Core Viewpoint - CRISPR Therapeutics has seen a significant stock increase of over 60% in 2023 following FDA approval of its first treatment, Casgevy, for sickle cell disease, raising questions about the company's future growth potential and stock valuation [1][2]. Company Overview - CRISPR Therapeutics is transitioning into a commercial-stage company with the launch of Casgevy, developed in partnership with Vertex Pharmaceuticals [1][4]. - Casgevy is a treatment for sickle cell disease, utilizing genetically altered stem cells to produce fetal hemoglobin, with clinical trials showing 29 out of 31 patients went at least 12 months without vaso-occlusive crises [2][3]. Market Potential - There are approximately 16,000 eligible patients in the U.S. for Casgevy, who typically require extensive monitoring and hospitalization due to vaso-occlusive events [3]. - Despite a high list price of $2.2 million for Casgevy, it may be considered cost-effective compared to the estimated $4 million to $6 million lifetime management costs for patients with frequent vaso-occlusive events [3]. Competitive Landscape - Casgevy faces competition from other gene therapies, such as Lyfgenia from Bluebird Bio, which was approved on the same day and targets the same patient population [5]. - The clinical trial data for Casgevy is slightly better than that of Lyfgenia, but both therapies will compete for a limited market [5]. Financial Considerations - CRISPR Therapeutics received a $200 million milestone payment following Casgevy's approval, but future cash flows remain uncertain [6]. - The company has a market cap of $5.2 billion and ended September 2023 with approximately $1.7 billion in cash and marketable securities, having burned through $234 million in the first nine months of the year [6][7]. Future Prospects - CRISPR Therapeutics is also developing additional therapies, including off-the-shelf cancer treatments and regenerative treatments for diabetes, which could provide future growth opportunities [4]. - However, the success of these initiatives is uncertain, and the company may face challenges in achieving expected sales from Casgevy [7].

Financial Data and Key Metrics Changes - In Q3 2023, bluebird bio reported total revenue of $12.4 million, primarily driven by product revenue from ZYNTEGLO and SKYSONA, indicating strong linear growth [18][19] - The company has a cash position of $227 million as of September 30, 2023, with a cash burn guidance for the full year 2023 in the range of $270 million to $300 million [20][18] - The company anticipates a potential $63 million in gross revenue from 22 combined patient starts for ZYNTEGLO and SKYSONA [18][19] Business Line Data and Key Metrics Changes - ZYNTEGLO has seen 16 patient starts since launch, with a significant increase in Qualified Treatment Centers (QTCs) activated, now totaling 29 across 16 states [11][12] - SKYSONA has completed six patient starts and activated four QTCs, maintaining a guidance of five to ten patient starts for the year [15] - The company has signed outcomes-based agreements for ZYNTEGLO with Michigan and Massachusetts state Medicaid agencies, demonstrating payer support [13][14] Market Data and Key Metrics Changes - The company estimates that approximately 50% of sickle cell disease patients are covered by Medicaid, with ongoing negotiations for outcomes-based agreements with national payers [33][17] - The potential market for lovo-cel is significantly larger, with about 20,000 severe sickle cell patients in the U.S. compared to approximately 1,500 for beta-thalassemia [75] Company Strategy and Development Direction - bluebird bio aims to leverage its unique position as a standalone commercial gene and cell therapy company to drive growth and profitability, particularly with the anticipated approval of lovo-cel [7][8] - The company plans to expand its QTC network to reach 95% of sickle cell patients within 200 miles of a planned QTC [16][66] - The focus is on ensuring timely and equitable access to lovo-cel at launch, with innovative contracting approaches being negotiated with payers [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming FDA approval of lovo-cel, viewing it as a significant milestone for the sickle cell disease community and a key driver of profitability [8][21] - The company is optimistic about the demand for gene therapy, with over 70% of patients indicating they would consider gene therapy if recommended by their doctor [15][16] - Management highlighted the importance of long-term follow-up data in differentiating their products in the market [44][45] Other Important Information - The company has entered into an advanced agreement to sell a priority review voucher for $103 million, which could strengthen its financial position ahead of the lovo-cel launch [19] - bluebird bio is applying learnings from ZYNTEGLO to optimize commercial manufacturing processes for lovo-cel [17] Q&A Session Summary Question: Can you provide details on patients infused and revenue recognition? - The company has infused 22 patients across ZYNTEGLO and SKYSONA, translating to about $63 million in gross revenue, with $8.5 million of deferred revenue expected to be recognized before year-end [23][25] Question: What are the expectations for R&D burn related to lovo-cel? - R&D expenses are expected to decrease post-approval of lovo-cel, but there will still be costs associated with long-term follow-up and optional patient registry [27][28] Question: How will Medicaid reimbursement dynamics affect revenue recognition? - The company anticipates that Medicaid patients may take longer to process compared to commercial patients, but expects fair coverage based on past experiences with ZYNTEGLO [30][33] Question: What is the expected capacity at Qualified Treatment Centers? - Capacity at QTCs is not expected to be an issue, as hospitals have built significant capabilities for gene therapy [38] Question: How will outcomes-based agreements impact revenue recognition? - Revenue will be constrained based on estimated patient flow and outcomes, with conservative estimates to avoid significant reversals of revenue [40][41] Question: What is the plan for pricing lovo-cel? - The company will consider clinical benefits and cost savings when pricing lovo-cel, but will not comment on competitor pricing [80] Question: What is the status of the two patients who developed AML in trials? - There have been no cases of insertional oncogenesis with lovo-cel, but safety events related to the procedure will likely be mentioned in the label [81]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 __________________________________________________________________ FORM 10-Q __________________________________________________________________ (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Num ...

