On February 12, 2026 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases, reported its financial results for the quarter and year ended December 31, 2025.

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"The year ahead marks an important turning point for the company, as we approach two potential product launches and a pivotal data readout that, together, could significantly accelerate our commercial revenue trajectory," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "We are implementing a strategic restructuring plan to reduce our operating expenses and ensure our resources are squarely aligned with our highest-impact opportunities, while leading the future of rare disease with multiple first ever treatments."

Fourth Quarter 2025 Selected Financial Data Tables and Financial Results

Revenues (dollars in millions), (unaudited)

Three Months Ended December 31, Year Ended December 31,
2025 2024 2025 2024
Crysvita
Product sales – Latin America and Türkiye $ 40 $ 22 $ 177 $ 135
Royalty revenue – U.S. and Canada 97 87 275 249
Royalty revenue – Europe 8 7 29 26
Total Crysvita Revenue 145 116 481 410
Dojolvi 32 31 96 88
Evkeeza 17 10 59 32
Mepsevii 13 8 37 30
Total revenues $ 207 $ 165 $ 673 $ 560


Revenues
Ultragenyx reported $207 million in total revenue for the fourth quarter 2025, which represents 25% growth compared to the same period in 2024. Crysvita revenue in the fourth quarter 2025 was $145 million, which includes product sales of $40 million from Latin America and Türkiye. Dojolvi revenue in the fourth quarter 2025 was $32 million. Evkeeza revenue in the fourth quarter 2025 was $17 million.

Total revenue for the year ended December 31, 2025 was $673 million, which represents 20% growth compared to the prior year. Full year 2025 Crysvita revenue was $481 million, which represents 17% growth compared to the prior year. This includes product sales of $177 million from Latin America and Türkiye, which represents 31% growth compared to the prior year. Dojolvi revenue in 2025 was $96 million, which represents 9% growth compared to the prior year. Evkeeza revenue in 2025 was $59 million, which represents 84% growth compared to the prior year, as demand continues to build following launches in the company’s territories outside of the United States.

Selected Financial Data (dollars in millions, except per share amounts), (unaudited)

Three Months Ended December 31, Year Ended December 31,
2025 2024 2025 2024
Total revenues $ 207 $ 165 $ 673 $ 560
Operating expenses:
Cost of sales 29 17 109 77
Research and development 203 188 750 698
Selling, general and administrative 89 82 349 321
Total operating expenses 321 287 1,208 1,096
Net loss $ (129 ) $ (133 ) $ (575 ) $ (569 )
Net loss per share, basic and diluted $ (1.29 ) $ (1.39 ) $ (5.83 ) $ (6.29 )

Operating Expenses

Total operating expenses for the fourth quarter 2025 were $321 million. Total operating expenses for the year ended December 31, 2025 were $1.2 billion, including $153 million of non-cash stock-based compensation.

Net Loss

Net loss for the fourth quarter 2025 was $129 million, or $1.29 per share basic and diluted, compared with a net loss for the fourth quarter 2024 of $133 million, or $1.39 per share basic and diluted. Net loss for the year ended December 31, 2025 was $575 million, or $5.83 per share basic and diluted, compared with a net loss the prior year of $569 million, or $6.29 per share, basic and diluted.

Cash Balance and Net Cash Used in Operations

Cash, cash equivalents, and marketable securities were $737 million as of December 31, 2025. For the three months ended December 31, 2025, net cash used in operations was $100 million and for the year ended December 31, 2025 was $466 million.

Financial Guidance and Strategic Restructuring Plan

2026 revenue guidance

Total revenues, excluding potential revenue from new product launches, in the range of $730 million to $760 million, an increase of 8% to 13% compared to 2025
Crysvita revenue in the range of $500 million to $520 million, reflecting growing underlying global demand partially offset by expected timing of ordering patterns in Brazil
Dojolvi revenue in the range of $100 million to $110 million

Strategic restructuring plan and path to profitability in 2027

Ultragenyx has initiated a strategic restructuring plan designed to reduce its headcount and expenses and focus resources on its largest value drivers. The significant reduction and partial reinvestment of expenses, and the planned growth in revenue from current and new product launches, are designed to keep the company on its path to profitability in 2027.

