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[Formula presented] There is an unmet need for novel therapies with distinct modes of action to offer clinical benefit for patients with myelofibrosis (MF) who become resistant or intolerant to JAK inhibitors. Lysine-specific demethylase-1 (LSD1) is a histone demethylase critical for self-renewal potential of malignant myeloid cells for hematopoietic differentiation, e.g., LSD1 licenses maturation of megakaryocytes, one cell type critical to the pathogenesis of MF. Bomedemstat is an orally active LSD1 inhibitor that in mouse models of MPNs reduced peripheral cell counts, splenomegaly, inflammatory cytokines, marrow fibrosis, mutant cell burden and overall survival (Jutzi et al. 2018). IMG-7289-CTP-102 is a global, open-label Phase 1/2 study evaluating bomedemstat dosed once daily in MF patients (NCT03136185). Data from this ongoing study are presented. Key eligibility criteria include IPSS int.-1 or -2 or high-risk patients refractory or resistant to, inadequately controlled by or intolerant of available approved therapy, or in the Investigator's judgment, are not candidates for available approved therapy, peripheral blast count <=10%, absolute neutrophil count >=0.5 x 10 9/L, and platelet count >=100 x 10 9/L. Key objectives are safety and reduction of spleen volume (SVR) by MRI/CT and total symptoms scores (TSS) using the MPN-SAF instrument. Serial bone marrow (BM) biopsies and imaging studies are read centrally. Of 261 genes recurrently mutated in AML/MPN/MDS, germline and somatic baseline and follow-up sequencing is conducted to quantify existing or new mutant alleles frequencies (MAF). Dosing is individually tailored using platelet count as a biomarker of bomedemstat activity on megakaryocyte function, targeting a range between 50-100 x 10 9/L and titrating as needed. At data cutoff (15 July 2021), the study is fully enrolled with 89 patients: 49% primary MF, 30% post-essential thrombocythemia-MF, 21% post-polycythemia vera-MF. Median age is 68 (35-88) with 52%

Background: For patients with essential thrombocythaemia (ET) intolerant of or resistant to hydroxyurea (HU), interferon or anagrelide, there is a need for therapies with distinct MOAs that reduce thromboses, improve the patient experience and potentially offer distinct clinical benefits. Lysine-specific demethylase-1 (LSD1) is a histone H3K4 demethylase critical for the self-renewal potential of malignant myeloid cells and the differentiation of myeloid progenitors, e.g., LSD1 licenses progenitors to mature into megakaryocytes, a cell central to the pathogenesis of ET. IMG-7289 (bomedemstat) is an orally active LSD1 inhibitor that reduced peripheral cell counts, splenomegaly, inflammatory cytokines, and mutant cell burdens in mouse models of MPNs (Jutzi et al. 2018). In an ongoing study of IMG-7289 for the treatment of myelofibrosis (MF) (NCT03136185), symptoms, platelets, neutrophils, mutant allele burdens and inflammatory cytokines were favorably impacted (Pettit et al. 2020). Aim(s): IMG-7289-CTP-201 is an ongoing, multi-national, open-label, 24-week Phase 2b study of bomedemstat taken once daily in patients with ET who are resistant to or intolerant of at least one standard of care treatment (NCT04254978). Key objectives are safety and reduction in the platelet count to <=400k/muL in the absence of thromboembolic events. Dosing is individually tailored targeting a platelet count between 200- 400k/muL. All patients were started at a dose of 0.6mg/kg/d and titrated as needed to the target platelet count range. Method(s): At the censoring date (16 Feb 2021), 10 patients had enrolled. All patients remain on study. The median duration of treatment is 85 days (6-141). Median age, 66 years (55-84), 20% males. 60% were deemed resistant to or intolerant of HU (by ELN criteria), 20% to anagrelide and 10% to interferon or busulfan. 40% had received at least one additional previous treatment. After a 14- to 28-day washout of prior ET treatment, the mean platelet and WBC co

