AbbVie wasn’t a part of the primary wave of cell therapies developed for most cancers, however it’s positioning itself to contend within the subsequent one, which is increasing to therapies made by engineering immune cells inside a affected person’s physique and the applying of those cells to autoimmune illness. The pharmaceutical large is committing as much as $2.1 billion to accumulate Capstan Therapeutics, a cell remedy startup whose in vivo therapies are primarily based on analysis from biotechnology pioneers on the College of Pennsylvania.
No monetary breakdown was offered for the money sum. However the deal introduced Monday brings AbbVie a lead Capstan program that not too long ago started a Section 1 check in autoimmune illness in addition to CellSeeker, the platform know-how that produced it.
The primary cell therapies to succeed in sufferers have been CAR T-therapies, that are made by harvesting a affected person’s personal T cells and engineering them in a lab to go after a selected most cancers goal. After these cells are multiplied, they’re infused again into the affected person. The whole course of can take weeks, although many firms are engaged on methods to make it sooner and extra environment friendly. In vivo engineering of a affected person’s immune cells would keep away from this costly, multi-step manufacturing course of altogether.
The method of San Diego-based Capstan makes use of messenger RNA to reprogram immune cells to go after disease-driving cells. The mRNA is encapsulated in a lipid nanoparticle. Whereas viral vectors are a broadly used supply car for genetic medicines, they’re usually one-time therapies. These engineered viruses immediate the physique to provide antibodies in opposition to them, so subsequent doses can be rendered ineffective. Against this, a lipid nanoparticle doesn’t immediate that immune response, making redosing attainable. That’s essential for bringing cell remedy to immunology, the place remedy of persistent illness usually requires redosing.
Immunology and irritation is already a power of AbbVie, however the firm has been seeking to broaden its prospects on this space as its blockbuster antibody drug Humira loses market share to biosimilar competitors. The corporate is offsetting among the income declines with Skyrizi, an antibody drug, and Rinvoq, an oral small molecule. Each merchandise are increasing their labels to a number of immunology indications. Capstan brings a brand new modality to AbbVie’s immunology pipeline.
Probably the most superior Capstan program is CPTX2309, which is being developed as a remedy for B cell-mediated autoimmune issues. The remedy is meant to deplete pathogenic reminiscence B cells, enabling the immune system to repopulate with naïve B cells that don’t keep in mind attacking wholesome tissue. This method might “reset” the immune system, doubtlessly stopping illness development and even resulting in scientific remission.
In preclinical analysis offered on the latest annual assembly of the American Society of Cell & Gene Remedy, Capstan reported its CAR T-therapy led to in vivo engineering of immune cells adopted by depletion of B cells in blood and tissues. Moreover, the remedy didn’t require lymphodepletion, which is suppression of the immune system. This preconditioning helps make sure the engineered cells are taken up by the physique. It’s a required step of ex vivo CAR T-therapies for most cancers.
A Section 1 check of CPTX2309 is underway enrolling wholesome volunteers. Whereas the principle targets are to evaluate security and efficacy, the trial might additionally present indicators of how the remedy is working. Secondary examine targets embody measuring ranges of elements of CPTX2309 and ranges of circulating B cells.
William Blair analyst Matt Phipps spoke with AbbVie administration, who mentioned a preliminary have a look at information from the Section 1 examine present “sufferers reaching fast and strong B-cell depletion, which offers some scientific validation of CPTX2309,” he wrote in a word despatched to traders. Whereas this program continues to be in early scientific growth, William Blair believes the acquisition demonstrates AbbVie’s strategic effort to strengthen its immunology franchise with novel, disease-modifying approaches.
“Given the stage of growth, this asset clearly comes with scientific threat, however given the potential of in vivo CAR-T, which doesn’t require lymphodepletion and has potential for larger manufacturing scalability, it gives important long-term upside if profitable,” Phipps mentioned.
Capstan’s co-founders embody Carl June, a professor of immunotherapy at Penn who developed Kymriah, which underneath Novartis grew to become the primary FDA-approved CAR T-therapy. Drew Weissman, a Penn professor in vaccine analysis and an skilled in mRNA, is one other Capstan co-founder. The startup launched in 2022, revealing $165 million raised so far. Capstan final raised cash in 2024, a $175 million Collection B spherical of funding. In addition to its lead program for B cell-mediated autoimmune illness, Capstan’s pipeline consists of preclinical in vivo CAR T-programs in growth for plasma cell issues and fibrotic issues.
Different firms in numerous levels of growth with CAR T-therapies for autoimmune illness embody Kyverna Therapeutics and Autolus Therapeutics, albeit with therapies which might be made ex vivo. Medical-stage startup Umoja Biopharma has know-how for in vivo CAR T-therapies. Final 12 months, AbbVie licensed an Umoja in vivo CAR T-program in growth for blood cancers. Umoja has one other in vivo CAR T-program for autoimmune illnesses in growth underneath a partnership with Iaso Biotherapeutics.
Photograph: Smith Assortment/Gado, through Getty Pictures
