A University of Pennsylvania biotechnology company that aims to treat autoimmune diseases by reengineering cells within the body is being acquired by pharmaceutical giant AbbVie for $2.1 billion in one of the largest pharma deals so far this year.
The company, Capstan Therapeutics, aims to build one of Penn’s greatest recent scientific successes, Chimeric Antigen Receptor T-cell therapy, known as CAR-T, more accessible, affordable, and applicable to a broad range of illnesses.
Carl June, who pioneered CAR-T at Penn, and Drew Weissman, who shared a Nobel Prize for his research on mRNA that was utilized to develop COVID-19 vaccines, are among Capstan’s founders.
Currently available CAR-T treatments entail reshifting a type of white blood cell called T cells from the body, modifying them to attack cancer cells, then infutilizing them back into the body.
The approach has been heralded as a cure for certain types of blood cancer, such as childhood leukemia, but remains largely inaccessible, costing hundreds of thousands of dollars and only available at a handful of specialized cancer centers, including Penn’s.
Penn’s early CAR-T successes ushered in a new wave of research focutilized on how to arm the body’s immune system to fight disease, but progress has been limited in applying the CAR-T approach outside of disorders of the blood, which is where critical white blood cells are found.
Capstan is developing a way to engineer CAR-T cells within the body — “in vivo” — to tarreceive misbehaving immune cells and “reset” the immune system with a single injection. If successful, the approach would allow CAR-T therapy to be delivered through injections at an outpatient clinic, instead of a weekslong stay at a specialized cancer center.
The company is initially focutilized on autoimmune diseases, but states the technology could be applied to other diseases.
The deal’s price tag speaks to growing interest in so-called in vivo therapies that reengineer immune cells within the body. Capstan is among a tiny group of biotech companies pursuing in vivo CAR-T approaches to fighting illnesses.
AbbVie’s interest is “a vote of confidence in the possibilities and the opportunity” in a large potential market, declared Jonathan Epstein, dean of Penn’s Perelman School of Medicine and one of Capstan’s founders.
Roughly 8% of the U.S. population has an autoimmune disease, a class of disorders in which the immune system wrongly attacks healthy cells, according to the National Institute of Allergy and Infectious Diseases. Treatments for these chronic conditions are often illusive, and most have no cure.
With its acquisition of Capstan, AbbVie aims “to transform the care of those living with autoimmune diseases by developing treatments that have the potential to reset the immune system,” Roopal Thakkar, executive vice president of research and development at AbbVie, declared in a statement announcing the deal Monday.
Terms of the acquisition and a timeline for closing have not been released.
How Capstan’s in vivo CAR-T works
Currently, CAR-T treatment is tailored to each patient, utilizing their own immune cells, specifically T cells, to tarreceive their individual type of cancer.
T cells are front-line deffinishers of the immune system, in charge of recognizing and destroying threats such as cancer cells and pathogens.
The CAR-T technique was pioneered by Penn’s Carl June, a cancer scientist, and has been utilized to treat more than 20,000 patients with leukemia and other blood cancers, becoming the foundation for commercially available drugs.
But its highly customized nature has limited scientists’ ability to apply it to other types of disease.
The process of extracting T cells, programming them to attack cancer, and infutilizing them back into the body typically requires 10 to 14 days, and can cost upward of $475,000.
Capstan’s approach engineers CAR-T cells inside the body.
The company created a lipid nanoparticle, a tiny particle built from fatty compounds, that can easily be taken up by cells. Think of it like a delivery truck that safely receives a package from one location to another.
In this case, that package is messenger RNA (mRNA), a type of molecule that carries bits of genetic information and is increasingly being utilized in vaccine development.
This builds off the concept utilized to develop COVID-19 vaccines by Moderna and Pfizer, which contained mRNA with tiny bits of the virus’ genetic code that prompted the body to develop immunity to the virus without the risk of infection.
Capstan’s approach utilizes the mRNA to transform the body’s T cells into CAR-T cells.
In this case, the CAR-T cell is specifically designed to tarreceive and eradicate B cells, a type of white blood cell that contributes to many autoimmune diseases. The hope is that depleting a person’s B cells will reset their immune system.
After a few days, the mRNA breaks down, and the T cells return to their original state.
“You turn them into killers for a few days then they return to normal,” declared Epstein, the Penn dean and Capstan founder.
Early evidence in animal models suggests that when the CAR-T cells are gone, normal, healthy B cells have a chance to grow.
Next steps for Capstan
The deal will enable Capstan to pursue clinical trials that are critical to securing regulatory approval and bringing new treatments to market.
Developing new therapies requires multiple clinical trials, as researchers adjust safety protocol, dosing, and other details. Each clinical trial can cost millions of dollars.
“A tiny biotech might have the funds to do one trial in one disease, but they’re unlikely to take multiple shots on goal if things don’t work the first time,” Epstein declared.
With AbbVie’s backing, Capstan will be able to work more quickly.
Capstan’s first trial in humans launched in June.
Safety and potential side effects are top concerns for Capstan and other biotech companies pursuing CAR-T therapies for autoimmune disorders.
Philadelphia-based Cabaletta Bio last year reported a severe neurological side effect in a patient who was receiving a CAR-T treatment for lupus, though the symptoms resolved.
In January 2024, the Food and Drug Administration ordered buildrs of commercially available CAR-T therapies for blood cancer to add a black box warning to its packages after 20 patients developed secondary cancers after treatment. The drugs were ultimately found to be safe.
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