Post-polycythemia vera myelofibrosis

WILMINGTON, Del.--( BUSINESS WIRE )--Incyte (Nasdaq:INCY) today reports 2023 fourth quarter financial results, provides 2024 financial guidance and provides a status update on the Company’s research and development portfolio. "We delivered a strong 2023 with total net product and royalty revenues of $3.7 billion, increasing 14% versus 2022. In the fourth quarter, we achieved for the first time, a new milestone of $1 billion in total quarterly revenues, driven by the continued growth of Jakafi ® (ruxolitinib) and the successful launch of Opzelura ® (ruxolitinib) cream," said Hervé Hoppenot, Chief Executive Officer, Incyte. "Throughout 2023, we focused our R&D efforts on high potential programs and believe we are positioned to deliver more than ten high impact launches by 2030." Key Product Sales Performance Jakafi: Net product revenues for the fourth quarter of 2023 of $695 million; 2023 full year net product revenues of $2.59 billion Fourth quarter 2023 net product revenues grew 7% compared with the fourth quarter of 2022 and grew 8% for the full year 2023 when compared to 2022. Fourth quarter revenues were negatively impacted by an increase in the number of Medicare Part D patients receiving free product and were positively impacted by an increase in channel inventory. Opzelura: Net product revenues for the fourth quarter of 2023 of $109 million; 2023 full year net product revenues of $338 million: Net product revenues of $109 million grew 78% compared with the fourth quarter of 2022, driven by growth in patient demand, refills and expansion in payer coverage as the launch in atopic dermatitis (AD) and vitiligo continues. For the full-year, 2023 net product revenues grew 162% over the prior year to $338 million. On January 31, 2024, Incyte received approval in France to promote and distribute Opzelura for vitiligo under a process called “Accès Direct.” This process is intended to allow for early access to a therapy while a final price is negotiated, which is expected to take up to twelve months. Once price reimbursement is determined, Incyte will begin recognizing revenue in France. Key Recent Updates In February 2024, Incyte entered into an asset purchase agreement with MorphoSys AG which gave Incyte exclusive global rights for tafasitamab, a humanized Fc-modified CD19-targeting immunotherapy marketed in the U.S. as Monjuvi ® (tafasitamab-cxix) and outside of the U.S. as Minjuvi ® (tafasitamab). Under the terms of the agreement, MorphoSys received a payment of $25 million from Incyte, and Incyte gained global development and commercialization rights for tafasitamab. Incyte will recognize revenue and cost for all U.S. commercialization and clinical development and MorphoSys will no longer be eligible to receive future milestone, profit split and royalty payments. In January 2024, Incyte announced the primary endpoint was met in 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. The Phase 2 data is anticipated to be presented at an upcoming scientific meeting in 2024. A Phase 3 study is currently being evaluated. In January 2024, Incyte highlighted promising early clinical efficacy data for its selective inhibitor of CDK2 (INCB123667), which demonstrated its potential use as monotherapy or combination therapy for late-stage cancers. In a Phase 1 study of INCB123667, early clinical activity was observed with several partial responses (PR) achieved in patients with amplification/over expression of CCNE1, a cell cycle regulator and potential predictive biomarker. Tumor shrinkage was observed across multiple tumor types, including CCNE1 patients with ovarian cancer. The safety profile of for INCB123667 aligns with the mechanism of action. Additional data is expected to be presented in 2024. In December 2023, in collaboration with Syndax Pharmaceuticals, the Biologics License Application (BLA) was submitted for axatilimab in chronic graft-versus-host disease (cGVHD) with approval anticipated in the second half of 2024. Plans are underway to initiate two combination trials with axatilimab in cGVHD in mid-2024, including a Phase 2 combination trial with ruxolitinib and a Phase 3 combination trial with steroids. JAK2V617Fi (INCB160058), a potent and selective JAK2 pseudokinase domain binder, cleared the Investigational New Drug (IND) process with the FDA and a Phase 1 study is anticipated to initiate in the first half of 2024. INCB160058 has the potential to be a disease modifying therapy and to address a significant patient population. The JAK2 mutation is found in 55% of primary myelofibrosis, 95% of polycythemia vera and 60% of essential thrombocythemia patients. A Phase 1 study of KRASG12D (INCB161734) in patients with advanced metastatic solid tumors with a KRAS G12D mutation was recently initiated and the first patient was dosed. KRAS mutations are one of the most common genetic abnormalities in cancer, especially pancreatic and colorectal cancers. In December 2023, Incyte received FDA feedback and agreed to the path forward for once daily (QD) ruxolitinib (XR). The potential approval of QD ruxolitinib (XR) is anticipated in approximately two years. Additional Pipeline Updates Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) – key highlights In December 2023, Incyte presented more than 40 hematology and oncology abstracts including a Plenary Scientific Session at the 2023 ASH Annual