Periodic Reporting for period 2 - The Angelvalve Project AVVie (Advancing Transcatheter Mitral Valve Repair)
Reporting period: 2024-02-01 to 2025-01-31
Mitral regurgitation (MR) occurs when the mitral valve leaflets do not close properly, resulting in a leakage of blood backward through the mitral valve. With acute severe mitral valve regurgitation, open-heart surgery is considered the standard gold treatment to either repair or replace the diseased valve, depending on the condition's cause. In Europe and the US, approximately 13 million people have been diagnosed with MR. However, today, less than 5% of patients with moderate to severe disease receive treatment. However, untreated valve incompetency results in volume overload and backward failure, affecting lung function and continuing to right heart failure and, subsequently, organ failure and death.
AVVie is developing the Mitral Butterfly (MB) system, a novel, innovative solution for patients suffering from MR and subsequent heart failure. The Mitral Butterfly is a hemi valve replacing the function of the native, dysfunctioning posterior leaflet. The Mitral Butterfly restores full coaptation with a nitinol-based frame and a pericardial membrane by sliding over the diseased leaflet while preserving the motion and function of the anterior leaflet. The Mitral Butterfly has been designed to have a stable atraumatic implant seating without penetration of the myocardium, preventing unphysiological inflow (regurgitation) caused by diverse pathophysiologic origins like DMR and FMR and minimizing the outflow obstruction (stenosis) with low artificial footprint. The delivery can be done by both minimally invasive surgery and by transseptal delivery.
While today, surgical repair and/or replacement is considered first-line therapy for patients with severe MR, many patients are inoperable. Today, Mitral Transcatheter Edge-to-Edge Repair (M-TEER) and Transcatheter Mitral Valve Replacement (TMVR) offer an alternative to some of the inoperable patients. Nevertheless, due to the high screen failure rates of up to 90% and suboptimal outcomes there is a further need for innovative mitral repair options for patients in need.
Within the EIC Accelerator program, AVVie integrates an innovation loop to standardize testing and iterate the best available implant based on anatomy and pathophysiology. Building a digital twin for preprocedural planning and facilitating implantation and navigation is part of the success. The ease of use is shown in our schematic and its integration into the anatomy, targeting a successful repair using the Hemi Valve Mitral Butterfly. Unlike competitors, as seen in the schematic, our Mitral Butterfly device follows the anatomic and pathophysiologic assumptions for a successful repair. Acceleration using the EIC Fund allows us to show that AVVie is more than a mitral repair option by integrating imaging for navigation, preprocedural planning, and new concepts for manufacturing.
AVVie is developing the Mitral Butterfly (MB) system, a novel, innovative solution for patients suffering from MR and subsequent heart failure. The Mitral Butterfly is a hemi valve replacing the function of the native, dysfunctioning posterior leaflet. The Mitral Butterfly restores full coaptation with a nitinol-based frame and a pericardial membrane by sliding over the diseased leaflet while preserving the motion and function of the anterior leaflet. The Mitral Butterfly has been designed to have a stable atraumatic implant seating without penetration of the myocardium, preventing unphysiological inflow (regurgitation) caused by diverse pathophysiologic origins like DMR and FMR and minimizing the outflow obstruction (stenosis) with low artificial footprint. The delivery can be done by both minimally invasive surgery and by transseptal delivery.
While today, surgical repair and/or replacement is considered first-line therapy for patients with severe MR, many patients are inoperable. Today, Mitral Transcatheter Edge-to-Edge Repair (M-TEER) and Transcatheter Mitral Valve Replacement (TMVR) offer an alternative to some of the inoperable patients. Nevertheless, due to the high screen failure rates of up to 90% and suboptimal outcomes there is a further need for innovative mitral repair options for patients in need.
Within the EIC Accelerator program, AVVie integrates an innovation loop to standardize testing and iterate the best available implant based on anatomy and pathophysiology. Building a digital twin for preprocedural planning and facilitating implantation and navigation is part of the success. The ease of use is shown in our schematic and its integration into the anatomy, targeting a successful repair using the Hemi Valve Mitral Butterfly. Unlike competitors, as seen in the schematic, our Mitral Butterfly device follows the anatomic and pathophysiologic assumptions for a successful repair. Acceleration using the EIC Fund allows us to show that AVVie is more than a mitral repair option by integrating imaging for navigation, preprocedural planning, and new concepts for manufacturing.