Background: Patients with myelofibrosis (MF) require treatment when the clinical benefits of JAK inhibitors are exhausted; there is a clear need for novel therapies. Lysine-specific demethylase-1 (LSD1) is an enzyme critical for malignant stem cells and the differentiation, e.g., LSD1 licenses maturation of megakaryocytes, a key cell in MF pathogenesis. IMG-7289 (bomedemstat) is an orally active LSD1 inhibitor that in mouse models of MPNs reduced peripheral cell counts, splenomegaly, inflammatory cytokines, marrow fibrosis and, importantly, mutant cell burdens (Jutzi et al. 2018). Aim(s): IMG-7289-CTP-102 is an ongoing, multi-national, open-label, 24-week Phase 2 study of IMG-7289 taken once daily in MF patients resistant to all approved therapies. Key objectives are safety, and reduction a in spleen volume (SVR) and total symptoms scores (TSS). A platelet count >=100k/muL is a key inclusion criterion. Bone marrow (BM) biopsies and imaging studies are read centrally. Dosing is individually tailored using platelet count as a biomarker targeting a platelet count of 50-100k/muL. Method(s): At the censoring date (15Feb2021), 62 patients had enrolled, 24 patients remain on study. The median duration of treatment is 98 days (14-567). Median age is 68 (35-88) with 50% males; 47% had PMF, 34%, PET-MF, 19%, PPV-MF. All but 6 patients were previously treated with ruxolitinib; 47% had received up to 3 additional treatments. 33% were transfusion-dependent. 58% were IPSS high-risk, 42% intermediate risk-2. Of driver mutations, 66% were JAK2, 27% CALR, 6% MPL and one triple-negative. Of a panel of 261 genes mutated in AML/MPN/MDS, 65% had >=2 mutation, 46% had >=1 HMR mutations, 94% were in ASXL1. Result(s): Of all enrolled patients evaluable at 24 weeks for TSS (N=13), 85% recorded a reduction in TSS (mean change -31%; -81% to 21%) with 31% reporting >50% reduction. Of all patients evaluable for SVR after 24 weeks (N=19), 81% had a reduction in SV from baseline (mean SVR: -8%;

Background: For patients with essential thrombocythaemia (ET) intolerant of or resistant to hydroxyurea (HU), interferon or anagrelide, there is a need for therapies with distinct MOAs that reduce thromboses, improve the patient experience and potentially offer distinct clinical benefits. Lysine-specific demethylase-1 (LSD1) is a histone H3K4 demethylase critical for the self-renewal potential of malignant myeloid cells and the differentiation of myeloid progenitors, e.g., LSD1 licenses progenitors to mature into megakaryocytes, a cell central to the pathogenesis of ET. IMG-7289 (bomedemstat) is an orally active LSD1 inhibitor that reduced peripheral cell counts, splenomegaly, inflammatory cytokines, and mutant cell burdens in mouse models of MPNs (Jutzi et al. 2018). In an ongoing study of IMG-7289 for the treatment of myelofibrosis (MF) (NCT03136185), symptoms, platelets, neutrophils, mutant allele burdens and inflammatory cytokines were favorably impacted (Pettit et al. 2020). Aim(s): IMG-7289-CTP-201 is an ongoing, multi-national, open-label, 24-week Phase 2b study of bomedemstat taken once daily in patients with ET who are resistant to or intolerant of at least one standard of care treatment (NCT04254978). Key objectives are safety and reduction in the platelet count to <=400k/muL in the absence of thromboembolic events. Dosing is individually tailored targeting a platelet count between 200- 400k/muL. All patients were started at a dose of 0.6mg/kg/d and titrated as needed to the target platelet count range. Method(s): At the censoring date (16 Feb 2021), 10 patients had enrolled. All patients remain on study. The median duration of treatment is 85 days (6-141). Median age, 66 years (55-84), 20% males. 60% were deemed resistant to or intolerant of HU (by ELN criteria), 20% to anagrelide and 10% to interferon or busulfan. 40% had received at least one additional previous treatment. After a 14- to 28-day washout of prior ET treatment, the mean platelet and WBC co

[Formula presented] There is an unmet need for novel therapies with distinct modes of action to offer clinical benefit for patients with myelofibrosis (MF) who become resistant or intolerant to JAK inhibitors. Lysine-specific demethylase-1 (LSD1) is a histone demethylase critical for self-renewal potential of malignant myeloid cells for hematopoietic differentiation, e.g., LSD1 licenses maturation of megakaryocytes, one cell type critical to the pathogenesis of MF. Bomedemstat is an orally active LSD1 inhibitor that in mouse models of MPNs reduced peripheral cell counts, splenomegaly, inflammatory cytokines, marrow fibrosis, mutant cell burden and overall survival (Jutzi et al. 2018). IMG-7289-CTP-102 is a global, open-label Phase 1/2 study evaluating bomedemstat dosed once daily in MF patients (NCT03136185). Data from this ongoing study are presented. Key eligibility criteria include IPSS int.-1 or -2 or high-risk patients refractory or resistant to, inadequately controlled by or intolerant of available approved therapy, or in the Investigator's judgment, are not candidates for available approved therapy, peripheral blast count <=10%, absolute neutrophil count >=0.5 x 10 9/L, and platelet count >=100 x 10 9/L. Key objectives are safety and reduction of spleen volume (SVR) by MRI/CT and total symptoms scores (TSS) using the MPN-SAF instrument. Serial bone marrow (BM) biopsies and imaging studies are read centrally. Of 261 genes recurrently mutated in AML/MPN/MDS, germline and somatic baseline and follow-up sequencing is conducted to quantify existing or new mutant alleles frequencies (MAF). Dosing is individually tailored using platelet count as a biomarker of bomedemstat activity on megakaryocyte function, targeting a range between 50-100 x 10 9/L and titrating as needed. At data cutoff (15 July 2021), the study is fully enrolled with 89 patients: 49% primary MF, 30% post-essential thrombocythemia-MF, 21% post-polycythemia vera-MF. Median age is 68 (35-88) with 52%

