The Biotech Pulse S1E4 - the role of biotech as the ‘discovery engine’ for pharma

An edited transcript of the podcast follows below.

Dima: Welcome to “The Biotech Pulse” - a Forbion podcast. My name is Dmitrij (Dima) Hristodorov I am a General Partner at Forbion. In this episode of the podcast we will discuss the role of biotech as a discovery engine for pharma in a high risk area of research and development. To do that we will feature one of Forbion's portfolio companies called Seamless Therapeutics which is active in the area of gene editing. In that context, we will discuss multiple topics, including the history of Seamless, the role of biotech within the pharma ecosystem, and where gene editing and specifically Seamless is sitting.

We will learn from Albert and Felix, my two guests today, how to best grow a biotech from a small startup to a globally acting company. With that a very special welcome to Albert and Felix. To start the conversation, Albert and Felix, I would like to ask you to introduce yourselves and tell us a little bit more how you got to work with Seamless.

Albert, welcome.

Albert Seymour: Thanks so much Dima and it is a pleasure to be part of this Forbion podcast. Albert Seymour, the President CEO of Seamless therapeutics, just recently joined as of February of this year. Prior to that, I was President and CEO of Homology Medicines, which was another genetic medicines company where we were developing AAB based products to treat a variety of rare genetic disorders. Before that, I was head research at Shire Human Genetic Therapies, and then really cut my teeth, if you will, on the pharmaceutical industry with more than 14 years at Pfizer. I am a human geneticist by training, and I have always used that science as my north star from a career on how I wanted to take the applications and knowledge of human genetics and bring therapies to those patients. And so it is a pleasure again to be on this podcast and I look forward to the discussion.

Dima: Thanks for joining.

Felix Lansing: Tthank you very much, Dima, for having us on “The Biotech Pulse”. I am Felix Lansing. I am the CTO of Seamless Therapeutics. I have a PhD in genetics and genome engineering. I started working with the technology we are using now in Seamless since 2017. I am also co-founder of Single Therapeutics . I am happy to share my insights on how we grew Seamless from founding in 2022 until now.

Dima: That sounds great. So before we get into the details of the technology and how Seamless is going to change the treatment paradigm for many diseases, Albert, it would be great to hear from you. How you would describe the differentiation of Seamless compared to other technologies, other companies that are out there in the similar space, and how you plan to make a difference for patients on a product level as well.

Albert Seymour: So when we think about bringing treatments to diseases, most of them are due to variance or mutations within the genomic DNA. And so, we need a technology that we can apply to correct those different mutations. However, there is a challenge in the field in that these mutations are numerous, and so within a population, you may have multiple mutations. And so we need a technology that can come in with a single molecule and address all of those mutations. And that is one key component that Seamless brings that really differentiates it from others. We can take advantage of these recombinases or these enzymes that are naturally derived, and you will hear a little bit more about that from Felix in a minute. These enzymes we can program so that they can go in, find certain regions of the GENA , and make what we call large edits. What I mean by that is that you may have a span of a gene that has different mutations in it across different people. We want to be able to correct that with a single one across everybody. So that is one unique pillar, if you will, of what Seamless can bring that others do not, these large edits. The second, and I think a very important part, is as we go in, we want to modify or correct the genome. We also want to be sure that we can predict what that modification will be at the DNA level. The basic principles and properties of these new enzymes that we are developing, allow them to make these changes in the DNA that are not dependent on the DNA's normal DNA repair or the cell’s DNA repair machinery.What that allows us to do is to make these changes predict what they are going to be, and then they are seamless. What I mean by that is, if we want to put in a series of nucleotides or a DNA molecule, we see it right to exactly what we want to put in. We do not see any unwanted or carry mutations within that side of entry. So those are, I think, two key themes: large edits, and truly seamless predicting what we are doing to the genome. That is, I think, a big foundation and hallmark of how we want to apply the differentiated technology of Seamless.

Dima: That sounds quite sophisticated. Thanks, thanks for these. Felix, Albert already promised that you will tell us a little bit more about your recombinases. So ,maybe you can explain to our listeners why only Seamless can leverage those enzymes and not anyone else, because these enzymes are obviously naturally occurring, and everyone would have access to those. So what is the special trick that you apply to make them usable for therapeutic applications.

