EP-262

WILMINGTON, Del.--( BUSINESS WIRE )--Incyte (Nasdaq:INCY) today reports 2024 second quarter financial results, and provides a status update on the Company’s clinical development portfolio. "In the second quarter of 2024, total revenues grew 9% year-over-year, surpassing $1.0 billion for the quarter. The commercial performance during this period was driven by strong patient demand for Opzelura ® (ruxolitinib) and growth across all indications for Jakafi ® (ruxolitinib)," said Hervé Hoppenot, Chief Executive Officer, Incyte. "In R&D, we completed a strategic review of our pipeline and have further intensified our focus on clinical programs that we believe can be transformational for patients. The $2.0 billion share repurchase completed during the second quarter, underscores our confidence in our commercial portfolio, clinical pipeline and Incyte's long-term value." Transformation of Pipeline Incyte announces a strategic review of its pipeline with an increased focus on high potential impact programs including, but not limited to: IAI/Dermatology : povorcitinib and MRGPRX2 and MRGPRX4, which were recently acquired from Escient Pharmaceuticals MPNs/GVHD : mCALR, JAK2V617Fi, BETi, and ALK2i Oncology : CDK2i, KRASG12Di and TGFßR2×PD-1 The Company will discontinue further development of both oral, small molecule PD-L1 inhibitors, as well as LAG-3 monoclonal antibody, TIM-3 monoclonal antibody and LAG-3xPD-1 bispecific. Recent Company Updates Incyte announces positive topline results from two Phase 3 clinical studies evaluating retifanlimab (Zynyz ® ), a humanized monoclonal antibody targeting programmed cell death receptor-1 (PD-1), in squamous cell anal carcinoma (SCAC) and non-small cell lung cancer (NSCLC). The Phase 3 PODIUM-303 study in SCAC met its primary endpoint of progression free survival and the Phase 3 PODIUM-304 study in NSCLC met its primary endpoint of overall survival. The safety analysis from both studies demonstrated that retifanlimab was generally well-tolerated with no new safety signals observed. Incyte plans to share the Phase 3 data from both studies in the second half of 2024. POD1UM-303 is a Phase 3, global, multicenter, randomized, double-blind study evaluating carboplatin-paclitaxel with retifanlimab or placebo in patients with inoperable locally recurrent or metastatic SCAC who have not previously been treated with chemotherapy. POD1UM-304 is a Phase 3, global, multicenter, randomized, double-blind study evaluating platinum-based chemotherapy with retifanlimab or placebo in patients with first-line, metastatic squamous or nonsquamous NSCLC. In June 2024, Incyte repurchased a total of 33,325,849 shares of its common stock at a price of $60.00 per share, for a total cost of approximately $2.0 billion, excluding fees and expenses. These shares represented approximately 14.8 percent of the Company’s total outstanding shares of common stock as of June 7, 2024. In May 2024, Incyte announced it completed the acquisition of Escient Pharmaceuticals, a clinical-stage drug discovery and development company advancing novel small molecule therapeutics for systemic immune and neuro-immune disorders. Under the terms of the agreement, Incyte acquired Escient and its clinical development portfolio, including EP262, a first-in-class, potent, highly selective, once-daily small molecule antagonist of Mas-related G protein-coupled receptor (MRGPRX2) and EP547, a first-in-class oral MRGPRX4 antagonist. In April 2024, Incyte and China Medical System Holdings Limited announced the Companies entered into a Collaboration and License Agreement, through a wholly-owned dermatology medical aesthetic subsidiary CMS Skinhealth, for the development and commercialization of povorcitinib, a selective oral JAK1 inhibitor, in Mainland China, Hong Kong, Macau, Taiwan Region and eleven Southeast Asian countries. Jakafi: Net product revenues for the second quarter 2024 of $706 million (+3% Y/Y): Paid demand increased 9% in the second quarter of 2024 versus the same quarter in the prior year, with growth across all indications. Year over year net product revenue growth was lower than paid demand growth due to higher channel inventory levels at the end of the second quarter of 2023 versus the same period of 2024. Channel inventory at the end of the second quarter of 2024 was within the normal range. Opzelura: Net product revenues for the second quarter 2024 of $122 million (+52% Y/Y): Net product revenues growth in the second quarter of 2024 were driven by patient demand, refills and expansion in payer coverage in both atopic dermatitis (AD) and vitiligo. Net product revenues of $11 million in the second quarter of 2024 in Europe. Incyte