On May 14, 2020 Kaleido Biosciences, Inc. (Nasdaq: KLDO), a clinical-stage healthcare company with a chemistry-driven approach to targeting the microbiome to treat disease and improve human health, reported financial results for the first quarter 2020 (Press release, Kaleido Biosciences, MAY 14, 2020, View Source [SID1234557994]).

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"The COVID-19 pandemic is having an unprecedented impact on the global healthcare system. We continue to adapt our work to prioritize the safety of our employees, as well as patients and clinical staff as study sites limit certain activities in light of the ongoing pandemic," said Alison Lawton, Kaleido’s President and Chief Executive Officer. "We are fortunate that our product platform and efficient development model provide Kaleido flexibility in responding to the current situation. We have rapidly initiated new clinical programs aimed at addressing the unmet need for outpatients with mild-to-moderate COVID-19 disease and are further exploring the potential of MMTs in immune-mediated and inflammatory diseases in ulcerative colitis. We anticipate data readouts from these and other programs starting in Q4 2020 and throughout 2021."

Pipeline Update

COVID-19 Program and KB109

As announced separately today, Kaleido has initiated a clinical program evaluating KB109 when added to Supportive Self-Care for outpatients with mild-to-moderate COVID-19 disease. The program aims to enroll a total of approximately 400 patients in two non-IND controlled clinical studies. Top-line data from the larger, multi-center study are expected in Q4 2020.

COVID-19 infection has been associated with activation of an inappropriate inflammatory cascade, which in some patients can cause an abnormally aggressive immune response that can lead to pneumonia and respiratory failure. Scientific evidence indicates that metabolites such as short chain fatty acids (SCFAs) produced by the microbiome through fermentation of glycans, are modulators of the immune response and therefore could potentially play a role in limiting this inflammatory cascade. KB109 is Generally Recognized as Safe (GRAS) and was selected for evaluation in these COVID-19 clinical studies based on its demonstrated ability to increase production of SCFAs as well as to promote commensal bacteria and reduce pathogenic bacteria ex vivo.

Due to prioritization of KB109 in COVID-19 and anticipated delays due to the pandemic, Kaleido has elected to pause the VITORA clinical study in patients colonized with multidrug-resistant pathogens. The Company is evaluating next steps for its pathogens program, including evaluating KB109 in a patient population at high-risk of infections such as Hematopoietic Stem Cell Transplantation (HSCT) recipients.

Immune-mediated and Inflammatory Diseases Programs

In addition to exploring immune pathways involved in respiratory viral infections with the COVID-19 program, Kaleido is expanding its efforts to understand the potential of MMTs in addressing immune-mediated and inflammatory diseases, including:

Initiating a clinical study later this year evaluating a new MMT candidate, KB295, in approximately 30 patients with mild-to-moderate ulcerative colitis (UC). Top-line results are expected in mid-2021.

In its immuno-oncology program, selecting clinical ready, lead MMT candidates that improve therapeutic responses in advanced preclinical models in Q4 2020.

Identifying lead MMTs from preclinical studies in validated models of immune-mediated diseases in the first half of 2021.

Metabolic and Liver Diseases Programs

KB195 is being evaluated in a Phase 2 clinical trial (UNLOCKED) in patients with urea cycle disorders who are inadequately controlled on standard of care. Given limitations on patient visits and the impact on new enrollment due to COVID-19, the Company now anticipates the availability of top-line data will be delayed into the second half of 2021.

Kaleido has received IND clearance and CTA approvals in nine countries, activated more than 20 sites and recently submitted a protocol amendment that expands the eligibility age to adolescents as young as 12 and adults up to age 70 (previously between 18 and 65), which will help facilitate enrollment.

In the hepatic encephalopathy program, Kaleido is ready to initiate the next clinical study evaluating KB174 in patients with the disease. Study initiation is dependent on partnering the program and resolution of COVID-19 impact at trial sites.

Preclinical work for the cardiometabolic and liver diseases program remains on track for results in Q4 2020.

Key Anticipated 2020 Milestones

Abstracts featuring clinical and ex vivo data from KB174 have been accepted for poster presentations during The Digital International Liver Congress (EASL 2020), rescheduled for August 27-29, 2020. Two of these abstracts were accepted for presentation and published to the online portal for Digestive Disease Week, which was cancelled due to the COVID-19 pandemic.

Top-line data from clinical study of KB109 in patients with mild-to-moderate COVID-19 disease expected in Q4 2020.

Data from preclinical programs in immuno-oncology and cardiometabolic and liver diseases expected in Q4 2020.

First Quarter 2020 Financial Results

For the first quarter 2020, Kaleido reported a net loss of $19.6 million, or $0.64 per common share, compared to $20.2 million, or $1.56 per common share, for the first quarter 2019. The 2020 first quarter net loss includes non-cash stock-based compensation expenses of $2.7 million, as compared to $2.5 million in the first quarter of 2019.

Research and development (R&D) expenses were $13.1 million for the three months ended March 31, 2020, compared to $15.2 million for the three months ended March 31, 2019. The decrease in R&D expense was primarily driven by decreased external manufacturing and research costs.

General and administrative (G&A) expenses were $5.9 million for the first quarter 2020, compared to $5.4 million for the first quarter of 2019. The first quarter 2020 increase in G&A, as compared to the first quarter of 2019, was primarily due to increased facility-related expenses.

As of March 31, 2020, the Company reported cash and cash equivalents of $53.8 million. Kaleido continues to manage its operating expenses in-line with its pipeline priorities and, as a result, has extended its cash runway further into the first quarter of 2021.

Conference Call and Webcast Information

Kaleido will host a conference call and webcast today, May 14, 2020, at 8:30 a.m. ET to discuss these pipeline updates. To access the live conference call, please dial (833) 423-0448 (domestic) or (956) 394-3566 (international) and reference conference ID 4182326. The live webcast can be accessed in the Investors & Media section of Kaleido’s website at: View Source Due to current high volume accessing virtual events, participants are encouraged to connect at least 15 minutes prior to the call to ensure a timely connection or to utilize the webcast link for listen-only access. An archived webcast will be made available on Kaleido’s website shortly after the event and accessible for 90 days.

About Microbiome Metabolic Therapies (MMT)

Kaleido’s Microbiome Metabolic Therapies, or MMTs, are designed to drive the function and distribution of the microbiome’s existing microbes in order to decrease or increase the production of metabolites, or to advantage or disadvantage certain bacteria in the microbiome community. The Company’s initial MMT candidates are targeted, synthetic glycans that are orally administered, have limited systemic exposure, and are selectively metabolized by enzymes in the microbiome. Kaleido utilizes its discovery and development platform to study MMTs in microbiome samples to rapidly advance MMT candidates rapidly into clinical studies in healthy subjects and patients. These human clinical studies are conducted under regulations supporting research with food, evaluating safety, tolerability and potential markers of effect. For MMT candidates that are further developed as therapeutics, the Company conducts clinical trials under an Investigational New Drug (IND) or regulatory equivalent outside the U.S., and in Phase 2 or later development.

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.

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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]).

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"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]).

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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.

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"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.