Felix Lansing: It sounds very simple to answer, but it is not. I will try to find the right words here. So, recombinases are modifying a given sequence in the genome. However, that sequence does not exist in humans, so we do not have it in the human genome. What we need to do is to teach these enzymes to recognize that sequence or a specific sequence in the human genome. We do so by breeding these enzymes. So it is really an evolution that we are doing with this enzyme that allows us to teach it step-by-step to recognize a sequence of choice, and this combines our directed evolution platform protein engineering, but also deep learning, that we then bring together to reprogram recombinases for a given sequence in the human genome to then allow the therapeutic application of the recombinants.

Dima: It sounds like a lot of know how sitting in the company. So very good. Albert, I was curious, you know, to see that in the in the mix of gene editing companies, if you look back the last 10 to 15 years the first gene editing company from one of the first being CrispR Therapeutics founded in 2013, right? So a little bit more than 10 years ago, most of these companies remained unsold. If you look at the ecosystem of the biotech, which is really investors, biotech and pharma, why is there no transition from biotech to pharma? Why is Pharma not buying into this concept yet and not being aggressive in terms of acquiring those companies? Do you have an idea of why that could be?

Albert Seymour: It is a fantastic question Dima. I think it is just if you look at the history of the pharmaceutical industry as a whole, I think some of its starting to make sense. A lot of pharmaceutical industry, particularly big Pharma, started as chemistry companies. o they were got very familiar with small molecule medicinal chemistry and made huge strides in bringing therapies, transformational therapies to patients to address a lot of un-met medical needs. That's what they were really good at and so you could see that as they were building only small molecules. One of the things that big pharma then likes to look at is if it is a new technology. So really expanding off what what Felix had just gone through, about how him and his team can take these recombinases and engineer them to go to a specific site in the genome. That is a lot of very unique know-how within the small biotech company. So Pharma likes to allow those small biotech companies to work within the investment community to really develop and validate that, because it has got a tremendous amount of potential, but it still needs a lot of work, and with respect to developing it, and then ultimately validating it within a clinical setting that comes with all of that. Not only just the science, but how do you manufacture it? How do you run the clinical development programs to get that validation? It is at that point that big pharma comes, can look at it and say this is probably something. A great example of that. If you go back several decades is the acceptance, if you will, or internalization of antibody technology. So for a while Big Pharma was not in antibody technology. So they really let these small biotech companies that were developing unique novel antibody technology because the thought was at the time these are large molecules, how could you possibly manufacture them to treat at the scale that that big pharma would treat with these large common diseases? What you saw that it was biotech driven, they would get to a certain point that would show they would validate it clinically.

Then Big Pharma started to pay attention, first through partnerships, and then as the as the technology matured, not only the science and the technology to make new antibodies that go to different targets, but also how to manufacture, because the early manufacturing of biologics that are more complicated was very challenging. They had to work not only on the on the molecule, but then how to make the molecule consistent once all that came to fruition? Then you saw Pharma start to bring it in into that. I think that's how we are the same, I kind of look at it similar for the whole genetic medicine space, We are more at that inflection point where antibody companies were, say, several decades ago. We are now starting to see from a gene therapy perspective around AV. We are seeing multiple programs that have been approved. Then as you had mentioned, the very first gene editing. So they have now started to crack, not only how to develop the technology, get it into clinic show that it is validated, but how to manufacture it at scale and consistency, so that they can then start to distribute this to the patients worldwide. So it is a fantastic time to be within the industry, because we are at that initial inflection point around genetic medicines.

Dima: Right that makes a lot of sense. It is as you said, it is overcoming the initial visitation on a new modality plus showing that you can execute right on your ideas and bring it to a product level rather than to a scientific ideal level. So fully agree, and as an investor at Seamless, I will not challenge you on that right, and we will see this transition very soon as well.

I will switch gears now a little bit Felix back to you, and would like to understand a little bit more your personal journey as an as a young entrepreneur. I am pretty sure your story serves as inspiration to many young scientists just entering the field. I think it is fair to say that you have a couple of things under your belt already. you have a very successful scientific career: published in highly ranked journals, you have co-founded Seamless, you attracted investors and raised about 25 million US Dollars so far. Now, with Albert and more new colleagues on board on the US side you are also pivoting towards a globally acting biotech company. So maybe you can share a little bit of your feelings, impressions, experiences during all those years. The excitement and disappointments - Everything is interesting and we can learn from your experiences.

