Q&A – Jeff Drew, Chief Innovation Officer

1. Tell us about your career before founding iosBio.

I was a relatively late starter into a scientific career. I have always been interested in science and microorganisms, but my interest wasn’t properly ignited until I undertook a technical qualification at a south Wales college. This led me to my undergraduate degree in Microbiology and Virology at Manchester University and subsequently on to a PhD in Molecular Virology from The Institute of Animal Health at Pirbright & Reading University. During my career I’ve covered a wide range of research areas including virology, cancer, gene therapy and genetic research at a number of institutions including University of Oxford, Marie Curie Research Institute, the Exotic Virus Research Laboratories at the Institute of Animal Health, and the Institute of Cancer Research.

2. How did you become interested in the field of virology?

There was always a boyhood fascination with microbiology, however my exposure to the undergraduate study of viruses re-focussed my interest and I became spellbound with how they work, are able to avoid the immune system and cause disease, and how vaccines can be used to eradicate those diseases. My first degree cemented that fascination, provided context and detail and instigated some of my early thinking of how to utilise the core features of viruses, i.e. essentially avoiding the immune system to deliver genetic information to cells, to immunise against infectious disease but also the potential to treat genetic diseases.

3. How did you come to develop iosBio’s proprietary OraPro™ technology?

Our original work at iosBio was aimed at alleviating the cold chain for vaccines, a system which often fails and leads to around 50% of all vaccines being wasted, largely due to storage at incorrect temperatures. The thermal stability our core technology provides to vaccines and viral vectors enables 25°C storage for years and 56°C for short periods of time – sufficient for cold chain free delivery to locations anywhere in the world. As we began developing our own viral vector-based pipeline we explored other routes of vaccine administration, which ultimately led to our OraPro™ technology.

4. Can you tell us a bit about how OraPro™ works?

Viral vectors are used to deliver DNA to a cell so a particular protein, such as a SARS-CoV-2 antigen or a therapeutic protein, can be produced from that cell to provide a patient with immunity or therapy. Typically, viral vectors are engineered to be non-replicating, that is they cannot make more viral vector copies of themselves within a patient’s cells, so preservation of vector activity is pivotal for maintaining efficacy.

When delivered via injection, a patient’s immune system will develop immunity to the viral vector, meaning subsequent uses of that viral vector will be less effective or have no effect in causing cells to produce the protein. However, as the gastrointestinal tract is home to a huge microbiome (bacteria, yeasts, viruses) it has intrinsic tolerance mechanisms which mean repeated use of a viral vector would be possible. However, viruses and viral vectors are typically very sensitive to both temperature and acidic environments – oral delivery of a vaccine relies on transit through the stomach for several hours at 37°C and a low pH, which would cause rapid breakdown of a viral vector.

Our OraPro™ platform combines both thermal and acidic protection for a non-replicating viral vector through the stomach and a controlled release in the small intestine where the viral vector can cause gut cells to produce antigens for vaccines or proteins for therapeutics. The oral delivery allows us to reuse our viral vector repeatedly without generation of an anti-vector response. When viewed from a patient and healthcare perspective oral medicines are much preferred and far easier to distribute.

5. Tell us about your role as Chief Innovation Officer. What does a typical day look like for you?

Whilst every day is different, typically there’s a lot of technical dialogue and data interpretation and providing scientific direction. We’re fortunate to run a closely knit scientific team where everyone supports each other & our work dovetails across our development programmes so technical debriefs are intellectually rewarding and push our science forward rapidly. I also dedicate a reasonable proportion of my time to developing new IP.

6. What excites you about iosBio?

The progression from a preclinical company into clinical company has been an incredibly rewarding time for us; building up the strength in depth of our team of scientists, expanding our manufacturing expertise to transition our technology from pilot/small scale to manufacturing at commercial scale with ImmunityBio has also been rewarding. Taking our oral delivery technology to address other vaccines and using it to increase vaccine coverage and improve their effectiveness will be incredibly exciting for me and the whole iosBio team.

7. What do you see as the biggest challenges facing vaccination programmes around the world?

The emergence of COVID-19, the rapid development of vaccines has shone a light on the two aspects that our technology address – thermal stability and reliance on needles for administration.

8. Why are oral vaccines poised to transform the future of vaccination?

Protection at the surfaces where most infectious diseases gain entry to their target is provided by the mucosal immune system. Typically, by administration of an injected vaccine a systemic level of immunity is provided, but limited mucosal immunity is generated – thus a pathogen can often still gain entry, replicate and cause onward transmission to those who are not vaccinated or immune. Oral vaccines engage with mucosal associated lymphoid tissue and Peyer’s patch to induce antibody and T cell responses both systemically and at the mucosal surfaces, ultimately resulting in enhanced protection.

From an administration perspective, oral vaccines are self-administered by the individual which means no physical contact required between the healthcare professional and the patient – in pandemic/epidemic situations this will reduce risk of transmission during the vaccination process. There’s also the possibility of vaccines being delivered by mail or door to door which has been successfully demonstrated in typhoid vaccine studies in Nigeria, Zambia and Guinea.

9. With no need for cold chain storage, tell us about the impact that oral vaccines can have on developing countries.

The WHO produced a report on vaccine wastage that showed around 50% of all vaccines are wasted. A large proportion of these are due to lack of temperature control and the logistics required for an unbroken cold chain. Thermally stable vaccines will mean all nations should have the ability to access effective vaccines for prevalent or emergent infectious diseases.

It’s also worth pointing out that this isn’t just an issue for developing countries, controlled cold chain logistics are prone to errors or failures – an audit within the USA found that 76% of vaccine centres exposed their vaccines to inappropriate temperatures, whilst in Korea recently they had to dispose of 5 million flu vaccine doses after they were stored at an incorrect temperature.

10. What are you hoping to achieve at iosBio?

The ultimate goal is to transform vaccinology through thermally robust vaccines, delivered without the need for needles, which provide the broadest immunity possible.