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).

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“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
Aberdeen, UK
Tel: +44 (0)1224 711377

Go to the profile of NovaBiotics Ltd

NovaBiotics Ltd

NovaBiotics Ltd is a leading clinical-stage biotechnology company focused on the design and development of first-in-class anti-infectives for difficult to treat, medically unmet bacterial and fungal diseases. The Company’s advanced portfolio of antimicrobial therapeutic candidates targets large and important markets with significant unmet clinical needs, including Lynovex (in oral and inhaled form), an orphan drug candidate for cystic fibrosis (CF), Novexatin, a potential step change therapy for onychomycosis (being co-developed with and out-licensed to Taro Pharmaceuticals) and Novamycin, a novel antifungal peptide in development for the treatment of aspergillosis, candidiasis and cryptococcosis. Novexatin and Novamycin are among the first-in-class peptide anti-infectives which the company continues to derive from its proprietary antimicrobial peptide rational drug design platform. Lynovex and Nylexa have been developed as novel antimicrobial adjunct therapies from the company's more recently established aminothiol platform. NovaBiotics has a strong portfolio of granted and pending patents which are wholly owned by the Company. NovaBiotics was founded by our CEO, Dr. Deborah O’Neil in 2004 with the goal of fully developing and realizing the therapeutic and commercial potential of innate immune system effector based antibacterials and antifungals. NovaBiotics is a privately held company, based in Aberdeen, UK & Raleigh, NC, U.S.

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