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 based mostly 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 Part 1 take a look at 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 complete course of can take weeks, although many corporations 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 strategy 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 extensively used supply automobile for genetic medicines, they’re usually one-time therapies. These engineered viruses immediate the physique to supply antibodies towards them, so subsequent doses can be rendered ineffective. Against this, a lipid nanoparticle doesn’t immediate that immune response, making redosing potential. That’s vital for bringing cell remedy to immunology, the place remedy of continual illness usually requires redosing.
Immunology and irritation is already a power of AbbVie, however the firm has been trying 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 problems. The remedy is meant to deplete pathogenic reminiscence B cells, enabling the immune system to repopulate with naïve B cells that don’t bear in mind attacking wholesome tissue. This strategy might “reset” the immune system, probably 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 Part 1 take a look at of CPTX2309 is underway enrolling wholesome volunteers. Whereas the principle objectives are to evaluate security and efficacy, the trial might additionally present indicators of how the remedy is working. Secondary examine objectives embody measuring ranges of elements of CPTX2309 and ranges of circulating B cells.
William Blair analyst Matt Phipps spoke with AbbVie administration, who stated a preliminary take a look at knowledge from the Part 1 examine present “sufferers attaining fast and sturdy 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 improvement, William Blair believes the acquisition demonstrates AbbVie’s strategic effort to strengthen its immunology franchise with novel, disease-modifying approaches.
“Given the stage of improvement, this asset clearly comes with scientific danger, however given the potential of in vivo CAR-T, which doesn’t require lymphodepletion and has potential for higher manufacturing scalability, it affords important long-term upside if profitable,” Phipps stated.
Capstan’s co-founders embody Carl June, a professor of immunotherapy at Penn who developed Kymriah, which below 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 thus 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 contains preclinical in vivo CAR T-programs in improvement for plasma cell problems and fibrotic problems.
Different corporations in varied phases of improvement with CAR T-therapies for autoimmune illness embody Kyverna Therapeutics and Autolus Therapeutics, albeit with therapies which can be made ex vivo. Medical-stage startup Umoja Biopharma has know-how for in vivo CAR T-therapies. Final yr, AbbVie licensed an Umoja in vivo CAR T-program in improvement for blood cancers. Umoja has one other in vivo CAR T-program for autoimmune ailments in improvement below a partnership with Iaso Biotherapeutics.
Photograph: Smith Assortment/Gado, through Getty Photographs
