Scenic Aims To Move 'Genetic Modifiers' Science Forward

Co-founded by Sebastian Nijman and Thijn Brummelkamp in 2017, Scenic Biotech is a spinout of the Netherlands Cancer Institute and Oxford University. It was established with a focus on identifying genetic modifiers, or genes that suppress or block the disease-causing effects of a mutated gene in the body. In Vivo spoke with incoming CEO Oscar Izeboud about the company’s next steps, and the potential for genetic modifiers to address unmet needs in the rare disease space, and beyond.

Source: Scenic Biotech

Scenic Biotech CEO Oscar Izeboud

For the past 15 years, Oscar Izeboud worked in corporate finance, conducting equity research and then managing M&A and equity capital market transactions in life sciences at Kempen & Co, a Dutch merchant bank, before joining NIBC Bank as managing director of corporate finance, capital markets. But it was during his earlier experience at
Crucell N.V., a Netherlands-based biotech acquired by Johnson & Johnson in 2011, that he “really started to enjoy the combination of science, licensing, capital markets and growing a company.”

In July 2020, Izeboud joined Scenic Biotech as CEO. A return to the biotech sector was “always part of the plan.” Izeboud was impressed with Scenic Biotech’s founders, especially their combination of academic strength and entrepreneurial success. In Europe, academics tended to stay in academia, said Izeboud, but in the case of Nijman and Brummelkamp, they had already founded – and sold – Haplogen GmbH, a genomics platform company focused on haploid cells. In starting Scenic Biotech, Nijman and Brummelkamp “had assembled an interesting group of people around themselves, but they wanted a CEO to bring it to the next level. To me, it was like a homecoming,” said Izeboud. In an exclusive interview with In Vivo, Izeboud discussed Scenic Biotech's approach to partnering, communicating with regulators, disease targets in the pipeline and conducting preclinical research during COVID-19. 

In Vivo: As an early stage biotech company, what are your primary short term goals?

Oscar Izeboud: In biotech, in the absence of cash flow you need news flow. And you need validation for your start-up company. With respect to validation, I think the science is great, the publications are great, but it would definitely help in the short term to have some industry validation, so we're working on business partnerships. And it always helps to put the company on the radar for a new group of investors. Business development is one of my key focus areas now. The other focus is on people. We have so much work to do, we need to hire a lot more people, so the visibility of the company is important. We are developing some structures, but also starting to think about the medium term, things like VC exits – not now, not tomorrow, but in a few years. In the short term the focus is on business development, and the medium term focus is on corporate development. How are we going to develop the company further and what would be the way forward? How can I also take into account the needs of the VCs for management here?

What is your approach to partnering, and what kinds of partnerships are you exploring?

There are two ways to look at it. First of all, currently with genetic modifiers, we do rare diseases, and we have an oncology program. I think that's a lot for a young small company, so we need to focus. There are several reasons to consider partnering, for example you may consider one program or therapeutic area to partner, which allows you to focus on the other, and use the proceeds you make from the partnership. That could be one reason. The other thing I've learned working over the years in the biopharma sector is typically the large indications are heavy lifting for a small company. With large indications, you typically partner with big pharma or a big biotech firm, but you can have niche indications that allow you to go the whole way, from discovery to clinical and beyond. This is what I will focus on. If you have a partner with muscle in rare diseases, you can go much further in that area. These considerations will determine the type of partnerships we establish in the shorter term.

Targeting genetic modifiers to treat diseases is an intriguing and relatively new science. Can you describe the concept and also the company’s proprietary Cell-Seq platform?

Siblings provide a good example – not twins but siblings. There are quite a few diseases where a brother and sister have a very similar genetic makeup, but the brother, for example, doesn’t develop a disease, and the sister does. Why is that? Similarly, we see differences in genotype and phenotype, for example you have two of the same flowers, both identified as brown. But when I plant one flower in America it becomes blue, and when I plant the other in the Netherlands it becomes yellow. The hope was that the genotype was the gene, and the phenotype was the environment, which determines the color. But it is not that binary. It's way more complex. So, you can switch on a gene, but there's a whole genetic structure around it that includes these modifier genes. One gene could make you sick, but apparently there are many other factors that compensate for that. What the company founders did was to develop a very smart genetic sequencing system. There are all kinds of single gene disorders, monogenetic diseases, so the gene that causes the disease has been identified. You knock the gene out, and then activate all kinds of other genes and look to see how they compensate for the change. The Cell-Seq tool allows us to go from these single gene disorders to find the modifier gene, and normally in the cell there is so much going on, it would be like looking for a needle in the haystack. This system is smart enough to allow you to go from the disease gene, to the modifier gene. And you almost find it, it's more like an educated guess to move from the diseased gene to the modifier gene, and look to see which gene compensates. If you can activate or deactivate that one, or the protean it makes, then you might have a clue about the cure for a disease. It is actual gene sequencing. Some people think we do data mining, but that’s not the play, we work with the genes and diseases.

