Biotechnology

6 protein degradation companies you should know about in 2023

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Protein degradation platforms have revolutionized drug discovery aimed at incurable targets. Biopharmaceutical companies around the world have become involved in the field of protein degradation, with hopes of harnessing the ability of these compounds to successfully design drugs to treat diseases such as cancer and neurodegenerative disorders.

The discovery of the mechanism of ubiquitin and proteolysis – protein degradation – in the 1980s drew attention to the potential of target protein degradation as a new drug modality. Since then, companies have attempted to apply this function to therapeutic research.

With more biopharma entering the drug discovery arena, here are six companies, presented in alphabetical order, doing some interesting research in the area of ​​protein degradation.

Arvinas

Because dealing with incurable targets can be quite difficult, the US-based company Arvinas is focusing on a novel approach in induced affinity to initiate target protein degradation.

The company’s technology, PROTAC – a protein scavenger that tags proteins by binding weakly to them – targets disease-causing proteins, after which, the protein copies are sequentially degraded. For the treatment of central nervous system (CNS) diseases, the platform has successfully undergone preclinical trials to demonstrate its efficacy – its ability to penetrate the blood-brain barrier. Depending on the disorder, PROTAC can be given intravenously and even orally.

The Arvinas PROTAC-based pipeline consists of more than 12 drug candidates, which are being studied in immuno-oncology and neuroscience research. Its lead candidate, ARV-471, is an investigative oral protein scavenger targeting the estrogen receptor (ER) for the treatment of breast cancer. Signaling from the ER – which is a hormone receptor – can drive metastatic breast cancer.

As 80% of breast cancer cases are ER positive, Arvinas’ focus on targeting signaling could be efficacious therapeutically in patients where aggressive manifestations of the disease continue to progress despite hormone treatment and chemotherapy. ARV-471 is being developed in collaboration with Pfizer global pharmaceuticals.

Founded in 2013, and headquartered in Connecticut, the company has received over $111 million in investments, with the most recent funding being raised in a Series C round in 2018.

C4 Therapy

Regulated at biotech hotspot Cambridge, Massachusetts, C4 Therapeutics explores the field of targeted protein degradation (TPD) to eliminate disease-causing proteins, prone to ubiquitination processes, to exploit its drug discovery potential.

Its proprietary technology, the C4T Target ORIiented ProtEin Degrader Optimizer (TORPEDO) platform synthesizes small molecules designed to specifically target disease-causing proteins that are considered incurable targets.

Since the company’s inception in 2016, it has collected and analyzed data from many protein-degrading molecules, and with the help of computational models, has observed the role of these decomposers in attacking target proteins, enabling the platform to be optimized to enhance its capabilities. specialty. The platform has two types of degraders – one binds to the E3 ligase to initiate the binding of the E3 ligase to the target protein, while the other binds to the target disease-causing protein as well as the E3 ligase on either side.

In line, a protein degradation company specializing in cancer treatment. One drug candidate, CFT7455, targets IKZF1/3 expression for relapsed or refractory multiple myeloma (RRMM) and non-Hodgkin lymphoma (NHL), and is currently in the early stages of clinical trials. Other drug candidates also focus on solid tumors, and are in various stages of development, as well as preclinical and clinical trials.

After completing five funding rounds, the company has raised $273.8 million, with its most recent investment secured in August 2022. Venture capital Taiwania Capital Management Corporation and Lightchain are its most recent investors.

Fluid Analysis

Based in Cambridge, UK, Fluidic Analytics has set up a protein interaction laboratory that observes protein interactions, including challenging and incurable targets.

The company’s research primarily focuses on neurodegenerative disorders and infectious diseases, particularly COVID-19.

His Fluidity One system, which is based on microfluidic diffusion size (MDS) – a method for measuring particle size – was used to characterize protein interactions. The company recognizes that there is a need for new approaches to target CNS diseases such as Alzheimer’s and Parkinson’s disease because they are caused by the accumulation of misfolded proteins; paved the way for protein degrader-based treatment options.

Since 99% of Alzheimer’s drug trials have failed in the last 10 years, according to Fluidic Analytics, the company plans to address the challenge through its tests – biochemical tests at the cellular level – for researchers to learn how viable drug candidates are related to them. interaction with the appropriate target.

Founded a decade ago, the company has raised more than $40 million in funding over the last 10 years in four rounds, with its most recent investors being US manufacturer BGF Industries and investment firm Delin Ventures, among a total of eight investors.

NEosphere biotechnology

Just two years old, NEOsphere Biotechnologies was founded in Germany in 2022, and is another company excited by the potential of targeted protein degradation to address unmet medical needs in patients.

TPD uses the cell’s waste disposal system as its method of destroying disease-causing proteins. Catalytic degraders are small molecules that divert ubiquitin E3 ligases – proteins that regulate homeostasis, a process that stabilizes the body’s physiochemical conditions for the best chance of survival – to substrate proteins to form substrate-altering complexes, which are then degraded. . This technology beats other available platforms in that it does not require an active binding site to exert its effect.

For its pursuit of drug discovery, the company studied the scope of TPD using mass spectroscopy, which is an analytical tool used to measure the mass of molecules.

The company closes Series A funding for further development of its technology in July 2022.

Origami Therapy

Based in California since 2016, the company’s ORICISION platform, focused on protein degradation, enables the discovery of protein decomposers and conformation correctors, to unravel protein structures and target abnormal protein functions.

Drug discovery platforms, which have the potential to prevent the spread of disease-causing proteins, are being studied in the treatment of neurological disorders such as Alzheimer’s disease, Huntington’s disease and Parkinson’s disease.

Huntington’s disease is a rare genetic disorder in which nerve cells in the brain become damaged and, as a result, can affect a person’s movement, cognition and mental health.

For treatment, Origami technology is able to limit the formation of HTT toxic mutant protein fragments, which are released due to HTT protein misfolding caused by reduced proteostasis – a process involved in protein regulation in cells.

Although the platform appears promising, all candidates in line have not undergone preclinical testing to assess efficacy and risk.

Initially self-funded, the discovery stage company has received funding from startup accelerator Y Combinator, and is raising its first round in 2022.

Therapy Room

Headquartered in Hangzhou, China, Ranok Therapeutics is a preclinical biotech company focused on the role of chaperone proteins, mediating proper protein folding to regulate proteostasis. These chaperone proteins can also direct proteins to the ubiquitin-proteasome system – which is responsible for unwanted protein degradation.

The product, Chaperone-mediated Protein Degradation/Degrader (CHAMP), can loosely bind the target and the chaperone protein complex together, by linking the two elements on either side, to stimulate target degradation. The technology has been designed to treat cancer, and has proven safety when targeting solid tumors.

In August 2022, Ranok Therapeutics announced the start of patient dosing in clinical trials for the class one protein-degrading drug RNK05047, which is an application of CHAMP technology.

The protein degradation company has raised a total of $50 million over two series of funding rounds with the latest in 2021, and their most recent investors are Wu Capital and Shanghai Healthcare Capital.

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