Meeting. The plenary presentation featured the full data from AGAVE-201 evaluating axatilimab, an anti-CSFR-1R monoclonal antibody, in patients with cGVHD. Other key highlights included additional data from the Phase 1/2 Study of zilurgisertib (INCB000928), Phase 1 data of BETi (INCB057643) and preclinical data of JAK2V617Fi (INCB160058). Combination trials of ruxolitinib twice daily (BID) with zilurgisertib (INCB000928) and BETi (INCB057643) are ongoing and continue to enroll. Incyte anticipates initiating a Phase 3 study for BETi in the second half of 2024 and achieving clinical proof-of-concept for zilurgisertib by mid-2024. The Phase 1 study evaluating the mCALR monoclonal antibody (INCA033989) is ongoing and enrolling patients. MPN and GVHD Programs Indication and Phase Ruxolitinib XR (QD) ( JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD Ruxolitinib + zilurgisertib J AK1/JAK2 + ALK2) Myelofibrosis: Phase 2 Ruxolitinib + INCB57643 ( JAK1/JAK2 + BET) Myelofibrosis: Phase 2 Ruxolitinib + CK0804 1 ( JAK1/JAK2 + CB-Tregs) Myelofibrosis: Phase 1 (LIMBER-TREG108) Axatilimab (anti-CSF-1R) 2 Chronic GVHD: Pivotal Phase 2 (third-line plus therapy) (AGAVE-201); BLA under review in the U.S. Ruxolitinib + axatilimab 2 ( JAK1/JAK2 + anti-CSF-1R) Chronic GVHD: Phase 1/2 in preparation INCA033989 ( mCALR) Myelofibrosis, essential thrombocythemia: Phase 1 INCB160058 ( JAK2V617Fi) Phase 1 1 Development collaboration with Cellenkos, Inc. 2 Clinical development of axatilimab in GVHD conducted in collaboration with Syndax Pharmaceuticals. Other Hematology/Oncology – key highlights CDK2i (INCB123667) In January 2024, Incyte highlighted promising early clinical efficacy data for its selective small molecule inhibitor of CDK2 (INCB123667), which demonstrated its potential use as monotherapy or combination therapy for late-stage cancers. In a Phase 1 study of INCB123667, early clinical activity was observed with several partial responses (PR) achieved in patients with amplification/over expression of CCNE1, a cell cycle regulator and potential predictive biomarker. Tumor shrinkage was observed across multiple tumor types, including CCNE1+ patients with ovarian cancer. The safety profile of for INCB123667 aligns with the mechanism of action. Additional data is expected to be presented in 2024. Oncology Programs Indication and Phase Pemigatinib (Pemazyre ® ) ( FGFR1/2/3) Myeloid/lymphoid neoplasms (MLN): approved in the U.S. and Japan Cholangiocarcinoma (CCA): Phase 3 (FIGHT-302) Glioblastoma: Phase 2 (FIGHT-209) 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. 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) INCB99280 ( Oral PD-L1) Solid tumors (combination): Phase 1 Solid tumors (monotherapy): Phase 2 Cutaneous squamous cell carcinoma (cSCC): Phase 2 INCB99318 ( Oral PD-L1) Solid tumors: Phase 1 INCB123667 ( CDK2i) Solid tumors with Amplification/ Overexpression of CCNE1: Phase 1 INCB161734 ( KRASG12D) Advanced metastatic solid tumors with a KRAS G12D mutation: Phase 1 1 Retifanlimab licensed from MacroGenics. Inflammation and Autoimmunity (IAI) – key highlights Dermatology Ruxolitinib Cream Incyte announced the primary endpoint was met in its randomized, placebo-controlled, Phase 2 study evaluating the safety and efficacy of ruxolitinib cream (Opzelura ® ) in adults with mild/moderate 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 is consistent with previous data, and no new safety signals were observed. The Phase 2 data is anticipated to be presented at an upcoming scientific meeting in 2024. A Phase 3 study is currently being evaluated. Two 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 met its primary endpoint. A Phase 3 study in PN is being planned. Asthma and chronic spontaneous urticaria: Two Phase 2 trials in asthma and chronic spontaneous urticaria are enrolling. IAI and Dermatology Programs Indication and Phase Ruxolitinib cream (Opzelura ® ) 1 ( JAK1/JAK2) AD: 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 being evaluated 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 2; Phase 3 in planning Asthma: Phase 2 Chronic spontaneous urticaria: Phase 2 INCA034460 ( anti-IL-15Rβ) Vitiligo: Phase 1 initiated 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 Discovery and other early development Modality Candidates Monoclonal antibodies INCAGN2385 (LAG-3) 1 , INCAGN2390 (TIM-3) 1 Bi-specific antibodies INCA32459 (LAG-3xPD-1) 2 , INCA33890 (TGFβR2xPD-1) 2 1 Discovery collaboration with Agenus. 2 Development in collaboration with Merus. 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. 2023 Fourth Quarter and Year-end Financial Results The financial measures presented in this press release for the quarter and year ended December 31, 2023 and 2022 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, 2023 2022 2023 2022 Total GAAP revenues $ 1,013,341 $ 926,700 $ 3,695,649 $ 3,394,635 Total GAAP operating income 187,270 70,093 620,525 579,440 Total Non-GAAP operating income 267,702 152,503 892,783 801,545 GAAP provision for income taxes 69,877 52,154 236,616 188,456 GAAP net income 201,079 28,461 597,599 340,660 Non-GAAP net income 239,124 139,661 795,449 622,676 GAAP basic EPS $ 0.90 $ 0.13 $ 2.67 $ 1.53 Non-GAAP basic EPS $ 1.07 $ 0.63 $ 3.56 $ 2.80 GAAP diluted EPS $ 0.89 $ 0.13 $ 2.65 $ 1.52 Non-GAAP diluted EPS $ 1.06 $ 0.62 $ 3.52 $ 2.78 Revenue Details Revenue Details (unaudited, in thousands) Three