JAK-STAT Pathway–Targeting Approaches in Myelofibrosis Are Evolving

Posted on February 19, 2024February 19, 2024 by mpn_admin

February 15, 2024

Targeted Oncology Staff

During a Targeted Oncology™ Case-Based Roundtable™ event, Raajit K. Rampal, MD, gave an overview of the classification, risk assessment, and current therapy options for patients with myelofibrosis.

Targeted Oncology: What is the latest understanding of the classification and pathogenesis of myeloproliferative neoplasms (MPNs)?

RAAJIT K. RAMPAL, MD, PHD: Nothing has changed in terms of the 2022 [World Health Organization] classification, unlike what has happened with myelodysplastic syndrome.¹ JAK-STAT signaling is a hallmark of MPN pathogenesis, and all of the mutations that we’re aware of at the moment—JAK2, CALR [calreticulin], and MPL—function in the JAK-STAT pathway. MPL is the thrombopoietin receptor which complexes with JAK [Janus kinase].

CALR is interesting, because CALR was discovered in 2013 but we think at the moment CALR complexes with MPL and results in the aberrant activation of MPL, but CALR does traffic to the cell surface.^2,3 That makes it a target for immunotherapy. That is the target of a couple of clinical trials; one is open [LIMBER (NCT06034002)] and the other is about to open, which is really interesting [and] could change everything in MPNs.

All that being said, there are still at least 8% to 15% of myelofibrosis cases that are “triple negative.”^2,3 If you look at those cases by gene expression profiling, they have the JAK-STAT signature. The issue with those cases is that we haven’t identified the particular lesion that occurs there, but it is a JAK-STAT–activated lesion, regardless of what the actual driver is. Those are the important things to think about with regards to how the disease is driven.

Study Reveals Real-World Characteristics of Patients With Secondary Myelofibrosis

Posted on February 7, 2024February 7, 2024 by mpn_admin

February 6, 2024

Jonathan Goodman, MPhil

A study published in the Annals of Hematology has highlighted the characteristics of patients with post-essential thrombocythemia or post-polycythemia vera myelofibrosis (PET-MF and PPV-MF, respectively) treated during the ruxolitinib era.

Although the characteristics of patients with primary MF are well-established, less research has evaluated real-world data from patients with PET-MF or PPV-MF. Given that primary and secondary forms of the disease may have different prognoses, a greater understanding of the clinical and patient characteristics in the latter group is important. For this prospective study, researchers in Japan aimed to determine the real-world characteristics and prognoses among patients with PET-MF or PPV-MF.

Overall, data from 314 patients were evaluated, among whom 197 had PET-MF while 117 had PPV-MF. At the time of diagnosis, in the PET-MF and PPV-MF groups, the median ages were 70 and 70 years, respectively, 49.7% and 53.8% of patients were male, and the periods from ET or PV diagnosis to MF progression were 9.64 and 10.38 years. The majority of patients in both groups received ruxolitinib treatment (74.6% in the PET-MF group and 83.8% in the PPV-MF group).

Health Canada Slated to Review New Drug Submission for Momelotinib in Myelofibrosis

Posted on February 7, 2024February 7, 2024 by mpn_admin

February 5, 2024

Kristi Rosa

Health Canada has accepted for review the new drug submission seeking the approval of momelotinib in patients with myelofibrosis, according to a recent announcement from GlaxoSmithKline.¹The submission is based on findings from the phase 3 SIMPLIFY-1 (NCT01969838) and MOMENTUM (NCT04173494) trials.

Specifically, SIMPLIFY-1 data showed that of the 86 patients who received momelotinib, 31.4% (95% CI, 21.8%-42.3%) experienced a spleen volume response (SVR) reduction of 35% or higher vs 32.6% (95% CI, 23.4%-43.0%) of the 95 patients who received danazol.²

Moreover, findings from MOMENTUM indicated that a tumor symptom score (TSS) of at least 50% was observed in 25% of the 130 patients given momelotinib per the Myelofibrosis Symptom Assessment Form (MFSAF v4.0), representing a treatment difference of 16% (95% CI, 6%-26%; P < .01).^2,3 The MFSAF v4.0 TSS change from baseline in the momelotinib and danazol arms were -9.4 and -3.1, respectively, equating to a difference of -6.2 (95% CI, -10 to -2.4; P = .001).

Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements

Posted on February 1, 2024February 1, 2024 by mpn_admin

by Tanvi Verma¹, Nikolaos Papadantonakis², Deniz Peker Barclift¹ and Linsheng Zhang

Simple Summary

Myelofibrosis refers to fibrosis in the bone marrow associated with certain bone marrow cancers. It is a characteristic of primary myelofibrosis and may develop later in other bone marrow cancers with overproduction of blood cells, such as polycythemia vera and essential thrombocythemia. It has been confirmed that mutations in three key genes, Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia oncogene (MPL), can increase the activity of blood-producing cells, make them grow more actively, and are associated with the development of myelofibrosis. Approximately 80% of myelofibrosis cases carry additional mutations that often involve proteins that control how genes are turned on and off. The presence of mutations provides evidence of a cancerous process. The order in which these mutations occur can influence how the disease manifests. Studies have shown that fibrosis is secondary to the cancerous process and is closely linked to abnormal cell growth driven by mutations. Sophisticated scoring systems have been developed to guide treatment decisions. Specific mutations and genetic changes significantly affect the scores and survival of individual patients. Currently, common treatment involves JAK inhibitors, which can help improve clinical symptoms; however, only a small number of patients show significant alleviation in the biology of the malignant process. New treatments being explored in clinical trials include drugs that target the regulation of genes and substances that modulate the immune system or inflammatory processes. Combining these with JAK inhibitors shows promising results, especially in patients with complex genetic profiles. In the future, by studying more genes, it is expected that researchers will uncover the reasons behind cases where mutations are not found in the three key genes and understand how genetic changes are connected to variable disease presentations, ultimately guiding personalized treatment plans for better outcomes with a chance for cures.

Abstract

Myelofibrosis (MF) is an essential element of primary myelofibrosis, whereas secondary MF may develop in the advanced stages of other myeloid neoplasms, especially polycythemia vera and essential thrombocythemia. Over the last two decades, advances in molecular diagnostic techniques, particularly the integration of next-generation sequencing in clinical laboratories, have revolutionized the diagnosis, classification, and clinical decision making of myelofibrosis. Driver mutations involving JAK2, CALR, and MPL induce hyperactivity in the JAK-STAT signaling pathway, which plays a central role in cell survival and proliferation. Approximately 80% of myelofibrosis cases harbor additional mutations, frequently in the genes responsible for epigenetic regulation and RNA splicing. Detecting these mutations is crucial for diagnosing myeloproliferative neoplasms (MPNs), especially in cases where no mutations are present in the three driver genes (triple-negative MPNs). While fibrosis in the bone marrow results from the disturbance of inflammatory cytokines, it is fundamentally associated with mutation-driven hematopoiesis. The mutation profile and order of acquiring diverse mutations influence the MPN phenotype. Mutation profiling reveals clonal diversity in MF, offering insights into the clonal evolution of neoplastic progression. Prognostic prediction plays a pivotal role in guiding the treatment of myelofibrosis. Mutation profiles and cytogenetic abnormalities have been integrated into advanced prognostic scoring systems and personalized risk stratification for MF. Presently, JAK inhibitors are part of the standard of care for MF, with newer generations developed for enhanced efficacy and reduced adverse effects. However, only a minority of patients have achieved a significant molecular-level response. Clinical trials exploring innovative approaches, such as combining hypomethylation agents that target epigenetic regulators, drugs proven effective in myelodysplastic syndrome, or immune and inflammatory modulators with JAK inhibitors, have demonstrated promising results. These combinations may be more effective in patients with high-risk mutations and complex mutation profiles. Expanding mutation profiling studies with more sensitive and specific molecular methods, as well as sequencing a broader spectrum of genes in clinical patients, may reveal molecular mechanisms in cases currently lacking detectable driver mutations, provide a better understanding of the association between genetic alterations and clinical phenotypes, and offer valuable information to advance personalized treatment protocols to improve long-term survival and eradicate mutant clones with the hope of curing MF.