achieved full reimbursement in Spain and Italy at the end of the second quarter 2024 and in France in July 2024. Additional Pipeline Updates Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) – key highlights Combination trials of ruxolitinib twice daily (BID) with zilurgisertib and BETi are ongoing and continue to enroll. A Phase 3 study for BETi is expected to advance into Phase 3 with an expected update later this year. Clinical proof-of-concept for zilurgisertib is anticipated in the second half of 2024. The Phase 1 studies evaluating mCALR and JAK2V617Fi are ongoing and enrolling patients. Initial data for both studies is anticipated in 2025. MPN and GVHD Programs Indication and status Ruxolitinib XR (QD) (JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD Ruxolitinib + zilurgisertib (JAK1/JAK2 + ALK2i) Myelofibrosis: Phase 2 Ruxolitinib + INCB57643 (JAK1/JAK2 + BETi) Myelofibrosis: Phase 2 Axatilimab (anti-CSF-1R) 1 Chronic GVHD: Pivotal Phase 2 (third-line plus therapy) (AGAVE-201); BLA under review in the U.S. Ruxolitinib + axatilimab 1 (JAK1/JAK2 + anti-CSF-1R) Chronic GVHD: Phase 2 in preparation Steroids + axatilimab 1 (Steroids + anti-CSF-1R) Chronic GVHD: Phase 3 in preparation INCA33989 (mCALR) Myelofibrosis, essential thrombocythemia: Phase 1 INCB160058 (JAK2V617Fi) Phase 1 1 Clinical development of axatilimab in GVHD conducted in collaboration with Syndax Pharmaceuticals. Other Hematology/Oncology – key highlights Heme/Oncology Programs Indication and status Pemigatinib (Pemazyre ® ) (FGFR1/2/3) Myeloid/lymphoid neoplasms (MLN): approved in the U.S. and Japan Cholangiocarcinoma (CCA): Phase 3 (FIGHT-302) 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) and relapsed or refractory marginal zone lymphoma (MZL): Phase 3 ( in MIND) Retifanlimab (Zynyz ® ) 1 (PD-1) Merkel cell carcinoma (MCC): approved in the U.S. and Europe 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 Amplification/ Overexpression of CCNE1: Phase 1 INCB161734 (KRASG12D) Advanced metastatic solid tumors with a KRAS G12D 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 Dermatology Opzelura In March 2024, Incyte presented data at the 2024 AAD Annual Meeting from its randomized, placebo-controlled, Phase 2 study evaluating the safety and efficacy of ruxolitinib cream (Opzelura ® ) in adults with mild/moderate hidradenitis suppurativa (HS). At Week 16, patients receiving ruxolitinib cream 1.5% twice daily (BID) had significantly greater decreases from baseline versus placebo in total abscess and inflammatory nodule (AN) count, the primary endpoint of the study. The overall safety profile of ruxolitinib cream was consistent with previous data, and no new safety signals were observed. A Phase 3 study is expected to initiate in 2025. Ruxolitinib cream in other indications: Phase 2 studies in lichen planus and lichen sclerosus have completed enrollment. Two Phase 3 trials evaluating ruxolitinib cream in prurigo nodularis (PN) are ongoing. Povorcitinib (INCB54707) The Phase 2, randomized, double-blind, placebo-controlled, dose ranging study evaluating the efficacy and safety of povorcitinib in participants with PN were presented at the 2024 AAD Annual Meeting with the study meeting its primary and secondary endpoints following 16 weeks of treatment across all dosing groups, reinforcing povorcitinib’s potential role in treating PN. A Phase 3 study in PN is expected to initiate in 2024. Two Phase 2 trials in asthma and chronic spontaneous urticaria are enrolling. IAI and Dermatology Programs Indication and status Ruxolitinib cream (Opzelura ® ) 1 (JAK1/JAK2) Atopic dermatitis: Phase 3 pediatric study (TRuE-AD3) Vitiligo: Approved in the U.S. and Europe Lichen planus: Phase 2 Lichen sclerosus: Phase 2 Hidradenitis suppurativa: Phase 2; Phase 3 expected to initiate in 2025 Prurigo nodularis: Phase 3 (TRuE-PN1, TRuE-PN2) Ruxolitinib cream + UVB (JAK1/JAK2 + phototherapy) Vitiligo: Phase 2 Povorcitinib (JAK1) Hidradenitis suppurativa: Phase 3 (STOP-HS1, STOP-HS2) Vitiligo: Phase 3 (STOP-V1, STOP-V2) Prurigo nodularis: Phase 3 expected to initiate in 2024 Asthma: Phase 2 Chronic spontaneous urticaria: Phase 2 INCB000262 (EP262) (MRGPRX2) Chronic spontaneous urticaria: Phase 2 Chronic inducible urticaria: Phase 1b Atopic dermatitis: Phase 2a INCB000547 (EP547) (MRGPRX4) Cholestatic pruritus: Phase 2a INCA034460 (anti-IL-15Rβ) 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 Partnered Partnered Programs Indication and Phase Ruxolitinib (Jakavi ® ) 1 (JAK1/JAK2) Acute and chronic GVHD: Approved in Europe and Japan Baricitinib (Olumiant ® ) 2 (JAK1/JAK2) AD: Approved in Europe and Japan Severe alopecia areata (AA): Approved in the U.S., Europe and Japan Capmatinib (Tabrecta ® ) 3 (MET) NSCLC (with MET exon 14 skipping mutations): Approved in the U.S., Europe and Japan 1 Ruxolitinib (Jakavi ® ) licensed to Novartis ex-U.S. for use in hematology and oncology excluding topical administration. 