Zilurgisertib

WILMINGTON, Del.--( BUSINESS WIRE )--Incyte (Nasdaq:INCY) today announced financial results for the fourth quarter and full year ended December 31, 2024 and provided full year 2025 financial guidance. "2024 was an important year for Incyte, with a 15% increase in total revenues, driven by strong growth from both Jakafi and Opzelura, as well as significant progress across our R&D pipeline," said Hervé Hoppenot, Chief Executive Officer, Incyte. "Looking ahead to 2025, we anticipate a year of continued strong revenue growth and diversification, as well as several defining milestones that will serve as an inflection point for Incyte. A year ago, we set the goal to achieve more than 10 impactful product launches by 2030. In 2025, a number of key catalysts across the entire portfolio will bring that goal closer to reality." 2025: A Year of Defining Catalysts Incyte expects to deliver at least 18 key milestones in 2025. These include: Four new product launches: Niktimvo™ in 3L+ chronic graft-versus-host disease (GVHD), ruxolitinib cream in pediatric atopic dermatitis (AD), tafasitamab in relapsed/refractory follicular lymphoma (FL), and retifanlimab in squamous cell anal carcinoma (SCAC). At least three Phase 3 study initiations: BET inhibitor in 2L myelofibrosis (MF), ruxolitinib cream in mild to moderate hidradenitis suppurativa (HS) and CDK2 inhibitor in ovarian cancer. Four pivotal readouts: Povorcitinib in moderate to severe HS, ruxolitinib cream in prurigo nodularis (PN), tafasitamab in 1L diffuse large B-cell lymphoma (DLBCL), and ruxolitinib XR for MF, polycythemia vera (PV), and GVHD. Seven proof of concept readouts: Povorcitinib in chronic spontaneous urticaria (CSU) and asthma, mutCALR in MF and essential thrombocythemia (ET), JAK2V617F mutant-specific inhibitor in MF, and both KRASG12D and TGFβR2xPD-1 in solid tumors. Key Recent Company Updates A bioequivalence study of ruxolitinib extended-release (XR) has been completed. These data are anticipated to be submitted to the U.S. Food and Drug Administration (FDA) by year-end 2025 once the stability studies are complete. In January 2025, Incyte and Syndax Pharmaceuticals announced that the FDA approved Niktimvo™ (axatilimab-csfr) in 9 mg and 22 mg vial sizes. Niktimvo is now commercially available in the U.S. and the commercial launch is underway. In December 2024, additional results from the pivotal Phase 3 inMIND trial evaluating treatment with tafasitamab (Monjuvi ® ), a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody, in combination with lenalidomide and rituximab compared with placebo plus lenalidomide and rituximab in patients with relapsed or refractory follicular lymphoma were featured in the late-breaking session at the 2024 American Society of Hematology (ASH) Annual Meeting. The study met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) by investigator assessment in 548 patients with relapsed or refractory FL. Tafasitamab was generally well-tolerated, and safety was consistent with other CD19 and immunotherapy combination regimens. These data have been submitted to the FDA and approval for this indication is expected in the second half of 2025. In December 2024, Incyte shared additional data from its BET inhibitor (INCB057643) in patients with relapsed or refractory myelofibrosis and other advanced myeloid neoplasms at the 2024 ASH Annual Meeting. These results showed treatment with INCB057643 was generally well tolerated and improvements in anemia, spleen size, and symptom burden were observed in patients receiving INCB057643 monotherapy and in combination with ruxolitinib. Incyte plans to initiate a Phase 3 monotherapy study in the post Jakafi patient population in 2025. In December 2024, the supplemental Biologics License Application (sBLA) submission for retifanlimab (Zynyz ® ) in advanced/metastatic squamous cell anal carcinoma was filed with the FDA with approval anticipated in the second half of 2025. In October 2024, the sNDA submission for ruxolitinib cream (Opzelura ® ) in pediatric atopic dermatitis was filed with the FDA with approval anticipated in the second half of 2025. Jakafi: Net product revenues for the fourth quarter of 2024 of $773 million; 2024 full year net product revenues of $2.79 billion Fourth quarter 2024 net product revenues increased 11% compared to the fourth quarter of 2023 and 8% for the full year 2024 when compared to 2023. Net product revenues were primarily driven by paid demand, which increased 14% in the fourth quarter of 2024 and 9% for the full year 2024 when compared to the same periods in 2023, with growth across all indications. Channel inventory at the end of the fourth quarter of 2024 was within the normal range. Opzelura: Net product revenues for the fourth quarter of 2024 of $162 million; 2024 full year net product revenues of $508 million: Fourth quarter 2024 net product revenues increased 48% compared to the fourth quarter of 2023 and 50% for the full year 2024 when compared to 2023. Net product revenues were primarily driven by patient demand and refills for both atopic dermatitis and vitiligo and increased contribution from Europe. Additional Pipeline Updates Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) – key highlights The Phase 1 studies evaluating mutCALR in myelofibrosis (MF) and essential thrombocythemia (ET) and JAK2V617Fi in MF are ongoing and enrolling patients. Initial proof of concept data for both studies are anticipated in 2025. A Phase 2 trial evaluating the safety and efficacy of axatilimab (Niktimvo ™ ) in combination with ruxolitinib (Jakafi ® ) in patients with newly diagnosed chronic GVHD was initiated in the fourth quarter of 2024 and is enrolling patients. A Phase 3, randomized, double-blind, placebo-controlled, multi-center trial that will investigate the use of axatilimab in combination with corticosteroids as initial treatment for chronic GVHD has been initiated and is enrolling patients. MPN and GVHD Programs Indication and Phase Ruxolitinib XR (QD) (JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD Ruxolitinib + INCB57643 (JAK1/JAK2 + BETi) Myelofibrosis: Phase 2 Ruxolitinib + axatilimab 1 (JAK1/JAK2 + anti-CSF-1R) Chronic GVHD: Phase 2 Steroids + axatilimab 1 (Steroids + anti-CSF-1R) Chronic GVHD: Phase 3 INCA33989 (mutCALR) Myelofibrosis, essential thrombocythemia: Phase 1 INCB160058 (JAK2V617Fi) Myelofibrosis: Phase 1 1 Clinical development of axatilimab in GVHD conducted in collaboration with Syndax Pharmaceuticals. Other Hematology/Oncology – key highlights 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 in first-line DLBCL is ongoing. The Phase 3 data are anticipated in the first half of 2025. The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 in solid tumors are ongoing and enrolling patients. Initial proof of concept data for both studies are anticipated in 2025. Heme/Oncology Programs Indication and Phase Tafasitamab (Monjuvi ® /Minjuvi ® ) (CD19) Relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Phase 3 (B-MIND) First-line DLBCL: Phase 3 ( front MIND) Relapsed or refractory follicular lymphoma (FL): Phase 3 ( in MIND) Retifanlimab (Zynyz ® ) 1 (PD-1) Squamous cell anal cancer (SCAC): Phase 3 (POD1UM-303) 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 Two Phase 3 trials (TRuE-PN1 and TRuE-PN2) evaluating ruxolitinib cream in prurigo nodularis (PN) are fully enrolled. Data from the Phase 3 studies are anticipated in the first half of 2025. The Phase 3 trial for ruxolitinib cream in mild to moderate hidradenitis suppurativa (HS) is on track to initiate in the first half of 2025 following achieving alignment on the study design with FDA. In February 2025, Opzelura was granted approval by the Swiss Agency for Therapeutic Products (Swissmedic) for the treatment of non-segmental vitiligo with facial involvement in patients 12 years of age and older. In October 2024, Opzelura was granted a Notice of Compliance by Health Canada for the topical treatment of both mild to moderate atopic dermatitis and nonsegmental vitiligo in patients 12 years of age and older. Povorcitinib (INCB54707) In October 2024, two Phase 3 studies (STOP-PN1 and STOP-PN2) evaluating povorcitinib in patients with PN versus placebo were initiated and are enrolling. The Phase 3 studies of povorcitinib in patients with HS (STOP-HS1 and STOP-HS2) are fully enrolled. Data from both pivotal studies are anticipated in the first half of 2025. Two Phase 2 trials evaluating povorcitinib in asthma and chronic spontaneous urticaria (CSU) are enrolling. Data for CSU are anticipated in the first half of 2025 and data in asthma are anticipated in the second half of 2025. IAI and Dermatology Programs Indication and Phase Ruxolitinib cream (Opzelura ® ) 1 (JAK1/JAK2) Atopic dermatitis: Phase 3 pediatric study (TRuE-AD3) Hidradenitis suppurativa: Phase 2; Phase 3 expected to initiate in 2025 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 2024 Fourth Quarter and Year-end Financial Results The financial measures presented in this press release for the quarter and year ended December 31, 2024 and 2023 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. As changes in exchange rates are an important factor in understanding period-to-period comparisons, Management believes the presentation of certain revenue results on a constant currency basis in addition to reported results helps improve investors’ ability to understand its operating results and evaluate its performance in comparison to prior periods. Constant currency information