On November 5, 2025 X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare hematology diseases, reported financial results for the third quarter ended September 30, 2025 and provided a corporate update.

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"The third quarter of 2025 was a time of corporate restructuring at X4 with the start of a new leadership team and a renewed focus on chronic neutropenia," said Adam Craig, M.D., Ph.D., Executive Chairman of X4 Pharmaceuticals. "With a strengthened financial position through two successful financings totaling $240.3 million, our primary focus is now on the completion of the 4WARD Phase 3 pivotal trial of mavorixafor in patients with moderate and severe chronic neutropenia, which has a potential addressable market of 15,000 patients in the US. With a cash runway to the end of 2028, we are now positioned to unlock mavorixafor’s full potential and to establish X4 as a world-class rare hematology company."

Recent Accomplishments and Updates
•Since early August, the Company has initiated a number of measures to restructure its operations:
◦A shift in the primary focus of the Company to the successful completion of the 4WARD Phase 3 pivotal trial of mavorixafor in patients with moderate and severe chronic neutropenia.
◦A deprioritization of the commercialization of mavorixafor (XOLREMDI) for patients with WHIM syndrome, while maintaining patient access.
◦A 50% reduction in the workforce (expected to generate approximately $13 million in annualized cost savings) with continued cost cutting measures.
◦An increase in the enrollment target for the pivotal Phase 3 4WARD study to 176 patients with enrollment now expected to be completed in third quarter of 2026.
◦The promotion of John Volpone to the role of Chief Operating Officer, in addition to his responsibilities as President.
◦Dr. Adam Craig expanded his role to include oversight of clinical development activities.
•Since August, the Company raised $240.3 million in gross proceeds from two successful financings: the closing of a $155.3 million underwritten public offering and an $85 million upsized private placement.
•With a strengthened cash runway to the end of 2028, X4 is now expected to be able to complete the 4WARD trial, file a potential sNDA for the chronic neutropenia indication, and, if successful, launch mavorixafor in this new indication by the end of 2028.

Third Quarter and Recent Financial Results
Net product sales of $1.6 million and $4.3 million for the three and nine months ended September 30, 2025, respectively, were entirely attributable to XOLREMDI product sales in the United States. Net product sales were $0.6 million and $1.1 million for the three and nine months ended September 30, 2024, respectively. License and other revenue of $0.2 million and $28.3 million for the three and nine months ended September 30, 2025, respectively, were entirely attributable to the Company’s Norgine out-licensing agreement. Operating loss was $27.5 million and $34.5 million for the three months ended September 30, 2025 and 2024, respectively, and $63.2 million and $0.7 million for the nine months ended September 30, 2025 and 2024, respectively. The decrease in operating loss between the three-month periods ended September 30, 2025 and 2024 was primarily attributable to the impact of our 2025 Strategic Restructuring activities. Operating expenses for the nine months ended September 30, 2024 are net of a gain of $105.0 million realized on the sale of a priority review voucher. Exclusive of this gain, the decrease in operating loss between the nine-month periods ended September 30, 2025 and 2024 was primarily attributable to the impact of the Company’s strategic restructuring activities undertaken in 2025.

Net loss for the three months ended September 30, 2025 was $29.8 million, or $0.69 for basic and diluted loss per share, compared to net loss of $36.7 million, or $5.48 for basic and diluted loss per share, for the same period in 2024. Net loss for the nine months ended September 30, 2025 was $55.3 million, or $2.87 for basic and diluted loss per share, compared to net income of $2.4 million, or $0.35 for basic and diluted income per share, for the same period in 2024.

Cash, cash equivalents and short-term investments totaled $122.2 million for the period ended September 30, 2025. On October 27, 2025, the Company completed a public offering with net proceeds of $145.6 million, which management believes will enable the Company to fund its operations into the end of 2028.

About Chronic Neutropenia and Mavorixafor
Chronic neutropenia is a primary, rare blood condition lasting more than three months, persistently or intermittently, and characterized by low levels of circulating neutrophils and increased risk of serious and life-threatening infections and reduced quality of life due to abnormally low levels of neutrophils circulating in the blood. Neutrophils are retained in the bone marrow by the CXCR4/CXCL12 axis, creating a reserve of cells. Downregulation of the CXCR4 receptor by mavorixafor, an orally active CXCR4 antagonist, has been shown to mobilize functional neutrophils from the bone marrow into the peripheral blood across multiple disease states. The level of circulating neutrophils is typically measured by drawing blood to determine the absolute neutrophil count (ANC).

