Periodic Reporting for period 1 - ProM (The ProM platform: New ways to drug the undruggable)
Okres sprawozdawczy: 2022-04-01 do 2023-03-31
Proline-rich motifs (PRMs) control the function of a diverse set of biological complexes associated with disease progression. As their bio-active form adopts a unique helical shape, their binding domains are regarded as “undruggable”.
Based on a decade of research, PROSION successfully established synthetic molecules called ProMs, as the first and currently only mimetics of this intricate helix pattern. As such, PROSION’s modular and patented ProM-technology enables the creation of drug candidates for this previously inaccessible class of proteins within the proteome, including those associated cancer, Alzheimer's and cardiovascular disease.
Based on its core technology, PROSION is currently working on the development of a drug candidate against a fundamental driver of tumor progression, able to trigger a dual mechanistic effect. In contrast to current cancer therapies, this new approach is highly unlikely to be susceptible for mutations - a common side-effect of existing therapeutic solutions leading to therapy-resistance and relapsing of metastatic cancer patients.
Based on a decade of research, PROSION successfully established synthetic molecules called ProMs, as the first and currently only mimetics of this intricate helix pattern. As such, PROSION’s modular and patented ProM-technology enables the creation of drug candidates for this previously inaccessible class of proteins within the proteome, including those associated cancer, Alzheimer's and cardiovascular disease.
Based on its core technology, PROSION is currently working on the development of a drug candidate against a fundamental driver of tumor progression, able to trigger a dual mechanistic effect. In contrast to current cancer therapies, this new approach is highly unlikely to be susceptible for mutations - a common side-effect of existing therapeutic solutions leading to therapy-resistance and relapsing of metastatic cancer patients.
Within the last 12 months, WP4, WP5 and WP6 were in the focus.
As part of WP4, we have invested a lot of capacity in further synthetic developments of the ProM-platform: From optimizing reaction and synthetic routes, to setting up SOPs and purity procedures, or even managing the outsourcing partner. We now have successfully documented knowhow and established quality standards for the ProM-production. In addition, we have setup internal quality controls to supervise the output from our Outsourcing Partner (CRO), which is continuously on-going.
The know-how that was documented, was then successfully transferred to our outsourcing partner with their onboarding. Since then, the CRO optimized several synthetic routes for larger batches and was successful in upscaling the synthesis of ProMs to the multi(kilo)gram scale, while maintaining quality standards.
In addition, we have generated several hundred drug leads and various new ProMs for efficacy and toxicity studies. Two of them are currently being synthesized in the larger scale before they will move into the in-vivo efficacy phase in WP5.
As part of WP5, we have achieved huge improvements of our ProM-based leads’ ADME profiles, which is now much more in line with the Quality Target Product Profile of an ideal small molecule drug than it was 12 months ago. Overall we could boost almost every pillar of SAR (bidning affinity & cellular activity) & SPR (metabolic stability, PK, solubility,etc.) – something that can take several years in the industry. Notably, safety-screen studies indicate no off-target effects at this stage.
As of writing, the two leads we have designated as the most promising ones have been submitted for in vivo PD studies. The aim is to receive efficacy and toxicity results in animal models. Prior to this, we went through a long RFP process with 4 different CROs, to decide on the best suited company for this crucial job.
In addition to this, we have also setup a clean documentation system to collect all scientific data that is being generated.
As part of WP6, we are aiming to build out the drug development pipeline based on our proprietary platform. We are collaborating with Institut Pasteur to test our compounds in the field of infectious diseases in Listeriosis (with 400 deaths/year within the EU). As part of this collaboration, in-vitro and in-vivo tests are planned to be conducted in order to show the efficacy of our compounds for listeriosis. In addition we’re building up an in-silico screening engine for our technology, to fully profit from the untapped potential of targeting PRMs.
As part of WP4, we have invested a lot of capacity in further synthetic developments of the ProM-platform: From optimizing reaction and synthetic routes, to setting up SOPs and purity procedures, or even managing the outsourcing partner. We now have successfully documented knowhow and established quality standards for the ProM-production. In addition, we have setup internal quality controls to supervise the output from our Outsourcing Partner (CRO), which is continuously on-going.
The know-how that was documented, was then successfully transferred to our outsourcing partner with their onboarding. Since then, the CRO optimized several synthetic routes for larger batches and was successful in upscaling the synthesis of ProMs to the multi(kilo)gram scale, while maintaining quality standards.
In addition, we have generated several hundred drug leads and various new ProMs for efficacy and toxicity studies. Two of them are currently being synthesized in the larger scale before they will move into the in-vivo efficacy phase in WP5.
As part of WP5, we have achieved huge improvements of our ProM-based leads’ ADME profiles, which is now much more in line with the Quality Target Product Profile of an ideal small molecule drug than it was 12 months ago. Overall we could boost almost every pillar of SAR (bidning affinity & cellular activity) & SPR (metabolic stability, PK, solubility,etc.) – something that can take several years in the industry. Notably, safety-screen studies indicate no off-target effects at this stage.
As of writing, the two leads we have designated as the most promising ones have been submitted for in vivo PD studies. The aim is to receive efficacy and toxicity results in animal models. Prior to this, we went through a long RFP process with 4 different CROs, to decide on the best suited company for this crucial job.
In addition to this, we have also setup a clean documentation system to collect all scientific data that is being generated.
As part of WP6, we are aiming to build out the drug development pipeline based on our proprietary platform. We are collaborating with Institut Pasteur to test our compounds in the field of infectious diseases in Listeriosis (with 400 deaths/year within the EU). As part of this collaboration, in-vitro and in-vivo tests are planned to be conducted in order to show the efficacy of our compounds for listeriosis. In addition we’re building up an in-silico screening engine for our technology, to fully profit from the untapped potential of targeting PRMs.
Having decided on our two most promising ProM-based Ena/VASP leads, we’re now expecting in vivo data on their potency against tumor. We have chosen explicitly to study their effect on patient tumor tissue, to fully demonstrate their potential on a setup as close as possible to “clinical conditions”. It is difficult to make predictions on the outcome at this stage. In case the results turn out to be not fully satisfactory, we would prefer to further improve these to leads in a medchem program, instead of “rushing into the clinic”.
As for fundraising, there is a lot of interest from VCs. Based on the scientific progress that we already have made since April 2022 and the start of the EIC project - amongst others, improving the compounds overall ADME and PK profile - we recognise an increased interest from VC investors, who would have called us “too early” by end of last year. On that note, we do appreciate the support of Dealflow.
As for fundraising, there is a lot of interest from VCs. Based on the scientific progress that we already have made since April 2022 and the start of the EIC project - amongst others, improving the compounds overall ADME and PK profile - we recognise an increased interest from VC investors, who would have called us “too early” by end of last year. On that note, we do appreciate the support of Dealflow.