4SC AG is a clinical-stage biopharmaceutical company developing small-molecule drugs targeting key mechanisms in cancer. Its lead candidate, resminostat, is an orally administered histone deacetylase (HDAC) inhibitor under development for advanced-stage cutaneous T-cell lymphoma.
Can you take us through the evolution of 4SC and its focus on cutaneous T-cell lymphoma (CTCL)?
4SC has been around for almost 20 years. Early on, it explored different business models, acquiring a pool of compounds from Nycomed, which it began screening for anti-cancer potential. Ultimately, that research culminated in a decision to focus on targeting cutaneous T-cell lymphoma (CTCL) – a disease for which there is no cure – with a key molecule called resminostat. This has remained our focus.
I joined 4SC in 2016 because they were just initiating a pivotal clinical study in this area. It represented a rare opportunity to help bring a drug through late stage development and regulatory approval and onto the market for a patient group with very limited and ineffective treatment options.
Why do you believe in small molecules for treating diseases like CTCL when much of the industry is focused on biologics and CAR T-cell therapies?
Monoclonal antibodies have been incredibly successful, but they generally target cell surface antigens. Small molecules, on the other hand, can be absorbed into cells and target internal processes, such as epigenetic modulation. This makes them particularly useful in cancers where intracellular pathways play a key role.
CAR T-cell therapy, while promising, comes with significant manufacturing challenges and is often tailored to individual patients. In contrast, small molecules offer the potential for broader applicability. In CTCL, two antibodies are already approved, but they only address subsets of patients due to their target specificity. Our goal is to develop a therapy that can benefit the majority of refractory or relapsed later stage CTCL patients, which is why we see small molecules as the best approach.
Resminostat is expected to be approved by the European Medicines Agency this year. If it is approved, what can patients expect?
The application for resminostat in cutaneous T-cell lymphoma (CTCL) is based on a single clinical trial RESMAIN, since CTCL is an orphan disease and only requires one study for approval. RESMAIN was one of the largest trials ever conducted in advanced-stage CTCL, enrolling 201 patients in a randomized, double-blind, placebo-controlled format—therefore one of the highest standards for clinical evidence. It is the only CTCL study of this kind, and the data showed that resminostat significantly delayed disease progression, and almost doubling progression-free survival to over eight months compared to the placebo group.
Since there is no cure for CTCL, current treatments mainly aim to stabilize the disease. Complete remission rates are low, at around 10%, and most patients ultimately progress on all available therapies. The median survival for advanced-stage patients is under five years. Resminostat was shown to provide a statistically significant improvement in progression-free survival, and, in combination with prior therapy, it could extend progression-free survival to nearly two years on average. This is a very meaningful addition to the treatment landscape, and we hope the EMA will grant marketing authorization around mid-year.
4SC licenses its drugs out to other companies for further development. One example is vidofludimus, which a company in Munich is now developing for multiple sclerosis. How did this approach come about and what are its benefits?
Vidofludimus was one of the compounds acquired in that initial pool and was originally explored in various cancer indications, though it did not show strong success. It ended up, in a sense, sitting on the shelf. Daniel Vitt, one of 4SC’s founding chemists and former CSO, was very familiar with the compound and, after leaving 4SC, arranged a licensing deal to take it forward in a different direction. The licensing agreement allowed 4SC to monetize the earlier work done on the drug while enabling its potential development in a field better suited to it—multiple sclerosis—since 4SC’s focus has remained in oncology.
What are the advantages of operating in the E.U. versus the U.S. as a biotech company?
The quality of science in Europe is exceptionally high—at least on par with the U.S.—but it remains underexploited due to the differences in investment environments. The U.S. has a much larger and more established venture capital sector, while in Europe, there are still plenty of opportunities. The regulatory environments differ as well. The EMA and FDA have distinct ways of evaluating clinical trials, and, for example, our RESMAIN study design does not currently meet U.S. requirements but is sufficient for EMA approval.
Operationally, Europe offers strong scientific expertise and talent. Running a biotech company in Europe is much less expensive, particularly for publicly listed companies. We are listed on the Frankfurt Stock Exchange, and compared to a Nasdaq listing, the compliance costs are far lower, allowing us to allocate more resources to drug development. While the U.S. is the largest pharmaceutical market in dollar terms, Europe has a larger population, which is great for patient access, especially in orphan indications like CTCL. This also means clinical studies can often be conducted more cost- and time-effectively in Europe.
If resminostat is approved, what can we expect from 4SC in the coming years?
This is an incredibly exciting time for us. We have spent more than six years on this clinical study, recruiting our first patient in late 2016 and publishing the topline data from the trial in 2023—navigating the challenges of COVID along the way. Now, our priority is making the drug available to patients as quickly as possible.
We are evaluating two paths forward. Due to the strong data, multiple companies have expressed interest in licensing or acquiring the asset, which would allow a larger, more experienced organization to handle commercialization. Alternatively, we are assessing whether to bring the drug to market ourselves, and we are actively gaining hands-on experience in the necessary commercialization tasks. By mid-2025, we expect to have clarity on whether we will proceed with a partnership, a licensing agreement, or an asset sale.
