The haemophilia A programme SIG-001, which has orphan drug status, leads the companys pipeline for rare diseases.Mr Vivaldi has form when it comes to haemophilia: he was formerly chief commercial officer atSpark, one of the groups developing a gene therapy for the disorder and a takeover target of Roche.

Haemophilia A, in which patients cannot produce clotting factor VIII, is the subject of intense gene therapy research, by companies including Biomarin, Sangamo and Spark. Clinical progress was initially highly promising, but long-term effectiveness remains to be proven (Two more patients bolster Sangamos haemophilia A gene therapy, July 6, 2019).

Mr Vivaldi says Sigilons technology could have several advantages over gene therapy, even if these projects do make it through the clinic to market. Haemophilia gene therapies tend to be unsuitable for children, liver or kidney disease patients, or those with pre-existing antibodies to viral vectors. This could exclude up to 80% of patients, he says.

Gene therapies cannot be re-dosed if their efficacy starts to wane; Mr Vivaldi says that patients can be re-treated with SIG-001 if necessary or have some spheres removed if the dose is too high.

The most important potential advantage is cost. Gene therapies are hugely expensive and no satisfactory payment model has so far been worked out. SIG-001is off-the-shelf and,according to Mr Vivaldi, easily scalable and more cost-effective.

Ofcourse this is all academic until SIG-001 justifies itself in human trials.He explains that the studies will be essentially the same as those for haemophilia A gene therapies, with endpoints including factor VIII levels, bleeding rates and quality of life measures. Data could appear by the end of next year or beginning of 2021.

Diabetes

The other main area of the groups research is diabetes. The timing of clinical trials here is under wraps for now owing to the collaboration agreement Sigilon has with Lilly. In April 2018 Lilly paid $63m up front and made what Mr Vivaldi calls a small equity investment in Sigilon. Milestones of up to $410m and high single-digit royalties on worldwide sales are also part of the package.

The cells are intended to provide a functional cure for type 1 diabetes a condition with which Mr Vivaldi himself lives.This is the same goal being chased by Semma Therapeutics, which was bought by Vertex this month and whose projects are also still preclinical (Vertex spends nearly $1bn on Semmas unproven diabetes cell tech, September 3, 2019). Two other companies, Viacyte and Sernova, have posted very early human data.

The central problem with implanted cell therapies is that unshielded cells have tended to work, but prompted an immune response, whereas encapsulated ones are non-immunogenic but have limited efficacy. Mr Vivaldi believes that Sigilons platform can overcome this, but proof is still some way away.

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Sigilon Therapeutics approaches the clinic - Vantage