European Commission Approves Momelotinib for Myelofibrosis/Anemia

Posted on February 1, 2024February 1, 2024 by mpn_admin

January 29, 2024

Ariana Pelosci

The European Commission granted marketing authorization to momelotinib (Omjjara) for patients with primary myelofibrosis who have disease-related splenomegaly or moderate to severe anemia, according to a press release from GSK.¹

This indication also covers patients with post polycythemia vera myelofibrosis or post essential thrombocythemia myelofibrosis who are JAK inhibitor naïve or received previous treatment with ruxolitinib (Jakafi). The authorization is based on results from the phase 3 MOMENTUM trial (NCT04173494), which analyzed the use of momelotinib and danazol in patients with symptomatic and anemic myelofibrosis.²

“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 anemia. The authorization of [momelotinib] brings a new treatment option with a differentiated mechanism of action to these patients in the European Union,” Nina Mojas, senior vice president of Oncology Global Product Strategy at GSK, said in the press release.

In the trial, the total symptom score response at week 24 was 24.6% (95% CI, 17.49%-32.94%) for patients receiving momelotinib vs 9.2% (95% CI, 3.46%-19.02%) in the danazol arm (P = .0095). Additionally, a reduction of splenic volume by 25% occurred in 40.0% (95% CI, 31.51%-48.95%) of patients in the momelotinib arm vs 6.2% (95% CI, 1.70%-15.01%; P <.0001) in the danazol arm. A 35% reduction in spleen volume was also observed in 23.1% (95% CI, 16.14%-31.28%) in the momelotinib arm and 3.1% (95% CI, 0.37%-10.68%; P = .0006) in the danazol arm.

In September 2023, the FDA approved momelotinib for patients with intermediate- or high-risk myelofibrosis, including primary and secondary myelofibrosis, who are experiencing anemia.³ In November 2023, the European Medicine’s Agency’s Committee for Medicinal Products for Human Use expressed a positive opinion for momelotinib.⁴ The positive opinion was one of the final steps leading to the approval of the drug in the European Union.

“I think [momelotinib] will make an immediate impact. There clearly are individuals now who are on JAK inhibitors like ruxolitinib or fedratinib [Inrebic] who have significant anemia who will immediately be potential candidates,” Ruben A. Mesa, MD, FACP, said in an interview with CancerNetwork^® prior to the FDA approval. Mesa is the president of the Enterprise Cancer Service Line and senior vice president at Atrium Health; executive director of the National Cancer Institute-designated Atrium Health Wake Forest Baptist Comprehensive Cancer Center; and vice dean for Cancer Programs at Wake Forest University School of Medicine.

References

European Commission authorises GSK’s Omjjara (momelotinib). News release. GSK. January 29, 2024. Accessed January 29, 2024. https://shorturl.at/ntuvy
Mesa RA, Gerds AT, Vannucchi A, et al. MPN-478 MOMENTUM: phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. J Clin Oncol. 2022;40(suppl 16):7002. doi:10.1200/JCO.2022.40.16_suppl.7002
Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia, News release. GSK. September 15, 2023. Accessed January 29, 2024. https://shorturl.at/jnNQY
GSK receives positive CHMP opinion recommending momelotinib for myelofibrosis patients with anaemia. News release. GSK. November 13, 2023. Accessed January 29, 2024. https://bit.ly/3MEYpOl

SOHO State of the Art Updates and Next Questions | Diagnosis, Outcomes, and Management of Prefibrotic Myelofibrosis

Posted on January 30, 2024January 30, 2024 by mpn_admin

Pankit Vacchani, Sanam Lohgavi, Prithviraj Bose

Abstract

Prefibrotic primary myelofibrosis (prefibrotic PMF) is a myeloproliferative neoplasm with distinct characteristics comprising histopathological and clinico-biological parameters. It is classified as a subtype of primary myelofibrosis. In clinical practice, it is essential to correctly distinguish prefibrotic PMF from essential thrombocythemia especially but also overt PMF besides other myeloid neoplasms. Risk stratification and survival outcomes for prefibrotic PMF are worse than that of ET but better than that of overt PMF. Rates of progression to overt PMF and blast phase disease are also higher for prefibrotic PMF than ET. In this review we first discuss the historical context to the evolution of prefibrotic PMF as an entity, its presenting features and diagnostic criteria. We emphasize the differences between prefibrotic PMF, ET, and overt PMF with regards to presenting features and disease outcomes including thrombohemorrhagic events and progression to fibrotic and blast phase disease. Next, we discuss the risk stratification models and contextualize these in the setting of clinical management. We share our view of personalizing treatment to address unique patient needs in the context of currently available management options. Lastly, we discuss areas of critical need in clinical research and speculate on the possibility of future disease course modifying therapies in prefibrotic PMF.