2 Baricitinib (Olumiant ® ) licensed to Lilly: approved as Olumiant in multiple territories globally for certain patients with moderate-to-severe rheumatoid arthritis; approved as Olumiant in EU and Japan for certain patients with atopic dermatitis. 3 Capmatinib (Tabrecta ® ) licensed to Novartis. 2024 Second Quarter Financial Results The financial measures presented in this press release for the three and six months ended June 30, 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 June 30, Six Months Ended June 30, 2024 2023 2024 2023 Total GAAP revenues $ 1,043,759 $ 954,610 $ 1,924,648 $ 1,763,283 Total GAAP operating (loss) income (478,130 ) 193,780 (386,232 ) 218,550 Total Non-GAAP operating (loss) income (378,801 ) 262,058 (217,618 ) 351,787 GAAP net (loss) income (444,601 ) 203,548 (275,053 ) 225,251 Non-GAAP net (loss) income (396,132 ) 223,029 (263,413 ) 307,606 GAAP basic EPS $ (2.04 ) $ 0.91 $ (1.24 ) $ 1.01 Non-GAAP basic EPS $ (1.82 ) $ 1.00 $ (1.19 ) $ 1.38 GAAP diluted EPS 1 $ (2.04 ) $ 0.90 $ (1.24 ) $ 1.00 Non-GAAP diluted EPS 1 $ (1.82 ) $ 0.99 $ (1.19 ) $ 1.36 1. All stock options and stock awards were excluded from the diluted share calculation for the three and six months ended June 30, 2024 because their effect would have been anti-dilutive, as we were in a net loss position. 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 2024 2023 2024 2023 Net product revenues: Jakafi $ 705,973 $ 682,384 3 % 3% $ 1,277,812 $ 1,262,353 1 % 1% Opzelura 121,695 80,233 52 % 52% 207,419 136,785 52 % 52% Iclusig 26,862 29,087 (8 %) (7%) 57,205 56,772 1 % —% Pemazyre 20,269 21,572 (6 %) (6%) 37,945 44,047 (14 %) (14%) Minjuvi/ Monjuvi 31,116 13,159 136 % 137% 54,990 19,715 179 % 179% Zynyz 651 570 14 % NM 1,118 570 96 % NM Total net product revenues 906,566 827,005 10 % 10% 1,636,489 1,520,242 8 % 8% Royalty revenues: Jakavi 99,317 90,448 10 % 14% 188,912 167,140 13 % 16% Olumiant 31,702 32,009 (1 %) 4% 62,291 66,164 (6 %) (3%) Tabrecta 5,298 4,799 10 % NA 10,532 8,976 17 % NA Pemazyre 876 349 151 % NM 1,424 761 87 % NM Total royalty revenues 137,193 127,605 8 % 263,159 243,041 8 % Total net product and royalty revenues 1,043,759 954,610 9 % 1,899,648 1,763,283 8 % Milestone and contract revenues — — — % —% 25,000 — NM NM Total GAAP revenues $ 1,043,759 $ 954,610 9 % $ 1,924,648 $ 1,763,283 9 % NM = not meaningful NA = not available 1. Percentage change in constant currency is calculated using 2023 foreign exchange rates to recalculate 2024 results. Product and Royalty Revenues Product revenues and product and royalty revenues for the quarter ended June 30, 2024 increased 10% and 9%, respectively, over the prior year comparative period, primarily driven by the following; Jakafi net product revenue increased 3% driven by a 9% increase in paid demand. Year over year net product revenue growth was lower than paid demand growth due to higher channel inventory levels at the end of the second quarter of 2023 versus the same period of 2024. Channel inventory at the end of the second quarter of 2024 was within the normal range. Opzelura net product revenue increased 52% due to continued growth in new patient starts and refills. Minjuvi/Monjuvi net product revenue increased 136% following the acquisition of the exclusive global rights to tafasitamab in February 2024. Jakavi royalty revenues increased 10%. Operating Expenses Operating Expense Summary (unaudited, in thousands) Three Months Ended June 30, % Change Six Months Ended June 30, % Change 2024 2023 2024 2023 GAAP cost of product revenues $ 76,634 $ 68,326 12 % $ 137,590 $ 125,148 10 % Non-GAAP cost of product revenues 1 70,899 62,150 14 % 125,858 112,819 12 % GAAP research and development 1,138,380 400,750 184 % 1,567,640 807,391 94 % Non-GAAP research and development 2 1,089,089 367,921 196 % 1,477,526 743,541 99 % GAAP selling, general and administrative 305,982 283,929 8 % 606,238 599,535 1 % Non-GAAP selling, general and administrative 3 262,572 263,030 — % 539,907 557,047 (3 %) GAAP (gain) loss on change in fair value of acquisition-related contingent consideration 893 8,374 (89 %) 437 14,570 (97 %) Non-GAAP (gain) loss on change in fair value of acquisition-related contingent consideration 4 — — — % — — — % GAAP (profit) and loss sharing under collaboration agreements — (549 ) — % (1,025 ) (1,911 ) (46 %) 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, and Escient acquisition related compensation expense related to cash settled unvested Escient equity awards and severance payments. 