Core Viewpoint - Vertex Pharmaceuticals' stock has increased following its fourth-quarter results, but long-term investment potential lies with its partner CRISPR Therapeutics, which developed the gene-editing therapy Casgevy [1][2]. Group 1: Vertex Pharmaceuticals - Vertex reported higher sales projections for Casgevy, a gene-editing therapy for sickle cell disease and beta thalassemia, contributing to its profitability and revenue from cystic fibrosis treatments [2]. - The company's share price experienced a short-term spike but moderated afterward, losing most of its gains [2]. Group 2: CRISPR Therapeutics - CRISPR Therapeutics, based in Switzerland, is the developer of Casgevy, the first CRISPR-based gene therapy approved by the FDA, and stands to benefit from increased sales of this therapy [3]. - The company has a strong position in the market, as evidenced by its significant holding in Cathie Wood's Ark Innovation ETF, indicating investor confidence in its potential [4]. - CRISPR has five additional gene therapy candidates in clinical trials, which target larger patient populations than Casgevy, enhancing its long-term growth prospects [4]. - Notable candidates include CTX310, which has shown to reduce triglycerides and LDL cholesterol by over 80%, and CTX320 for atherosclerotic cardiovascular disease [5]. - The company is also developing SRSD107, a long-acting gene therapy for thrombosis, and CTX211, which aims to restore insulin production in type 1 diabetes patients [6]. - Despite not being profitable and experiencing a 64% decline in share price over the past five years, CRISPR has over $1.9 billion in cash, positioning it well for future development if Casgevy sales increase as anticipated [7].

Core Insights - Jacob Funds released its fourth-quarter 2025 investor letter, noting a slight correction in equity markets in November despite robust economic growth throughout the year [1] - Divergent data on consumer spending and the labor market has raised doubts about future economic projections, a trend that has become common in recent years [1] - The Fund's strategy indicates that moderation in AI tech companies may benefit small companies, potentially leading to expansion in valuation multiples and favorable performance compared to peers [1] Company Focus: Prime Medicine, Inc. - Prime Medicine, Inc. (NASDAQ:PRME) is highlighted as a biotechnology company specializing in gene editing technology, with a market capitalization of $597.49 million [2] - As of February 17, 2026, Prime Medicine's stock closed at $3.31 per share, with a one-month return of -17.46% and a 12-month increase of 0.76% [2] - Jacob Funds added Prime Medicine to its portfolio, expressing confidence in its gene editing technology and the potential for significant upside if the technology proves viable [3] - The company acknowledges challenges in the gene therapy field, including safety, durability, and cost, but remains optimistic about the potential for effective cures for chronic and deadly diseases [3] - Promising efficacy and safety signals were observed in Prime Medicine's first clinical trial, indicating early positive developments in its gene editing capabilities [3]

February 2026 Investor Presentation We're in. For patients. 1 Forward Looking Statements The forward-looking statements in this presentation are based upon the Company's current expectations and beliefs, and involve known and unknown risks, uncertainties and other factors, which may cause the Company's actual results, performance and achievements and the timing of certain events to differ materially from the results, performance, achievements or timings discussed, projected, anticipated or indicated in any ...

Core Insights - Krystal Biotech reported strong revenue growth for Q4 2025 and full-year 2025, with net revenue from VYJUVEK reaching $107.1 million in Q4 and $389.1 million for the year, representing approximately 34% year-over-year growth [3][4][6] Financial Performance - R&D expenses for Q4 2025 were $14.8 million, up from $13.5 million a year earlier, while SG&A expenses increased to $41.4 million from $31.3 million, primarily due to higher headcount and costs associated with global launches [1] - Gross margin remained strong at 94% for both the quarter and the full year, with expectations to maintain margins in the 90% to 95% range for the foreseeable future [2] Market Expansion - The company is experiencing momentum in international markets, particularly in Europe and Japan, with over 90 DEB patients prescribed VYJUVEK across these regions [13] - U.S. commercial momentum is also strong, with more than 660 reimbursement approvals and over 500 unique prescribers since launch [6][9] Pipeline Developments - Krystal is advancing multiple programs, including KB407 for cystic fibrosis, with expected registrational readouts before year-end [5][18] - Protocol changes for KB801 and KB803 aim to facilitate at-home dosing, with data expected before year-end [19][20] Cash Position - The company ended 2025 with $955.9 million in cash and investments, providing a strong financial foundation for future growth [8]

