Niktimvo (axatilimab-csfr) / Knight Therap, Syndax Pharma, UCB, Incyte, Royalty - LARVOL DELTA

Monocytosis as prognostic factor for chronic graft versus host disease (ASH 2025) - "Elevated and activated monocyte levels have been documented in cGvHD and therapies such as CSF-1R inhibition with axatilimab have shown benefit in refractory cases...CONCLUSIONS In conclusion, monocytosis onset following allo-HSCT is a prognostic biomarker of cGvHD. Monocytes' count ≥ 1.0 10 9 / L may help to identify patients at a higher risk of cGvHD, particularly those with moderate and severe forms."

Biomarker • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • TNFA

Axatilimab in combination with ruxolitinib in patients with newly diagnosed chronic graft-versus-host disease: Interim safety analysis of a phase 2, randomized study (ASH 2025) - P2 | "In this interim analysis of a randomized phase 2 trial, the combination of AXA+RUX was welltolerated with no evidence of additive toxicity."

Clinical • Combination therapy • P2 data • Bone Marrow Transplantation • Chronic Graft versus Host Disease • CNS Disorders • Constipation • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Insomnia • Otorhinolaryngology • Respiratory Diseases • Sleep Disorder • Vertigo • CSF1R • JAK1 • JAK2

Long-term treatment duration and safety of axatilimab among patients with chronic graft-versus-host disease in AGAVE-201 (ASH 2025) - P2 | "Initial data from the AGAVE-201 study showed a promising overall response rate and safetyprofile for AXA in patients with cGVHD. Long-term safety follow-up showed a continued tolerable safetyprofile with a prolonged duration of exposure. Of 239 patients who received AXA, 33 (14%) havecontinued on treatment with a median duration of therapy of 2.8 years, suggesting long-term safety andclinical benefit from treatment."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Safety analysis of axatilimab in patients with chronic graft-versus-host disease in an expanded access program (ASH 2025) - P, P2 | "The most common concomitant cGVHDmedications were belumosudil (65.4%), prednisone (60.6%), and ruxolitinib (51.0%). This EAP represents the largest collated experience of AXA treatment in cGVHD outside ofthe AGAVE-201 trial. The safety profile of AXA was consistent with that observed in clinical trials, and nonew or unexpected toxicities were reported. Patients received prior cGVHD treatments and had multi-organ involvement."

Clinical • Bone Marrow Transplantation • Cardiovascular • Chronic Graft versus Host Disease • Cough • Fibrosis • Gastrointestinal Disorder • Graft versus Host Disease • Heart Failure • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock • CSF1R

Phase 1b/2 study of axatilimab in combination with azacitidine in advanced Phase MPN, MDS/ MPN overlap and high-risk CMML (ASH 2025) - P1/2 | "Current therapies are limited to hydroxyurea for pts with proliferativephenotypes and hypomethylating agents for pts with dysplastic phenotype with complete response (CR)rates <20% and second-line options lacking. The secondary objectives includeevaluation of safety and tolerability of the combination with a focus on immune-related side effects fromAxa and QoL assessment using the MPNSAF scores. Correlative studies will evaluate markers of myeloiddifferentiation, mechanisms of intrinsic and acquired resistance to the regimen by tracking morphologic,signaling and epigenetic changes over time, and biomarkers specific to CSF-1R biology."

Combination therapy • Metastases • P1/2 data • Chronic Graft versus Host Disease • Chronic Myelomonocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Myelodysplastic Syndrome

Trial in progress: A phase 3, randomized, double-blind, placebo-controlled study of axatilimab and corticosteroids as initial treatment for moderate to severe chronic graft-versus-host disease (ASH 2025) - P2, P3 | "Patients will be randomized in a 1:1ratio to intravenous axatilimab 0.3 mg/kg Q2W or placebo, in combination with prednisone at a startingdose of 1.0 mg/kg/day (or equivalent dose of methylprednisolone or prednisolone), with a recommendedtapering schedule starting at Week 2. This phase 3 study will provide insight into the efficacy and safety of axatilimab with systemiccorticosteroids as first-line therapy for patients aged ≥12 years with moderate to severe cGVHD."

