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Results from an ongoing phase II study of IMG-7289 (bomedemstat) in patients with advanced MF

Feb 16, 2021

Many patients with myelofibrosis (MF) become intolerant or resistant to currently approved JAK inhibitors, indicating the need for new treatments. IMG-7289 (bomedemstat), a lysine-specific demethylase-1 inhibitor, has been granted priority review under the European Medicines Agency PRIME (priority medicines) scheme based on early favorable results in patients with MF.1

Lysine-specific demethylase-1 plays a role in epigenetic regulation supporting differentiation of progenitors to mature megakaryocytes. It has been linked to clonogenic expansion of malignant cells and is often overexpressed in myeloproliferative neoplasms (MPN). In MPN mouse models, bomedemstat has shown to deplete malignant stem cells, decrease bone marrow fibrosis, reduce cytokine release, and improve survival. At the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, Kristen Pettit presented initial safety and efficacy results of IMG-7289 in patients with advanced MF (NCT03136185),2 an extension of a 12-week pharmacokinetic and dose range-finding phase I/IIa study.

Study design

Patients with International Prognostic Scoring System intermediate-2 or high-risk MF, who were refractory or resistant to the approved therapies ruxolitinib or fedratinib and had a platelet count ≥100 × 109/L, self-administered oral IMG-7289 once daily for 24 weeks.

Primary endpoints were:

  • Safety and tolerability
  • Pharmacokinetics
  • Spleen volume reduction assessed by magnetic resonance imaging or computerized tomography

Exploratory endpoints included:

  • Symptom reduction measured by the self-administered MPN symptom assessment form total symptom score
  • Changes in variant allele frequency (VAF)
  • Changes in cytokine profiles and bone marrow fibrosis

Dosing was titrated for each patient using platelet count as a biomarker for megakaryocyte suppression. As all patients in the phase I/IIa study required uptitration from a starting dose of 0.25 mg/kg, during phase IIb a starting dose of 0.5 mg/kg was used.


At the time of data presentation, 18 patients were enrolled in phase I/IIa, of which 14 had 12-week data available, and eight had completed 24 weeks of treatment. A further 31 patients were enrolled in phase IIb. Characteristics for all patients in the study so far are summarized in Table 1.

Table 1. Characteristics of all patients receiving IMG-7289 in the study2

IPSS, International Prognostic Scoring System; MPN-SAF, myelofibrosis neoplasm symptom assessment form; PET-MF, post-essential thrombocytosis myelofibrosis; PMF, primary myelofibrosis; PPV-MF, post-polycythemia vera myelofibrosis; TSS, total symptom score.


N = 49

Median age, years (range)

68 (34–88)

Male, %


Disease subtype, %








IPSS risk classification, %






≥2 mutations, %


Median spleen volume, cm3 (range)

1,452 (193–6,819)

Median TSS by MPN-SAF (range)

33 (1–82)

Mean hemoglobin, g/dL (range)

10.2 (7.1–15.1)

Platelets, ×109/L (range)

325 (100–1,585)


IMG-7289 has not shown any deaths or dose-limiting toxicities at doses up to 6 mg/kg and no serious safety signals after > 4 years follow-up in different studies. Of the 917 adverse events (AEs) that were reported, 307 were considered related to IMG-7289, with dysgeusia the most common non-hematologic AE (35%). There were six treatment-related serious AEs, five of which were classified as Grade 3, including one case each of headache, heart failure, painful splenomegaly, rectal bleeding, upper gastrointestinal bleeding, and vertigo.


After 12 weeks of IMG-7289, the majority of patients reported an improvement in total symptom score, such as fatigue (Table 2). In those patients included in the phase IIb study, spleen volume at 12 weeks was mostly modest with only two patients experiencing a spleen volume reduction of >35%. No cases of progression to acute myeloid leukemia were reported. Improvements in anemia and bone marrow fibrosis were also noted in some patients.

Table 2. Changes in spleen volume and TSS in patients with myelofibrosis treated with IMG-72892

SVR, spleen volume reduction; TSS, total symptom score.

Phase of study

Efficacy measure

Week 12 results

Phase I/II (n = 32)

Reduction in TSS at 12 weeks, n (%)

25 (78)


TSS reduction ≥50%, n (%)

8 (25)

Phase IIb (n = 14)

SVR at 12 weeks, n (%)

12 (86)


Median change in spleen volume, %



SVR ≥35%, n (%)

2 (14)


SVR ≥20%, n (%)

4 (29)

From serial tracking of distinct VAFs across 22 patients, a decrease in some or all somatic mutations was observed in seven patients (32%). Stable VAFs were seen in 12 patients (55%), and three patients (14%) had an increase in VAFs. No new mutations were identified in those patients who were in the study for ≥550 days. Interestingly, extensive germline sequencing studies lead to the identification of rare germline mutation in BOD1L1 in 7 out of 42 patients with MF. Loss of BOD1L1 is linked with genome instability.


The results from this ongoing phase IIb study are encouraging, with IMG-7289 demonstrating adequate safety and good tolerability in patients with advanced MF. As a monotherapy, clinical activity was also shown in these patients, including improvements in symptoms, and reductions in spleen volume and bone marrow fibrosis. Mutant allele frequencies were decreased for some mutations with IMG-7289 treatment, although the clinical significance of these genomic findings has yet to be determined. In addition, no new mutations or progression to acute myeloid leukemia occurred. Recruitment for this study in MF is continuing, alongside further studies in essential thrombocytosis and polycythemia vera. A combination study of IMG-7289 plus ruxolitinib will commence soon.

  1. Jutzi JS, Kleppe M, Dias J, et al. LSD1 inhibition prolongs survival in mouse models of MPN by selectively targeting the disease clone. Hemasphere. 2018;2(3):e54. DOI: 1097/HS9.0000000000000054
  2. Yacoub A, Pettit KM, Bradley TJ, et al. A phase 2 study of the LSD1 inhibitor IMG-7289 (bomedemstat) for the treatment of advanced myelofibrosis. Oral abstract #51. 62nd ASH Annual Meeting and Exposition; Dec 5, 2020; Virtual.