Krystal Biotech (NasdaqGS:KRYS) Q4 2025 Earnings call February 17, 2026 08:30 AM ET Company ParticipantsChristine Wilson - SVP and Head of U.S. CommercialGavin Clark-Gartner - Managing Director of Biotechnology Equity ResearchJoshua Fleishman - Equity Research AssociateKate Romano - Chief Accounting OfficerKrish Krishnan - Chairman and CEOLaurent Goux - SVP and General Manager for EuropeStéphane Paquette - VP of Corporate DevelopmentSuma Krishnan - President of Research and DevelopmentConference Call Partic ...

Ultragenyx Pharmaceutical (NasdaqGS:RARE) Q4 2025 Earnings call February 12, 2026 05:00 PM ET Speaker10Good afternoon, and welcome to the Ultragenyx's fourth quarter and full year 2025 financial results conference call. At this time, all participants are in a listen-only mode. At the end of the prepared remarks, you will have an opportunity to ask questions during the Q&A portion of the call. It is now my pleasure to turn the call to Joshua Higa, Vice President of Investor Relations.Speaker5Thank you. We've ...

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]

Core Insights - The article highlights the potential of isaralgagene civaparvovec (ST-920) as a one-time, well-tolerated, and durable gene therapy for Fabry disease, which could significantly change the treatment landscape for this condition [1][3][5] Study Results - The STAAR study showed a positive mean annualized estimated glomerular filtration rate (eGFR) slope of 1.965 mL/min/1.73m²/year at 52 weeks across all 32 patients, indicating improved renal function [4] - Among 19 patients with 104 weeks of follow-up, the mean annualized eGFR slope was 1.747 mL/min/1.73m²/year, further supporting the therapy's efficacy [4] - Cardiac function remained stable over one year, with consistent cardiac structural stability observed across various clinical and demographic subgroups [4] Safety and Regulatory Pathway - Isaralgagene civaparvovec demonstrated a favorable safety profile without the need for preconditioning, making it a viable option for patients [4][5] - The FDA has agreed that the data from the STAAR study can serve as the primary basis for approval under the Accelerated Approval pathway, with a rolling submission of the Biologics License Application (BLA) initiated [1][6] Clinical Implications - The therapy shows potential to improve kidney function and stabilize cardiac health, addressing the multi-organ challenges posed by Fabry disease [3][5] - The ability to withdraw from current enzyme replacement therapy (ERT) is a significant advantage, offering a durable treatment option for patients [3][5] Future Presentations - Detailed data from the STAAR study will be presented at the 22nd Annual WORLDSymposium in San Diego, CA, from February 2-6, 2026, with multiple platform and poster presentations scheduled [2][12]

Core Insights - CRISPR Therapeutics (CRSP) is expected to exceed expectations in its fourth-quarter and full-year 2025 results, with earnings having beaten estimates by 11.36% in the last reported quarter [1] - The Zacks Consensus Estimate for quarterly sales is $4.00 million, while the earnings estimate is a loss of $1.15 per share [1] Financial Performance - CRISPR Therapeutics' revenue includes grants and collaboration income from its partnership with Vertex Pharmaceuticals (VRTX) [2] - The company has shown a decent performance over the past four quarters, beating earnings estimates in three of those quarters, with an average surprise of 15.23% [8] Product Development - The one-shot gene therapy, Casgevy, developed in partnership with VRTX, was approved for sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT) in late 2023/early 2024, marking it as the only marketed product in CRISPR's portfolio [3] - Casgevy sales have been increasing, which is likely to improve collaboration expenses for the upcoming quarter [4] Future Prospects - Investors are keen on updates regarding global regulatory submissions planned for the first half of 2026, aiming for label expansion of Casgevy for younger patients [5] - CRISPR Therapeutics is developing novel CAR-T cell therapies, including zugo-cel, which is being evaluated in early-stage studies for various conditions [6] - The company is also advancing its in-vivo pipeline with candidates CTX310 and CTX320, and plans to introduce two more programs, CTX340 and CTX450, into clinical development by the end of the year [7] Earnings Prediction - The model predicts an earnings beat for CRISPR Therapeutics, supported by a positive Earnings ESP of +15.85% and a Zacks Rank of 3 [11][12] - The Most Accurate Estimate stands at a loss of $0.97 per share, compared to the Zacks Consensus Estimate of a loss of $1.15 [12]