Months Ended December 31, % C hange ( as reported) % C hange ( constant currency) 1 Twelve Months Ended December 31, % C hange ( as reported) % C hange ( constant currency) 1 2023 2022 2023 2022 Net product revenues: Jakafi $ 695,127 $ 647,493 7 % 7 % $ 2,593,732 $ 2,409,225 8 % 8 % Opzelura 109,243 61,281 78 % 78 % 337,864 128,735 162 % 162 % Iclusig 27,130 27,616 (2 %) (6 %) 111,623 105,838 5 % 3 % Pemazyre 20,653 23,016 (10 %) (11 %) 83,642 83,445 — % 1 % Minjuvi 8,994 4,809 87 % 79 % 37,057 19,654 89 % 87 % Zynyz 582 — NM NM 1,250 — NM NM Total net product revenues 861,729 764,215 13 % 13 % 3,165,168 2,746,897 15 % 15 % Royalty revenues: Jakavi 103,892 91,189 14 % 14 % 367,583 331,575 11 % 12 % Olumiant 40,359 35,858 13 % 12 % 136,138 134,547 1 % 4 % Tabrecta 4,678 4,233 11 % NA 17,793 15,411 15 % NA Pemazyre 683 1,205 NM NM 1,967 1,205 NM NM Total royalty revenues 149,612 132,485 13 % 523,481 482,738 8 % Total net product and royalty revenues 1,011,341 896,700 13 % 3,688,649 3,229,635 14 % Milestone and contract revenues 2,000 30,000 (93 %) (93 %) 7,000 165,000 (96 %) (96 %) Total GAAP revenues $ 1,013,341 $ 926,700 9 % $ 3,695,649 $ 3,394,635 9 % NM = not meaningful NA = not available 1 Percentage change in constant currency is calculated using 2022 foreign exchange rates to recalculate 2023 results. Product and Royalty Revenues Product revenues and product and royalty revenues for the quarter ended December 31, 2023 both increased 13%, and product revenues and product and royalty revenues for the year ended December 31, 2023 increased 15% and 14%, respectively, over the prior year comparative periods, primarily driven by increases in Jakafi and Opzelura net product revenues. Jakafi fourth quarter revenues were negatively impacted by an increase in the number of Medicare Part D patients receiving free product and were positively impacted by an increase in channel inventory. Opzelura net product revenues for the quarter were $109 million, representing a 78% increase year-over-year driven by growth in new patient starts and refills. Olumiant royalties for the quarter were impacted by favorable changes in foreign currency exchange rates. Operating Expenses Operating Expense Summary (unaudited, in thousands) Three Months Ended December 31, % C hange Twelve Months Ended December 31, % C hange 2023 2022 2023 2022 GAAP cost of product revenues $ 69,751 $ 59,163 18 % $ 254,990 $ 206,997 23 % Non-GAAP cost of product revenues 1 63,575 53,022 20 % 230,308 182,737 26 % GAAP research and development 444,494 501,360 (11 %) 1,627,594 1,585,936 3 % Non-GAAP research and development 2 408,488 469,048 (13 %) 1,500,897 1,473,420 2 % GAAP selling, general and administrative 293,865 272,819 8 % 1,161,293 1,002,140 16 % Non-GAAP selling, general and administrative 3 270,673 253,209 7 % 1,069,616 928,960 15 % GAAP loss on change in fair value of acquisition-related contingent consideration 15,058 24,347 (38 %) 29,202 12,149 140 % Non-GAAP loss on change in fair value of acquisition-related contingent consideration 4 — — — % — — — % GAAP (profit) and loss sharing under collaboration agreements 2,903 (1,082 ) (368 %) 2,045 7,973 (74 %) 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. 3 Non-GAAP selling, general and administrative expenses exclude the cost of stock-based compensation and asset impairments. 4 Non-GAAP 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 December 31, 2023 increased 18% and 20%, respectively, and for the year ended December 31, 2023 increased 23% and 26% compared to the same periods in 2022 due to growth in net product revenues and inventory reserves for obsolescence. Research and development expenses GAAP and Non-GAAP research and development expense for the quarter ended December 31, 2023 decreased 11% and 13%, respectively, and for the year ended December 31, 2023 increased 3% and 2%, respectively, compared to the same periods in 2022. The decrease for the quarter was primarily due to the $70 million upfront payment made as part of the Villaris asset acquisition during the fourth quarter of 2022, offset in part by the $20 million development milestone payment to former Villaris stockholders in the fourth quarter of 2023. The increase for the full year was primarily due to continued investment in our late stage development assets. Selling, general and administrative expenses GAAP and Non-GAAP selling, general and administrative expenses for the quarter ended December 31, 2023 increased 8% and 7%, respectively, and for the year ended December 31, 2023 increased 16% and 15%, respectively, compared to the same periods in 2022, primarily due to expenses related to promotional activities to support the launch of Opzelura for the treatment of vitiligo. 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, 2023, compared to the same periods in 2022, 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 year ended December 31, 2023 increased 7% and 11%, respectively, compared to the same period in 2022, primarily driven by growth in product revenues. Cash, cash equivalents and marketable securities position As of December 31, 2023 and 2022, cash, cash equivalents and marketable securities totaled $3.7 billion and $3.2 billion, respectively. 