Phoenix and MD Anderson expand cell therapy safety switches

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Cross-licensing agreement brings reformulated rimiducid to cell and gene therapies, with implications for oncology and longevity medicine.

The University of Texas MD Anderson Cancer Center and Phoenix SENOLYTIX have announced a global cross-licensing agreement around CaspaCIDe, the preeminent cell therapy “safety switch” technology validated in multiple human CAR T cell therapies. The deal provides Phoenix’s proprietary enhanced formulation of rimiducid, a therapeutic agent that activates inducible switch technologies such as CaspaCIDe, to MDACC for their continued exclusive use in their ex vivo cell therapies in exchange for their materials and support for Phoenix’s exclusive development of the technology in their two novel gene therapy platforms, ApoptiCIDe-CE, a purposeful cell elimination gene therapy platform, and ApoptiCIDe-RGT, a regulated gene therapy platform. Both use Phoenix’s proprietary, enhanced cell elimination switch technology, ApoptiCIDe, that Phoenix’s founders originally developed as CaspaCIDe (as founders of Bellicum Pharmaceuticals), for use in T cells.

The CaspaCIDe safety switch has been deployed in multiple patients suffering acute, life threatening toxicities from T cell therapies, with resolution of those toxicities often within minutes but universally within 24-48 hours of administration of the rimiducid activating agent [1,2]. Rimiducid is also the activating agent for the “go” switch, iMC, deployed in GoCAR-T, GoTCR, GoDCVaX and Dual Switch technologies acquired by MD Anderson from Bellicum Pharmaceuticals, Inc. In those circumstances when rimiducid is dosed repeatedly, the current IV formulation of rimiducid is cumbersome, compared with Phoenix’s novel SC/IM formulation. Phoenix has reimagined the CaspaCIDe safety switch, designed to be used in ex vivo cell therapies, rarely, only in the case of life threatening toxicity, as ApoptiCIDe-CE, designed to be used as an in vivo gene therapy in every patient, targeted to selective populations of cells for their purposeful elimination. ApoptiCIDe-RGT, Phoenix’s novel proprietary regulated gene therapy platform, that works as a “rheostat” by giving lower doses of rimiducid to turn down, but not necessarily turn off a therapy, is another potentially important advance in the field of gene therapy, in which regulating dose can be imprecise without this second level of regulation available.

Longevity.Technology: Safety switches rarely win the headlines, yet they are the quiet enablers of ambition; an inducible kill-switch turns CAR T cell therapy from a cliff-edge proposition into a controllable platform, which is precisely why this Phoenix–MD Anderson cross-license matters. Reformulating rimiducid from an IV drip to SC/IM is not a cosmetic change – it lowers friction at the bedside and broadens the contexts in which switches like CaspaCIDe and Phoenix’s ApoptiCIDe can be used; practicality is the difference between a clever mechanism and a deployable one. The signal here is bigger than oncology – a validated safety net built in cancer immunotherapy is being pulled through into longevity applications, where purposeful cell elimination and regulated gene expression will live or die on controllability. Furthermore, Phoenix’s reimagined uses of this technology, bringing it for the first time into in vivo gene therapies, may significantly enhance the efficacy and safety of those therapies, as it has done for ex vivo CAR T cell therapies.

Institutional alignment adds weight – MD Anderson brings clinical depth and diffusion channels, Phoenix brings a next-gen formulation and a push into in vivo programs – and the joint advisory board suggests this is a platform play, not a one-off license. Phoenix’s access to MDACC’s supply of GMP rimiducid drug substance and its FDA clinical regulatory documents, including its FDA Drug Masterfile, pushes Phoenix’s clinical development of its programs forward at pace. Finally, it may be unglamorous to say so, but switches are infrastructure; regulators sleep better, investors underwrite bolder trials and clinicians have a fail-safe – in other words, the technology that lets the field drive faster is also the one that keeps it on the road.

A reformulated approach

Rimiducid has traditionally been administered intravenously, but Phoenix has reformulated it into a simpler intramuscular or subcutaneous injection, with the potential to evolve into an autoinjector format. Kevin Slawin, MD, Phoenix founder and CEO, emphasized the significance. “This cross license opens the door to advancement of our novel reimagination of this proven technology, ApoptiCIDe, extending it for the first time from ex vivo cell therapies to in vivo gene therapies,” he said.

