On July 29, 2025 Incyte (Nasdaq:INCY) reported 2025 second quarter financial results, and provides a status update on the Company’s clinical development portfolio (Press release, Incyte, JUL 29, 2025, View Source [SID1234654599]).

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"As I begin my tenure as CEO, I look forward to leading Incyte through its next phase of growth and value creation for patients, partners and shareholders. Our second quarter results reflect strong growth for Jakafi (ruxolitinib), Opzelura (ruxolitinib) cream and Niktimvo (axatilimab), positioning us well to deliver on our 2025 objectives," said Bill Meury, Chief Executive Officer, Incyte. "During the quarter, we achieved two regulatory milestones with the approvals of Zynyz (retifanlimab-dlwr) for squamous cell anal carcinoma and Monjuvi (tafasitamab-cxix) for follicular lymphoma, further expanding our ability to address patients’ needs. Continued progress and diversification of our portfolio, including advancements with povorcitinib and mutCALR, are strengthening the foundation for sustainable, long-term growth."

Key Commercial Highlights
Jakafi:
Net product revenues for the second quarter 2025 of $764 million (+8% Y/Y):
▪Net product revenue growth in the second quarter of 2025 versus the same quarter in the prior year, was driven by an increase in paid demand of 8% reflecting continued demand growth in all indications. Jakafi inventory levels were within normal range at the end of the second quarter of 2025.

Opzelura:
Net product revenues for the second quarter 2025 of $164 million (+35% Y/Y):
▪U.S. net product revenue of $132 million in the second quarter of 2025 increased 19% compared to the second quarter of 2024 driven by increased patient demand and refills in both atopic dermatitis (AD) and vitiligo. Opzelura inventory levels were within normal range at the end of the second quarter of 2025.
▪Ex-U.S. net product revenues of $32 million in the second quarter of 2025 were primarily driven by continued growth in sales in France, and the recent launches in Italy and Spain.
Pipeline Updates
Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) – key highlights
▪In June 2025, data from the Phase 1 study evaluating INCA033989 in mutCALR positive patients with essential thrombocythemia (ET) were presented during a late-breaking session at the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Milan, Italy. The data showed rapid and durable normalization of platelet counts across all dose levels and importantly, a reduction in peripheral blood mutCALR variant allele frequency (VAF) correlating with hematologic response. INCA033989 was well tolerated with a favorable safety profile with no dose limiting toxicities reported. Together, the data demonstrates the potential of INCA033989 for disease modification by directly inhibiting and eliminating oncogenic mutCALR cells, while sparing healthy cells and restoring normal blood cell production. The Phase 1 data in patients with myelofibrosis (MF) as monotherapy and in combination with ruxolitinib are anticipated in the second half of 2025.
▪A Phase 1 study evaluating JAK2V617Fi in MPNs is ongoing. Initial proof of concept data are anticipated in the first half of 2026.
▪A Phase 2 trial evaluating axatilimab (Niktimvo) in combination with ruxolitinib (Jakafi) in patients with newly diagnosed chronic GVHD is ongoing.
▪A Phase 3 trial evaluating axatilimab in combination with corticosteroids in patients with newly diagnosed chronic GVHD is ongoing.
MPN and GVHD Programs Indication and status
Ruxolitinib XR (QD)
(JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD
Ruxolitinib + INCB57643
(JAK1/JAK2 + BETi) Myelofibrosis: Phase 2
Ruxolitinib + axatilimab1
(JAK1/JAK2 + anti-CSF-1R)
Chronic GVHD: Phase 2
Steroids + axatilimab1
(Steroids + anti-CSF-1R)
Chronic GVHD: Phase 3
INCA033989
(mutCALR) Myelofibrosis, essential thrombocythemia: Phase 1
INCB160058
(JAK2V617Fi) Myeloproliferative Neoplasms (MPNs): Phase 1

