Eric Shaff
Analyst · Goldman Sachs
Thanks, Carlo and good morning everyone. 2019 has been an important year of focus and advancement for Seres and as we move into the final months of the year, we are pleased to note that we are in the stronger position to deliver on our mission to advance our microbiome therapeutics platform and to execute on the development of our promising pipeline of drug candidates. To summarize some of our accomplishments, we have focused our pipeline on our highest priority programs, modified the SER-109 Phase 3 study to expediting top line results, initiated our SER-287 and SER-401 clinical studies, entered into a collaboration with AstraZeneca in immuno-oncology, nominated our SER-301 lead candidate, and strengthened our balance sheet with a $51 million equity raise. More recently, we further strengthened our balance sheet with access to up to an additional $50 million in debt financing. All of these efforts lay the foundation for Seres to execute on a data rich 2020 that we believe could be transformative for the company. Seres differentiated core competencies include our field leading R&D capabilities and deep domain expertise in microbiome therapeutic drug discovery, manufacturing, and clinical development. We are able to identify key signatures in the microbiome associated with disease and design tailored oral therapeutic microbial candidates aimed at improving patient outcomes by establishing a healthy and more diverse microbiome. Turning now to an update on our development programs. Let me begin with SER-287, which is in a potentially pivotal Phase 2b study in patients with mild to moderate active ulcerative colitis. SER-287 is an orally administered biologically derived live drug candidate comprised of commensal bacterial spores derived from the healthy human gastrointestinal tracts. Our objective with SER-287 is to develop a first-in-class microbiome therapeutic that modulates the microbiome in microbe associated metabolites in UC patients. This approach is intended to reduce the impact of a dysfunctional microbiome as a trigger and amplifier of inflammation. We believe this drug candidate has the potential to result in significant improvements in patient outcomes by providing a novel, non- immunosuppressive treatment option for this serious disease. A prior completed SER-287 Phase 1b proof-of-concept study demonstrated a statistically significant difference in the clinical remission rate between patients treated with vancomycin followed by daily SER-287 for eight weeks, compared to the placebo group. In that study, we observed a 40% remission rate with SER-287 versus 0% with placebo. Following those encouraging initial clinical results, we obtained additional microbiome, metabolite, and transcriptomic data sets that provide mechanistic insights associated with the observed clinical therapeutic activity. Changes in both species and metabolites were identified as associated with treatment in clinical remission consistent with published data from the human microbiome project. Importantly, the safety profile for SER-287 was highly favorable with no imbalance in adverse events seen in patients administered SER-287, compared to placebo. Supported by these compelling data, we subsequently initiated the ongoing SER-287 Phase 2b ECO-RESET study. Based on written FDA feedback, we expect that this study could serve as one of two pivotal studies to support product registration. In addition, our feedback from the European Medicines' Agency Committee on Human Medicinal Products also indicated that ECO-RESET could serve as one of two registrational studies to support a European regulatory marketing application. The SER-287 ECO-RESET study is a randomized placebo-controlled three arm induction trial designed to enroll 201 patients with active mild-to-moderate ulcerative colitis who have failed prior therapy. In the first of three arms, patients receive vancomycin pretreatment followed by 10 weeks of the same daily regimen used in the arm of the Phase 1b trial that showed the highest clinical remission rate. In the second arm, patients also receive vancomycin pretreatment followed by two weeks of the same SER-287 daily regimen as in the first arm, followed by eight weeks of a lower dose. In the prior Phase 1b trial, engraftment, the germination and vegetative growth of SER-287 bacteria in the gastrointestinal tract was seen to plateau after two weeks of SER-287 administration. So, this arm evaluates a regimen based on our mechanistic learnings from the study. In the third arm, patients receive only placebo. ECO-RESET is primarily an induction study, however the effects of SER-287 as a maintenance therapy will also be evaluated. We continue to recruit patients for this study and we now have over 100 sites open across the U.S. and Canada, and 70% of these sites have screened patients to date. We expect to have top line data in the second half of 2020 well within the company’s cash operating runway. I'll now turn to the SER-109 ECOSPOR III Phase 3 study. SER-109 is an orally administered by a logically derived drug candidate designed to restructure the microbiome to increase the diversity of commensal microbes in patients with recurrence C. difficile or C. diff infection. SER-109 was designed using bioinformatic insights suggesting that a complex spore ecology includes keystone organisms that could address the underlying depletion in commensal microbes. SER-109 is an ecology of bacterial spores enriched and purified from healthy, screened human donors. We employ a robust manufacturing process that includes steps that inactivate vegetative bacteria, including species such as E. coli, which has been linked with FMT. Indeed, last week, the New England Journal of Medicine published a report describing cases of Drug-Resistant E. coli Bacteremia that were transmitted by FMT and unapproved an unregulated procedure, including one that led to an unfortunate patient death. Also, just yesterday, Seres attended an FDA meeting focused on the use of FMT for C. Diff infection and other diseases. The meeting presentations and discussions have reaffirmed our conviction in the dire need for an FDA approved microbiome therapeutic. The meeting highlighted the risks associated with unregulated FMT. We came away further encouraged and the advantages of our purified spore-based approach that uses both extensive donor screening and rigorous product purification. We believe that both these steps are essential to ensure product safety. We continue to enroll the ECOSPOR III trial, which is evaluating efficacy and safety in 188 patients with recurrent C. diff infection. Importantly, all patients enrolled in ECOSPOR III are required to test positive for C. diff cytotoxin to ensure high quality data by enrolling only patients with an active C. diff infection. ECOSPOR III is a randomized placebo-controlled study where all patients are treated with standard of care antibiotics to address the qualifying acute C. diff infection, and subjects then receive either SER-109 or placebo. The primary endpoint compares the C. diff recurrence rate in subjects who receive SER-109 versus placebo up to eight weeks after dosing. We continue to make steady progress with the study in the phase of wide-spread continued views of unapproved and unregulated FMT to treat C. diff infection. As of October 31, this study was more than 85% enrolled and we expect to report top line study results in mid-2020. We are nearing full enrollment for ECOSPOR III and we are very excited by the potential for this program. I will remind you that SER-109 has both break-through therapy and orphan drug designations from the FDA. We are very much looking forward to seeing the top line study results. Based on prior discussions with the FDA, we believe this study, if successful, has the potential to be a single pivotal study supporting product registration. However, this would depend on the strength of the data and additional safety data maybe required. If successful, SER-109 could represent a major breakthrough for patients suffering from our recurrent C. diff infection, considered one of the top 3 most urgent antibiotic resistant bacterial threats in the U.S. according to the centers for disease control. It is also the leading cause of hospital acquired infection in the U.S. and is responsible for the deaths of approximately 29,000 Americans each year. Furthermore, we believe that a positive result from ECOSPOR III would provide definitive clinical validation more broadly for the promise of microbiome therapeutics. I’d like to now pass the call to Matt to discuss our immuno-oncology programs, and our next generation development candidate SER-301.