4 Non-GAAP (gain) loss on change in fair value of acquisition-related contingent consideration is null. Cost of product revenues GAAP and Non-GAAP cost of product revenues for the quarter ended June 30, 2024 increased 12% and 14%, respectively, compared to the same period in 2023 primarily due to growth in net product revenues. Research and development expenses GAAP and Non-GAAP research and development expense for the quarter ended June 30, 2024 increased 184% and 196%, respectively, compared to the same period in 2023 primarily due to $679.4 million of expense relating to the IPR&D assets acquired in the Escient acquisition, $12.5 million of Escient acquisition related compensation expense related to cash settled unvested Escient equity awards and severance payments, as well as continued investment in our late stage development assets. Excluding the upfront consideration paid related to the Escient transaction and other upfront and milestone payments, research and development expense for the quarter ended June 30, 2024 increased 13% compared to the same period in 2023 due to continued investment in our late stage development assets and timing of certain expenses. Selling, general and administrative expenses GAAP selling, general and administrative expenses for the quarter ended June 30, 2024 increased 8% compared to the same period in 2023 primarily due to $21.5 million of Escient acquisition related compensation expense related to cash settled unvested Escient equity awards and severance payments and timing of consumer marketing activities and of certain other expenses. Excluding the upfront consideration paid related to the Escient transaction, selling, general and administrative expenses for the quarter ended June 30, 2024 were flat compared to the same period in 2023. Other Financial Information Change in fair value of acquisition-related contingent consideration The change in fair value of contingent consideration during the quarter ended June 30, 2024, compared to the same period in 2023, was due primarily to fluctuations in foreign currency exchange rates impacting future revenue projections of Iclusig. Operating income GAAP and Non-GAAP operating income for the three months ended June 30, 2024 decreased 347% and 245%, respectively, compared to the same period in 2023, driven primarily by the aforementioned costs relating to the Escient acquisition. Provision for income taxes The income tax expense for the three months ended June 30, 2024 was $54.8 million on a pre-tax loss of $389.8 million primarily due to the impact of non-tax deductible charges of $710.9 million associated with the acquisition of Escient. Cash, cash equivalents and marketable securities position As of June 30, 2024 and December 31, 2023, cash, cash equivalents and marketable securities totaled $1.4 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 during June 2024, and the total cash consideration paid to Escient shareholders of $783 million. Share Repurchase In June 2024, Incyte completed a $2.0 billion share repurchase reflecting our confidence in the future outlook of our business, the strength of our commercial portfolio and the clinical development pipeline. In total, approximately 33.3 million shares of common stock were repurchased at $60.00 per share and represented approximately 14.8% of our common shares outstanding at the time of the repurchase. As of June 30, 2024, there were 191.6 million common shares outstanding. 2024 Financial Guidance Incyte is raising the low end of its full year 2024 Jakafi revenue guidance as well as updating its full year 2024 research and development guidance to reflect the ongoing impact of the acquisition of Escient Pharmaceuticals. The research and development guidance excludes $691 million of upfront consideration recorded relating to the acquisition of Escient Pharmaceuticals. Incyte is maintaining its full year 2024 other hematology/oncology revenue guidance, as well as its cost of product revenue and selling, general and administrative guidance. Incyte’s guidance is summarized below. Guidance does not include revenue from any potential new product launches or the impact of any potential future strategic transactions. Current Previous Jakafi net product revenues $2,710 - $2,750 million $2,690 - $2,750 million Other Hematology/Oncology net product revenues (1) Unchanged $325 - $360 million GAAP Cost of product revenues Unchanged 7 – 8% of net product revenues Non-GAAP Cost of product revenues (2) Unchanged 6 – 7% of net product revenues GAAP Research and development expenses $1,755 - $1,800 million $1,720 - $1,760 million Non-GAAP Research and development expenses (3) $1,615 - $1,655 million $1,580 - $1,615 million GAAP Selling, general and administrative expenses Unchanged $1,210 - $1,240 million Non-GAAP Selling, general and administrative expenses (3) Unchanged $1,115 - $1,140 million 1 Pemazyre in the U.S., EU and Japan; 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, 13747471. 