2024 Financial Guidance Incyte's guidance includes revenues and expenses related to the recently announced acquisition of exclusive global rights to tafasitamab and excludes any potential impact related to the accounting treatment of the $25 million purchase price paid. Guidance does not include revenue from any potential new product launches or the impact of any potential future strategic transactions. Incyte’s guidance is summarized below. Current Jakafi net product revenues $2,690 - $2,750 million Other Hematology/Oncology net product revenues (1) $325 - $360 million GAAP Cost of product revenues 7 – 8% of net product revenues Non-GAAP Cost of product revenues (2) 6 – 7% of net product revenues GAAP Research and development expenses $1,720 - $1,760 million Non-GAAP Research and development expenses (3) $1,580 - $1,615 million GAAP Selling, general and administrative expenses $1,210 - $1,240 million Non-GAAP Selling, general and administrative expenses (3) $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, 13744020. 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, 13744020. 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 1.5% Opzelura, 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 ® /Minjuvi ® (tafasitamab) Tafasitamab is a humanized Fc-modified CD19 targeting immunotherapy. 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). In the United States, Monjuvi ® (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Please see the U.S. full Prescribing Information for Monjuvi for important safety information. In Europe, Minjuvi ® (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi ® monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT). Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials. Its safety and efficacy for these investigational uses have not been established in pivotal trials. Minjuvi ® and Monjuvi ® are registered trademarks of Incyte. Tafasitamab is marketed by under the brand name Monjuvi ® in the U.S., and under the brand name Minjuvi ® in Europe and Canada. Xencor is eligible to receive tiered royalties on global net sales of tafasitamab in the single-digit to sub-teen double-digit percentage range. XmAb ® is a registered trademark of Xencor, Inc. About Pemazyre ® (pemigatinib) Pemazyre 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 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 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 2024, including its expectations regarding sales of Jakafi; expectations regarding demand for and sales of Opzelura, among other products; expectations regarding the potential and progress of programs in our pipeline, including INCB123667, INCB160058 and INCB161734; expectations regarding ongoing clinical trials and clinical trials to be initiated, including combination trials of ruxolitinib twice daily (BID) with zilurgisertib (INCB000928) and BETi (INCB057643), a phase 3 study of BETi and achieving clinical proof-of-concept for zilurgisertib, a phase 1 study evaluating the mCALR monoclonal antibody (INCA033989), a phase 3 trial of povorcitinib in prurigo nodularis, a phase 1/2 trial of ruxolitinib and axatilimab in chronic GVHD, various trials in our oral small molecule PD-L1 program, various phase 2 and 3 trials for ruxolitinib cream, and additional clinical trials across our MPH/GVHD, oncology, IAI and dermatology programs; our expectations regarding regulatory filings; expectations regarding the potential approval of QD Ruxolitinib (XR) in approximately two years; expectations regarding the number of products Incyte may launch by 2030, and our 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 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, 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 December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 GAAP GAAP Revenues: Product revenues, net $ 861,729 $ 764,215 $ 3,165,168 $ 2,746,897 Product royalty revenues 149,612 132,485 523,481 482,738 Milestone and contract revenues 2,000 30,000 7,000 165,000 Total revenues 1,013,341 926,700 3,695,649 3,394,635 Costs and expenses: Cost of product revenues (including definite-lived intangible amortization) 69,751 59,163 254,990 206,997 Research and development 444,494 501,360 1,627,594 1,585,936 Selling, general and administrative 293,865 272,819 1,161,293 1,002,140 Loss on change in fair value of acquisition-related contingent consideration 15,058 24,347 29,202 12,149 (Profit) and loss sharing under collaboration agreements 2,903 (1,082 ) 2,045 7,973 Total costs and expenses 826,071 856,607 3,075,124 2,815,195 Income from operations 187,270 70,093 620,525 579,440 Interest income and other, net 50,436 26,637 172,348 39,932 Interest expense (804 ) (667 ) (2,551 ) (2,666 ) Unrealized gain (loss) on long term investments 34,054 (15,448 ) 43,893 (87,590 ) Income before provision for income taxes 270,956 80,615 834,215 529,116 Provision for income taxes 69,877 52,154 236,616 188,456 Net income $ 201,079 $ 28,461 $ 597,599 $ 340,660 Net income per share: Basic $ 0.90 $ 0.13 $ 2.67 $ 1.53 Diluted $ 0.89 $ 0.13 $ 2.65 $ 1.52 Shares used in computing net income per share: Basic 224,226 222,615 223,628 222,004 Diluted 226,125 224,840 225,928 223,958 INCYTE CORPORATION CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands) December 31, 2 023 December 31, 2 022 ASSETS Cash, cash equivalents and marketable securities $ 3,656,043 $ 3,238,965 Accounts receivable 743,557 644,879 Property and equipment, net 751,513 739,310 Finance lease right-of-use assets, net 25,535 26,298 Inventory 269,937 120,959 Prepaid expenses