On June 11, 2021 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel therapies targeting diseases resulting from dysfunction of the CXCR4 pathway, reported positive preliminary efficacy and safety data from its ongoing Phase 1b clinical trial of its lead candidate mavorixafor, in combination with ibrutinib, in Waldenström’s macroglobulinemia patients with both MYD88 and CXCR4 mutations (Press release, X4 Pharmaceuticals, JUN 11, 2021, View Source [SID1234583905]). These data are included in a poster published today at this year’s European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

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"We are very pleased to present this exciting first look at the data from our ongoing Phase 1b trial in double-mutation Waldenström’s patients," said Diego Cadavid, M.D., Chief Medical Officer of X4 Pharmaceuticals. "Despite still being in the low- and mid-dose ranges of mavorixafor, we are already seeing robust decreases in IgM levels – an important signal of clinical response – showing the potential benefit for mavorixafor in combination with ibrutinib. The combination therapy is demonstrating good tolerability and promising results across additional pharmacodynamic parameters, including increases in total hemoglobin and mobilization of white blood cells. We look forward to presenting longer-term data and an expanded data set from this trial later in the year."

"While ibrutinib has significantly advanced the treatment of Waldenström’s macroglobulinemia, we have observed that there remains a clinical unmet need for patients with concurrent CXCR4 and MYD88 mutations," said Steven Treon, M.D., Ph.D., FACP, FRCP, Director of the Bing Center for Waldenström’s Macroglobulinemia at Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School, and the poster’s lead author. "I am encouraged by the preliminary safety and efficacy data from the ongoing combination trial of ibrutinib and mavorixafor in this difficult-to-treat patient population and look forward to continuing this important research."

Key Highlights of the Preliminary Low- and Mid-Dose Phase 1b Results

As of April 15, 2021, 8 patients had been enrolled in the Phase 1b clinical trial with a median duration of treatment of 156 days; data presented are primarily from patients in Cohort A who received low- and mid-range doses of mavorixafor plus ibrutinib; 4 patients were treated for more than six 28-day cycles.
Mavorixafor exposures tracked with sustained and dose-dependent increases in white blood cell counts, confirming target engagement and mavorixafor mechanism of action.
All patients (100%) experienced reductions in serum IgM and no patients’ disease progressed while on treatment.
At 6 months, mavorixafor plus ibrutinib showed signs of meaningful reductions in IgM versus comparable, previously published data of ibrutinib monotherapy in double-mutation patients:
Patients achieved median reductions of 60%-75% in serum IgM levels normalized to baseline; this compares to published ibrutinib monotherapy reductions of 38%-45% in double-mutation patients.
2 out of 4 patients (50%) had >50% reduction in serum IgM from baseline; comparable reductions have been reported in only 28%-38% of double-mutation patients on ibrutinib monotherapy.
One patient achieved IgM levels within normal range, a key criterion for a complete response.
All patients with hemoglobin levels below normal at baseline had increases during treatment, with a median change in hemoglobin of >20 g/L, approaching normal levels and suggesting reduction in cancer burden in the bone marrow.
Mavorixafor and ibrutinib exposures were consistent with previous single-agent studies, suggesting no drug-drug interactions.
Data suggest that mavorixafor plus ibrutinib is well tolerated with no serious adverse events reported.
Patient enrollment and dose escalation to the highest mavorixafor dose (600 mg) continues.
The e-poster (EP784) entitled: "Preliminary Clinical Data From a Phase 1b Study of Mavorixafor and Ibrutinib in Patients With Waldenström’s Macroglobulinemia With MYD88 and CXCR4 Mutations" is now available on the X4 corporate website. Conference attendees can access an accompanying audio presentation by Dr. Treon on the Congress website.