During the first half of the grant period, we iterated our concept, running the innovation loop and analyzing the results. To be able to run the innovation loop in an effective, agile, and timely manner, AVVie has developed inhouse a pulsatile flow bench testing model that can be used for porcine, ovine, or human isolated hearts, allowing for complete control of the flow dynamics and real-time visualization of the implant performance.
One of the major achievements during the first part of the EIC Accelerator Program is realizing the option of improved atraumatic anchoring for our implant as well as updating the frame and neo-leaflet design using the "open edge" concept of the Mitral Butterfly showing excellent coaptation and stability in the bench testing. This is advancing our concept beyond any known competitor using leaflet extension therapies. Furthermore, the performed bench testing addresses the implant's fixation and stability, paravalvular leakage, central coaptation eliminating mitral regurgitation, mitral inflow pattern, and anatomical interactions limiting tissue damage.
The implant sizing analysis conducted on human, porcine, and ovine CTs enables us to perform precise implant sizing. It provides relevant inputs for the implant design, leading to better implant fixation, functionality, and elimination of paravalvular leakage. Pre-procedural planning for the Mitral Butterfly implantation is required to allow precise measurement and determine which implant will fit the patient's cardiac structure. During this process, it became apparent that two to three sizes for each of the two most important pathologies, DMR and FMR, are sufficient to meet the requested functionality of the implant.
In addition, AVVie has focused the development process on the first iterations of transcatheter delivery of the implant. After performing computer simulations of tensile stress and plastic deformation for crimping and deploying the device, we have conducted successful bench tests of crimping the Mitral Butterfly to the lowest possible profile. We have demonstrated in the bench the feasibility of deployment of the valve out of the delivery capsule and the successful expansion of wings and clasps actuation.
We have conducted the initial hazard analysis using the regulatory framework of the risk management process laid down in MDR and ISO 14971:2019.
With the updated design, most identified risks and the corresponding harms can be mitigated to acceptable levels.
One of the major achievements during the first part of the EIC Accelerator Program is realizing the option of improved atraumatic anchoring for our implant as well as updating the frame and neo-leaflet design using the "open edge" concept of the Mitral Butterfly showing excellent coaptation and stability in the bench testing. This is advancing our concept beyond any known competitor using leaflet extension therapies. Furthermore, the performed bench testing addresses the implant's fixation and stability, paravalvular leakage, central coaptation eliminating mitral regurgitation, mitral inflow pattern, and anatomical interactions limiting tissue damage.
The implant sizing analysis conducted on human, porcine, and ovine CTs enables us to perform precise implant sizing. It provides relevant inputs for the implant design, leading to better implant fixation, functionality, and elimination of paravalvular leakage. Pre-procedural planning for the Mitral Butterfly implantation is required to allow precise measurement and determine which implant will fit the patient's cardiac structure. During this process, it became apparent that two to three sizes for each of the two most important pathologies, DMR and FMR, are sufficient to meet the requested functionality of the implant.
In addition, AVVie has focused the development process on the first iterations of transcatheter delivery of the implant. After performing computer simulations of tensile stress and plastic deformation for crimping and deploying the device, we have conducted successful bench tests of crimping the Mitral Butterfly to the lowest possible profile. We have demonstrated in the bench the feasibility of deployment of the valve out of the delivery capsule and the successful expansion of wings and clasps actuation.
We have conducted the initial hazard analysis using the regulatory framework of the risk management process laid down in MDR and ISO 14971:2019.
With the updated design, most identified risks and the corresponding harms can be mitigated to acceptable levels.
In the current period of our EIC funding stage, we can demonstrate all necessary deliveries and milestones. We must overcome the current financial restrictions affecting our targeted results for further success in the second period. The design freeze of our implant is scheduled after our newly designed devices are implanted in chronic animals. New patents are scheduled in 2024 and continue into 2025. We need support in regulatory standardization, especially for the FIH since not all standards are applicable in this period. We will focus on the delivery method and technology to facilitate implantation.