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Conversation with Cellino founder Nabiha Saklayen

During the holidays, Alex Morgan, Partner at Khosla Ventures, sat down with Nabiha Saklayen, CEO and co-founder of Cellino, to learn more about her and the company.  Cellino has a unique technique technology for AI-guided laser editing of stem cells for personalized therapies. The company’s goal is to make autologous stem cell manufacturing scalable for the first time.  What follows is a transcript of that discussion.

Alex Morgan:

I know you’ve lived in many countries. Can you tell me a bit about your background and your life before graduate school?

Nabiha Saklayen:

I had a nomadic upbringing. My father was a foreign service officer for Bangladesh. However, I was born in Saudi Arabia. It was normal to be living in a different country and speaking a myriad of foreign languages, Bengali at home and English at school. We moved to Germany when I was six, where I learned German. I moved to Sri Lanka for high school and then the US for college. I’ve been here ever since. 

Alex Morgan:

My understanding is you lived in Sri Lanka during a troubled time. Can you tell me about that?

Nabiha Saklayen:

We moved to Sri Lanka in 2004, the year the tsunami hit South Asia. Over 200,000 people died in about a dozen countries. We lived in the capital, Colombo, which wasn’t hit hard, but the rest of the country suffered a tremendous loss. The fallout from the tsunami triggered a resurgence of the civil war. We went from living on a peaceful island to being in the epicenter of a war zone. There were suicide bombings in my neighborhood every week. Dinner table conversations were somber. There was a real possibility that something terrible might happen to us, and we may not come home the next day. I decided to channel all my energies into academics, and it paid off. I graduated top of my class and received a full scholarship to attend college in the US. It was a transformative phase of my life. I learned for the first time that if I set my mind to it, I can do anything.

Alex Morgan:

In very trying circumstances.

Nabiha Saklayen:

Yes, in very trying circumstances. I also taught English at a girls’ orphanage for tsunami victims at the time. It was the most rewarding role I’ve ever had. It helped me develop a strong sense of wanting to impact and be the best version of myself.

Alex Morgan:

You started engaging with physics at an early age. What excited you about physics?

Nabiha Saklayen:

I was obsessed with space and the universe growing up — that’s how I found my way to physics. I also found physics to be more challenging than most subjects. That appealed to me because I enjoy a challenge. Thankfully my mom supported me whole-heartedly. She was the first woman in her family to go to university in Bangladesh and has been an elementary school teacher for thirty years. She is my biggest role model and the reason I am who I am today.

Alex Morgan:

For a while, I was obsessed with Richard Feynman, like many people who study physics. I taught myself multivariate calculus from the second volume of the Red Books.  Even now I will sometimes give people the book Surely You’re Joking as a present. Do you have any science role models like this?

Nabiha Saklayen:

Yes, Marie Curie! She was a physicist, chemist and won two Nobel prizes. I admire many other incredible physicists: Max Born, Max Planck, Heisenberg, to name a few. To me, the most exciting time in fundamental physics has passed, about 100 years ago. For my generation of physicists, the most compelling specialties are string theory, quantum physics, particle physics, and biophysics. I decided on biophysics.

Alex Morgan:

Let’s explore this a little bit. How did you decide which graduate school and lab you wanted to join? 

Nabiha Saklayen:

If I were to pick a discipline based on my intellectual curiosity, it would be particle physics. However, I decided to study biophysics to be closer to real-world applications. I chose Harvard University because the physics program offered a lot of flexibility. I joined a laser physics and nanofabrication lab. That’s when I started to engage with many brilliant biologists. I learned about a significant need in biology to deliver cargoes into cells, such as gene-editing tools, DNA, or RNA. It’s not easy to deliver something into a cell while keeping it healthy and alive. 

Alex Morgan:

Tell me more about your research.

Nabiha Saklayen:

The laser-based delivery techniques I invented during my Ph.D. combine pulsed lasers and patterned nanosurfaces. When you shine pulse light onto the nanosurface in a liquid environment, you create vapor bubbles. The bubbles open up transient pores in cells for materials to diffuse into the cytoplasm. Larger bubbles can kill unwanted cells. This light-mediated method allows scientists to pattern cells with precision, to either deliver cargos or remove unwanted cells, making it a versatile tool for bioengineering.