X4 will host a conference call and webcast at 7:00 am ET today that will include presentations by X4 senior executives and a "Fireside Chat" and Q&A with poster co-author Christian Buske, M.D., Director of the Institute of Experimental Cancer Research and Attending Physician, Senior Consultant at the University Hospital of Ulm, and Founder and Coordinator of the European Consortium for Waldenström’s Macroglobulinemia.

The conference call can be accessed by dialing (866) 721-7655 (domestic) or (409) 216-0009 (international), followed by the conference ID: 4492859. The live webcast will be accessible on the Events & Presentations page of the company’s website at investors.x4pharma.com. The conference call slide deck will be made available upon completion of the event and the webcast replay will be available approximately two hours after the completion of the event on X4’s website.

This Phase 1b clinical trial is being conducted with the support of AbbVie Inc. and The Leukemia & Lymphoma Society’s Therapy Acceleration Program (LLS TAP).

About Waldenström’s Macroglobulinemia and Associated CXCR4 Mutations
Waldenström’s macroglobulinemia is a rare B-cell lymphoproliferative disorder characterized by increased immunoglobulin M (IgM). Greater than 90% of patients with Waldenström’s have acquired mutations in the MYD88 gene, with a subset (30%–40%) also having mutations in chemokine receptor CXCR4. The presence of the CXCR4 mutation is associated with greater cancer burden, higher serum IgM levels, and increased risk of developing a serious emergent condition called symptomatic hyperviscosity syndrome. Importantly, the presence of CXCR4 mutations has been shown to negatively impact patients’ response to ibrutinib (a BTK inhibitor), as manifested by delayed response, inferior depth of response, and/or shorter progression-free survival.

About Mavorixafor and the Phase1b Clinical Trial in Waldenström’s Macroglobulinemia
Mavorixafor is an oral small-molecule antagonist of the CXCR4 receptor with a demonstrated ability to inhibit binding of its ligand, CXCL12; this inhibition of CXCR4 has been shown to sensitize Waldenström’s cells with both MYD88 and CXCR4 mutations to BTK antagonists, such as ibrutinib. The ongoing Phase 1b, open-label, multicenter, single-arm study (NCT04274738) examines intra-patient dose escalation, safety, pharmacokinetics, and pharmacodynamics of mavorixafor in combination with ibrutinib in patients with a diagnosis of Waldenström’s macroglobulinemia and confirmed MYD88 and CXCR4 genetic mutations. In the study, patients are initiated on oral, once-daily doses of ibrutinib 420 mg and mavorixafor 200 mg (low dose); in Cohort A, patients are escalated to 400 mg mavorixafor (mid-dose) after 28 days if fewer than two dose-limiting toxicities are observed at the low dose; in Cohort B, patients are escalated from 200 mg to 400 mg and finally to 600 mg (high dose) after each dose level is deemed tolerable. Patients are followed for adverse events and change from baseline in serum IgM and hemoglobin, pharmacokinetics, and pharmacodynamic markers, including peripheral white blood cell counts (WBCs).

On June 11, 2021 HiFiBiO Therapeutics, a multinational biotechnology company with unique expertise in immune modulation and single-cell science, reported a publication in Science Advances with its collaborators at Nankai University, ShanghaiTech University, and Jiao Tong University about the development of a high-throughput droplet-based approach to identify novel antibodies with functional readouts beyond simple binding (Press release, HiFiBiO Therapeutics, JUN 11, 2021, View Source [SID1234583928]). Innovative therapeutics such as bispecific T-cell engager (BiTE) antibodies and agonist antibodies against costimulatory receptors can reach their full potential through such functional screening.

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This approach improves upon conventional screening by allowing for the analysis and screening of functional antibodies at the single-cell level with unprecedented throughput, allowing for more diverse candidates and successful hits. To demonstrate the technical capabilities of the platform, researchers successfully identified functional antibodies for CD40 agonism with low frequency (<0.02%) in two rounds of screening. Additionally, the versatility of the system was shown by combining an anti-Her2 x anti-CD3 BiTE antibody library with functional screening, enabling efficient identification of active anti-Her2 x anti-CD3 BiTE antibodies.

