Seres expects to move forward with plans for SER-109 as a novel treatment for CDI.
It is notoriously difficult to treat clostridium difficile infections (CDI), particularly in hospitals.
In data presented at the 2021 Digestive Disease Week (DDW) Virtual Meeting, researchers presented new data on SER-109, an investigational microbiome therapeutic consisting of purified Firmicutes spores.
In the phase 3 randomized controlled trial, the researchers examined 287 adult patients with recurrent CDI and found SER-109 results in a 73% relative risk reduction at week 8 when compared to placebo (11.1% vs 41.3%, respectively; P <0.001).
In an interview with HCPLive®, Matthew Henn, PhD, Chief Scientific Officer at Seres Therapeutics, explained the promising new treatment and why CDI is such a difficult disease to treat.
HCPLive: Now that you have 24 weeks of data, are you convinced that SER-109 is a viable option to treat CDI?
Henn: We continue to be very excited about our SER-109 program, and the potential of this novel technology to truly transform the treatment of patients with recurrent C. difficile infections.
We have been working as a company for close to a decade now on really building the capabilities, the know-how, the knowledge that we need to be able to bring this novel technology forward.
Our 8 week data showed a highly statistically significant reduction in recurrence, and those data carried through the 24 week endpoint as well.
And so while we did see some change in the total recurrence numbers, the absolute risk reductions were on par with one another. And we're highly encouraged by the 24 week data.
Importantly, as well, we have we have discussed and disclose data speaking to the mechanism of the drug as well.
In our mechanistic studies to date and the pharmacokinetics and pharmacodynamics data that are coming out of the phase 3 data support what are hypothesized mechanisms of the drug and as well support the clinical outcome.
So we are certainly highly excited about this program. And we are actively in the process of enrolling an open label safety study to get the required number of patients we need on drug to move towards licensure with this drug.
HCPLive: What makes this treatment novel? What separates it from existing CDI Treatments?
Henn: This is a drug that's designed to target the root cause of disease. So CDI and the development of recurrence, and particularly in multiple recurrent patients, is really a 2 hit process.
Well, the first thing is someone has to have a microbiome that is susceptible to C difficile infection. And then second is they have to have exposure to C diff, and C diff has to take root and then kind of become a vegetatively grow such that we you ultimately will generate toxin, and which leads to leads to the disease.
So traditional antibiotics that are used to treat C difficile infection are the very antibiotics that can lead to the microbiome becoming susceptible to disease. So in a sense, what you're using to treat the disease are the same thing that helps lead to the disease in the first place.
Our technologies are novel because we’re leveraging the human microbiome to be a therapeutic agent.
Our technology is designed to first restructure the microbiome and do so rapidly. And so we bring back the bacteria in the gastrointestinal tract that are important bacteria to be in your gut to prevent C. difficile infection. And then our drugs are designed for those bacteria to actually engraft.
So what we mean by engraftment is that those bacteria actually establish themselves in the gastrointestinal tract, and then they change and shift the metabolic landscape in the gut, to be unfavorable to C. difficile infection.
HCPLive: Do you believe this novel technologies can be used to treat other types of diseases outside of C difficile?
Henn: Seres has been really applying a proprietary scientific data driven approach to developing this technology's capabilities. And that starts both with our research engine that we've developed to be able to go through both the discovery of targets that can be that are druggable, with a microbiome based therapeutic, all the way through to manufacturing capabilities and the ability to bring these drugs to market and everything in between.
As we've gone through that, and built that platform up, it has been highly focused on understanding what are those targets of different diseases that can be modulated by microbes that are in our drugs?
We do believe that this is a technology that that can be applied broadly across a host of different diseases, both in the infectious disease space, as well as in the ability to actually modulate the immune system or the inflammatory state of humans.
And we actually have data in the context of ulcerative colitis, where we have a phase 1B study where we saw we were able to have a statistically significant increase in clinical remission over placebo in mild and moderate ulcerative colitis patients.
HCPLive: What makes C difficile so difficult to treat?
Henn: C diff is a real challenge because it forms spores and spores are really recalcitrant, biological entities. These things go up to space and come back and we'll still be able to germinate. It can be exposed to incredible conditions and still germinate.
So what happens in the context of C diff is that not only the folks microbiome become susceptible to infection because they've lost the diversity of microbes that are in their gastrointestinal tract, that are the natural fighters of C diff. But then as well, they wind up in this situation where in their home or in hospital settings, where there can be high levels of spores of C diff around their chance of exposure is very high.
To treat this disease, you need to address both of those issues. You need to you need to bring the bacteria back and repair that susceptible microbiome so that even if patients are still exposed to those spores, which they are highly likely to be, the bad bacteria will not take root and grow in the way that it needs to ultimately produce toxins and lead to disease.
HCPLive: What is next for SER-109?
Henn: SER-109 has breakthrough therapy designation, as well as fast track designation from the US FDA. We've obviously as well been in communications with European regulators and to continue that path forward. What the company is focused on right now is to continue enrollment in the open-label safety study. we had discussed with the FDA, the requirements for our phase three to be a single pivotal study. And we, if I may be so bold, we really blew the efficacy benchmark out of the water. The other predefined benchmark was to have a safety database of 300 patients on commercial dose.