Clinical • P3 data • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology

CSF1R-CSF1 axis blockade with axatilimab effectively targets leukemia stem cells and monocytes in AML resistant to BH3 mimetics (ASH 2025) - "Background : The BCL2 inhibitor venetoclax (VEN), in combination with hypomethylating agents, ishighly effective in inducing remissions in AML...The effects on cytokine production, AML blasts, stem cells, andmonocytes were evaluated. MV4-11 cells with acquired resistance to BH3 mimetics targeting BCL2 or MCL1,peculiarly to VEN and VEN plus MCL-1 inhibitor AMG176, exhibited elevated levels of cytokinesincluding CSF1, TGF-1ß, IL-4, and IL-10 compared to parental cells... CSF1, TGF-1ß, IL-4, IL-10, and numerous other cytokines are increased in BH3mimetic resistant AML cell lines and patient samples. Inhibition of CSF1R targets ERK and AKTsignaling and significantly enhances the cytotoxic effects of BH3 mimetics against AML cells,stem/progenitor cells, and monocytes resistant to VEN. Furthermore, blockage of CSF1R-CSF1axis suppresses multiple cytokines in vitro and in vivo, and markedly improves the therapeuticefficacy of BH3 mimetics in a VEN/AZD5991/Decitabine..."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • ANXA5 • CSF1R • IL10 • IL4 • TP53

CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation (ASH 2025) - "We used cereblon (CRBN)-transgenic mice that are geneticallymodified to allow engagement of thalidomide and its derivatives (including lenalidomide), resulting indegradation of the IMiD targets, Aiolos and Ikaros. The ability of CSF-1R inhibition to deplete CSF-1R+ macrophages and prevent tissue fibrosishas previously been demonstrated in preclinical models of chronic graft-versus-host disease (GVHD).Subsequent clinical trials have proven axatilimab, a human anti-CSF-1R antibody, to be well tolerated andeffective for the treatment of chronic GVHD, leading to FDA approval. Given lenalidomide is already astandard maintenance therapy, combination therapy with axatilimab represents a readily testable clinicalstrategy for augmenting progression-free survival in patients with multiple myeloma after ASCT."

IO biomarker • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Malignancies • Immunology • Multiple Myeloma • Transplantation • CD163 • CRBN • IKZF1 • ITGAM • ITGAX • PD-L1 • PVR • SIGLEC1

CSF-1R+ macrophages orchestrate human skin chronic graft-versus-host disease (ASH 2025) - "However, spatial and temporal analysis of immune responses at high resolutionhas not been possible in human tissue to date, a major limitation to our understanding of diseasepathophysiology and responses to therapy.We undertook sub-cellular spatial transcriptomics with the 10x Xenium platform to dissect tissueimmune networks involved in human patient skin, first from lichenoid cGVHD biopsies relatively earlyafter HCT (n=8), then before and after treatment with the CSF-1R-blocking antibody axatilimab in latersclerotic phases in patients enrolled in the AGAVE-201 trial that led to FDA approval (Wolff D et al, NEJM 2024) (n=5 responders + 5 non-responders).Skin with confirmed lichenoid cGVHD histopathology segregated into high (HI) and low (LI) immune cell-infiltrated tissue that reflected macrophage and T cell abundance...The deletion of CSF-1R+ macrophages withaxatilimab in more sparsely infiltrated sclerotic phases of cGVHD was associated with Treg expansion andclinical..."

Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • CD74 • CD8 • CSF1R • FOXP3 • IL17A • TBX21 • TGFB1 • ZEB2

Pharmacodynamic analysis of AGAVE-201 indicates changes in CSF-1R–expressing cells and associated biomarkers potentially contributing to chronic graft-versus-host disease resolution (ASH 2025) - P2 | "Treatment with axatilimab(AXA), a high-affinity monoclonal antibody targeting CSF-1R, depletes CSF-1R–dependent monocytes andmacrophages... Proteomic analysis of AGAVE-201 revealed changes in soluble markers associated with CSF-1R–expressing cells and were consistent with a reduction in the number and cellular function of CSF-1R–regulated monocyte lineage, contributing to disease resolution. Biomarkers that correlate with skintightening improvement may indicate potential involvement in cGVHD skin disease and/or resolution inresponse to AXA. These findings support the mechanism of action of AXA and provide hemodynamicevidence of target engagement and tissue-specific effects."

