Nabriva Therapeutics Forschungs GMBH
This article was originally published in Start Up
Executive Summary
In January, Sandoz spun out Nabriva Therapeutics to initiate clinical development of three classes of antibiotics. Using medicinal chemistry, Sandoz had created thousands of compounds derived from intermediates used in the manufacture of generic antibiotics, which were themselves active against bacteria.
Hitting the ground running, with thousands of leads
Brunnerstraße 59
Vienna 1235, Austria
Phone: +43 1 866 59 569
Fax: +43 1 866 59 785
Web Site: http://www.nabriva.com
Contact: Rodger Novak, MD, COO
Industry Segment: Antibiotic Drug Development
Business: Antibiotics for community and hospital-based infections
Founded: January 2006
Founders: Sandoz spinout
Employees: 39
Financing to date: €42 million ($53 million)
Investors: Nomura Phase4 Ventures; HBM Partners; The Wellcome Trust; Global Life Sciences Ventures; Novartis BioVenture Fund
Board of Directors: David Chiswell (founder and former CEO, Cambridge Antibody Technology); Denise Pollard-Knight, PhD (Nomura Phase4 Ventures); Ernst Meijnders (Sandoz); Gerd Ascher, PhD (Sandoz); Peter Reinisch, PhD (Global Life Sciences Ventures); Axel Bolte, PhD (HBM Partners)
When process development specialists at the Sandoz unit of Novartis AG discovered that some of the intermediates used in the manufacture of generic antibiotics were themselves active against bacteria, it made sense to establish a research unit within the company to exploit that finding. Sandoz therefore established the Antibiotic Research Institute (ABRI) in 2001 to apply medicinal chemistry to those molecules and develop new antibiotic chemical entities, moving the group from its site near the headquarters in Tyrol to the more research-friendly environs of Vienna.
But as the generics portion of Sandoz grew—in particular with the acquisition of Hexal AG , the second-largest generics company in Germany, in February 2005 [See Deal]—its board of directors decided to restructure and focus solely on generics. Although parent company Novartis, for its part, was increasing its investment in the antibiotic therapeutic area, its focus was on antivirals and novel antibacterial mechanisms. Moreover, ABRI had 50 people, making a spin-off more attractive than the prospect of integrating the unit into the upcoming Novartis therapeutic area," explains Rodger Novak, who had been recruited as deputy head of ABRI in early 2003.
In January 2006, ABRI spun out of Sandoz, and with Novak as COO, it became Nabriva Therapeutics Forschungs GMBH . Sandoz transferred all of the programs and virtually all the intellectual property residing at ABRI, along with the ABRI facility. Coincident with the spinout, the new entity also raised €42 million in venture capital to fund operations. [See Deal]
ABRI had generated three distinct sets of compounds from the intermediates they'd been working with, and these remain the value drivers of Nabriva, according to Novak. One set is in the well-known class of cephalosporins, whereas the other two are pleuromutilins, a group of antibiotics used extensively in veterinary applications to prevent mycoplasma enzootic pneumonia syndrome in swine. Pleuromutilins are active against gram-positive anaerobic organisms and mycoplasma, as well as a few gram-negative aerobic species.
From 2001 to 2005, as a captive unit of a large organization, ABRI focused on generating leads: it created 2,000 cephalosporins, for example, all derived using medicinal chemistry, not by screening libraries. "We wanted to have enough compounds in each program," Novak explains, to maximize the odds for success in the clinic later on. With that mission accomplished, Nabriva is now "clearly focused on development—late preclinical and clinical," he says. Although Sandoz holds a minority stake in Nabriva, "we're an entirely different entity from it or Novartis," adds Ralf Schmid, Nabriva's CFO.
Nabriva's two pleuromutilin programs are its most advanced. Out of the more than 300 oral pleuromutilin formulations in the ABRI portfolio, the start-up intends to advance BC-3205, a compound to treat respiratory tract infections, into the clinic this year. BC-3205 appears active against resistant gram-positive organisms, in particular methicillin-resistant Staphylococcus aureus (MRSA) as well as other species of staph, and it has demonstrated no potential of cross-resistance against any known class of antibiotics.
Nabriva is also completing toxicology on a second oral molecule, in keeping with its strategy to have a back-up in position for each of its clinical programs. "We can do this for two reasons," Novak points out: not only does Nabriva already have the molecules to work with, it knows the characteristics of the leads very well. "The follow-ons have the potential to address additional needs in future antibiotic therapy," he says—a broader spectrum of activity and slower development of resistance. The second pleuromutilin-based program targets bacterial-associated dermatological diseases, using a topical formulation. Nabriva has selected BC-7103, based on its pharmacodynamics and pharmacokinetics in skin and demonstrated preclinical activity against resistant gram-positive pathogens. Phase I clinical trials of BC-7103 are anticipated to start in the first quarter of 2007.
To round out its clinical plans, Nabriva is in the process of selecting a lead development candidate among its cephalosporin derivatives, many of which are anti-MRSAs. Importantly, in addition to possessing broad gram-positive activity, Nabriva wants its cephalosporins to also be capable of treating infections from gram-negative organisms, including producers of extended spectrum beta-lactamases (ESBLs)—a growing concern in the treatment of hospital-based infections, Novak points out.
Having a broad-spectrum drug with activity also against gram-negative bacteria will help differentiate Nabriva's cephalosporin from those in the same class in late-stage development in Big Pharma, which is focusing on anti-MRSAs. Nabriva's goal in cephalosporin development, says Novak, is to obtain a first-line indication as broad as possible, to give physicians a parenteral drug they can use with high confidence in hospital settings against hospital-acquired pneumonia, bacteremia, septicemia, and urinary tract infections. Similarly for respiratory tract infections, Nabriva expects to be able to address a wide range of pathogens with its drugs. "When we were able to do that, we were able to move forward," he suggests.
With confidence in its ability to move all three programs forward, Nabriva foresees having a mix of commercial strategies, including co-development and the option to move forward with a niche application on its own. "We have a stated goal to develop some compounds to commercialization," Novak says. He would likely partner or out-license the oral pleuromutilin program, given the resources a small company would need to effectively reach the bulk of physicians treating respiratory tract infections.
Compelling proof-of-concept data with one or two molecules will influence future financings and could give Nabriva the option to monetize the value of other assets: those decision points could come by the end of 2008. Existing resources should cover its burn for the next few years, including the addition of five or six people with regulatory experience to assist in clinical development and project management. Nabriva will run early clinical trials in Europe on its own, and enlist CROs in the US.
In addition to Novak, Nabriva's management team includes CFO Ralf Schmid, previously head of treasury at Sandoz, where he executed the spinout of ABRI into Nabriva; head of biology Rudolf Badegruber; and head of chemistry Werner Heilmayer, PhD—all of whom were at ABRI prior to Nabriva.--Mark L. Ratner