Financial Data and Key Metrics Changes - The company reported net VYJUVEK revenue of $107.1 million in Q4 2025, marking a growth of almost 10% compared to the previous quarter and approximately 18% year-over-year [26][27] - Year-to-date VYJUVEK net revenue reached $389.1 million, an increase of approximately 34% compared to full year 2024 revenue [26] - Gross margin for Q4 was 94%, down from 96% in Q3 and 95% in Q4 of 2024, attributed to increased sales outside the U.S. which carry higher costs [27] Business Line Data and Key Metrics Changes - The U.S. commercial performance showed strong momentum with over 660 reimbursement approvals since launch and over 500 unique prescribers [10] - In Europe, the launch of VYJUVEK is progressing well, with over 90 DEB patients prescribed the treatment across Germany, France, and Japan [12][16] - The company aims to expand its distributor agreements to over 40 countries in 2026, having already signed agreements covering more than 20 countries [5] Market Data and Key Metrics Changes - The company is experiencing strong demand for VYJUVEK in various markets, with significant patient adoption in Germany and Japan [12][16] - Pricing negotiations are ongoing in Germany and France, with expectations to finalize agreements in the second half of 2026 for Germany and in 2027 for France [13][16] Company Strategy and Development Direction - The company is focused on expanding global access for VYJUVEK while advancing a pipeline of genetic therapies, with plans to initiate two additional registrational programs later in the year [6][34] - The strategy includes disciplined capital allocation and a commitment to self-launching new indications if approved [8][34] - The company is also exploring stock buyback options but prioritizes investments in its pipeline and potential M&A opportunities [52] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth potential from international markets, noting that there are more DEB patients outside the U.S. than within it [32] - The company anticipates that revenue may not track linearly with patient counts due to accruals and ongoing pricing negotiations [33] - Management highlighted the importance of registrational programs and the positive impact of recent FDA designations on development timelines [25][34] Other Important Information - The company ended the year with $955.9 million in combined cash and investments, positioning it well for future commercial launches and pipeline milestones [31] - The company received a Fast Track designation for KB111 and an RMAT designation for KB707, which can accelerate development timelines [25] Q&A Session Summary Question: Visibility into Q1 and contribution from ex-U.S. vs U.S. in 2026 - Management indicated that while ex-U.S. markets will be the predominant growth driver, U.S. demand is also accelerating, with expectations to break out revenue in Q1 [36][38] Question: Compliance rates in EU and Japan - Compliance in Europe is similar to the U.S. at launch, but Japan has a two-week prescription requirement that may affect long-term compliance [44][48] Question: Updates on pricing negotiations in Europe - Management expects to reach a pricing agreement in Germany in Q3 and anticipates that negotiations in France will extend into the first half of next year [55][56] Question: Changes in dosing regimens for ocular studies - The modified dosing regimens were designed to enhance patient compliance and convenience, with no changes to the dose volume or potency [75][76] Question: Patient distribution for VYJUVEK in Europe - Management noted that estimating patient numbers in Europe is challenging due to varying laws and logistics, but they are optimistic about the launch progress [63][64]