Other Hematology/Oncology – key highlights
▪In May 2025, Zynyz was approved by the U.S. Food and Drug Administration (FDA) in combination with chemotherapy and as a single agent for the treatment of adult patients with advanced squamous cell carcinoma of the anal canal (SCAC). The Priority Review and FDA approval were based on data from two trials: the Phase 3 POD1UM-303/InterAACT2 and the Phase 2 POD1UM-202 trial. Incyte has also submitted a Type II variation Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) and a Japanese New Drug Application (J-NDA) for retifanlimab in advanced SCAC.
▪In June 2025, Monjuvi was approved by the FDA for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) in combination with rituximab and lenalidomide. The Priority Review and FDA approval were based on data from the pivotal Phase 3 inMIND trial.
▪Incyte plans to initiate Phase 3 studies for its potentially first-in-class CDK2 inhibitor (INCB123667), in ovarian cancer in 2025 and is also evaluating INCB123667 in combination with other treatments.
▪The Phase 3 study evaluating tafasitamab as first-line treatment for diffuse large B-cell lymphoma (DLBCL) is ongoing. The Phase 3 data are anticipated in the second half of 2025.
▪The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 in solid tumors are ongoing. Initial proof of concept data for both studies are anticipated in the second half of 2025.
Heme/Oncology Programs Indication and status
Tafasitamab (Monjuvi/Minjuvi)
(CD19)
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Phase 3 (B-MIND)
First-line DLBCL: Phase 3 (frontMIND)
Retifanlimab (Zynyz)1
(PD-1)
Non-small cell lung cancer (NSCLC): Phase 3 (POD1UM-304)
MSI-high endometrial cancer: Phase 2 (POD1UM-101, POD1UM-204)
INCB123667
(CDK2i) Solid tumors with CCNE1 amplification/Cyclin E overexpression: Phase 1
INCB161734
(KRASG12D) Advanced metastatic solid tumors with a KRASG12D mutation: Phase 1
INCA33890
(TGFßR2×PD-1)2
Advanced or metastatic solid tumors: Phase 1

1 Retifanlimab licensed from MacroGenics.
2 Development in collaboration with Merus.
Inflammation and Autoimmunity (IAI) – key highlights
Ruxolitinib Cream
▪In April 2025, Incyte announced positive topline results from the Phase 3 (TRuE-AD4) study evaluating ruxolitinib cream in adult patients with moderate atopic dermatitis. The study met the co-primary endpoints at Week 8, with a statistically significant proportion of patients achieving both Investigator’s Global Assessment Treatment Success (IGA-TS) and EASI75, which is defined as a 75% or greater improvement in the Eczema Area Severity Index score from baseline. In addition, the study met all key secondary endpoints. Ruxolitinib cream was well tolerated with no new safety signals. The full dataset will be presented at an upcoming medical conference.
▪In June 2025, two Phase 3 studies (TRuE-HS2 and TRuE-HS2) evaluating ruxolitinib cream in mild to moderate hidradenitis suppurativa (HS) were initiated and are ongoing.
▪In June 2025, the FDA extended the review period for the supplemental New Drug Application (sNDA) for ruxolitinib cream (Opzelura) for the treatment of children 2-11 years old with mild to moderate atopic dermatitis (AD). The Prescription Drug User Fee Act (PDUFA) action date was extended by three months to September 19, 2025.

Povorcitinib (INCB54707)
▪Two Phase 3 studies (STOP-V1 and STOP-V2) evaluating povorcitinib versus placebo in patients with vitiligo are ongoing. The Phase 3 data are anticipated in 2026.
▪Two Phase 3 studies (STOP-PN1 and STOP-PN2) evaluating povorcitinib versus placebo in patients with PN are ongoing. The Phase 3 data are anticipated in 2026.
▪A Phase 2 trial evaluating povorcitinib in asthma is ongoing. Data are anticipated in the second half of 2025.
IAI and Dermatology Programs Indication and status
Ruxolitinib cream (Opzelura)1
(JAK1/JAK2)
Atopic dermatitis: Phase 3 pediatric study (TRuE-AD3); sNDA under review in the U.S.
Hidradenitis suppurativa: Phase 3 (TRuE-HS1, TRuE-HS2)
Prurigo nodularis: Phase 3 (TRuE-PN1, TRuE-PN2)
Povorcitinib
(JAK1) Hidradenitis suppurativa: Phase 3 (STOP-HS1, STOP-HS2)
Vitiligo: Phase 3 (STOP-V1, STOP-V2)
Prurigo nodularis: Phase 3 (STOP-PN1, STOP-PN2)
Chronic spontaneous urticaria: Phase 2
Asthma: Phase 2
INCA034460
(anti-CD122) Vitiligo: Phase 1

1 Novartis’ rights to ruxolitinib outside of the United States under our Collaboration and License Agreement with Novartis do not include topical administration.
Other
Other Program Indication and Phase
Zilurgisertib
(ALK2) Fibrodysplasia ossificans progressiva: Pivotal Phase 2

2025 Second Quarter Financial Results
The financial measures presented in this press release for the three and six months ended June 30, 2025 and 2024 have been prepared by the Company in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"), unless otherwise identified as a Non-GAAP financial measure. Management believes that Non-GAAP information is useful for investors, when considered in conjunction with Incyte’s GAAP disclosures. Management uses such information internally and externally for establishing budgets, operating goals and financial planning purposes. These metrics are also used to manage the Company’s business and monitor performance. The Company adjusts, where appropriate, for expenses in order to reflect the Company’s core operations. The Company believes these adjustments are useful to investors by providing an enhanced understanding of the financial performance of the Company’s core operations. The metrics have been adopted to align the Company with disclosures provided by industry peers.
Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used in conjunction with and to supplement Incyte’s operating results as reported under GAAP. Non-GAAP measures may be defined and calculated differently by other companies in our industry.

Revenue Details
Revenue Details
(unaudited, in thousands)
Three Months Ended
June 30, %
Change
(as reported)
%
Change
(constant currency)1
Six Months Ended
June 30, %
Change
(as reported)
%
Change
(constant currency)1
2025 2024 2025 2024
Net product revenues:
Jakafi $ 763,788 $ 705,973 8 % NA $ 1,473,200 $ 1,277,812 15 % NA
Opzelura 164,499 121,695 35 % 34 % 283,204 207,419 37 % 36 %
Iclusig 32,729 26,862 22 % 16 % 62,273 57,205 9 % 8 %
Pemazyre 22,192 20,269 9 % 8 % 40,632 37,945 7 % 7 %
Minjuvi/ Monjuvi 31,131 31,116 0 % (1 %) 60,682 54,990 10 % 10 %
Niktimvo 36,154 — NM NA 49,767 — NM NA
Zynyz 8,921 651 1,270 % NA 11,930 1,118 967 % NA
Total net product revenues 1,059,414 906,566 17 % 16 % 1,981,688 1,636,489 21 % 21 %
Royalty revenues:
Jakavi 109,714 99,317 10 % 7 % 201,859 188,912 7 % 8 %
Olumiant 33,482 31,702 6 % 4 % 64,282 62,291 3 % 5 %
Tabrecta 6,632 5,298 25 % NA 13,045 10,532 24 % NA
Other 1,287 876 47 % NM 2,553 1,424 79 % NM
Total royalty revenues 151,115 137,193 10 % 281,739 263,159 7 %
Total net product and royalty revenues 1,210,529 1,043,759 16 % 2,263,427 1,899,648 19 %
Milestone and contract revenues 5,000 — NM NM 5,000 25,000 (80 %) (80 %)
Total GAAP revenues $ 1,215,529 $ 1,043,759 16 % $ 2,268,427 $ 1,924,648 18 %

NM = not meaningful
NA = not applicable
1 Percentage change in constant currency is calculated using 2024 foreign exchange rates to recalculate 2025 results.
Product and Royalty Revenues Total net product revenues for the quarter ended June 30, 2025 increased 17% over the prior year comparative period. Total net product and royalty revenues for the quarter ended June 30, 2025 increased 16% over the prior year comparative period, primarily driven by the following:
•Jakafi net product revenue increased 8% versus the prior year comparable period, driven by an increase in paid demand of 8% reflecting continued demand growth in all indications. Jakafi inventory levels were within normal range at the end of the second quarter of 2025.
•Opzelura net product revenue increased 35% due to increased patient demand and refills in the U.S. in both AD and vitiligo, and increased contribution from ex-U.S. driven by continued uptake in France, and growth from the recent launches in Italy and Spain. Opzelura inventory levels were within normal range at the end of the second quarter of 2025.
•Niktimvo net product revenue reflects continued strong uptake of the product following its commercial launch during the first quarter of 2025.
•Zynyz net product revenue increase driven by the approval of the product in squamous cell anal carcinoma in the second quarter of 2025.