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, 13747471. 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. In the United States, Monjuvi ® (tafasitamab-cxix) received accelerated approval by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). In Europe, Minjuvi ® (tafasitamab) received conditional Marketing Authorization from the European Medicines Agency in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for ASCT. 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 and the Pemazyre logo are registered trademarks of Incyte. * Pemazyre ® (pemigatinib) [Package Insert]. Wilmington, DE: Incyte; 2020. About Iclusig ® (ponatinib) tablets Ponatinib (Iclusig ® ) 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-dlwr), 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 and the Zynyz logo are registered trademarks of Incyte. Forward-Looking Statements Except for the historical information set forth herein, the matters set forth in this press 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 2024, including its expectations regarding sales of Jakafi; expectations regarding demand for and sales of Opzelura, among other products; expectations regarding reimbursement for Opzelura in Europe; where we intend to focus R&D efforts; plans to deliver sustainable innovation through 2028 and beyond; expectations regarding the potential and progress of our pipeline, including expectations for ruxolitinib cream, povorcitinib, INCB000262, INCB000547, axatilimab, mCALR, JAK2V617Fi, retifanlimab, INCB123667, KRASG12Di and our TGF-β program; Incyte’s ability to develop new transformative therapies to treat myeloid disease and cure MPNs; expectations regarding ongoing clinical trials and clinical trials to be initiated; expectations regarding data flow/readouts; expectations regarding regulatory filings, potential regulatory approvals and potential product launches; and expectations regarding 2024 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 possibility that results of clinical trials will be negative and/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 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 supply of and/or 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, 2023. 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 June 30, Six Months Ended June 30, 2024 2023 2024 2023 GAAP GAAP Revenues: Product revenues, net $ 906,566 $ 827,005 $ 1,636,489 $ 1,520,242 Product royalty revenues 137,193 127,605 263,159 243,041 Milestone and contract revenues — — 25,000 — Total revenues 1,043,759 954,610 1,924,648 1,763,283 Costs, expenses and other: Cost of product revenues (including definite-lived intangible amortization) 76,634 68,326 137,590 125,148 Research and development 1,138,380 400,750 1,567,640 807,391 Selling, general and administrative 305,982 283,929 606,238 599,535 Loss on change in fair value of acquisition-related contingent consideration 893 8,374 437 14,570 (Profit) and loss sharing under collaboration agreements — (549 ) (1,025 ) (1,911 ) Total costs, expenses and other 1,521,889 760,830 2,310,880 1,544,733 (Loss) income from operations (478,130 ) 193,780 (386,232 ) 218,550 Interest income and other, net 49,769 42,668 94,513 75,541 Interest expense (657 ) (655 ) (1,087 ) (1,124 ) Realized and unrealized gain on equity investments 39,241 41,811 139,188 36,493 (Loss) income before provision for income taxes (389,777 ) 277,604 (153,618 ) 329,460 Provision for income taxes 54,824 74,056 121,435 104,209 Net (loss) income $ (444,601 ) $ 203,548 $ (275,053 ) $ 225,251 Net (loss) income per share: Basic $ (2.04 ) $ 0.91 $ (1.24 ) $ 1.01 Diluted $ (2.04 ) $ 0.90 $ (1.24 ) $ 1.00 Shares used in computing net (loss) income per share: Basic 218,175 223,248 221,329 223,104 Diluted 218,175 225,649 221,329 225,541 INCYTE CORPORATION CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands) June 30, 2024 December 31, 2023 ASSETS Cash, cash equivalents and marketable securities $ 1,449,500 $ 3,656,043 Accounts receivable 739,050 743,557 Property and equipment, net 762,009 751,513 Finance lease right-of-use assets, net 25,535 25,535 Inventory 355,972 269,937 Prepaid expenses and other assets 231,504 236,782 Short and long term equity investments 99,543 187,716 Other intangible assets, net 113,536 123,545 Goodwill 155,593 