David Spencer, PhD, co-founder of Phoenix and scientific founder of Bellicum, described the broader opportunity. “We are excited about the broad medical opportunities presented by the dimerizer applications that would be enhanced with this new formulation of rimiducid,” he said. “This reflects a potentially major advance that should further expand the adoption of cell and gene therapies.”

Safety switches in practice

CaspaCIDe, also known as inducible caspase-9, was originally developed at Bellicum Pharmaceuticals and is a clinically validated safety switch used across multiple cell therapy programs. It allows rapid elimination of transduced cells in the event of severe treatment-related toxicities. “While we have had very promising safety results with our engineered cell therapies, it is critical that we include effective technologies to rapidly eliminate transduced cells in the event of treatment-related toxicities,” said Katy Rezvani, MD, PhD, professor of Stem Cell Transplantation and Cellular Therapy and vice president and head of the Institute for Cell Therapy Discovery & Innovation at MD Anderson.

Rezvani added that her team has already incorporated CaspaCIDe into multiple programs, including CAR-NK therapies, and has made the switch technology available via non-exclusive licenses to other research institutions and biotech companies.

Longevity connections

Phoenix SENOLYTIX is one of the four subsidiaries created under the recently reorganized SENOTHERAPEUTIX hub-and-spoke model, giving the company both independence in its gene therapy focus and shared access to the wider group’s resources and technologies. Phoenix is pursuing longevity-focused applications through its ApoptiCIDe platforms, extending the switch concept from oncology into gene therapies targeting aging and obesity-related disorders.

According to Phoenix SENOLYTIX, its lead senolytic gene therapy clinical candidate, ApoptiCIDe-CE-GERO-002 plus proprietary rimiducid formulation PTC-2102, eliminated ~60 to 70% of senescent cells in the spleens of treated naturally aged 75-week-old mice as assayed by SA-β-gal and Lamin B1. The elimination of senescent cells has been shown to improve tissue function and extend healthspan and lifespan in preclinical mouse models.

Slawin told Longevity.Technology that Phoenix’s current programs build directly on the landmark academic discoveries that inspired him to enter the longevity field.

“Baker et al’s senescent cell elimination technology, incorporated into their p16^Ink4a ATTAC genetic mouse model, and the astounding results they and their collaborators published demonstrating improvements in healthspan and lifespan in that model, was invented and owned by Bellicum Pharmaceuticals, Inc [3,4],” he explains. “Their studies and my desire to create a gene therapy using our Bellicum technology is what prompted me to enter the longevity field. Now, eight years later, we have successfully achieved that at Phoenix SENOLYTIX, and discovered MitoXcel Technology which powers Eos SENOLYTIX and Perseus SENOLYTIX, serendipitously along the journey. This cross license with MDACC allows us to continue to support our Bellicum technology at MDACC for ex vivo cell therapies, while we break new ground with it in in vivo gene therapies and bring Phoenix’s exciting new products utilizing it more quickly towards human clinical trials.”

The company positions ApoptiCIDe-CE as a purposeful cell elimination platform and ApoptiCIDe-RGT as a regulated gene therapy platform capable of adjusting or halting therapeutic protein production in vivo. This broadens the relevance of safety switches beyond oncology and into gerotherapeutics, where controllability is likely to prove essential for regulatory approval and clinical adoption.

Shared development and future direction

As part of the cross-license, Phoenix and MD Anderson will convene a scientific advisory board including Spencer, Slawin and Daniel Jasinski, PhD, on the Phoenix side, and Rezvani with two additional experts from MD Anderson. The aim is to inform development across both organizations’ programs and ensure alignment of clinical priorities.

Phoenix is headquartered in Miami with research facilities in Houston, while MD Anderson advances cell therapy through its Institute for Cell Therapy Discovery & Innovation. Both partners present the agreement as a platform for shared progress in making cell and gene therapies safer, more practical and more widely deployable.

Quiet infrastructure, significant impact

Safety switches may not carry the glamour of novel targets or the promise of senolytic peptides, but their role is no less central. As cell and gene therapies move from oncology into metabolic and age-related conditions, having mechanisms that can eliminate or modulate cells, both engineered or native, on demand will become indispensable. The Phoenix–MD Anderson agreement signals that infrastructure is being built alongside innovation, and that the longevity field may benefit directly from oncology’s cautious but determined path.