Today, in connection with the restructuring plan, the company announced a 10% workforce reduction, impacting approximately 130 employees.

Based on the progression of the business and the reductions from the restructuring plan:

In 2026, combined R&D and SG&A expenses are expected to be flat to down low-single digits versus 2025. This includes the impact of spend reductions and approximately $50 million for severance, manufacturing, and other non-recurring restructuring charges.
In 2027, R&D expenses are expected to decrease from 2025 levels by 38%, or approximately $280 million, driven by the completion of multiple phase 3 studies and reduction of early-stage research efforts. SG&A expenses are expected to increase in support of new product launches and existing approved products. On a combined basis, 2027 R&D and SG&A expenses are expected to decrease at least 15% versus 2025.

2026 Clinical and Regulatory Catalysts

DTX401 (pariglasgene brecaparvovec) AAV8 gene therapy for glycogen storage disease type Ia (GSDIa): Biologics License Application (BLA) rolling submission completed in December 2025, with an anticipated Prescription Drug User Fee Act (PDUFA) action date in the third quarter of 2026.

UX111 (rebisufligene etisparvovec) AAV9 gene therapy for Sanfilippo syndrome type A (MPS IIIA): The BLA was resubmitted in January 2026 and included substantial longer-term data, that were recently presented at the 2026 WORLDSymposium, on multiple measures of neurologic benefit to support an intermediate clinical endpoint for accelerated approval supported further by CSF heparan sulfate and other biomarker data, as agreed with the FDA during the last clinical review.
Earlier today the company received an Incomplete Response Letter (IRL) regarding its resubmitted BLA. The IRL requests additional supportive documentation related to its CRL CMC responses, which the company will provide in a resubmission.
GTX-102 (apazunersen) antisense oligonucleotide (ASO) for the treatment of Angelman syndrome (AS): Data from the fully enrolled, pivotal, Phase 3 Aspire study in patients with a genetically confirmed diagnosis of UBE3A deletion is expected in the second half of 2026. Enrollment in the Phase 2/3 Aurora study is also underway in other genotypes and ages, with the first patient dosed in October 2025.

UX701 (rivunatpagene miziparvovec) AAV9 gene therapy for Wilson disease: Enrollment is complete for the fourth cohort in the ongoing, dose-finding stage of the pivotal Cyprus2+ study. Data from this stage are expected in 2026.

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Thursday, February 12, 2026, at 2 p.m. PT/5 p.m. ET to discuss the fourth quarter and full year 2025 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source The replay of the call will be available for three months.

(Press release, Ultragenyx Pharmaceutical, FEB 12, 2026, View Source [SID1234662646])

On February 12, 2026 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported an update letter from its President and Chief Executive Officer, Dr. Christopher J. Schaber. The content of this letter is provided below.

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Dear Friends and Shareholders,

I would like to start by thanking you for your continued support, and by wishing you and your families a Happy New Year. With 2026 being an important year for us, we remain energized by the promise of our late-stage rare disease pipeline as we continue to evaluate potential strategic options, including, but not limited to, partnership and merger and acquisition opportunities. The previously publicly disclosed upcoming key clinical events and milestones are summarized below.

Top-line results from the actively enrolling 80 patient confirmatory Phase 3 FLASH2 (Fluorescent Light And Synthetic Hypericin 2) clinical trial for HyBryte (SGX301 or synthetic hypericin) in the treatment of early-stage cutaneous T-cell lymphoma (CTCL) are expected in the second half of 2026, with an interim analysis fast approaching in 2Q. Patient enrollment continues to progress nicely with 66 patients enrolled in the study as of February 10th. Importantly, the overall blinded aggregate response rate remains consistent with what was reported in November and higher than the estimated overall response rate used to design the study, increasing our confidence in the interim analysis and final study results. Just to remind you, this second Phase 3 trial (FLASH2) essentially replicates the first successful Phase 3 (FLASH) study, with the exception of shifting the primary endpoint assessment from 6 weeks in FLASH to 18 weeks in FLASH2, in keeping with findings in both the FLASH study and other recent supportive studies that have all shown that the longer we treat with HyBryte, the better it works.

