HLH Drug Pipeline: Emapalumab & JAK Inhibitors — PatSnap Eureka
Hemophagocytic Lymphohistiocytosis: Emapalumab, JAK Inhibitors & Cytokine Storm Approaches
HLH is a life-threatening hyperinflammatory syndrome driven by dysregulated innate immunity and cytokine storm. Explore the emerging patent landscape across anti-IFN-γ, JAK1, anti-IL-18, CDK8/19, and SIRP-alpha therapeutic strategies — powered by PatSnap Eureka.
HLH: A Cytokine Storm Syndrome Driven by Innate Immune Dysregulation
Hemophagocytic lymphohistiocytosis (HLH) is characterized by "dysregulated, pathological overactivation of innate immunity leading to cytokine storm, multi-organ failure and a very high mortality." The underlying molecular mechanism in primary HLH involves genetic defects affecting the perforin-mediated cytolytic pathway — including mutations in PRF1, RAB27A, and STX11 — which result in incomplete silencing of immune reactions and aberrant antigen-presenting cell (APC) to CD8+ T cell crosstalk.
Among retrieved patent and literature records, IFN-γ emerges as the dominant pathogenic cytokine in HLH. Multiple NovImmune SA patent filings establish IFN-γ as a therapeutic target, noting that elevated CXCL9 — a downstream IFN-γ-inducible chemokine — serves as a pharmacodynamic and diagnostic biomarker for active disease. The JAK-STAT signaling axis, particularly JAK1, is identified as a convergence point for multiple cytokines driving HLH pathology, including those involved in cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).
A clinical literature case report from Sheffield Teaching Hospital links alemtuzumab treatment to iatrogenic HLH mediated by cytokine storm in multiple sclerosis patients, underscoring the broader relevance of cytokine-driven hyperinflammation across therapeutic contexts. IL-18 is additionally flagged as a relevant pathogenic mediator: Avalo Therapeutics patents explicitly include HLH/MAS among conditions targeted by anti-IL-18 antibodies, including virus-associated cases.
A critical care literature review frames HLH as a self-propelling positive feedback loop of pro-inflammatory cytokines precipitated by viral triggers (notably Epstein-Barr virus), malignancy, or autoimmune disease, noting that "only timely proper diagnosis and treatment can reverse this dismal outcome."
Six Mechanistic Approaches Across the HLH Drug Pipeline
Patent and literature analysis identifies six distinct mechanistic classes targeting HLH and related cytokine storm syndromes, from established anti-IFN-γ strategies to emerging transcriptional and myeloid checkpoint approaches.
Emapalumab Mechanism Class: IFN-γ Neutralization
NovImmune SA holds the dominant patent portfolio covering methods and compositions for treating HLH using agents that "interfere with or otherwise antagonize interferon gamma (IFN-γ) signaling, including neutralizing anti-IFNγ antibodies." A 2025 JP filing reassigned to Swedish Orphan Biovitrum (Sobi) signals continued commercial IP activity. Murine models of perforin- and Rab27a-deficiency demonstrated that IFN-γ neutralization defeats haemophagocytosis.
Incyte JAK1 Inhibitors: Broad Cytokine Signaling Blockade
Incyte Corporation holds the most active patent family for JAK1 inhibitor use in cytokine-related disorders explicitly including HLH, CRS, MAS, and CRES, with two active US patents filed in 2024 and 2025. The mechanistic rationale is inhibition of downstream cytokine signaling through JAK1 heterodimerization, addressing the polycytokine nature of HLH. Preclinical evidence cites that "JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice" has a therapeutic effect.
Avalo Therapeutics: IL-18 Blockade in Virus-Triggered HLH/MAS
Avalo Therapeutics holds two retrieved patents (Israel, Mexico) for anti-IL-18 antibodies targeting ARDS and HLH/MAS in patients with elevated IL-18 levels, including virus-associated cases. The antibody is defined by specific CDR sequences and is positioned to address the IL-18-driven component of hyperinflammation that may not be fully controlled by IFN-γ neutralization alone. Coronavirus-associated HLH/MAS is explicitly included as a target indication.
