Making personalized, autologous cell therapies accessible
Apr 11, 2022
Nabiha Saklayen is CEO and Co-Founder of Cellino. Cellino's proprietary technology makes stem cell-derived therapies scalable for the first time. Nabiha was selected as a Pioneer in MIT Tech Review's 35 Innovators under 35 list for her patented inventions in cellular laser editing. She received her PhD in physics from Harvard University as a Howard Hughes Medical Institute (HHMI) International Fellow. She is also the inaugural Tory Burch Foundation Fellow in Genomics at the Innovative Genomics Institute led by Nobel laureate, Dr Jennifer Doudna. Nabiha is also a TED speaker and co-creator of I Am a Scientist, an educational program running in 50 states that inspires children to explore science. Marinna Madrid is Chief Product Officer and Co-Founder at Cellino. She received her MA and PhD in applied physics from Harvard University, where she co-invented laser-based intracellular delivery techniques. She received her BSc in biophysics from the University of California, Los Angeles, after transferring from Riverside Community College. She is the recipient of the Harvard Graduate Prize Fellowship, the Catalyst Accelerator Grant from Harvard Medical School, and was on the Forbes 30 Under 30 list for healthcare in 2019. She has several patents, peer-reviewed publications and wrote the first review paper on autologous induced pluripotent stem cell (iPSC)-based cell therapies. She is also passionate about access to education and the role the community college system plays in providing upward mobility for historically disadvantaged groups. The interview was conducted on February 8, 2022, by Alice Soteriou, Commissioning Editor of Regenerative Medicine. Keywords:
Cellino's mission is to make personalized, autologous cell therapies more accessible to patients. What inspired you to set up your company? Nabiha: Thank you for having us. We're excited to talk to you. I guess a good place to start is to mention that Marinna and I are both physicists and we trained at Harvard University, where we were developing new laser-based methods of perturbing and engineering living cells. It was an exciting time because we had the incredible opportunity to work with some brilliant biologists, such as George Church, Derrick Rossi and David Scadden, just to name a few. As we were doing experiments with them in the laboratory, they became very excited about the potential of the technology to bring precision to cell culture and cell manipulation. That was the original genesis of the company. We respect all our collaborators, therefore we had to take their advice very seriously about launching a start-up. That's how our commercial and entrepreneurial journey launched. Also, it's worth mentioning that Marinna and I never had any intentions of becoming entrepreneurs, but our story is an example of deep and tough technologies emerging in the most unexpected places. We were physicists looking to develop tools to help biologists, and because the biologists were so enthusiastic about our solution, they encouraged us to become entrepreneurs, and that's why we're here today. It's remarkable and more than anything we ever imagined. What were the challenges you needed to overcome when founding your company? Marinna: There were a lot of parallel efforts that had to be run in the early days. On the scientific side, we were doing CRISPR-based gene editing experiments with our laser technology. I was spearheading those, in collaboration with the George Church lab at Harvard. But, at the same time, there were also a lot of business development questions to be answered. We had our technology, but there were different business model options that we could have pursued. We could have pursued a tools-based business model where we sell an instrument and put it in other people's labs, we could have sold a service or decided to make our own cell therapies. So, Nabiha really took the lead on doing hundreds of expert and customer interviews that summer to narrow our scope and focus to understand what the most pressing problems were that we could solve with our technology. Something that is unique about this laser technology is that it's relatively biology- and application-agnostic, so there are a lot of different opportunities that we could pursue. We also wanted to have an experienced entrepreneur on our team, so we pulled on Matthias Wagner, a serial entrepreneur from Boston. He's built several successful optical companies in semiconductors and biology. He was a strong fit for the team personally as well, so Matthias became a co-founder and then we started to work together before we were in the same physical space. When we first started working, I was mainly in Harvard, Nabiha was out and about doing hundreds of customer interviews and Matthias was working in his basement building the alpha version of the laser scanning system. So, we embraced Slack, and Slack was what we used to communicate remotely. Even to this day, it's one of our favorite tools. It's allowed our team to work closely and communicate in real-time, even when we're all working remotely. I think that set us up really well to continue to be productive as a team during COVID. As international women's day is soon approaching, I was wondering if you could shed light on some of the difficulties you have faced as women in the field of biotechnology? Nabiha: Happy early International Women's Day! We're really excited to have this conversation with you. It's definitely worth mentioning that Marinna and I are used to being the only women in the room, given our training in physics where most physics programs are 20% women or even less. So that wasn't unusual for us. One of the stories I remember from my PhD days is having to ride the elevator between different labs, carrying lab samples between the optics lab to the nanofabrication lab. A lot of people who were riding the elevator with me would strike up a conversation asking, “what are you doing? What's in your container?” and so on. I would respond “well, I'm going to the cleanroom” or “I'm going to the optics lab” and there were a lot of surprised looks. “What, you're a physicist? Really?” These experiences really got me thinking about representation and its importance. When you look