Kevin Friedman, PhD, has spent most of his career working on the cargo to engineer cell therapies. As vice president at Bluebird Bio, he was instrumental in the development of Abecma (idecabtagene vicleucel), the first anti-BCMA (B-cell maturation antigen) chimeric antigen receptor (CAR) T cell therapy for relapsed or refractory multiple myeloma. 

When Friedman launched Kelonia Therapeutics in 2022 to optimize in vivo gene delivery to create new medicines, he focused the company’s lead program on what he knew—anti-BCMA CAR T. 

At Kelonia, Friedman says, “We are focusing on targeting and getting genetic cargo there… in really hard-to-treat diseases, designing the right cargo is an entire project in itself. Entire companies focus on that, throwing millions of dollars at it. As a small start-up biotech company, we can’t solve all the world’s problems, so we want to focus our effort on the gene delivery side.” 

Instead of reinventing the wheel when it comes to genetic cargo, for the past couple of years, Friedman has been looking for “yin” to Kelonia’s “yang”—the in vivo gene placement system (iGPS®), which uses lentiviral particles to efficiently deliver genetic cargo precisely to the desired target cells inside the patient’s body. When Friedman spoke to GEN last year, he said the system would be perfect for creating a universal, off-the-shelf CAR T cell therapy. 

When Friedman learned about a platform technology from Astellas subsidiary Xyphos Biosciences, which creates a universal CAR to enable the detection of multiple tumor-associated antigens, he saw an ideal match that could unlock the potential of iGPS.  

Xyphos, a wholly owned subsidiary of Astellas Pharma, and Kelonia announced a nearly $800 million research collaboration and license agreement to develop innovative universal, off-the-shelf in vivo CAR T cell therapies. 

Across the (cancer) universe 

The process for generating CAR T cells, which have been a revelation for cancer treatment, has been ex vivo. The most important parts of this process—extracting, engineering, and reintroducing T cells to a patient being treated with chemotherapy—have some issues with dosage, effectiveness, and cell manufacturability. 

With an in vivo approach, there is no need to culture the extracted immune cells outside the body and then return them to the patient after conditioning chemotherapy. It is expected to be more tolerable and accelerate treatment to improve the patient’s access to the therapy. 

“A lot of people get tripped up by potency, and they end up having to get very massive [CAR T] doses or multiple doses to achieve a therapeutic benefit,” said Friedman. “Because of our in vivo gene delivery potency, we can give one very low dose, which can cause therapeutic benefits, at least in all the preclinical models. And it’s manufacturable. We can make this thing, and we can do it in a scalable process.” 

However, to be widely applicable, in vivo CAR T cells have to be made in a way that can be adapted to target different tumor antigens in different patients. 

To make universal CAR T cells, Xyphos developed two key technologies: ACCEL (Advanced Cellular Control through Engineered Ligands) and convertibleCAR. ACCEL is based on a synthetic biology approach that utilizes the binding of an engineered protein ligand to an orthogonal engineered receptor, which forms the extracellular domain of a convertible CAR. The convertibleCAR is aimed at tumor cells with an engineered antibody-like molecule that recognizes the tumor antigen and has an engineered ligand attached to it. 

“They have this really great universal CAR technology where we can deliver the same genetic cargo regardless of disease indication to every single patient, and, then, we target [immune cells] in vivo,” said Friedman. “When you pull this all together, you have this off-the-shelf in vivo gene delivery approach that does not require preparative chemotherapy or cell manufacturing, and we modify every single patient’s cells with the exact same genetic sequence, and then we target them at will with Astellas proprietary targeting agents.” 

Concept CAR 

Under the terms of the agreement, the companies plan to combine Kelonia’s iGPS with Xyphos’ ACCEL technology to develop innovative in vivo CAR T cell therapies targeting up to two programs. Xyphos will be responsible for developing and commercializing products created from the collaborative research. 

Kelonia will receive $40 million upfront for the first program and an additional $35 million should Xyphos exercise its options for the second program, with potential milestones and contingency payments approaching $800 million in total. Additionally, Kelonia will receive R&D funding for work performed in the collaboration and is eligible for tiered royalties on net sales up to a double-digit percentage.  

“From a company perspective, they bring the capabilities that we don’t intend to build,” said Friedman. “They bring the vast commercial and manufacturing capabilities, and we can just bring our know-how in cell and gene therapy, having done this before, as well as what we think is this groundbreaking in vivo approach. We’re at the starting line now, so we’ll work with our sales partners to get this into the clinic as quickly as possible.” 

Kelonia will continue to develop its internal pipeline. Besides indicating that they will continue working in the realm of T cells, Friedman and Kelonia haven’t disclosed additional indications they’re pursuing. But Friedman did share that they’re going after indications requiring tunability, antigen heterogeneity, or loss. He expects their lead anti-BCMA CAR program to be in the clinic within the next year, which will likely be before anything from the partnership with Xyphos. 

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