"Our single-cell microfluidic platform’s robustness and versatility has enabled the efficient and unbiased discovery of active antibodies with markedly increased throughput and accuracy," said Bingqing Shen, PhD, Director, Antibody Discovery of HiFiBiO Therapeutics. "We look forward to further leveraging our technology towards identification of functional antibodies for agonist and bispecific antibodies to ensure a sustainable pipeline of next generation novel immunotherapies."

"This technology addresses two main bottlenecks plaguing conventional screening methods for novel immunotherapies, namely, candidate functionality and diversity in a high throughput manner," said Professor Zhang, "Functional droplet-based screening enables direct linking of antibody discovery to functional outcomes which could optimize screening efforts significantly and accelerate the antibody drug discovery process. I can envision that the platform can be applied to screening of other types of molecules such as cytokines and to high-throughput analysis of cell-cell interactions. For example, dendritic cells expressing a library of neoantigens are co-encapsulated with tumor-infiltrating T cells to map the pairs of cognate antigens and T cell receptors (TCRs)."

On June 11, 2021 Bristol Myers Squibb (NYSE: BMY) and Acceleron Pharma Inc. (NASDAQ: XLRN) reported the first data from the Phase 2 BEYOND study evaluating Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, plus best supportive care in adult patients with non-transfusion dependent (NTD) beta thalassemia, were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress as part of its Presidential Symposium (Abstract #S101) (Press release, Bristol-Myers Squibb, JUN 11, 2021, View Source [SID1234583847]). Results demonstrated that 77.7% of patients treated with Reblozyl achieved a hemoglobin increase (≥1.0 gram/deciliter) compared to 0% of patients in the placebo arm. Changes in patient-reported outcomes also correlated with increases in hemoglobin. NTD beta thalassemia is a term used to describe patients who do not require lifelong regular red blood cell (RBC) transfusions for survival, although they may require occasional or even frequent transfusions, usually for defined periods of time.

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"Patients with non-transfusion dependent beta thalassemia experience chronic anemia and iron overload, which may lead to a range of clinical complications, and treatment options are greatly needed," said Ali Taher, M.D., Ph.D., FRCP, of American University of Beirut and BEYOND study investigator. "Results from the BEYOND study show the clinical potential of luspatercept to sustain the elevation of hemoglobin levels in a majority of patients regardless of their baseline hemoglobin status, and improvements were noted in quality of life outcomes in adults with non-transfusion dependent beta thalassemia."

Reblozyl is the first and only erythroid maturation agent approved in the European Union, United States and Canada to address anemia-associated beta thalassemia and lower-risk myelodysplastic syndromes, representing an important class of therapy for eligible patients.1,2,3

"We are very encouraged by the magnitude of improvement seen among Reblozyl-treated patients in the BEYOND trial," said Habib Dable, President and Chief Executive Officer of Acceleron. "These data further strengthen our confidence in Reblozyl’s potential to become a meaningful option for this important, underserved patient population around the world."

"The results we are presenting at EHA (Free EHA Whitepaper) continue to highlight multiple benefits observed with Reblozyl to treat anemia and achieve transfusion independence, as well as show its potential for patients with non-transfusion dependent disease who face a range of serious, often lifelong health complications," said Noah Berkowitz, M.D., Ph.D., senior vice president, Hematology Development, Bristol Myers Squibb. "Along with our partners at Acceleron, we are committed to advancing our clinical program for Reblozyl for patients living with anemia-associated blood disorders."

