Booster launches to treat neurodegenerative diseases with proteasome activation

Photo credits: Milad Fakurian
20S proteasome activation: Berlin biotech Booster Therapeutics secures $15 million for innovative therapies to tackle neurodegenerative diseases

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Booster Therapeutics, a Berlin-based biotech startup, has emerged from stealth with a $15 million seed financing led by Apollo Health Ventures and Novo Holdings. The company is developing a novel class of small molecule therapies built around 20S proteasome activation – key components of the cellular machinery responsible for degrading damaged and misfolded proteins. This approach could offer new treatments for neurodegenerative diseases like Parkinson’s and Alzheimer’s, where the accumulation of harmful proteins plays a central role in disease progression.

A couple of months back, we wondered if tau protein represented the future of Alzheimer’s treatment after Novo Holdings led Asceneuron’s $100 million series C round, and now the fund has invested in another company showing great promise for treating neurodegenerative diseases, but with what seems to be a wider scope. 

“Booster’s differentiated approach to clearing damaged proteins was unlike any other approaches we had seen within the protein degradation space. That, together with their data, convinced us,” said Joao Ribas, the investor in charge of Booster Therapeutics at Novo Holdings.

With an initial focus on neurodegenerative diseases and support from Apollo Health Ventures and Novo, Booster Therapeutics launches with solid foundations. Let’s take a closer look into its proteasomes targeting approach.

Booster Therapeutics’s 20S proteasome activation to tackle neurodegenerative diseases

Booster Therapeutics is pioneering a new class of medicines focused on activating the 20S proteasome, part of the cell’s natural quality control system responsible for clearing damaged, misfolded, or aggregated proteins. This strategy is particularly important for diseases where multiple proteinopathies – conditions caused by the accumulation of malfunctioning proteins – are present simultaneously, as seen in neurodegenerative diseases like Parkinson’s and Alzheimer’s​.

“We’re starting in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s. We know that proteasome dysfunction is present in these diseases, and multiple pathways are going wrong, so we believe there’s a strong case for a broader-spectrum approach such as proteasome activation,” said Diogo Feleciano, Booster’s co-founder and chief scientific officer (CSO). 

Feleciano’s experience in neurodegeneration research raised his awareness of why single-target approaches were failing in diseases such as Parkinson’s and Alzheimer’s. “It seemed clear that part of the problem is that these are complex diseases with many things going wrong, and it was frustrating to see drug development constantly cherry-picking at the causes. This is probably part of what motivated me to pursue a broader approach with a company like Booster.”

But how does it work and what makes 20S proteasome activation relevant? “20S proteasomes clear a wide variety of – let’s say ‘unhealthy’ – proteins from cells. Many complex diseases involve several proteinopathies at once. Proteasome activation might be a way to more thoroughly address these complex diseases instead of trying to target just one protein at a time,” explained Feleciano.

Unlike conventional protein degradation therapies such as PROTACs (proteolysis-targeting chimeras), which tag individual proteins for degradation by the 26S proteasome, Booster’s approach is broader. PROTACS and other targeted protein degraders use ubiquitin, a protein, to tag proteins that are damaged, misfolded, or no longer needed by the cell for degradation. 

“With our approach, we’re going after deviant proteins more broadly – damaged, misfolded, aggregated – whatever form of issue that healthy 20S proteasomes normally address in a ubiquitin-independent manner. This gives us a much wider potential reach in terms of diseases. We can target diseases that are derived from multiple misfolded or ‘unhealthy’ proteins accumulating at once,” explained Feleciano

And it seems that this approach could be even broader and expanded beyond neurodegenerative diseases.

20S proteasome activation beyond neurodegenerative diseases

The versatility of Booster’s proteasome activation was also a key element in Novo’s commitment to the company. “Booster’s approach is ideal for complex proteinopathies. There is a strong focus on neurodegenerative diseases but also potential to expand further,” confirmed Ribas. 

Feleciano is conscious of the broad potential of the company’s approach but wants to build the pipeline without rushing things. “We aim to build a multi-indication pipeline. Beyond the initial indications, complex proteinopathies are present in a range of disease areas, such as cardiometabolic, but they’re not a current priority for our pipeline. We plan to broaden our pipeline as the company grows.”

In addition to cardiometabolic disorders that Feleciano pointed out, proteasome activation could potentially benefit oncology and other complex diseases where protein misfolding and aggregation are significant factors. 

For instance, in oncology, misfolded proteins and defective protein degradation mechanisms contribute to tumor growth and cancer progression. While proteasome inhibitors like bortezomib are already used in cancer therapy, activating the 20S proteasome could represent a complementary strategy to improve the degradation of tumor-related proteins and enhance the effectiveness of cancer treatments​.

Similarly, in cardiometabolic disorders, such as heart disease and diabetes, abnormal protein aggregation has been identified as a contributing factor. In type 2 diabetes, amyloid fibrils derived from the misfolded islet amyloid polypeptide (IAPP) accumulate in pancreatic beta cells, contributing to disease progression. Booster’s 20S proteasome activators, by promoting the clearance of these misfolded proteins, could provide a novel therapeutic strategy in these areas as well​.

The possibilities are numerous for 20S proteasome activation but it is still very early in Booster’s journey to risk forecasting the future. Will Booster’s technology succeed in treating neurodegenerative diseases and other proteinopathies? Only time will tell.

Although the technology is new, Booster’s CSO noted the regulatory framework is already well established and shouldn’t be an obstacle going forward. “Our mechanism is novel, but the actual development and regulatory processes around small molecule development and CMC (chemistry, manufacturing, and controls) are well characterized and understood now. Other than what we see as a strong baseline translatability, we’re obviously going to stay in close contact with regulatory agencies about what they want to see specifically around our mechanism, and how we demonstrate that for them.”

An increasingly diverse landscape for neurodegenerative diseases

In July, when we took a closer look at Asceneuron’s tau-targeting approach to treating Alzheimer’s disease, we noted that the landscape was highly dominated by amyloid-beta plaques-focused therapies. 

Lately, it seems that new approaches are bringing a breath of fresh air to neurodegenerative disease treatment and Booster’s proteasome activation is definitely part of this transition, and so is Novo. “Overall, there is a high level of unmet need in multiple neurodegenerative diseases, and we will keep monitoring the space looking for differentiated approaches that can tackle the different aspects of the biology of each therapeutic indication,” said Ribas.

We will follow Ribas’ lead and also keep an eye on the field as it looks to be catching a second wind and Booster is well-positioned to capitalize on this resurgence.