Fulcrum Therapeutics, Inc.

Once again today's conference will begin shortly. Please continue to stand by. Thank you for your patience. Thank you. Thank you. Good morning and welcome to Fulcrum Therapeutics 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. Christy Warwick. Director of Investor Relations and Corporate Communications for Fulcrum. Ma'am, please proceed.

Thank you, Operator. 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. All 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 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 Moxon, Chief Scientific Officer, and Chris Moravito, Chief Medical Officer. Let me quickly run through this morning's agenda. Given today's news, we're going to focus our call on the 6058 Phase 1 Healthy Adult Volunteer Results. Brian will begin the call with a corporate overview and key updates from the quarter. Chris Moxon will provide a review of the FTX 6058 preclinical data. Chris Moravito will review the clinical results and next steps for the programs. and Brian will open the call for Q&A. With that, it's my pleasure to turn the call over to Brian. Brian?

Thank you, Christy. Good morning, everyone, and thank you for joining us today. This past quarter was particularly notable for the significant progress in both of our clinical stage programs. In June, we announced positive results from the Phase 2b Redux 4 trial, where we were able to show that losmapamod slowed disease progression and improved function in patients with FSHD. a severe and progressive form of muscular dystrophy that currently has no approved treatments available. These results strongly support our belief that losmapamod has the potential to be a safe and effective therapy for FSHD patients. With these promising data from Redux4 in hand, we plan to meet with the FDA in the second half of 2021 to discuss potential next steps. Moving to FTX6058, today we are very pleased to report compelling results from our ongoing Phase I trial in healthy adult volunteers. As many of you know, the current treatment landscape for sickle cell disease includes therapies that target only select symptoms. The introduction of an oral therapy that can successfully target the root cause of sickle cell disease would represent a major advancement. We are especially excited about the results from this trial, both in terms of tolerability as well as the impact we see in the induction of fetal hemoglobin mRNA and increase in F-verticulocyte. In this trial, we saw an impressive 4.5-fold induction of fetal hemoglobin mRNA. We also saw a 4.2-fold increase in efforticulocytes, which indicates fetal hemoglobin production. And we achieved maximal target engagement. Building on our extensive preclinical research, these results provide proof of biology and mechanisms. We are also pleased to share that FTX6058 has been generally well-tolerated to date, and the pharmacokinetics support once-daily oral administration. Encouragingly, these results provide the first evidence that STX6058 may be able to achieve or exceed the two- to three-fold HPF induction we observed preclinically. This two- to three-fold HPF induction threshold would not only be superior to hydroxyurea, the current standard of care, but is also predicted to provide meaningful clinical benefits to single-cell patients. With these results in hand, we remain on track to initiate a phase 1B trial in sickle cell patients by the end of the year and plan to initiate a clinical trial in non-sickle cell hemoglobinopathies in 2022. I'll note that both of our development programs came from our FulcrumSeq discovery platform, which is a powerful and differentiated approach to drug target identification and the innovation backbone of our company. This has allowed us to rapidly identify novel, high-quality targets then modulate the root cause of genetically defined rare diseases. By enabling drug discovery at unprecedented scale in disease-relevant settings, FulcrumSeq creates an unparalleled opportunity to efficiently grow our pipeline. We expect the work we are doing with FulcrumSeq will enable us to submit two new INDs by the first quarter of 2023. In addition, FulcrumSeq has also enabled our ongoing collaborations with both Acceleron and Myocardia, which continue to proceed well. As you can see, we continue to make important progress across our clinical development programs, research collaborations, and discovery platform. And with a cash runway that takes us into the first quarter of 2023, we expect to have meaningful updates from multiple key initiatives in the near term. With that, I'll turn the call over to Chris Moxon to speak more about our preclinical work with FTX 6058.