To prevent organ rejection, a lifelong, daily regimen of chronic immunosuppression is necessary to suppress the transplant recipient’s immune system.
Although chronic immunosuppressant treatment can be effective at preventing organ rejection, it can have many drawbacks, including:
kidney damage, potentially leading to loss of the transplanted organ
increased risk of cancer and infections
significant cardiovascular, metabolic, or neurologic complications that prompt need for many other medications (often 20 or more pills per day)
cost and lifestyle burdens, which can lead to non-compliance, thereby adversely affecting outcomes
We believe that our Facilitated Allo-HSCT Therapy has the potential to reprogram the immune system of recipients of solid organ transplants to recognize the donated organ as “self,” thereby avoiding organ rejection without the degree of toxicities, risks, co-morbidities, and burden of compliance associated with chronic immunosuppression.
Facilitated allogeneic HSCT for living donor kidney transplant
Our initial focus is on living donor kidney transplant (LDKT). Long-term outcomes in LDKT are suboptimal due to the complications associated with taking lifelong chronic immunosuppression medications. We believe FCR001 has the potential to establish durable allogeneic tolerance in LDKT recipients to their transplanted organ, thereby permitting the LDKT recipient to discontinue all chronic immunosuppression within approximately twelve months of their transplant, without rejecting the transplanted organ. FCR001 has been granted Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations by the U.S. Food and Drug Administration (FDA) in this indication.
Phase 2 clinical trial results
In our Phase 2 trial of 37 adult LDKT patients treated with FCR001, 26 of 37 patients (70%) were able to completely discontinue their chronic immunosuppression approximately one year after receiving their transplant. After mid-course optimizations to the Phase 2 protocol, 14 of the last 17 patients (82%) in the trial were able to discontinue their chronic immunosuppression by approximately one year post-transplant. Every transplant recipient who was weaned off immunosuppression has remained off chronic immunosuppression, without any organ rejection, for the duration of their follow-up.
As of January 31, 2021, we have followed these patients for a median of over six years post-transplant, and the longest for over 11 years post-transplant, with no evidence of biopsy-proven acute rejection. These results were achieved despite significant degrees of immune system human leukocyte antigen (HLA) mismatch between the donors and recipients, and the degree of immune mismatch between the donor and recipient did not appear to impact the safety or efficacy of our therapy candidate. Moreover, preliminary data indicates that patients who were weaned off immunosuppression with FCR001 had preserved kidney function and third-party data suggests a markedly lower reliance on cardiovascular medications at four years post-transplant compared to traditional transplants with chronic immunosuppression over a similar time frame.
We continue to monitor the patients in our Phase 2 trial for long term safety and durability of effect. Through January 31, 2021, we have accumulated approximately 235 patient-years of exposure to FCR001 in LDKT, and the safety profile in our patients is generally consistent with that expected if a patient were to separately receive both a standard kidney transplant and an allo-HSCT with nonmyeloablative conditioning. As of January 31, 2021, five-year survival rates of the patients enrolled in our Phase 2 and of their transplanted kidneys were comparable to what is reported for standard LDKT according to the United Network for Organ Sharing (UNOS).
Other programs in kidney transplantation
We have initiated a clinical development program in “delayed tolerance” in living donor kidney transplant in which we will evaluate whether FCR001 can induce durable immune tolerance to the transplanted organ when it is administered to LDKT recipients up to one year following their kidney transplant. We are also conducting preclinical research to explore whether we can successfully procure and process cells from deceased donors. If these efforts are successful, this could extend the potential of our Facilitated Allo-HSCT Therapy to benefit recipients of organs from deceased donors, significantly expanding our approach to kidney transplant and other solid organ transplant patients.
Ongoing and planned clinical trials
We are running a Phase 3 trial of FCR001 in living donor kidney transplant, called FREEDOM-1. We will also be initiating a Phase 2 trial in “delayed tolerance” living donor kidney transplant, called FREEDOM-2. Learn more >>