Editas Medicine, Inc. Q4 FY2022 earnings call

• Last year was landmark with two chemical proof-of-concepts in patients using in-vivo and ex-vivo approaches. In November, human proof-of-concept for EDIT-101 AV in LCA-10 was announced but patient enrolment in BRILLIANCE trial paused. In December, encouraging initial data from RUBY Phase 1/2 clinical study of EDIT-301 in sickle cell disease was shared.
• New strategy has three pillars: sharpened discovery focus to in-vivo administered genome editing medicines, strengthened discovery engine and technological capabilities, and expanded business development approach.
• Reallocated investment resources to accelerate EDIT-301's clinical development. Split research division into technology and drug discovery groups. Pursuing leadership in HSC therapeutics for hemoglobinopathies by reallocating investment, developing milder patient preconditioning, and in-vivo approach for editing HSCs.
• Completed safety review of Sentinel patients in RUBY trial for sickle cell disease, seeing favorable safety profile, and commenced parallel patient dosing. On track to dose 20 total patients in RUBY program by year-end, dose first patient in EDIT-301 EDITHAL trial for TDT this quarter, and provide early data from it by year-end.

Revenue for 2022 was approximately $20 million, compared to $26 million in 2021. The decrease was mostly driven by a decrease in revenue recognized related to the collaboration agreement with BMF. G&A expenses decreased from $76 million in 2021 to $71 million in 2022. R&D expenses increased from $143 million in 2021 to $175 million in 2022, principally due to manufacturing and clinical related costs for EDIT-301 and a one-time charge from pausing enrollment in the BRILLIANCE trial.

• Plan to hire new CSO with specific expertise aligned to vision. Refocus discovery group and advance discovery on in-vivo editing of HSCs and other tissues.
• Provide clinical updates from EDIT-301 RUBY study in mid-2023 and end of 2023, including longer term data from initial patients and additional RUBY trial patients. Dose 20 total patients in EDIT-301 RUBY program by year-end. Dose first patient in EDIT-301 EDITHAL trial for TDT this quarter and provide early data by year-end.

Q: Do you expect or already have takers for AsCas12a and slick technology? How similar or different is the AsCas12a you are using from Cas12a Ultra?

A: The most recent deal was with Shoreline, giving them exclusive license to sleek knock-in technology for iNK and oncology derived iMac platform and non-exclusive license for AsCas12a. Have a comfortable IP estate with no interferences or disputes around IP for AsCas12a.

Q: What experience or expertise are you looking for specifically in your next CSO, and when could they be appointed?

A: Looking for experience in developing and bringing drugs into clinic, expertise with complex genomics groups, and significant collaborative leadership. Timing depends on choosing best CSO, progress being made with interesting candidates but no specific timeline yet.

Q: Dosing 20 patients into RUBY by year-end. Do you think that is sufficient for regulatory filing or pivotal trial? Thoughts on milder conditioning and differentiation?

A: 20 patients will generate important clinical data for regulatory needs, but details of regulatory filing will be discussed with agencies. Milder conditioning broadens eligible patient population, and other approaches are actively explored.

Q: In terms of the mid-year update in the RUBY trial, preliminary sense of number of patients in follow-up? Design of EDIT-301 in TDT similar to RUBY?

A: Will share longer term data for initial patients dosed last year and additional data from RUBY trial. EDIT-301 in TDT has sentinel patients and details will be shared when more data is available.

Q: When could Editas move milder preconditioning into clinic? Thoughts on complementary technologies needed for business development?

A: More details on milder preconditioning will be shared in future. Complementary technologies needed include targeted delivery and additional targeted editing approaches.

Q: Reasons for choosing in-vivo editing of stem cells as initial area of focus? Limitations in manufacturing capacity for dosing 20 patients by year-end?

A: Aligns with active pipeline, human validated enzyme and target enable focus on target delivery. Substantially invested in CMC and have strong CMC team, confident in achieving dosing goal with strong patient recruitment momentum.

Q: Update on IP dynamics surrounding CRISPR/Cas9 and strategic options for LCA-10 and IRD?

A: Broads IP upheld by PTAB in Feb 2022. For LCA-10 and IRD, exploring potential divestitures, ideal partner would be sponsor interested in rare ocular diseases and AV delivery.

Q: Feedback from independent data monitoring community on RUBY trial? Implications for operating expenses or capital allocation strategy?

A: IDMC reviewed data from Sentinel patients and agreed for continued dosing and parallel dosing. Refocus strategy extends cash runway into 2025, continuing to invest in EDIT-301 trials and in-vivo discovery.

Q: RUBY trial potentially becoming registrational? Number of patients and follow-up needed for registrational package? Update on LCA-10 strategic options?

A: Dosing 20 patients by year-end is separate from registrational package, will engage with regulators to finalize data package. For LCA-10, exploring divestitures, ideal partner is sponsor interested in rare ocular diseases and AV delivery.

Q: Have you dosed the third patient in the sickle cell trial yet? When to reach out to regulator about path forward for EDIT-301? Is 301s manufacturing process commercial grade?

A: Did dose the third patient and started parallel dosing. Will discuss with health authority to finalize registration data package. On potency matrix, patients dosed in RUBY will support marketing application, details on commercial process will be updated later.

Q: Remind on shoreline deal term, economics, closing, and impact on cash guidance? Venue for mid-2023 301 update? Top organ to explore for in-vivo programs beyond HSC?

A: Received upfront payment, deal closed, impact considered in financials. Plan to release RUBY data middle and end of 2023, specific venue to be decided later. Top organ to explore will be balance of multiple factors in selecting targets and tissues.

Q: Renewed interest in using CRISPR/Cas9 in addition to Cas12 for internal product development? Performance requirements in licensing agreement with broad?

A: Pipeline focused on AsCas12a, believes it has advantages like higher efficiency and fidelity. Licensing agreements have conditions/requirements related to business development and execution.

Q: Venue for mid 2023 301 update? Thoughts on regulatory path in in-vivo CRISPR in U.S.?

A: Plan to release RUBY data middle and end of 2023, specific venue to be decided. Feel good about regulatory path with investment and expertise in research and CMC analytics.

Q: Possibility of filing for SCD in 2024? Update on BMS collaboration progress into clinic?

A: Timing of filings is matter of negotiation with agencies. BMS collaboration is progressing, BMS has received data and nominated targets, progress driven by BMS.

Q: All questions answered