Group 1 - The article discusses the analytical approach of a healthcare and tech stock analyst who combines clinical insights with valuation methods to identify investment opportunities [1] - The analyst specializes in scenario-based DCF modeling, sensitivity analysis, and Monte Carlo simulations to assess asymmetric risk-reward profiles [1] - The focus is on translating complex scientific and market dynamics into actionable investment theses, influenced by concepts from "Superforecasting" and "Fooled by Randomness" [1] Group 2 - The article emphasizes the importance of independent verification of information and conducting thorough research before making investment decisions [3] - It highlights that past performance is not indicative of future results and that no specific investment recommendations are provided [4]

Core Insights - CRISPR Therapeutics AG reported topline results from a Phase 1 trial for CTX310, targeting ANGPTL3 to address atherosclerotic heart disease risk factors [1][4] - The trial involved 10 patients across four cohorts, showing dose-dependent reductions in ANGPTL3, triglycerides (TGs), and low-density lipoprotein (LDL) [2][9] - CTX310 demonstrated a favorable safety profile with no severe adverse events reported [3] Trial Details - The trial included lean body weight-based doses of DL1 (0.1 mg/kg), DL2 (0.3 mg/kg), DL3 (0.6 mg/kg), and DL4 (0.8 mg/kg) with at least 30 days of follow-up for each participant [2] - A DL4 patient experienced an 82% reduction in triglycerides from a baseline of 1073 mg/dL, while a DL3 patient had an 81% reduction in LDL-C from a baseline of 256 mg/dL [9] Financials and Market Response - As of March 31, CRISPR reported cash, cash equivalents, and marketable securities totaling $1.85 billion [4] - Following the announcement, CRSP stock increased by 2.99% to $34.15 [7] Analyst Commentary - Chardan Research lowered the price target for CRISPR from $84 to $82, maintaining a Buy rating, indicating that while the topline results show safety and activity, further data in 2H25 will be crucial for assessing competitiveness [4][5] - The topline readout did not include patient-level data, which may introduce variability, but biomarker results align with benchmarks set by RNAi assets for ANGPTL3 [5]

Core Insights - CRISPR Therapeutics reported a first-quarter 2025 loss of $1.58 per share, wider than the Zacks Consensus Estimate of a loss of $1.27 per share, and compared to a loss of $1.43 per share in the same period last year [1] - Total revenues for the quarter were $0.86 million, significantly missing the Zacks Consensus Estimate of $5 million, and up from $0.5 million in the year-ago period [1] - The company's shares fell nearly 12% following the weak quarterly performance, with a year-to-date decline of 15.8%, compared to the industry decline of 2.3% [2] Financial Performance - Research and development expenses decreased by approximately 5% year over year to $72.5 million, attributed to reduced employee-related costs [6] - General and administrative expenses increased by 7.2% year over year to $19.3 million [6] - Collaboration expenses rose to $57.5 million in the first quarter from $47.0 million in the previous year, driven by costs related to the Casgevy therapy [6] - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling $1.86 billion, down from $1.90 billion as of December 31, 2024 [7] Product Development and Pipeline - CRISPR Therapeutics and Vertex Pharmaceuticals' Casgevy therapy received approval for treating sickle cell disease and transfusion-dependent beta thalassemia in several countries [4] - Vertex reported Casgevy sales of $14.2 million in the first quarter, with over 65 authorized treatment centers activated and more than 90 patients initiating cell collection [5] - The company is evaluating two in-vivo candidates, CTX310 and CTX320, in separate phase I clinical studies targeting atherosclerotic heart disease [8] - Initial data from the CTX310 study showed dose-dependent decreases in LDL and TG levels, with peak reductions of up to 82% in TG and 81% in LDL [9] - CTX320 is targeting the LPA gene in patients with elevated Lp(a), with updates expected in the second quarter of 2025 [10] - CRISPR is also conducting phase I/II studies on next-generation allogeneic CAR T product candidates, CTX112 and CTX13, with updates anticipated in mid-2025 [10][11]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to . Switzerland Not Applicable (State or other jurisdiction of incorporation or organization) Baarerstrasse 14 6300 Zug, Switzerland Not Applicable (A ...

