Highlife SAS, a Paris-based med-tech company focused on the development of a transcatheter mitral valve replacement (TMVR) system to treat patients suffering from mitral regurgitation, recently closed a €32 million (US$36.4 million) round of equity financing.

Proceeds are slated to help complete the development of the company's transcatheter transseptal mitral valve implantation program, which includes regulatory approval trials in Europe and the first clinical trial in the U.S. via an early feasibility study.

This series B round was co-led by U.S. Venture Partners (USVP) and Andera Partners. Sectoral Asset Management and Jose Calle Gordo, the company's chair, also participated. Sofinnova Partners, which led the series A round, also joined.

"We are in the transcather valve field, which started with aortic valve replacement," Georg Börtlein, who also is the company's CEO, told BioWorld MedTech. Over time, interest grew for treating the mitral side. "It was a request from the market, so to speak, to have development occur to treat that valve."

Casey Tansey, general partner at USVP, expressed enthusiasm about Highlife's technique. "Highlife's creative approach has already generated convincing data in this competitive field of mitral valve replacement. I am confident that the experienced management team will bring this technology to the level where it becomes an undisputed treatment option for mitral valve regurgitation patients," Tansey noted.

Highlife was started in 2010 by Börtlein, who previously served as a co-founder with Jacques Séguin at Corevalve Inc. That Irvine, Calif.-based company was focused on transcatheter aortic valve replacement and was acquired by Dublin-based Medtronic plc in 2009 for more than $700 million. (See BioWorld MedTech, Feb. 24, 2009.) In 2017, Highlife closed a $14.3 million investment round led by Sofinnova Partners. (See BioWorld MedTech, Oct. 31, 2017.)

Highlife's technology

Highlife's technology is intended to be delivered transseptally via the femoral vein in a reversible manner, and it self-locates inside the native annulus. The company noted that this is the preferred route for both interventionists and patients, as it avoids surgery.

The system consists of two components, a valve prosthesis and a ring-shaped subannular implant (SAI). The valve self-centers and aligns itself upon delivery inside the SAI ring, aiming for easy, safe delivery. In addition, the Highlife valve covers with one size the majority of mitral valve regurgitation patients. It can be implanted in native annuli with the largest axis starting at 35 mm up to 50 mm.

Evolving field

In the past, companies have focused on the transapical approach, which involved a puncture in the heart muscle. However, industry has sought an approach that not only involves not puncturing the muscle, but also requires a smaller catheter.

Indeed, much has changed over the past decade. "We're in the situation where there has been a shift in the last 10 years toward beating-heart techniques, but there is still a debate over whether repair or replacement is superior. And if they can coexist, what are the patient populations that benefit more from one or the other," Börtlein added.

The repair side is led by Abbott Laboratories' Mitraclip. The Abbott Park, Ill.-based company picked up that device in 2009, and it has been a leader in the mitral valve regurgitation space for some time. The device has encountered some speedbumps. For example, there were issues in a study matching the device against optimal medical management for 304 patients in France. (See BioWorld MedTech, Aug. 29, 2018.) However, observers have questioned the enrollment in that study. Further, Abbott spokesperson Kristina Becker told BioWorld MedTech that study involved the first-generation device. Abbott noted last July that the FDA had approved the third iteration of the device.

Abbott did make a splash in September, with the company unveiling positive two-year pivotal data for Mitraclip at the Transcatheter Cardiovascular Therapeutics meeting in San Diego, as well as publishing it simultaneously in the Sept. 23, 2018, issue of The New England Journal of Medicine. (See BioWorld MedTech, Sept. 25, 2018.) Specifically, the COAPT study met its primary and secondary endpoints, including reduced all-cause mortality at two years after the procedure.

"Both the MitraFR and COAPT studies provide valuable insightsand ultimately show that long-term results are importantconsiderations when evaluating the benefits of a MitraClipprocedure as well as determining which patients may benefitmost. The differences in the results of the MitraFR and COAPTtrials help to show which patients benefit most from thetreatment," said Mary Kokkinen, senior manager of publicaffairs for Abbott s Structural Heart business.

"Mitraclip has made a lot of progress, and today, things are much better," Börtlein noted. With that said, "there is still a consensus that there is merit in evaluating replacement devices that completely eliminate the mitral insufficiency." A lot of clinical data need to be generated, however, to determine if one method is better than the other.

"All of the major corporations in this field are hedging their bets by developing or acquiring technologies that both target repair and replacement," Börtlein said. That was evident last week, with Abbott exercising its option to purchase Cephea Valve Technologies Inc., of Santa Clara, Calif. (See BioWorld MedTech, Jan. 17, 2019.) Last year, Abbott revealed the start of the pivotal clinical study in the U.S. with the Tendyne system for the treatment of mitral regurgitation. (See BioWorld MedTech, July 27, 2018.)

For its part, Medtronic is sponsoring the APOLLO trial in TMVR assessing Intrepid. In 2015, Edwards Lifesciences Corp., of Irvine, Calif., picked up hometown Cardiaq Valve Technologies. During last year's third-quarter earnings call, Michael Mussallem Edwards's CEO, highlighted progress. "In mitral valve replacement, we're encouraged by the positive scientific presentations at TCT last month on our new Evoque system, which is built on the learnings and experiences of Cardiaq. We continue to make good clinical progress with Evoque and Sapien M3 systems and remain confident in our transseptal mitral replacement strategy." Boston Scientific Corp. completed its acquisition in December 2018 of Millipede Medical Inc., of Santa Rosa, Calif., for an additional $325 million, and it noted that it expects the mitral valve repair and replacement market to hit $1 billion by 2021.

Also in the field is Livanova plc of London, which last year concluded the 20-patient PRELUDE feasibility study of the Caisson TMVR device that it acquired in 2017. (See BioWorld MedTech, Aug. 7, 2018.) It is now moving ahead, noting at the time that it will focus on enrolling patients in the INTERLUDE CE mark trial and finalizing the protocol for the U.S. pivotal trial, known as ENSEMBLE.

Highlife expects to gain the CE mark in 2021, with a market launch the following year. However, R&D will continue, and the triscuspid valve could be a target, but no activity has begun on this front.