Financial Data and Key Metrics Changes - For 2025, the company reported total revenue of $673 million, representing a 20% growth over 2024, exceeding the upper end of guidance [10] - The net loss for the year was $575 million, or $5.83 per share, with cash, cash equivalents, and marketable securities totaling $738 million as of December 31 [11] Business Line Data and Key Metrics Changes - Crysvita contributed $481 million, with a 17% growth over 2024, exceeding guidance [10] - Dojolvi generated $96 million, reflecting a 9% growth over 2024 [10] - Evkeeza saw significant growth, contributing $59 million, representing an 84% increase over 2024 [10] - Mepsevii contributed $37 million, continuing to treat patients in an ultra-rare indication [10] Market Data and Key Metrics Changes - The commercial business delivered a significant 20% year-over-year growth in 2025, with treatments reaching over 35 countries [6] - The company anticipates total revenue in 2026 to be between $730 million and $760 million, representing an 8%-13% growth over 2025 [11][12] Company Strategy and Development Direction - The company is focused on achieving profitability by 2027 through a strategic restructuring plan that includes a 10% workforce reduction and realignment of resources towards high-impact opportunities [7][9] - The company aims to launch three additional treatments over the next two years while continuing to grow its existing commercial products [9][22] Management's Comments on Operating Environment and Future Outlook - Management highlighted 2026 as a significant year with potential approvals in key programs and pivotal data readouts [3] - The company is addressing the FDA's incomplete response letter regarding UX111 and is working to provide additional documentation for resubmission [5][20] - Management expressed confidence in the ability to deliver the next phase of growth required to reach profitability [19] Other Important Information - The company is implementing a strategic restructuring plan to reduce operating expenses while advancing its product pipeline [7][9] - The company expects combined R&D and SG&A expenses to be flat to down low single digits in 2026 compared to 2025 [12] Q&A Session Summary Question: Regarding the primary endpoint for the phase 3 Angelman study - The decision to use cognition over expressive communication was based on its fundamental importance and the complexities of communication development [24][25] Question: Can you provide insights on the patient baseline profile for the phase 3 study? - The baseline data from the phase 3 program is comparable to the expansion trial, providing confidence in the study's design [29][30] Question: How does the company plan to achieve profitability in 2027? - The pathway to profitability includes continued growth from current products and cost reductions, with expectations for combined R&D and SG&A expenses to decrease significantly by 2027 [35][36] Question: Can you clarify the timeline for the IRL resubmission? - The resubmission timeline is similar to the original submission, with a PDUFA date expected approximately six months after resubmission [68][69] Question: What is the expected launch trajectory for DTX-401? - The launch is expected to develop steadily, with strong demand anticipated, but not an immediate steep uptake [72]

Corporate Presentation February 2026 Confidential and Proprietary Forward looking statements Cautionary note regarding forward-looking statements: This presentation contains forward-looking statements, including, but not limited to, statements regarding our expectations, estimates, assumptions, and projections regarding our future operating results and financial performance, including our expectations for profitability in 2027, anticipated cost or expense management, including the company's expectations rel ...

Core Viewpoint - The FDA has issued a Complete Response Letter (CRL) for RGX-121, raising concerns about study eligibility criteria and surrogate endpoints, which may complicate the path to approval for this gene therapy targeting MPS II [2][4]. Regulatory Developments - The FDA accepted the RGX-121 Biologics License Application (BLA) under the accelerated approval pathway, but the Prescription Drug User Fee Act (PDUFA) goal date has been extended from November 9, 2025, to February 8, 2026 [1]. - The CRL outlines several potential paths forward, including conducting a new study, treating additional patients, and using an untreated control arm, which poses challenges in the ultra-rare disease population [2]. Company Actions - REGENXBIO plans to request a Type A meeting to discuss the CRL and aims to resubmit the BLA with additional evidence from global experts to clarify the neuronopathic patient population [3]. - The BLA for RGX-121 was supported by positive biomarker, functional, and safety data from the CAMPSIITE I/II/III trial, demonstrating good tolerability across all patients [3]. Analyst Insights - Analysts note that the CRL reflects structural reasons for not approving the gene therapy rather than safety issues related to a clinical hold [4]. - The FDA's cautious approach indicates a preference for placebo-controlled data before granting accelerated approvals [4]. Market Performance - REGENXBIO's stock carries a Buy Rating with an average price target of $31.38, despite facing regulatory challenges [5]. - The stock showed strong momentum, outperforming the broader market, although it experienced a decline of 10.99% to $9.17 during premarket trading [5][6]. - Recent analyst ratings include Buy from Chardan Capital with a target of $52.00, and Stifel raised its target to $45.00 [6].

