From Collapse to Comeback: Behind the Scenes of Pixium Vision’s Revival with Dr. Brian Burg

Dr. Burg, thank you for joining us today. Let’s start from the top. How did you get into bionic vision and how did you find your way to Pixium?

[Brian Burg (BB)]: I was born and raised in Luxembourg. Luxembourg doesn't have a university, so like Michael here, I went to study at ETH Zurich in Switzerland. My PhD in Mechanical Engineering focused on interfacial transport phenomena and thermodynamics, which allowed me to gain significant experience in cleanroom processing. Post-PhD, I studied the transition between heat conduction and heat radiation at MIT, and a bit later joined IBM's Research Lab in Zurich, where I worked on hot-water cooling for data centers with subsequent heat reuse. When IBM sold their server business to Lenovo, I sought better prospects and joined a project between ETH Zurich and the University Hospital Zurich on liver perfusion, requiring my fluid manipulation skills. This venture led me into medical devices. After a few years, I relocated to Paris as my wife was pregnant with our first child.

My first position in Paris was with a pre-clinical startup developing a cardiac assist device, before joining another startup in the structural heart space, this time at a clinical stage. Ultimately I was drawn to Pixium who were looking to fill a project manager position. This role was a perfect merger of my expertise in microfabrication—essential for implant fabrication—and active implantable medical device development, which are among the more challenging projects in the field.

Could you tell us more about your first position at Pixium and how it led to your current responsibilities?

[BB]: I had been working as a project manager on the next generation of our product for about a year, when my boss, Guillaume Buc, who had hired me, decided to leave for an opportunity outside of Paris in the south-west of France. That’s when I was propelled into his position as the Director of R&D.

At that point, PRIMA, our major project, was already in clinical trials. Technically speaking, my contribution to the pre-clinical phase was minimal, as it began around 2014. The implant was licensed from Stanford, invented and designed by Prof. Daniel Palanker based on photovoltaic cell principles. The key role of Pixium’s original employees, of which a number are still around, was in the realm of industrializing the microfabrication processes. This involved refining semiconductor manufacturing and MEMS processing to meet stringent quality requirements. Additionally, a surgical delivery system had to be developed to implant the device, including its sterilization process. Custom wearables were created to stimulate the implant via a laser source, incorporating components such as laser diodes, fiber optics, lenses, microprocessors, data transmission cables, printed circuit boards, batteries, cameras, projectors and embedded software.

The first human implantation took place in 2017, and by the time I joined, nine patients had already been implanted. During the pivotal study that started in 2021, we managed to implant an additional 38 patients to our 9 patients from our first in human studies, and we recently reached our primary data endpoint in February this year. So, the journey from project manager to Director of R&D at Pixium has been deeply involved with both the development and execution of critical technological advancements.

Could you give us a preview of the PRIMAvera trial results that will be published soon?

[BB]: Yes, although some details must remain confidential for now. Currently, we have only the raw data from the study, which hasn’t yet been statistically analyzed. To clarify, we have some patients who, due to unrelated reasons and their advanced age, unfortunately passed away during the study. The data accounting for these events has not been fully processed, and the comprehensive report is still pending.

However, I can share that the preliminary results are promising. The initial published findings from the first human study have not only been confirmed but in some cases exceeded. A significant outcome is that we've been able to restore form vision, enabling patients to read and significantly improve their visual acuity on an ETDRS chart. In fact, we target to achieve our primary endpoint, which was improving visual acuity by at least two lines on an ETDRS chart for more than 70% of the participants.

Regarding safety, which is crucial for any implant, all adverse events have been reviewed by a Data and Safety Monitoring Board (DSMB) which recommended continuing the study.

Could you explain what it means for participants to be able to read with the implant? With previous implants, users could recognize large-print letters after looking at them for a while, which is quite different from what most people think of as 'reading'.

[BB]: I know what you mean, but I can assure you our patients can really read—although the reading speed is still slower than for natural readers. Our implant has a resolution of roughly 20x20 pixels, which allows for the projection of two to three letters at a time on the implant. The projected image on the retina covers a larger area than the size of the implant. This setup facilitates some degree of eye scanning over what is projected, enhancing the user’s ability to perceive more complex visual stimuli.

However, there is definitely a training phase where users have to learn how to use PRIMA. To clarify, our patients undergo a rehabilitation phase after implantation to adapt to the device. This involves learning to focus their gaze directly into our projector, where the laser exits, and aligning the entire system, including the glasses. It’s crucial for patients to learn to maintain a straight gaze, particularly because they often still possess some peripheral vision, which can make fixing their gaze challenging without training.

