Periodic Reporting for period 1 - RESEE (A Revolutionary Artificial Cornea and Surgical Procedure)
Reporting period: 2022-02-01 to 2023-01-31
Corneal opacity is the second leading cause of blindness worldwide with 29.5 million patients and 2 million cases each year. Only 185,000 cases are treated with donor tissue annually. Globally, there is an acute shortage of corneal grafts, with only one cornea available for every 70 needed. Approximately 53% of the world's population have no access to donor tissue. Anatomical success whereas the cornea remains clear averages 85%, but this significantly varies with indication. 20% of patients are not suitable for transplantation, as the tissue will not maintain its transparency. Visual outcome is poor with ~50% of cases resulting in high astigmatism. 20%-30% of transplantations performed in the US and the EU are repeated grafts.
All attempts to develop an artificial cornea (KPro) have failed to reliably integrate with the native eye. Due to complications and retention issues, they are only used today as a last resort (1,100 cases a year). Current KPros rely on harvested tissue as the means of integration. The challenge in keratoplasty lies in adequately anchoring an artificial cornea into the eye in a manner that is long-lasting, comfortable, aesthetic, and affordable.
The CorNeat KPro, which is the context of the RESEE project, is a patented synthetic cornea, keratoprosthesis (KPro), which provides a long-lasting medical solution for corneal blindness, pathology and injury. The CorNeat KPro allows corneally blind patients to fully rehabilitate normal vision, immediately following a relatively straightforward novel implantation procedure. It’s a unique and innovative device that utilizes a biomimetic skirt made from a revolutionary permanent tissue-integrating material technology to integrate artificial optics within resident ocular tissue, relieving the need for donor tissue.
The CorNeat KPro will provide an efficient, therapeutic, and affordable remedy for millions of people with cornea-related visual impairments and is far superior to any available alternative.
The main objective of the RESEE project is to advance the CorNeat KPro product to commercialization by providing CorNeat Vision with resources for executing clinical trials and a usability study that are required for regulatory approval, establish the infrastructure needed for scaled manufacturing, set up the infrastructure for enabling initial sales, and execute a set of dissemination and education activities required for driving initial demand. These include physician training, scientific publications, as well as participation and exhibition in key ophthalmic events and conferences.
All attempts to develop an artificial cornea (KPro) have failed to reliably integrate with the native eye. Due to complications and retention issues, they are only used today as a last resort (1,100 cases a year). Current KPros rely on harvested tissue as the means of integration. The challenge in keratoplasty lies in adequately anchoring an artificial cornea into the eye in a manner that is long-lasting, comfortable, aesthetic, and affordable.
The CorNeat KPro, which is the context of the RESEE project, is a patented synthetic cornea, keratoprosthesis (KPro), which provides a long-lasting medical solution for corneal blindness, pathology and injury. The CorNeat KPro allows corneally blind patients to fully rehabilitate normal vision, immediately following a relatively straightforward novel implantation procedure. It’s a unique and innovative device that utilizes a biomimetic skirt made from a revolutionary permanent tissue-integrating material technology to integrate artificial optics within resident ocular tissue, relieving the need for donor tissue.
The CorNeat KPro will provide an efficient, therapeutic, and affordable remedy for millions of people with cornea-related visual impairments and is far superior to any available alternative.
The main objective of the RESEE project is to advance the CorNeat KPro product to commercialization by providing CorNeat Vision with resources for executing clinical trials and a usability study that are required for regulatory approval, establish the infrastructure needed for scaled manufacturing, set up the infrastructure for enabling initial sales, and execute a set of dissemination and education activities required for driving initial demand. These include physician training, scientific publications, as well as participation and exhibition in key ophthalmic events and conferences.
