• In vivo influenza protection was achieved at a significantly lower antibody dose with intranasal compared to systemic administration
• In contrast to what is observed with systemic administration, Leyden Labs’ lead influenza antibody CR9114 has a unique mechanism of protection when administered intranasally
• The unmatched breadth of CR9114 is further supported by the discovery of binding to influenza C and D alongside A and B viruses – an essential attribute for durability of protection against new, emerging strains

LEIDEN, Netherlands–(BUSINESS WIRE)–Leyden Laboratories B.V. (the “Company” or “Leyden Labs”) today announced the publication of new findings that showcase the advantages of intranasal administration of monoclonal antibodies over systemic administration for protection against airborne viruses.

The studies reported in this paper demonstrate the uniqueness of intranasal administration of broadly protective antibodies as a novel, non-vaccine approach to protect against respiratory viral infection. These new insights pave the way towards intranasal antibody delivery to provide protection against influenza and other airborne viruses.

Key Findings:

• Intranasal antibody administration is effective at significantly lower dosages compared to systemic administration. Central to the strategy of Leyden Labs is to deliver broadly protective antibodies directly at the gate of viral entry, namely, to the respiratory mucosa. With these in vivo data, it is demonstrated that intranasal administration of CR9114 is efficacious at significant lower dosages than required for systemic administration. CR9114 is the monoclonal antibody component of the Company’s PanFlu candidate. CR9114 was shown to have a more potent (low dose) protective effect when administered intranasally vs intravenously in mice. Typically, there is a trade-off between potency and breadth in antibody activity: broadly-neutralizing antibodies often are less potent in vitro. This publication however shows that intranasal administration resolves this trade-off in vivo: by administering CR9114 intranasally, low-dose protection is effective.

• Intranasal antibody administration enables protection that is not dependent on Fc-mediated effector functions. CR9114 protection against influenza was shown to be Fc-independent with intranasal administration in vivo. Although Fc-mediated effector functions play a large role in the mechanism of action of systemically administered antibodies, they are not required for efficacy following intranasal administration. Intranasal CR9114 can provide protection through its front-end (Fab) alone, both against strains that are neutralized in vitro and strains that are not neutralized in vitro. Importantly, this observation further highlights the opportunity to redefine criteria for preclinical evaluation of the protective potential of an antibody based on the route of administration.

Clarissa Koch, PhD, Chief Research Officer of Leyden Labs commented, “We are excited to share this great work from our team and collaborators as we continue to expand our understanding about the nuances of administration of protective antibodies directly to the respiratory mucosa. We expect to publish additional data later this year regarding intranasal antibody dynamics as well. Under our Mucosal Protection Platform, findings such as these help in important ways to inform the ongoing development of PanFlu, as well as to shape additional pipeline programs by our team.”

Nigel Temperton, Professor of Molecular Virology and Director of Viral Pseudotype Unit at the Medway School of Pharmacy, University of Kent and University of Greenwich UK, who collaborated with Leyden Labs on these studies, said, “These findings have the potential to meaningfully impact the field of viral prophylaxis using antibodies. Although many valuable efforts have been made over time to optimize antibody composition for prophylactic use, contribution of the route of administration may have been underappreciated.”

Not only does this paper report discoveries about the uniqueness of intranasal administration, it also demonstrates that the breadth of activity of CR9114 is even greater than previously recognized. In addition to its known affinity for influenza A and B subtypes, it has now been shown that CR9114 also binds influenza C and D. Although influenza C and D are less at the forefront of current healthcare concerns – they mostly circulate in cattle and other animals – this finding reinforces the unique breadth of activity of CR9114 achieved by targeting a highly conserved domain. Since it is known that breadth is important for the effectiveness and durability of antibody prophylaxis, particularly when seeking to protect against new, emerging strains, this too is a significant discovery.

The article published in Scientific Reports is entitled, “Intranasal administration of a panreactive influenza antibody reveals Fc-independent mode of protection.”

About Leyden Laboratories B.V.

Leyden Labs is working to free people from the threat of respiratory viruses. Leyden Labs is leveraging its Mucosal Protection Platform to develop a portfolio of candidates aimed at providing protection against influenza, coronaviruses, and other respiratory viruses through a new class of broadly protective nasal sprays.

Systemically administered antibodies or vaccines primarily generate systemic protection. Airborne viruses, including influenza and coronaviruses, enter the body through the nose and mouth. Thus, what we need is protection right at the gate, at the respiratory mucosa, to more effectively prevent initial infection and subsequent illness.

Leyden Labs is pursuing this strategy by developing nasal sprays that administer broadly protective antibodies directly to the respiratory mucosa. These antibodies aim to protect against full viral families, so they keep working even when a virus mutates and evolves. In addition, this intranasal strategy is beneficial for people with weakened immune systems because it does not require a fully functional immune response.

To learn more, visit www.leydenlabs.com.

About PanFlu candidate CR9114

CR9114, Leyden Labs’ lead product candidate for the PanFlu program, is a human monoclonal antibody that protects against influenza in preclinical models. Leyden Labs holds an exclusive license from Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to develop and commercialize CR9114.

Contacts

Investor Contact
Elizabeth Goodwin

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investors@leydenlabs.com

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