and other assets 236,782 194,144 Long term investments 187,716 133,676 Other intangible assets, net 123,545 129,219 Goodwill 155,593 155,593 Deferred income tax asset 631,886 457,941 Total assets $ 6,782,107 $ 5,840,984 LIABILITIES AND STOCKHOLDERS’ EQUITY Accounts payable, accrued expenses and other liabilities $ 1,347,669 $ 1,216,603 Finance lease liabilities 32,601 33,262 Acquisition-related contingent consideration 212,000 221,000 Stockholders’ equity 5,189,837 4,370,119 Total liabilities and stockholders’ equity $ 6,782,107 $ 5,840,984 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, 2023 2022 2023 2022 GAAP Net Income $ 201,079 $ 28,461 $ 597,599 $ 340,660 Adjustments 1 : Non-cash stock compensation from equity awards (R&D) 2 36,006 32,312 126,697 112,516 Non-cash stock compensation from equity awards (SG&A) 2 23,192 19,610 86,046 73,180 Non-cash stock compensation from equity awards (COGS) 2 792 757 3,146 2,724 Non-cash interest 3 108 143 463 431 Changes in fair value of equity investments 4 (34,054 ) 15,448 (43,893 ) 87,590 Amortization of acquired product rights 5 5,384 5,384 21,536 21,536 Loss on change in fair value of contingent consideration 6 15,058 24,347 29,202 12,149 Asset impairment 7 — — 5,631 — Tax effect of Non-GAAP pre-tax adjustments 8 (8,441 ) 13,199 (30,978 ) (28,110 ) Non-GAAP Net Income $ 239,124 $ 139,661 $ 795,449 $ 622,676 Non-GAAP net income per share: Basic $ 1.07 $ 0.63 $ 3.56 $ 2.80 Diluted $ 1.06 $ 0.62 $ 3.52 $ 2.78 Shares used in computing Non-GAAP net income per share: Basic 224,226 222,615 223,628 222,004 Diluted 226,125 224,840 225,928 223,958 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, 2023 are milestones of $2,000 and $7,000, respectively, earned from our collaborative partners, as compared to milestones of $30,000 and $165,000, respectively, for the three and twelve months ended December 31, 2022. 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, 2023 are upfront consideration and milestones of $24,000 and $36,650, respectively, related to our collaborative partners, as compared to upfront consideration and milestones of $70,000 and $125,950, respectively, for the three and twelve months ended December 31, 2022. 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 Unrealized gain (loss) on long term 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 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. The tax benefit for the three months ended December 31, 2022 includes a true up from the interim quarters related to valuation allowances against deferred tax assets associated with the loss on equity investments.

LONDON, UK I January 29, 2024 I GSK plc (LSE/NYSE: GSK) today announced the European Commission* granted marketing authorisation for Omjjara (momelotinib), a once-a-day, oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor. Omjjara is the first authorised medicine in the EU for disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with moderate to severe anaemia who have primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis and who are Janus kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. Nina Mojas, Senior Vice President, Oncology Global Product Strategy, GSK, said: “The challenges of living with myelofibrosis can be burdensome, and symptomatic patients can experience spleen enlargement, fatigue, night sweats and bone pain. Until now, there have been no options specifically indicated to treat these symptoms in patients who also experience anaemia. The authorisation of Omjjara brings a new treatment option with a differentiated mechanism of action to these patients in the EU.” Myelofibrosis is estimated to affect 1 in 10,000 people in the EU. 5,6 About 40% of patients have moderate to severe anaemia at the time of diagnosis and nearly all patients are estimated to develop anaemia over the course of the disease. 1,2,3,4 Myelofibrosis patients with anaemia require additional supportive care, including transfusions, and more than 30% will discontinue treatment due to anaemia. 7 Patients who are transfusion dependent have a poor prognosis and shortened survival. 8,9,10,11,12,13,14,15,16 Francesca Palandri, MD, PhD, IRCCS S. Orsola-Malpighi, Bologna University Hospital, Italy, said: “The EU authorisation of Omjjara represents a meaningful advancement for eligible patients with myelofibrosis, and particularly for those with moderate to severe anaemia who need new treatment options that may reduce their disease-related burden. The availability of a single therapy for key manifestations of myelofibrosis is a clear step forward for eligible patients.” The authorisation of momelotinib is based on the MOMENTUM pivotal phase III trial and a subpopulation of adult patients with moderate to severe anaemia (haemoglobin <10 g/dL) from the SIMPLIFY-1 phase III trial. 17,18 MOMENTUM was designed to evaluate the safety and efficacy of momelotinib versus danazol for the treatment and reduction of key manifestations of myelofibrosis in an anaemic, symptomatic, JAK inhibitor-experienced population. SIMPLIFY-1 was designed to evaluate the efficacy and safety of momelotinib versus ruxolitinib in myelofibrosis patients who had not received a prior JAK-inhibitor therapy. In these clinical trials, the most common adverse reactions were diarrhoea, thrombocytopaenia, nausea, headache, dizziness, fatigue, asthenia, abdominal pain, and cough. 