compares results between periods as if exchange rates had remained constant period over period. The Company calculates constant currency by calculating current year results using prior year foreign currency exchange rates and generally refers to such amounts calculated on a constant currency basis as excluding the impact of foreign exchange or being on a constant currency basis. These results should be considered in addition to, not as a substitute for, results reported in accordance with GAAP. Results on a constant currency basis, as the Company presents them, may not be comparable to similarly titled measures used by other companies and are not measures of performance presented in accordance with GAAP. Financial Highlights Financial Highlights (unaudited, in thousands, except per share amounts) Three Months Ended December 31, Twelve Months Ended December 31, 2024 2023 2024 2023 Total GAAP revenues $ 1,178,698 $ 1,013,341 $ 4,241,217 $ 3,695,649 Total GAAP operating income 301,513 187,270 61,366 620,525 Total Non-GAAP operating income 376,265 267,702 413,883 892,783 GAAP net income 201,212 201,079 32,615 597,599 Non-GAAP net income 281,353 239,124 227,591 795,449 GAAP basic EPS $ 1.04 $ 0.90 $ 0.16 $ 2.67 Non-GAAP basic EPS $ 1.46 $ 1.07 $ 1.10 $ 3.56 GAAP diluted EPS $ 1.02 $ 0.89 $ 0.15 $ 2.65 Non-GAAP diluted EPS $ 1.43 $ 1.06 $ 1.08 $ 3.52 Revenue Details Revenue Details (unaudited, in thousands) Three Months Ended December 31, % Change (as reported) % Change (constant currency) 1 Twelve Months Ended December 31, % Change (as reported) % Change (constant currency) 1 2024 2023 2024 2023 Net product revenues: Jakafi $ 773,114 $ 695,127 11 % 11 % $ 2,792,107 $ 2,593,732 8 % 8 % Opzelura 161,602 109,243 48 % 48 % 508,293 337,864 50 % 50 % Iclusig 27,369 27,130 1 % 1 % 114,319 111,623 2 % 2 % Pemazyre 23,142 20,653 12 % 12 % 81,748 83,642 (2 %) (2 %) Minjuvi/ Monjuvi 32,807 8,994 265 % 265 % 119,236 37,057 222 % 222 % Zynyz 1,373 582 136 % 136 % 3,185 1,250 155 % 155 % Total net product revenues 1,019,407 861,729 18 % 18 % 3,618,888 3,165,168 14 % 14 % Royalty revenues: Jakavi 114,187 103,892 10 % 13 % 418,840 367,583 14 % 16 % Olumiant 38,485 40,359 (5 %) (3 %) 135,572 136,138 — % 2 % Tabrecta 6,286 4,678 34 % NA 22,746 17,793 28 % NA Pemazyre 333 683 NM NM 2,171 1,967 NM NM Total royalty revenues 159,291 149,612 6 % 579,329 523,481 11 % Total net product and royalty revenues 1,178,698 1,011,341 17 % 4,198,217 3,688,649 14 % Milestone and contract revenues — 2,000 — % — % 43,000 7,000 514 % 514 % Total GAAP revenues $ 1,178,698 $ 1,013,341 16 % $ 4,241,217 $ 3,695,649 15 % NM = not meaningful NA = not applicable 1. Percentage change in constant currency is calculated using 2023 foreign exchange rates to recalculate 2024 results. Product and Royalty Revenues Total net product and royalty revenues for the quarter and year ended December 31, 2024 increased 17% and 14%, respectively, over the prior year comparative periods, primarily driven by the following: For the quarter ended December 31, 2024, Jakafi net product revenue increased 11% primarily driven by a 14% increase in paid demand. Channel inventory at the end of the fourth quarter of 2024 was within the normal range. For the year ended December 31, 2024, Jakafi net product revenue increased 8% primarily driven by a 9% increase in paid demand. For the quarter and year ended December 31, 2024, Opzelura net product revenue increased 48% and 50%, respectively, driven by continued growth in new patient starts and refills in the U.S. and increased contribution from Europe. Opzelura net product revenues included $24 million and $61 million ex-U.S. revenue for the fourth quarter and full year, respectively. For the quarter and year ended December 31, 2024, Minjuvi/Monjuvi net product revenue increased 265% and 222%, respectively, as we recognize all revenue from sales of Monjuvi in the United States following the acquisition of exclusive global rights for tafasitamab in February 2024. For the quarter and full year ended December 31, 2024, total royalty revenues increased by 6% and 11%, respectively, primarily driven by growth in Jakavi royalty revenues. Operating Expenses Operating Expense Summary (unaudited, in thousands) Three Months Ended December 31, % Change Twelve Months Ended December 31, % Change 2024 2023 2024 2023 GAAP cost of product revenues $ 88,485 $ 69,751 27 % $ 312,068 $ 254,990 22 % Non-GAAP cost of product revenues 1 82,427 63,575 30 % 288,266 230,308 25 % GAAP research and development 466,034 444,494 5 % 2,606,848 1,627,594 60 % Non-GAAP research and development 2 420,297 408,488 3 % 2,423,167 1,500,897 61 % GAAP selling, general and administrative 326,710 293,865 11 % 1,242,157 1,161,293 7 % Non-GAAP selling, general and administrative 3 299,709 270,673 11 % 1,116,926 1,069,616 4 % GAAP (gain) loss on change in fair value of acquisition-related contingent consideration (4,044 ) 15,058 (127 %) 19,803 29,202 (32 %) Non-GAAP (gain) loss on change in fair value of acquisition-related contingent consideration — — — % — — — % GAAP (profit) and loss sharing under collaboration agreements — 2,903 — % (1,025 ) 2,045 (150 %) 1 Non-GAAP cost of product revenues excludes the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc. and the cost of stock-based compensation. 