Talaris Therapeutics Inc., a company developing an allogeneic cell therapy intended to eliminate the need for chronic immunosuppression among organ transplant recipients, has closed a $100 million series A financing. The financing was led by Blackstone Life Sciences, with participation from Longitude Capital and Qiming Venture Partners USA.

Talaris, a privately held company formerly known as Regenerex LLC, said it will use the funds to start a pivotal phase III study of the therapy, FCR-001, later this year in living donor kidney transplant (LDKT) recipients as well as two additional phase II studies in other high-need indications. The Boston-based company, which also named a new CEO, will expand its in-house cell processing capabilities in Louisville, Ky. to support the development programs and its early commercial launch needs, it said.

In addition, Talaris reported new data from a phase II study in which investigators found that 26 of 37 (70%) LDKT recipients of FCR-001 were able to be weaned off all of their immunosuppression treatments, with some patients having even survived for 10 years without immunosuppression to date. Initiated in 2009, the study ran through 2016, the year in which Regenerex's then-partner Novartis AG decided to discontinue its advancement of the program as it dismantled its broader cell and gene therapy unit outside of oncology. As a result, rights to the program reverted to Regenerex.

Reducing need for immunosuppression

Scientific substantiation of the concept of acquired immunological tolerance and the ability to induce it in mice drew a shared Nobel prize for Peter Medawar in 1960, setting scientists on a decades-long quest to produce the same effect in adults, Talaris' chief scientific officer and former CEO, Suzanne Ildstad, told BioWorld. (See BioWorld Today, March 12, 2012.)

FCR-001's genesis rests in Ildstad's 1990 discovery in bone marrow of tolerogenic graft facilitating cells, which can act as a chaperone for an organ donor's stem cells, helping them "to migrate to the bone marrow and set up shop there," she said. That assistance takes the form of both facilitating engraftment of the donated stem cells and up-regulating tolerogenic pathways in a self-sustaining way, eventually leading at least some cell recipients to develop a chimeric immune system.

In addition to the phase II study, Talaris CEO Scott Requadt told BioWorld that the company's team has also compared the three- and five-year outcomes for patients of Northwestern Memorial Hospital who received FCR-001 following their transplants to the outcomes of a cohort of transplant recipients at the same hospital who did not, but who would have been eligible for the trial. In the cohort that didn't receive the experimental therapy, investigators saw a decline in renal function and other side effects of immunosuppression, he said. By contrast, in those LDKT recipients who did receive FCR-001, investigators saw normal ranges of renal function, hypertension and high cholesterol.

"It's that data that has triggered a lot of investor interest and ultimately led to the syndicate betting $100 million to support the company," Requadt said. It also convinced Requadt himself, previously a managing director at Clarus, to join the company as CEO.

With a regenerative medicine advanced therapy designation from the FDA for FCR-001 in hand, the company has been in close communication with the agency about the design of its phase III trial. Though that design has yet to be finalized, Requadt said the regulator will want "to see that you can not only get people off immunosuppression, but they'll want to see some durability to that."

Availability of a regimen to overcome the need for immunosuppressive drugs following organ transplant could be transformative for organ recipients. They typically need to take two to three immunosuppression drugs on a daily basis for the rest of the life of the transplant, said Ildstad, who has completed extensive training in transplant surgery. Unfortunately, the same drugs that help prevent organ rejection can cause high blood pressure, hyperlipidemia and cardiovascular disease, as well as increased risks of cancer and infection, she said. Some are also even toxic to the kidney, which can eventually lead to renal failure necessitating the kidney be replaced.

Talaris' process starts a few weeks before a kidney transplant, at which point its team administers a few injections of granulocyte-colony stimulating factor to the living kidney donor to coax stem cells out of the donor's bone marrow and into their circulatory system. Next, apheresis is used to harvest and isolate stem cells and other immune cells from the donor's system to be shipped to the company's Novartis-built and validated processing site in Louisville, where potentially harmful cells are removed before the stems cells are frozen and shipped to the clinical site.

A few days prior to the kidney transplant recipient receiving the transplant, they undergo a mild conditioning regimen with chemotherapy and low-dose full-body radiation to create room for the stem cells to take hold. A few days after the transplant is complete, FCR-001 is thawed and transfused by I.V. into the patient. Within a few months, investigators look for chimerism, or signs that a certain proportion of the recipient's T cells and blood cells are donor-derived. If the chimeric immune system is verified, at six months post-transplant, immunosuppression can start to be tapered until, barring emergent organ rejection, they reach a 12-month endpoint of being fully weaned from immunosuppression.

Next up, the company will work to launch one phase II study in a severe autoimmune indication and another testing FCR-001 for the induction of delayed tolerance. That study, for which the company has already secured FDA permission to proceed, "will open the door for deceased donor liver transplant, heart transplant and all the other organs," Ildstad said.