Felix Lansing: I still wonder how this all came together in the end. But when I started my Ph.D., I definitely did not have the idea of making a company but I think at the end of the PhD I realized that we had a platform in hand to reprogram recombinases. When thinking of that, the team and I that were developing the platform, we said this knowledge we gathered over the last years, and this hard work we put into this platform, we need to try to generate value not only for us, but also for people with severe diseases. So we realize that we have something very unique in hand that could be become a company. So first thing we did is or basically I did, is to try to make a story out of it that is also appealing for investors. So we went to different pitching events and business competitions, and it was great to see that not only we are thinking this is a good platform and a good idea to bring this technology to patients, but also investors. Eventually we were able then to convince Forbion and Wellington partners to invest in Seamless. From there on it went very quickly. Only just after more than a year we have roughly 30 employees, and, as you said, we now have operations in Europe and in the US. I am also very happy that we could convince Albert to join Seamless. I think his expertise is really leveraging what we started - to bring this technology to patients.

When it comes to excitements and disappointments there are many along the way. I think the first biggest excitement I had was also during the PhD when I realized we can use recombinase to move specifically 140,000 base per fragment in the genome that is causing a disease. Then on the other side, what was very exciting, that it is not only us seeing the potential of recombinases, but also the investor community. Then, definitely when the investment was signed this was a very big excitement. Also during that whole journey there are a lot of disappointments. I think the biggest one for me as a very focused person that likes to having a plan is that nothing happens as it is planned. So I think really that journey taken together. This it is a great experience I have had, but also the disappointment of making a good plan trying to execute, but it does not go as you plan. I think that is one thing I took away is the big learning.

Dima: That is a very good lesson, and I think that is why we have Albert on board now to help us execute according to plan. Albert, with you joining there is a lot of hope and promise that Seamless, and also the Board of Seamless can piggyback on your previous experience as well. For you it's not the first time building a company. It is not the first time building a genetic company. Actually so, tell us a little bit more about your feelings now joining Seamless a very young startup. Is it just press repeat and do the same? Or is it the new challenge? Also, maybe reminding that you are dealing with two different cultures, Germany and US. Curious to hear your thoughts.

Albert Seymour: I really like this question Dima because, as I thought about it, Seamless brings a variety of aspects that I really like. So it will not be press the repeat button. The reason for that is that we have learned in every single experience what works and what does not. So what we can do is take some of those lessons where it does work, apply those and where it did not work, try to learn from that and mitigate some of those risks going forward. I will say, with the experiences, particularly at Shire and at Pfizer, these were multi country organizations. So that is one of the components that attracted me to Seamless because of the German site. If you take that, you are building this biotech you have got a core set of expertise in Dresden, Germany, with Felix and his team that really understand the enzyme. that is a key component, because without that you could not build the genetic medicine company around recombinases. Then coupling that with that there is an unmet medical need that that requires this kind of technology. So taking the team in Dresden, building a team in the US that all are rowing in the same direction because it will require a lot of focus. As Felix had alluded to sometimes plans change, and that a lot of that is driven based on data as we accumulate. So if you have a team with the expertise and the experience that can pivot quickly, understand that what we are seeing with the data and makes decisions based on that, I think we can be very successful as a team. So it is really what I have learned is having a great technology is one thing, but then coupling it with a team, that is all rowing in the same direction. So the people are probably more important to see that execution and translation part. That is the component that I want to work with the group. It is not just me. It is the whole team in order to move this company to the translational space.

Dima: I would like to follow up on exactly that point. So you mentioned, you need to have a great technology. You need to have a great team. What else is in front of you as a hurdle that you see to make Seamless successful as a company and successful can mean getting closer to an efficacious and safe product and getting closer to become attractive for a bigger part of it.

Albert Seymour: 100% because when you think about what is required for a company, especially a small company, we cannot do it alone. It requires support from investors like Forbion so that we can continue to bring value to our investors. It also that we are developing this. We have a mindset to reach out and understand. So some of the challenges that we may face as a small company. I think we can develop the technology and get it to a point, perhaps to file an IND or a CTA. But then, as we think about clinical development, the challenges or manufacturing, we have to reach out to partnerships and that and as you know the investment required the further you go along increases over time. Having partnerships with whether it is Pharma, whether itis other biotech is going to be a critical component to the success of a company, like Seamless.

