On May 14, 2020 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that data from the pivotal phase 2 study HORIZON, and additional clinical and preclinical data that further evaluate the therapeutic peptide-drug conjugate platform, have been accepted by the European Hematology Association (EHA) (Free EHA Whitepaper) (Press release, Oncopeptides, MAY 14, 2020, View Source [SID1234557993]). The abstracts are now published online.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Melflufen (melphalan flufenamide) is a first-in-class anticancer peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Melflufen is in late stage clinical development for a potential treatment of patients with relapsed refractory multiple myeloma (RRMM).

"The primary read-out of the HORIZON-data represents an important milestone for Oncopeptides. They lay the ground for the New Drug Application to the FDA, seeking accelerated approval for intravenous melflufen in combination with dexamethasone, says Klaas Bakker, CMO of Oncopeptides. "Melflufen could provide a novel treatment option with a unique mechanism of action for a group of myeloma patients with a particularly poor prognosis".

Below is a brief description of the abstracts that have been accepted by the European Hematology Association (EHA) (Free EHA Whitepaper). The full EHA (Free EHA Whitepaper) abstract book can be found on www.ehaweb.org.

HORIZON (OP-106): Melflufen plus dexamethasone in relapsed/refractory multiple myeloma (RRMM) refractory to pomalidomide and/or an anti-CD38 monoclonal antibody – primary and subgroup analysis.
Final Abstract Code: EP945. First author: Paul G Richardson.The primary read-out of the data from the pivotal, phase II study HORIZON demonstrates clinical efficacy and a manageable safety profile of the peptide-drug conjugate melflufen in combination with dexamethasone in patients with RRMM, including patients with high-risk features and triple-class–refractory disease.
HORIZON (OP-106): An exploratory analysis of time to next treatment in patients with relapsed/refractory multiple myeloma who received melflufen plus dexamethasone.
Final Abstract Code: EP1029. First author: Maria-Victoria MateosThe abstract includes a time to next treatment analysis: The sub-analysis of the HORIZON clinical study is the first to provide important insights on time to subsequent treatment in patients with advanced RRMM (medium 5 lines of previous lines).
LIGHTHOUSE (OP-108): A phase 3 study of melflufen in combination with daratumumab versus daratumumab in patients with relapsed/refractory multiple myeloma.
Final Abstract Code: PB2018. First author: Maria-Victoria MateosThe planned randomized phase 3 trial LIGHTHOUSE will study the impact of melflufen, dexamethasone and subcutaneous daratumumab compared with subcutaneous daratumumab alone. The results will be important to confirm the preliminary efficacy, safety and tolerability results from phase 1/2 ANCHOR study, combining melflufen, dexamethasone and daratumumab supporting further regulatory milestones for Oncopeptides
Adverse event and outcome patterns in patients with advanced multiple myeloma in the US
Final Abstract Code: PB2039. First author: Joshua RichterThis real-world data study provides evidence, that albeit introduction of additional treatment options for patients with advanced multiple myeloma, their prognosis remains poor and the need for additional treatment options are high
Melflufen is a highly effective anti-neoplastic agent in bortezomib-resistant multiple myeloma models.
Final Abstract Code: EP915. First author: Konstantin ByrgazovMelflufen is more efficacious in bortezomib-resistant myeloma cell lines than in their bortezomib-naive parental cells in vitro. Bortezomib-resistant myeloma cells lines overexpress Aminopeptidase B encoded by RNPEP gene, and myeloma patients with high RNPEP expression have shorter PFS on bortezomib-containing therapies.
Melflufen efficacy in multiple myeloma with TP53 aberrations.
Final Abstract Code: EP903. First author: Ana Slipicevic.Melflufen can trigger myeloma cell death regardless of cells TP53 status and overcome the p53-deficiency-mediated melphalan resistance. Melflufen response rate in the del 17p patient subpopulation from the phase 2-study HORIZON is comparable to the general RRMM population suggesting that melflufen might be a therapeutic option for these difficult-to-treat patients.
Aminopeptidase expression in multiple myeloma associates with disease progression and sensitivity to melflufen.
Final Abstract Code: EP897. First author: Juho MiettinenAminopeptidases play a role in multiple myeloma biology. Their expression levels are dysregulated during disease progression, and majority are increased in RRMM compared to NDMM patients. Aminopeptidases LAP3 and TPP2 are identified as prognostic markers in myeloma patients, and inhibition of aminopeptidases reduces myeloma cell viability in vitro. Melflufen, an aminopeptidase substrate, is a highly efficient anticancer agent in myeloma cells resistant to other alkylators, bortezomib and selinexor.