2 Non-GAAP research and development expenses exclude the cost of stock-based compensation, MorphoSys transition costs, and Escient acquisition related compensation expense related to cash settled unvested Escient equity awards and severance payments. 3 Non-GAAP selling, general and administrative expenses exclude the cost of stock-based compensation, MorphoSys transition costs, Escient acquisition related compensation expense related to cash settled unvested Escient equity awards and severance payments, and asset impairments. Cost of product revenues GAAP and Non-GAAP cost of product revenues for the quarter and year ended December 31, 2024 increased 27% and 30%, and 22% and 25%, respectively, compared to the same periods in 2023 primarily due to growth in net product revenues, increased royalty expense and increased manufacturing related costs. Research and development expenses GAAP and Non-GAAP research and development expense for the quarter ended December 31, 2024 increased 5% and 3%, respectively, compared to the same period in 2023, primarily driven by continued investment in our late-stage development assets and timing of certain expenses. GAAP and Non-GAAP research and development expense for the year ended December 31, 2024 increased 60% and 61%, respectively, compared to the same period in 2023, primarily due to the Escient acquisition upfront consideration and related compensation expense and severance payments, and other milestone payments. For the year ended December 31, 2024, excluding the Escient acquisition upfront payment, related compensation expense and severance payments and other milestone payments, research and development expense increased 14% compared to the same period in 2023 as a result of continued investment in our late-stage development assets and timing of certain expenses. Selling, general and administrative expenses GAAP and Non-GAAP selling, general and administrative expenses for the quarter ended December 31, 2024 increased 11% compared to the same period in 2023, primarily due to the timing of consumer marketing activities and of certain other expenses. GAAP and Non-GAAP selling, general and administrative expenses for the year ended December 31, 2024 increased 7% and 4%, respectively, compared to the same period in 2023, primarily due to $22.1 million of Escient acquisition related compensation expense including severance payments, and timing of consumer marketing activities and of certain other expenses. Excluding the Escient acquisition related compensation expense and severance payments, selling, general and administrative expenses for the year ended December 31, 2024 increased 5% compared to the prior year. Other Financial Information Change in fair value of acquisition-related contingent consideration The change in fair value of contingent consideration during the quarter and year ended December 31, 2024, compared to the same periods in 2023, was primarily due to fluctuations in foreign currency exchange rates impacting future revenue projections of Iclusig. Operating income GAAP and Non-GAAP operating income for the quarter ended December 31, 2024 increased 61% and 41%, respectively, compared to the same period in 2023, primarily driven by growth in total revenues and stable operating expenses. GAAP and Non-GAAP operating income for the year ended December 31, 2024 decreased 90% and 54%, respectively, compared to the same period in 2023, primarily driven by the $679.4 million of expense relating to the IPR&D assets acquired in the Escient acquisition, $38.0 million of Escient acquisition related compensation expense and severance payments, and the $100.0 million milestone payment made to MacroGenics. Excluding upfront and milestone payments and the Escient acquisition related compensation expense and severance payments, operating income for the year ended December 31, 2024 increased 34% compared to the prior year primarily driven by growth in net product revenue. Cash, cash equivalents and marketable securities position As of December 31, 2024 and 2023, cash, cash equivalents and marketable securities totaled $2.2 billion and $3.7 billion, respectively. The decrease in cash, cash equivalents and marketable securities during 2024 was driven primarily by the $2.0 billion share repurchase completed in June 2024, and the total cash consideration paid to Escient shareholders of $783 million, partially offset by proceeds of sales of equity investments and operating cash flows during the year ended December 31, 2024. 