From The Editor | September 19, 2022

Capstan Therapeutics' Next Steps For In Vivo CAR Therapies


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1


Capstan Therapeutics is a brand-new biotech company dedicated to developing and delivering precise in vivo cell engineering to patients. With $165 million in financing, Capstan Therapeutics aims to build on the foundational insights of leaders in mRNA and cell therapy from the University of Pennsylvania. Laura Shawver, Ph.D., leads the company as President and CEO, and on the heels of the biotech’s recent news, I caught up with her to learn more about the company’s plans for developing in vivo CAR therapies.

It’s been stated that Capstan Therapeutics’ initial efforts will focus on developing in vivo CAR therapies with the goal to deliver treatments in an outpatient setting for patients who have diseases for which there are no effective treatments. How does the outpatient setting impact in vivo delivery?

Shawver: The COVID-19 vaccine taught us is that you can deliver mRNA in a lipid nanoparticle that allows for that mRNA to be translated into a protein that results in a biological consequence. And cell therapy has taught us that if you can activate T cells ex vivo to recognize a tumor antigen and cure patients with certain cancers.

The first-in-class in vivo CAR therapeutic candidates we’re developing unite these two breakthrough technologies—which were pioneered by our founders— with the potential to accomplish this inside the body.

This is a completely different paradigm from how current ex vivo CAR-T therapies are delivered. First-generation CAR-T therapies were transformative breakthroughs for oncology patients, but they involve complex manufacturing, require patients to be close to teaching hospitals that have specialized CAR-T floors for hospitalization and monitoring of potential serious adverse events. As a result, CAR-T treatments are inaccessible to the vast number of patients around the world.

Because our therapies are designed to deliver a specific mRNA payload within a targeted LNP for a therapeutic effect inside the body, as we’ve demonstrated in a mouse model that was published by our founders in Science earlier this year, and as seen with the mRNA-based COVID-19 vaccines, you could imagine the ease of delivery we have the potential to offer patients and the medical community.

That said, it’s too early to speculate on exactly what specific form this would take as our near-term goal is to remain focused on our foundational science and advancing our programs through optimization of each of the components, preclinical development and then into clinical development. But our vision is that our therapies would be delivered in outpatient settings.

The company plans to use the funds to further its mission of advancing the clinical promise of cell-based therapies by enabling precise in vivo engineering of cells with payloads necessary to benefit patients across multiple disease categories. Why is the in vivo engineering component critical, and how will precise in vivo engineering move forward the progress of cell-based therapies?

Shawver: Capstan is uniting the most exciting clinical breakthroughs of the last decade within one platform that enables a novel scientific approach that is only now possible: the precise control of certain cells in the body. We believe that we can demonstrate this first in T cells and this could lead to control of other cell types. Building on the clinical progress of mRNA, CAR-T and LNP delivery technology pioneered by our scientific founders, we are bringing to reality the potential to engineer cells in vivo – which has the potential to ultimately expand the applicability and accessibility of cell and gene therapy to more patients with a broader range of diseases. Our technology has the potential to transform cell therapy, gene editing and mRNA therapeutics, from broadening the indications each can address, to streamlining manufacturing, to bringing these medicines to patients in an earlier treatment setting and in more remote geographical areas, and likely in a more cost effective manner.

Explain the significance of mRNA and targeted LNP technologies regarding cell-based therapies that are enabled by precise in vivo engineering.

Shawver: We know that cell therapies result in cures for some people with certain cancers.  Targeted LNPs with a mRNA payload are designed to do the same thing and if we can prove this out in people, it will be broadly applicable to other cell types, for more patients and in other disease types outside oncology.  With our targeted delivery system, Capstan could unlock the full potential of mRNA medicines, a modality that saw incredible success in addressing the COVID-19 pandemic.

What is the plan for manufacturing?

Shawver: It’s unlikely that we will need in-house manufacturing capabilities. When you think about the components of our platform—mRNA, LNPs, antibodies or antibody fragments— many organizations across the biopharma industry know how to make these components. Our work ahead lies in optimizing these components and combining them but because these modalities are well-established as this point, we don’t anticipate we will face manufacturing hurdles or require specialized manufacturing capabilities.

How does translational science play a role in the success of the therapies?

Shawver: Our origins began with the 2019 publication of research in Nature by our co-founder and Vice President of Research showing that ex vivo CAR-T could be applied to diseases outside of cancer. In 2022, our founders published landmark research in Science demonstrating this approach could be achieved in vivo.

Capstan was born when our founders and founding executive team recognized that this novel approach could transform medicine because not only does it unlock cell and gene therapy for far more diseases beyond oncology, but bypasses many of the hurdles the first and second generations of these therapies currently face, which include costly and time-consuming ex vivo engineering that is further limited by safety and tolerability issues. While our founding science began with CAR-T, we believe Capstan will be able to extend this to many cell types.