For more information, please contact:
Klaas Bakker, MD, PhD, Chief Medical Officer of Oncopeptides
E-mail: [email protected]
Cell: +44 7818 523903

Fredrik Lehmann, EVP Research and CMC at Oncopeptides
E-mail: [email protected]
Phone: +46 8 615 20 40

Rein Piir, Head of Investor Relations at Oncopeptides
E-mail: [email protected]
Cell : +46 70 853 72 92

This information was submitted for publication at 15.00 CET May 14, 2020.

About melflufen
Melflufen (melphalan flufenamide) is a first-in-class anti-cancer peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.

On May 14, 2020 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on the registration and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, reported that Dose Intensity and Long-Term Safety data for momelotinib will be presented in two posters at the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress taking place from June 11-21, 2020 (Press release, Sierra Oncology, MAY 14, 2020, View Source [SID1234557992]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In these new analyses of data from the previously completed Phase 3 SIMPLIFY studies, momelotinib displayed favorable long-term efficacy, safety and tolerability consistent with its differentiated pharmacological and clinical profile. These data reinforce the remarkable durability of momelotinib treatment, which was achieved while maintaining sustained active and well tolerated dose intensity," said Dr. Barbara Klencke, Chief Development Officer of Sierra Oncology. "Specifically, momelotinib showed an absence of significant rates of high-grade hematological and other toxicities, which reinforce the compound’s potential to safely and effectively address the unmet needs of patients with intermediate/high risk myelofibrosis. Importantly, no new safety signals or evidence of cumulative toxicity were observed during extended momelotinib daily dosing."

"Momelotinib’s demonstrable anemia benefits facilitate sustained dose intensity and prolonged clinical activity across the continuum of JAK inhibitor naïve and previously JAK inhibitor treated myelofibrosis patients. These properties are in stark contrast to ruxolitinib, where progressive dose reductions due to induced or exacerbated myelosuppression are common, resulting in markedly diminished dose intensity compared to momelotinib," said Dr. Mark Kowalski, Chief Medical Officer of Sierra Oncology. "Critically, patients who subsequently switched from ruxolitinib treatment to momelotinib achieved an immediate and sustained improvement in both hemoglobin and platelets, and generally went on to receive full-dose momelotinib over an extended period, affirming momelotinib’s potential to successfully treat myelofibrosis patients with JAKi-induced hematological toxicity."

The long-term safety data and dose intensity data to be reported at EHA (Free EHA Whitepaper) draw from the extensive clinical dataset available for momelotinib from the two previously conducted SIMPLIFY Phase 3 studies and their subsequent ongoing extended treatment periods. The SIMPLIFY-1 trial was conducted in JAKi-naïve myelofibrosis patients (n=432) randomized 1:1 to momelotinib or ruxolitinib. SIMPLIFY-2 was conducted in prior ruxolitinib-treated myelofibrosis patients with hematological toxicity (n=156) randomized 2:1 to momelotinib or best available therapy (consisting of ruxolitinib in 88% of patients). Patients randomized to ruxolitinib in SIMPLIFY-1 and best available therapy in SIMPLIFY-2 were eligible to cross-over to momelotinib at the end of the 24-week randomized treatment period in both studies, subsequently receiving momelotinib for an extended treatment period.

Sierra is currently enrolling patients in the MOMENTUM clinical trial for patients with myelofibrosis. The randomized double-blind global Phase 3 trial is designed to confirm the efficacy of momelotinib on myelofibrosis symptoms, transfusion independence and splenomegaly, as compared to danazol. The trial is targeting enrollment of 180 myelofibrosis patients who are symptomatic, anemic and have been treated previously with a JAK inhibitor. The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; 2-sided alpha of 0.05). Data from MOMENTUM, along with data from more than 820 myelofibrosis patients previously treated with momelotinib in prior clinical studies, will form the basis of the global registration strategy for momelotinib.

