Comprising of Kevin Alessandri, CEO/CTO, Treefrog Therapeutics, Vincent Ronfard, Chief Innovation Officer, CUTISS and Rob Schutte, Executive Director, Process Development Humacyte, the panel shared the journeys of their respective companies – all the way from the back of the napkin to the bedside.
From the back of the napkin – the origin stories
David Hodl, Invetech’s Head of Business Development for Cell Therapy who chaired the panel, opened the discussion by inviting each company to share their origin story. Hodl highlighted how regenerative medicine companies often have fascinating origin stories and face unique challenges because of the novel technologies they are bringing to market.
Since their incorporation in late 2018, TreeFrog Therapeutics has developed a high-throughput cell encapsulation technology which allows the mass-production and differentiation of stem cells in industrial bioreactors. Kevin Alessandri said: “I’m a researcher by training, and the origin of the company was when I met my co-founder Maxime [Feyeux, PhD] who is a specialist in stem cell biology. At the time, I was developing an encapsulation technology for cells, and Max was looking for a way to cultivate and scale up high-quality stem cells. We put our knowhow together to develop this technology, and that’s how the company came to be.”
Vincent Ronfard shared the origins of CUTISS, a Swiss company that has developed a personalized skin technology to treat skin defects. The company was founded in 2013 by Dr. Daniela Marino during her postdoctoral research at the University of Zurich’s Tissue Biology Research Unit. Dr Marino helped the Unit secure a European Union grant to advance the skin technology they were developing and having seen an opportunity to develop the technology further, decided to make the leap from researcher to CEO. CUTISS is currently developing an automated production process to improve the scalability of their technology and has received funding from the European Union’s Horizon program.
Humacyte’s Rob Schutte described how the founder of the company, Dr. Laura Niklason, had an ‘A-ha’ moment as a postdoctoral researcher at MIT. “Watching surgery, she saw the process of removing a vein from a patient’s leg that was going to be used for a coronary artery bypass and thought ‘There has to be a better way’”. Since its foundation in 2004, Humacyte has developed a proprietary technology and process to create bioengineered human acellular vessels (HAVs) that have the potential to significantly improve treatment outcomes.
Transitioning from the lab towards commercial scale
The panel shifted to discuss the challenge of transitioning from the academic lab to developing technology into a prototype and beyond. Schutte first shared Humacyte’s experience, “It was around 2012 when we implanted our product into our first human patient. And from there, we were moving forward towards developing a platform technology so that we could manufacture a product for a Phase III clinical trial – and at the same time have our eyes on the end goal of having a commercial process. So, we developed this platform technology, where we could demonstrate kind of the founding principles of how we make an HAV.”
Schutte continued, “Instead of redeveloping the process and undergoing the risk of having to change our process significantly between Phase III and commercial, we were able to develop a platform where we could scale out and have minimal change in the process where we can increase the batch size to add to our production capacity. Automation was certainly a part of some of that, single use technologies were certainly a part of that.”
Ronfard shared how CUTISS has been able to develop their process, “Firstly, we are in the autologous business, so we are producing a limited quantity of bioengineered skin. The first thing that we needed to consider was between automation and robots, and robots are not suitable for this type of business model because the segregation is more difficult.”
He continued, “With automation, we had two choices; do we want to go for the fully integrated machine or do we want to go with a modular approach where we can go step-by-step and also, not only develop our own modular automation, but add some modules that are already available on the market. We went with the modular approach and now we are able to have an inline process with different modules.“
Critical decision points when scaling the process
The panel shared some of the critical decision points the companies have faced as they have scaled their production and moved towards commercialization. Ronfard first talked about CUTISS’s approach, “The key point is to always be safe and preserve the biological capacity of your cells or your tissue – all of these decisions are driven with the biological validation in mind. You can have the best machine, the best equipment, but if the output is not equivalent to the one you get from a manual process, you will have a lot of problems during your clinical trial to show that you have an equivalent product. So, the key point is always the biological validation.”
TreeFrog Therapeutics’ Allesandri shared how doing voice of customer work to understand the end-users was a key point for them. “Going to the lab to see the end-users’ facilities, to see how they were actually working, that was really a key point for us. I worked with these biologists while I was in the lab, and it was when we brought the prototype to the lab or they came to our facility to experiment with the prototype, that I very quickly understood that automation would be the key. We already had a concept around what the process should be, and I already knew there would be some automation.”
Humacyte has focused on scaling their process from the start, and Schutte shared some of the critical points in their journey. “We knew we had a long development pathway ahead of us and we got started early, and I think that was a very smart decision on Humacyte’s part. We spent quite a bit of time before we started working on the first prototype. We spent that time building our vision for what a commercial process would look like.”
Schutte continued, “We took the approach where we wanted to have that modular system in place prior to our Phase III clinical trials so that we minimize any risk, and then move from Phase III clinical trials to our commercial manufacturing process. And make it as easy as possible to demonstrate that the Phase III process is identical or similar enough so that it has no impact to the CQ ways of our product.”
To the bedside
Looking further afield, all three companies are accelerating their commercialization journeys. “For CUTISS, we did the main part of the development of the automation through grants and now we need to go to the next phase. Because we cannot do that organically – we don’t have the knowledge – we are looking at partnering,” Ronfard said. “And partnering is key because we have experienced different partnering with different outcomes and the problem, if you have the wrong partner, is that you have to delay or restart – and with restarting there is a steep learning curve. So, we are at this point and we expect that within 3-4 years we will be able to produce our first batch of de novo skin and deliver it to patient.”
TreeFrog Therapeutics’ focus is on bringing their C-StemTM technology to the clinic as fast as possible. Alessandri said, “We are going very fast, and with our prototype now in place, we aim to be able to develop within two years – by the end of 2022 – a GMP-compliant device for high-throughput stem cell encapsulation. We are very excited to be working with Invetech on the GMP-compliant device.”
Humacyte is also moving quickly, with Schutte commenting, “We’re late stage in the qualification process and working on new products at the same time. We have a pipeline and we are working towards different applications, different indications, different products that are a similar type of technology – blood vessels – and we are working towards our biologics license in the US and heading towards getting our process commercialized and getting our product to more patients.”
This panel aired live at Phacilitate Advanced Therapies Connect on 30 September 2020. The recording was first published on Phacilitate Exchange.
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