Editas Medicine, Inc.

Good morning and welcome to Editas Medicine fourth quarter and full year 2021 conference call. All participants are now in a listen-only mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Ron Moldaver, Investor Relations at Editas Medicine. Thank you and may begin.

Thank you, Laura, and good morning, everyone. Earlier this morning, we issued a press release providing our financial results and recent corporate updates. A replay of today's call will be available on the investor section of our website approximately two hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements, as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. Now I will turn the call over to our Chief Executive Officer, Jim Mullen.

Thanks, Ron, and good morning, everyone. I'm joined today by several members of the EDITAS executive team, including Mark Sherman, our Chief Scientific Officer, and Michelle Robertson, our Chief Financial Officer. I want to start off by providing a few highlights from last year and some important upcoming milestones for EDITAS. We achieved clinical proof of concept with EDIT 101 for LCA 10, a leading cause of inherited blindness in children. The initial trial data demonstrated successful delivery in in vivo editing with improvements in vision. We're on track to complete dosing of the pediatric mid-dose cohort in the first half of 2022 and expect to initiate dosing of the pediatric high-dose cohort later this year. We finalized the construct for edit 103 for a form of autosomal dominant retinitis pigmentosa, another disease of the retina. which leads to blindness and has no approved treatments. This program is progressing towards IND enabling studies. We plan on sharing additional preclinical data at the ARBO conference this spring. Our pipeline of in vivo products is expanding quickly. We now have four wholly owned ocular programs and more ocular opportunities. We're also well positioned to explore additional indications outside of the eye with ongoing preclinical work. With our Edit 301 program for sickle cell disease, we have successfully edited cells ex vivo, are on track to dose the first patient in the first half of this year. And we are also pleased to obtain IND clearance for Edit 301 in transfusion-dependent beta thalassemia, and we're in the process of setting up the clinical sites and beginning to screen potential study subjects. We expect to dose the first beta thalassemia patient sometime this year. We announced EDIT-202, a highly differentiated iPSC-derived NK cell investigational medicine with four gene edits. We presented data demonstrating how our approach has the potential to create an allogenic, off-the-shelf NK cell therapy medicine with enhanced activity against solid tumors. And finally, we advanced our collaboration with Professor Myers-Squibb in alpha-beta T cells. BMS has opted into six programs with one declared development candidate in IND-enabling studies. To date, we have received over $125 million in payments, plus have potential for further milestones and royalties in the future. Now I'd like to spend a few minutes reviewing our clinical programs. Last year, we treated the important in vivo clinical proof of concept with Edit 101 for LCA 10. The initial brilliance trial data demonstrates successful delivery and editing with meaningful improvements in vision. These improvements were quantified by several assessments, including a patient's ability to maneuver through mazes at different light levels, improvements in full field light sensitivity testing, and best corrected visual acuity. We're very excited by these results, and our progress on Edit 101 was highlighted as one of the top breakthroughs last year by the American Association for the Advancement of Science. At the end of last year, we completed dosing of the adult high dose cohort, and thus far, we have not seen any dose limiting toxicities or serious adverse events. Any reported adverse events have been attributed to surgical procedure and have subsequently been resolved. The strong safety profile across all three dose levels is very encouraging as we advance the trial in pediatric patients. Our next milestone is complete dosing of the pediatric mid-dose cohort in the first half of the year. review the safety with the IDMC, and initiate dosing of the pediatric high-dose cohort. We're also expanding patient enrollment in one or more of the previously completed adult cohorts. That expansion will help further explore the dose responses and provide us with additional data as we design the registrational trial and select appropriate endpoints. A clinical update for Edit 101 will be provided in the latter half of the year, which will include 12-month data of the mid-dose adult cohort, and six-month data of the high-dose dog cohort. Thus far, we've received very encouraging feedback on this trial from investigators, clinicians, and most importantly, the patients. Some of the study participants have reported meaningful improvement upon their daily lives, including simple things like being able to walk through doorways or walking around outside a bit more independently. We are exploring the most relevant and sensitive endpoints to support further development of the trial. continuing to evaluate how we can most effectively interpret trial information and considering what is most meaningful to patients. In addition to the trial data, we're also looking at our natural history study data to identify the most reproducible measures, and we expect to have that data available later this year. Moving on to EDIT-301 and our ex vivo platform. We've developed a potentially one-time treatment for both sickle cell disease and transfusion-dependent beta thalassemia. Our unique approach disrupts the binding site of BCL11A, consistent with what is seen for naturally occurring mutations that result in hereditary persistence of fetal hemoglobin, or HPFH. Patients who co-inherit one or more of these protective mutations generally don't exhibit pain crises, experience fewer hospitalizations and organ damage, and have longer lifespans. Because of the natural validation of this approach in human genetics, we believe EDIT-301 is likely to be a safe and durable approach to treating both of these indications. As a reminder, we are editing the beta-globin promoter in patients to generate protective changes that increase fetal hemoglobin, similar to HPFH. This should reduce or potentially even eliminate disease symptoms in individuals with sickle cell disease or TDT. Edit 301 also utilizes our highly efficient and specific proprietary AS Cas12A enzyme. We believe the choice of editing site combined with the editing specificity and efficiency afforded by our unique enzyme could lead to a safer and more durable therapy. In the ruby trial of Edit 301 for sickle cell disease, we've successfully added patient cells ex vivo in our track for dosing in the first half of 2022. with initial clinical data expected by year end. The beta cell Semia IND was cleared by the FDA last December, and we're in the process of setting up the clinical sites, IRB approvals, and patient screening, and expect to dose the first TDT patients by year end. And finally, I want to update everyone on our clinical operations while the CMO search is underway. Our current clinical operations team, which has extensive ophthalmology and hematology experience, is continue to advance our clinical trials. The top-tier agency has been retained to assist us in the search, and we plan on reviewing initial candidates in the coming months. Our objective is to bring in someone with a proven track record of regulatory approvals for complex medicines, an organizational leader who can spearhead multiple clinical trials, and someone who will work closely with Mark's team as we strategically build out our pipelines. We do not anticipate any disruption in our clinical programs or upcoming milestones, and I look forward to updating you once a decision is made. With that, let me turn the call over to Mark to review our preclinical programs and platform technologies.