Harnessing endolysins for feed efficiency and animal performance

Whilst it can be helpful to think of endolysins as enzymes with antimicrobial activity specific to the pathogen being targeted, for any of this to be commercially relevant, they have to deliver consistently in real-world settings.

Dr. Kane Miller
Founder and Chief Innovation Officer
Axitan

Feed & Additive talks to the founder and Chief Innovation Officer at Axitan, Dr Kane Miller, and his scientific team to better understand the power of endolysins and how the company has formulated them into products to improve feed efficiency and animal performance.

A lab on an industrial park some 30 miles south west of Cambridge, England, in the London commuter town of Stevenage, might not have the caché of the San Francisco Bay area (USA) or Cambridge, Boston, but sitting within the UK’s biotech “Golden Triangle” of Oxford-London-Cambridge, it is rapidly establishing itself as a place of significant interest in the field of endolysins thanks to the pioneering work of a company called Axitan.

“We have been exceptionally fortunate to be able to access leading minds throughout our development thanks to our proximity to three globally prominent universities,” explained Dr Kane Miller. “We were even more fortunate to meet with US investors from the ag sector relatively early in our journey meaning that today all of our global commercial operations can be run out of North America, led by our CEO, feed additives veteran, Alfred Zimmerman. Their involvement meant we were encouraged to look at issues through the lens of our customers – major animal protein producers – from the get-go and to fully understand their needs rather than just focusing on the science of endolysins for targeting pathogens that impact the livestock industry.”

“That meant fully embracing the notion that if we were going to be successful in the reduction and replacement of antibiotics in the animal protein industry, we had to demonstrate their real-world economic benefits, not just the pathogen mitigation efficacy of endolysins. Or put more prosaically, the improved performance indicators such as weight gain, livability and FCR that an endolysin-based product could deliver.”

SO WHY THE EXCITEMENT AROUND ENDOLYSINS?
Run any Google search on endolysins and three consistent messages emerge. Firstly, their efficacy in terms of the speed in which they will kill a pathogen; secondly, their specificity – they will only target the pathogen they have been designed to target and do not impact beneficial microbiota; and finally, the associated low/close-to-zero risk of their triggering antimicrobial resistance.

For Axitan, what makes them truly unique is their robustness. Dr Miller explained: “When people talk about endolysins they often overly focus people’s attention on their mode of action – how they are purely a cutting device able to break key bonds in the peptidoglycan layer of the targeted cell wall causing it to burst and die.”

“For us, what makes them special is how robust we’ve been able to make them so that they can comfortably withstand the commercialisation process. That means being able to grow them at industrial scale, formulate them with other synergistic ingredients such as mid- and long-chain fatty acids, and then ensuring they can be successfully applied in a feed mill.”
“In short, whilst it can be helpful to think of endolysins as enzymes with antimicrobial activity specific to the pathogen being targeted, for any of this to be commercially relevant, they have to deliver consistently in real-world settings.”

THE FEED EFFICIENCYAND ANIMAL PERFORMANCE OF FORC3® IN HEALTHY FLOCKS
Axitan’s first endolysin-based product in commercial production is FORC3® which was developed to address Clostridium perfringens in poultry, the causative agent of necrotic enteritis which is estimated to cause $6b of economic loss to the global poultry industry each year.

Whilst in vitro studies could point to the product being able to kill more than 99% of all CP bacteria within one hour, there was an initial reluctance amongst major producers to admit that they might even have a C. perfringens related issue.

When Axitan was able to demonstrate that FORC3® was able to achieve improvements in healthy flocks of up to 2.75 percentage points in livability, 3 points in FCR, consistent live weight gains at harvest across production models and an economic uplift of up to 14 cent a bird, the nature of the discussions started to change.
Gonzalo Prat, VP of Sales & Marketing at Axitan: “By focusing conversations on the economic benefits FORC3® could deliver in a healthy flock setting, we saw a fundamental shift in attitude. Discussions were no longer centred around whether CP was or wasn’t a current issue for the producer but around the value FORC3® could potentially deliver. It was a transformational moment that has spawned a swathe of opportunities.”

SPECIES EXTENSION
Central to these has been the recently announced strategic partnership between Axitan and QualiTech which covers the distribution of FORC3® into new market segments in North America – namely swine, ruminants and poultry, excluding broilers which Axitan continues to market directly.

The agreement also sees Axitan and QualiTech collaborating to develop novel endolysin-based products to resolve pathogenic issues in the swine and ruminant segments, QualiTech retaining the exclusive distribution rights of these new products in North America.

Scott Hine, President of QualiTech’s Animal Nutrition and Agronomy businesses, was full of praise for what Axitan has achieved to date, “QualiTech is thrilled about the synergies between the Axitan product line and our existing solutions, enabling us to further our strategic focus on early-life vitality and performance, ensuring a strong start and sustained growth. Axitan’s proven success with their technology positions them as the ideal development partner for introducing the next generation of performance-enhancing, non-resistance-triggering, antibiotic-free feed additives.” He continued: “With consumer demand increasingly favoring antibiotic-free, high-protein food sources, QualiTech and Axitan are poised to lead the way.”

INTERNATIONAL EXPANSION BEYOND NORTH AMERICA
And interest in the pioneering work Axitan has done in the feed additives market is extending beyond North America to regions of the world where the declining efficiency of antibiotics to treat common pathogens is being most acutely seen with commercial sales into South Asia having already begun.

Dr Miller: “It is a source of immense pride to see a concept, originally born out of UK universities, now being commercially available in two continents. But for the Axitan team, this still very much remains the start of our journey and we remain hugely excited for the future ahead and the ongoing expansion of our product portfolio.”