About the 4WARD Clinical Trial
The 4WARD trial is a global, pivotal Phase 3 clinical trial (NCT06056297) evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without G-CSF) in patients with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 176 patients with confirmed trough ANC levels less than 1,000 cells per microliter at baseline screening and histories of two or more serious and/or recurrent infections in the prior year. The primary endpoints of the study are the reduction in annualized infection rate and positive ANC response.

(Press release, X4 Pharmaceuticals, NOV 5, 2025, View Source [SID1234659479])

On November 5, 2025 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the third quarter of 2025 and updated financial guidance for 2025.

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"Achieving the highest revenue quarter in Jazz’s history speaks to the strength of our diversified portfolio and the outstanding performance of our team. We were pleased to once again deliver solid execution across our sleep, epilepsy and oncology portfolios, led by double-digit percentage growth from Epidiolex and Xywav," said Renee Gala, president and chief executive officer of Jazz Pharmaceuticals. "In addition, we achieved several key milestones that will enhance our commercial portfolio, including receiving FDA approvals for Modeyso as well as the Zepzelca and atezolizumab first-line maintenance combination. We remain confident in the opportunity presented by zanidatamab and look forward to sharing the top-line data readout from the Phase 3 HERIZON-GEA-01 trial before the end of the year. With a proven portfolio and strong financial foundation, we are well-positioned to accelerate our evolution and deliver meaningful value for patients and shareholders alike."

Key Highlights

•Modeyso received accelerated approval from the FDA ahead of its PDUFA date; initiated commercial launch in August 2025 with strong initial uptake and sales of $11.0 million in 3Q25.
•Zepzelca and atezolizumab combination received FDA approval for 1L maintenance treatment of ES-SCLC based on positive data from the Phase 3 IMforte trial.
•Top-line PFS data from zanidatamab in Phase 3 1L GEA expected in 4Q25; updated intent-to-treat population for PFS to include all patients enrolled in the trial.
•Narrowed 2025 total revenue guidance range to $4.175 – $4.275 billion from $4.150 – $4.300 billion.
•Announced the appointment of Dr. Ted Love to the Board of Directors.

Business Updates

Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution:
•Net product sales increased 11% to $431.4 million in 3Q25 compared to 3Q24.
•Meaningful net patient adds in 3Q25 of approximately 450 patients. There were approximately 15,675 active patients exiting the quarter comprised of approximately 10,725 narcolepsy patients and approximately 4,950 idiopathic hypersomnia (IH) patients.

Epidiolex/Epidyolex (cannabidiol):
•Net product sales increased 20% to $302.6 million in 3Q25 compared to 3Q24.
•In 3Q25, volumes increased by 10%, driven by demand, and net product sales benefitted from lower gross to net deductions in the U.S.

Rylaze/Enrylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn):
•Net product sales increased 1% to $99.9 million in 3Q25 compared to 3Q24.

Zepzelca (lurbinectedin):
•Net product sales decreased 8% to $79.3 million in 3Q25 compared to 3Q24.
•Zepzelca and atezolizumab combination was included in National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a preferred regimen for patients whose disease has not progressed following four cycles of platinum-based chemotherapy and atezolizumab induction.

Ziihera (zanidatamab-hrii):
•Net product sales were $8.3 million in 3Q25 following product launch in December 2024.
•Updated the intent-to-treat population for the primary PFS (progression-free survival) and interim overall survival analyses of the HERIZON-GEA-01 trial to include the full patient population enrolled in the trial.

Modeyso (dordaviprone):
•Net product sales were $11.0 million in 3Q25 following product launch in August 2025.
•Modeyso was made commercially available quickly following FDA accelerated approval on August 6, ensuring patients with H3 K27M-mutant diffuse midline glioma (DMG) had access to the first and only targeted drug therapy for this ultra-rare and aggressive brain tumor.
•Modeyso was included in the NCCN Clinical Practice Guidelines in Oncology.

Corporate Development:
•The Company announced a global licensing agreement with Saniona to develop and commercialize SAN2355, a highly differentiated, subtype selective Kv7.2/Kv7.3 activator in preclinical development for epilepsy and other potential indications.