Dr Vincelette on MYC Expression in Myelofibrosis

Posted on January 29, 2024January 29, 2024 by mpn_admin

January 19, 2024

Nicole D. Vincelette, PhD

Nicole D. Vincelette, PhD, postdoctoral fellow, Moffitt Cancer Center, discusses findings from a study investigating the role of MYC expression and S100A9-mediated inflammation in a subgroup of triple-negative myeloproliferative neoplasms (MPNs).

To determine how MYC expression drives MPNs, such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis, Vincelette and colleagues conducted a study in which they generated a mouse model that overexpresses MYC in the stem cell compartment. This analysis demonstrated that MYC overexpression was associated with the mice developing a myelofibrosis-like phenotype, which included anemia, atypical megakaryocytes, splenomegaly, bone marrow fibrosis, liver fibrosis, spleen fibrosis. The mice also experienced adverse clinical outcomes, such as reduced overall survival (OS), compared with wild-type mice, Vincelette says.

Since the MYC-overexpressed mice developed myelofibrosis, the next step of this research was to investigate how MYC drives myelofibrosis, Vincelette explains. Investigators performed single-cell RNA sequencing to compare the bone marrow cells from MYC-overexpressed and wild-type mice. MYC overexpression correlated with upregulation of the S100A9 protein, which contributes to inflammation and innate immunity, according to Vincelette. Therefore, MYC drives the development of myelofibrosis through S100A9-mediated chronic inflammation. To validate the role of S100A9 downstream of MYC in myelofibrosis, investigators created a mouse model with S100A9 knockout in the presence of MYC overexpression, Vincelette notes. The S100A9 knockout protected against the development of myelofibrosis phenotype in that mouse model, Vincelette emphasizes.

By generating a mouse model that overexpresses S100A9, investigators also determined that S100A9 overexpression alone contributes to the development of myelofibrosis phenotypes, Vincelette says. When investigators treated the MYC-overexpressing mice with the S100A9 inhibitor tasquinimod (ABR-215050), the agent only partially abrogated the myelofibrosis phenotype, meaning the mice had reduced atypical megakaryocytes and splenomegaly. Additionally, the mice developed anemia and no OS difference occurred between tasquinimod and vehicle treatment, potentially because of off-target drug effects, Vincelette concludes.

Fedratinib Improves Myelofibrosis Management Compared With Ruxolitinib

Posted on January 18, 2024January 18, 2024 by mpn_admin

By Patrick Daly – Last Updated: January 17, 2024

Treatment with fedratinib, a Janus kinase inhibitor (JAKi), induced superior spleen volume reduction (SVR) and symptom response rates compared with best available therapy in patients with myelofibrosis (MF) who previously received ruxolitinib, according to data from the open-label phase III FREEDOM2 study, presented at the 65th American Society of Hematology Annual Meeting & Exposition.

“Most patients on best available therapy received ruxolitinib, highlighting a need for an alternative JAKi,” stated lead author of the study, Claire Harrison, MD, FRCP, from Guy’s and St. Thomas’ NHS Foundation Trust in London, England.

The FREEDOM2 trial enrolled patients aged 18 years or older with primary, post-polycythemia vera, or post-essential thrombocythemia MF with splenomegaly who were intolerant or refractory to, or relapsed after ruxolitinib. The primary endpoint was SVR ≥35% (SVR35) at the end of the sixth 28-day cycle.

Fedratinib for Myelofibrosis Treatment Superior to Ruxolitinib

In total, 201 patients were randomized to fedratinib (n=134) or best available therapy (n=67). The cohort had a median age of 70 (interquartile range, 64-74), 52.2% were male, 54.7% had primary MF, and 76.1% had a Dynamic International Prognostic Scoring System risk score of intermediate-2.