University of South Carolina: Transcriptional Cytokine Storm Suppression
The University of South Carolina discloses a novel mechanistic approach targeting CDK8 and CDK19 as transcriptional regulators of cytokine-storm mediating cytokines. Filed in WO and CA jurisdictions (2022), the mechanism involves inhibition of NF-κB-inducible inflammatory gene expression programs, with downstream reduction of cytokines including IL-8, IL-10, CCL2, CCL3, and CCL4. This represents a conceptually differentiated approach from single-cytokine neutralization strategies.
Electra Therapeutics: Myeloid Checkpoint Modulation
Electra Therapeutics discloses antibodies targeting SIRPα, SIRPβ1, and SIRPγ for conditions associated with lymphocyte/myeloid cell overactivation, explicitly listing HLH (primary and secondary), MAS, and Langerhans cell histiocytosis (LCH) among target indications. This represents an emerging mechanistic class acting at the interface of myeloid cell regulation and innate immune suppression, complementary to T cell-directed or cytokine-directed approaches.
Bristol-Myers Squibb & UPenn: CRS-Adjacent Cytokine Blockade
Bristol-Myers Squibb patent filings (2022, IL) disclose methods for treating cytokine-related adverse events, referencing IL-6 (blocked by tocilizumab) and IL-1β (targeted by anakinra) as central CRS mediators. The University of Pennsylvania's CAR-T CRS prevention patent further cites tocilizumab (anti-IL-6R) as a standard CRS intervention. Cytokine blockade strategies validated in CRS — a pathophysiological neighbor of HLH — are being actively pursued with IP protection.
HLH Therapeutic Landscape: Patent Signals & Target Coverage
Data derived from retrieved patent and literature records via PatSnap Eureka. Represents innovation signals within this dataset only.
HLH Pipeline: Patent Records per Therapeutic Modality
Anti-IFN-γ (emapalumab class) leads with 7+ records across 7 jurisdictions; JAK1 inhibitors follow with 3 active US filings including 2024–2025 patents.
HLH Cytokine Target Coverage by Modality Share
IFN-γ/CXCL9 axis dominates HLH-specific IP; JAK1 pathway provides broadest multi-cytokine coverage across CRS, MAS, and CRES.
Key Patent Holders in the HLH Drug Pipeline
The innovation landscape is predominantly patent-driven. NovImmune SA / Swedish Orphan Biovitrum holds the dominant HLH-specific IP position across multiple jurisdictions.
| Assignee | Therapeutic Focus | Key Jurisdictions | Most Recent Filing | Stage Signal |
|---|---|---|---|---|
| NovImmune SA / Swedish Orphan Biovitrum AG | Anti-IFN-γ mAbs; CXCL9 biomarker diagnostics | US, EP, AU, IN, CA, WO, JP | 2025 (JP) | Patent · Preclinical/Translational |
| Incyte Corporation / Incyte Holdings | JAK1 pathway inhibitors for HLH, CRS, MAS, CRES | US (2024, 2025) | 2025 (US) | Patent · Preclinical |
| Avalo Therapeutics, Inc. | Anti-IL-18 antibodies (CDR-defined) for HLH/MAS | IL, MX | 2023 | Patent · Early development |
Map Competitor IP Positions in HLH
PatSnap Eureka tracks every assignee, jurisdiction, and claim across the HLH patent landscape in real time.
Strategic Implications for HLH Drug Development & IP
Key signals from patent analysis for R&D teams, IP strategists, and biopharma decision-makers tracking the HLH pipeline.
IFN-γ Neutralization Holds Strongest HLH-Specific IP Position
NovImmune/Swedish Orphan Biovitrum controls a multi-jurisdictional patent estate covering composition of matter, method of use, and companion biomarker (CXCL9) diagnostics. New entrants pursuing this mechanism face a densely protected IP landscape across US, EP, AU, IN, CA, WO, and JP jurisdictions.