Financial Data and Key Metrics Changes - For Q2 2023, bluebird bio reported combined product revenue of $6.8 million for ZYNTEGLO and SKYSONA, with a cash position of $291 million as of June 30 [12][13] - The company anticipates a cash burn in the range of $270 million to $300 million for the full year 2023, with a cash runway extending into Q4 2024, including $45 million of restricted cash [12][13] Business Line Data and Key Metrics Changes - The company has achieved 16 patient starts for ZYNTEGLO and SKYSONA, translating to a potential $45 million in gross revenue over time [9][10] - The activation of 15 qualified treatment centers (QTCs) has been completed, with plans to ramp up to 40 to 50 QTCs by year-end to support the launch of lovo-cel [10][16] Market Data and Key Metrics Changes - The market opportunity for lovo-cel is significant, with over 20,000 individuals in the U.S. potentially suitable for gene therapy for sickle cell disease [11][20] - Market research indicates that lovo-cel could capture between 50% to 65% market share against direct competitors [21] Company Strategy and Development Direction - bluebird bio aims to evolve into an industry-leading gene therapy company with a focus on expanding its commercial footprint and achieving profitability in the near term [8][26] - The company is preparing for the commercial launch of lovo-cel in early 2024, pending FDA approval, and is focused on building a strong QTC network [11][26] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the commercial viability of their therapies, highlighting the positive momentum in patient starts and QTC activations [9][26] - The company anticipates continued growth and scale over the next five years, with a focus on maximizing stakeholder value [8][26] Other Important Information - The company has a unique strategic position in the gene therapy industry, with a robust clinical, regulatory, and commercial track record [6][7] - SKYSONA has seen five patient starts, with no ultimate denials from payers, although it carries a boxed warning for hematological malignancy [24][25] Q&A Session Summary Question: What is the current referral process for ZYNTEGLO? - Management noted that QTCs are treating their initial patient loads and beginning to accept referrals from outside their centers, which is a positive trend [31] Question: What barriers exist from collection to infusion? - Management indicated that there are minimal patient drop-offs, with delays primarily due to scheduling conflicts rather than patient interest [35] Question: What is the gross margin expectation? - The company expects a gross margin of at least 70%, with outcomes-based agreements in place for ZYNTEGLO [38][39] Question: What is the revenue breakdown for this quarter? - Management emphasized that patient starts are the key performance indicator, and revenue will follow as treatments are completed [45] Question: What is the status of the FDA review for lovo-cel? - The FDA has not requested an advisory committee meeting for lovo-cel, and the company is preparing for a potential approval [47] Question: What are the characteristics of patients undergoing treatment? - The company has seen a diverse range of patients, including both younger and older individuals, expressing interest in treatment [63]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 __________________________________________________________________ FORM 10-Q __________________________________________________________________ (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 __________________________________________________________________ FORM 10-Q __________________________________________________________________ (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 ___________________________________________________________________________ FORM 10-K ___________________________________________________________________________ (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission ...

Pipeline and Approvals - Bluebird bio anticipates 3 approvals by the end of 2023, all with wholly-owned global rights[5] - ZYNTEGLO® (beti-cel) received FDA approval on August 17, 2022, for beta-thalassemia requiring regular red blood cell transfusions, with commercial launch in Q4 2022[6] - The FDA Advisory Committee unanimously endorsed eli-cel (15-0) for treatment of early active CALD[6, 36] - A BLA submission for lovo-cel for sickle cell disease is planned for Q1 2023[6, 33, 34] Clinical Data and Patient Impact - In Phase 3 studies for ZYNTEGLO®, 89% of patients achieved transfusion independence (TI) and normal or near-normal hemoglobin levels[13] - Eli-cel maintained an estimated event-free survival rate of 86.8% (95% CI: 72.7%, 93.9%) through 7 years of follow-up[39] - Lovo-cel demonstrated complete resolution of severe vaso-occlusive events (VOEs) through up to 36 months of follow-up in evaluable patients[32] Commercial Strategy and Market Opportunity - ZYNTEGLO® is priced at $2.8 million with an outcomes-based agreement offering up to 80% rebate if transfusion independence is not achieved within 2 years[17, 18] - The company estimates that 55-60% of the ~1,500 patients with transfusion-dependent beta-thalassemia in the US may be eligible for ZYNTEGLO®[16] - The company plans to expand to ~50 Qualified Treatment Centers (QTCs) by year-end 2023 in anticipation of SCD launch[15] - Over 20,000 SCD patients in the US may be addressed by lovo-cel gene therapy[26, 27] Financial Status - The company's current cash runway extends into 1H23, with $218 million cash on hand as of June 30, 2022[41] - The company is targeting $60 million per quarter net cash burn by year-end 2022 and carry into 2023[41]