Dima: Felix is there anything on the technology on the science side that you see as a key level for yourself and for the for the company. I am sure you have a thousand ideas of what to improve here, you are never happy with what you have, but what is the key hurdle that you see that we need to solve?
Felix Lansing: I think when it comes to translating the technology to really treat patients, we need to get the enzymes to the cell of interest. Definitely, we are the experts on recombinases and reprogramming them, but we need to also leverage the expertise that is out there in the delivery space. So, can we combine our technology with a given delivery technology to bring the enzymes or reprogram recombinases to the set of interest to then do the correction of the genetic defect? I think that will be a key hurdle to take to really identify for the right indication the right delivery to bring together those 2 technologies to then really make a change for the for the patient.

Dima: So we have almost reached the end of our podcast, and we probably could have kept going like this for another hour, but we would like to conclude with a question that we ask all of our podcast guests on the Biotech Pulse. The question is, what advice did you receive in the past, or do you wish you had received that you would like to share with our listeners.
Felix, we will start with you.

Felix Lansing: That is a very good question. I think for me personally, advice I got was that you once you have an idea, and you want to pursue it you need to do it. Otherwise, you will never know if it works, and you will be frustrated, maybe in the future because you have not done it. I think that this is not only what drove me scientifically to pursue really an idea in this case a reprogramming recombinases, but also this holds true for building up Seamless. I think if I would not have been encouraged by that advice to really try to build Seamless it would have maybe not happened. And I am very happy that I got this advice. And really to all the listeners, I can just advise you to pursue the idea you have. If you are convinced, and you can sell it this way, then you will convince others, and I think that is the advice I want to give.

Dima: That's great. Thank you, Albert.

Albert Seymour: Yeah, thanks Dima. That was fantastic advice, Felix. I think that you can keep that with you well throughout your whole entire career because there are so many opportunities. I think one of the things that I would like to tell listeners is that when we think about building companies around these novel technologies, these platforms that have tremendous potential at the beginning. You can look at it and say there are so many things we can do, bBut to truly translate it I think requires two things. One is a real focus on where you think the biggest value is that you can move and progress to translate it into a therapy. So it is that big bump going from great technology to a therapy and so maintain that focus. Obviously, let the data tell you where to go, but maintain that focus as you do. Then the second, it is probably the more important, is building a team that you know all row together. They understand the focus they are continuing to go, and they are always asking themselves, what can I do to help the program versus what can I get out of this personally? I think that really helps pull teams together, that they are always asking, what can I do to help in order to pull that, and it makes it take a challenging opportunity and makes it fun.

Dima: Thank you for sharing these lessons. And also thank you for sharing all your thoughts on the gene editing space, and sharing with us what Seamless is about, and what the future might hold for Seamless. I can as a shareholder and board member of Seamless summarize that we are extremely excited about the future of Seamless and what Seamless can bring for patients.

As you know, one of the key investment criterion for Forbion is to impact the future of medicine, to impact lives of patients, and we truly believe that seamless is on a good way to achieve exactly that. Thanks for joining me today and I would like to invite you to provide any final closing statements for our listeners. Albert, maybe you want to start.

Albert Seymour: Thanks, Dima. It has been a pleasure. I think the past 30 or so minutes has really been interesting from my perspective as well. And again, we are very excited about the potential future and success of Seamless. I look forward to coming back on future podcasts as we continue to progress this technology.

Felix Lansing: Thank you very much. I can just agree with Albert, it was a pleasure speaking with you, also great questions. I really am looking forward for the future of where Seamless Therapeutics is maybe in a year from now. So happy to work to continue working with you and Forbion.

Dima: Thank you, gentlemen. Dima: I hope you enjoyed listening to "The Biotech Pulse" - a Forbion podcast, I am Dmitrij Hristodorov, General Partner at Forbion, and I have been discussing a pioneering gene editing approach based on recombinases with my guests Albert Seymour and Felix Lensing, who are currently CEO and CTO of Seamless Therapeutics. Do not forget to follow "The Biotech Pulse" wherever you get your podcasts, and remember, you can also access the podcast directly on our website, forbion.com. That is all for now. Thank you for listening and goodbye.