After patients become accustomed to the system, anecdotally speaking, a certain number of them can read entire pages, such as books to their grandchildren. It represents a significant improvement over prior devices, offering a more natural reading experience, though still not at the speed of unassisted reading.

Going back to your role as Director of R&D, could you give us a glimpse into the general research direction and what improvements the team was focusing on for the next generation of PRIMA?

[BB]: The primary limitation of today's devices is the field of view. There are two ways to increase it: by increasing the implant size or by decreasing the pixel spacing. Daniel Palanker’s group has been working on this, publishing and patenting their findings, which we have licensed. This will require a new implant design to achieve the necessary penetration depth to stimulate the bipolar cells. The ultimate goal would be to project more broadly across the iris, allowing patients to scan and capture images projected onto the retina. This would, however, introduce new challenges, such as higher radiation levels, which in turn would raise safety concerns due to potential heat generation on the retina. Eye tracking may also be considered in this context.

Another improvement involves the wearables, which we are aiming to make more minimalistic and smaller in size. Ideally, we would integrate everything into the glasses to eliminate the apparent projection module, thereby reducing the stigma for AMD patients who were accustomed to seeing normally prior to being struck by the disease.

As for commercialization, the plan has always been to first launch the current model. Given that these AMD patients currently have no other viable treatment options, introducing this initial version of the implant would be highly beneficial. I’m convinced that it will provide significant benefits to a substantial number of patients. The revenue generated from this would then fund the development of the next generation, which could potentially meet the needs of the entire patient population.

It seems like everything was going well: you had a successful clinical trial and were developing a new device, but then suddenly the company faced financial issues. What happened?

[BB]: The timing was most unfortunate. To answer this question, I need to give a bit of a backstory. As you know, Pixium was founded in 2011, and one of the first major steps was acquiring a German company called IMI, which was developing the IMI implant that would later become IRIS II. This implant reached commercialization a few years after Pixium went public on the French stock market. However, we soon encountered reliability issues with the IRIS II implant, forcing us to withdraw it from the market and refocus our efforts on developing a new implant, PRIMA.

Being a public company in Europe, and particularly in France, presented significant challenges in raising funds. This was compounded by the fact that we had already spent about 130 million Euros, and our historical investors were unwilling to invest further. Their reluctance raised questions among potential new investors about why the original backers were no longer supporting us. Additionally, the public company status added complexity to how we could distribute shares.

Over the last 9 months, this situation led us into a safeguard procedure, and we ultimately had to file for a state similar to U.S. Chapter 7 bankruptcy. The goal was to transition back to being a private company, with a plan for a new investor to buy out Pixium's assets and start afresh. However, this process was highly regulated due to our public status, and ultimately, the court rejected the investor’s bid due to insufficient proof of funding for future operations. The court decided to put us directly into liquidation on January 31, 2024, a decision that surprised everyone involved, including lawyers and judicial administrators. All employees were furloughed at that point.

The very next day after this decision, we closed the data for the primary endpoint of our clinical study—it felt like something out of a movie. Now, we’re in liquidation but there’s still an opportunity to purchase the assets and integrate them into a new company. That’s what we got working on, under an extremely tight deadline. The urgency was because we need to resume the clinical trial, which is ongoing beyond the primary endpoint at 12 months. If successful, this transition would allow us to start with a clean slate—no debt, no history—as a private company, but the time pressure was intense.

Our first contacts with Science stem from November 2022, whom we had approached for funding. After having passed twice, the raw data of our clinical study ultimately convinced them of the viability of the technology and its place in the market. Following reciprocal visits, they decided to hand in an offer the day bidding closed. Between competing bids, an opportunity to improve offers, a judge who had fallen ill and needed to be replaced, the assets were finally awarded to Science on April 15, 2024.

This story has all the ingredients for a John Grisham thriller - apart from the deaths! (laughs)

Going forward, what can people look forward to under this new stewardship?

[BB]: The clearly stated objective is to bring the PRIMA technology as quickly to the market as possible. To this end the entire Paris team will be reinstated and incorporated in Science, namely product development, operations and manufacturing, clinical, and quality and regulatory affairs. Rehiring is currently ongoing, while the liabilities of Pixium will be liquidated. Ongoing clinical trials will be resumed and with funds now available, pivotal clinical trials in the US initiated and the applications of the PRIMA technology to other pathologies studied.

We couldn’t be more excited to show the world what PRIMA is capable of. This technology has the potential to change the lives of millions of people. There aren’t that many missions out there more noble than giving back vision to the blind. This cause fills us with pride and we are determined to deliver.