Scene set for Scenic to take ‘top-notch science’ into the clinic

Scenic Biotech has progressed enormously since it was founded in 2017 as a spin-out from the Netherlands Cancer Institute and Oxford University by Sebastian Nijman and Thijn Brummelkamp.

The company’s recent achievements in the area of neurodegeneration may well result in the busiest year yet to come for the Netherlands-based firm, said chief executive Oscar Izeboud and Roland Bürli, chief scientific officer, on speaking to The Pharma Letter.

Pioneer in modifier therapies

Scenic is a pioneer in the field of modifier therapies for severe genetic disorders. It is modifier genes that explain why some people with genetic mutations linked to severe diseases have only mild symptoms or a late disease onset. However, modifier genes or compensatory genes have traditionally been difficult to identify, especially for genetic disorders.

Thanks to its proprietary Cell-Seq platform, Scenic is systemically exploring modifier genes for a large variety of disorders, including inherited diseases.

Investor and pharma endorsement

Both financial and strategic parties have endorsed Scenic Biotech right from the start. Seed funding came from VCs Oxford Science Enterprises and the Dutch pairing of Inkef Capital and BioGeneration Ventures – later followed by big pharma collaborators Bristol Myers Squibb (NYSE: BMY), Ono Pharmaceuticals (TYO: 4528), Alnylam (Nasdaq: ALNY) and Roche-Genentech (RO: SIX). Consecutively, the series A financing was co-led by EIR Ventures, Vesalius Biocapital and Biomed Partners.

This is largely due to the quality of its unique platform technology, allowing Scenic to unlock compensatory pathways to deliver disease-modifying treatments. Importantly, a successful modifier therapy seeks to rebalance health by acting on another function in the genome that can neutralize the disease impact, thus leading to a therapeutic benefit.

Scenic uses its platform to identify novel targets that re-balance disease pathways and open them up to alternative approaches for pharmacological intervention. In principle, these targets can be modulated by any therapeutic modality.

As well as having the platform, Scenic is building a cutting-edge pipeline with a focus on neurometabolic disorders.

“Large pharma eventually loves to see drugs, not just targets,” Dr Izeboud said. “So, we realized that we have to develop our own pipeline. At the same time, there are pharma companies that come to us and ask for help with innovative target discovery. We currently have collaborations with four top pharma organizations; if successful, these collaborations have potential to result in significant downstream milestones and royalties. Importantly, these projects are completely separate from our own pipeline.”

Huge response to Nature paper

Scenic’s lead program is centered around PLA2G15, an enzyme that breaks down bis(monoacylglycerol)phosphate (BMP), a lipid class that is critical for lysosomal function. In turn, lysosomal function is often hampered in neurodegenerative diseases and consequently, increasing BMP levels by inhibiting PLA2G15 has high potential for a therapeutic benefit. A collaboration with Professor Monther Abu-Remaileh at Stanford University, aimed at deconvolution of the function of PLA2G15, culminated in a widely read research article published in Nature last year.

“Essentially, it's all about lysosomal health,” Dr Bürli said. “The lysosomes are the cellular recycling centre and the question is, how can you maintain their biological function? How can you make sure that toxins and waste get efficiently eliminated from the cells? This is an important cellular process that becomes inefficient in neurodegeneration.

“It’s well known that in some contexts of neurodegenerative diseases, the BMP levels are low, likely resulting in reduced lysosomal activity. The question is, how can you elevate BMPs, restore lysosomal health and improve the recycling of the toxins? The relevance of this Naturepaper is that PLA2G15 was identified as the major driver for degradation of BMPs. So, high PLA2G15 activity basically depletes BMP levels in lysosomes.”

“Consequently, we developed an inhibitor of PLA2G15 to restore BMPs and improve lysosomal function,” Dr Bürli added. “The Nature paper spurred a lot of interest, including from pharma and the VCs world and, frankly, even myself. When I interviewed for this position at Scenic, I was absolutely attracted by the high quality of the science and the innovation shown by this particular paper, where Cell-Seq was able to uncover a mechanism that was previously unknown.”

Scenic worked hard to identify molecules that potently inhibit PLA2G15 and nominated a candidate molecule late last year, which acts highly specifically on PLA2G15. The compound has excellent brain permeability and pharmacokinetics, resulting in high target occupancy in the brain.

“So, SC6177 is the molecule we selected to scale up and advance through preclinical development this year, which includes the safety studies that are necessary prior to clinical trials,” Dr Bürli said.

“We're also working on a translational plan and develop biomarkers allowing us to monitor pathway engagement throughout the studies in healthy volunteers and patients.”

A long runway and more fundraising ahead

Clearly, conducting this research is not cheap and Scenic has raised funds from investors only twice so far, in the seed round and in the Series A in 2022.

“We created such a long runway because we make money from the collaborations and we reinvest everything into the company and its pipeline – that has helped to extend our runway considerably, on top of the investor money,” Dr Izeboud said.

“We still have ample runway, but to be able to execute the full clinical plan, we need a top-up of our investments.

With the preparation for the clinical trials and fundraising, the next year could prove particularly crucial in terms of providing a springboard for Scenic.

Thanks to the promise of the company’s platform and pipeline, as well as a good financial base, it is clear that the duo is optimistic when they envisage where Scenic might be in five years’ time.

“I think, first of all, we should be able to demonstrate that this platform and concept of genetic modifiers can yield various disease-modifying therapies, in the next five years,” Dr Izeboud said. “Secondly, to show proof of concept with our lead compound in the clinic in patients and get the first drug ready for the market.

A belief in making a difference

“Especially in Europe, the biotech companies that were successful in a more capital-restrained environment than the USA is, were often platform companies. And, if you look at Scenic with the number of unexplored targets that we uncovered, the top-notch collaboration partners as well as the two new Naturepapers in 2025 alone, I think it's impressive what the platform, the founders and the current team have been able to accomplish.

Dr Bürli added: “For me personally, I always liked to join a company with an innovative platform. And, I totally agree with Oscar: what drives us all is the idea to make a difference in our approach to devastating CNS illnesses and it would be a huge privilege if Scenic can contribute by uncovering disease-relevant pathways and develop a successful therapy.”