8 July 2020 - - The US Food and Drug Administration has approved US-based biotechnology company Talaris Therapeutics, Inc's Investigational New Drug application for the evaluation of Talaris' novel cell therapy FCR001 in the treatment of diffuse systemic sclerosis, a severe form of the rare autoimmune disease scleroderma, the company said.

Approval of this IND allows Talaris to initiate a Phase 1/2a trial at sites across the US, including Duke University and the University of Michigan.

Scleroderma, which derives from the Greek words "sclero," meaning hard, and "derma," meaning skin, is a rare and potentially fatal chronic autoimmune disease which causes progressive scarring, or fibrosis, of the body's connective tissues. Scleroderma can either be localized or systemic.

Systemic scleroderma, also called systemic sclerosis, is further divided into the limited cutaneous subset and the diffuse cutaneous subset, depending on the degree of skin involvement.

Both types affect the skin and vital internal organs, especially the lungs, kidneys, gut and heart, resulting in organ dysfunction. Patients with the diffuse subset generally have rapidly progressive skin and internal organ involvement and have worse outcomes than the limited subtype.

Based on encouraging data from randomized clinical trials, autologous hematopoietic stem cell transplant is increasingly used to treat severe cases of diffuse cutaneous SSc, where it has been shown to halt organ damage and induce clinical remission.

However, because patients are transplanted with their own stem cells, there is a risk of disease recurrence, and patients typically must first undergo full myeloablative conditioning with or without total body irradiation, which is associated with direct organ toxicity and increased risk of future cancers.

Talaris' allogeneic cell therapy, FCR001, is a novel, one-time treatment intended to induce immune tolerance in the recipient and which can be used across all levels of donor-recipient HLA mismatch. Treatment with FCR001 is preceded by non-myeloablative conditioning.

In a Phase 2 clinical trial in de novo living donor kidney transplant recipients, FCR001 resulted in durable immune tolerance in 70% of the 37 recipients treated; these individuals were able to successfully discontinue their anti-rejection medications and no tolerized patient has had to resume immunosuppression (median follow-up of over 5 years, longest follow-up is over 10 years).

Furthermore, seven of the successfully tolerized patients had kidney failure due to an underlying autoimmune disease, and none of these patients has experienced recurrence of their underlying autoimmune disease post-treatment.

Based on these encouraging data and its broad therapeutic potential in autoimmune disease, FCR001 will be evaluated in a planned Phase 1/2a trial of patients with diffuse cutaneous SSc.

FCR001 is an investigational, allogeneic cell therapy developed by Talaris Therapeutics to induce or restore patients' immune tolerance.

FCR001 builds on over 30 years of research by the company's founder, Dr. Suzanne Ildstad, into the means by which durable immune tolerance can be induced in a patient who receives a transplanted organ or can be restored in patients with certain immune-mediated or blood disorders.

FCR001 has received both Orphan Drug Designation and Regenerative Medicine Advanced Therapy designation from the US Food and Drug Administration.

A Phase 3 trial of FCR001 in living donor kidney transplant recipients, FREEDOM-1, is now enrolling patients.

Talaris Therapeutics is a late-clinical stage biotechnology company that is developing cell therapies with the potential to eliminate the burden of chronic immunosuppression for organ transplant recipients as well as induce durable remissions in patients with severe auto-immune and immune-mediated disorders.