Your lead product candidate is a CD47/QPCTL immuno-oncology drug. What are the next products in the pipeline, and what rare diseases are you targeting?

The CD47 pathway is quite hot in immuno-oncology at this stage. We found some specific inhibitors that allow you to work very effectively on these kinds of immuno-oncology diseases, that's the most advanced. This asset could be partnered, or we could raise money to bring it further ourselves. The next in line is Niemann-Pick [a rare disease affecting metabolization of fat in the cells], and then another one is Barth syndrome. I would say that we're developing a collection of metabolic rare diseases, and Niemann-Pick and Barth syndrome are the most advanced, apart from the immunoncology program, and we will focus more on these. On the metabolic diseases, think of mitochondrial diseases, lysosomal storage diseases, so its cultures, rare diseases.

How broad is the potential application for targeting genetic modifiers? Will you be able to go beyond the treatment of inherited genetic disorders?

It's a billion-dollar question. The simple answer is yes, there is broader application, but it's very difficult. If I tell you that it is like looking for a needle in a haystack for a single gene disorder, it's a little bit easier to find genetic modifiers. . I can image with multiple gene disorders or other diseases, it gets more and more complicated. But the good thing is, as science advances, every day, we may be able to go after more and more disease areas, but for now the low-hanging fruit is single gene disorders.

In June, Scenic Biotech received a €3.1 innovation credit from the Dutch government, to help advance preclinical work for your immuno-oncology product. Do you have a target date for when you hope to move that program into clinical trials?

We're working on the chemistry right now, toxicology, and I've looked at the timelines. Ideally, early 2022 is the year we could move into the clinic.

In some ways maybe it is fortunate that you are not in the clinic yet, given the challenges and delays other organizations are facing with respect to COVID-19. Are you seeing a material impact on your business operations due to COVID-19?

I was happy with myself for finding a company with great technology. Not being in the clinic, unless it's COVID-19 R&D related, is excellent, because I know that numerous companies are facing delays – and we are not. We do of course have our issues, it’s the same here in the Netherlands with social distancing and everything, we can't have more than a certain number of people at the same time in an office or in the lab, but we managed to have a sort of lockdown protocol where we could continue lab work, with fewer people than you would normally use. But we're lucky, it doesn't really effect our plans or speed. We were able to deal very well with the environment. I agree with you, it's maybe a blessing in disguise to not be in the clinic yet.

You are based in Amsterdam, and now the EMA is too. Have you started to have any conversations with regulators about potential clinical programs looking at genetic modifiers?

Only for the lead QPCTL candidate. There is one thing that's different between the EMA and the FDA – the FDA has from my perspective a more open mindset. You can go there and almost philosophize about potential approaches. The EMA doesn't do that, they work differently, they say, ‘Send your plan and we’ll say yes or no.’ The EMA’s view is that they aren’t here to help companies think about it, you do that with the key opinion leaders. So that’s what we do, we talk for now in the world of small molecule drugs that effect these modifier genes and active small molecule drugs – it’s pretty straight forward how you design your clinical program. We feel comfortable there. We approach KOLs and our engagement with regulators depends on where we will start our first clinical trial, whether it be the US or Europe. It depends also on what partner we will choose.

Any initial conversations with the FDA?

Not yet. Although our scientific advisory board is extremely well connected, so we use them to do some of the testing or to connect with people they know well at the FDA. But we have not had formal pre-meetings yet.

Maze Therapeutics, a San Francisco-based company, is also working on genetic modifiers. Are there other companies that you would view as competitors in this space?

Maze Therapeutics is a good reference or example for us, too. If you look at genetic modifiers, I think we're quite unique, there's not much out there. Some investors start talking about CRISPR and gene editing, but that's something completely different. With genetic modifiers, the only company that gets close to what we’re doing is indeed Maze. If you look specifically at our programs, then you could say for this QPCTL there are some more companies that try to work on that, but I think we are a very strong competitor. And on metabolic diseases, there's S, from Denmark, a public company, they work on protease treatments. Another US-based name that came up, although I think they had a setback in the clinic not long ago, is Stealth BioTherapeutics Inc., they work on other metabolic diseases that we are working on, like Barth syndrome. But Maze is by far our closest competitor.

Are there any companies that you look to as a model in terms of business strategy, approach to partnerships, culture or something else?

In Europe, there are some very exciting examples including S, Galapagos NV, and argenx N.V. – platform companies that developed into biotech powerhouses. If we can do something similar, these are good examples for us on how we'd like to develop ourselves.