Alex Morgan:

Using light-mediated editing and targeted delivery of transcription factors or CRISPR components, you could, in theory, print out a sheet of personalized cells where you control the differentiation and state of each single cell. At Cellino, you did a proof-of-concept demonstration of patterning by delivering different cargoes to adjacent cells. Is that a fair way of describing it?

Nabiha Saklayen:

That’s correct. The Cellino laser platform can remove cells or deliver payloads into them. Having single-cell processing capability opens up the possibility to generate complex cell systems in 2D. At Cellino, we can take an image-driven approach to cell editing – which has never been done before — enabling scalable cell manufacturing for many different diseases and applications. 

Alex Morgan:

There’s often a phase in graduate school where there’s a long period of things just not working. Was there a critical moment when you suddenly said, “this is going to work”?

Nabiha Saklayen:

The femtosecond lasers in my lab were a decade old and made it impossible to get reproducible results. I seriously thought this was the end of my Ph.D. project. Luckily, my team and I realized that it should be possible to get bubble formation using longer laser pulses. When I suggested the idea to my advisor, he said, “it’s never going to work. You shouldn’t waste your time on it.”

I’m glad that I didn’t listen to him. I borrowed a laser from a different lab, and the results were shockingly good. That’s when I knew my Ph.D. would work. Nanosecond lasers are much cheaper, and it makes this technology scalable.

Alex Morgan:

The crucial part of this story is that now we have a scalable technology. Cellino could enable a world where every hospital could have a system that takes a patient’s blood sample to produce a collection of differentiated cells for therapies. This brings me to autologous therapies, where you take cells from an individual, personalize them, and re-introduce them back as a therapeutic. The best example is in immuno-oncology, where a patient’s cells are re-engineered to fight cancer. But there are a lot of other possibilities in regenerative medicine. What are some of the challenges in developing autologous cell therapies, and how is Cellino addressing them?

Nabiha Saklayen:

In general, autologous therapies are safer for patients because they do not require immunosuppression. The next iteration of cell therapies would use patient-specific stem cells banked ahead of time. Anytime a patient needs new cells, such as blood cells, neurons, or skin cells, we would generate them from a stem cell bank. 

Today, patient-specific stem cell generation is a manual and artisanal process. A highly skilled scientist sits at a bench, looks at cells by eye, and removes unwanted cells with a pipette tip. Many upcoming clinical trials are using manual processes to produce stem cells for about ten to twenty patients. 

At Cellino, we are converging different disciplines to automate this complex process. We train machine learning algorithms to characterize cells before our AI-based laser system comes in and removes any unwanted cells. By making stem cells for every human in an automated, scalable way, our mission at Cellino is to democratize personalized regenerative medicine. That’s why our vision statement is “Every human. Every cell.”  

Alex Morgan:

The company is working on generating iPSCs in a fully automated manner. Let’s talk about some of the more complex tissues that Cellino might engineer, for example, making a cochlea or a retina. 

Nabiha Saklayen:

Let me talk about the retina example. The retina has about ten layers, but three layers are essential for cell therapies: the retinal pigment epithelial layer, the photoreceptors, and the retinal ganglion cells. Each layer would be useful as a transplant for a different degenerative or genetic disease. It would be possible to differentiate the different retinal layers on the Cellino platform in an automated, closed system. Those three layers could also be stacked together in an “artificial retina.” Vision loss is a significant burden on patients and being able to address that would be phenomenal.

Alex Morgan:

The retina is derived from the same germ layer as the brain. Can you talk a little bit about what you’ve done with neurons, and have you been able to create those with the Cellino platform?

Nabiha Saklayen:

There are a lot of exciting things happening in the neuron space. We worked on dopaminergic neurons, which would be a therapy for a Parkinson’s patient. We used CRISPR activators to shorten the differentiation timelines by about half.

Alex Morgan:

Besides creating cells for therapy, we could also take a patient sample and create many different cell types or organoids to discover small molecule or biologics-based medicines. Can you talk about what is possible?