Incyte JAK1 Portfolio Explicitly Extends to HLH
Active 2024–2025 US patents and an implied clinical development rationale supported by ruxolitinib murine HLH data represent a potentially approvable combinatorial or second-line strategy should the cytokine-broadening benefit of JAK inhibition translate clinically.
Beyond Single-Cytokine Targeting: Combination & Next-Generation HLH Strategies
JAK inhibition + CAR-T cytokine management: The University of Pennsylvania/Saar Gill patent (2022, JP) discloses combining JAK-STAT inhibitors (specifically ruxolitinib) with CAR-T therapy to prevent CRS — a pathophysiological continuum with HLH. This signals that JAK inhibitors may be positioned as prophylactic or therapeutic adjuncts in CAR-T-induced cytokine hyperactivation syndromes. The life sciences IP intelligence provided by PatSnap Eureka can help track these cross-indication filings.
Anti-IL-18 in virus-triggered HLH/MAS: Avalo Therapeutics' patents (2023) specifically include coronavirus-associated HLH/MAS as a target indication for anti-IL-18 antibodies, signaling an emerging recognition that pandemic-related cytokine storm syndromes overlap with classical HLH biology.
CDK8/19 transcriptional suppression as upstream cytokine storm control: The University of South Carolina's 2022 filings propose CDK8/CDK19 inhibition as a mechanism to suppress cytokine storm gene expression programs upstream of individual cytokine mediators — a conceptually differentiated approach from single-cytokine neutralization strategies. Downstream cytokines reduced include IL-8, IL-10, CCL2, CCL3, and CCL4.
SIRP-directed myeloid checkpoint modulation: Electra Therapeutics' 2021 patent encompasses both primary and secondary HLH among indications for SIRP-family antibodies, representing a myeloid cell regulatory strategy complementary to T cell-directed or cytokine-directed approaches. NIH research into HLH mechanisms continues to support the biological rationale for myeloid-targeted strategies.
HLH Pathogenic Cascade & Therapeutic Intervention Points
Six mechanistic intervention points identified across retrieved patent records, from upstream transcriptional regulation to downstream cytokine neutralization.
HLH Drug Pipeline — Key Questions Answered
IFN-γ emerges as the dominant pathogenic cytokine in HLH. Multiple NovImmune SA patent filings establish IFN-γ as a therapeutic target, noting that elevated CXCL9 — a downstream IFN-γ-inducible chemokine — serves as a biomarker for active disease. NovImmune SA (and its successor Swedish Orphan Biovitrum) describe IFN-γ neutralization as reversing haemophagocytosis in murine perforin- and Rab27a-deficient models.
The mechanistic rationale is the inhibition of downstream cytokine signaling through JAK1 heterodimerization (with JAK2 or JAK3), which transduces the signals of multiple inflammatory cytokines simultaneously — addressing the polycytokine nature of HLH. Preclinical evidence cites that JAK1/2 blockade lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis.
IL-18 is flagged as a relevant pathogenic mediator: Avalo Therapeutics patents explicitly include HLH/MAS among the conditions targeted by anti-IL-18 antibodies in subjects with elevated IL-18 levels, including virus-associated cases. IL-18 is positioned as a co-pathogenic cytokine in HLH/MAS, particularly in virus-triggered cases, addressing the IL-18-driven component of hyperinflammation that may not be fully controlled by IFN-γ neutralization alone.
The University of South Carolina discloses a novel mechanistic approach targeting cyclin-dependent kinase 8 (CDK8) and CDK19 as transcriptional regulators of cytokine-storm mediating cytokines. The mechanism involves inhibition of NF-κB-inducible inflammatory gene expression programs, with downstream reduction of cytokines including IL-8, IL-10, CCL2, CCL3, and CCL4. This approach is positioned for cytokine storm broadly, including the polycytokine environment relevant to HLH.