17,18 About Omjjara (momelotinib) Momelotinib has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor, type I (ACVR1). 8,17,19,20 Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly. 8,17,20 Additionally, inhibition of ACVR1 leads to a decrease in circulating hepcidin levels, potentially contributing to anaemia-related benefit. 8,17,19,20 In September 2023, the US Food and Drug Administration licensed ( https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia/ ) momelotinib under the brand name Ojjaara for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythaemia vera and post-essential thrombocythaemia), in adults with anaemia. Important Information for Omjjara in the EU Indication Omjjara is indicated for the treatment of disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with moderate to severe anaemia who have primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis and who are Janus kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. Refer to the Omjjara EMA Reference Information ( https://www.ema.europa.eu/en/medicines/human/EPAR/omjjara ) for a full list of adverse events and the complete important safety information in the EU. About myelofibrosis Myelofibrosis is a rare blood cancer that disrupts the body’s normal production of blood cells because of dysregulated JAK-signal transducer and activator of transcription protein signalling. The clinical hallmarks of myelofibrosis are splenomegaly (enlarged spleen), progressive anaemia and debilitating constitutional symptoms, such as fatigue, night sweats and bone pain, attributable to ineffective haematopoiesis and excessive production of proinflammatory cytokines. 21 About the pivotal clinical trials MOMENTUM was a phase III, global, multicentre, randomised, double-blind study investigating momelotinib versus danazol in patients (n=195) with myelofibrosis who were symptomatic and anaemic and had been previously treated with a licensed JAK inhibitor. The trial was designed to evaluate the safety and efficacy of momelotinib for treating and reducing key hallmarks of the disease: symptoms, blood transfusions (due to anaemia), and splenomegaly. The MOMENTUM trial met all its primary and key secondary endpoints, demonstrating statistically significant response with respect to constitutional symptoms, splenic reduction and transfusion independence in patients treated with momelotinib versus danazol (Total Symptom Score reduction of 50% or greater: 25% momelotinib, 9% danazol, p = 0.0095; reduction of spleen volume by 35% or greater: momelotinib 22%, danazol 3%, p = 0.0011; no transfusions and all haemoglobin values ≥8 g/dL in the 12 weeks prior to week 24: momelotinib 30%, danazol 20%).17 Results from the 24-week randomised treatment period were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published in The Lancet , 22,23 with 48-week data presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2022 and subsequently published in The Lancet . 24,25 SIMPLIFY-1 was a multicentre, randomised, double-blind, phase III study that compared the safety and efficacy of momelotinib to ruxolitinib in patients (n=432) with myelofibrosis who had not received prior treatment with a JAK inhibitor. Safety and efficacy results for SIMPLIFY-1 were based upon a subset of patients (n=181) with anaemia at baseline. The efficacy of momelotinib in the treatment of patients with myelofibrosis in SIMPLIFY-1 was based on spleen volume response (reduction of spleen volume by 35% or greater: 31% momelotinib, 33% ruxolitinib p = 0.026). 18 GSK in oncology GSK is committed to maximising patient survival through transformational medicines, with a current focus on breakthroughs in immuno-oncology and tumour-cell targeting therapies, and development in haematologic malignancies, gynaecologic cancers, and other solid tumours. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. Notes * The European Commission has the authority to authorise medicines for European Union member states, as well as in the European Economic Area (EEA) countries Iceland, Norway and Liechtenstein, and Northern Ireland. References SOURCE: GlaxoSmithKline

Accelerating Innovation and Growth Strategy with Top-Line Data Readouts Expected in 2H 2024 and 2025 from Three Pivotal Phase 3 Studies Evaluating Selinexor in Multiple Myeloma, Endometrial Cancer and Myelofibrosis Preliminary Unaudited Full Year 2023 Total Revenue and U.S. XPOVIO® (selinexor) Net Product Revenue Expected to be Approximately $146 Million and $112 Million, Respectively, Meeting Company's Guidance Potential for Selinexor to be a Novel Maintenance Treatment for Patients with TP53 Wild-Type Endometrial Cancer Further Strengthened with Long-Term Exploratory Subgroup Analyses from SIENDO Study; Recruitment Ongoing in the Company's Pivotal Phase 3 Study; Further Updates Planned to be Presented in 2024 Opportunity to Define a New Myelofibrosis Treatment Paradigm Based on the Encouraging Data Presented from the Phase 1 Study of Selinexor in Combination with Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis; Recruitment Ongoing in the Company's Pivotal Phase 3 Study; Further Updates Planned to be Presented in 2024 Expect Cash Runway into Late 2025 Supporting Company Through Multiple Potentially Value Generating Milestones NEWTON, Mass., Jan. 8, 2024 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced preliminary unaudited fourth quarter and full year 2023 total