About the EHA (Free EHA Whitepaper) Posters
Title: Long term Safety of Momelotinib in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Prof. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1113

Title: Momelotinib Dose-Intensity is Maintained in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Dr. Vikas Gupta, Princess Margaret Cancer Centre, Toronto, ON, Canada
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1103

The accepted abstracts are now available online on the EHA (Free EHA Whitepaper) conference websites at View Source

Both e-posters will be made available through the on-demand Virtual Congress platform and at www.sierraoncology.com as of Friday, June 12, 08:30 CEST.

On May 14, 2020 bluebird bio, Inc. (Nasdaq: BLUE) reported that data from its gene therapy programs for sickle cell disease (SCD), transfusion-dependent β-thalassemia (TDT) and its cell therapy program for relapsed and refractory multiple myeloma (RRMM) will be presented during the Virtual Edition of the 25thEuropean Hematology Association (EHA25) Annual Congress (Press release, bluebird bio, MAY 14, 2020, View Source [SID1234557991]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

New data from the company’s Phase 1/2 HGB-206 study of LentiGlobin gene therapy for SCD will be presented, including updated data from patients in Group C.

bluebird bio will also present data from its ongoing clinical studies of betibeglogene autotemcel (formerly LentiGlobin gene therapy for β-thalassemia), including the Phase 3 Northstar-2 (HGB-207) study in patients who do not have a β0/β0 genotype and the Phase 3 Northstar-3 (HGB-212) study in patients who have β0/β0, β0/β+IVS-I-110, or β+IVS-I-110/β+IVS-I-110 genotypes.

Data from studies of idecabtagene vicleucel (ide-cel; bb2121), the company’s anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy in development with Bristol Myers Squibb, will be presented, including an encore presentation of results from the pivotal Phase 2 KarMMa study.

Sickle Cell Disease Data at EHA (Free EHA Whitepaper)25

Oral Presentation: Outcomes in patients treated with LentiGlobin for sickle cell disease (SCD) gene therapy: Updated results from the Phase 1/2 HGB-206 group C study
Presenting Author: Julie Kanter, M.D., University of Alabama at Birmingham, Birmingham, Ala.

Transfusion-Dependent β-Thalassemia Data at EHA (Free EHA Whitepaper)25

Oral Presentation: Improvement in erythropoiesis in patients with transfusion-dependent β-thalassemia following treatment with betibeglogene autotemcel (LentiGlobin for β-thalassemia) in the Phase 3 HGB-207 study
Presenting Author: John B. Porter, MA, M.D., FRCP, FRCPath, University College London Hospital, London, UK

Poster: Betibeglogene autotemcel (LentiGlobin) in patients with transfusion-dependent β-thalassemia and β0/β0, β+IVS-I-110/β+IVS-I-110, or β0/β+IVS-I-110 genotypes: Updated results from the HGB-212 study
Presenting Author: Evangelia Yannaki, M.D., George Papanicolaou Hospital, Thessaloniki, Greece

Multiple Myeloma Data at EHA (Free EHA Whitepaper)25

Oral Presentation: Phase II KarMMa study: Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T cell therapy, in patients with relapsed and refractory multiple myeloma
Presenting Author: Jesus San-Miguel, M.D., Ph.D., Clinica Universidad de Navarra, Navarra, Spain

Poster: Quality of life in patients with relapsed and refractory multiple myeloma treated with the BCMA-targeted CAR T cell therapy Idecabtagene vicleucel (ide-cel; bb2121): results from the KarMMa Trial
Presenting Author: Michel Delforge, M.D., Ph.D., Leuven University College, Brussels, Belgium

Poster: Matching-adjusted indirect comparisons of efficacy outcomes for idecabtagene vicleucel from the KarMMa study vs selinexor PLUS dexamethasone (STORM part 2) and belantamab mafodotin (DREAMM-2)
Presenting Author: Paula Rodriguez-Otero, M.D., Clinica Universidad de Navarra, Navarra, Spain

Poster: Baseline and postinfusion pharmcodynamic biomarkers of safety and efficacy in patients treated with idecabtagene vicleucel (ide-cel; bb2121) in the KarMMa study
Presenting Author: Justine Dell’Aringa, Bristol Myers Squibb, Seattle, Wash.

