As orphan indications go, Breath Therapeutics believes it has found an ideal niche. The German company, supported by last week’s €43.5m ($46m) series A round, is developing an inhaled formulation of the immunosuppressant cyclosporine A for bronchiolitis obliterans syndrome, chronic inflammation that leads to the rejection of a lung transplant and the swift demise of the patient.
The disorder affects around 15,000 people worldwide so, if the product is approved, Breath should be able to commercialise it itself, chief executive Jens Stegemann tells EP Vantage – unless it attracts the interest of a bigger player. First, though, the group has to prove that the drug works in an upcoming phase III trial, and this is not a given judging by previous failures by others in the field.
Oral vs inhaled
Oral cyclosporine is already used to prevent the rejection of organ transplants, and while it is effective in most other organs its use in the lung is limited by biology, Mr Stegemann explains. It has a better success rate in acute lung rejection, which “is always related to an inflammation of the small blood vessels around the lung, so systemic treatment with cyclosporine A makes a lot of sense”.
However, chronic rejection caused by bronchiolitis obliterans syndrome (BOS) is another story. “This is inflammation inside the small respiratory airways. You cannot treat that with a systemic immunosuppressant because the therapeutic window of those drugs is very narrow, and you cannot increase the dose otherwise you’re running into nephrotoxic problems.”
“When BOS starts, it’s comparable to a very severe cancer prognosis,” Mr Stegemann continues. “The mean survival time is one to three years [and] there’s no treatment.”
This is one of the major reasons why outcomes for lung transplant patients are still so poor, he says: while heart and kidney transplant recipients now have five-year survival rates of 80% and 90% respectively, the rate is just 50% in those receiving a lung transplant.
Developing an inhaled version of cyclosporine A seems like an obvious solution; however, efforts to do so in the past have not fared well. Programmes by Chiron and APT Pharmaceuticals “were terminated because of problems with the nebuliser and the formulation”, says Mr Stegemann.
These companies used a “very slow” nebuliser, which required a 30-40 minute treatment twice daily, and the formulation was not well tolerated by patients, he adds.
The chief executive is confident that Breath will not be scuppered by these issues, saying its liposomal formulation of cyclosporine A is “well-tolerated”, and that it can be delivered in five or 10 minutes using the eFlow nebuliser marketed by Pari Pharma, from which Breath has been spun out.
Pari had been developing the inhaled cyclosporine A itself, but only got as far as proof-of-concept before shelving it for strategic reasons. “Pari decided to focus on medical devices and stopped its internal [pharmaceutical] programmes,” says Graziano Seghezzi, a partner at Sofinnova, one of the investors in Breath.
Mr Stegemann, who was director of business development for Pari at the time, formed Breath to take the asset forward. Meanwhile, “Pari is supporting the spin-off, they are investing in the company, and we have good licence and commercial supply agreements,” says Mr Seghezzi.
Mr Stegemann’s faith in the project will soon be put to the test. Breath plans to start enrolment in its phase III trial, which should require around 250 BOS patients and will have a digital health element to monitor patient compliance, in 15-20 months. The cost should be fully covered by the recent funding round, he adds.
If the trial is successful and approval follows, Breath is prepared to sell the product itself. “You could distribute this product with a marketing and sales force of, let’s say, 10 people – six in the US and four in Europe,” says Mr Stegemann. “You can imagine that this is one of the attractive things in this business case.”
This is indeed a factor that enticed Sofinnova, Mr Seghezzi says. “When we get the phase III data we could either get bought, because it’s a very interesting asset, but we could equally decide to commercialise it. We could really build a company and the commercial operations, and we really like that, because that gives us flexibility on what our exit is going to be.”
Breath now just has the small task of getting a result in phase III.