Financial Highlights
Three Months Ended
September 30, Nine Months Ended
September 30,
(In thousands, except per share amounts) 2025 2024 2025 2024
Total revenues $ 1,126,107 $ 1,054,969 $ 3,069,660 $ 2,980,777
GAAP net income (loss) $ 251,412 $ 215,055 $ (559,599) $ 369,005
Non-GAAP adjusted net income1
$ 500,653 $ 412,359 $ 101,037 $ 951,445
GAAP earnings (loss) per share $ 4.08 $ 3.42 $ (9.18) $ 5.63
Non-GAAP adjusted earnings per share1
$ 8.13 $ 6.54 $ 1.63 $ 14.25

(Press release, Jazz Pharmaceuticals, NOV 5, 2025, View Source [SID1234659464])

On November 5, 2025 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and autoimmune diseases, reported financial results for the third quarter ended September 30, 2025 and provided recent business and clinical program updates.

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"Xencor’s two novel, first-in-class, CD3 T-cell engaging bispecific antibodies, XmAb819 and XmAb541, have demonstrated compelling clinical data in advanced clear cell renal cell carcinoma and advanced gynecologic and germ cell tumors, respectively. As we continue to advance through dose escalation and cohort expansions in Phase 1 studies evaluating these programs, we expect to identify recommended Phase 3 doses during 2026 to support initiation of pivotal studies during 2027," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "The accelerating tempo of clinical development extends to our autoimmune portfolio. In the third quarter we dosed the first patient in our Phase 2b XENITH-UC study of XmAb942, our potential best-in-class antibody targeting TL1A for inflammatory bowel disease, to rapidly identify a pivotal dose regimen for those with moderately to severely active ulcerative colitis, and we dosed the first patient in our Phase 1b study of plamotamab in rheumatoid arthritis. We remain on-track to start clinical studies of XmAb657, our B-cell depleting TCE for the treatment of patients with autoimmune disease by year end 2025, and our lead TL1A x IL23p19 bispecific antibody, now designated XmAb412, in 2026."

Clinical Program Updates

Oncology

XmAb819 (ENPP3 x CD3), a novel, first-in-class, tumor-targeted T-cell engaging XmAb 2+1 bispecific antibody in development for patients with advanced clear cell renal cell carcinoma (ccRCC). The first dose-expansion cohort in the ongoing Phase 1 study is enrolling patients as dose-escalation continues. Xencor plans to select a recommended Phase 3 dose during 2026 to support initiation of a pivotal study in advanced ccRCC during 2027.

At the AACR (Free AACR Whitepaper)-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics in October 2025, Xencor presented initial results from the ongoing Phase 1 dose-escalation study of XmAb819. As of the data cut-off, 69 patients had received XmAb819 across 15 dose cohorts; patients were heavily pre-treated, having received a median of 4 prior lines of therapy. All patients received prior anti-PD1 therapy and prior VEGF-TKI therapy, and 36% of patients were previously treated with a HIF2α inhibitor. XmAb819 demonstrated evidence of anti-tumor activity and an acceptable safety profile that was generally well tolerated across dose levels. Of the 20 efficacy-evaluable patients treated at the dose levels that were preclinically predicted to be within the target dose range, 25% achieved a partial response (PR, per RECIST v1.1) as best response with a 70% disease control rate. The most common treatment-emergent adverse events (AEs) were cytokine release syndrome, rash and gastrointestinal-related toxicities that were primarily Grade 1 or 2 in severity and predominantly associated with prime-step dosing in the first four weeks of treatment. No cases of treatment-related immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. No Grade 5 events were reported. Four patients (6%) were dose-reduced due to treatment-related AEs, and three patients (4%) discontinued treatment due to treatment-related AEs.
XmAb541 (CLDN6 x CD3), a novel, first-in-class, tumor-targeted T-cell engaging XmAb 2+1 bispecific antibody in development for patients with advanced gynecologic and germ cell tumors. Xencor plans to select a recommended Phase 3 dose during 2026 to support initiation of a pivotal study during 2027.

