Interview with Scott Fleming (LinkedIn), Gilbert’s Chief Commercial Officer

Scott brings 30+ years’ experience in pharmaceuticals, drug delivery and digital health to Gilbert, where he’s been active since 2019. Before joining Gilbert, Scott worked at management firm PA Consulting, counseling major pharma & biotechs on drug delivery strategy and technology development before exiting to co-found MicroDose Therapeutx in Princeton, NJ, to develop its own proprietary inhalation technologies. As Head of Sales & Marketing he helped grow MicroDose from a start-up inhaler device company with an out-licensing model to an integrated pulmonary products company. This growth attracted buyers and in 2013 MicroDose was acquired by Teva Pharmaceuticals, and Scott joined their global respiratory group in Amsterdam as Brand Lead for eConnectivity and other specialty products, before going back to helping start-ups.

Can you give us some history on the main developments in pulmonary drug delivery? 

Sure, and as Gilbert is developing a ‘liquid inhaler’ format, I will focus on nebulization systems, which convert liquid medication into aerosols for inhalation.

The first electric nebulizers were developed in the 1930s, but by the 1950s Jet nebulizers, that used compressed gas to create a fine mist of medication, had become the most common form of delivery. These large machines required a fixed gas source and were typically used only in hospitals. As technology improved through the 1960s-1970s more portable versions were introduced allowing for at-home treatment. But these too were bulky, noisy and highly inefficient, with long nebulization times and delivering only 10-15% of the dose into the lungs. Jet nebs are also cumbersome to assemble/disassemble and to keep clean. The 1980s brought a new technology, ultrasonics, using high-frequency sound waves to create a mist, offering a quieter and faster option to jet nebulizers. Ultrasonic nebulizers were popular in the home-care market as they were smaller and quieter, but they are incompatible with suspensions and viscous solutions and also generate heat which can damage sensitive molecules like proteins. The 1990s introduced vibrating mesh (VM) nebulizers which force liquid through tiny holes in a vibrating membrane to create an aerosol. VM nebs are more efficient and portable than jet nebulizers, and today are widely used for both hospital and home care. But the fine mesh in VM nebs can become clogged or experience foaming, especially with suspensions and more viscous formulations.

In 2004 the first soft mist inhaler (SMI), Respimat(R) was launched. SMIs deliver a fine mist using mechanical energy from a spring to create a slow-moving mist. SMIs require manual activation which can be difficult for some patients (like the elderly), can only deliver a small dose per inhalation and are currently available for only a limited number of medications.

Are new advancements needed?

It’s been 20 years since we’ve seen a major innovation in the market, and in the meantime advancements in the development of therapeutics has continued to progress, creating new unmet needs and challenges for pulmonary delivery devices. Today, Inhaled therapies are a standard for chronic respiratory conditions, but most are small-molecules, whereas biologics could offer more targeted solutions with longer-lasting effects, especially for managing inflammation and immune responses. In the market overall, biologic-based treatments are replacing small molecule therapeutics at a rapid rate. In 1980 biologics made up less than 1% of the overall pharmaceuticals market, but today they make up 25-30% with projections to reach 45-50% by 2040. This in turn is driving the development of inhaled biologics, and by 2030 biologics like monoclonal antibodies (mAbs) and RNA-based therapies will likely be formulated for inhaled delivery, targeting a broad range of respiratory conditions like severe asthma, cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and COPD. And by 2040, inhaled gene therapies, stem cells, or growth factors to repair lung tissue damaged by COPD and pulmonary fibrosis are envisioned. These future inhaled therapies will require ever more complex formulations and processes, making them more expensive and requiring higher efficiency of delivery to be cost effective, along with greater precision and targeting in the lungs to be efficacious.

Is this where electrospray and Gilbert’s Smart Precision Inhaler comes in?

Yes, It is well known that for inhalation therapies to be effective they need to be deposited in the right region of the lungs to target the intended disease process and relevant receptors, and that aerosol particle size and distribution are the key determinants for lung deposition. But many of the technologies I’ve listed are limited in the particle sizes they can generate and most have fairly broad particle size distributions, which can limit the efficacy of treatment and potentially also contribute to undesired side effects. So there is a strong need for a technology that provides more customizable particle size AND tighter particle size distribution.