revenue and U.S. XPOVIO net product revenue estimates and outlined its 2023 achievements and 2024 objectives. "2023 was a year focused on accelerating our prioritized late-stage pipeline with updated data readouts from our studies in endometrial cancer and myelofibrosis, strengthening our potential to significantly improve outcomes for patients. We focused our resources and delivered on our revenue guidance as we continued to expand use of selinexor amidst a highly competitive multiple myeloma landscape. In 2024, we will continue to concentrate our investments to rapidly advance our pipeline and strengthen our foundation in multiple myeloma and deliver value for patients and our shareholders with multiple value driving catalysts expected throughout 2024," said Richard Paulson, President and Chief Executive Officer of Karyopharm. Key Program Highlights in 2023 Selinexor in Multiple Myeloma (MM) Total demand for XPOVIO grew in the community setting, which accounted for approximately two-thirds of XPOVIO net product revenue; in the academic setting, demand for XPOVIO was adversely impacted by increased competitive pressures in the later lines. XPOVIO net product revenue was adversely impacted year-over-year by increased utilization of the KaryForward Patient Assistance Program (PAP), due to multiple myeloma foundation closures1, contributing to ~10% of total demand in 2023 as compared to ~5% in 2022, leading to ~$6 million impact. Additionally, increased competition and higher gross-to-net, driven by increased 340B discounts and Medicaid rebates during the year, adversely impacted XPOVIO net product revenue. XPOVIO continued its strategic shift to earlier lines, with patient mix approaching 70% in the second to fourth lines versus 55% in 20222, contributing to an increase in duration of therapy. The National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines elevated XPOVIO in combination with bortezomib (Velcade®) and dexamethasone (XVd) to a preferred and category 1 regimen for lenalidomide-refractory patients with relapsed or refractory multiple myeloma who have received one-to-three prior lines of therapy in the September 2023 Clinical Practice Guidelines in Oncology. Clinical trial collaboration agreement executed with Bristol Myers Squibb (BMS) to evaluate selinexor in combination with BMS' proprietary investigational cereblon E3 ligase modulator (CELMoD™) agent mezigdomide in patients with relapsed/refractory multiple myeloma progressing after T-cell immunotherapies, adding to the growing combinations with selinexor that have shown benefit in multiple myeloma and enabling further evaluation of selinexor's role in maintaining an optimal T-cell environment. Selinexor has been approved in more than 40 countries and recently achieved national reimbursement in mainland China. In 1Q 2023, the Company's license agreement with the Menarini Group was expanded to include the Middle East and Africa regions. Selinexor in Endometrial Cancer (EC) Long-term exploratory subgroup analysis of the pre-specified subgroup of patients with advanced or recurrent TP53 wild-type EC from the Phase 3 SIENDO study (NCT03555422) was presented at medical conferences, with updated progression free survival and preliminary data showing improvement in overall survival. The SIENDO study manuscript was published in the Journal of Clinical Oncology. Selinexor in Myelofibrosis (MF) Presented updated results from the Phase 1 study (XPORT-MF-034) evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve MF at several medical conferences demonstrating encouraging spleen reduction, symptom improvement, long-term durability and disease modification data. Initiated pivotal Phase 3 portion of the XPORT-MF-034 clinical trial (NCT04562389) to assess the efficacy and safety of once-weekly selinexor 60mg in combination with ruxolitinib in JAKi-naïve patients with MF. Received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for selinexor for the treatment of patients with MF, including primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. Planned Phase 2 XPORT-MF-044 study (NCT05980806) to evaluate the efficacy and safety of selinexor monotherapy in subjects with JAK inhibitor-naïve MF and moderate thrombocytopenia. Entered into an agreement with SOBI for the supply of pacritinib as an optional add-on in the study for eligible patients. Eltanexor in Myelodysplastic Neoplasms (MDS) Reported interim data from the Phase 2 study of single-agent eltanexor in high risk relapsed/refractory MDS (NCT02649790). Further development of eltanexor in MDS is on hold in line with the Company's prioritization of its late-stage pipeline programs. Intellectual Property The United States Patent and Trademark Office issued a certificate extending the term of the patent covering the composition of matter of XPOVIO® (selinexor) (U.S. patent 8,999,996) by 342 days to July 3, 2033. The U.S. Patent and Trademark Office has issued patents directed toward the polymorphic form of selinexor present in XPOVIO, pharmaceutical compositions comprising the polymorphic form and methods of treatment using the polymorphic form and the pharmaceutical compositions. The newly issued patents will expire in August 2035. Optimization of Corporate Organization Further positioned the Company's organization to focus on and invest in its Phase 3 programs and drive agile execution of business priorities, through optimization of its cost structure with a ~ 20% reduction of the workforce, including full-time employees and contractors. Corporate and Financial Highlights for 2023 Based on preliminary unaudited financial information, the Company expects total revenue, which includes license and royalty revenue from partners, to be approximately $33.6 million for the fourth quarter 2023 and approximately $145.9 million for the full year 2023, and U.S. XPOVIO net product revenue to be approximately $25.0 million for the fourth quarter 2023 and approximately $112.0 million for the full year 2023, meeting Company's guidance. Cash, cash equivalents, restricted cash and investments as of December 31, 2023 was approximately $192.0 million, enabling an expected cash runway into late 2025. The financial information presented in this press release may be adjusted as a result of the completion of customary annual review and audit procedures. Near-Term Catalysts and Operational Objectives Anticipated in 2024 Report top-line results from pivotal Phase 3 study evaluating an oral combination of selinexor, pomalidomide and dexamethasone in patients with previously treated MM in 2H 2024. Publish and present efficacy and safety data on selinexor 40mg in combination with pomalidomide and dexamethasone from ongoing STOMP/028 Phase 2 studies in patients with MM. Report additional data on selinexor's preservation of T-cell fitness and potential combinability with multiple agents pre or post T-cell therapy in patients with MM. Complete enrollment in pivotal EC-042 Phase 3 trial in TP53 wild-type EC. Present updated exploratory subgroup analysis results in patients with TP53 wild-type EC from the SIENDO study. Report updated results from the Phase 1 study of selinexor in combination with ruxolitinib in patients with treatment-naïve MF. Report preliminary results from Phase 2 study evaluating the efficacy and safety of selinexor monotherapy in subjects with JAK inhibitor-naïve MF and moderate thrombocytopenia. Maintain the Company's commercial foundation in the competitive MM marketplace, driving increased XPOVIO revenues. Continue global launches and reimbursement approvals for selinexor by partners in ex-U.S. territories. Listen to the Webcast These achievements and updates will be discussed during a webcast presentation at the 42nd Annual J.P. Morgan Healthcare Conference to be held on January 10, 2024, at 5:15 p.m. Eastern Time/2:15 p.m. Pacific Time. A live webcast of the presentation and breakout session, along with accompanying slides, can be accessed under "Events & Presentations" in the Investor section of the Company's website, . An archived replay will be available for 30 days following the event. The presentation slides will also be available on the Company's website following the event. About XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO® in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm's global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: medicalinformation@karyopharm.com XPOVIO® (selinexor) is a prescription medicine approved: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd). For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care. Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors. Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care. Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care. Serious Infection: Monitor for infection and treat promptly. Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes. Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception. Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients. Use In Specific Populations Lactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit . To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or About Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in oral Selective Inhibitor of Nuclear Export (SINE) compound technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications and has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting multiple high unmet need cancer indications, including in multiple myeloma, endometrial cancer, myelodysplastic neoplasms and myelofibrosis. For more information about our people, science and pipeline, please visit and follow us on Twitter at @Karyopharm and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's preliminary financial information for the fourth quarter and full year 2023; guidance on its expected cash runway; expectations with respect to commercialization efforts; the ability of selinexor or eltanexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, diffuse large B-cell lymphoma, myelodysplastic neoplasms and other diseases; and expectations with respect to the clinical development plans and potential regulatory submissions of selinexor and eltanexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor and eltanexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm's business, results of operations and financial condition; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2023, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this release are the property of their respective owners. References: 1 Four multiple myeloma foundations provide financial support to Medicare patients with multiple myeloma 2 Based on Komodo claims data analysis, accessed in October 2023 View original content to download multimedia: SOURCE Karyopharm Therapeutics Inc. Company Codes: NASDAQ-NMS:KPTI