Fresh from announcing its merger with Longevity for an additional Nasdaq listing and promising IBS trial results, we openly discuss what’s next for 4D Pharma (AIM: DDDD) with Chief Executive Officer Duncan Peyton.
From the significance of the recent Blautix trial, through to other key developments and expectations for the share price going forward – keep reading to understand more about why DDDD is confident in a very successful future.
Firstly, could you tell us a little around Blautix and the context of IBS?
Irritable bowel syndrome, (IBS) is a complex condition. While it is a common condition – incidence in the US and Europe is 10-15% of the population – it is really not that well understood. IBS affects the digestive system, causing symptoms including stomach cramps and pain, bloating, diarrhoea and constipation. These symptoms can fluctuate, and seriously impact a person’s quality of life.
IBS is clinically categorised to different subtypes based on symptoms – constipation-predominant (IBS-C), diarrhoea-predominant (IBS-D) and mixed phenotype (IBS-M), which each comprise in the US roughly a third of diagnosed cases. Existing approved treatments for IBS only treat either sub-group (IBS-C or IBS-D), targeting just the symptom of constipation or diarrhoea. As a result of this approach to treating IBS to date, there are no approved therapeutics for IBS-M patients. 4D pharma’s Blautix is uniquely efficacous in treating both IBS-C and IBS-D, which suggests it could also be the first ever drug also able to adequately address the underserved IBS-M market, a third of IBS patients currently with no suitable treatment option. This could be a game-changer for doctors and patients, a single drug that could treat all sub-types of IBS, by addressing the underlying condition and not just the symptoms of constipation or diarrhoea.
Furthermore, while current IBS drugs may provide similar effects to Blautix, but only in either IBS-C or IBS-D, the safety profile of Blautix is another advantage which represents a potential game-changer for IBS patients. The safety profile is important because drugs currently on the market have significant side effects, as a direct consequence of their targeting solely of symptoms. For example the leading IBS-C drug leads to diarrhoea in 20% of patients – that is not an adequate solution for patients.
The Blautix safety benefit could change the dynamics of treatment for IBS patients. Currently, IBS patients commonly discontinue their treatment because of the significant side effects of current therapeutics. There is the potential that IBS patients could be initially treated by the primary care physician who can confidently and safely administer Blautix, given its excellent safety profile, before being referred to a specialist gastroenterologist.
What the Blautix trial was for and what it was to show?
The purpose of the Blautix Phase II trial was to determine whether there was an effect in both sub-types of IBS patient, namely IBS-C & IBS-D. Currently no drug works across both subtypes.
Furthermore, the trial was intended to generate the clinical data to inform and point us towards a trial design for a pivotal study, i.e. a larger phase III trial with the aim of getting regulatory approval for Blautix.
We believe we have a differentiated drug in Blautix that can meet the needs of a huge market, addressing both IBS-C and IBS-D, and potentially IBS-M, and this trial provides the clinical data to show this was the case.
What did it show and were there any negative surprises?
We were really pleased with the results. It achieved what it was designed to do and gave us the positive answers we need to take the next steps with Blautix.
The trial showed that Blautix was uniquely efficacious in both IBS-C and IBS-D, and that it had a highly favourable safety profile. The efficacy levels we saw in both disease subtypes were the same as those of marketed drugs that only work in only one or the other, and also have significant side effect profiles.
A particularly interesting finding from the Phase II trial is that Blautix has a particularly strong effect in helping improve bowel habits, again uniquely in both IBS-C and IBS-D. This is ground-breaking if you consider the way current IBS drugs work – drugs for IBS-C that give you diarrhoea and vice versa. The bowel habit aspect of IBS can be one of the most debilitating factors. ISB-D patients have told us that what they really want is normality, to be able to go about their daily lives like going on a journey and not having to plan for facility stops or take clean clothes. We are seeing that Blautix offers an improvement in bowel habits in both IBS-C and IBS-D, which is really exciting.
Importantly, the trial also reaffirmed the favourable safety profile of Blautix – in this study its adverse vent (or side effect) profile was indistinguishable from placebo. This is significant in IBS, where drugs currently on the market have negative side effects, and a major improvement for patients and their quality of life.
The results of the trial provide the basis and a path forward to develop a product that could be prescribed safely and be effective in all forms of IBS – a real differentiator – and one which could transform the way patients are treated.
Have the trial results halted any progress? What are the next steps with a view to commercialisation?
The study has provided us with the positive results to progress discussions with multiple potential partners, as well as with regulatory authorities about the next stage of development. We will continue to analyse the results, including for example additional sub-group analyses. Next steps will be to use the data and the learnings from this Phase II to understand what a large-scale Phase III study would look like.
Beyond the trial what other key developments are in the pipeline?
4D pharma has been making significant strides forward in its oncology programme which is really exciting at the moment. We recently announced the acceptance of three presentations at the prestigious Society for Immunotherapy of Cancer (SITC) Annual Meeting 2020. One of these posters describes for the first time initial immune modulation and safety data from our lead immuno-oncology candidate MRx0518 as a neoadjuvant monotherapy trial in patients awaiting surgical resection of solid tumours. This data will increase our understanding of the mechanism of action which could help shape the clinical development plan for MRx0518.
The other two posters provide updates on a clinical trial of MRx0518 in combination with Keytruda, the world’s biggest oncology drug, part of our collaboration with Merck & Co. The Part B cohort expansion phase of this trial is enrolling at multiple sites in the US. The study is open-label, which means we can continually review the data and provides updates as appropriate.
Beyond MRx0518 and Blautix, 4D pharma has a deep pipeline including a respiratory candidate MRx-4DP0004 which is in the clinic. An earlier stage programme we are very excited about is in neurodegenerative diseases like Parkinson’s. We also have a second separate collaboration with Merck & Co. in the vaccine field, which is an exciting project and endorsement of our approach and platform from an industry leader.
What would you say to shareholders who would be spooked by the recent fall in share price?
The strength of our science will always win out in the end. 4D’s share price has fluctuated before, and I’m sure it will go up again. We are confident in the long term value of our ground-breaking research and have multiple shots on goal, any one of which could be transformative for 4D, the microbiome field, and the broader pharmaceutical industry.
The Blautix trial, whilst large by microbiome standards, was three to five times smaller than approval studies of marketed IBS products, and was designed to identify signals to inform subsequent Phase III development. To this end, it was entirely successful and we are very positive. As we’ve already discussed, the results give us a clear path forward for the Blautix programme and gives us every confidence that we could have a valuable differentiated product in the making.
4D is not a one-trick pony. In addition to Blautix, 4D has utilised its platform drug discovery engine, which we call MicroRx, to make significant strides forward in areas from oncology to respiratory and neuro diseases, and continues to use that platform in new areas for example with partners such as Merck in the vaccine space.
This is not to take away from the recent IBS results – IBS is a complex disease, not well understood or sufficiently treated – and Blautix showed similar efficacy to drugs currently on the market based on much bigger trials, only in either IBS-C or IBS-D, and unable to match its safety profile. As we continue to analyse and learn more from the trial results and look into the strong signals we saw – for example in improvement in bowel habits and with the fact that Blautix provides a safe option for GPs across both subtypes – we will build those learnings into the design of a Phase III pivotal trial for approval, and our conversations with potential partners.
Ultimately, the key take home from the recent data is that we’ve shown Blautix is effective in both IBS-C and -D, with a great safety profile, supporting taking this program forward. This reinforces 4D pharma’s position leading the development of Live Biotherapeutics, a completely novel area of medical research, with potentially profound impacts on human health. I would like to say to the market – you need to watch this space.
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