at pop culture, your stereotypical scientists are older white men with tufts of white hair. That image of scientists has evolved so much in the past decade or so, and scientists come in all shapes and sizes. I would say in my experience I'm extremely optimistic that things are changing. Of course, there's more work that needs to happen and now that I've been an entrepreneur for almost five years, I'm really starting to appreciate how so many industry veterans and academic leaders in the regenerative medicine space have stepped up to be wonderful advisors and mentors to me and Marinna and we've had a fabulous experience working with each and every one of them. They've played a pivotal role in guiding the direction of the company and the platform, so we are extremely fortunate. I wanted to mention some of them. There's a very long list: Chris Mason, Devin Smith, Kapil Bharti, Dan Shoemaker, Emile Nuwaysir, Bastiano Sanna and Claudia Mitchell, just to name a few of them. I find that so incredibly generous and wonderful. The other aspect of our journey that I'd love to reflect on is, as our team continues to grow, we're hiring many biotech industry experts. We recently hired George Harb, who joined us from Vertex/Semma. Furthermore, I continue to appreciate how leaders and experts in regenerative medicine are extremely innovation-forward. They're excited about what we're doing. They're excited to engage with us, and I've felt incredibly welcome in this industry, and I think Marinna feels the same. It really comes down to this shared mission of being able to make cell therapies accessible to patients at scale, and that optimism and enthusiasm carries us forward, giving us the energy to create paradigm shifts as an industry that will be very important to scale therapies for patients. Another aspect that comes to mind is the idea of paying it forward and helping other women in STEM. I think that's going to be extremely important for us in the next decade. One example of this is the Tory Burch Foundation. Tory Burch is a visionary fashion designer and entrepreneur and she is on a mission to support women entrepreneurs. Just last year, the foundation launched the First Genomics Fellowship in partnership with Jennifer Doudna, a Nobel laureate who discovered CRISPR. I was very fortunate to have been selected for that fellowship as the inaugural fellow and it's an amazing example of female scientists and business leaders coming together to support the next generation of leaders in STEM. Cellino's unique multidisciplinary approach combines stem cell biology, machine learning & laser physics. Could you tell me a bit more about how this combination of technology can be used to tackle the existing challenges in this field? Marinna: Some of the biggest challenges in this field are in manufacturing; manufacturing cell products reproducibly, to scale and in a safe manner where you have no unwanted residual cells remaining in the final product. And so, our approach that combines image-guided machine learning and laser processing is meant to automate a lot of these highly variable, manual processes. Image-guided machine learning is used to automate any processes involving human visual decision making; it can be used to characterize individual cells and colonies and track them over time to develop a deep understanding of what that cell is and whether it belongs in that population or not. If a cell is unwanted, we can remove it with the laser with single-cell precision, which is something that most people are not able to do in typical well plate-based processes or other closed systems. That specific ability to do label-free characterization followed by single-cell removal is unique to our technology. But at a high level, we are automating these manufacturing processes and that makes them more reproducible, more scalable and safer for patients. An example that I would like to give here is of the semiconductor industry. This is an excellent example of a time where they took complex processes that had multiple steps, and that were also extremely precise, down to the nanometer scale, and scaled-up manufacturing of semiconductors massively and successfully. The reason that was able to be done was because a lot of the processes used in semiconductor fabrication, both for manufacturing and characterization, are optical techniques. And optical techniques are very amenable to automation, so that's the approach that we're taking to cell therapy manufacturing. We're using these optical techniques, image-guided machine learning to characterize cells and laser processing to manipulate cells, to automate cell therapy development and manufacturing. These processes are highly amenable to automation and they're also compatible with a closed system, which is important for processing many patient samples at the same time in the same facility. Congratulations on recently securing $80 million in Series A financing led by Leaps by Bayer to autonomize AI-driven stem cell therapy. What are your current plans around AI-driven stem cell therapy now that this funding has been secured? Nabiha: Thank you. It was very exciting to have the chance to work with the Leaps by Bayer team, and the round was also co-led by 8VC and Humboldt Fund, a fantastic group of investors we get to work with. This series is all about building our technology and automating all the pieces that need to be automated for clinical manufacturing. So, our main focus is to build the machine learning-based laser processing protocols to manufacture both stem cells and derived cells with greater precision and being able to do selected expansion of our target cells in real time. We are also in parallel developing the closed cassette approach to manufacturing that can effectively select and enrich for the target cell types. The other aspect of this Series A that I'm extremely excited about that Marinna is spearheading is a long-term collaboration with the Kapil Bharti Group at the National Institutes of Health (NIH), specifically the National Eye Institute. We're also building capabilities for low-volume GNP manufacturing to support partners in their upcoming clinical trials. Another aspect worth mentioning is that we are actively recruiting. The team will grow to about 50 people and we're hiring