LONDON – MGB Biopharma Ltd. is looking for new investors or a commercialization partner to take its lead program, MGB-BP-3, through to market, after reporting 100% initial and sustained cure of Clostridium difficile infections in a phase IIa dose-ranging study.
In the trial, 250-mg MGB-BP-3 enteric-coated tablets given twice a day for 10 days cured acute infections and prevented recurrence at eight weeks. That is in contrast to standard of care vancomycin where there is initial cure but the infection recurs in 20% to 30% of cases.
The company points to the ability to prevent recurrent infections as a key differentiator that gives the compound potential to become a first-line treatment.
MGB-BP-3 achieves that effect by rapidly killing vegetative C. difficile in the 10 to 15 hours before it sporulates and lies dormant in the gut.
“We are absolutely delighted to get that effect and to get a very clean safety profile,” said Chris Wardhaugh, chief business officer. “We’ve confirmed we have a compound that is both safe and highly effective in the target of reducing recurrence. There is a surprisingly high mortality from C. diff infections; it’s because the bugs aren’t killed,” he told BioWorld.
Glasgow, U.K.-based MGB Biopharma said the trial demonstrates the 250-mg dose is able to strike the right balance between maximal killing effects, whilst having a minimal effect on the normal gut flora.
That prevents MGB-BP-3 from sparking the usual vicious circle, in which broad-spectrum antibiotic treatment destroys the microbiota, giving resting C. difficile spores an opening to germinate and form vegetative cells that cause a further bout of diarrhea. Each recurrence is associated with increased risk of further recurrence.
The impact on the microbiome is one of the secondary endpoints, but that analysis is not completed yet. “We are still very much going through the data. We only got the safety and efficacy results last week,” Wardhaugh said. “But we’ve shown in previous studies that [MGB-BP-3] kills bacteria so they don’t form spores. We’ve been able to demonstrate in previous studies it is very rapidly bactericidal and wipes out bacteria in the vegetative state.”
It also has been demonstrated MGB-BP-3 is effective against a hypervirulent strain of C. difficile that is largely resistant to current therapy. That strain accounts for 20% of cases in Europe and 50% in North America.
The cure rate is impressive, but the numbers are small, with only 10 patients in each of three dose cohorts, of which 250 mg was the middle dose. The company has drawn up plans to move straight to phase III, with an interim analysis on the way.
The next step will be to hold a phase II meeting with the FDA, which Wardhaugh suspects will be delayed because of the COVID-19 pandemic. “So we can’t confirm the size of the phase III yet. We did have a post phase I meeting and looked at a number of options. That gave us comfort a single phase III demonstrating superiority over vancomycin, in particular in hypervirulent strains of C. difficile, would be enough for approval,” Wardhaugh said.
“Phase III is really beyond us, so we are looking for partners or investors to take it on. We have it planned out so we can complete clinical development and have started to talk to companies large and small.”
Eligible for incentives
MGB Biopharma has had a hand to mouth existence since it was spun out of Strathclyde University in Glasgow in 2010, to commercialize research of chemistry professor Colin Suckling into compounds that are selective binders of the minor groove of pathogen DNA.
The main backers are Archangel Investors, a syndicate of business angels, and the government-backed Scottish co-investment fund, but the company has not disclosed the value of any rounds of investment. The phase IIa trial, which took place in North America, was funded through a £2.78 million (US$3.4 million) U.K. government grant.
C. difficile infection is recognized as an urgent threat pathogen by the U.S. CDC and MGB-BP-3 has FDA qualified infectious disease product status. That could lead to fast track submission and five years of extra marketing exclusivity.
The product also will be eligible for the prescribing incentives being put in place under the DISARM (Developing an innovative strategy for antimicrobial resistant micro-organism) Act. MGB Biopharma has also talked up the chances of MGB-BP-3 being recommended as first-line treatment in the Infectious Diseases Society of America guidelines, if it makes it through to approval.
The phase IIa dataset has even more resting on it, in that MGB-BP-3 also is active against seven of 21 priority pathogens listed in the GAIN (Generating antibiotic incentives now) Act. Those include the gram-positive infections vancomycin-resistant Staphylococcus aureus and Enterococcus, and gram-negative Pseudomonas, Klebsiella and Escherichia coli.
MGB Biopharma has developed other formulations of MGB-BP-3, including liquid-filled capsules and a freeze-dried product which is designed to be reconstituted for intravenous administration.
Final formulation optimization and scale up of the intravenous formulation have been completed, as have preclinical proof-of-concept studies against Staphylococcus aureus, Streptococcus pyogenes and pneumoniae. There also is a topical formulation for treating MRSA-infected skin lesions in the works.