In October 2025, Xencor presented early efficacy data from a cohort in the ongoing Phase 1 dose-escalation study of XmAb541, ahead of previously guided timelines to begin characterizing target dose range cohorts by year-end 2025. As of the data cut-off, nine patients received XmAb541 in the most recently completed escalation cohort. Confirmed partial responses per RECIST v1.1 were observed in three patients: one patient with ovarian cancer and two patients with germ cell tumors.
Autoimmune & Inflammatory Diseases

Plamotamab (CD20 x CD3), a clinical-stage, B-cell depleting bispecific T-cell engager in development for patients with rheumatoid arthritis (RA). Xencor is evaluating plamotamab in a Phase 1b proof-of-concept study, for patients with RA who have progressed through prior standard-of-care treatment. The first patient has been dosed in the study, and enrollment is ongoing.
XmAb942 (Xtend anti-TL1A), a potential best-in-class, high-potency, extended half-life antibody in development for patients with inflammatory bowel disease. Xencor is conducting the global XENITH-UC Study, a Phase 2b study of XmAb942 in ulcerative colitis (UC). XENITH-UC is a randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe UC, whose disease has progressed after at least one conventional or advanced therapy. Patient enrollment in the study is ongoing.
Recent Partnership Developments

Amgen: Amgen initiated the Phase 3 XALience study of xaluritamig, a STEAP1 x CD3 XmAb 2+1 bispecific T-cell engager, in combination with abiraterone versus investigator’s choice therapy in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. XALute, a Phase 3 monotherapy study of xaluritamig in patients who have previously been treated with taxane-based chemotherapy, is enrolling. Amgen is exploring xaluritamig in other combinations and in earlier stages of prostate cancer with multiple Phase 1b studies ongoing. Xencor is eligible to receive $225 million in future milestone payments and tiered royalties on net sales that range from mid- to high-single digit percentages.
Astellas: In October 2025, the first clinical data from Astellas’ investigational Claudin18.2-targeted, XmAb 2+1 bispecific CD3 T-cell engager, ASP2138, both as a monotherapy and in combination with standard of care therapies, were presented during the European Society for Medical Oncology congress in Berlin. Astellas is advancing ASP2138 for the treatment of patients with gastric, gastroesophageal junction and pancreatic cancers, and Astellas has announced that planning is ongoing to potentially initiate registrational studies. ASP2138 utilizes the XmAb 2+1 multivalent format to enable activation of T cells against Claudin-18.2 expressing tumor cells. Xencor is eligible to receive $232.5 million in future milestone payments and tiered royalties on net sales that range from high-single to low-double digit percentages.
Zenas Biopharma: In October 2025, Zenas announced positive results from the Phase 2 MoonStone trial of obexelimab in relapsing multiple sclerosis, in which the primary endpoint of the study was met. Zenas announced it expects to report topline results for the pivotal study of obexelimab in IgG4-Related Disease around year-end with additional readouts through mid-2026. Obexelimab targets CD19 with its variable domain and uses an XmAb Immune Inhibitor Fc Domain. In November 2021, Xencor licensed obexelimab to Zenas. Xencor is eligible to receive $460 million in future milestone payments and tiered royalties on net sales that range from mid-single-digit to mid-teen percentages, dependent on geography. As of September 30, 2025, Xencor owns 3,098,380 shares of common stock in Zenas.
Financial Guidance: Based on current operating plans, Xencor expects to end 2025 with between $570 million and $590 million in cash, cash equivalents and marketable debt securities, and to have cash to fund research and development programs and operations into 2028.

Financial Results for the Third Quarter Ended September 30, 2025

Cash, cash equivalents and marketable debt securities totaled $633.9 million as of September 30, 2025, compared to $706.7 million as of December 31, 2024.

Revenue for the third quarter ended September 30, 2025 was $21.0 million, compared to $17.8 million for the same period in 2024. Revenue earned in the third quarters of 2025 and 2024 was primarily non-cash royalty revenue from Alexion and Incyte.

Research and development (R&D) expenses for the third quarter ended September 30, 2025 were $54.4 million, compared to $58.2 million for the same period in 2024. Decreased R&D spending for the third quarter of 2025 compared to 2024 reflects lower stock-based compensation and lower costs related to programs that are winding down or have been terminated.

General and administrative (G&A) expenses for the third quarter ended September 30, 2025 were $14.2 million, compared to $14.8 million for the same period in 2024. G&A spending for the third quarter of 2025 remained relatively consistent compared to the same period in 2024.

Other income, net, for the third quarter ended September 30, 2025 was $41.5 million, compared to $7.8 million for the same period in 2024. The increase for the third quarter of 2025, compared to 2024, is primarily driven by unrealized gains from marketable equity securities.

Net loss attributable to Xencor for the third quarter ended September 30, 2025 was $6.0 million, or $(0.08) on a fully diluted per share basis, compared to net loss of $46.3 million, or $(0.72) on a fully diluted per share basis, for the same period in 2024.

