaling of both ProMs and ProM-based drug leads. During the execution of this package, we built robust in-house capabilities and formed strategic collaborations with Contract Development & Manufacturing Organizations (CDMOs). These collaborations established clear communication channels that facilitated the transfer of technical know-how for ProM scaffold production, while rigorous quality assurance checks ensured a reliable and high-quality supply of ProMs. This, in turn, validated the synthetic capabilities of the ProM platform and set the stage for the preclinical validation of the first ProM-based inhibitor, a focus of Work Package 5.
Work Package 5 demonstrated the broad potential of the ProM platform in drug development, targeting a fundamental driver of tumor progression. This protein target is overexpressed in cancer, drives metastasis and is typically classified as "undruggable" using conventional therapeutic approaches. Through extensive lead optimization, we synthesized over 300 ProM-based inhibitors, refining their pharmacokinetics and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties. Both in vitro and in vivo studies showed that these inhibitors exhibited high affinity, specificity, and safety, with potent anti-cancer activity, particularly in aggressive cancers like pancreatic cancer and triple-negative breast cancer. At this stage, we are eager to advance this program in collaboration with a strategic partner who shares our commitment to unlock the full potential of our ProM-based inhibitors, particularly in clinical applications for hard-to-treat solid tumors.
Work Package 6 focused on advancing the ProM technology platform as a whole. Using in silico machine learning methods, we screened the human proteome and identified over 600 targets amenable to the ProM technology. These targets offer therapeutic potential not only in oncology but also for cardiometabolic diseases, chronic inflammation, and CNS disorders. This dataset initiated discussions with major pharmaceutical companies for collaboration on specific targets, exploring the potential of the ProM technology beyond oncology. Additionally, we translated the learning of our first program to establish an external collaboration focusing on infectious diseases, further validating the therapeutic potential of the ProM platform. To strengthen our internal platform capabilities, we implemented a high-throughput manufacturing process, increasing our lead structure generation capacities by more than 10-fold and expanding our library of ProM structures, significantly enhancing the diversity of our ProM structures and accelerating the discovery of novel therapeutic agents.
Overall, the successful execution of this project has significantly advanced PROSION’s ProM technology paving the way to develop novel medicines for patients.
At the heart of this project was Work Package 4, which focused on optimizing the ProM-synthesis process, enabling the upscaling of both ProMs and ProM-based drug leads. During the execution of this package, we built robust in-house capabilities and formed strategic collaborations with Contract Development & Manufacturing Organizations (CDMOs). These collaborations established clear communication channels that facilitated the transfer of technical know-how for ProM scaffold production, while rigorous quality assurance checks ensured a reliable and high-quality supply of ProMs. This, in turn, validated the synthetic capabilities of the ProM platform and set the stage for the preclinical validation of the first ProM-based inhibitor, a focus of Work Package 5.
Work Package 5 demonstrated the broad potential of the ProM platform in drug development, targeting a fundamental driver of tumor progression. This protein target is overexpressed in cancer, drives metastasis and is typically classified as "undruggable" using conventional therapeutic approaches. Through extensive lead optimization, we synthesized over 300 ProM-based inhibitors, refining their pharmacokinetics and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties. Both in vitro and in vivo studies showed that these inhibitors exhibited high affinity, specificity, and safety, with potent anti-cancer activity, particularly in aggressive cancers like pancreatic cancer and triple-negative breast cancer. At this stage, we are eager to advance this program in collaboration with a strategic partner who shares our commitment to unlock the full potential of our ProM-based inhibitors, particularly in clinical applications for hard-to-treat solid tumors.
Work Package 6 focused on advancing the ProM technology platform as a whole. Using in silico machine learning methods, we screened the human proteome and identified over 600 targets amenable to the ProM technology. These targets offer therapeutic potential not only in oncology but also for cardiometabolic diseases, chronic inflammation, and CNS disorders. This dataset initiated discussions with major pharmaceutical companies for collaboration on specific targets, exploring the potential of the ProM technology beyond oncology. Additionally, we translated the learning of our first program to establish an external collaboration focusing on infectious diseases, further validating the therapeutic potential of the ProM platform. To strengthen our internal platform capabilities, we implemented a high-throughput manufacturing process, increasing our lead structure generation capacities by more than 10-fold and expanding our library of ProM structures, significantly enhancing the diversity of our ProM structures and accelerating the discovery of novel therapeutic agents.
Overall, the successful execution of this project has significantly advanced PROSION’s ProM technology paving the way to develop novel medicines for patients.
During PROSION's EIC Accelerator program, the team identified over 600 potential targets that are amenable to the ProM technology. Building on these promising results, PROSION is now focused on developing its own internal pipeline of novel therapeutics aimed at targeting key oncology drivers. The team has pinpointed two additional oncogenic driver proteins that play a central role in cancer cell survival, as supported by patient-derived evidence. Work has already begun on developing ProM-based inhibitors to target these proteins.
In parallel, PROSION has established a strong network with major pharmaceutical companies, openly sharing the ProM technology target space in order to collaborate on developing ProM-based therapeutics beyond oncology.
Moreover, the team has demonstrated that ProM-based leads not only function as reversible inhibitors but can also be adapted into other therapeutic modalities, such as degraders, covalent binders, antibody-drug conjugates, and even degrader-antibody conjugates. This further expands the therapeutic application potential of the ProM technology.
The successful execution of the program has attracted investors who share PROSION’s vision of making innovative, effective medicines available to patients.
In parallel, PROSION has established a strong network with major pharmaceutical companies, openly sharing the ProM technology target space in order to collaborate on developing ProM-based therapeutics beyond oncology.
Moreover, the team has demonstrated that ProM-based leads not only function as reversible inhibitors but can also be adapted into other therapeutic modalities, such as degraders, covalent binders, antibody-drug conjugates, and even degrader-antibody conjugates. This further expands the therapeutic application potential of the ProM technology.
The successful execution of the program has attracted investors who share PROSION’s vision of making innovative, effective medicines available to patients.