Biomarker • PK/PD data • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Dermatology • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • CD14 • CD163 • CSF1R • IL34 • KRT5 • PTPRC

Safety and feasibility of 0.6 mg/kg every 4 weeks dosing of axatilimab in patients treated in the AGAVE-201 study (ASH 2025) - P2 | "Among these 19 patients, demographics (median [range] age, 50.0 [20–73] y; male,63.2%) and baseline clinical characteristics (median [range] number of organs involved at baseline, 3.0 [2–8]; severe disease, 73.7%; prior use of ibrutinib, ruxolitinib, or belumosudil, 89.5%) were comparable tothe full cohort initially randomized to 0.3 mg/kg Q2W. Transition to 0.6 mg/kg Q4W (without dose capping) is feasible and well tolerated in patientstreated with axatilimab 0.3 mg/kg Q2W on the AGAVE-201 study. The Q4W dosing strategy at the 0.6mg/kg dose identified no new safety signals. Patients had a prolonged duration of therapy, with a medianof 20.9 months (1.7 y), and 84% of patients continued treatment, suggesting ongoing clinical benefit.These data provide evidence of the safety and feasibility of a 0.6 mg/kg Q4W dosing strategy in alignmentwith the AGAVE-201 protocol."

Clinical • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • CSF1R

A Study to Evaluate Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft-Versus-Host Disease After at Least 2 Prior Lines of Systemic Therapy (AGAVE-256) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics

Niktimvo: “Transition to axatilimab 0.6 mg/kg Q4W was feasible and well tolerated in R/R cGVHD patients treated with 0.3 mg/kg Q2W in the AGAVE-201 trial”; Chronic graft versus host disease (Syndax) - ASH 2025

P2 data • Chronic Graft versus Host Disease • Immunology

…Results from the phase 2 AGAVE-201 trial (NCT04710576) presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition (Cancer Network) - "In the AGAVE-201 trial, patients who met pre-specified criteria could change their dosing schedule from 0.3 mg/kg every 2 weeks to 0.6 mg/kg every 4 weeks, without dose capping....Treatment with a dose of 0.6 mg/kg every 4 weeks led to an overall response rate of 94.7% (95% CI, 74.0%–99.9%), including partial and complete response rates of 89.5% and 5.3%, respectively....After switching doses, patients were on treatment for a median of 20.9 months (range, 2–32). At data cutoff, 16 patients (84.2%) maintained the 0.6 mg/kg dose. Of the 3 who did not, 2 patients switched back to the FDA-approved dose at 4.6 and 18.6 months following the switch, respectively, while 1 patient switched back due to an adverse event (AE) at 3.4 months."

P2 data • Chronic Graft versus Host Disease

Sarah Cannon Research Institute to Present Research on Advances in…Blood Disorders at 2025 ASH Annual Meeting & Exposition (Sarah Cannon Research Institute (SCRI))

Clinical data • Beta-Thalassemia • Chronic Graft versus Host Disease • Sickle Cell Disease

Trends in GVHD Epidemiology, Prophylaxis and Management: The Gruppo Italiano per il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare (GITMO) GVHD24 Study. (PubMed, Am J Hematol) - "Compared to historical reports, both aGVHD and cGVHD appeared to have decreased in the recent transplant era, possibly due to the extension of T-cell depletion, the availability of effective second-line approaches in SR/D GVHD and improved anti-infectious prophylaxis and treatments."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation

Real-World Clinical Outcomes of Severe, Treatment-Refractory Chronic Gvhd Patients Treated with Axatilimab Combination Therapies (ASH 2024) - "Current FDA approved agents for the treatment of refractory cGVHD include ibrutinib, ruxolitinib (rux) and belumosudil (bel). Patients tolerated combination axa with rux and/or bel with 4/8 patients receiving rux-bel-axa. This is the first report of the combination of axa with rux and/or bel, demonstrating that a combination approach with CSF1R/JAK2/ROCK2 inhibition is feasible, tolerable, and may yield clinical benefit in highly refractory cases of cGVHD with fibrotic manifestations."