155,593 Deferred income tax asset 729,561 631,886 Total assets $ 4,661,803 $ 6,782,107 LIABILITIES AND STOCKHOLDERS’ EQUITY Accounts payable, accrued expenses and other liabilities $ 1,438,125 $ 1,347,669 Finance lease liabilities 32,619 32,601 Acquisition-related contingent consideration 194,000 212,000 Stockholders’ equity 2,997,059 5,189,837 Total liabilities and stockholders’ equity $ 4,661,803 $ 6,782,107 INCYTE CORPORATION RECONCILIATION OF GAAP NET (LOSS) INCOME TO SELECTED NON-GAAP ADJUSTED INFORMATION (unaudited, in thousands, except per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 GAAP Net (Loss) Income $ (444,601 ) $ 203,548 $ (275,053 ) $ 225,251 Adjustments 1 : Non-cash stock compensation from equity awards (R&D) 2 34,541 32,829 71,333 63,850 Non-cash stock compensation from equity awards (SG&A) 2 21,748 20,899 44,121 42,488 Non-cash stock compensation from equity awards (COGS) 2 351 792 964 1,561 Non-cash interest 3 144 139 252 247 Realized and unrealized gain on equity investments 4 (39,241 ) (41,811 ) (139,188 ) (36,493 ) Amortization of acquired product rights 5 5,384 5,384 10,768 10,768 Loss on change in fair value of contingent consideration 6 893 8,374 437 14,570 MorphoSys transition costs 7 2,373 — 6,952 — Escient acquisition related compensation expense 8 34,039 — 34,039 — Tax effect of Non-GAAP pre-tax adjustments 9 (11,763 ) (7,125 ) (18,038 ) (14,636 ) Non-GAAP Net (Loss) Income 9 $ (396,132 ) $ 223,029 $ (263,413 ) $ 307,606 Non-GAAP net (loss) income per share: Basic $ (1.82 ) $ 1.00 $ (1.19 ) $ 1.38 Diluted 10 $ (1.82 ) $ 0.99 $ (1.19 ) $ 1.36 Shares used in computing Non-GAAP net (loss) income per share: Basic 218,175 223,248 221,329 223,104 Diluted 10 218,175 225,649 221,329 225,541 1 Included within the Milestone and contract revenues line item in the Condensed Consolidated Statements of Operations (in thousands) for the three and six months ended June 30, 2024 are milestones of $0 and $25,000 earned from our collaborative partners, as compared to no milestones earned for the three and six months ended June 30, 2023. Included within the Research and development expenses line item in the Condensed Consolidated Statements of Operations (in thousands) for the three and six months ended June 30, 2024 are upfront consideration and milestones of $414 and $1,414, respectively, related to our collaborative partners as compared to upfront consideration and milestones of $7,000 and $9,700, respectively, for the three and six months ended June 30, 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 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 (Gain) loss on change in fair value of acquisition-related contingent consideration line item in the Condensed Consolidated Statements of Operations. 7 Included within the Research and development line item in the Condensed Consolidated Statements of Operations is $2,232 and $6,263 for the three and six months ended June 30, 2024, respectively, and included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations is $141 and $689 for the three and six months ended June 30, 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. 8 Included within the Research and development line item in the Condensed Consolidated Statements of Operations is $12,518 for the three and six months ended June 30, 2024, and included within the Selling, general and administrative expenses line item in the Condensed Consolidated Statements of Operations is $21,521 for the three and six months ended June 30, 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. 9 Income tax effects of Non-GAAP pre-tax adjustments are calculated using an estimated annual effective tax rate, taking into consideration any permanent items and valuation allowances against related deferred tax assets. The Non-GAAP net income for the three months ended March 31, 2024 should have been $132,719 compared to the $145,269 previously disclosed to correct a transposition error in the tax effect of Non-GAAP pre-tax adjustments. For the three months ended March 31, 2024, the tax effect of Non-GAAP pre-tax adjustments should have been ($6,275) instead of $6,275. 10. All stock options and stock awards were excluded from the diluted share calculation for the three and six months ended June 30, 2024 because their effect would have been anti-dilutive, as we were in a net loss position.