Poster: Correlation of tumor BCMA expression with response and acquired resistance to idecabtagene vicleucel in the KarMMa study in relapsed and refractory multiple myeloma
Presenting Author: Nathan Martin, Bristol Myers Squibb, Seattle, Wash.

Abstracts outlining bluebird bio’s accepted data at the EHA (Free EHA Whitepaper)25 Virtual Congress have been made available on the EHA (Free EHA Whitepaper)25 conference website. On Friday, June 12 at 8:30 AM CEST, the embargo will lift for poster and oral presentations accepted for EHA (Free EHA Whitepaper)25.

About betibeglogene autotemcel
The European Commission granted conditional marketing authorization (CMA) for betibeglogene autotemcel, marketed as ZYNTEGLO gene therapy, for patients 12 years and older with TDT who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available. On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for ZYNTEGLO, supported by data from 32 patients treated with ZYNTEGLO including three patients with up to five years of follow-up.

TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Betibeglogene autotemcel adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

Non-serious adverse events (AEs) observed during the clinical studies that were attributed to betibeglogene autotemcel were abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnoea, pain in extremity, and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to LentiGlobin for β-thalassemia for TDT.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

The CMA for ZYNTEGLO is only valid in the 28 member states of the EU as well as Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration granted betibeglogene autotemcel Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT. Betibeglogene autotemcel is not approved in the United States.

Betibeglogene autotemcel continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212).

About LentiGlobin for Sickle Cell Disease
LentiGlobin for sickle cell disease is an investigational gene therapy being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the ongoing Phase 1/2 HGB-206 study and the ongoing Phase 3 HGB-210 study.

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive crises (VOCs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complications—such as acute chest syndrome (ACS), stroke, and infections, which can contribute to early mortality in these patients.

LentiGlobin for SCD received Orphan Medicinal Product designation from the European Commission for the treatment of SCD.

The U.S. Food and Drug Administration (FDA) granted Orphan Drug status and Regenerative Medicine Advanced Therapy designation for LentiGlobin for the treatment of SCD.

LentiGlobin for SCD is investigational and has not been approved by the European Medicines Agency (EMA) or FDA.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of betibeglogene autotemcel and LentiGlobin for SCD. For more information visit: View Source or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About idecabtagene vicleucel (ide-cel; bb2121)
Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem. Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

In addition to the pivotal KarMMa trial evaluating ide-cel in patients with relapsed and refractory multiple myeloma, bluebird bio and Bristol Myers Squibb’s broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.

Ide-cel was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and PRIority Medicines (PRIME) designation, as well as Accelerated Assessment status, by the European Medicines Agency for relapsed and refractory multiple myeloma.

Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio.

Ide-cel is not approved for any indication in any geography.

About KarMMa
KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multicenter, multinational, Phase 2 study evaluating the efficacy and safety of ide-cel in adults with relapsed and refractory multiple myeloma in North America and Europe. The primary endpoint of the study is overall response rate as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria. Complete response rate is a key secondary endpoint. Other efficacy endpoints include time to response, duration of response, progression-free survival, overall survival, minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay and safety. The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 10P6P CAR+ T cells after receiving lymphodepleting chemotherapy. All enrolled patients had received at least three prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

On May 14, 2020 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST) reported that three abstracts relating to the MANIFEST clinical trial of CPI-0610 in myelofibrosis were published online in association with the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting (Press release, Constellation Pharmaceuticals, MAY 14, 2020, View Source [SID1234557982]). The abstracts include an analysis of data from 157 patients based on a data cutoff of January 9, 2020. An upcoming presentation of posters at EHA (Free EHA Whitepaper) on June 12 will reflect an analysis of a larger patient population based on a later data cutoff. Constellation expects to present 12-week data in about 50 first-line patients and 24-week data in 25-30 first-line patients and 70-80 second-line patients at the EHA (Free EHA Whitepaper) meeting.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data from the abstracts include 35% reductions in spleen volume (SVR35), 50% improvement in Total Symptom Scores (TSS50), hemoglobin improvements, conversions to transfusion independence in transfusion-dependent (TD) patients, and bone marrow fibrosis improvements," said Claire Harrison, D.M., Professor of Haematology, and Clinical Director, Guy’s and St Thomas’ NHS Foundation Trust, and a MANIFEST investigator. "Evidence of clinical activity was seen both as monotherapy and in combination with ruxolitinib. If these preliminary data are confirmed in further testing, CPI-0610 may have the potential for disease modification and could become part of a new standard of care in myelofibrosis."

