Periodic Reporting for period 2 - TRS (A paradigm change in the treatment of blinding ocular diseases)
Periodo di rendicontazione: 2020-07-01 al 2021-06-30
Uveitis – inflammation of the uvea – is an ophthalmic emergency requiring urgent treatment. Uveitis is one of the leading causes of irreversible blindness worldwide, generating a total healthcare burden of over €100B in Europe alone and the average cost for uveitis patients are similar or higher than those for diabetes or hypertension patients, as well as some cancers such as prostate cancer.
Uveitis may occur at any age, with disease onset usually at the working population between the age of 20 and 59 years, and lasts for decades, as this is a chronic condition. Around 16% of patients will be diagnosed at childhood.
The prevalence of blindness secondary to uveitis has not been reduced in the past 30 years, which strongly reflects the inadequacy of current approaches and the unmet need for effective therapies.
Glaucoma is a serious ocular disease and according to the WHO is first leading cause for irreversible blindness. It is also a known and devastating complication of uveitis, occurring in approx. 20% of patients and resulting in a condition named uveitic glaucoma. Uveitic glaucoma is a sight-threatening orphan disease that cannot be treated with corticosteroids and lacks market-approved treatment options to mitigate ocular inflammation. Clinical management of uveitic glaucoma patients is therefore extremely challenging and the condition poses an even greater risk of blindness than uveitis alone.
The project aims to clinically validate our therapy in a Phase I/IIa clinical trial, with the hope of bringing a breakthrough, game-changing novel treatment to this patient population with unmet medical need.
Uveitis may occur at any age, with disease onset usually at the working population between the age of 20 and 59 years, and lasts for decades, as this is a chronic condition. Around 16% of patients will be diagnosed at childhood.
The prevalence of blindness secondary to uveitis has not been reduced in the past 30 years, which strongly reflects the inadequacy of current approaches and the unmet need for effective therapies.
Glaucoma is a serious ocular disease and according to the WHO is first leading cause for irreversible blindness. It is also a known and devastating complication of uveitis, occurring in approx. 20% of patients and resulting in a condition named uveitic glaucoma. Uveitic glaucoma is a sight-threatening orphan disease that cannot be treated with corticosteroids and lacks market-approved treatment options to mitigate ocular inflammation. Clinical management of uveitic glaucoma patients is therefore extremely challenging and the condition poses an even greater risk of blindness than uveitis alone.
The project aims to clinically validate our therapy in a Phase I/IIa clinical trial, with the hope of bringing a breakthrough, game-changing novel treatment to this patient population with unmet medical need.
A Phase I/II dose-ranging, randomized controlled clinical trial has been completed on 34 patients, in five clinical sites, aiming to investigate the safety of our novel TRS01.
To reach this stage, several main milestones were achieved from the beginning of the project to the end of the period covered by the report:
1. Production of GMP material of the Drug Substance in sufficient quantities to allow production of sufficient drug product to cover both the requirements for the clinical trial as well as the requirements for stability studies.
2. Successful production of the GMP Drug Product – eye drops (4 batches – 3 active dosages and placebo).
3. Stability testing of the clinical batches of the Drug Substance and Drug products.
4. Submission and approval of all the regulatory dossiers required in order to initiate the clinical trial.
5. Successful recruitment of sites, PIs, patients, and streamlined clinical management of the trials.
6. At the end of the trial, a Clinical Study Report was issued (CSR) and submitted as deliverable.
Importantly, we managed to carry out this clinical trial despite the COVID-19 restrictions and difficulties.
In addition, we achieved another important milestone: receiving an Orphan Drug Designation status from the EMA, providing important commercial and R&D incentives for the program with benefits such as extended market exclusivity, tax reliefs and shorter time to market.
We have also achieved already a few milestones for our future plans to initiate phase-3 trials:
Completion of study design for phase-3 pivotal trials in non-infectious anterior uveitis including patients with uveitic glaucoma
• Final study protocol and approval by ethical committee.
• Regulatory submissions to the EMA and FDA
• Recruitment of first 20 sites.
In addition, two new patent applications have been filed to strengthen the IP protection of our novel compound, and, in collaboration with uveitis experts, we have published a scientific article about a new visual analogue grading scale to assess uveitis.
To reach this stage, several main milestones were achieved from the beginning of the project to the end of the period covered by the report:
1. Production of GMP material of the Drug Substance in sufficient quantities to allow production of sufficient drug product to cover both the requirements for the clinical trial as well as the requirements for stability studies.
