In an interaction with BioPharma APAC, Noxopharm CEO Dr. Gisela Mautner discussed the company's newly announced proprietary product candidate, SOF-VAC™, and its potential to enhance mRNA vaccines. SOF-VAC™ is based on Noxopharm's Sofra™ technology platform, which uses very short nucleic acid sequences to modulate inflammation at its source. Dr. Mautner explained how the vaccine enhancer can reduce unwanted side effects of mRNA vaccines, improve vaccination program outcomes, and potentially make mRNA vaccine manufacturing more cost-effective. She also highlighted the significance of SOF-VAC™ being the smallest known molecule of its type to demonstrate strong activity against inflammation, and how this could reduce the risk of off-target effects.

Can you tell us more about Noxopharm's newly announced proprietary product candidate, SOF-VAC^TM, and how it works to enhance mRNA vaccines?

“Our Sofra™ technology platform is based upon very short nucleic acid sequences, which are the building blocks of DNA or RNA and are known as oligonucleotides, or oligos for short. These oligos provide a novel treatment approach, acting on specific sensors of the immune system to modulate inflammation at its source. Importantly, mRNA vaccines and some of their degradation products bind to the same inflammation receptors and activate them, which results in a variety of unwanted side effects.

“Because SOF-VAC blocks these inflammation receptors, when administered in conjunction with mRNA vaccines, we believe that we can significantly reduce these unwanted side effects.”

What are the potential benefits of SOF-VAC^TM in making mRNA vaccines safer, better tolerated by patients, and more cost-effective to manufacture?

“Millions of people around the world have benefitted greatly from mRNA vaccines developed in response to the COVID pandemic, and we recognise the achievements of the scientific community in creating these vaccines and rolling them out at a time of desperate need. However, these vaccines are not perfect and there is room for improvement. Perhaps the biggest challenge is to minimise the side effects people can experience after receiving their jabs, and this is where we come in.

“Currently, the need to minimise side effects restricts the amount of mRNA that can be used in a vaccine dose, which in turn limits the vaccines’ activity on the immune system, and the degree and duration of immunity gained from vaccination. Technologies like SOF-VAC^TM that could reduce side effects should improve vaccination program outcomes.

“Regarding manufacturing, we’re not going into too much detail yet, but we believe using SOF-VAC^TM could enable mRNA vaccines to be produced without the need for a specific component that currently plays an essential role in vaccine production.”

Can you explain the significance of SOF-VAC^TM being the smallest known molecule of its type to demonstrate strong activity against inflammation, and how this reduces the risk of off-target effects?

“When an mRNA vaccine is injected, the mRNA gives the body signals to develop an immune response to the target virus, for example SARS-CoV-2 for COVID-19. However, this mRNA breaks down into fragments, some of which bind to Toll-like receptor 7 (TLR7) inflammation receptors, which can result in over-stimulation causing inflammatory side effects.

“The effect of mRNA vaccines on TLR7 is a major limiting factor influencing vaccine tolerability and efficacy, so creating a vaccine enhancer that reduces these unwanted effects would represent a step forward in mRNA vaccine technology.

“SOF-VAC^TM relies on artificial DNA/RNA fragments of three bases. Our discovery that such short synthetic DNA/RNA molecules can have a strong biological function on TLR7-driven inflammation challenges many preconceptions that such short molecules can have an activity – most oligos used to date are longer than 10 bases. Because of their short length, our SOF-VAC^TM oligos represent a new class of molecules in themselves: they are less likely to bind to other proteins and nucleic acids, which is a concern with longer oligonucleotides. This in turn limits off-target activities.”

How was SOF-VAC^TM developed, and what role did the Hudson Institute of Medical Research play in its development?

“We have been working very closely with the outstanding team at the Hudson Institute for a few years now, having originally in-licensed this technology in 2021 via our Pharmorage subsidiary. The Hudson Institute has a very important role in this program as it houses Australia’s largest group of inflammation researchers. The team we work with is led by Associate Professor Michael Gantier, a renowned expert who has been active in this field of research for over 20 years.

“Together, we all work very closely on a daily basis to shape our R&D strategy and then execute it. This currently involves conducting several studies related to the SOF-VAC^TM vaccine enhancer, but there is also another area of cooperation involving the drug development part of the Sofra^TM platform, where we are developing standalone treatments for autoimmune diseases such as lupus.

“Put simply, Noxopharm and the Hudson Institute have a strategic relationship that is going from strength to strength as these promising research programs move forward.”

 What kind of preclinical studies have been conducted to demonstrate the efficacy of SOF-VAC^TM, and what are the next steps in its development?

“We have done some work in human cells and in other areas, but for commercial and intellectual property reasons we can’t reveal too much about these yet. We expect to be in a position to release more information later in the year.”

Can you tell us more about the growing worldwide activity in the multi-billion dollar mRNA market, and how Noxopharm's technology fits into this market?

“Beyond COVID vaccines, one of the key drivers of the market right now is a growing realisation of the diverse range of diseases that could be mitigated via mRNA therapeutics. People can see where this technology is heading and how it might create value for companies as this potential becomes more apparent and solidifies into real-world opportunities. This has been borne out by increasing activity in the commercial world, where it’s not hard to find evidence of companies building up their capabilities in this area, whether through in-house investments, acquisitions or strategic stakes – plus there’s also greater interest from the wider investment community.

“We believe SOF-VAC^TM has the capacity to outperform mRNA modification and therefore addresses a current challenge regarding vaccine manufacture, as well as efficacy and side effect profile.”

How has Noxopharm been building a robust IP position around its lead vaccine candidate, and what patent applications are currently in progress?

“We have a robust patent strategy in place, and will continue to file applications related to this technology in order to provide stronger protection and longer effective patent terms. The IP is commercially sensitive, and for these reasons we cannot go into details right now.” 

Can you provide any details on the progress of Noxopharm's drug development program, which includes the development of standalone treatments for autoimmune diseases such as lupus?

“Along with the SOF-VAC^TM vaccine enhancer we are also working with the Hudson Institute on a related program under our Sofra^TM technology platform, again involving short oligonucleotides but with a focus on drug development for autoimmune diseases. We believe our core technology has the potential to be effective against diseases like lupus because of the way these proprietary ultra-short oligos block overactivated inflammation receptors. We are currently progressing various in vivo and in vitro studies with the goal of building up our assets and commercialising them in due course.”

What are Noxopharm's plans for the future of SOF-VAC^TM, and how does the company aim to generate interest in its assets?

“We believe SOF-VAC^TM has the potential to be of interest to companies already involved in existing mRNA vaccine supply chains, or those that want to get into the mRNA market. This vaccine enhancer is proprietary, novel and backed by solid data and a very experienced team.”

Lastly, what do you see as the future potential of mRNA technologies in medicine, and how does Noxopharm fit into this picture?

“mRNA technologies represent one of the most exciting areas of medicine right now, and the scientific community, companies and governments are increasingly confident that mRNA investments made today will pay off in the future as a broad range of opportunities opens up. Together with the Hudson Institute, we have a strong team that is developing unique technology that we believe will be of interest as the mRNA market experiences strong growth over the coming years – there is a lot more to come for mRNA, and like everyone we’re fascinated to see how it develops.”