BEYOND Study Results

BEYOND is a Phase 2, randomized, double-blind, placebo-controlled multi-center study to determine the efficacy and safety of Reblozyl versus placebo in adults with non-transfusion dependent (NTD) beta thalassemia. Eligible patients were ≥18 years with beta thalassemia or hemoglobin (Hb) E beta thalassemia and received ≤5 red blood cell (RBC) units in the 24 weeks prior to randomization, with mean baseline Hb ≤10.0 gram/deciliter (g/dL).4

In the study, 145 patients were randomized 2:1 to receive Reblozyl, 1 milligram/kilogram (titration up to 1.25 mg/kg) or placebo subcutaneously every 3 weeks for ≥48 weeks. Patients in both arms continued to receive best supportive care, including RBC transfusions as indicated and iron chelation therapy. The primary endpoint was achievement of ≥1.0 g/dL mean Hb increase from baseline over a continuous 12-week interval from weeks 13-24 in the absence of RBC transfusions. Secondary endpoints included proportion of patients who remained transfusion free over weeks 1-24, who achieved mean Hb increase of ≥1.5 g/dL from baseline to weeks 13-24, and mean change in NTD beta thalassemia patient-reported outcome tiredness and weakness (NTDT-PRO T/W) domain scores (higher scores reflect worse quality of life; QoL).4

Over a continuous 12-week interval from weeks 13-24 in the absence of RBC transfusions, 74 of 96 (77.1%) patients in the Reblozyl treatment arm achieved the study’s primary endpoint, ≥1.0 g/dL mean Hb increase from baseline, versus 0 of 49 (0%) patients in the placebo arm (P<0.0001). The primary endpoint was achieved by 40 of 55 (72.7%) patients in the Reblozyl arm with mean baseline Hb of <8.5 g/dL versus 0 (0%) of patients in the placebo arm (P<0.0001), and 34 of 41 patients (82.9%) with mean baseline Hb of ≥8.5 g/dL versus 0 patients (0%) in the placebo arm (P<0.0001). In a key secondary endpoint of the study, during weeks 13-24, 50 of 96 patients (52.1%) in the Reblozyl arm achieved mean Hb increase of ≥1.5 g/dL compared to baseline versus 0 patients (0%) in the placebo arm (P<0.0001). 89.6% of patients in the Reblozyl arm remained transfusion free at weeks 1-24 versus 67.3% of patients in the placebo arm (P=0.0013). Improvements in patient-reported QoL outcomes (tiredness and weakness) were also observed to correlate with Hb increases.

The most common treatment-emergent adverse events of any grade occurring in ≥5% of patients were bone pain (36.5% Reblozyl versus 6.1% placebo), headache (30.2% versus 20.4%), and arthralgia (29.2% versus 14.3%). No malignancies or thromboembolic events were reported in patients treated with Reblozyl.

About Beta Thalassemia

Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. It is one of the most common autosomal recessive disorders, and the total annual incidence of symptomatic individuals is estimated at 1 in 100,000 people globally and 1 in 10,000 people in the European Union.5 The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy red blood cells (RBCs), often leading to severe anemia—a condition that can be debilitating and can lead to other complications for patients—as well as other serious health issues. Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of frequent RBC transfusions that have the potential to contribute to iron overload, which can cause serious complications such as organ damage.5 Non-transfusion dependent thalassemia is a term used to describe patients who do not require lifelong regular transfusions for survival, although they may experience a range of clinical complications and require occasional or even frequent transfusions, usually for defined periods of time.6

About Reblozyl

Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, promotes late-stage red blood cell maturation in animal models. Bristol Myers Squibb and Acceleron are jointly developing Reblozyl as part of a global collaboration. Reblozyl is currently approved in the U.S. for the treatment of:

anemia in adult patients with beta thalassemia who require regular red blood cell transfusions, and
anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Reblozyl is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.

U.S. Important Safety Information

WARNINGS AND PRECAUTIONS

Thrombosis/Thromboembolism

In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.

Hypertension

Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 1.8% to 8.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In adult patients with MDS with normal baseline blood pressure, 26 (29.9%) patients developed SBP ≥130 mm Hg and 23 (16.4%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Embryo-Fetal Toxicity

REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.