2. Successful production of the GMP Drug Product – eye drops (4 batches – 3 active dosages and placebo).
3. Stability testing of the clinical batches of the Drug Substance and Drug products.
4. Submission and approval of all the regulatory dossiers required in order to initiate the clinical trial.
5. Successful recruitment of sites, PIs, patients, and streamlined clinical management of the trials.
6. At the end of the trial, a Clinical Study Report was issued (CSR) and submitted as deliverable.
Importantly, we managed to carry out this clinical trial despite the COVID-19 restrictions and difficulties.
In addition, we achieved another important milestone: receiving an Orphan Drug Designation status from the EMA, providing important commercial and R&D incentives for the program with benefits such as extended market exclusivity, tax reliefs and shorter time to market.
We have also achieved already a few milestones for our future plans to initiate phase-3 trials:
Completion of study design for phase-3 pivotal trials in non-infectious anterior uveitis including patients with uveitic glaucoma
• Final study protocol and approval by ethical committee.
• Regulatory submissions to the EMA and FDA
• Recruitment of first 20 sites.
In addition, two new patent applications have been filed to strengthen the IP protection of our novel compound, and, in collaboration with uveitis experts, we have published a scientific article about a new visual analogue grading scale to assess uveitis.
Ocular inflammatory diseases are affecting hundreds of millions of people worldwide, putting them at risk of vision loss and blindness. Blindness was ranked third (after cancer and heart disease) as people's major fear from health problems in general and first as people’s major fear from disability and has severe effect on health-related quality of life (HRQoL) in multiple ways. The global ocular inflammation treatment market is expected to exceed more than US$ 500 Billion by 2024 at a CAGR of 6% in the given forecast period.
Today, corticosteroids are the most common method used to treat ocular non-infectious inflammation of any kind. Rather than treating the disease itself, however, steroids merely relieve its symptoms, and long-term use can result in devastating consequences, e.g. glaucoma. The TRS Platform Technology has the potential to effectively treat a broad array of autoimmune and inflammatory ocular diseases. Untreated, these diseases can have devastating effects, and may eventually lead to blindness.
The first indication for TRS is uveitic glaucoma – a sight-threatening orphan disease that cannot be treated with corticosteroids and lacks market-approved treatment options to mitigate ocular inflammation.
There is a great unmet medical need for non-steroidal therapies able to control ocular inflammation to prevent vision loss. TRS – being a potent and safe non-steroidal anti-inflammatory agent has the potential to become a game-changer in the treatment of blinding, inflammatory eye diseases.
TRS approaches inflammatory diseases from within the immune system. It was developed to ‘re-engineer’ the immune system and modulate the immune system rather than suppressing it. We believe that this approach will have the capability to disrupt the immune mechanism that causes the disease in order to provide patients with a safe and long-lasting therapeutic effect, with the goal of saving their sight.
Available drugs for treatment of ocular inflammation target an individual cytoplasmic receptor or secreted protein, but ignore the complexity of the immune system, which results in many limitations of such products. Our synthetic, patent-protected compound has a dual-target approach with a unique mechanism of action. TRS is not expected to cause any steroid-associated complications (e.g. glaucoma or cataract).
Today, corticosteroids are the most common method used to treat ocular non-infectious inflammation of any kind. Rather than treating the disease itself, however, steroids merely relieve its symptoms, and long-term use can result in devastating consequences, e.g. glaucoma. The TRS Platform Technology has the potential to effectively treat a broad array of autoimmune and inflammatory ocular diseases. Untreated, these diseases can have devastating effects, and may eventually lead to blindness.
The first indication for TRS is uveitic glaucoma – a sight-threatening orphan disease that cannot be treated with corticosteroids and lacks market-approved treatment options to mitigate ocular inflammation.
There is a great unmet medical need for non-steroidal therapies able to control ocular inflammation to prevent vision loss. TRS – being a potent and safe non-steroidal anti-inflammatory agent has the potential to become a game-changer in the treatment of blinding, inflammatory eye diseases.
TRS approaches inflammatory diseases from within the immune system. It was developed to ‘re-engineer’ the immune system and modulate the immune system rather than suppressing it. We believe that this approach will have the capability to disrupt the immune mechanism that causes the disease in order to provide patients with a safe and long-lasting therapeutic effect, with the goal of saving their sight.
Available drugs for treatment of ocular inflammation target an individual cytoplasmic receptor or secreted protein, but ignore the complexity of the immune system, which results in many limitations of such products. Our synthetic, patent-protected compound has a dual-target approach with a unique mechanism of action. TRS is not expected to cause any steroid-associated complications (e.g. glaucoma or cataract).