across stem cell biology, automation and machine learning. Receiving funding can be a major challenge for smaller companies. Could you tell me about any difficulties you may have had previously in receiving funding & how you overcame these? Nabiha: Yes, that's a fantastic question. I'm happy to share my thoughts. We met The Engine, which is a venture fund that came out of MIT just a few months into our journey very early in 2017 and they made it incredibly easy for Cellino to get started by giving us our first check and lab space. The Engine's model is to support scientists turned entrepreneurs in their ambitious early days of getting a tough tech venture off the ground and honestly, I'm not sure we would be here today without their early support. So, thank you Ann and Katie, the two general partners at The Engine who launched us. And of course, there's a theme there of women supporting other women. I think it's phenomenal. Having The Engine as a support system in our early days gave us several years to really explore product-market fit in depth and in collaboration with key opinion leaders in the industry to build a technology that solves a real problem for regenerative medicine. I think that was an absolute privilege. We're very, very grateful and once we had those early years of prototyping, the next step in our journey was to make that jump to raising larger rounds of financing to continue to build and scale our technology. In that moment, I was very fortunate to build a strong relationship with Khosla Ventures and Humboldt Fund. Khosla Ventures is out in California and the Humboldt Fund is a family office out of South America. By building a strong group of investors in the early days of Cellino, the financing rounds so far have come together with increasing momentum. That really helped get this Series A together very quickly, which I was very grateful for. My advice in general to founders is to find your allies in the investor world early in your journey. It takes a lot of effort because there are many different kinds of people in the world and who work in venture capital. But you just need at least one relationship to be a foundational relationship that helps you grow and build your network and build your narrative. I also realized that I built friendships and relationships with investors that maybe I wouldn't have expected on the surface, so I also encourage founders to explore all possible avenues because you never know who you will build a connection with and who you have a shared experience with. It's very important to talk to many different types of people in the early days to see who you connect with. As Marinna mentioned, I have this philosophy of talking to hundreds of experts. So, for example, when we're interviewing or trying to hire for a role that's very difficult to hire for, I will contact hundreds of people and experts on LinkedIn and do that very proactively. Being proactive about building my network from the very early days has paid off so incredibly, and it's not something that is easy. It takes a lot of energy, but it's such a good investment because you just don't know how those early relationships will pay off in the long run. What do you think are the key milestones that this field will have to reach before personalized autologous cell therapies become more accessible in the clinic? Marinna: The biggest challenge in personalized cell therapies is manufacturing these cell products in a reproducible, consistent, scalable way. A lot of the current processes are highly manual, highly dependent on a skilled operator and very expensive to manufacture. So, automation, advancements in manufacturing technologies and making sure that cell therapy developers have access to those advanced manufacturing technologies are all going to be very important to making personalized cell therapies more accessible. On the regulatory side, a standardization of regulatory expectations and guidelines would go a long way in strengthening this industry as well. Right now, the standards for what defines a high-quality or good iPSC are being set collaboratively by experts in the industry, such as Stephen Sullivan at the Global Alliance for iPSC Therapies. But we're going to reach a point, and the sooner this happens the better, where the experts have reached a strong consensus in terms of how iPSCs should be characterized and defined. Then, those experts will need to work closely with regulatory agencies to ensure that those definitions become standard across the globe. How do you think the field of regenerative medicine, particularly cell therapy, will evolve in the next 5 years? Marinna: I think we'll see an exponential increase in the number of personalized iPSC-derived cell therapies that enter clinical trials. We'll have additional safety and efficacy data for those iPSC-derived cell therapies, which is very important. Up until now, most of the data that we've seen have come from landmark single-patient studies, in both Japan and the USA, transplanting iPSC-derived retinal epithelial cells or iPSC-derived dopaminergic neurons. Now, we're starting to see the initiation of phase I/IIa clinical trials with a larger number of patients enrolled, and the vast majority of these initial clinical trials will begin phase I/IIa with a cell product that was manufactured using the more traditional manual techniques. However, in parallel to those early-stage clinical trials being run, advanced manufacturing techniques like those we're building at Cellino will continue to evolve. These advanced manufacturing techniques will be necessary to push clinical trials into the later stages, such as phase III, where for a Parkinson's trial, for example, you might be transplanting into 400 patients. I also think in the next 5 years we might see the first iPSC-derived cell therapy product cross the finish line in terms of getting regulatory approval. Cynata's iPSC-derived cell therapy should just about be in phase III right now, and that would be a huge, remarkable milestone for the industry. Interview disclosure
The opinions expressed in this interview are those of interviewees and do not necessarily reflect the views of Future Medicine Ltd/Future Science Ltd/Newlands Press Ltd.
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