Clinical • Clinical data • Combination therapy • Real-world • Real-world evidence • Anemia • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Rheumatology • Scleroderma • Systemic Sclerosis • Thrombocytopenia • JAK2

Details on Incyte data presentations at ASH include: Poster Presentations (Incyte Press Release)

Clinical data • Acute Graft versus Host Disease • Anemia • Chronic Graft versus Host Disease • Essential Thrombocythemia • Follicular Lymphoma • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera

Safety and Efficacy of Axatilimab at 3 Different Doses in Patients with Chronic Graft-Versus-Host Disease (AGAVE-201) (ASH 2023) - P1/2, P2 | "Concomitant use of corticosteroids, calcineurin inhibitors, or mammalian target of rapamycin inhibitors (sirolimus or everolimus) was allowed...Patients were heavily pretreated with a median of 4 prior lines of therapy, including ruxolitinib (74%), belumosudil (23%), and ibrutinib (31%)... The AGAVE-201 pivotal trial met its primary endpoint for all doses studied. Axatilimab treatment of refractory cGVHD in heavily pretreated patients resulted in robust clinical activity and durable responses in all 3 dose cohorts, with the highest ORR and least toxicity at the 0.3 mg/kg Q2W dose. Adverse events consisted primarily of transient laboratory abnormalities and other on‑target effects known to be associated with CSF-1R block."

Clinical • Chronic Graft versus Host Disease • Cytomegalovirus Infection • Fibrosis • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation

Combination ruxolitinib, belumosudil, and axatilimab yields clinically significant symptomatic improvements in treatment-refractory chronic GVHD. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Dynamics of Overall and Organ-Specific Responses to Axatilimab in Chronic Graft-Versus-Host Disease: Analysis from the Agave-201 Study (ASH 2024) - P2 | "Patients received a median of 4 prior therapy lines (range, 2–15), including ruxolitinib (74.3%), ibrutinib (31.1%), and belumosudil (23.2%). Median times to organ-specific responses ranged from 1.0 to 3.7 months across organs; lower GI, upper GI, esophagus, liver, and joints/fascia were fastest to respond, whereas lung, mouth, eye, and skin responses were slower due to the highly fibrotic nature of these organ manifestations. Overall, these data highlight the potential for rapid onset of clinical activity and symptom improvement with AXA in inflammatory and fibrotic manifestations of cGVHD among a heavily pretreated population with longstanding cGVHD."

Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Inflammation • CSF1R

Efficacy of Axatilimab in the Management of Chronic Graft-Versus-Host Disease (ASH 2024) - "The pooled incidence of drug discontinuation due to treatment-related adverse events was 16% (95% CI : 0.12-0.20, I²=0%, p=0.94).CONCLUSIONIn this systematic review, axatilimab exhibited promising therapeutic outcomes for refractory cGVHD based on the findings from Phase I and II clinical trials, with an acceptable safety profile. However, prospective clinical trials with randomization are needed to consolidate these findings."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Musculoskeletal Diseases

Axatilimab Ameliorates Inflammation and Fibrosis By Targeting Macrophages in a Preclinical Model of Chronic GVHD (ASH 2023) - "Blocking CSF-1R signaling in primary, differentiated macrophages dramatically alters the secretomes and gene expression profiles of these cells. Macrophages are key inducers of fibroblast growth factors, which in turn promote fibrotic disease. These data confirm that production of inflammatory and pro-fibrotic factors by pro-inflammatory macrophages is inhibited in the presence of axatilimab, thereby supporting the notion that axatilimab provides a unique opportunity to therapeutically intervene or prevent fibrosis in cGVHD."

Preclinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • Transplantation • CCL2 • CCL22 • CSF1R • IL10 • IL1B • IL34 • IL4 • IL5 • MYC

Axatilimab Abrogates Inflammatory Cytokines and Chemokines and Interrupts the Differentiation of Monocytes to Macrophages, a Pathogenic Driver of Inflammation and Fibrosis in cGVHD (ASH 2024) - P1/2, P2 | "Conclusions : Taken together, these data suggest that blocking CSF-1/CSF-1R signaling by axatilimab reduces proinflammatory signaling in monocytes and monocyte-derived macrophages and specifically reduces the number of monocytes and macrophages in the peripheral blood and peritoneal lavages of human CSF-1R knock-in mice. These data support the observation from clinical studies (phase 1/2 and pivotal AGAVE-201 study) that nonclassical monocytes were depleted in patients with cGVHD treated with axatilimab."

Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • CCL4 • CCL8 • CD14 • CXCL5 • CXCL6 • CXCL8 • ITGAM • PTPRC • TGFB1

Details on Incyte data presentations at ASH include: Oral Presentations (Incyte Press Release)

Clinical data • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera