Periodic Reporting for period 4 - HUMANeye (Implantable nitinol net to combat pathological corneal shape deformations)
Período documentado: 2022-11-01 hasta 2023-12-31
The HUMANeye partners are developing a breakthrough nitinol net, GROSSO Implant, precisely matching the shape of the human cornea and comprehensively supporting its structure in patients with pathological corneal shape deformations (PCSDs) such as keratoconus (KC). The main objective of this novel device will be correcting severe refractive errors to a greater extent and in a higher proportion of patients than any of the current techniques. HUMANEYE is produced by a state-of-the-art femtosecond laser micromachining and implanted via a novel minimally-invasive surgery cutting care costs and improving patient recovery.
Globally, 660 M people suffered from uncorrected refractive error in 2013. In severe cases, sufferers are left out of work or with less skilled employment. Mapped to global population growth and associated societal costs from a prior study, 706 M (including 39M clinically blind) individuals will represent a loss in terms of potential human economic productivity of €1.2 T in 2019. Europe shares 9.7% of this burden, equal to €116 B in 2019. Uncorrected refractive error is second only to cataracts as a leading cause of blindness, accounting for 36.4% of cases in 2015. Recent studies suggest that PCSDs account for 16.5% of severe refractive error cases, equivalent to 175 M people, especially in the stage 2 to 4 of KC which is our target group of patients. PCSD involves progressive weakening and thinning of the cornea that alters its shape. As the cornea is a key refractor of light into the eye, this results in a swift progression to severe refractive errors such as astigmatism and myopia.
Globally, 660 M people suffered from uncorrected refractive error in 2013. In severe cases, sufferers are left out of work or with less skilled employment. Mapped to global population growth and associated societal costs from a prior study, 706 M (including 39M clinically blind) individuals will represent a loss in terms of potential human economic productivity of €1.2 T in 2019. Europe shares 9.7% of this burden, equal to €116 B in 2019. Uncorrected refractive error is second only to cataracts as a leading cause of blindness, accounting for 36.4% of cases in 2015. Recent studies suggest that PCSDs account for 16.5% of severe refractive error cases, equivalent to 175 M people, especially in the stage 2 to 4 of KC which is our target group of patients. PCSD involves progressive weakening and thinning of the cornea that alters its shape. As the cornea is a key refractor of light into the eye, this results in a swift progression to severe refractive errors such as astigmatism and myopia.
The agreement with EC started in November 2019. However, the project started earlier. In September 2019, pre-clinical tests were carried out with the titanium devices provided by Recornea. These tests concluded that the material of these devices did not allow the shape memory necessary for non-invasive implantation in patients. For this reason, at the official starting of the project, the material was changed to nitinol.
During the first months of the project, Blueacre, with the technical support of REC, adapted the tasks for the creation of the devices in nitinol. At this point, it required the support of suppliers whose delivery times were greatly delayed by the global pandemic situation. In particular, there was a delay in the dies and in the press.
These delays and the difficulties to replicate the design proposed in the project by Blueacre, caused that the devices created were not delivered to CHU and IMO for their pre-clinical study until the last week of the 12th month of the project.
The preclinical tests concluded that the devices created by Blueacre did not have the necessary shape memory nor did they meet the curvature criteria or other necessary technical specifications for a human clinical trial.
Since Blueacre was not able to produce a viable prototype and spent almost all of its project budget in year 1, the Consortium decided to completely rethink the project, without Blueacre's participation, to outsource the production of the devices. During year 2 of the project, alternatives have been found that meet the technical and qualitative requirements necessary for a device to be implanted in human eyes.
In its third year, the project successfully scaled up production of the GROSSO Implant, implementing numerical simulations and quality control to meet regulatory standards. With an additional €600k from third parties, the Humaneye project remains on track according to the January amendment. Despite delays, the team plans to complete device production, biocompatibility, and animal testing by year 4's end. Pending ethical committee approval, and considering war-induced delays and rising material costs, human study recruitment is slated to begin in year 5.
In the project's fourth year, the GROSSO Implant's production and provider processes were validated, enabling successful pre-clinical testing for regulatory compliance, including MR conditional certification and various safety evaluations. REC secured €805k in investments, with an additional €150k under negotiation with Scientifica VC. The consortium is focused on completing the first-in-human (FIH) study, pending final approval from Spain's AEMPS, although it has already received a favorable review from the Ethics committee in February 2024.
During the first months of the project, Blueacre, with the technical support of REC, adapted the tasks for the creation of the devices in nitinol. At this point, it required the support of suppliers whose delivery times were greatly delayed by the global pandemic situation. In particular, there was a delay in the dies and in the press.
These delays and the difficulties to replicate the design proposed in the project by Blueacre, caused that the devices created were not delivered to CHU and IMO for their pre-clinical study until the last week of the 12th month of the project.
The preclinical tests concluded that the devices created by Blueacre did not have the necessary shape memory nor did they meet the curvature criteria or other necessary technical specifications for a human clinical trial.
Since Blueacre was not able to produce a viable prototype and spent almost all of its project budget in year 1, the Consortium decided to completely rethink the project, without Blueacre's participation, to outsource the production of the devices. During year 2 of the project, alternatives have been found that meet the technical and qualitative requirements necessary for a device to be implanted in human eyes.
In its third year, the project successfully scaled up production of the GROSSO Implant, implementing numerical simulations and quality control to meet regulatory standards. With an additional €600k from third parties, the Humaneye project remains on track according to the January amendment. Despite delays, the team plans to complete device production, biocompatibility, and animal testing by year 4's end. Pending ethical committee approval, and considering war-induced delays and rising material costs, human study recruitment is slated to begin in year 5.
In the project's fourth year, the GROSSO Implant's production and provider processes were validated, enabling successful pre-clinical testing for regulatory compliance, including MR conditional certification and various safety evaluations. REC secured €805k in investments, with an additional €150k under negotiation with Scientifica VC. The consortium is focused on completing the first-in-human (FIH) study, pending final approval from Spain's AEMPS, although it has already received a favorable review from the Ethics committee in February 2024.
We estimate that HUMANEYE will deliver an economic benefit of €14,336/patient versus current treatment for late-stage KC based on corneal transplantation. Based on our commercial roll-out estimates, 300+ k patients will receive GROSSO Implant by Y5, of which at least 255k patients (85%) will reach a clinically successful outcome, so total direct healthcare savings will amount to €3.65bn. In addition, a study of severe refractive visual impairment in the US indicated that indirect productivity costs for patients, such as forced unemployment, amount to 49% of the patient's direct healthcare costs.
Based on this, we project indirect economic benefits of €1.81B by Y5 (€7.1k per patient). Together, the total economic benefits for HUMANEYE reach €5.46B by Y5. In commercializing HUMANEYE, REC’s financial projections collectively show €117M in revenues by Y5 with more than 167 implants sold globally in the first five years.
KC onset is often at puberty or early adulthood and progresses into prime earning and child-rearing years. HUMANEYE is a unique a-priori match to the shape of the human cornea that removes the random chance, subjectivity and human error involved in current Intra Corneal Ring Segments implants. As a result, 85% of patients will present with a positive clinical outcome versus 50% with ICRS, equivalent to 255k by Y4 versus a hypothetical total of only 75k for ICRS (source: Market Scope). Using our device to correct refractive error and halt disease progression in these patients will avoid the significant negative impacts of KC on vision-related quality of life.
Many KC patients experience a continuous decline in Vision-related quality of life (VRQoL) over time. HUMANEYE will avoid complications and patient suffering associated with inadequate current treatments, such as graft rejection and failure, microbial infections, astigmatism and glaucoma or cataracts after corneal transplantation. Based on statistics, 40-64-year-olds suffer of severe refractive error in the US, successful intervention with HUMANEYE on 300k patients by Y5 will permit 50k patients to return to employment and a further 44k to achieve higher-skilled positions after treatment.
HUMANEYE will revolutionise the treatment of all corneal irregularities far beyond just KC.
IMO and CHU provide primary healthcare and medical research and teaching. Their exploitation of the project developments will be in the form of (1) knowledge dissemination via scientific publications and presentations on the project results, (2) the education of clinicians, researchers and postgraduate students in the most up-to-date developments in KC, severe refractive error and surgical interventions in the cornea and (3) ensuring best clinical practice for treating PCSDs with HUMANEYE. The project will strengthen their involvement in innovative research, an important part of their future research strategy.
Based on this, we project indirect economic benefits of €1.81B by Y5 (€7.1k per patient). Together, the total economic benefits for HUMANEYE reach €5.46B by Y5. In commercializing HUMANEYE, REC’s financial projections collectively show €117M in revenues by Y5 with more than 167 implants sold globally in the first five years.
KC onset is often at puberty or early adulthood and progresses into prime earning and child-rearing years. HUMANEYE is a unique a-priori match to the shape of the human cornea that removes the random chance, subjectivity and human error involved in current Intra Corneal Ring Segments implants. As a result, 85% of patients will present with a positive clinical outcome versus 50% with ICRS, equivalent to 255k by Y4 versus a hypothetical total of only 75k for ICRS (source: Market Scope). Using our device to correct refractive error and halt disease progression in these patients will avoid the significant negative impacts of KC on vision-related quality of life.
Many KC patients experience a continuous decline in Vision-related quality of life (VRQoL) over time. HUMANEYE will avoid complications and patient suffering associated with inadequate current treatments, such as graft rejection and failure, microbial infections, astigmatism and glaucoma or cataracts after corneal transplantation. Based on statistics, 40-64-year-olds suffer of severe refractive error in the US, successful intervention with HUMANEYE on 300k patients by Y5 will permit 50k patients to return to employment and a further 44k to achieve higher-skilled positions after treatment.
HUMANEYE will revolutionise the treatment of all corneal irregularities far beyond just KC.
IMO and CHU provide primary healthcare and medical research and teaching. Their exploitation of the project developments will be in the form of (1) knowledge dissemination via scientific publications and presentations on the project results, (2) the education of clinicians, researchers and postgraduate students in the most up-to-date developments in KC, severe refractive error and surgical interventions in the cornea and (3) ensuring best clinical practice for treating PCSDs with HUMANEYE. The project will strengthen their involvement in innovative research, an important part of their future research strategy.