Novel antimicrobial strategies harnessing innate immunity
Leveraging defense strategies of the innate immune system, NovaBiotics is developing first-in-class antibacterial and antifungal therapies that could provide a solution to the global problem of antimicrobial resistance (AMR).
“We differ from other companies tackling infection,” explained NovaBiotics CEO Deborah O’Neil; “we are addressing the problem from the host’s perspective and harnessing ‘AMR status agnostic’ components of the innate immune system that would normally deal with infection.” Clinical-stage biotechnology company NovaBiotics is focused on the design of first-in-class anti-infectives for difficult-to-treat diseases via two technology platforms. “Drug candidates from both platforms have mechanisms of action that are agnostic to the antimicrobial resistance status of target pathogens and minimize, if not negate, the development of future acquired resistance,” said O’Neil.
NovaBiotics was founded in 2004 by O’Neil, an immunologist with 20 years’ experience in antimicrobial design and development. NovaBiotics is a privately held company based in Aberdeen, UK, and Raleigh, North Carolina, USA. The company is addressing poorly served, medically unmet bacterial and fungal diseases with therapeutic candidates derived from its cysteamine and antimicrobial peptide (AMP) platforms, both of which are underpinned by a wholly-owned, solid patent portfolio.
In nature, AMP and cysteamine are components of the body’s first line of defense against pathogens. By harnessing the beneficial properties of these natural infection-fighting agents, NovaBiotics has created its dual drug development platforms. Candidates derived from its cysteamine platform are adjunct therapies to existing standard-of-care antibiotics. Cysteamine has antibiotic, antibiofilm and antivirulence properties in its own right, but it is also a potent, broad-spectrum chemopotentiator that improves the performance of other existing antibiotic classes.
O’Neil explained, “Narrow-spectrum antibiotic adjuncts such as β-lactamase inhibitors have made a significant clinical impact since their discovery and validate the concept of antibacterial adjuncts. We have something that has much broader utility and can actually reverse antibiotic resistance outright when used as an adjunct to existing antibiotics.” Cysteamine has already been in clinical use for over 25 years as a treatment for unrelated metabolic diseases, and so has the advantages, including a somewhat expedited regulatory pathway, of a repurposed therapy.
Candidates in development
The first drug candidate from NovaBiotics’ cysteamine stable was Lynovex (NM001). It provides a completely novel approach to treating the cause and symptoms of cystic fibrosis (CF)-associated respiratory infections in all CF patients, regardless of CFTR genotype/ mutation status. Lynovex is also potently mucolytic and therefore represents a breakthrough in CF treatment, with orphan drug status granted in the United States and Europe. An oral (hard gel capsule) ‘high-dose’ form is being developed as an acute-use adjunct for CF infectious exacerbations and is currently in global preregistration clinical studies (product launch is anticipated in 2019). An inhaled, ‘low-dose’ version for long-term CF therapy is also in development (launch is anticipated in 2021).
NovaBiotics’ second platform is generating novel, synthetic antibacterial and antifungal peptide drug candidates with membrane-targeted, rapidly microbicidal modes of action. These compounds are derived, but wholly distinct from endogenous AMPs. They share common, highly desirable properties with their endogenous AMP predecessors, including rapid time of kill and activity against a broad range of fungal, bacterial and polymicrobial infections, including multiple-drug-resistant pathogens, but are synthetic, therapeutically viable, novel peptide structures.
The company’s most advanced asset from this platform is Novexatin (NP213), a topical treatment for nail fungus. A large phase 2b study is under way with the company’s global licensing and codevelopment partner, Taro Pharmaceuticals, and results are expected in 2018. Studies to date show that Novexatin is the first topical agent with the potential to resolve infection and deliver rapid cosmetic benefits after only a few weeks of treatment, compared with months for currently available treatments.
Additional earlier-stage candidates derived from both of NovaBiotics’ platforms include Novarifyn (NP432), a potent bactericidal peptide that outperforms traditional therapy classes in terms of kill time; Novamycin (NP339), an antifungal peptide active against Aspergillus, Cryptococcus and Candida spp., as well as emerging fungal pathogens (anticipated to enter clinical development in 2018); and Nylexa (NM002), a systemically administered cysteamine-based antibiotic adjunct for a broad range of drug-resistant or treatment recalcitrant infections, including those caused by pathogens deemed ‘urgent’ or ‘priority’ threats by the World Health Organization and the US Centers for Disease Control and Prevention.
Tackling the antibiotic-resistance crisis
NovaBiotics approach offers potential solutions to the looming global crisis of antibiotic and antifungal drug resistance. The mechanisms of action of the drug candidates from both of the company’s platforms are such that the compounds are active against currently drug-resistant pathogens and mitigate opportunities for future drug-resistance development. Furthermore, as ‘synthetic biologics’, they also display no or very limited off-target pharmacology and so have placebo-like safety profiles.
A rational drug-design approach has enabled NovaBiotics to create smaller, simpler, more potent and ‘druggable’ derivatives of innate immune factors. The company has streamlined its discovery and development process such that product candidates have been delivered to the clinic in less than 5 years from patent priority dates.
The clinical and commercial potential of NovaBiotics’ compounds has been validated through the commercial partnerships and collaborations already achieved for Novexatin (Taro Pharmaceuticals) and oral Lynovex (undisclosed partner), and this paves the way for the further development and commercialization of related, earlier-stage compounds derived from NovaBiotics’ dual platforms.
“With our highly differentiated approach to R&D, we have come very far, quickly on a relatively modest spend; that makes us a good bet,” said O’Neil. “But the real strength of our anti-infective technologies is that they mitigate AMR challenges now and are highly unlikely to re-create the antimicrobial-resistance challenge in decades to come.”
Deborah O’Neil, CEO
Tel: +44 (0)1224 711377