Clinical Trials and Investigational Therapies - CTX310™ Phase 1 clinical trial shows dose-dependent reductions in triglycerides (TG) of up to 82% and low-density lipoprotein (LDL) of up to 81%[1] - CTX320™ targeting the LPA gene is in an ongoing Phase 1 clinical trial, with top-line data expected in Q2 2025[1] - CTX112™ and CTX131™ are in clinical trials targeting CD19 and CD70, with updates anticipated in 2025[1] - CTX211, an investigational therapy for type 1 diabetes, is currently in a Phase 1 clinical trial[18] - The company is advancing its investigational therapies, including CTX310 and CTX320, which are in ongoing clinical trials for cardiovascular diseases[17] Financial Performance - Cash, cash equivalents, and marketable securities totaled $1.86 billion as of March 31, 2025, down from $1.90 billion at the end of 2024[15] - R&D expenses for Q1 2025 were $72.5 million, a decrease from $76.2 million in Q1 2024, primarily due to lower employee-related expenses[15] - General and administrative expenses increased to $19.3 million in Q1 2025 from $18.0 million in Q1 2024[15] - Collaboration expenses rose to $57.5 million in Q1 2025, compared to $47.0 million in Q1 2024, mainly due to costs related to CASGEVY[15] - Net loss for Q1 2025 was $136.0 million, compared to a net loss of $116.6 million in Q1 2024[15] - Total revenue for Q1 2025 was $865,000, an increase from $504,000 in Q1 2024, representing a 71.5% growth[26] - Research and development expenses for Q1 2025 were $72,484,000, a decrease from $76,172,000 in Q1 2024, reflecting a 4.5% reduction[26] - Net loss for Q1 2025 was $135,996,000, compared to a net loss of $116,591,000 in Q1 2024, indicating a 16.7% increase in losses[26] - Cash and cash equivalents as of March 31, 2025, were $235,184,000, down from $298,257,000 as of December 31, 2024[28] - Total assets decreased to $2,166,102,000 as of March 31, 2025, from $2,242,034,000 as of December 31, 2024[28] - The comprehensive loss for Q1 2025 was $133,701,000, compared to a comprehensive loss of $120,056,000 in Q1 2024[26] Product Approvals and Market Activity - As of May 1, over 65 authorized treatment centers (ATCs) activated globally for CASGEVY®, with approximately 90 patients having cells collected[7] - CASGEVY® is approved in multiple jurisdictions, with ongoing launches and a manufacturing license application submitted to the FDA[7] - The company celebrated the approval of CASGEVY® (exa-cel) in several countries for treating sickle cell disease and transfusion-dependent beta thalassemia[19] Strategic Partnerships - CRISPR Therapeutics has formed strategic partnerships with leading companies, including Vertex Pharmaceuticals, to accelerate its efforts[19]

Core Insights - CRISPR Therapeutics has reported promising initial Phase 1 clinical data for CTX310™, showing significant dose-dependent reductions in triglycerides (TG) and low-density lipoprotein (LDL), with reductions of up to 82% in TG and 81% in LDL, alongside a well-tolerated safety profile [1][3][7] - The company continues to advance its innovative therapies, including CASGEVY®, which has over 65 authorized treatment centers activated globally and is expected to see significant patient growth in 2025 [1][6][7] - Ongoing clinical trials for CTX320™ and next-generation CAR T product candidates CTX112™ and CTX131™ are on track, with updates anticipated in 2025 [1][3][7] Financial Overview - As of March 31, 2025, the company has a strong balance sheet with approximately $1.86 billion in cash, cash equivalents, and marketable securities [1][18] - For the first quarter of 2025, research and development expenses were $72.5 million, a decrease from $76.2 million in the same period of 2024, while general and administrative expenses rose to $19.3 million from $18.0 million [18] - The net loss for the first quarter of 2025 was $136.0 million, compared to a net loss of $116.6 million in the first quarter of 2024 [18][27] Clinical Development Highlights - CTX310™ targets the ANGPTL3 gene, which is crucial for regulating LDL and TG levels, addressing a significant patient population in the U.S. affected by elevated LDL and TG levels [3][19] - The ongoing Phase 1 trial for CTX310 has shown that doses DL3 and DL4 resulted in reductions of up to 75% in ANGPTL3 levels, with no severe adverse events reported [3][4][7] - CTX320™ is also in a Phase 1 trial targeting the LPA gene, with updates expected in the second quarter of 2025 [1][3][7] Pipeline and Future Prospects - The company is advancing two preclinical programs, CTX340™ for refractory hypertension and CTX450™ for acute hepatic porphyrias, both in IND/CTA-enabling studies [1][3][19] - CASGEVY® has been approved in multiple jurisdictions for treating sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), with ongoing launches and reimbursement agreements enhancing patient access [1][6][14] - The company plans to present further clinical updates and data at medical meetings in the second half of 2025 [1][7]