(Press release, Xencor, NOV 5, 2025, View Source [SID1234659480])

On November 4, 2025 Delcath Systems, Inc. (Nasdaq: DCTH) ("Delcath" or the "Company"), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported financial results and business highlights for the third quarter ended September 30, 2025.

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Third Quarter 2025 Financial Results

Total revenue of $20.6 million, compared with $11.2 million in the third quarter of 2024
HEPZATO KIT revenue of $19.3 million, compared to $10.0 million in the third quarter of 2024
CHEMOSAT revenue of $1.3 million, compared to $1.2 million in the third quarter of 2024
Gross margins of 87%, compared to 85% in the third quarter of 2024
Net income of $0.8 million, compared to a net income of $1.9 million in the third quarter of 2024
Non-GAAP positive adjusted EBITDA in the third quarter of $5.3 million, compared to a positive adjusted EBITDA of $1.0 million in the third quarter of 2024
Cash provided by operations of $4.8 million in the quarter; compared to $3.6 million used by operations in the third quarter of 2024
Cash and investments of $88.9 million as of September 30, 2025
Business Highlights

There are currently 25 active centers across the U.S.
In August, the first patient was dosed at City of Hope National Medical Center in the global Phase 2 trial of HEPZATO in combination with trifluridine-tipiracil and bevacizumab for liver-dominant metastatic colorectal cancer. The study will enroll approximately 90 patients across 20+ sites in the U.S. and Europe, with topline data expected in 2028
Announced that results from the investigator-initiated Phase 2 CHOPIN trial at Leiden University Medical Center evaluating CHEMOSAT with ipilimumab and nivolumab in metastatic uveal melanoma were presented at the October 2025 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress by Principal Investigator Ellen Kapiteijn, MD, showing a significant improvement in one-year progression-free survival versus CHEMOSAT alone
"In the third quarter, we made strong progress with our clinical programs, reporting compelling positive CHOPIN results and first-patient dosing in our global Phase 2 trial in liver-dominant metastatic colorectal cancer," said Gerard Michel, Chief Executive Officer of Delcath Systems. "While revenue results in the quarter reflected the impact of NDRA discounts and seasonal factors, our fundamentals remain strong. We are confident that the growing clinical validation of HEPZATO positions us well to drive continued progress and long-term value for patients and shareholders."

2025 Full Year Financial Guidance

The Company’s financial outlook for fiscal year 2025:

Total CHEMOSAT and HEPZATO KIT revenue to be in the range of $83 to $85 million, an increase in volume of approximately 150% over 2024
Gross margins in the range of 85% to 87%
Positive adjusted EBITDA and cashflow in each quarter of 2025
Third Quarter 2025 Results

Total revenue for the quarter ending September 30, 2025 was $20.6 million compared to $11.2 million for the same period in the prior year. Revenue in the quarter includes sales of $19.3 million of HEPZATO in the U.S. and $1.3 million of CHEMOSAT in Europe.

Research and development expenses for the quarter ending September 30, 2025, were $8.0 million compared to $3.9 million for the same period in the prior year. The increase is primarily due to costs associated with expanding the clinical team including the share-based compensation expense related to an increase in headcount and initiation of the Phase 2 clinical trial evaluating HEPZATO in combination with standard of care for metastatic colorectal cancer and Phase 2 clinical trial in metastatic breast cancer. In 2024, these costs primarily related to medical affairs and regulatory costs associated with the approved products.

Selling, general and administrative expenses for the quarter ended September 30, 2025, were $10.3 million compared to $7.0 million for the same period in the prior year. The increase is primarily due to continued commercial expansion activities including marketing-related expenses, additional personnel in the commercial team and share-based compensation expenses.

Net income for the quarter ended September 30, 2025 was $0.8 million compared to net income of $1.9 million for the same period in the prior year.

Non-GAAP adjusted EBITDA for the quarter ended September 30, 2025 was $5.3 million compared to adjusted EBITDA of $1.0 million for the same period in the prior year. A table reconciling non-GAAP measures is included in this press release for reference.

As of September 30, 2025, the Company had $88.9 million in cash and investments, and no debt.

Conference Call Information

To participate in this event, dial in approximately 5 to 10 minutes before the beginning of the call.