作者｜小鱼 在药物开发过程中，商业交易与科学突破同样至关重要。 很多当今“最赚钱”的药物，如Keytruda、Enbrel，都是通过并购才得以走到大众面前，获得今日的辉煌成就。或许在今年上半年的并购案中，也能出现“爆款”明星药品。 2024年上半年，已经有25家biotech被收购，整理如下（按时间排序）： 从表格可见，在25个Biotech并购案中，并购金额最大三起为Vertex收购Alpine（ 49亿美元）、Gilead收购CymaBay（43亿美元）、诺华收购Morphosys（29亿美元）。6起并购案超过20亿美元，15起并购案超过10亿美元，分布在癌症、免疫疾病、罕见病、视网膜疾病、肝脏疾病领域。从中，我们能看到并购活动不仅集中在肿瘤和免疫疾病领域，还扩展到了肝脏疾病、眼科疾病以及罕见病等。其次，跨国药企重视新型药物技术，如双抗/三抗疗法、ADC药物、靶向放射性药物、RNA药物等。   01   6.8亿美元：默沙东收购Harpoon 1月8日，默沙东（MSD）公司宣布以6.8亿美元收购Harpoon Therapeutics。默沙东将获得一系列T细胞接合器在研疗法，包括处于1/2期临床开发阶段的HPN328，扩展其肿瘤学研发管线。 HPN328（此后称为MK-6070）是基于TriTAC平台构建的DLL3靶向T细胞结合器，通过靶向激活T细胞，对表达DLL3的肿瘤细胞进行杀伤。DLL3是一种抑制性Notch配体，在小细胞肺癌（SCLC）和神经内分泌肿瘤中高度表达。目前，HPN328正处于临床开发阶段，用于治疗SCLC/NEPC与其他神经内分泌肿瘤。其他候选药物包括HPN217，一种靶向B细胞成熟抗原（BCMA）的T细胞接合剂，目前处于一期临床开发阶段，用于治疗复发/难治性多发性骨髓瘤患者，以及几种临床前阶段候选药物，包括HPN601，一种条件激活的靶向上皮细胞粘附分子（EpCAM），用于治疗某些表达EpCAM的肿瘤患者。   02   20亿美元：强生收购Ambrx 1月8日，强生（Johnson & Johnson）宣布与Ambrx Biopharma达成最终协议，将斥资20亿美元收购Ambrx。此次收购，强生的重点是加速ARX517在晚期前列腺癌中的1/2期试验APEX01的进展，同时推进一系列新颖的候选产品。 ARX517由人源化的抗PSMA单抗与Ambrx专有的强效微管抑制剂AS269连接而成。在临床前研究中，ARX517的癌细胞杀伤有效载荷AS269通过单抗释放到癌细胞中时具有很强的细胞毒性。ARX517的位点特异性连接、稳定的共轭化学性质和不可裂解的连接体使ADC具有均匀的药物抗体比、类似单抗的生物物理特性和优异的稳定性。因此，Ambrx公司认为ARX517可以促进对肿瘤细胞的高度特异性杀伤，同时将脱靶毒性降至最低。ARX517有潜力成为“first-in-class”和“best-in-class”的抗PSMA ADC，以满足转移性去势抵抗性前列腺癌（mCRPC）患者的巨大未竟医疗需求。   03   2.5亿美元：诺华收购Calypso 1月8日，诺华宣布将以2.5亿美元收购Calypso生物技术公司(Calypso Biotech)，并支付高达1.75亿美元的开发里程碑付款。此次收购，诺华将获得Calypso唯一一个项目CALY-002。 CALY-002是一种潜在的同类最佳治疗抗体，可结合并中和IL-15。IL-15是一种广泛的、未开发的免疫轴，在许多慢性自身免疫性疾病中控制屏障功能和下游免疫级联反应。CALY-002目前正在Celiac病和嗜酸性粒细胞性食管炎患者的1b期试验中进行评估。   04   10亿美元：GSK收购Aiolos 1月9日，GSK宣布已与一家专注于解决呼吸和炎症性疾病公司Aiolos达成收购协议，GSK将支付后者10亿美元的预付款和高达4亿美元的成功监管里程碑付款。此次收购使GSK获得了Aiolos的候选药物AIO-001（SHR-1905），扩大了GSK的呼吸道疾病管线。 AIO-001是一种潜在“best-in-class”的长效抗胸腺基质淋巴细胞生成素（TSLP）单克隆抗体，由于其药效具差异性、半衰期长，每6个月只需给药1次。TSLP是经过临床验证的哮喘治疗靶点，无论患者的生物标志物状态如何。靶向TSLP通路解决了主要过敏性和炎症性反应的关键驱动因素。AIO-001目前处于二期临床阶段，用于治疗成年哮喘者，并有可能用于其他适应症，包括慢性鼻窦炎伴鼻息肉。   05   3.48亿美元：太阳制药收购Taro 1月17日，印度第一大仿制药巨头太阳制药（Sun Pharma）以3.48亿美元正式全资收购以色列老牌皮肤科仿制药公司Taro Pharmaceutical。此前，太阳制药已经拥有Taro 78.5%的股份。 Taro Pharmaceutical Industries 是一家以研究为基础的制药商，在纽约证券交易所上市。公司开发、生产、销售和分销高品质的仿制药、品牌处方药和非处方药产品。该公司拥有 200 多种产品，主要涉及皮肤科、镇痛药、胃药、中枢神经系统、心脏病等多个治疗领域。   06   17亿美元：赛诺菲收购Inhibrx 1月23日，赛诺菲宣布，其与临床阶段生物制药上市公司Inhibrx已达成一项最终协议，将以17美元的股权价值和1.96亿美元的或有价值权益收购Inhibrx，扩赛默飞的单域抗体领域。 INBRX-101是一种重组人AAT-Fc融合蛋白，由2个与人lgG4 Fc结构域连接的重组人AAT分子组成，进过优化，比pdAAT有更长的半衰期和更高的暴露量，防止因氧化而失去活性。目前INBRX-101正在开发用于治疗α-1抗胰蛋白酶缺乏症（AATD），于2022年3月获得FDA的“孤儿药”认定，2023年6月获FDA快速通道指定。Inhibrx临床在研的管线还有DR5激动剂、OX40激动剂。   07   29亿美元：诺华收购Morphosys 2月5日，诺华宣布与Morphosys达成全现金收购协议，收购对价27亿欧元，约合29亿美元。此次诺华收购的重点是Pelabresib——目前全球进展最快的BET抑制剂（Pelabresib），此次收购也将进一步强化诺华在肿瘤领域的布局。 溴结构域和末端外结构域（BET）蛋白家族包括四种蛋白(BRD2,BRD3,BRD4和BRDT)，它们具有表观遗传修饰因子的功能，能够调控一系列异常致癌信号的基因表达途径。Pelabresib是一种BET抑制剂，它可以选择性地与BET蛋白结合，降低癌症中异常表达基因的表达，从而抑制肿瘤的发生发展。目前BET抑制剂已被证明可以靶向多种MF驱动机制，与JAKi联合治疗具有协同作用。pelabresib联合芦可替尼治疗初治骨髓纤维化患者三期研究达到主要终点。   08   43亿美元：吉利德收购CymaBay 2月12日，吉利德科学公司（Gilead Sciences）和CymaBay Therapeutics宣布达成最终协议，吉利德将以总金额43亿美元收购CymaBay。吉利德将获得Cymabay的核心管线PPARδ激动剂Seladelpar，以扩充其肝脏产品线。 Seladelpar为一在研、口服、潜在“first-in-class”的强效选择性过氧化物酶体增殖物活化受体（PPARδ）激动剂。PPARδ表达在肝脏的多种细胞类型中，对调控胆汁酸合成、炎症、纤维化过程的多种基因有调节作用。也在2月12日收购协议达成日，CymaBay宣布美国FDA接受seladelpar用于治疗原发性胆汁性肝硬化患者，包括其瘙痒症状（pruritus）的新药申请（NDA），并授予其优先审评资格，该药物的PDUFA目标日期为2024年8月14日。   09   0.9亿美元：诺华收购IFM Due 3月13日，诺华宣布将收购私人控股公司IFM Therapeutics的子公司IFM Due，IFM Due将获得9000万美元预付款，并有资格获得高达7.45亿美元的里程碑付款。根据收购协议，诺华将获得IFM Due的STING拮抗剂产品组合的全部权利。 IFM Due专注于针对cGAS-STING通路引发的先天免疫系统异常炎症反应开发小分子口服候选药物。cGAS-STING通路通过侦测细胞质内的DNA（细胞危险信号）并启动STING依赖性炎症反应而在先天免疫系统中发挥作用。由于突变或线粒体功能障碍等原因所导致该通路不正常的激活，会引起过度的干扰素/细胞因子信号传导，进而导致多种严重炎症疾病的发生。目前该抑制cGAS/STING途径的免疫疗法还在临床前阶段。   10   8亿美元：阿斯利康收购Amolyt 3月14日，阿斯利康宣布已达成最终协议，拟斥资10.5亿美元收购Amolyt Pharma，包括8亿美元的预付款以及2.5亿美元的特定里程碑付款。这次收购讲使AZ获得Amolyt研发项目Eneboparatide（AZP-3601）。 Eneboparatide是一种研究性治疗肽，旨在与甲状旁腺激素（PTH）受体的特定构型高亲和力结合，以在血液中产生持续稳定的钙水平，从而管理甲状旁腺功能减退症的症状，并通过恢复肾脏对钙的重吸收来限制尿钙排泄，预防肾功能的逐渐下降和慢性肾病的发展。Amolyt Pharma公司与5月2日宣布，Eneboparatide已获得FDA授予的快速通道指定，三期Calypso试验正在美国、欧洲、加拿大和英国的50多个中心进行。   11   24亿美元：阿斯利康收购Fusion 3月19日，阿斯利康宣布将斥资24亿美元，收购专注于开发新一代放射性偶联药物（RDC）的生物制药公司Fusion Pharmaceuticals。这次收购是阿斯利康在核药领域的又一次重大布局。 Fusion核心产品FPI-2265是一款针对前列腺特异性膜抗原（PSMA）的靶向药物，目前正处于二期临床开发阶段，用于治疗转移性去势抵抗性前列腺癌（mCRPC）。这一药物的研发，体现了核药在癌症治疗中的巨大潜力和独特优势。另一款临床在研产品为FPI-1434，靶向表达IGF-1R（IGF-1R是一种在许多肿瘤类型上过表达的受体）癌细胞并递送发射α的医用同位素，目前正处于一期临床开发阶段。   12   1.38亿美元：艾伯维收购Landos 3月25日，艾伯维宣布将收购Landos Biopharma，获得其炎症性肠病研发管线NX-13，艾伯维支付1.375亿美元现金，以及7500万美元里程碑付款。 NX-13是一款口服NLRX1激动剂，开发用于治疗溃疡性结肠炎和克罗恩病。NX-13可以通过胞外、胞内两种路径来减少炎症循环，发挥双重机制，具有抗炎作用并促进上皮修复的潜力。目前处于二期临床阶段，溃疡性结肠炎二期临床数据预计2024年四季度读出。   13   18亿美元：Genmab收购ProfoundBio 4月3日，Genmab和ProfoundBio（普方生物）共同宣布签署了一项确定性协议，Genmab将以18亿美元现金收购ProfoundBio。此次收购将使Genmab在全球范围内拥有三个临床开发候选药物的权利，包括rinatabart sesutecan（Rina-S），以及ProfoundBio的新型抗体-药物偶联物（ADC）技术平台。 Rina-S是一种新型的、下一代的、潜在的同类最佳Topo1 ADC，靶向叶酸受体α（FRα）。FRα在一系列实体瘤中过表达，在正常组织中表达有限，因此是ADC有吸引力的靶标。Rina-S由人FRα的单克隆抗体、一种新型可裂解亲水接头、拓扑异构酶1抑制剂有效载荷Exatecan组成。目前正在招募晚期实体瘤患者进行首次人体1/2期研究。此外，普方生物披露的在研药物还有靶向CD70的ADC、靶向PTK7的ADC、靶向EGFR和cMET的双特异性ADC等。   14   49亿美元：Vertex收购Alpine 4月10日，Vertex宣布，将斥资49亿美元收购Alpine immune science，收获该公司主打产品Povetacicept（ALPN-303），并扩大其肾脏和免疫系统疾病的业务。 