A clinical update was provided for the ongoing open-label, investigator-initiated study (IIS) sponsored by Ellen Kim, MD, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, and Professor of Dermatology at the Hospital of the University of Pennsylvania who was a leading enroller in the Phase 3 FLASH study and is the Principal Investigator for the confirmatory Phase 3 FLASH2 study for the treatment of early-stage CTCL. The IIS evaluated extended HyBryte (synthetic hypericin) treatment for up to 54 weeks in patients with early-stage CTCL, with a similar design to that of the active HyBryte arm in FLASH2. Following 18 weeks of continuous "real world" treatment, 75% of patients achieved "Treatment Success," with three of the eight evaluable patients achieving a complete response over the course of the study. These results reinforce HyBryte’s potential as a safe and fast-acting therapy for this chronic and underserved cancer and may explain, in part, the higher aggregate blinded response rate seen in FLASH2.

We continue to work with our lead investigators in CTCL, including pursuing publications to enhance both medical and scientific awareness of HyBryte. We anticipate additional publications around HyBryte in the first half of the year.

Top-line results from the Phase 2a proof of concept clinical trial in Behçet’s Disease (BD) with SGX945 (dusquetide) were reported in July and achieved the study objective of demonstrating biological efficacy. The Phase 2a study was an open-label study designed to be highly comparable (e.g., study endpoints, inclusion-exclusion criteria) to the published Phase 3 study of apremilast (Otezla) used to support marketing approval for oral ulcers in BD. SGX945 outcomes were compared to both the apremilast and placebo arms in this Phase 3 study. Over 4 weeks of treatment, the area under the curve (AUC; a composite measurement of both peak number of oral ulcers and the time to resolution of the oral ulcers), average number of oral ulcers, and improvements in oral pain for SGX945 were similar to outcomes obtained in the apremilast study. Notably, outcomes in weeks 5 through 8 continued to show similar outcomes to the apremilast study, even though apremilast treatment was continued through this period whereas SGX945 treatment was stopped at Week 4, per study design. These results were published in Rheumatology (Oxford) in December. With these results, we intend to embark on a reformulation of SGX945 to enable home-based treatment and look forward to interacting with the health authorities in designing a follow-on placebo-controlled Phase 2b study in 2026.

Top-line results were reported in December for the last cohort of four patients in the Phase 2a clinical trial in mild-to-moderate psoriasis with SGX302 (synthetic hypericin), where SGX302 gel therapy was well tolerated by all patients with no drug related adverse events identified. On average over the three evaluable patients (one patient discontinued for personal reasons), there were improvements in the Investigator Global Assessment (IGA), the Psoriasis Activity and Severity Index (PASI), the simplified psoriasis index, the dermatology life quality index and the Skindex-29 questionnaire. One patient achieved a disease status of "Almost Clear" using the IGA, which is considered a standard clinical measure for treatment success in psoriasis, with a substantial improvement in their PASI score, exceeding 50%. In totality, the initial exploratory phase of the study has confirmed that SGX302 improves psoriasis lesions, consistent with the general success of photodynamic therapies in psoriasis, and is well tolerated, potentially providing a non-carcinogenic, non-mutagenic treatment for the thicker lesions found in psoriasis. With the completion of this pilot study, the table has been set for a more detailed evaluation in this large underserved market.
Additionally, we continue to follow through on our financing strategies, and have sufficient capital and cash runway to meet our goals through 2026. We expect peak annual net sales of HyBryte in the U.S. to exceed $90 million, with the total addressable worldwide CTCL market estimated at greater than $250 million annually. Preliminary analysis of the total addressable worldwide psoriasis market opportunity with SGX302, which uses the same active ingredient as HyBryte, is significant and estimated to exceed $1 billion annually. SGX945 in BD is another meaningful worldwide market opportunity estimated at approximately $200 million annually. Overall, we are excited about our near-term and future upcoming catalytic milestones across our rare disease pipeline, with the potential for significant commercial returns of ~$2B in global annual sales.

