Synlogic, Inc.

Good morning. Welcome to Synlogic's fourth quarter 2020 conference call. At this time, all participants are in a listening mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded. I would now like to turn the call over to Daniel Roseanne, Head of Finance and Investor Relations. Please proceed.

Thank you, Operator. Good morning, and thanks for joining us on today's conference call. This morning, we issued a press release which outlines our fourth quarter and full year 2020 financial results and additional business updates. The release is available on the investor section of our website at SynlogicTX.com. Joining me on this call are Dr. Aoife Brennan, President and CEO, Greg Beloff, Interim CFO, and Dr. Richard Reese, Chief Medical Officer, Dr. David Hava, Chief Scientific Officer, Tony Awad, Chief Operating Officer, and our newly appointed Chief Development Officer, Dr. Carolyn Kurtz, will also be available during the Q&A. During this call, IFA will provide a review of fourth quarter highlights and recent progress. Richard will provide an update on our metabolic portfolio, including our recent clinical update on SINB 8802 in enteric hyperoxyluria. And Greg will summarize our financial results for the quarter and year. Following our prepared remarks, we will open the call for your questions. As we begin, I'd like to remind everyone that comments today may include forward-looking statements made under the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made as of the date hereof and are subject to numerous factors, assumptions, risks, and uncertainties which change over time. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including those described under the heading forward-looking statements in Synlogic's press release from earlier today, or under the heading Risk Factors in Synlogic's most recent Form 10-K or in later filings with the SEC. Synlogic cautions you not to place undue reliance on any forward-looking statement. Now, I'd like to turn the call over to Aoife.

Thanks, Dan. Good morning, everyone, and thank you for joining us. I'm thrilled to share with you today our financial results from 2020, as well as recent progress across our portfolio including the initial clinical results from our enteric hyperoxaluria program, SYNB 8802, which we announced yesterday. Across our programs and platforms, the groundwork of the last year has catapulted us into a data-rich 2021, with anticipated clinical readouts in three programs and increasing momentum in our research engine, focused on advancing additional clinical candidates. As we emerge from the winter months, Synlogic hasn't missed a beat. We've done anything but hibernate. We are rapidly progressing our metabolic disease pipeline, which leverages the ability of our platform to engineer synthetic biotic medicines and deliver them safely into the human GI tract to consume a toxic metabolite. We believe that there are a wide variety of disease states where this approach could transform patients' lives. Based on the initial readout from CINB 8802, which we will discuss in more detail in a moment, we now have two metabolic programs that have demonstrated the ability to consume a metabolite within the human gastrointestinal tract. Both programs have done so at levels that have the potential to be clinically meaningful in patients with disease. And in both cases, we have clinical trials ongoing in patients to demonstrate impact on critical endpoints, with readouts anticipated later this year. Spearheading our portfolio strategy and program leadership across Synlogix's portfolio of synthetic biotic medicines is Dr. Caroline Kurtz, our newly promoted Chief Development Officer. Caroline has been an industry leader for decades, and she has developed blockbuster products. More importantly, she is the team mindset which is critical to drug development. As we move into later stages of development, Caroline's ability to harness the best thinking from across all disciplines of drug development will be critical to our success. We're thrilled to recognize her experience and the role she will play in the success of our programs with this promotion. In the clinical metabolic portfolio, we have two exciting programs leading the way, CINB 1618 in PKU and CINB 8802 in enteric hyperoxaluria. Our lead candidate in PKU is CINB 1618. We have previously demonstrated that a lyophilized formulation of CINB1618 was able to consume phenylalanine in the GI tract of healthy volunteers. We are currently evaluating this strain in adult PKU patients in an ongoing Phase II study called Symphony 1. This trial continues to enroll well, and we're delighted to see so much patient-driven interest despite a challenging COVID winter. We continue to hear from patients and caregivers that a safe oral therapy, which reduces plasma fee by consuming fee in the GI tract, would be a welcome addition to the market. While SYNB1618 has been progressing in the clinic, the research team have been evaluating additional synthetic biology tools to optimize the activity of the strains. They have successfully deployed directed evolution to create an evolved version of CINB 1618, which we are now moving into IND-enabling work. We call this strain CINB 1934, so named because 1934 was the year in which PKU was first characterized. CINB 1934 has demonstrated higher activity compared to CINB 1618 in preclinical models of fee consumption. We will provide additional updates as the strain progresses. CYMB-8802 is our other lead metabolic program. It is designed to consume oxalate in the GI tract in patients with enteric hyperoxaluria, a devastating condition resulting from excess absorption of oxalate from the GI tract, for which there is currently no approved therapy. Yesterday, we shared some very exciting top-line data from the Phase Ia portion of the ongoing trial. In this study, we placed healthy volunteers on a high oxalate diet and increased the urine oxalate levels, thereby inducing dietary hyperoxaluria. Subjects were then randomized to either CINB 8802 or placebo. and provided daily 24-hour urine collection throughout the dosing period. The data demonstrate robust and dose-responsive urinary oxalate reduction relative to placebo. Coming only 15 months after we nominated CINB 8802 as a program, these data also demonstrate the speed and power of the synthetic biotic platform. Richard will walk you through the data in a moment, but I want to emphasize that we are moving rapidly towards clinical proof of concept in patients with enteric hyperoxaluria. Part B of the Phase I study has already been initiated. This study gives us an opportunity this year to demonstrate what very well may be the most clinically attractive profile for patients suffering from enteric hyperoxaluria. Our immunomodulation portfolio also continues to advance. STING-B1891 has moved into combination arm dosing with a PD-1L1 checkpoint inhibitor in an ongoing phase one study in patients with advanced solid tumors or lymphoma. Part A of the study has demonstrated target engagement and activation of the STING pathway. An update on the study will be shared at the American Association of Cancer Research meeting in April. Data from both arms will continue to be reported over the course of 2021, with mature combination therapy data expected by the end of the year. Our team has done a tremendous job executing across multiple programs during a challenging time for everyone over the past 12 months. This resilience and teamwork has allowed us to set the stage for multiple meaningful readouts in 2021. Thanks to our careful stewardship, all milestones occur well within our cash window, which has been extended into 2023. In summary, 2021 has already been an incredibly exciting year for the company. We now have demonstrated proof of mechanism in humans from both of our lead metabolic programs, PKU and enterokyproxyurea. We believe that we have the potential to demonstrate proof of concept in both programs later this year. Now, let me turn the call over to Richard to share progress on the metabolic program. Thank you, Aoife.