20S proteasome

The company will focus on creating small molecule therapeutics that enhance the natural function of proteasomes. Credit: Gorodenkoff/Shutterstock. Booster Therapeutics has announced its inception, backed by a $15m investment, to develop a new class of proteasome activator medicines aimed at treating neurodegenerative diseases and other complex conditions. Apollo Health Ventures and Novo Holdings spearheaded the financing round. The company’s focus is on creating small-molecule therapeutics that enhance the natural function of proteasomes, the cellular machinery responsible for eliminating harmful proteins. Proteasomes are vital in maintaining cellular health by degrading damaged or misfolded proteins. When proteasomes are impaired, these defective proteins can accumulate, potentially leading to severe diseases. See Also: Evergreen Theragnostics Radiopharmaceutical Manufacturing Facility, New Jersey, US Merck Biotech Development Center, Corsier-sur-Vevey, Switzerland Unlike existing protein degradation therapies that target individual proteins for destruction, Booster’s approach treats diseases caused by multiple protein dysfunctions. Their compounds activate 20S proteasomes, which can identify and degrade disordered proteins without the need for ubiquitin tagging, a marker protein used in other therapies. Booster leverages its DGRADX platform for the small molecule discovery process, employing automated high-throughput screening along with advanced structural and computational techniques. This platform is tailored to augment the activity of 20S proteasomes, thereby enhancing the body’s capacity to eliminate disease-causing proteins. With an extensive library of activator compounds, Booster plans to develop a diverse pipeline of treatments targeting proteinopathies and diseases caused by abnormal proteins. Booster Therapeutics co-founder and chief scientific officer Dr Diogo Feleciano stated: “Proteasome activation offers important advantages over more limited conventional protein degradation approaches and provides a powerful lever to combat the effects of the many types of deviant proteins that can accumulate in cells when proteasome function declines through age or disease. The implications for solving major degenerative conditions, such as Parkinson’s and Alzheimer’s, are enormous. “We’re grateful for the support of our investors, who have enabled us to assemble a world-class team to realise the untapped potential of proteasome activation against a range of difficult-to-treat diseases.”

Booster Therapeutics raises $15 million seed financing led by Apollo Health Ventures and Novo Holdings Booster Therapeutics’ proteasome activation approach designed to achieve wider degradation of harmful proteins than current targeted protein degraders Harmful protein accumulation implicated in range of complex diseases also linked to proteasome dysfunction COPENHAGEN, Denmark I October 10, 2024 I Novo Holdings, a leading global life sciences investor, today announced the launch of Booster Therapeutics (Booster / the Company), a biotechnology company developing a new class of proteasome activator medicines to treat neurodegenerative and other diseases. The launch is accompanied by a $15 million seed financing round led by Apollo Health Ventures and Novo Holdings. Novo Holdings will play a central role in helping to further build Booster in its next phase of growth, bringing hands-on operational expertise, strategic guidance and helping the Company access a larger network of talent. Novo Holdings will further leverage the expertise in its group of entrepreneurs-in-residence, as well as the Seed Lab wet-lab capabilities in Copenhagen, Denmark. Proteasomes play an important role in the clearing of dysfunctional proteins. Booster is leading a new field of protein degradation via small molecules that activate and restore the function of 20S proteasomes. These proteasomes naturally and directly recognise and degrade a wide range of misfolded or otherwise damaged proteins in contrast to conventional protein degradation therapeutics, which only degrade one target protein at a time. Activation of the 20S proteasome can remove a wide range of disease-causing proteins and thus address more complex diseases caused by multiple concurrent proteinopathies. With a vision of a multi-disease pipeline, Booster will initially focus on major neurodegenerative diseases such as Parkinson’s and Alzheimer’s. This group of diseases generally carries a tremendous burden of disease for patients, families and the healthcare system due to their progressive and severe nature and a lack of disease-modifying therapeutics. Booster was founded by the pioneering work of Dr. Diogo Feleciano and University of California Irvine Professor Dr. Darci Trader, as part of the company creation efforts of Apollo Health Ventures. The Company was built on the idea that small molecules could be used to trigger natural proteasome processes. Their DGRADX™ platform, which was conceived in Prof. Trader’s laboratory, combines proprietary methods for automated high-throughput screening with advanced structural and computational tools to develop Booster’s novel proteasome activator compounds. “Proteasome activation is a truly novel concept because it can potentially transform how we address some of the most multi-factorial diseases. Booster’s deep expertise in proteasome biology means it is well positioned to deliver on first-in-class medicines and expand the protein degradation landscape to more comprehensively address protein dysfunction and impact more disease areas,” said Dr. João Ribas, Principal at Novo Holdings, Seed Investments and Interim Chief Business Officer and Board Member, Booster Therapeutics. “We’re excited to join efforts with Apollo and the Booster team in order to take this novel therapeutic concept forward for the benefit of patients.” The Company and corporate strategy will be led by Dr. Diogo Feleciano as Chief Scientific Officer and Dr. João Ribas as interim Chief Business Officer. Dr. Patrick Trojer, Co-Founder of Constellation Pharmaceuticals and current Chief Executive Officer & President of TRIANA Biomedicines will serve as Chair of Booster’s Board of Directors. About Booster Therapeutics Booster Therapeutics is pioneering a new class of medicines that activate the cell’s natural quality control machinery to treat a range of complex indications. Booster’s small molecule therapeutics, discovered through the DGRADX™ platform, are designed to directly boost the activity of 20S proteasomes to restore the body’s ability to clear disease-causing proteins. The Company is developing a multi-disease pipeline, with an initial focus on neurodegenerative diseases associated with impaired proteasome function such as Parkinson’s disease and Alzheimer’s disease. Booster is based in Berlin, Germany. For more information, visit www.boostertx.com About Novo Holdings A/S Novo Holdings is a holding and investment company that is responsible for managing the assets and the wealth of the Novo Nordisk Foundation. The purpose of Novo Holdings is to improve people’s health and the sustainability of society and the planet by generating attractive long-term returns on the assets of the Novo Nordisk Foundation. Wholly owned by the Novo Nordisk Foundation, Novo Holdings is the controlling shareholder of Novo Nordisk A/S and Novonesis A/S and manages an investment portfolio with a long-term return perspective. Novo Holdings is a world-leading life sciences investor. Through its Seed, Venture, Growth, Principal Investments, Planetary Health Investments and Asia teams, Novo Holdings invests directly in life science companies at all stages of development. In addition, it manages a broad portfolio of Capital Investments, including equities, bonds, fixed income, real estate, and infrastructure assets. As of year-end 2023, Novo Holdings had total assets of EUR 149 billion. www.novoholdings.dk SOURCE: Novo Holdings