With approximately $10.5 million in cash reported in our Form 10-Q for the quarter ended September 30, 2025, not including approximately $500 thousand in non-dilutive funding received through New Jersey’s net operating loss (NOL) sales program, we remain focused on advancing our development programs in our Specialized BioTherapeutics rare disease business segment, most notably, completion of our confirmatory Phase 3 HyBryte clinical trial, where we currently anticipate achieving multiple important and potentially transformational milestones through 2026. We also continue to evaluate strategic options before us to better position the company for growth and success.

We remain steadfast in our plans for partnership in the ex-U.S. markets and continue to pursue discussions with potential partners with similar reputation and expertise in this therapeutic area, as we advance towards successful completion of the FLASH2 confirmatory trial in order to aggressively pursue HyBryte marketing authorizations worldwide. Given HyBryte’s clinical success in CTCL, we also are evaluating other potential cutaneous indications that might similarly benefit from the use of our first-in-class synthetic hypericin.

In closing, thank you again for your interest and your ongoing support of Soligenix. Looking ahead, 2026 has the potential to be an exciting time for the Company, as we further advance our development programs towards commercialization.

(Press release, Soligenix, FEB 12, 2026, View Source [SID1234662645])

On February 12, 2026 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage rare disease company focused on treating hypoglycemia caused by all forms of hyperinsulinism (HI), reported financial results and provided a business update for the three months ended December 31, 2025.

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Congenital Hyperinsulinism (HI)

· In December 2025, Rezolute reported topline results from sunRIZE, a Phase 3, multicenter, double-blind, randomized, placebo-controlled safety and efficacy study of ersodetug for the treatment of congenital HI. The study did not meet its primary or key secondary endpoints.

· The study demonstrated reductions from baseline in hypoglycemia events by self-monitored blood glucose at both ersodetug dose levels, but reductions were not statistically significant compared to placebo, due to a pronounced study effect.

· A reduction in hypoglycemia time by continuous glucose monitoring (CGM) was also demonstrated with both dose levels of ersodetug, which was statistically significant compared to placebo at the Week 16 timepoint, but did not meet significance at the Week 24 end of pivotal timepoint.

· In sunRIZE, pharmacologic activity was observed, with target therapeutic drug concentrations achieved in both treatment groups, along with highly sensitive biomarker responses of decreased insulin cell signaling in the active treatment groups, indicating drug activity.

· Notably, all 59 participants who completed the study continued into the ongoing open-label extension portion, including the roll-over of placebo participants onto ersodetug, and the vast majority remain on therapy. Some of the children have been able to stop taking their standard congenital HI therapies and are now receiving ersodetug as monotherapy.

· Subsequent to the announcement of the topline results of the primary and key secondary endpoints, the Company is undertaking extensive analysis of the results and other endpoints, in preparation for its upcoming FDA meeting.

· The Company will be meeting with FDA prior to the end of the first quarter under Breakthrough Therapy Designation to determine next steps for the program.

Tumor HI

· upLIFT, a Phase 3, single-arm, open label study in up to 16 hospitalized participants for the treatment of tumor HI, is ongoing.

§ Enrollment is underway and topline results are expected in the second half of 2026.

· In January 2026, the Company shared aggregate data from the initial 9 tumor HI patients treated under the historical Expanded Access Program (EAP).

§ The data show that 75% of the patients receiving IV dextrose/total parenteral nutrition (TPN) in the EAP achieved a complete discontinuation of IV dextrose/TPN, providing additional evidence of the activity and potential efficacy of ersodetug across various forms of HI.

§ This cohort was the basis for FDA to grant Breakthrough Designation and agree to a single-arm, open-label registrational study design.

§ The glucose infusion rate (GIR) assessment in the EAP is the primary endpoint in upLIFT, which measures the number of participants (out of approximately 16) who achieve at least a 50% reduction in GIR.

§ The full EAP data table, filed on Form 8-K with the U.S. Securities and Exchange Commission, can be found here.

Corporate Updates

· In November 2025, the Company hosted a virtual Investor Event during which Rezolute Chief Commercial Officer, Sunil Karnawat, discussed the anticipated commercial opportunities for ersodetug as a potential treatment for congenital and tumor HI. The event also featured presentations from two leading physician experts who provided perspectives on disease background and the significant unmet clinical need in HI.

§ A replay of the virtual event is available on the Investor Relations section of the Company’s website here.

Second Quarter Fiscal 2026 Financial Results

Cash, cash equivalents and investments in marketable securities were $132.9 million as of December 31, 2025, compared with $167.9 million as of June 30, 2025.

Research and development (R&D) expenses were $14.3 million for the second quarter of fiscal 2026, compared with $12.6 million for the same period a year ago. The increase from fiscal year 2025 to fiscal year 2026 was primarily due to (i) increased expenditures in clinical trial activities and (ii) higher employee-related expenses, which included one-time severance benefits related to the December 2025 reduction in force, partially offset by a decrease in manufacturing costs for ersodetug.

General and administrative (G&A) expenses were $9.9 million for the second quarter of fiscal 2026, compared with $4.5 million for the same period a year ago. The increase was primarily attributable to increased professional fees and employee-related expenses, which included one-time severance benefits related to the December 2025 reduction in force.

Net loss was $22.8 million for the second quarter of fiscal 2026 compared with a net loss of $15.7 million for the same period a year ago.

About Ersodetug

Ersodetug is a fully human monoclonal antibody that binds allosterically to the insulin receptor to decrease receptor over-activation by insulin and related substances (such as IGF-2) in the setting of hyperinsulinism (HI), thereby improving hypoglycemia. Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any congenital or acquired form of HI.

(Press release, Rezolute, FEB 12, 2026, View Source [SID1234662644])

On February 12, 2026 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that data across multiple genitourinary cancers from several approved and investigational medicines will be presented at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO GU) Cancers Symposium from Feb. 26-28. These data, including three studies that will be featured in the symposium’s press program, underscore Merck’s commitment to advancing research across its broad portfolio to improve patient outcomes.

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"We’re excited to share new results from our portfolio and pipeline for more patients with certain types of bladder and kidney cancers, with new data in muscle invasive bladder cancer and earlier stages of renal cell carcinoma," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "The results we’re presenting at ASCO (Free ASCO Whitepaper) GU underscore our leadership across the genitourinary cancer landscape and our commitment to advance standards of care for these patients."

Data presentations will feature new findings from Merck’s broad portfolio of cancer medicines, including key data for KEYTRUDA (pembrolizumab), WELIREG (belzutifan) and LENVIMA (lenvatinib), in collaboration with Eisai, as well as new results for the investigational antibody-drug conjugate (ADC) from Merck’s innovative pipeline: sacituzumab tirumotecan (sac-TMT), a TROP2-directed ADC being developed in collaboration with Kelun-Biotech.

Key data from Merck’s portfolio and pipeline to be presented at the 2026 ASCO (Free ASCO Whitepaper) GU Cancers Symposium:

First-time data from the Phase 3 KEYNOTE-B15/EV-304 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, plus Padcev (enfortumab vedotin-ejfv) as neoadjuvant and adjuvant treatment (before and after surgery) for patients with muscle-invasive bladder cancer who are eligible for cisplatin (abstract #LBA630, Oral abstract session B: Urothelial carcinoma), which will be featured in the official ASCO (Free ASCO Whitepaper) GU Press Program.1
Results from the first interim analysis of the Phase 3 LITESPARK-022 trial evaluating KEYTRUDA in combination with WELIREG, Merck’s first-in-class oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, as a treatment for patients with clear cell renal cell carcinoma (RCC) following nephrectomy (abstract #LBA418, Oral abstract session C: Renal cell cancer and testicular cancer), which will be featured in the official ASCO (Free ASCO Whitepaper) GU Press Program.
First presentation of data from the Phase 3 LITESPARK-011 trial evaluating WELIREG plus LENVIMA, an orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, as a treatment for patients with advanced RCC whose disease progressed on or after treatment with anti-PD-1/L1 therapy (abstract #LBA417, Oral abstract session C: Renal cell cancer and testicular cancer), which will be featured in the official ASCO (Free ASCO Whitepaper) GU Press Program.2
First-time data presentation for the Phase 2 MK-2870-002 study evaluating sac-TMT plus KEYTRUDA for patients with advanced urothelial carcinoma (abstract #744, Poster session B: Prostate cancer and urothelial carcinoma).3
Details on abstracts listed above and additional key abstracts for Merck

Bladder cancer

Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, Phase 3 KEYNOTE-B15 study. M. D. Galsky.1

Abstract #LBA630, Oral abstract session B: Urothelial carcinoma

Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (pembro) in participants (Pts) with advanced urothelial carcinoma (UC): Results from the Phase 2 2870-002/SKB264-II-06 study. X. Bian.3

Abstract #744, Poster session B: Prostate cancer and urothelial carcinoma

Pathological outcomes and disease-free survival (DFS) in KEYNOTE-905: Neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible. To be determined.1

Abstract #638, Rapid oral abstract session B: Urothelial carcinoma

KEYMAKER-U04 substudy 04B: First-line (1L) enfortumab vedotin (EV) plus pembrolizumab (pembro)-based immune checkpoint inhibitor (ICI) combinations for advanced urothelial cancer (UC). A. Peer.1

Abstract #634, Rapid oral abstract session B: Urothelial carcinoma

SWOG 2427: Single arm Phase II study of bladder preservation with immunoradiotherapy after a clinically meaningful response to neoadjuvant therapy in patients with muscle invasive bladder cancer (BRIGHT). L. K. Ballas.4

Abstract #TPS913, Trials in progress poster session B: Urothelial carcinoma

Kidney cancer

Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): The randomized Phase 3 LITESPARK-022 study. T. K. Choueiri.

Abstract #LBA418, Oral abstract session C: Renal cell cancer and testicular cancer

Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti-PD-(L)1 therapy: Open-label Phase 3 LITESPARK-011 study. R. J. Motzer.2

Abstract #LBA417, Oral abstract session C: Renal cell cancer and testicular cancer

Ascending dose escalation of belzutifan plus palbociclib for previously treated advanced clear cell renal cell carcinoma (ccRCC): Phase 1/2 LITESPARK-024 study Part 1. D. F. McDermott.5

Abstract #423, Rapid oral abstract session C: Renal cell cancer and testicular cancer

KEYMAKER-U03 substudy 03B: Novel investigative regimens for previously treated advanced clear cell renal cell carcinoma (ccRCC). L. Albiges.

Abstract #505, Poster session C: Renal cell cancer; adrenal, penile, testicular and urethral cancers

Phase 2 trial of belzutifan in participants from China and Japan with von Hippel-Lindau disease-associated tumors: Results from LITESPARK-015 cohort B1. G. Naik.

Abstract #494, Poster session C: Renal cell cancer; adrenal, penile, testicular and urethral cancers

Prostate cancer

Efficacy and safety of the DLL3 T-cell engager gocatamig in participants (pts) with neuroendocrine prostate cancer (NEPC) and other neuroendocrine neoplasms (NEN). H. Beltran.6

Abstract #182, Poster session A: Prostate cancer

(Press release, Merck & Co, FEB 12, 2026, View Source [SID1234662643])

On February 12, 2026 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation chimeric antigen receptor (CAR) T-cell therapies for patients with cancer, reported that the first patient has been dosed in the PiNACLE – H2H Phase 3 trial evaluating rondecabtagene autoleucel (ronde-cel, also known as LYL314) compared to lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) receiving treatment in the second-line (2L) setting.