Event Date: Thursday, November 6, 2025
Time: 8:30 AM Eastern Time

Participant Numbers:
Toll Free: 1-877-407-3982
International: 1-201-493-6780
Webcast: View Source;tp_key=a3bb91787b

A replay of the webinar will be available shortly after the conclusion of the call and will be archived on the company’s website View Source

(Press release, Delcath Systems, NOV 4, 2025, View Source [SID1234659352])

On November 4, 2025 Prelude Therapeutics Incorporated (Nasdaq:PRLD), a clinical-stage precision oncology company, reported an exclusive option agreement with Incyte (Nasdaq:INCY) focused on Prelude’s previously undisclosed mutant selective JAK2V617F JH2 inhibitor program in development for patients with myeloproliferative neoplasms (MPNs). Per the agreement, Incyte secures an exclusive option to acquire the JAK2V617F program in exchange for an upfront payment and a strategic equity investment in Prelude, plus potential downstream milestones and royalties.

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Kris Vaddi, Ph.D., Chief Executive Officer of Prelude stated, "We’re pleased to put this agreement in place with Incyte, recognized global leaders in the MPN field. Prelude and Incyte both aim to deliver transformational treatments to improve upon the standard of care established with first generation JAK2 JH1 inhibitors like Jakafi (ruxolitinib). Our research team made significant progress discovering the first known inhibitors that bind into the JAK2 JH2 ‘deep pocket’ where the V617F mutation resides. These potent and orally bioavailable compounds demonstrate mutant specific inhibition and the potential for disease modification in multiple preclinical models of MPNs. Today’s agreement with Incyte provides us with the capital needed to advance further our JAK2V617F program, while also allowing us to advance the development of our other pipeline programs."

"The agreement with Prelude provides an opportunity to enhance our robust portfolio of clinical and preclinical JAK2V617F candidates for patients with MPNs," said Bill Meury, President and Chief Executive Officer of Incyte. "This transaction aligns with our strategy to develop new and innovative therapies poised to make a meaningful difference for patients."

Terms of the Agreement
Under the terms of the Transaction Agreement, Incyte secures an exclusive option to acquire Prelude’s mutant selective JAK2V617F JH2 inhibitor program, including Prelude’s library of preclinical candidates. Prelude will receive $60 million in capital, comprised of an upfront payment of $35 million, plus a $25 million equity investment by Incyte in Prelude. Incyte will purchase 6.25 million shares of Prelude non-voting common stock at a price of $4.00 per share at deal close. Prelude intends to apply the upfront payment and net proceeds from the sale of the purchased shares to advance the JAK2V617F program and other pipeline assets, and for working capital and general corporate purposes.

Prelude expects to advance the JAK2V617F program to pre-defined milestones. Incyte may elect to exercise its exclusive option during the option period to acquire the program and associated assets from Prelude for $100 million. As the JAK2V617F program candidates advance in the clinic, Prelude would be eligible to receive up to $775 million in additional clinical and regulatory milestones, and single digit royalties on global net sales. Combined, total potential cash payments from the transaction, excluding royalties, could reach up to $910 million.

If Incyte elects to not exercise its option to acquire the program, all JAK2V617F global program rights and interests would remain in the sole ownership and control of Prelude.

Prelude Therapeutics was advised on the transaction by Morgan Lewis & Bockius LLP as legal counsel.

Mutant selective JAK2V617F JH2 inhibitor program
JAK2V617F is the primary driver mutation responsible for disease progression in the majority of patients living with myeloproliferative neoplasms (MPNs). The mutation impacts approximately 95% of patients with polycythemia vera (PV), 60% of patients with essential thrombocythemia (ET) and 55% of patients with myelofibrosis (MF). Identifying JAK2 JH2 inhibitors that selectively target V617F+ cells has long been a shared goal and challenge for industry. If successful, this approach has potential to reduce mutant allele burden, modify disease progression, and transform treatment outcomes for MPN patients. Prelude has discovered novel allosteric inhibitors that bind into the JAK2 JH2 "deep pocket" where the V617F mutation resides. These candidates demonstrate mutant specific inhibition in multiple preclinical models of MPNs. The first disclosure of program data was accepted for oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 67th Annual Meeting taking place in Orlando, FL December 6-9, 2025. The abstract can be found on the ASH (Free ASH Whitepaper) 2025 website ASH (Free ASH Whitepaper) Annual Meeting & Exposition – Hematology.org.

(Press release, Prelude Therapeutics, NOV 4, 2025, View Source [SID1234659368])