•Total royalty revenues for the quarter increased 10% versus the prior year comparable period, primarily driven by growth in Jakavi royalty revenue.
Operating Expenses
Operating Expense Summary
(unaudited, in thousands)
Three Months Ended
June 30, %
Change Six Months Ended
June 30, %
Change
2025 2024 2025 2024
GAAP cost of product revenues $ 78,766 $ 76,634 3 % $ 151,954 $ 137,590 10 %
Non-GAAP cost of product revenues1
72,544 70,899 2 % 139,489 125,858 11 %
Contract dispute settlement (242,251) — NM (242,251) — NM
Non-GAAP contract dispute settlement2
— — NM — — NM
GAAP research and development 494,917 1,138,380 (57 %) 932,196 1,567,640 (41 %)
Non-GAAP research and development3
455,635 1,089,089 (58 %) 855,655 1,477,526 (42 %)
GAAP selling, general and administrative 331,022 305,982 8 % 656,713 606,238 8 %
Non-GAAP selling, general and administrative4
304,771 262,572 16 % 607,063 539,907 12 %
GAAP loss (gain) on change in fair value of acquisition-related contingent consideration 22,761 893 NM 34,333 437 NM
Non-GAAP loss (gain) on change in fair value of acquisition-related contingent consideration — — NM — — NM
GAAP (profit) and loss sharing under collaboration agreements — — NM — (1,025) NM

On July 29, 2025 ImmunoPrecise Antibodies Ltd. ("IPA", "Company", "we" or "us") (NASDAQ: IPA), a bio-native AI company operating at the intersection of TechBio and next-generation drug discovery, reported its financial results for the fiscal year ended April 30, 2025. All numbers are expressed in Canadian dollars unless otherwise noted (Press release, ImmunoPrecise Antibodies, JUL 29, 2025, View Source [SID1234654598]).

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Financial Highlights:

•
Achieved record revenue for Fiscal Year 2025 of $24.5 million
•
Delivered highest-ever fourth quarter revenue of $7.0 million
•
Reported record fourth quarter Adjusted EBITDA of ($0.3) million, reflecting improved operating efficiency
•
Achieved fourth quarter gross margin of 64%, representing strongest margin performance since Q3 of Fiscal Year 2021
•
BioStrand segment grew over 180% in Fiscal year 2025 and had gross margins approaching 90%
•
BioStrand currently represents over 5% of total annual revenue this year, up from less than 2% in Fiscal Year 2024
Recent Corporate Highlights:

•
The Company’s LENSai platform demonstrated that its in silico epitope mapping achieves results on previously unseen antibody–antigen complexes with results that are on par with gold-standard X-ray crystallography—delivering structural insights in hours instead of weeks.
•
An important breakthrough using the Company’s HYFT-powered LENSai platform, as it identified a highly conserved epitope across all four dengue virus serotypes, a key milestone toward developing a potential universal dengue vaccine. Subsequently announced in silico data supporting the vaccine candidate’s safety and its ability to activate a balanced immune response.
•
IPA’s AI-designed GLP-1 peptides outperformed or matched semaglutide in independent receptor activation studies, further validating the Company’s HYFT-driven LENSai platform.
•
Entered into a strategic USD $8M – 10M partnership with a biotechnology company focusing on advancing the discovery and development of Antibody-Drug Conjugates and bispecific antibodies for the cancer treatment.
•
Realigned internal R&D strategy to focus on launching an AI-powered therapeutic pipeline, reinforcing IPA’s shift toward a bio-native AI drug discovery model.
•
ImmunoPrecise subsidiary signed material transfer agreement with Biotheus (now BioNTech), who is evaluating the antibody asset for bispecific tumor-targeting.

•
Successfully engineered antibodies in silico to a challenging tumor target using LENS, advancing IPA’s vision for accessible, next-gen therapeutics.
•
Appointed industry veteran Jon Lieber to its Board of Directors, bringing over 30 years of strategic leadership across biotech, capital markets, and public company governance, further strengthening IPA’s financial oversight and commercial execution.
•
Named Jeff Fried, a recognized healthcare data visionary, to its Advisory Board. Fried has played a key role in advancing IPA’s AI platform capabilities, particularly the integration of vector search to support large-scale, AI-driven discovery within LENSai ecosystem.
•
Regained compliance with Nasdaq minimum bid price requirement, reflecting strengthened investor confidence and continued alignment with strategic listing standards.
"Fiscal 2025 was a record-setting year for IPA across multiple dimensions," said Dr. Jennifer Bath, ImmunoPrecise Antibodies CEO. "We delivered our highest-ever annual and fourth quarter revenues, significantly improved gross margins, and achieved one of our strongest adjusted EBITDA performances in recent years, with a loss of only $316,000. This reflects our continued progress toward profitability while accelerating innovation through our HYFT-powered LENSai platform. Our BioStrand segment alone grew by more than 180% in Fiscal 2025, highlighting the strength of our AI-driven pipeline. These results underscore the growing commercial validation of our technology, our strategic collaborations, and our ability to deliver real-world impact through next-generation antibody discovery and therapeutic design."