Povetacicept是BAFF/APRIL双重拮抗剂，BAFF/APRIL可促进B细胞、T细胞和髓系细胞的活化、分化和存活，在多种自身免疫性疾病的发病机制中发挥关键作用，包括但不限于系统性红斑狼疮（SLE）和IgA肾病等。目前Povetacicept有3条临床管线：针对自身免疫性肾小球肾炎处于临床二期阶段、针对系统性红斑狼疮（SLE）处于临床一期阶段、针对自身免疫性血细胞减少症处于临床二期阶段。   15   7.5亿美元：Incyte收购Escient 4月23日，Incyte和Escient Pharmaceuticals宣布达成最终协议，Incyte同意以约7.5亿美元款项收购Escient，并收获该公司两款潜在FIC小分子疗法EP262和EP547，扩大其在炎症与自身免疫疾病领域的研发管线。 EP262是一种强效、高选择性、每日一次的小分子MRGPRX2拮抗剂，通过阻断MRGPRX2和肥大细胞颗粒释放，EP262有潜力治疗多种肥大细胞介导的疾病，包括特应性皮炎（AD）、慢性诱发性荨麻疹（CIndU）和慢性自发性荨麻疹（CSU），目前均处于临床一期阶段。EP547则是一种强效、高选择性MRGPRX4小分子拮抗剂，可阻断各种胆汁酸、胆红素和尿胆素激活MRGPRX4，有望成为治疗胆汁淤积性和尿毒症性瘙痒症的潜在有效疗法。   16   24亿美元：小野制药收购Deciphera 4月29日，小野制药（ONO Pharmaceutical）宣布以24亿美元收购Deciphera Pharmaceuticals，届时Deciphera将成为小野制药全资子公司。这一收购将增强小野制药的肿瘤学研发管线。 Deciphera公司擅长激酶药物发现和开发，其小分子抑制剂Qinlock已经在美国和其他40多个国家和地区获批上市，用于治疗经治胃肠间质瘤（GIST）患者。Deciphera还拥有CSF-1R抑制剂、ULK抑制剂、pan-RAF抑制剂、pan-KIT抑制剂、GCN2激活剂等多种研发管线，包括Vimseltinib、DCC-3116（一种ULK抑制剂）以及多个其他的肿瘤学候选药物。   17   10亿美元：诺华收购Mariana 5月2日，专注于开发新型放射性配体疗法（RLT）的生物技术公司Mariana Oncology宣布，诺华将以10亿美元的预付款和高达7.5亿美元的潜在里程碑付款收购该公司。次收购将Mariana Oncology的创新放射性药物管线和平台与诺华公司成熟的临床开发和商业化专业技术相结合。 Mariana 公司由Atlas Venture、Access Biotechnology和RA Capital Management于2021年创立，并从Deep Track Capital和Forbion等其他顶级投资者处筹集了额外资金。 Mariana Oncology公司已开发出一系列基于多肽的新型放射性药物，可用于治疗多种实体瘤癌症，并在生产能力、广泛的同位素供应链和新型配方方面进行了投资，以提高最终产品的保质期。公司的领先项目MC-339是一款RTL，专门针对小细胞肺癌。   18   8.5亿美元：强生收购Proteologix 5月16日，强生宣布以8.5亿美元收购专注于开发免疫介导疾病双特异性抗体的私营生物技术公司Proteologix，已签订最终协议，并有可能支付额外的里程碑付款。 Proteologix的研发管线中包括PX128，这是一种靶向IL-13和TSLP的双特异性抗体，准备进入针对中度至重度特应性皮炎（AD）和中度至重度哮喘的一期开发。另一款在研疗法PX130是一种靶向IL-13和IL-22的双特异性抗体，正在进行针对中度至重度AD的临床前开发。由于AD和哮喘都是异质性疾病，不同患者亚群的疾病由不同信号通路驱动，靶向多条信号通路有可能实现更好的疗效和疾病缓解。 PX128和PX130之外，此外收购还将为强生提供其他双特异性抗体研发项目，这些项目可应用于各种其他疾病，进一步增强公司在开发新型双特异性治疗方案方面的能力。   19   11.5亿美元：渤健收购HI-Bio 5月22日，Biogen（渤健）和免疫疗法公司Human Immunology Biosciences（HI-Bio）宣布，两家公司已达成收购协议。根据协议条款，渤健将向HI-Bio支付11.5亿美元的预付款。如果Felzartamab项目达成某些开发里程碑，HI-Bio还有资格获得高达6.5亿美元的额外款项，总交易款项可能高达18亿美元。 HI-Bio的主要资产Felzartamab（菲泽妥单抗）是一款靶向CD38的单抗，主要用于开发自免适应症。目前，Felzartamab用于原发性膜性肾病、抗体介导的排斥反应、IgA肾病等临床试验处于二期阶段，狼疮性肾炎处于临床一期阶段。 除了Felzartamab外，HI-Bio的管线还包括izastobart/HIB210，这是一种C5aR1靶向抗体，目前处于临床一期试验阶段，具有用于治疗一系列补体介导疾病的潜力。HI-Bio还拥有处于发现阶段的肥大细胞靶向管线，该管线亦具有在多种免疫介导疾病中应用的潜力。   20   12.5亿美元：强生收购YJT 5月28日，强生宣布已与Numab therapeutics达成最终协议，将以约12.5亿美元的现金收购其全资子公司Yellow Jersey therapeutics（YJT），该公司将分拆给Numab的股东。将其新型、在研一流双特异性抗体NM26的全球权利收入囊下。 NM26是一种用于治疗特应性皮炎（AD）的同类首创双特异性抗体，靶点是AD中两种经临床验证的通路-IL-4Rα和IL-31，前者会引发Th2介导的皮肤炎症，后者会影响皮肤骚痒和随后的骚抓，从而使病情恶化。NM26除了有可能改变AD的治疗标准外，对其他涉及Th2炎症和骚痒的炎症性皮肤病也有疗效。   21   11亿美元：旭化成收购Calliditas 5月28日，日本公司旭化成注株式会社（Asahi Kasei）拟提出以118亿瑞典克朗（约合11亿美元）收购瑞典药企Calliditas Therapeutics，以扩大在肾脏和自身免疫性疾病领域的产品规模，并在欧洲建立业务，扩充研发管线。同日，Calliditas宣布已经接受旭化成的收购要约。该收购要约受到了Calliditas董事会的支持。 Calliditas在售产品是Nefecon（布地奈德肠溶胶囊）。作为全球第一款上市的IgA肾病疗法，Nefecon通过特殊的制作工艺，将布地奈德靶向释放于回肠末端的黏膜B细胞，胶囊溶解后，三层包衣微丸持续稳定释放布地奈德，高浓度覆盖整个靶区域，从而减少诱发IgA肾病的半乳糖缺陷的IgA1抗体产生，达到治疗IgA肾病的作用。 目前，Calliditas主打在研药品为NOX1/4抑制剂Setanaxib（潜在FIC药物）。该产品用于治疗一系列纤维化罕见疾病和实体瘤，预计今年将有三项临床二期研究结果公布，分别针对原发性胆汁性胆管炎、特发性肺纤维化以及头颈部鳞状细胞癌。   22   13亿美元：默沙东收购EyeBio 5月29日，默沙东（MSD）和EyeBiotech Limited（EyeBio）联合宣布，两家公司已达成最终协议，默沙东将通过一家子公司以13亿美元的前付款和高达17亿美元的里程碑付款收购EyeBio公司。本次收购潜在总价值30亿美元。 通过这一收购，默沙东将收获EyeBio的先导候选药物Restoret（EYE103），一种治疗糖尿病性黄斑水肿（DME）和新生血管性年龄相关性黄斑病变性（NVAMD）的新型晚期候选药物，以及一种针对视网膜疾病的临床前管线。 Restoret是一种四价、三特异性Wnt抗体，可以同时与受体LRP5和FZD4结合，激活Wnt信号通路。Wnt信号通路在恢复和维持血网膜屏障方面具有关键性作用。临床前研究显示，Restoret可持久减少DME和额NVAMD相关的视网膜血管渗漏。Restoret预计将于2024年下半年进入糖尿病性黄斑水肿关键研究。   23   0.5亿美元：GSK收购Elsie 6月7日，GSK宣布以5000万美元的款项收购了致力于开发寡核苷酸疗法的Elsie Biotechnologies公司。此次收购使GSK能够整合Elsie的寡核苷酸发现、合成和递送技术，以增强GSK平台的研发能力。 Elsie的发现平台是超高通量专有工艺，能够对寡核苷酸化学空间进行全面评估。通过应用专有编码技术，Elsie能够评估所有潜在的序列或化学修饰模式，旨在增强活性、降低毒性并改善寡核苷酸治疗候选药物的递送。此外，Elsie还采用专有的P（V）化学技术，包括一套新型试剂和工艺，通过精确的合成控制合成多种寡核苷酸疗法。   24   3.81亿美元：ANI收购Alimera 6月24日，仿制药公司ANI Pharmaceuticals（ANI）宣布以3.81亿美元收购Alimera Science。 Alimera 是一家全球性的专门从事用于治疗视网膜疾病处方药商业化开发的制药公司，因其两款主要产品而闻名：Iluvien是一种可注射的、非生物降解的氟轻松玻璃体内植入物，用于治疗糖尿病性黄斑水肿 (DME) ，以及慢性非感染性葡萄膜炎(NIU-PS)；Yutiq是一种氟轻松玻璃体内植入物，治疗NIU-PS。   25   2.5亿美元：艾伯维收购Celsius 6月27日，艾伯维（AbbVie）宣布以2.5亿美元款项收购Celsius Therapeutics。艾伯维将收获一款潜在“first-in-class”候选药物CEL383。 CEL383是一种针对TREM1的实验性抗体，已完成治疗炎症性肠病（IBD）的一期临床研究。TREM1已被确认为IBD中的关键致病基因，主要表达于炎性单核细胞和中性粒细胞上。在这些及其他细胞类型中，TREM1位于多个已知炎症通路的上游，能够放大炎症反应。CEL383已被证明可以抑制TREM1信号传导，降低炎症条件下具有高临床相关性的多种炎症介质的水平。   写在最后   2024年上半年生物医药行业发生了25个并购案，其中我们不难看出交易集中在癌症（7起）和免疫系统疾病（11起）上，交易金额随着药物研发平台的含金量、管线的临床进展和临床重大成果而水涨船高。 对于跨国制药巨头来说，并购重组能够获取优质资产，填补专利悬崖带来的销售缺口，并切入新兴赛道，重塑自己的产品管线和销售体系。 对于Biotech企业来说，通过并购实现退出，这不仅为股东带来回报，也为Biotech的早期投资机构提供了退出渠道。同时，也意味着几乎不再面临资本市场的不确定性和资金链的挑战。 如何促成并购案呢？上述成功的并购案例显示，具有创新技术平台和研发管线的企业更受青睐。如Elsie的寡核苷酸合成平台、Mariana的创新放射性药物管线和平台、Ambrx的非天然氨基酸的定点插入技术平台等。因此，面对市场寒冬，Biotech企业需要聚焦核心竞争力，对管线进行评估，避免局限于me-too或fast-follow药物。 资料来源：公司官网、咨询类订阅号 共建Biomedical创新生态圈！ 如何加入BiG会员？