On November 6, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported that ELZONRIS (tagraxofusp; SL-401), a novel targeted therapeutic directed to CD123, will be featured in three presentations, including an oral presentation of ELZONRIS clinical data in myelofibrosis, at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, to be held December 7-10, 2019 in Orlando, FL (Press release, Stemline Therapeutics, NOV 6, 2019, View Source [SID1234550550]).

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Details on the ASH (Free ASH Whitepaper) presentations are as follows:

Myelofibrosis – Clinical (monotherapy); oral presentation
Title: Results from a Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Intermediate, or High Risk, Relapsed/Refractory Myelofibrosis
Presenter: Naveen Pemmaraju, MD; MD Anderson Cancer Center
Abstract: 558
Session: 634. Myeloproliferative Syndromes: Clinical: Emerging and Novel Targeted Therapies
Date/Time: Monday, December 9, 2019 8:15 AM ET
Location: Orange County Convention Center, W304EFGH

Multiple Myeloma – Clinical (combination therapy); poster presentation
Title: Results from Phase 1/2 Trial of Tagraxofusp in Combination with Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
Presenter: Paul G. Richardson, M.D.; Dana-Farber Cancer Institute
Abstract: 3145
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II
Date/Time: Sunday, December 8, 2019 6:00 PM–8:00 PM ET
Location: Orange County Convention Center, Hall B

Myeloproliferative Neoplasms – Preclinical (combination therapy); poster presentation
Title: Evaluation of Tagraxofusp (SL-401) Alone and in Combination with Ruxolitinib for the Treatment of Myeloproliferative Neoplasms
Presenter: Aishwarya Krishnan, MD; Memorial Sloan Kettering Cancer Center
Abstract: 2967
Session: 635. Myeloproliferative Syndromes: Basic Science: Poster II
Date/Time: Sunday, December 8, 2019 6:00 PM–8:00 PM ET
Location: Orange County Convention Center, Hall B

Ivan Bergstein, M.D., CEO of Stemline Therapeutics, commented, "We are honored that ASH (Free ASH Whitepaper) has selected ELZONRIS data as the subject of three presentations, including an oral presentation of clinical trial data in myelofibrosis (MF). Moreover, given the very encouraging trial results to date that we have witnessed, we are expanding the current cohort to enable additional patient enrollment. Two other presentations, including ELZONRIS clinical combination data in patients with multiple myeloma, and ELZONRIS preclinical combination data in myeloproliferative neoplasms, highlight ELZONRIS’ potential utility across indications. In addition, as we now transition our chronic myelomonocytic leukemia (CMML) program to registration-directed, we remain on track to begin enrollment of the Stage 3a cohort in patients with CMML in the coming months, with the goal of reporting data from this cohort, in both the relapsed/refractory and first-line settings, by 2H20."

About ELZONRIS
ELZONRIS (tagraxofusp-erzs), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.

On November 6, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a late-stage drug development company focused on the development and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, reported that it intends to offer and sell shares of Series A convertible preferred stock, together with Series A warrants and Series B warrants, each to purchase shares of common stock, in an underwritten public offering (Press release, Sierra Oncology, NOV 6, 2019, View Source [SID1234550548]). All of the securities to be sold in the offering will be offered by Sierra Oncology. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Sierra Oncology intends to use the net proceeds from the public offering to fund MOMENTUM, its planned Phase 3 clinical trial of momelotinib, as well as for general corporate purposes.

Each share of Series A preferred stock will be initially convertible into that number of shares of common stock equal to the purchase price of the Series A preferred stock divided by the conversion price of the Series A preferred stock. Each share of Series A preferred stock will automatically convert to shares of common stock upon the fifth day of trading following the announcement of stockholder approval of the first reverse stock split following the offering, subject to certain beneficial ownership limitations. Each share of Series A preferred will be entitled to vote together with the common stock on an as-converted basis, subject to certain limitations, without regard to the beneficial ownership limitation, until such time that the shares of Series A preferred stock automatically convert to common stock. Following the automatic conversion described above, the Series A preferred stock will be non-voting.

Each share of Series A preferred stock will be accompanied by (i) a Series A warrant to purchase shares of common stock that will equate to 100% warrant coverage, and (ii) a Series B warrant to purchase shares of common stock that will equate to 33% warrant coverage. Each Series A warrant and Series B warrant will have an exercise price equal to the initial conversion price of the Series A preferred stock, and will become exercisable following stockholder approval of an increase in authorized common stock sufficient to allow for the exercise of the warrants, subject to certain beneficial ownership limitations. The Series A warrants will expire five years from the date they first become exercisable and the Series B warrants will expire on the 75th day anniversary following the announcement of top-line date from Sierra Oncology’s planned Phase 3 clinical trial of momelotinib.

Jefferies is acting as the sole book-running manager for the offering.

The securities described above are being offered by Sierra Oncology pursuant to a registration statement on Form S-3 (File No. 333-225650) that was declared effective by the Securities and Exchange Commission ("SEC") on June 21, 2018. A preliminary prospectus supplement and an accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s web site at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at (877) 821-7388, or by email at [email protected].

This press release shall not constitute an offer to sell, or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 6, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a late-stage drug development company focused on the development and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, reported that new analyses of RBC transfusion data from SIMPLIFY-1, a double-blind Phase 3 trial of its investigational drug momelotinib vs ruxolitinib in JAK inhibitor naïve patients, will be presented in a poster at the 61st American Society of Hematologists (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida (Press release, Sierra Oncology, NOV 6, 2019, View Source [SID1234550547]). These retrospective analyses, to be presented by renowned myelofibrosis expert, Dr. Ruben Mesa, demonstrate that patients who received momelotinib had significantly decreased transfusion requirements compared to those treated with ruxolitinib, including a decreased risk of receiving a transfusion and a longer transfusion-free period.