Background: Patients with myelofibrosis (MF) require treatment when the clinical benefits of JAK inhibitors are exhausted; there is a clear need for novel therapies. Lysine-specific demethylase-1 (LSD1) is an enzyme critical for malignant stem cells and the differentiation, e.g., LSD1 licenses maturation of megakaryocytes, a key cell in MF pathogenesis. IMG-7289 (bomedemstat) is an orally active LSD1 inhibitor that in mouse models of MPNs reduced peripheral cell counts, splenomegaly, inflammatory cytokines, marrow fibrosis and, importantly, mutant cell burdens (Jutzi et al. 2018). Aim(s): IMG-7289-CTP-102 is an ongoing, multi-national, open-label, 24-week Phase 2 study of IMG-7289 taken once daily in MF patients resistant to all approved therapies. Key objectives are safety, and reduction a in spleen volume (SVR) and total symptoms scores (TSS). A platelet count >=100k/muL is a key inclusion criterion. Bone marrow (BM) biopsies and imaging studies are read centrally. Dosing is individually tailored using platelet count as a biomarker targeting a platelet count of 50-100k/muL. Method(s): At the censoring date (15Feb2021), 62 patients had enrolled, 24 patients remain on study. The median duration of treatment is 98 days (14-567). Median age is 68 (35-88) with 50% males; 47% had PMF, 34%, PET-MF, 19%, PPV-MF. All but 6 patients were previously treated with ruxolitinib; 47% had received up to 3 additional treatments. 33% were transfusion-dependent. 58% were IPSS high-risk, 42% intermediate risk-2. Of driver mutations, 66% were JAK2, 27% CALR, 6% MPL and one triple-negative. Of a panel of 261 genes mutated in AML/MPN/MDS, 65% had >=2 mutation, 46% had >=1 HMR mutations, 94% were in ASXL1. Result(s): Of all enrolled patients evaluable at 24 weeks for TSS (N=13), 85% recorded a reduction in TSS (mean change -31%; -81% to 21%) with 31% reporting >50% reduction. Of all patients evaluable for SVR after 24 weeks (N=19), 81% had a reduction in SV from baseline (mean SVR: -8%;

BACKGROUND: Gastric cancer is the second-leading cause of global cancer deaths, with metastatic disease representing the primary cause of mortality. To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. This involves a comparison between a primary tumor from a hereditary diffuse gastric cancer syndrome proband and its recurrence as an ovarian metastasis.

BACKGROUND: Gastric cancer is the second-leading cause of global cancer deaths, with metastatic disease representing the primary cause of mortality. To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. This involves a comparison between a primary tumor from a hereditary diffuse gastric cancer syndrome proband and its recurrence as an ovarian metastasis.

Ruxolitinib (Jakafi) is the one approved therapy for myelofibrosis (MF) based on reduction of splenomegaly and symptoms but JAK inhibition has not proven to significantly modify disease progression. There remains the need for novel therapies with distinct modes of action that can improve the patient experience of MF and impact progression. Lysine-specific demethylase, LSD1, is an epigenetic enzyme critical for self-renewal of malignant myeloid cells and differentiation of myeloid progenitors. LSD1 bound to GFI1b permits maturation of progenitors to megakaryocytes and enables their normal function. IMG-7289 (bomedemstat) is an orally available LSD1 inhibitor. In mouse models of myeloproliferative neoplasms (MPN), IMG-7289 reduced elevated peripheral cell counts, spleen size, inflammatory cytokines, mutant allele frequencies, and marrow fibrosis (Jutzi et al. 2018) supporting its clinical development. IMG-7289-CTP-102 is an ongoing, multi-center, open-label study that recently transitioned from a Phase 1/2a dose-range finding study to a Phase 2b study of IMG-7289 administered orally once-daily in adult patients with intermediate-2 or high-risk MF resistant to or intolerant of ruxolitinib. The key objectives are safety, PD, changes in spleen volume (MRI/CT) and total symptoms scores (TSS) using the MPN-SAF instrument. Inclusion criteria included a platelet count >=100K/muL. Bone marrow (BM) biopsies and imaging studies (both centrally-read) were conducted at baseline and during washout (post-Day 84). The MPN-SAF was self-administered weekly. Phase 1/2a patients were treated for 84 days followed by a washout of up to 28 days. Patients demonstrating clinical benefit could resume treatment for additional 12 week cycles. Dosing was individually tailored using platelet count as a biomarker of effective thrombopoiesis. Patients were started at a presumed sub-therapeutic dose of 0.25 mg/kg/d and up-titrated weekly until the platelet count rested between 50 and 100K/muL. This