Data Highlights

Arm 3 (1L) – CPI-0610 + ruxolitinib in JAK-inhibitor-naïve patients

21 of 29 evaluable patients (72%) achieved SVR35 at 12 weeks
Of 15 patients evaluable for SVR at week 24, 14 completed 24 weeks of treatment (one discontinued), with 10 patients (67%) achieving SVR35
The median spleen volume change in those 14 patients was 54% at 24 weeks
TSS50 responses at 12 and 24 weeks were 56% (15 of 27 evaluable patients) and 79% (11 of 14 evaluable patients), respectively
5 of 11 (46%) patients evaluable for bone marrow fibrosis had a >1 grade improvement at 24 weeks
Arm 1 (2L) – CPI-0610 monotherapy in JAK-inhibitor-experienced or -ineligible patients

2 of 10 (20%) and 4 of 11 (36%) evaluable non-transfusion-dependent (non-TD) patients achieved SVR35 (the primary endpoint for cohort 1B) and TSS50, respectively, at 24 weeks
3 of 10 (30%) evaluable non-TD patients had a >1 grade improvement in bone marrow fibrosis at 24 weeks
13 of 22 (59%) evaluable non-TD patients had > 1.5 g/dL increase in hemoglobin
2 of 6 (33%) evaluable TD patients converted to transfusion independence (the primary endpoint for cohort 1A)
No evaluable TD patients achieved SVR35 or TSS50 at 24 weeks
Arm 2 (2L) – CPI-0610 + ruxolitinib in ruxolitinib-experienced patients

7 of 19 (37%) evaluable TD patients converted to TI (the primary endpoint for cohort 2A)
3 of 18 (17%) and 10 of 18 (56%) evaluable TD patients achieved SVR35 and TSS50, respectively, at 24 weeks
9 of 14 (64%) evaluable TD patients had a > 1 grade improvement in bone marrow fibrosis at 24 weeks
No evaluable non-TD patients achieved SVR35 (the primary endpoint for cohort 2B) and 4 of 13 (31%) evaluable non-TD patients achieved TSS50 at 24 weeks
Safety

CPI-0610 in MANIFEST, both as monotherapy and in combination with ruxolitinib and in both JAK-inhibitor-naïve and JAK-inhibitor-experienced and -ineligible patients, was generally well tolerated.

Among the most common treatment-emergent adverse events (AEs) for CPI-0610 monotherapy in 43 safety-evaluable patients in Arm 1, those that were ≥ Grade 3 were thrombocytopenia (14.0%), anemia (7.0%), and diarrhea (4.7%). Two patients discontinued treatment because of AEs (blood creatinine increase, fatigue, and pleuritic pain). There were no Grade 5 AEs.

Among the most common treatment-emergent AEs in 61 safety-evaluable patients in Arm 2, those that were ≥ Grade 3 were thrombocytopenia (21.3%), anemia (8.2%), diarrhea (4.9%), infections (4.9%), nausea (1.6%), abdominal pain (1.6%), and vomiting (1.6%). Seven patients discontinued treatment due to AEs, including three previously reported Grade 5 AEs.

Among the most common treatment-emergent AEs in 53 safety-evaluable patients in Arm 3, those that were ≥ Grade 3 were anemia (15.1%), thrombocytopenia (5.7%), infections (3.8%), and dyspnea (3.8%). Two patients discontinued treatment due to AEs (infections); one of them was Grade 5 within 30 days of treatment discontinuation.

