Cell therapy started as highly personalized, with treatments made by taking a patients own immune cells and engineering them in a lab. Multiple efforts are underway to develop off-the-shelf cell therapies but these treatments made from donor cells are not personalized and could prompt immune responses. Kelonia Therapeutics is proposing another alternative: an off-the-shelf cell therapy that is also personalized to the patient. The biotech company aims to offer both features with technology that enables the cell engineering to happen inside of the patient.
Were solving for something that no one else is solving for right nowthat in vivo gene delivery, said Kevin Friedman, Kelonias president and chief scientific officer.
The Cambridge, Massachusetts-based startup recently emerged from stealth with $50 million in financing closer to bring its research closer to clinical testing. The Series A round includes participation from Alta Partners, Horizon Ventures, and Venrock.
The cells used in cell therapy are engineered with lentiviruses that deliver a genetic payload. In a CAR T therapy, that genetic payload gets the cell to express a receptor that targets a protein on cancer cells. The multi-step process for making these therapies is expensive, laborious, and time consuming. It can take a month or more to turn a patients immune cells into a CAR T treatment.
Kelonia builds on work done with lentiviruses. Friedman said the problem with current lentiviral technology is that the virus binds to a receptor expressed on a broad number of tissues. That means some of it goes to unintended targets, leading to toxic effects. Kelonias technology enables targeted delivery. The technology modifies the envelope of the lentivirus, which detargets it, Friedman said. The virus is then decorated with antibodies that redirect the virus. Infused into the body, those viruses go to the desired cells taking with them their genetic cargos. The cells then express a therapeutic protein, such as a cancer-targeting receptor. Friedman said Kelonias approach avoids the multi-step manufacturing process required of currently available cell therapies.
Were eliminating all that, Friedman said. Were eliminating that and ending up with essentially a personalized medicine.
Kelonias detargeting technology comes from the MIT lab of Michael Birnbaum, a professor of biological engineering and a co-founder of the startup. He is among the authors of a research paper published last month in Nature Methods describing the detargeting and redirecting of lentivirus-like particles.
Kelonia is pushing forward with two partners that are helping the biotech develop its new therapies. Antibody specialist Adimab will discover the antibodies used to decorate the lentiviral envelope, directing it to the desired cells. The lentiviral particles will be manufactured by ElevateBio in its facility. Kelonia will codevelop the manufacturing process with ElevateBio. Friedman said that working with ElevateBio will reduce what are typically long lead times for transferring technology from process discovery labs to GMP facilities.
The first CAR T-therapies to reach the market were treatments for blood cancers. Kelonia is also going after blood cancers as its first indication, aiming to use its technology to offer an off-the-shelf CAR that avoids the adverse effects associated with the current treatments. Those risks include brain toxicities and a dangerous immune response called cytokine release syndrome. Friedman contends that Kelonias approach of producing the anticancer therapy inside the patient should be safer, but the company will need to prove it in clinical trials, of course.
Friedman declined to offer a timeline for beginning human testing, but he said that by getting this technology into the clinic quickly, Kelonia would leapfrog ex-vivo cell therapy approaches while also generating the clinical data to further understand the platform and lay the groundwork for additional therapies. Pursuing a new indication can be accomplished simply by switching out the cargo and engineering the lentivirus for delivery to different tissue. In addition to CARs, Friedman said the Kelonia technology can be applied to T cell receptors or a range of genetic cargos. Beyond cancer, the biotech aims to develop its technology for delivery to neurological, muscular, and renal tissues.
In addition to manufacturing advantages, Friedman said Kelonias technology offers the potential to improve the accessibility of these medicines. Without the need for a complex manufacturing process, Kelonia wont need to be administered only at major medical centers. It could also be offered at community hospitals, making the incredible clinical benefit democratized to the patient no matter where they are, Friedman said.
Kelonia already has big pharma competition. Last year, Sanofi spent $160 million up front to acquire Tidal Therapeutics, a preclinical startup with technology for in vivo delivery of messenger RNA to immune cells in order to reprogram them to address disease targets. Sanofi said Tidals technology could improve the safety profile of cell therapies while also enabling repeat dosing. The pharma giant added that this technology brings the potential for an off-the-shelf approach that could broaden the reach of these therapies to more patients. In addition to cancer, Sanofi said the technology also has applications in autoimmune diseases.
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CAR T without the toxicity: Kelonia gets $50M for a new take on cell therapy - MedCity News
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