ADVERSE REACTIONS

Beta Thalassemia

Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML). Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).
Myelodysplastic Syndromes

Grade >3 (≥2%) adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. A fatal adverse reaction occurred in 5 (2.1%) patients.
The most common (≥10%) adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection.
LACTATION

It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.

Please see full Prescribing Information and Summary of Product Characteristics for REBLOZYL

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

On June 11, 2021 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported that three posters relating to the MANIFEST clinical trial of pelabresib (CPI-0610) in myelofibrosis (MF) were published online in association with the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting (Press release, Constellation Pharmaceuticals, JUN 11, 2021, View Source [SID1234583890]). The data in these posters are based on a data cutoff of September 29, 2020 from the MANIFEST Phase 2 clinical trial and reflect an analysis of pelabresib clinical and translational activity.

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"We are particularly enthusiastic about the publication of centrally reviewed translational data, which describe early improvements in bone marrow fibrosis in patients treated with pelabresib, and we believe these results support our thesis of disease-modifying treatment effects that go beyond symptom management," said Patrick Trojer, chief scientific officer of Constellation Pharmaceuticals. "We are currently enrolling patients in the Phase 3 pivotal study of MANIFEST-2 and our goal is to transform the standard of care for the treatment of myelofibrosis."

Data Highlights

Translational data, across all three arms of the Phase 2 MANIFEST study, support the disease-modifying potential of pelabresib

Centrally reviewed bone marrow fibrosis (BMF) pathology conducted in 63 patients showed similar improvements as reported previously for local review of BMF grade. 23 out of 63 patients (37%) achieved at least a 1 grade improvement in BMF. Of these patients, 83% achieved improvements in BMF by 24 weeks.
17% of the patients with BMF improvement (4 out of 23), improved by at least 2 grades.
31 out of 63 patients (49%) were stabilized or had no change, and only 4 out of 63 patients (6%) worsened.
An increase in BM erythroid progenitor cells and reduction of the number and cluster formation of megakaryocytes in the BM was observed in 59% and 65%, respectively, of 37 samples from patients treated with pelabresib either as a monotherapy or in combination with ruxolitinib.
Pelabresib durably reduced inflammatory cytokines such as tumor necrosis factor alpha (TNF alpha) and interleukin 18 (IL18) as early as 2 weeks and maintained through 24 weeks of treatment, based on an analysis of patient samples.
Arm 3 (1L) – CPI-0610 + ruxolitinib interim efficacy subgroup analysis in JAK-inhibitor-naïve patients

As previously reported at ASH (Free ASH Whitepaper) 2020, 42 of 63 evaluable patients (67%) achieved a ≥35% reduction in spleen volume (SVR35) at 24 weeks (the primary endpoint for Arm 3). 34 of 60 evaluable patients (57%) achieved a ≥50% reduction in Total Symptom Scores (TSS50) at 24 weeks.
Strong response was observed with pelabresib, irrespective of baseline risk status or demographic and disease characteristics.
Central pathology review of 27 1L patient bone marrow samples showed at least a one-grade improvement in bone marrow fibrosis in 9 out of 27 patients (33%); in all of these patients, improvement was observed within 6 months of starting treatment. 16 out of 27 patients (59%) showed stabilization of bone marrow fibrosis, while only 1 out of 27 patients (4%) showed worsening.
Arm 1 and 2 (2L) – Interim analysis demonstrating that pelabresib monotherapy in JAK-inhibitor-experienced or -ineligible patients, and with pelabresib + ruxolitinib in ruxolitinib-experienced patients, resulted in improvements in anemia

As previously reported at ASH (Free ASH Whitepaper) 2020, 3 of 14 evaluable Transfusion Dependent (TD) patients (21%) in Arm 1A achieved transfusion independence (the primary endpoint for arms 1A and 2A) and 13 of 36 evaluable TD patients (36%) in Arm 2A achieved transfusion independence.
9 out of 15 evaluable TD patients (60%) in Arm 1A, and 25 out of 47 of evaluable TD patients (53%) in Arm 2A achieved a ≥50% reduction in red blood cell transfusions.
Safety

As of the September 29, 2020 data cutoff, pelabresib was generally well tolerated in MANIFEST, both as monotherapy and in combination with ruxolitinib, and in both JAK-inhibitor-naïve and -ineligible as well as JAK-inhibitor-experienced patients.