2025 Financial Guidance Incyte's guidance for the fiscal year 2025 is summarized below. Guidance for Opzelura includes net product revenue for pediatric atopic dermatitis which has an anticipated approval in the second half of 2025. Guidance for other oncology net product revenues include net product revenue for Monjuvi in follicular lymphoma and Zynyz in squamous cell anal carcinoma. Approvals for these indications are anticipated in the second half of 2025. Current Jakafi net product revenues $2,925 - $2,975 million Opzelura net product revenues $630 - $670 million Other oncology net product revenues (1) $415 - $455 million GAAP Cost of product revenues 8.5% - 9.0% of net product revenues Non-GAAP Cost of product revenues (2) 7.5% - 8.0% of net product revenues GAAP Research and development expenses $1,930 - $1,960 million Non-GAAP Research and development expenses (3) $1,780 - $1,805 million GAAP Selling, general and administrative expenses $1,280 - $1,310 million Non-GAAP Selling, general and administrative expenses (3) $1,160 - $1,185 million 1 Pemazyre in the U.S., EU and Japan; Niktimvo, Monjuvi and Zynyz in the U.S.; and Iclusig and Minjuvi in the EU. 2 Adjusted to exclude the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc. and the estimated cost of stock-based compensation. 3 Adjusted to exclude the estimated cost of stock-based compensation. Conference Call and Webcast Information Incyte will hold a conference call and webcast this morning at 8:00 a.m. ET. To access the conference call, please dial 877-407-3042 for domestic callers or 201-389-0864 for international callers. When prompted, provide the conference identification number, 13751174. If you are unable to participate, a replay of the conference call will be available for 90 days. The replay dial-in number for the United States is 877-660-6853 and the dial-in number for international callers is 201-612-7415. To access the replay you will need the conference identification number, 13751174. The conference call will also be webcast live and can be accessed at investor.incyte.com . About Incyte A global biopharmaceutical company on a mission to Solve On ., Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia. For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn , X , Instagram , Facebook , YouTube . About Jakafi ® (ruxolitinib) Jakafi ® (ruxolitinib) is a JAK1/JAK2 inhibitor approved by the U.S. FDA for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea; intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults; steroid-refractory acute GVHD in adult and pediatric patients 12 years and older; and chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Jakafi is a registered trademark of Incyte. About Opzelura ® (ruxolitinib) Cream Opzelura ® (ruxolitinib) cream, a novel cream formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib, approved by the U.S. Food & Drug Administration for the topical treatment of nonsegmental vitiligo in patients 12 years of age and older, is the first and only treatment for repigmentation approved for use in the United States. Opzelura is also approved in the U.S. for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Use of Opzelura in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants, such as azathioprine or cyclosporine, is not recommended. In Europe, Opzelura (ruxolitinib) cream 15mg/g is approved for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age. Incyte has worldwide rights for the development and commercialization of ruxolitinib cream, marketed in the United States as Opzelura. Opzelura and the Opzelura logo are registered trademarks of Incyte. About Monjuvi ® (tafasitamab-cxix) Monjuvi ® (tafasitamab-cxix) is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb® engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP). MorphoSys and Incyte entered into: (a) in January 2020, a collaboration and licensing agreement to develop and commercialize tafasitamab globally; and (b) in February 2024, an agreement whereby Incyte obtained exclusive rights to develop and commercialize tafasitamab globally. Following accelerated approval by the U.S. Food and Drug Administration in July 2020, Monjuvi ® (tafasitamab-cxix) is being commercialized in the United States by Incyte. In Europe, Minjuvi ® (tafasitamab) received conditional Marketing Authorization from the European Medicines Agency in August 2021. XmAb ® is a registered trademark of Xencor, Inc. Monjuvi, Minjuvi, the Minjuvi and Monjuvi logos and the “triangle” design are (registered) trademarks of Incyte. About Pemazyre ® (pemigatinib) Pemazyre ® (pemigatinib) is a kinase inhibitor indicated in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test*. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Pemazyre is also the first targeted treatment approved for use in the United States for treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene, worsening after cancer chemotherapy. In Europe, Pemazyre is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy. Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations. Pemazyre is marketed by Incyte in the United States, Europe and Japan. Pemazyre is a trademark of Incyte. * Pemazyre ® (pemigatinib) [Package Insert]. Wilmington, DE: Incyte; 2020. About Iclusig ® (ponatinib) tablets Iclusig ® (ponatinib) targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs. In the EU, Iclusig is approved for the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation. Click here to view the Iclusig EU Summary of Medicinal Product Characteristics. Incyte has an exclusive license from Takeda Pharmaceuticals International AG to commercialize ponatinib in the European Union and 29 other countries, including Switzerland, UK, Norway, Turkey, Israel and Russia. Iclusig is marketed in the U.S. by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. About Zynyz ® (retifanlimab-dlwr) Zynyz ® (retifanlimab) is an intravenous PD-1 inhibitor indicated in the U.S. for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Zynyz is marketed by Incyte in the U.S. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab. Zynyz is a trademark of Incyte. Forward-Looking Statements Except for the historical information set forth herein, the matters set forth in this release contain predictions, estimates and other forward-looking statements, including any discussion of the following: Incyte’s potential for continued performance and growth; Incyte’s financial guidance for 2025, including its expectations regarding sales of and demand for Jakafi and Opzelura; the launch of Niktimvo and the expected revenue contribution from near-term launches; additional label expansion opportunities; the possibility for 2025 to be a transformational year for Incyte in terms of potential launches, phase 3 study initiations, pivotal readouts and proof of concept readouts; Incyte’s potential to have more than 10 high impact launches by 2030; the potential and progress of programs in our pipeline, including povorcitinib and mutCALR; ongoing clinical trials and clinical trials that may be initiated, including a BETi phase 3 study, pivotal studies in three indications for povorcitinib and phase 3 studies for Incyte’s CDK2 inhibitor; and expectations regarding regulatory filings, regulatory approvals and 2025 newsflow items. These forward-looking statements are based on Incyte’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials and the ability to enroll subjects in accordance with planned schedules; determinations made by the FDA, EMA, and other regulatory agencies; Incyte’s dependence on its relationships with and changes in the plans of its collaboration partners; the efficacy or safety of Incyte’s products and the products of Incyte’s collaboration partners; the acceptance of Incyte’s products and the products of Incyte’s collaboration partners in the marketplace; market competition; unexpected variations in the demand for Incyte’s products and the products of Incyte’s collaboration partners; the effects of announced or unexpected price regulation or limitations on reimbursement or coverage for Incyte’s products and the products of Incyte’s collaboration partners; sales, marketing, manufacturing and distribution requirements, including Incyte’s and its collaboration partners’ ability to successfully commercialize and build commercial infrastructure for newly approved products and any additional products that become approved; greater than expected expenses, including expenses relating to litigation or strategic activities; variations in foreign currency exchange rates; and other risks detailed in Incyte’s reports filed with the Securities and Exchange Commission, including its annual report on form 10-K for the year ended December 31, 2024. Incyte disclaims any intent or obligation to update these forward-looking statements. INCYTE CORPORATION CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited, in thousands, except per share amounts) Three Months Ended December 31, Twelve Months Ended December 31, 2024 2023 2024 2023 GAAP GAAP Revenues: Product revenues, net $ 1,019,407 $ 861,729 $ 3,618,888 $ 3,165,168 Product royalty revenues 159,291 149,612 579,329 523,481 Milestone and contract revenues — 2,000 43,000 