In 2017, the Judges’ Choice of the most serendipitous innovation went to Jeff Weers of Respira Therapeutics for his previous work on the successful commercialisation of TOBI® Podhaler®, the first dry‐powder, inhaled antibiotic for cystic fibrosis.
And while Jeff can’t talk about the specifics his latest work regarding Respira’s partnership with United Therapeutic for commercially sensitive reasons, the Chief Technology Officer’s passion for science and innovation – and his abiding interest in what actually lies behind that ‘eureka’ moment – means he is only too happy to explain the long genesis that eventually bore fruit in a truly revolutionary new technology.
One crucial requirement, he says (but without any hint of arrogance), is having the courage to be different to what the rest of the industry is doing: “My background is centred around how to engineer particles to accomplish different things and we haven’t let ourselves be bound by what the rest of the industry is doing. The teams I've had the pleasure to work alongside are renowned for taking risks, challenging current norms and trying to change the field.”
That willingness to take risks led the team at Inhale to develop the first-ever inhaled protein delivered for systemic action (inhaled insulin, Exubera®) – which required nothing less than having “to change how medicine was being done at the time.” While everyone else was taking a micronised drug and blending it with lactose, the team decided stabilize the protein in an amorphous glass via spray drying, thereby creating the first room-temperature stable insulin product on the market.
Continued advances in the spray drying technology used in Exubera now enables up to 95% of the insulin dose that is delivered from a portable dry powder inhaler to be deposited in patient’s lungs. Current marketed inhalers deliver between 10% and 40% of the dose into the lungs.These dramatic improvements in “lung targeting” reduce the potential for side effects, while also improving the consistency of dosing.
The other critical aspect to the breakthrough – and this is where Jeff’s fascination with baseball came in – lay in an appreciation of the critical role of aerodynamics; not something one would normally associate with pulmonary drug delivery systems.
There is a rather charming short video on the Novartis YouTube channel titled “How baseball transformed particle engineering” in which Jeff explains how the concept came about. Having been a decent pitcher – capable of hurling a hard rubber sphere wrapped in cowhide down at over 90mph – he was struck by the difference between the aerodynamic properties of a baseball and those of a wiffle ball. Although roughly the same size as a baseball, this perforated, light-weight, hollow plastic orb designed originally for kids play behaves dramatically differently in aerodynamic terms. One key difference is speed: “When you inhale porous particles, as opposed to solid ones, they are able to move much more slowly and with less inertia than a solid particle, so they are much more effective in passing the bend from the mouth to the throat and down into the lungs. This allows the delivery of much higher doses of the drug than had been previously possible with solid particles.”
“In some ways that’s how innovation takes place. You leverage innovation you’ve done to continue to move forward”
While the idea of using concepts from aerodynamics in pulmonary drug delivery strikes the lay person as nothing short of brilliant, Jeff insists that this is only the start: “There are a lot of smart people out there and coming up with the idea is the easy part. The concepts around what you’re trying to do is often the hard part. It comes down to figuring out what the true end need is and that’s not as easy as it seems.”
This is where his refusal to be bound by prevailing industry wisdom – to “step outside of conventional thinking” – paid dividends: “There are lots of misconceptions about what’s important and it’s hard work figuring out what’s true. Understanding what those misconceptions are often leads to opportunities.”
So, while the team was “really excited at changing the aerodynamics of particles,” in order to convert the concept into an actual product that could be delivered into the lungs, the challenge remained of how to translate the aerodynamic characteristics of a wiffle ball into drug particles with a size less than the width of a human hair.
If that was yet another moment of inspiration, the deep reservoir of scientific and engineering knowledge and capacity for sheer hard graft would not have borne fruit without an element of apparently pure chance: “We weren’t in [the inhalation market at that time at Alliance] and weren’t looking to do it – we stumbled upon it when doing other work.” In fact, Alliance had another product with pharma giant GSK, who asked Alliance “if we had anything else"? We started thinking about it. That’s when we went into the inhalation field. It was accidental in the sense that the product we were making and got marketed was for a totally different field that had nothing to do with inhalation … so it was serendipitous in the sense that that’s not what [the spray dried powders] were being developed for. But we noticed their aerodynamic properties, started thinking about it and made those analogies back to baseball.”
This begs the question: is there such a thing as pure chance? Collins English Dictionary defines serendipity as “the faculty of making fortunate discoveries by accident”. While allowing that there is faculty in the process, even this doesn’t fully account for the alchemy that lies behind true innovation. Jeff has his own theory: “You draw on all of your experiences to try and move forward. When first developing PulmoSpheres, we were doing it for something different than the broad application that it actually evolved into. We were leveraging two other products (a blood substitute and an ultrasound contrast agent) and ended up creating a whole new technology. In some ways that’s how innovation takes place. You leverage innovation you’ve done in one field in to a whole new opportunity.”
And while the problem-solving and creative aspects of his work are both immensely satisfying, ultimately it is his innate humanitarianism that is really the driver behind Jeff’s thirst for innovation, as the Novartis video makes clear: “What really keeps me going and doing this work is getting out and meeting the people we’re actually developing these drugs for. It is very gratifying to see the benefits people get from taking the medications you’re working on. It’s a great feeling.”
For more information on the 2018 Real Innovation Awards and to nominate view here. Nominations are closing on 25 May 2018.
How TOBI Podhaler was born
The history of how TOBI Podhaler was created is a classic example of how innovation, rather than resting purely on a sudden, blinding revelation, often stems from an unlikely series of events. The story began when Jeff’s team at Alliance Pharmaceutical Corp in San Diego came up with the concept “way back” in the mid-1990s. The technology was subsequently acquired by Inhale Therapeutic Systems (later Nektar Therapeutics) in 1999; Nektar then made a deal with Chiron to develop it; Chiron was then acquired by Novartis; Novartis later also acquired the pulmonary business unit of Nektar in 2009... and eventually completed development of TOBI Podhaler. (Jeff left Novartis in 2017 and is now at Respira, who had no role in the development or marketing of TOBI Podhaler, which Novartis continues to own and market.) Child’s play...
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