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"Ronde-cel is a dual-targeting CD19/CD20 CAR T-cell product candidate that has demonstrated impressive clinical data in patients with aggressive large B-cell lymphoma," said Krish Patel, MD, Director of Lymphoma Research at Sarah Cannon Research Institute (SCRI). "One of our SCRI CAR T-cell sites is the first to enroll in this important trial designed to provide physicians the data we need to make the best treatment decisions for our patients. Furthermore, this trial represents a milestone in the field of cellular therapy, being the first trial to randomize patients between different CAR T-cell therapies."

"Data from Lyell’s single-arm pivotal PiNACLE trial in patients with later-stage large B-cell lymphoma are expected to be submitted for marketing approval to the FDA next year," said David Shook, MD, Lyell’s Chief Medical Officer. "We are now pleased to have underway PiNACLE – H2H, the first-of-its-kind Phase 3 head-to-head randomized controlled CAR T-cell trial. This strategy demonstrates Lyell’s confidence in ronde-cel’s potential to be the best-in-class CAR T-cell treatment for patients with relapsed or refractory disease."

PiNACLE – H2H is a Phase 3 head-to-head CAR T-cell randomized controlled clinical trial of ronde-cel versus Investigator’s choice of either liso-cel or axi-cel in patients with R/R LBCL receiving treatment in the 2L setting. Patients randomized to ronde-cel will be treated with a dose of 100 x 106 CAR T cells; patients in the control arm will be treated as per the product label. The primary endpoint of this superiority trial is event-free survival and the trial plans to enroll approximately 200 patients per arm (N = 400) with R/R LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, Grade 3B follicular lymphoma, or transformed follicular or transformed mantle cell lymphoma who have not previously received CAR T-cell therapy. Patients may be treated with ronde-cel in either the inpatient or outpatient setting.

More information about the PiNACLE – H2H trial can be found on clinicaltrials.gov (NCT07188558) here.

Ronde-cel is also being studied in PiNACLE, a pivotal single-arm trial in the third- or later-line (3L+) setting. This registration trial is a seamless expansion of the 3L+ cohort from the multi-cohort multi-center Phase 1/2 trial and will enroll approximately 120 patients at approximately 25 sites. The dose is 100 x 106 CAR T cells and the primary endpoint is overall response rate. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535) here.

At the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2025, Lyell reported positive updated clinical data in patients with aggressive LBCL in the 3L+ and 2L settings from the Phase 1/2 trial. The oral presentation included updated data from the 3L+ cohort (now the ongoing PiNACLE pivotal trial), including a best overall response rate of 93% and a complete response rate of 76% in 29 efficacy-evaluable patients with R/R LBCL. The median progression-free survival was 18 months as of the data cutoff date of September 5, 2025. Updated data were also presented from the 2L cohort, including 18 efficacy evaluable patients (94% with high-risk primary refractory disease), and demonstrated an 83% best overall response rate and a 61% complete response rate. The safety profile was appropriate for outpatient administration of ronde-cel. Data from 25 patients treated with ronde-cel and receiving dexamethasone prophylaxis revealed no reports of Grade 3 or higher cytokine release syndrome (CRS) and one case (4%) of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS).

About Rondecabtagene Autoleucel (Ronde-cel)

Rondecabtagene autoleucel (ronde-cel, also known as LYL314) is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the approved CD19-targeted CAR T-cell therapies for the treatment of R/R LBCL.

Ronde-cel is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both, each with full potency. Ronde-cel is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity.

Ronde-cel has received Regenerative Medicine Advanced Therapy (RMAT) designation as well as Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of adults with R/R diffuse LBCL (DLBCL) in the 3L+ setting and has also received RMAT designation for the treatment of LBCL in the 2L setting. The FDA has also granted ronde-cel Orphan Drug Designation for the treatment of DLBCL/high grade B-cell lymphoma with MYC and BCL2 rearrangements.

(Press release, Lyell Immunopharma, FEB 12, 2026, View Source [SID1234662642])