Overall, 70.1% of patients in the best available therapy arm received ruxolitinib, 10.4% received hydroxyurea, and 7.5% received ruxolitinib plus hydroxyurea. Additionally, 46 (68.7%) patients in the best available therapy arm crossed over to fedratinib after either disease progression or the sixth cycle response assessment.

With a median follow-up of 15 months at the data cutoff, researchers reported the fedratinib group had a significantly higher SVR35 rate of 35.8% at the end of cycle six compared with best available therapy at 6.0% (P<.0001). Fedratinib also yielded superior SVR ≥25% at the cycle six assessment and superior SVR35 at any point during treatment. The rate of symptom response at the end of cycle six was 34.1% with fedratinib versus 16.9% with best available therapy (P=.0033).

In short, “fedratinib demonstrated superior SVR and symptom response rates compared with [best available therapy]” in patients with MF and prior ruxolitinib treatment, concluded Dr. Harrison and colleagues.

Reference

Harrison CN, Mesa RA, Talpaz M, et al. Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib: results from the phase 3 randomized FREEDOM2 study. Abstract #3204. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.

GB2064 Displays Preliminary Efficacy, Tolerability in Myelofibrosis

Posted on January 17, 2024January 17, 2024 by mpn_admin

January 16, 2024

Kyle Doherty

The potential first-in-class, oral, lysyl oxidase-like 2 (LOXL2) inhibitor GB2064 displayed efficacy with a generally acceptable tolerability profile in the treatment of patients with myelofibrosis, according to topline findings from the phase 2a MYLOX-1 trial (NCT04679870).¹

Among evaluable patients with myelofibrosis who were treated with GB2064 monotherapy for a minimum of 6 months (n = 10), 6 experienced a reduction in collagen fibrosis of the bone marrow of at least 1 grade. All patients who achieved this reduction in bone marrow fibrosis displayed stable hematological parameters, including hemoglobin, white blood cell count, and platelet count. This indicates the agent’s potential impact on disease progression and disease-modifying capabilities. At 6 months of treatment, 1 patient experienced a reduction in spleen volume of at least 35%, 2 reduced their Total Symptom Score (TSS) by over 50%, and another patient experienced an anemia response.

“It is exciting and encouraging to see that the data from the MYLOX-1 trial affirms the safety and effectiveness of LOXL-2 inhibition in the challenging landscape of myelofibrosis,” Claire Harrison, MD, FRCP, FRCPath, chair of the Safety Review Committee for the MYLOX-1 trial, a professor of myeloproliferative neoplasms, and the clinical director of Guy’s and St Thomas’ NHS Foundation Trust in London, England, said in a press release. “I am especially intrigued by the unique observed improvements in bone marrow collagen fibrosis, showcasing the targeted impact on a crucial aspect of this relentless disease.”

MYLOX-1 was an open-label, single-arm study that enrolled adult patients with primary or secondary myelofibrosis who were ineligible, refractory, or intolerant to treatment with a JAK inhibitor. Patients had intermediate-2 or high-risk disease by the Dynamic International Prognostic Scoring System-plus, or low-risk disease with symptomatic splenomegaly. Eligible patients were also required to have an ECOG performance status of 2 or less, not be receiving JAK inhibitor therapy, display required baseline laboratory counts, and have a documented history of transfusion records in the preceding 12 weeks to day 1 of study treatment.²

All patients on the study treatment received 1000 mg of oral GB2064 twice daily for 9 months. Patients underwent bone marrow biopsies at the beginning of the trial and again at 3, 6 and 9 months. The primary end point was the safety and tolerability of GB2064; key secondary end points included evaluating hematological parameters and the direct anti-fibrotic activity of GB2064 by blocking LOXL2 in an indication that allows for repeated tissue biopsies.^1,2

The study dosed a total of 18 patients with myelofibrosis. Most patients (61%) had previously received the JAK inhibitor ruxolitinib (Jakafi); 8 of these patients were refractory to JAK inhibitor therapy and 3 were intolerant.¹

Additional assessment of bone marrow biopsies in MYLOX-1 revealed that GB2064 penetrated the bone marrow and could exert its anti-fibrotic effect directly in the disease compartment. Additionally, the agent displayed systemic target engagement by binding to LOXL2 in plasma. Four patients who experienced clinical benefit with GB2046, as determined by the treating physician, have entered the extension phase of MYLOX-1. Notably, 1 of these patients has received treatment for over 30 months.