When proteins cause disease, the body has ways to tackle them. An emerging class of therapies that leverage a cell’s built-in systems to eliminate rogue proteins has already reached the clinic via several companies. But there’s more than one way to get cells to degrade disease-causing proteins, and Booster Therapeutics is developing drugs that could expand this approach to more proteins and more diseases. Neurodegeneration is Booster’s initial focus, and the startup launched out of stealth Thursday backed by $15 million in funding. The protein-degrading drugs currently in clinical development direct disease-causing proteins to a component of a cell called the proteasome. The drugs themselves are small molecules that recruit a molecular tag that marks a protein for disposal by the proteasome. Companies developing targeted protein degraders include Kymera Therapeutics, Arvinas, and Nurix Therapeutics. All three have research alliances with big pharmaceutical companies. Most of the degraders currently in development are for cancer, but this field is also pursuing immunological disorders. There are limitations to the current approach of degrading proteins, said Booster co-founder and Chief Scientific Officer Diogo Feleciano. These protein-degrading drugs each address only a single disease-causing protein, but some diseases are driven by multiple proteins. Targeted protein degradation also requires a molecular tag. Without it, the proteasome leaves proteins alone. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Cells have other types of proteasome besides the one that’s the focus of targeted protein degradation, and Feleciano says it’s here where Booster stands apart. Berlin-based Booster focuses on the 20S proteasome, which is capable of addressing multiple proteins without needing a tag to mark them for degradation. Cells have ways to control whether proteins are degraded or not, Feleciano said. The 20S proteasome naturally addresses proteins that are misfolded. In some diseases, these problem proteins aggregate and overwhelm the proteasome, which then becomes inactive. The startup is developing small molecules that specifically target 20S proteasomes to give them a pharmacological boost. “What we are aiming to do with our molecules: Restart, reactivate that function to homeostatic levels,” Feleciano said. “By doing that, we can improve the degradation of proteins and alleviate the accumulations that are known to be toxic.” Drug research has already yielded drugs that target the proteasome. For example, proteasome inhibitors treat multiple myeloma by stopping proteasomes from getting rid of proteins that are no longer useful. The resulting protein accumulation leads to death of cancer cells. But scientists have been pursuing ways to activate proteasomes to treat disease, a field that Feleciano acknowledges did not start with Booster. Feleciano’s Ph.D. research covered neurodegeneration, including the role of the proteasome in such diseases. He said that work sparked interest in therapeutics that could address the proteasome and form the basis of a company. He found promising science in the lab of Darci Trader, a professor in the department of pharmaceutical sciences at the University of California, Irvine, whose research focuses on chemically stimulating the 20S proteasome in neurons. Parkinson’s disease is one area of focus of Trader’s research. Booster incorporated in 2020 with Trader as its scientific co-founder. The startup has been incubating within Apollo Health Ventures, the venture capital firm where Feleciano is an entrepreneur in residence. Sponsored Post Get Ready for HLTH 2024: A Preview Guide HLTH 2024, scheduled for October 20-23 at the Venetian Expo Center in Las Vegas, will highlight new programming, a physicians roundtable, generative AI, the shifting landscapes of telemedicine, retail health, women's health, and lots more. By Stephanie Baum Booster’s foundation is DGRADX, a platform technology that employs computational techniques to understand the structure of the 20S proteasome. The platform also employs proprietary methods to automate high-throughput screening to identify and optimize small molecule proteasome activators. For now, Booster is not saying much about its pipeline. But besides Parkinson’s, Feleciano said his company’s approach also has potential applications to Alzheimer’s disease. Booster’s seed financing announced Thursday was led by Apollo Health Ventures and Novo Holdings. With the capital, Feleciano said Booster will continue to build the company and advance the development of its programs. “We are not only pioneering activation of the proteasome, we are pioneering knowledge of what that means,” he said. “We are building more knowledge of what is out there. This is an area that is untapped.” Image: akindo, Getty Images