For further details, please see the EHA (Free EHA Whitepaper) abstracts in the Investors and Media/Other Presentations section of Constellation’s website, View Source

EHA Poster Presentations

TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, in Combination with Ruxolitinib, in JAK Inhibitor Treatment Naive Myelofibrosis Patients: Update of MANIFEST Phase 2 Study (Submission ID: EHA (Free EHA Whitepaper)-2731, Final Abstract Code: EP1084)

TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, as Monotherapy in Advanced Myelofibrosis Patients Refractory/Intolerant to JAK Inhibitor: Update from Phase 2 MANIFEST Study (Submission ID: EHA (Free EHA Whitepaper)-3245, Final Abstract Code: EP1091)

TITLE: CPI-0610, Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, as "Add-on" to Ruxolitinib (Rux), in Advanced Myelofibrosis Patients with Suboptimal Response: Update of MANIFEST Phase 2 Study (Submission ID: EHA (Free EHA Whitepaper)-2790, Final Abstract Code: EP1083)

Session: Myeloproliferative Neoplasms—Clinical

Date and Time: June 12, 2020, 8:30 AM CEST/2:30 AM EDT

Investor Event

Constellation will host a virtual investor meeting and conference call to discuss these interim data on June 12. Details will be announced later.

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of 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 CPI-0610 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 is also evaluating CPI-0610, 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 TI for 12 consecutive weeks. The primary endpoint for the 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 May 14, 2020 Boehringer Ingelheim reported the acquisition of Northern Biologics Inc., a wholly owned subsidiary of Northern LP (Press release, Boehringer Ingelheim, MAY 14, 2020, View Source [SID1234557981]). By acquiring this entity, which focuses on therapeutic antibodies targeting the tumor microenvironment, Boehringer Ingelheim is now positioned at the forefront of the stromal biology space – an emerging area in cancer immunology . The seller will retain the Northern Biologics name and will continue to drive certain preclinical efforts on one of the programs, while Boehringer Ingelheim will be responsible for clinical, regulatory and commercial development of the acquired programs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The total transaction includes an upfront payment, milestones and other consideration payments.

The first program, now in late preclinical development, is an antibody inhibitor of Periostin, a secreted matricellular protein overexpressed in the immunosuppressive stroma microenvironment of many solid tumor types. Targeting these stromal cells can help turn previously ‘cold’ tumors – non-reactive, immunologically inactive tumors – to ‘hot’ tumors – those that are susceptible or accessible to host immune system attack. The antibody program targeting Periostin has emerged as a promising therapy to overcome stromal mechanisms of immune exclusion and suppression.

The second program targets a key regulator of myeloid cells that is important for enhancing anti-tumor T-cell function. Targeting myeloid cells is a focus area of research and clinical development for Boehringer Ingelheim and the acquired program offers combination opportunities across Boehringer Ingelheim’s portfolio.

"This acquisition provides Boehringer Ingelheim with two complementary assets to our existing cancer immunology portfolio and supports our strategy to target ‘cold’ tumors with synergistic combination approaches," said Jonathon Sedgwick, Ph.D., Senior Vice President and Global Head, Cancer Immunology & Immune Modulation Research, Boehringer Ingelheim. "Driving innovation in tumor stroma and myeloid cell biology is yet another example of how we are ‘Taking Cancer On’ by exploring first-in-class approaches to provide the best treatment options for cancer patients."

"We are gratified by this transaction with Boehringer Ingelheim, which simultaneously accelerates these promising assets into the clinic," said Philip Vickers, Ph.D., President and CEO of Northern Biologics. "I am proud of the Northern R&D team, which discovered and advanced these compounds in the emerging field of tumor stroma and myeloid cell biology."

Founding investor Versant Ventures established Northern Biologics in Toronto’s MaRS Discovery District in collaboration with the University of Toronto and Princess Margaret Cancer Centre in 2014. The programs acquired by Boehringer Ingelheim were discovered and translated into clinical candidates by Northern’s Toronto-based research team. Northern Biologics retains rights to its lead asset, MSC-1, an anti-LIF 1 antibody that recently successfully completed Phase 1 clinical trials.

The Northern Biologics-Boehringer Ingelheim acquisition represents the second recent transaction for a Versant-built company operating out of the MaRS discovery district in Toronto. It follows the August 2019 acquisition of BlueRock Therapeutics, which also drew on technology locally developed by Canadian scientists.

This acquisition positions Boehringer Ingelheim as a leader in the field of stromal targeting biology and, along with a series of strategic acquisitions and collaborations over the past two years, further strengthens the company’s broad and diverse oncology pipeline. By combining its world-class, in-house research and development with that of highly innovative biotechnology companies, Boehringer Ingelheim is developing innovative cancer immunology therapies and accelerating the delivery of the next generation of cancer treatments.