Core Insights - 4D Molecular Therapeutics has completed enrollment for the 4FRONT-1 Phase 3 clinical trial of 4D-150 in patients with wet age-related macular degeneration (wet AMD) [1][4] - The trial achieved enrollment in approximately 11 months, exceeding initial projections and reflecting strong interest from both investigators and patients [2][4] - Topline data from the 4FRONT-1 trial is expected in the first half of 2027, with a second Phase 3 trial, 4FRONT-2, on track for completion in the second half of 2026 [4] Company Overview - 4D Molecular Therapeutics is a late-stage biotechnology company focused on developing durable and disease-targeted therapeutics, particularly for retinal diseases [7] - The lead product candidate, 4D-150, aims to provide sustained delivery of anti-VEGF biologics through a single intravitreal injection, potentially reducing the treatment burden for patients [5][7] - The company is also developing 4D-710, a genetic medicine for cystic fibrosis, demonstrating its commitment to innovative therapeutic solutions [7] Clinical Trial Details - The 4FRONT-1 trial is a multicenter, randomized, double-masked study comparing intravitreal 4D-150 to aflibercept, with the primary endpoint being non-inferiority in best corrected visual acuity (BCVA) at 52 weeks [2][4] - The trial is specifically targeting treatment-naïve wet AMD patients across North America, with plans for supplemental aflibercept injections for participants [2][4] - The second Phase 3 trial, 4FRONT-2, will include both treatment-naïve and recently diagnosed treatment-experienced patients, with an identical design to 4FRONT-1 [4] Market Context - Wet AMD is a prevalent condition, with over 4 million individuals expected to be affected in major markets within the next five years, and 200,000 new diagnoses annually in the U.S. [6] - The disease is characterized by abnormal blood vessel growth in the retina, leading to vision loss, which underscores the need for effective treatment options [6]

Core Insights - The article discusses updated preliminary safety and exploratory efficacy data from uniQure's Phase I/IIa trial of AMT-191, a gene therapy for Fabry disease, presented at the WORLDSymposium [1][7] Group 1: Efficacy Data - All 11 patients in the trial exhibited elevated α-galactosidase A (α-Gal A) activity across three dosing cohorts [2] - Dose-dependent increases in α-Gal A activity were observed, ranging from 0.34- to 82.2-fold at the lowest dose, 1.6- to 312.52-fold at the mid dose, and 27.7- to 223.7-fold at the highest dose, with durability noted over follow-up periods [3] - Six out of 11 patients discontinued enzyme replacement therapy after meeting pre-specified criteria, including elevated α-Gal A activity, while stable plasma lyso-Gb3 levels were maintained post-dose across all cohorts [4] Group 2: Safety Profile - The safety profile of AMT-191 was manageable, with no serious adverse events (SAEs) related to the therapy observed at the lower doses [5] - Two patients at the mid dose experienced asymptomatic Grade 3 liver enzyme elevations, confirmed as dose-limiting toxicity, leading to a pause in additional dosing in mid- and high-dose cohorts [5][6] - At the highest dose, five SAEs were reported, including two unrelated to AMT-191, and one patient experienced an asymptomatic Grade 3 liver enzyme elevation that resolved with corticosteroid therapy [6] Group 3: Clinical Trial Overview - The Phase I/IIa trial is a multi-center, open-label study in the U.S. with three dosing cohorts, exploring safety, tolerability, and early efficacy signs [8] - Patients were not excluded based on pre-existing neutralizing antibodies to AAV5 and will be followed for 24 months [8] - AMT-191 has received Orphan Drug and Fast Track designations from the U.S. FDA, indicating its potential significance in treating Fabry disease [9] Group 4: Background on Fabry Disease - Fabry disease is an X-linked genetic lysosomal storage disorder caused by α-Gal A deficiency, leading to toxic accumulation of lyso-Gb3, which can damage various organs [10] - The current standard treatment involves bi-weekly enzyme replacement therapy, which has limited effectiveness due to poor cross-correction and substrate clearance [10] Group 5: Company Overview - uniQure is focused on advancing gene therapies for severe diseases, with a history of significant achievements in the field, including a gene therapy for hemophilia B [11] - The company is developing a pipeline of gene therapies for various conditions, including Fabry disease, and aims to deliver potentially curative treatments [11]