Activities performed during the first year of the RESEE project include:
- Conclusion of a first-in-human clinical study, implanting the CorNeat KPRo device in 10 patients, most of whom were previously defined as terminally blind. The study proved the CorNeat KPro's ability to integrate with the native eye, enabling patients to regain their sight and independence, some, following decades of blindness. Our first patient, who is now two years post op (implanted prior to the RESEE project initiation) and has just completed the formal follow-up period, is still enjoying his vision and independence. He previously failed four transplantations and was blind over the last decade. Our fourth patient, a lady from Paris, who previously went through six transplantations and 12 failure episodes, recently completed 12 months follow up. Surgical challenges that were encountered during the first 5 patients were addressed by the company, these resulted in formal amendments to the clinical protocol, implementing changes in the surgical technique, patient selection, and pre-post op treatment. A subsequent decision to conclude the first-in-human study and initiate a pivotal trial, opened up the opportunity to implement several minor modifications in the device which will accelerate its bio-integration and increase production yield.
- Initial design of a robotic cell for fabricating the bio-mimetic (electrospun) tissue-integrating skirt around the CorNeat KPro optics rim. The conceptual design selected supports the production of ~200 devices a day by integrating a customized industrial electrospinning machine, a robotic arm and a set of production and testing technologies, which include a coating station, laser cutting station, high precision touchless laser thickness measurement station and more. A clean room for hosting the production line was designed and is being built in the Company's building. This clean room, which will host the manual production line that is currently being transferred from the UK, can double its size to support increasing demand.
- Production and release of an initial batch of improved CorNeat KPro implantation kits for supporting the upcoming pivotal study. The new kits implement several modifications such as thinner skirt (promoting faster bio-integration), a set of holes around the edge of the skirt that allows the conjunctiva to directly adhere to the sclera hence anchor the skirt in the subconjunctival space. This also provides the conjunctiva with closer supply of nutrients and oxygen which are critical to its viability.
- Conclusion of a first-in-human clinical study, implanting the CorNeat KPRo device in 10 patients, most of whom were previously defined as terminally blind. The study proved the CorNeat KPro's ability to integrate with the native eye, enabling patients to regain their sight and independence, some, following decades of blindness. Our first patient, who is now two years post op (implanted prior to the RESEE project initiation) and has just completed the formal follow-up period, is still enjoying his vision and independence. He previously failed four transplantations and was blind over the last decade. Our fourth patient, a lady from Paris, who previously went through six transplantations and 12 failure episodes, recently completed 12 months follow up. Surgical challenges that were encountered during the first 5 patients were addressed by the company, these resulted in formal amendments to the clinical protocol, implementing changes in the surgical technique, patient selection, and pre-post op treatment. A subsequent decision to conclude the first-in-human study and initiate a pivotal trial, opened up the opportunity to implement several minor modifications in the device which will accelerate its bio-integration and increase production yield.
- Initial design of a robotic cell for fabricating the bio-mimetic (electrospun) tissue-integrating skirt around the CorNeat KPro optics rim. The conceptual design selected supports the production of ~200 devices a day by integrating a customized industrial electrospinning machine, a robotic arm and a set of production and testing technologies, which include a coating station, laser cutting station, high precision touchless laser thickness measurement station and more. A clean room for hosting the production line was designed and is being built in the Company's building. This clean room, which will host the manual production line that is currently being transferred from the UK, can double its size to support increasing demand.
- Production and release of an initial batch of improved CorNeat KPro implantation kits for supporting the upcoming pivotal study. The new kits implement several modifications such as thinner skirt (promoting faster bio-integration), a set of holes around the edge of the skirt that allows the conjunctiva to directly adhere to the sclera hence anchor the skirt in the subconjunctival space. This also provides the conjunctiva with closer supply of nutrients and oxygen which are critical to its viability.
The initial results as obtained from the CorNeat KPro First In Human study are truly groundbreaking. While some difficulties during the implantation procedure as well as an unfortunate case of suspected infection led to the explanation of some device, clinical and histopathological analysis of the explanted devices confirmed that the device adhered and was integrated to the ocular wall. Explanation actually required dissecting out the CorNeat KPro skirt. It is important to note that patients who underwent explantation, were provided with a tectonic corneal graft so maintained their vision potential. As far as vision acuity the study also proved the ability of the device to optically provide optimal and stable vision. Success with patients that suffer from scarred cornea (following acid burns and multiple failed grafts) provides hope to patients that have no viable solution today.