LONDON – Motif Bio plc is now prospecting for commercialization partners to market its hospital-administered antibiotic iclaprim after recruiting the first patient to the pivotal phase III trial at the start of this month.

The company has been taking soundings and CEO Graham Lumsden said he aims to sign one or more deals in 2016. "What we are hearing is that there are pharma companies with marketing infrastructures and not much in the way of products to fill them," Lumsden told BioWorld Today.

While it will retain rights in the U.S., Motif is looking for partners for all other territories. Lumsden is expecting these deals to include cash up front, citing Trius Therapeutics Inc.'s $94 million agreement with Bayer AG in July 2011, in which the San Diego-based company took $25 million on signing over certain rights to its antibiotic torezolid.

Lumsden said Motif is well funded for now, having raised $40 million over the past 11 months, in a listing and follow-on funding round on the Alternative Investment Market (AIM) in London. However the company will need more money to fund the iclaprim development plans.

"At some point in 2016, we will have to do something. Our approach is that we want to have choices. We can choose to go back to the capital markets or we can bring in money from licensing deals," said Lumsden.

The phase III program will recruit a total of 1,200 patients with acute bacterial skin and skin structure infections. Iclaprim, a dihydrofolate reductase inhibitor, which is effective against multidrug-resistant bacteria, is being compared to standard-of-care treatment with vancomycin, with the aim of demonstrating non-inferiority.

The study is due to finish in the second half of 2017, with all data analyzed by the end of the year. "With our QIDP [qualified infectious disease product] designation, the FDA will then take the file and turn it around in six months, giving us potential to commercialize in 2018," Lumsden said.

The patents on iclaprim, which was originally discovered by Roche AG, have expired, but FDA incentives for developing antibiotics will give the product 10 years of market exclusivity.

London-based Motif also is preparing the ground to test iclaprim in hospital-acquired bacterial pneumonia. A 700-patient phase III trial will get off the ground later in 2016, but Lumsden said this will be much slower to recruit.

"It will take three years; these patients are seriously ill, with a 25 to 50 percent mortality rate. They are so sick it is difficult to get them signed up," he said.

Motif has made considerable headway in the year since announcing plans to float on AIM to raise funds to revive the fortunes of iclaprim, which was turned down by the FDA in January 2009, on the grounds that the data did not demonstrate non-inferiority to the comparator, Pfizer Inc.'s Zyvox (linezolid).

That verdict, and the call for further phase III trials, signaled the end for then-owner, Arpida AG, of Reinach, Switzerland, and the file was subsequently withdrawn from the EMA, too.

Lumsden has always maintained iclaprim was a victim of circumstance, with the FDA in a cautious mood after it became evident that another antibiotic, Sanofi SA's Ketek (telithromycin) approved in the U.S. in 2004, was causing liver toxicity.

Other antibiotics caught in the crosshairs were oritavancin (Targanta Therapeutics Corp., later acquired by The Medicines Co.), telavancin (Theravance Inc.), ceftobiprole (Basilea Pharmaceutica AG), and cethromycin (Advanced Life Sciences Inc.). A new drug application (NDA) by New York-based Pfizer Inc. for another antibiotic, dalbavancin, was pulled after the FDA asked for a new trial.

Of these products, dalbavancin, brand name Dalvance, was approved in May 2014, leading on to the acquisition of its then owner, Durata Therapeutics Inc. by Actavis plc for up to $809 million. (See BioWorld Today, Oct. 7, 2014.)

The Medicines Co. won approval for oritavancin, now branded Orbactiv, in August 2014.

Given the chequered history of these and other antibiotics, Motif is taking a deliberately cautious approach in its new attempt to steer iclaprim through phase III.

As one case in point, Lumsden mentioned the September 2015 failure of Tetraphase Pharmaceutical Inc.'s eravacycline in its second phase III trial, in which the antibiotic was tested in both intravenous and oral formulations in complicated urinary tract infections.

The product previously met the endpoint in its first phase III trial in intra-abdominal infections. (See BioWorld Today, Sept. 10, 2015.)

"We decided, looking at what has happened to other antibiotic companies that the mandate should be to de-risk development," Lumsden said. "For that reason, we are doing the two phase III pivotal trials in the same indication, using the same intravenous formulation."

In another risk reduction measure, it has been decided to give a fixed dose, rather than a weight-based dose, as was the case in the Arpida phase III trial of iclaprim.

"The FDA said some patients were underdosed [in the Arpida trial]. Unusually, we have been able to use the pharmacokinetic data from that phase III to select a single dose that is optimized for efficacy and safety," said Lumsden.

In addition to testing the intravenous formulation, Motif is working on an oral formulation of iclaprim, with potential for use in indications including osteomyelitis and prosthetic joint infections.

The company also is in discussion with potential partners to license antibiotics with novel mechanisms, for treating gram-positive and gram-negative pathogens.