CELLVIE featured in Biocentury`s Emerging Company Profile

Harvard spinout cellvie is pioneering therapeutic mitochondria transplantation as a way to rescue cell energy metabolism and save cells that would otherwise die.

James McCully, a cellvie AG co-founder, developed the approach at Harvard Medical School to ameliorate ischemia-reperfusion injury, which is the tissue damage caused when the blood supply returns after a period of ischemia.

"What Jim observed in conditions of ischemia and reperfusion, like a heart attack, is that the mitochondria within the cells get damaged due to the undersupply of oxygen, ultimately leading to cell death," cellvie CEO Alexander Schueller told BioCentury.

"Interestingly, when you reintroduce the blood flow, there`s a the second wave of cell death, as the oxygen streaming into the cells can no longer be processed by the impaired mitochondria.

So, to treat ischemia-reperfusion injury, one must treat that mitochondria damage," he added.

Schueller said he "fell into the medical space" when he cofounded
Adhesys Medical, a surgical adhesive company in Germany. During his time at Adhesys, he interacted with Pedro del Nido, chairman of the Department of Cardiac Surgery at Boston Children`s Hospital, whom he had "always wanted to work with."

After Schueller`s company was acquired, del Nido introduced him to McCully and the concept of therapeutic mitochondrial transplantation. Schueller said he was "immediately intrigued" at the potential of mitochondria as a new treatment modality, not only for ischemia-reperfusion injury, but for any indication that has a dimension of mitochondrial damage.

The three of them founded cellvie along with Sitaram Emani, who was the first person to use mitochondrial transplantation in the clinic. In a pilot study of 24 pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia reperfusion injury, 10 were treated with intramyocardial autologous mitochondrial transplantation.

"Mitochondria get taken up by the damaged cells, reinvigorate the cell energy metabolism and help cells survive," said Schueller.

Reported in The Journal of Thoracic and Cardiovascular Surgery, patients who received the transplantation were more likely to successfully separate from ECMO, had a shorter median time to functional recovery after revascularization, and experienced fewer cardiovascular events.

The mitochondria are suspended in a delivery solution and administered either directly to the area that lacked blood flow or through a catheter immediately following revascularization. "For instance, in the kidney, you would use the renal artery as the port to introduce the mitochondria," said Schueller.

The mitochondria get taken up by the cells through endocytosis.

Schueller said they`ve only used autologous mitochondria in patients, but, in animal models, the therapeutic effect doesn`t change when using allogeneic mitochondria derived from a cell source.

"It seems that mitochondria are immune privileged — we have not seen that they elicit an immune response or any rejection or deterioration of cell functions by transplanting foreign mitochondria," stated Schueller.

The company`s goal is an allogeneic product. Off-the-shelf mitochondria are a challenge, however, because they get damaged when frozen. cellvie is actively working on methods to increase shelf life, and is considering an "espresso-like machine" that prepares therapeutic mitochondria at  the press of a button.

cellvie envisions applying its mitochondrial transplantation platform to many diseases, starting with ischemia-reperfusion injury after kidney
transplantation, for which it plans to start a Phase I trial in 2023.

The company anticipates raising a $15-$30 million series A round in late 2022 or early 2023 to support the trial.

Schueller said cellvie is also interested in using therapeutic mitochondrial transplant to slow or reverse degenerative processes of aging linked to the mitochondria, and Kizoo Technology Capital, who led the company`s $5 million seed round in January, "brings in a wealth of know-how in the aging field and a particular interest in pursuing it."

At least one other company is leveraging mitochondria for therapeutic use, but instead of direct transplantation of the organelle, Minovia Therapeutics Ltd. is enriching CD34+ stem cells with blood-derived mitochondria and using the cells to treat primary mitochondrial
diseases. Its lead product, MNV-BLD, is in a Phase I/II trial to treat Pearson syndrome.