Core Insights - Ultragenyx Pharmaceutical (RARE) has resubmitted its biologics license application (BLA) to the FDA for accelerated approval of its gene therapy candidate UX111, aimed at treating Sanfilippo syndrome type A (MPS IIIA) [1][8] - The company’s shares have decreased by 44.6% over the past year, contrasting with a 15.2% increase in the industry [2] BLA Resubmission Details - The FDA issued a Complete Response Letter (CRL) in July 2025, requesting additional information regarding chemistry, manufacturing, and controls (CMC) elements, which were facility- and process-related issues not tied to product quality [3][10] - The resubmitted BLA addresses all CMC observations from the CRL and includes long-term data supporting neurological benefits, along with biomarker data in line with FDA agreements [4][11] Regulatory Timeline - A target action date from the FDA is expected within a month, with a review period of up to six months anticipated, aiming for a decision in the third quarter of 2026 [5][8] Clinical Data and Efficacy - The original BLA submission was supported by data from the phase I/II/III Transpher A study, which showed that UX111 treatment led to a significant reduction in heparan sulfate (HS) levels in cerebrospinal fluid (CSF) and improved long-term cognitive development [9][11] - The updated clinical data in the resubmission includes an additional year of patient follow-up, demonstrating durable treatment benefits and increasing separation from untreated outcomes [11] Disease Context - Sanfilippo syndrome type A is a rare, fatal lysosomal storage disorder affecting the central nervous system, with approximately 3,000 to 5,000 patients in commercially accessible areas and a median life expectancy of 15 years [14]

FDA Approvals & Rejections - Intellia Therapeutics has received FDA approval to resume its MAGNITUDE-2 Phase 3 trial for nexiguran ziclumeran (nex-z) targeting hereditary transthyretin amyloidosis with polyneuropathy, increasing target enrollment from 50 to 60 patients [2][4] - Outset Medical's next-generation Tablo Hemodialysis System has been granted FDA 510(k) clearance, making it the first dialysis device to meet enhanced cybersecurity standards, with shipping expected to begin in Q2 2026 [6][7] - OKYO Pharma has received positive feedback from the FDA for its Phase 2b/3 trial design for Urcosimod, a candidate for neuropathic corneal pain, with plans to start the trial in the first half of 2026 [8][9] - REGENXBIO has faced clinical holds on its RGX-111 and RGX-121 gene therapy programs due to a case of CNS tumor in a child treated with RGX-111, although no similar findings were reported in other patients [10][11] - Almirall has received NMPA approval for Seysara in China for treating moderate-to-severe acne vulgaris, expanding its dermatology portfolio in the region [12][13] Clinical Trials - Breakthroughs - Aprea Therapeutics reported early clinical activity for APR-1051 in endometrial cancer, achieving a 50% reduction in target lesion size in a patient with PPP2R1A-mutated uterine serous carcinoma [19][21] - Fractyl Health's Revita demonstrated positive results in weight maintenance after GLP-1 drug discontinuation, showing a 4.5% weight regain compared to 7.5% in the sham group [22][24] - Ascletis Pharma announced positive Phase 3 results for Denifanstat in moderate-to-severe acne vulgaris, focusing on long-term safety in a trial with 240 patients [25][26] - GRI Bio reported new gene expression data from its Phase 2a study of GRI-0621 in idiopathic pulmonary fibrosis, showing significant improvements in lung injury and fibrosis progression [27][28] - Cardiff Oncology announced encouraging results from its Phase 2 trial of Onvansertib in RAS-mutated metastatic colorectal cancer, with a well-tolerated regimen and plans to advance to a registrational program [31][32] - Genentech's CT-388 Phase 2 trial for obesity showed a significant placebo-adjusted weight loss of 22.5% at 48 weeks, with a high percentage of participants achieving significant weight loss [34][36] - Sarepta Therapeutics reported positive three-year results from its EMBARK study for ELEVIDYS in Duchenne muscular dystrophy, showing significant slowing of disease progression in treated patients [38][41] Deals - YD Bio Limited has signed a letter of intent to acquire Safe Save Medical for approximately $26.87 million, aiming to enhance its capabilities in advanced cellular therapeutics [14][15][17]