Among the most common treatment-emergent adverse events (TEAEs) for CPI-0610 monotherapy in 46 safety-evaluable patients in Arm 1, those that were Grade 3 were thrombocytopenia (15%), anemia (13%), diarrhea (4%), constipation (2%), respiratory tract infection (2%), and weight decrease (2%). Amongst the most common TEAEs, there were no Grade 4. Other Grade 3/4 TEAEs (≥5%) include hyperuricemia (9%), hyperkalemia (7%) and dyspnea (7%). Nine patients discontinued treatment because of TEAEs. No Grade 5 events were observed.

Among the most common TEAEs in 78 safety-evaluable patients in Arm 2, those that were Grade 3 were thrombocytopenia (23%), anemia (10%), respiratory tract infections (5%), diarrhea (4%), asthenic conditions (4%), and nausea (3%). Amongst the most common TEAEs, Grade 4 events included thrombocytopenia (3%) and anemia (1%). Nine patients discontinued treatment due to TEAEs, including six Grade 5 TEAEs, which were acute kidney injury, traumatic subdural hematoma, brain stem hemorrhage (no concomitant thrombocytopenia), disease progression, congestive heart failure, and transformation to AML.

Among the most common TEAEs in 78 safety-evaluable patients in Arm 3, those that were Grade 3 were anemia (28%) and thrombocytopenia (5%). Amongst the most common TEAEs, Grade 4 events included thrombocytopenia (3%), anemia (1%), and respiratory tract infection (1%). Two patients discontinued treatment due to TEAEs. In addition, there were two Grade 5 TEAEs, each resulting from multi-organ failure due to sepsis.

EHA Poster Presentations

TITLE: Pelabresib (CPI-0610) improved anemia associated with myelofibrosis: interim results from MANIFEST Phase 2 study (Abstract Code: EP1077)

TITLE: Clinical benefit of pelabresib (CPI-0610) in combination with ruxolitinib in JAK-inhibitor treatment naïve myelofibrosis patients: Interim efficacy subgroup analysis from Arm 3 of MANIFEST Phase 2 study (Abstract Code: EP1085)

TITLE: BET inhibitor pelabresib decreases inflammatory cytokines, improves bone marrow fibrosis and function, and demonstrates clinical response irrespective of mutation status in myelofibrosis patients (Abstract Code: EP1080)

Date and Time: June 11, 9:00 AM CEST/ 3:00 AM EDT

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of pelabresib (CPI-0610) in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating pelabresib in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. Constellation Pharmaceuticals is also evaluating pelabresib either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to transfusion independence for 12 consecutive weeks. The primary endpoint for patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

On June 11, 2021 BeyondSpring Inc. ("BeyondSpring") (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, reported that management will host a conference call to report its financial results for the first quarter ended March 31, 2021 and provide an update on recent corporate events on June 16, 2021 at 8:30 AM Eastern Time (Press release, BeyondSpring Pharmaceuticals, JUN 11, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-to-host-first-quarter-financial-results-and-corporate-update-conference-call-on-june-16-2021 [SID1234585697]).

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The conference call may be accessed by dialing 877-451-6152 (U.S.) or 201-389-0879 (International) and referencing conference ID: 13720525. A live webcast will be available on BeyondSpring’s website at www.beyondspringpharma.com under "Events & Presentations" in the Investors section. An archived replay of the webcast will be available for 90 days.