GB2064 displayed a tolerable safety profile, with 8 of the 18 dosed patients completing treatment in the core phase of MYLOX-1. The remaining 10 patients discontinued treatment due to adverse effects or progressive disease. The most common any-grade treatment-related adverse effects were manageable with standard therapy and gastrointestinal in nature. The lone treatment-related serious adverse effect was a case of fall, which was determined to be possibly related to GB2064 treatment.

“We believe that the topline results from the MYLOX-1 trial reaffirm the anti-fibrotic activity observed in the intermediate assessment of the trial announced in September 2022,” Hans T. Schambye, MD, PhD, the president and chief executive officer of Galecto, said in the press release. “We are very excited with the proof of principle achieved with GB2064, showcasing its strong anti-fibrotic impact in a very challenging patient population. The encouraging topline results from the MYLOX-1 trial reinforce our confidence in GB2064’s potential as a transformative therapy for various cancers and a range of fibrotic diseases, but we will not make any decisions relating to funding additional trials with GB2064 until we complete our previously announced strategic alternative process.”

In September 2023, Galecto announced that it completed a review of its business and would conduct a comprehensive exploration of strategic alternatives focused on maximizing shareholder value. Galecto did not set a timetable for completion of the evaluation and said it did not intend to disclose further developments or guidance on the status of its programs unless it determined that further disclosure is appropriate or necessary.³

References

Topline results from MYLOX-1 trial demonstrate reduction in fibrosis of the bone marrow in patients with myelofibrosis. News release. Galecto, Inc. December 21, 2023. Accessed January 16, 2024. https://www.biospace.com/article/releases/topline-results-from-mylox-1-trial-demonstrate-reduction-in-fibrosis-of-the-bone-marrow-in-patients-with-myelofibrosis/
A study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of oral GB2064 in participants with myelofibrosis. ClinicalTrials.gov. Updated May 6, 2023. Accessed January 16, 2024. https://clinicaltrials.gov/study/NCT04679870
Galecto announces plans to explore strategic alternatives. News release. Galecto, Inc. September 26, 2023. Accessed January 16, 2024. https://ir.galecto.com/news-releases/news-release-details/galecto-announces-plans-explore-strategic-alternatives

INCA-033989 by Incyte for Myelofibrosis: Likelihood of Approval

Posted on January 15, 2024January 15, 2024 by mpn_admin

January 12, 2024

GlobalData tracks drug-specific phase transition and likelihood of approval scores, in addition to indication benchmarks based off 18 years of historical drug development data. Attributes of the drug, company and its clinical trials play a fundamental role in drug-specific PTSR and likelihood of approval.

INCA-033989 overview

INCA-033989 is under development for the treatment of myelofibrosis (MF), essential thrombocythemia (ET). The drug candidate is a monoclonal antibody which acts by targeting calreticulin (CALR).

It was also under development for post-essential thrombocythemia myelofibrosis (Post-ET MF) and primary myelofibrosis (PMF).

Incyte overview

Incyte is a biopharmaceutical company, which discovers, develops and commercializes proprietary cancer therapeutics. The company’s lead product, Jakafi (ruxolitinib) is marketed in the US for the treatment of patients with high-risk myelofibrosis; and polycythemia vera who are intolerant to hydroxyurea. The company distributes Jakafi through a network of specialty pharmacy providers and wholesalers. In collaboration with Incyte, Novartis International Pharmaceutical Ltd (Novartis) develops and commercializes ruxolitinib outside the US for hematologic and cancer indications under the name Jakavi. The company’s pipeline portfolio encompasses drugs for the treatment of lung cancer, graft versus host disease, b-cell malignancies, solid tumors, non-small cell lung cancer, glioblastoma, liver cancer, and advanced malignancies. Incyte is headquartered in Wilmington, Delaware, the US.