NovImmune SA / Swedish Orphan Biovitrum AG hold the dominant assignee position for HLH-specific IP, with at least 7 retrieved patent records across US, EP, AU, IN, CA, WO, and JP jurisdictions covering anti-IFN-γ methods and CXCL9 biomarker diagnostics for HLH. Incyte Corporation holds multiple active patent families for JAK1 inhibitors, with two recent US patents (2024, 2025) explicitly targeting HLH among cytokine-related disorders.
Retrieved results signal several combination and emerging directional themes: JAK inhibition combined with CAR-T cytokine management; anti-IL-18 in virus-triggered HLH/MAS (including coronavirus-associated cases); CDK8/19 transcriptional suppression as upstream cytokine storm control; and SIRP-directed myeloid checkpoint modulation. Combining anti-IL-18 with anti-IFN-γ approaches could address complementary cytokine axes.
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References
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — NOVIMMUNE SA, 2016, US [Patent]
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — NOVIMMUNE SA, 2018, EP [Patent]
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — NOVIMMUNE SA, 2018, IN [Patent]
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — NOVIMMUNE SA, 2017, AU [Patent]
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — NOVIMMUNE SA, 2016, WO [Patent]
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — NOVIMMUNE SA, 2016, CA [Patent]
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — NOVIMMUNE SA, 2023, JP [Patent]
- Methods and compositions for diagnosis and treatment of disorders in patients with elevated levels of CXCL9 and other biomarkers — Swedish Orphan Biovitrum AG, 2025, JP [Patent]
- JAK1 pathway inhibitors for the treatment of cytokine-related disorders — INCYTE CORPORATION, 2024, US [Patent]
- JAK1 pathway inhibitors for the treatment of cytokine-related disorders — INCYTE CORPORATION, 2025, US [Patent]
- Treatment and prevention of cytokine release syndrome using chimeric antigen receptors in combination with kinase inhibitors — SAAR GILL, 2022, JP [Patent]
- Treatment and prevention of cytokine release syndrome using a chimeric antigen receptor in combination with a kinase inhibitor — THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, 2019, SG [Patent]
- Methods and treatment involving antibodies to IL-18 — AVALO THERAPEUTICS, INC., 2023, IL [Patent]
- Methods and treatment involving antibodies to IL-18 — AVALO THERAPEUTICS, INC., 2023, MX [Patent]
- CDK8/19 inhibitors for the treatment of cytokine storm — UNIVERSITY OF SOUTH CAROLINA, 2022, CA [Patent]
- CDK8/19 inhibitors for the treatment of cytokine storm — UNIVERSITY OF SOUTH CAROLINA, 2022, WO [Patent]
- SIRPα, SIRPβ1, and SIRPγ antibodies and uses thereof — ELECTRA THERAPEUTICS, INC., 2021, CA [Patent]
- Compositions and Methods for the Treatment of Macrophage Activation Syndrome — CHILDREN'S HOSPITAL MEDICAL CENTER, 2021, US [Patent]
- Methods of treating cytokine-related adverse events — BRISTOL-MYERS SQUIBB COMPANY, 2022, IL [Patent]
- P041 Alemtuzumab-related haemophagocytic lymphohistiocytosis: negotiating the cytokine storm — Sheffield Teaching Hospital, Neurology, 2021 [Paper]
- Your critical care patient may have HLH (hemophagocytic lymphohistiocytosis) — Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, 2016 [Paper]
- Hemophagocytic Lymphohistiocytosis — National Center for Biotechnology Information (NCBI), StatPearls
- Epstein-Barr Virus and Cancers — World Health Organization (WHO)
- Understanding Hemophagocytic Lymphohistiocytosis — National Institutes of Health (NIH)
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. This report is derived from a limited set of patent and literature records retrieved across targeted searches and represents a snapshot of innovation signals within this dataset only. It should not be interpreted as a comprehensive view of the full field, clinical pipeline, or regulatory landscape.
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