Group 1 - Gene therapy stocks, including CRISPR Therapeutics (CRSP) and Intellia Therapeutics (NTLA), experienced significant volatility in Q1 2025, resulting in year-to-date share price declines of -2.82% and -24.19%, respectively [1] - The decline in share prices may be partially linked to the overall instability in the biotechnology sector [1] - The analysis focuses on the potential of novel treatments, particularly in Cell & Gene Therapies (CGT), and their ability to generate returns for shareholders [1]

Group 1: Iovance Biotherapeutics - Iovance Biotherapeutics specializes in cancer treatment and received approval for Amtagvi, a therapy for advanced melanoma, which is the first of its kind for solid tumors [3][4] - The company generated $164.1 million in revenue last year, a significant increase from the previous year when it had minimal revenue [4] - Despite the approval and revenue growth, the stock has underperformed due to market dynamics and the complexity of administering TIL therapies, which take 34 days to manufacture [5] - The stock is currently priced under $4 per share, and the company is pursuing regulatory approvals and label expansions for Amtagvi, which could lead to significant upside potential [6] Group 2: CRISPR Therapeutics - CRISPR Therapeutics develops gene-editing therapies using the CRISPR/Cas9 technique and received approval for Casgevy, the first CRISPR medicine, which treats rare blood disorders [8] - The company has not generated substantial revenue since the approval, as manufacturing ex vivo gene-editing therapies is complex and time-consuming [9] - Casgevy is priced at $2.2 million in the U.S., targeting a market of approximately 58,000 patients with minimal competition, indicating potential for significant revenue once it gains traction [10] - The company has delivered returns comparable to the broader market since its IPO in 2016, and long-term investors may benefit from future breakthroughs in gene-editing products [11][13]

Company Performance - CRISPR Therapeutics AG (CRSP) closed at $39.11, with a daily increase of +1.48%, underperforming the S&P 500's gain of 2.03% [1] - The company's stock has decreased by 1.63% over the past month, which is better than the Medical sector's decline of 8.57% and the S&P 500's drop of 5.07% [1] Earnings Expectations - The upcoming earnings report is expected to show an EPS of -$1.27, reflecting an 11.19% improvement from the same quarter last year [2] - Revenue is anticipated to be $5.24 million, indicating a significant increase of 947.2% compared to the previous year’s quarter [2] Full Year Estimates - For the full year, analysts project an EPS of -$5.09 and revenue of $56.98 million, representing changes of -17.28% and +52.69% respectively from the prior year [3] Analyst Sentiment - Recent changes in analyst estimates suggest a positive outlook for CRISPR Therapeutics AG, indicating optimism regarding the company's business and profitability [4] - The Zacks Rank system, which reflects these estimate changes, currently rates CRISPR Therapeutics AG at 3 (Hold) [6] Industry Context - The Medical - Biomedical and Genetics industry, which includes CRISPR Therapeutics AG, has a Zacks Industry Rank of 79, placing it in the top 32% of over 250 industries [7] - Research indicates that the top 50% rated industries outperform the bottom half by a factor of 2 to 1 [7]

Group 1 - CRISPR Therapeutics AG closed at $38.54, reflecting a -1.76% change from the previous day, underperforming compared to the S&P 500's gain of 1.67% [1] - The company has experienced a 4.06% decline in share price over the past month, while the Medical sector and S&P 500 have lost 9.34% and 6.57%, respectively [1] Group 2 - Analysts expect CRISPR Therapeutics AG to report earnings of -$1.27 per share, indicating a year-over-year growth of 11.19%, with revenue projected at $5.24 million, a significant increase of 947.2% compared to the same quarter last year [2] - For the full year, earnings are anticipated to be -$5.09 per share and revenue at $56.98 million, reflecting changes of -17.28% and +52.69% from the previous year [3] Group 3 - Recent changes to analyst estimates for CRISPR Therapeutics AG are important as they reflect the company's business dynamics and potential profitability [4] - The Zacks Rank system, which evaluates estimate changes, indicates that CRISPR Therapeutics AG currently holds a Zacks Rank of 3 (Hold) [6] Group 4 - The Medical - Biomedical and Genetics industry, which includes CRISPR Therapeutics AG, is ranked 77 in the Zacks Industry Rank, placing it in the top 32% of over 250 industries [7] - The top 50% rated industries outperform the bottom half by a factor of 2 to 1, indicating a favorable environment for companies within this industry [7]