7,000 Total revenues 1,178,698 1,013,341 4,241,217 3,695,649 Costs, expenses and other: Cost of product revenues (including definite-lived intangible amortization) 88,485 69,751 312,068 254,990 Research and development 466,034 444,494 2,606,848 1,627,594 Selling, general and administrative 326,710 293,865 1,242,157 1,161,293 (Gain) loss on change in fair value of acquisition-related contingent consideration (4,044 ) 15,058 19,803 29,202 (Profit) and loss sharing under collaboration agreements — 2,903 (1,025 ) 2,045 Total costs, expenses and other 877,185 826,071 4,179,851 3,075,124 Income from operations 301,513 187,270 61,366 620,525 Interest income 21,198 46,482 128,710 158,414 Interest expense (419 ) (804 ) (2,280 ) (2,551 ) Realized and unrealized (loss) gain on equity investments (10,181 ) 34,054 116,025 43,893 Other, net 1,613 3,954 12,809 13,934 Income before provision for income taxes 313,724 270,956 316,630 834,215 Provision for income taxes 112,512 69,877 284,015 236,616 Net income $ 201,212 $ 201,079 $ 32,615 $ 597,599 Net income per share: Basic $ 1.04 $ 0.90 $ 0.16 $ 2.67 Diluted $ 1.02 $ 0.89 $ 0.15 $ 2.65 Shares used in computing net income per share: Basic 193,152 224,226 207,110 223,628 Diluted 197,423 226,125 210,530 225,928 INCYTE CORPORATION CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands) December 31, 2024 December 31, 2023 ASSETS Cash, cash equivalents and marketable securities $ 2,158,092 $ 3,656,043 Accounts receivable 853,154 743,557 Property and equipment, net 763,411 751,513 Finance lease right-of-use assets, net 30,803 25,535 Inventory 407,199 269,937 Prepaid expenses and other assets 181,382 236,782 Equity investments 18,814 187,716 Other intangible assets, net 113,803 123,545 Goodwill 155,593 155,593 Deferred income tax asset 762,071 631,886 Total assets $ 5,444,322 $ 6,782,107 LIABILITIES AND STOCKHOLDERS’ EQUITY Accounts payable, accrued expenses and other liabilities $ 1,765,733 $ 1,347,669 Finance lease liabilities 37,961 32,601 Acquisition-related contingent consideration 193,000 212,000 Stockholders’ equity 3,447,628 5,189,837 Total liabilities and stockholders’ equity $ 5,444,322 $ 6,782,107 INCYTE CORPORATION RECONCILIATION OF GAAP NET INCOME TO SELECTED NON-GAAP ADJUSTED INFORMATION (unaudited, in thousands, except per share amounts) Three Months Ended December 31, Twelve Months Ended December 31, 2024 2023 2024 2023 GAAP Net Income $ 201,212 $ 201,079 $ 32,615 $ 597,599 Adjustments 1 : Non-cash stock compensation from equity awards (R&D) 2 44,110 36,006 161,251 126,697 Non-cash stock compensation from equity awards (SG&A) 2 26,935 23,192 102,542 86,046 Non-cash stock compensation from equity awards (COGS) 2 674 792 2,266 3,146 Non-cash interest 3 82 108 415 463 Realized and unrealized loss (gain) on equity investments 4 10,181 (34,054 ) (116,025 ) (43,893 ) Amortization of acquired product rights 5 5,384 5,384 21,536 21,536 Loss on change in fair value of contingent consideration 6 (4,044 ) 15,058 19,803 29,202 Asset impairment 7 — — — 5,631 MorphoSys transition costs 8 — — 7,084 — Escient acquisition related compensation expense 9 1,693 — 38,035 — Tax effect of Non-GAAP pre-tax adjustments 10 (4,874 ) (8,441 ) (41,931 ) (30,978 ) Non-GAAP Net Income $ 281,353 $ 239,124 $ 227,591 $ 795,449 Non-GAAP net income per share: Basic $ 1.46 $ 1.07 $ 1.10 $ 3.56 Diluted $ 1.43 $ 1.06 $ 1.08 $ 3.52 Shares used in computing Non-GAAP net income per share: Basic 193,152 224,226 207,110 223,628 Diluted 197,423 226,125 210,530 225,928 1 Included within the Milestone and contract revenues line item in the Condensed Consolidated Statements of Operations (in thousands) for the three and twelve months ended December 31, 2024 are milestones of $0 and $43,000, respectively, earned from our collaborative partners, as compared to milestones of $2,000 and $7,000, respectively, for the three and twelve months ended December 31, 2023. Included within the Research and development expenses line item in the Condensed Consolidated Statements of Operations (in thousands) for the three and twelve months ended December 31, 2024 are upfront consideration and milestones of $3,000 and $104,414, respectively, related to our collaborative partners, as compared to upfront consideration and milestones of $24,000 and $36,650, respectively, for the three and twelve months ended December 31, 2023. 2 As included within the Cost of product revenues (including definite-lived intangible amortization) line item; the Research and development expenses line item; and the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations. 3 As included within the Interest expense line item in the Condensed Consolidated Statements of Operations. 