"As we look ahead to the next fiscal year, we are well-positioned to build on our momentum. We are poised to refocus our business on our AI-based product development utilizing our LENSai platform, powered by our HYFT technology. We anticipate the near-term completion of the previously announced divestiture of our Dutch subsidiary, as part of our continued focus on streamlining operations and aligning resources with strategic priorities. Together, these strategic steps will sharpen our focus, strengthen our core capabilities, and set the stage for an even brighter future for IPA," concluded Dr. Bath.

Fourth Quarter 2025 Financial Results

Revenue for the three months ended April 30, 2025, was $7.0 million, representing an 8% increase compared to $6.5 million for the same period in 2024. This growth was primarily driven by a $0.6 million increase in project revenues.

Gross profit for the three months ended April 30, 2025, was $4.5 million, up from $3.1 million in the same period last year. Gross margin rose sharply to 64%, compared to 48% in the same period in 2024. This improvement was driven, in part, by a greater contribution from high-margin BioStrand revenues.

Research and development ("R&D") expenses totaled $1.1 million, down from $1.3 million in the prior-year quarter, due to reallocating project-related R&D efforts to cost of sales.

Sales and marketing expenses increased to $1.0 million, compared to $0.9 million in the same period last year, due to an increase in digital campaign expenses.

General and administrative expenses declined to $3.7 million from $4.1 million, driven by ongoing cost control efforts.

Operating loss, excluding amortization and non-recurring charges, improved significantly to $1.4 million, compared to $3.2 million in the fourth quarter of Fiscal Year 2024.

Net loss narrowed to $2.2 million, a marked improvement from a net loss of $17.6 million in the same quarter last year, which included a $15 million non-cash impairment charge related to BioStrand’s goodwill and intangible assets.

Adjusted EBITDA loss improved to $0.3 million, compared to a loss of $1.7 million in the fourth quarter of Fiscal Year 2024, reflecting improved gross profits and enhanced operating efficiency.

Full Year 2025 Financial Results

Revenue for Fiscal Year 2025, was $24.5 million, up slightly versus $24.5 million in Fiscal Year 2024.

Gross Profit for Fiscal Year 2025 was $13.5 million, a 12.4% increase compared to $12.1 million in Fiscal Year 2024. Gross margin expanded by 600 basis points to 55%, up from 49% in the prior year. This margin improvement was driven by a greater revenue contribution from the high-margin BioStrand segment, coupled with an increased focus on cost efficiencies.

Research and development expenses were $4.9 million in Fiscal Year 2025, up from $4.0 million in Fiscal Year 2024, reflecting increased investment in R&D activities within the BioStrand segment.

Sales and marketing expenses were $4.3 million in Fiscal Year 2025, compared to $3.5 million in Fiscal Year 2024, reflecting increased spending on advertising related to digital campaign expenses.

General and administrative expenses totaled $14.7 million in Fiscal Year 2025, down from $15.6 million in Fiscal Year 2024, reflecting the Company’s continued focus on operational efficiency and cost discipline.

Operating loss in Fiscal Year 2025, excluding amortization and non-recurring charges, improved to $10.4 million, compared to $11.1 million in Fiscal Year 2024.

Net loss in Fiscal Year 2025 was $30.2 million, or $(0.91) per share on a basic and diluted basis, compared to a net loss of $26.1 million or $(1.02) on a basic and diluted basis in Fiscal Year 2024.

Total cash, cash equivalents, and marketable securities, including restricted cash, were $10.8 million as of April 30, 2025.

The reconciliation of Net Loss to Adjusted EBITDA is presented in the table below:

Three Months Ended
April 30,

Year Ended
April 30,

(in thousands)

2025
$

2024
$

2025
$

2024
$

Net loss

(2,161

)

(17,610

)

(30,234

)

(26,115

)

Income taxes

261

(1,214

)

(4,033

)

(2,588

)

Amortization and depreciation

913

1,579

5,119

5,735

Accretion

2

4

10

19

Asset impairment charge

—

15,031

21,184

15,031

Foreign exchange realized gain (loss)

(33

)

18

(5

)

142

Interest expense

209

323

948

849

Interest and other income

(3

)

3

283

(23

)

Unrealized foreign exchange loss (gain)

443

(65

)

594

(86

)

Share-based expense

53

237

445

1,535

Adjusted EBITDA

(316

)

(1,694

)

(5,689

)

(5,501

)

*All financial figures are in Canadian Dollars (CAD) unless otherwise stated.