Nabiha Saklayen:

Right now, the industry norm is to test conventional drugs on animal models. However, those results don’t always match patient outcomes—the industry is moving towards using organoids and human-on-chip models. However, nobody has taken a personalized approach yet, where the cells are created from patient samples. 

Alex Morgan:

Therapies are becoming more specific to humans, where animal models aren’t very good, and sometimes very personalized and focussed on specific genomic features unique to an individual.  I think that’s an exciting direction for the company and might unlock a lot of innovation. It could be possible to create a 2D personalized homunculus to screen drugs, with personalized liver cells, retinal cells, or a little kidney model, and you can test a drug in cells from the individual whom you want to treat. 

Nabiha Saklayen:

We’re very interested in enabling the drug discovery, organoid, and organ-on-chip industry down the line. We could think of creating a human homunculus with ten or twenty different cell types to test a range of drugs for a specific patient. There’s a strong possibility that if we push down this path of personalizing drug screening, we start to democratize more traditional medicine as well.

Alex Morgan:

The company is actively working on the automation capability to build robotic systems that can produce cells at scale. Is that correct?

Nabiha Saklayen:

That’s our focus for 2021 and onward. Our goal is to produce autologous iPSCs at scale. 

Alex Morgan:

Let me step back for a moment and talk about your transformation from an academic researcher into a biotech entrepreneur. That transformation has been rapid over the past couple of years. How was teaching in graduate school, and does that relate to anything you now do as a leader at your company?

Nabiha Saklayen:

I taught an intro physics lab for pre-meds. I enjoyed it a lot. My mission is to share our story and science in a way that’s easy to process and understand. Even within the team, we spend a lot of time training to communicate effectively as a team and with the external world. 

Alex Morgan:

Part of storytelling that you certainly experienced is going out to pitch and raise money. Can you tell me a little bit about that experience and what you’ve learned?

Nabiha Saklayen:

The storytelling aspect evolved a lot from my Ph.D. days. Now I get to talk more about why this science matters for regenerative medicine and patients. I also talk more about my own story, which I never did in graduate school. The investors I connect with all want to build companies that improve patient outcomes and decrease healthcare system costs. It’s rewarding to work alongside investors and think about how we can change regenerative medicine. 

Alex Morgan:

Is there any advice that you would want to give to a graduate student or postdoc thinking about translating their work into a company?

Nabiha Saklayen:

I recommended building a strong founding team with complementary skills. The second piece of advice is not to be super attached to your original Ph.D. work. The core concept of applying lasers to cells still exists at Cellino, but we do it differently, and we do much more beyond that. So keep an open mind!

Alex Morgan:

I mentioned Richard Feynman before, and he wrote a piece in the late ’50s, “There’s Plenty of Room at the Bottom.” Cellino’s technology can modify and address individual cells adjacent to one another. This could potentially be a way to create “bio-nano machines.” Have you thought at all about what we might do, and if this is possible, and where we might go?

Nabiha Saklayen:

I have, thanks to synthetic biology being at such an exciting place today. Like CRISPR or CRISPRa/i, most synthetic biology tools can be merged with the Cellino platform at the single-cell level. Layering on different modalities with single-cell precision and creating intricate mosaics is a powerful concept. We could even think about intentionally making different circuits of cells on a plate, mixtures of neurons in muscle cells, or artificial cochleas in a dish with intrinsic mechanical properties. Cellino is excited to be building parts of the toolkit that will realize these futuristic concepts.

Alex Morgan:

Are there any other things you want to share about the technology or the company we haven’t touched on?

Nabiha Saklayen:

The only way to achieve meaningful progress towards scalable stem cell manufacturing is to interweave normally disparate fields towards a single mission. I’m proud to have built and attracted a diverse team at Cellino – a world-class, multi-disciplinary team of physicists, computational biologists, machine learning scientists, and engineers, and take them on this journey with me. When you look at the fabric of the company, everybody is unique and different. 

Alex Morgan:

Well, that’s fantastic. I certainly look forward to seeing how the technology, company, and team evolves over the years ahead. Thank you for talking to me, and I hope you have a great 2021.

Nabiha Saklayen:

Thank you, Alex, you too.