4 As included within the Realized and unrealized gain (loss) on equity investments line item in the Condensed Consolidated Statements of Operations. 5 As included within the Cost of product revenues (including definite-lived intangible amortization) line item in the Condensed Consolidated Statements of Operations. Acquired product rights of licensed intellectual property for Iclusig is amortized utilizing a straight-line method over the estimated useful life of 12.5 years. 6 As included within the Loss on change in fair value of acquisition-related contingent consideration line item in the Condensed Consolidated Statements of Operations. 7 As included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations. 8 Included within the Research and development line item in the Condensed Consolidated Statements of Operations (in thousands) is $0 and $6,489 for the three months and year ended December 31, 2024, respectively, and included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations (in thousands) is $0 and $595 for the three months and year ended December 31, 2024, respectively. MorphoSys transition costs primarily represent employee related costs to transition research and development and selling, general and administrative activities to us under the former collaboration agreement with MorphoSys. 9 Included within the Research and development line item in the Condensed Consolidated Statements of Operations (in thousands) is $1,627 and $15,941, respectively, for the three months and year ended December 31, 2024, and included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations (in thousands) is $66 and $22,094, respectively, for the three months and year ended December 31, 2024. Escient acquisition related compensation expense represents non-recurring charges associated with (i) cash settled unvested Escient equity awards in connection with the acquisition, and (ii) severance payments to former Escient employees. 10 Income tax effects of Non-GAAP pre-tax adjustments are calculated using the applicable statutory tax rate for the jurisdictions in which the charges are incurred, while taking into consideration any valuation allowances against related deferred tax assets.

由于减肥、自免等疾病领域的兴起，正在转移药企们的兴趣，肿瘤药物的开发似乎有所萎缩。 而上周四，更是一连三家药企，因为临床的数据不佳，而宣布停止开发各自的肿瘤候选药物。 Incyte放弃ALK2抑制剂 在上周四的投资者电话会议中，Incyte透露，将不再推进ALK2抑制剂zilurgisertib的开发。 Zilurgisertib是一种小分子药物，旨在抑制ALK2蛋白，ALK2蛋白的升高会导致血液中功能性缺铁，从而引发贫血。Zilurgisertib的作用机制为，通过与ALK2结合，阻断其下游信号下调hepcidin表达，恢复运铁蛋白缓解功能性缺铁，动员铁促进红细胞生成，从而改善因骨髓纤维化（MF）和其他血液恶性肿瘤导致的贫血。 目前，Zilurgisertib正在进行骨髓纤维化相关贫血和进行性骨化纤维发育不良的研究。但在Incyte所披露的Zilurgisertib数据更新中显示，Zilurgisertib未能改善MF患者的贫血。 正是因为1期研究显示出的“疗效有限”，Incyte决定放弃Zilurgisertib的开发，目前尚不清楚Incyte是否会在其他疾病领域继续开发zilurgisertib。 事实上，Zilurgisertib的失败并不令人感到惊讶。因为早在10月时发布的第三季度财报中，Incyte就曾表示，“zilurgisertib的剂量需要高于最初的预期，才能看到更有希望的疗效。”这可能表明zilurgisertib的整体活性偏疲弱。 最近，Incyte的失败信号有些多。上个月，由于MRGPRX4抑制剂INCB000547的II期数据低于预期，Incyte决定停止对其的开发；以及MRGPRX24抑制剂INCB000262在临床前体内毒理研究中观察到的毒理学信号，暂停了其针对慢性自发性荨麻疹（CSU）的II期临床。 iTeos放弃A2AR抑制剂 上周四，iTeos Therapeutics宣布，将取消肿瘤候选药物A2AR抑制剂Inupadenant的优先级，将资源集中在其他项目上。 做出这一决定的原因是，Inupadenant+卡铂/培美曲塞治疗非鳞状NSCLC的II期试验A2A-005中，Inupadenant未能达到足够的临床活性水平。 iTeos公司在ESMO 2024年会上更新的A2A-005的中期数据显示： 在所有可评估患者中的总体缓解率（ORR）为63.9%，中位PFS为7.7个月；推荐2期剂量（RP2D）的Inupadenant 80mg+卡铂/培美曲塞队列中的ORR为73.3%，mPFS未达到，64.6%的患者达到具有里程碑意义的6个月PFS；40mg队列的ORR为53.3%，mPFS为5.6月；60mg队列的ORR为66.7%，mPFS为6.6月。 探索性生物标志物CXCL13观察到在化疗耗竭后被inupadenant恢复，在PFS＞6个月的患者中具有快速恢复的动力学特征。 截至数据截止日期，仍有8名患者在接受治疗（40mg队列1名，60mg队列1名，80mg队列6名）。 安全性方面，Inupadenant+卡铂/培美曲塞的安全性可控，耐受性良好，无剂量限制性毒性。 尽管Inupadenant显示出具有较高的缓解率，iTeos还是决定降低Inupadenant的优先级。iTeos的总裁兼首席执行官Michel Detheux在一份声明中表示：“虽然与单独的化疗相比，A2A-005试验中，RP2D的Inupadenant初始信号令人鼓舞并支持其差异化、不可逾越的特征，但我们以及我们的科学和临床顾问委员会认为，它没有达到足够的临床活性水平，需要进一步的投资。” iTeos取消了对Inupadenant的优先级，将资源集中其他管线上。目前，尚不清楚该公司将专注于哪些候选药物。iTeos公司将在2025年提供更多管线细节。 第一个失败的ecDNA疗法 12月12日，Boundless Bio宣布，不再推进BBI-825的临床开发。 BBI-825是一款口服选择性核苷酸还原酶（RNR）抑制剂。RNR是dNTP生产的限速酶，而dNTP是ecDNA组装和修复所需的DNA组分，抑制RNR对ecDNA激活的癌细胞具有合成致死作用。BBI-825目前正在对耐药基因扩增的实体瘤患者（包括结直肠癌）进行首次人体1/2期临床试验。 BBI-825试验第一部分的初步药代动力学数据显示，缺乏剂量比例暴露；以及不断发展的BRAF V600E和KRASG12C突变的癌症治疗前景、开发的复杂性、成本增加，Boundless已经做出战略决策，不再继续BBI-825的第1部分剂量递增和STARMAP试验的第2部分。 今年3月，Boundless以全球首家染色体外DNA（ecDNA）疗法的名头亮相纳斯达克。 然而8个月后的现在，第一个ecDNA管线就失败了，以及首席医疗官 （CMO） Klaus Wagner和首席商务官 （CBO） Neil Abdollahian同时离职。这使得Boundless股价大跌。 此外，令人担忧的是，Boundless的核心管线BBI-355的临床招募出现了问题，根据Boundless Bio公司的说法，BBI-355增强试验的联合队列中登记的患者数量比最初预计的要低。这可能和入组标准和排除标准有关，ecDNA是和肿瘤基因扩增相关的，因此这一标准可以体现在患者入组和排除标准里。 延伸阅读：首个ecDNA公司，上市5个月，现在裁员 小结 另外，在12月16日默沙东宣布终止了TIGIT抗体Vibostolimab和LAG-3抗体Favezelimab的开发。 原因也是因为临床试验的失败。 参考资料： 1.https://investor.incyte.com/static-files/ef7f51e8-2419-4958-914f-35c5af6f8e03 2.https://investors.iteostherapeutics.com/news-releases/news-release-details/iteos-therapeutics-presents-interim-a2a-005-clinical-trial-data 本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·