Conference Call and Webcast Details

The Company will host a live conference call and webcast to discuss these results and provide a corporate update on Friday, July 29, 2025, at 10:30AM ET.

The conference call will be webcast live and available for replay via a link provided in the Events section of the Company’s IR pages at View Source

***Participant Dial-In Details***

Participants call one of the allocated dial-in numbers (below) and advise the Operator of either the Conference ID 3224490 or Conference Name.

USA / International Toll +1 (646) 307-1963
USA – Toll-Free (800) 715-9871
Canada – Toll-Free (800) 715-9871

***Webcast Details***

Attendee URL:
View Source

Please call the conference telephone number five minutes prior to the start time. An operator will register your name and organization.

Anyone listening to the call is encouraged to read the company’s periodic reports available on the company’s profile at www.sedarplus.com and www.sec.gov, including the discussion of risk factors and historical results of operations and financial condition in those reports.

On July 29, 2025 Ikena Oncology presented its corporate presentation (Presentation, Ikena Oncology, JUL 29, 2025, View Source [SID1234654597]).

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On July 29, 2025 Eli Lilly and Company (NYSE: LLY) reported positive topline results from the Phase 3 BRUIN CLL-314 clinical trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, versus Imbruvica (ibrutinib), a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) (Press release, Eli Lilly, JUL 29, 2025, View Source [SID1234654596]). This study enrolled patients with treatment-naïve CLL/SLL and those who had been previously treated but were BTK inhibitor-naïve. The study met its primary endpoint of non-inferiority on overall response rate (ORR) as assessed by an independent review committee (IRC) in both the pre-treated and intent-to-treat populations. ORR favored pirtobrutinib with a nominal P-value for superiority1 (p <0.05). Progression free survival (PFS), a key secondary endpoint, was not yet mature at this analysis, but was trending in favor of pirtobrutinib. A formal PFS analysis testing for superiority is planned at a future analysis. No detriment was observed for overall survival (OS).

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BRUIN CLL-314 is the first ever head-to-head trial versus ibrutinib in CLL to include treatment-naïve patients. This important subpopulation (n=225) had the longest follow-up and a particularly pronounced PFS effect size in favor of pirtobrutinib.

The overall safety profile of pirtobrutinib in BRUIN CLL-314 was similar to previously reported trials. Detailed results will be presented at a medical congress later in 2025.

"We launched the pirtobrutinib randomized development program with an ambitious suite of clinical trials, including head-to-head studies against modern standards of care and examinations of patient populations that reflect real world use, such as BTK inhibitor-pretreated patients," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "These data mark the second positive Phase 3 study in the program, as we continue to build evidence supporting the potential role of pirtobrutinib in treating people with CLL/SLL and hopefully enabling future regulatory approvals that allow physicians to use the medicine in various disease settings, whether treatment-naïve or BTK inhibitor-pretreated."

These data build on the previously reported positive results from the BRUIN Phase 1/2 trial and the Phase 3 BRUIN CLL-321 trial, the first randomized, controlled study ever conducted in an exclusively post-covalent BTK inhibitor population. The BRUIN CLL-313 Phase 3 study of pirtobrutinib versus chemoimmunotherapy in treatment naïve CLL/SLL is expected to read out later in 2025 and combined with the results of BRUIN CLL-314, will form the basis of regulatory submissions globally. For more information on the BRUIN Phase 3 clinical trial program, please visit clinicaltrials.gov.

About BRUIN CLL-314
BRUIN CLL-314 is a Phase 3, randomized, open-label study of pirtobrutinib versus ibrutinib in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who were either treatment-naïve, or who were previously treated and were BTK inhibitor-naïve. The trial planned to enroll 650 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or ibrutinib (420 mg orally, once daily). The primary endpoint is overall response rate (ORR) as assessed by blinded independent review committee (IRC). Secondary endpoints include investigator and IRC assessed progression-free survival (PFS), duration of response (DoR) and event-free survival (EFS), and time to next treatment (TTNT), overall survival (OS), safety and tolerability, and patient-reported outcomes (PRO).

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.2 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).3,4 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is a kinase inhibitor indicated for the treatment of

Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred (4.4%). Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (17%). Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%). Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. Upon confirmation of DILI, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Serious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%).

Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis.

Most common ARs (≥20%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Special Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.

On July 29, 2025 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that management will be attending the Canaccord Genuity 45th Annual Growth Conference on Tuesday, August 12, 2025 at The InterContinental Boston in Boston, MA (Press release, Delcath Systems, JUL 29, 2025, View Source [SID1234654595]).

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