Fulcrum Therapeutics, Inc.

Good morning and welcome to the Fulcrum Therapeutics Third Quarter 2021 Conference Call. Currently, all participants are in a listen-only mode. There will be a question and answer session at the end of this call. I would now like to turn the call over to Ms. Naomi Aoki, Senior Vice President of Corporate Communications and Investor Relations at Fulcrum. Ma'am, please proceed.

Thank you, Henry. Good morning and welcome to the Fulcrum Therapeutics Conference Call. Please be reminded that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about our future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent our views as of today, they should not be relied upon as representing our views in the future. We may update these statements in the future, but we are not taking on an obligation to do so. please refer to our most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with our business. With me on today's call are Brian Stewart, President and Chief Executive Officer, Chris Morabito, Chief Medical Officer, and Peter Thompson, Vice President of Finance and Accounting. Judy Dunn, our President of R&D, and Paul Bruno, our Senior Director of Corporate Development, will also be available for Q&A. Let me run quickly through this morning's agenda. Brian will begin the call with a corporate overview and key updates. Chris Morabito will review our programs in sickle cell disease and FFHD. Peter will cover our financials, and then Brian will open the call for Q&A. With that, it's my pleasure to turn the call over to Brian.

Thank you, Naomi. Good morning, everyone, and thank you for joining us today. 2021 has been a remarkable year for Fulcrum, and we continue to make great strides in the third quarter across our pipeline, our product engine, our business, bringing us closer to our mission of delivering life-changing medicines to people with rare genetic diseases. This past quarter was particularly notable for the compelling clinical data we reported on FTX6058, our oral HBF inducer for sickle cell disease and other hemoglobinopathy. In August, we reported results from our ongoing phase one trial in healthy adult volunteers. As many of you know, the current treatment landscape in sickle cell disease consists of therapies that only target select symptoms. Human genetics clearly demonstrate that by inducing fetal hemoglobin, or HBF, that HBF treats the root cause of sickle cell disease. And by inducing HBF, we believe FTX 6058 has the potential to address the broad range of symptoms of sickle cell disease, providing a functional cure with an oral therapy. As you'll hear from Chris Morabito later on, we are excited about the results from this trial, both in terms of the tolerability profile and the robust induction of HBG mRNA, which has been highly correlated in our preclinical studies with HBF induction. Looking ahead, we remain on track to provide an update from our ongoing Phase I trial by year end, including data from our 20 and 30 milligram dose cohorts and healthy volunteers. At that time, we also plan to share new data, further elucidating the relationship between EED inhibition via FTX 6058 and HBG mRNA expression. Meanwhile, we are moving quickly to initiate our Phase 1b trial in people living with sickle cell disease and are on track to begin enrolling patients by the end of the year. We also plan to submit an IND for FTX6058 by year-end in additional hemoglobinopathies, including beta thalassemia. Now let's turn to Los Matamod, our candidate for FSHD. FSHD is the second most prevalent form of muscular dystrophy. There are currently no approved drugs and nothing else in the clinic for this devastating disease. People with FSHD are typically diagnosed in their late teens or early 20s. As fat progressively infiltrates their muscles, people with FSHD lose strength, function, and independence. There is an urgent need for a drug that can slow or stop disease progression. The data we reported earlier this year from our Phase IIb Redux IV trial highlights LosMapimod's potential to do just that, demonstrating delayed progression and even improvement across a number of measures of muscle health, function, and patient-reported outcomes. We remain on track to meet with regulators before the end of this year and look forward to providing an update on those discussions in the first quarter of 2022. Turning to FulcrumSeq, our product engine and innovation backbone of the company. FTX 6058 and LosMapimod, as well as our ongoing collaborations with Acceleron and Myocardia, are a testament to the power of FulcrumSeq. which has allowed us to rapidly identify novel, high-quality targets that modulate the root cause of genetically defined rare diseases. Notably, in addition to our IND in hemoglobinopathies, we expect to submit an additional IND by the first quarter of 2023. We have also made tremendous advancements with FulcrumSeq to enable our drug discovery efforts at what we believe is an unprecedented scale in disease-relevant settings positioning us to dramatically increase the pace of discovery. As we shared this morning, Chris Moxham, our chief scientific officer, will be leaving Fulcrum to pursue new opportunities. We are grateful for his contributions and wish him the best in the next chapter of his career. During this transition, the discovery organization will continue to report into Judy Dunn, our president of R&D. With her leadership and strong organization already in place, we're well positioned to execute against our discovery goals. Finally, we continue to build out our leadership team this quarter with the appointments of Mel Hayes as our Chief Commercial Officer, Mani Sundaranjan as our Senior Vice President of Technical Operations, and Naomi Aoki as our Senior Vice President of Corporate Communications and Investor Relations. These newly created roles help us build out our downstream capabilities and further strengthen our team as we move closer towards becoming a commercial organization. Fulcrum is in a tremendous position as we look to build a leading rare disease company. We are advancing two potentially life-changing therapies in clinical development, progressing additional early-stage programs, scaling up our discovery efforts, and building downstream capabilities, all on a strong financial foundation with a cash runway that now takes us into 2024. With that, I'd like to turn the call over to Chris Morabito. Chris?