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"We explored the relative burden of transfusions, a tangible and significant concern to clinicians and patients with myelofibrosis, by examining the SIMPLIFY-1 data comprising more than 400 myelofibrosis patients through statistical models utilizing a variety of novel dynamic anemia benefit endpoints, including the proportion of patients who remained transfusion free, the odds of requiring zero transfusions, the time to first transfusion in patients who remain transfusion requiring and the overall transfusion burden," said Dr. Ruben Mesa, Director of the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center. "Overall, these highly persuasive statistical analyses further confirm that momelotinib treatment elicits a substantive mechanistically-driven anemia benefit, including a significantly greater proportion of momelotinib patients remaining transfusion free, a 50% lower risk of receiving a transfusion and nearly 10-fold higher odds of receiving no transfusions during the 24-week study period, directly compared to ruxolitinib."

Historically, myelofibrosis clinical studies have employed landmark analyses of transfusion independence or dependence to describe anemia benefit. While momelotinib is the only JAK inhibitor to have demonstrated superior head-to-head landmark anemia benefits compared to ruxolitinib, these static measures of anemia alone do not fully describe the significant, clinically meaningful anemia benefit observed following momelotinib administration. In conjunction with the statistical consulting group at the International Drug Development Institute (IDDI), Sierra has developed additional sophisticated dynamic statistical analyses of anemia benefit in order to complement those assessments typically presented in the myelofibrosis literature.

"Chronic, progressive anemia is a key hallmark feature of myelofibrosis and the most important negative prognostic indicator of reduced survival in this disease. Approximately 60% of patients are anemic and 45% are transfusion dependent within one year of diagnosis, with most patients ultimately progressing to transfusion dependency. Unfortunately, currently approved JAK inhibitor therapies induce or worsen anemia, exacerbating this significant unmet medical need in anemic myelofibrosis patients," said Dr. Barbara Klencke, Chief Development Officer of Sierra Oncology. "The marked systemic inflammation seen in myelofibrosis leads to increased ACVR1 activity which in turn increases secretion of hepcidin, resulting in perturbed iron homeostasis and an iron-restricted anemia. Momelotinib’s inhibition of ACVR1 in addition to JAK1 and JAK2, unique amongst the JAK inhibitor class, results in notable reductions of both hepcidin and inflammation, restoring iron homeostasis and RBC production, thereby alleviating anemia and transfusion dependency."

The SIMPLIFY-1 trial is a double-blind, active-controlled Phase 3 study in which 432 patients received randomized treatment with momelotinib or ruxolitinib for 24 weeks (JCO. 2017;35:3844–50). In addition to a significant reduction in splenomegaly and improvements in constitutional symptoms, previously reported analyses of the SIMPLIFY-1 data demonstrated that patients in the momelotinib arm achieved nominal-statistical significance for all anemia endpoints tested, including a higher rate of transfusion independence (p < 0.001) and lower rates of transfusion dependence (p = 0.019) at Week 24, compared to patients on ruxolitinib, consistent with momelotinib’s pro-erythropoietic effect.

New retrospective analyses of the SIMPLIFY-1 transfusion data demonstrated that:

The Kaplan-Meier (K-M) proportion of patients who did not require any transfusions during the randomized treatment period was significantly greater for the momelotinib treated group (73%) than those who received ruxolitinib (46%; p<0.0001)
The K-M proportion of patients requiring fewer than 5 RBC units over the treatment period was also significantly greater for momelotinib (83%) than ruxolitinib (62%; p<0.0001).
The odds of a momelotinib patient receiving no transfusions was approximately 10-fold higher including covariates, compared to a patient treated with ruxolitinib
The overall transfusion burden during momelotinib therapy was approximately half of that for ruxolitinib (HR 0.522; p<0.0001) for models both with and without baseline characteristics from patients as covariates.
These dynamic measures of transfusion requirement will be further evaluated as exploratory endpoints in MOMENTUM, a planned Phase 3 study of momelotinib in anemic myelofibrosis patients previously treated with a JAK inhibitor, anticipated to launch in the fourth quarter of 2019. The MOMENTUM trial has been designed to re-confirm momelotinib’s ability to address each of the three hallmark features of myelofibrosis, namely constitutional symptoms, anemia, and splenomegaly. Dr. Srdan Verstovsek, MD, PhD, Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, has been named Chief Investigator of the trial.

About the ASH (Free ASH Whitepaper) 2019 Poster:
Title: Dynamic and Time-To-Event Analyses Demonstrate Marked Reduction in Transfusion Requirements for Janus Kinase Inhibitor–Naïve Myelofibrosis Patients Treated with Momelotinib Compared Head to Head with Ruxolitinib
Session Name: 634. Myeloproliferative Syndromes: Clinical: Poster I
Date: Saturday, December 7, 2019
Presentation Time: 5:30 PM – 7:30 PM
Location: Orange County Convention Center, Hall B

On November 6, 2019 Sanofi Analyses from the ICARIA-MM trial for isatuximab, an investigational anti-CD38 monoclonal antibody, reported that will highlight outcomes in an elderly patient population, depth of response and associated long-term outcomes, and health-related quality of life (Press release, Sanofi Genzyme, NOV 6, 2019, View Source [SID1234550546]). These results are among data for isatuximab, being investigated for the treatment of multiple myeloma, that will be presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition from December 7-10 in Orlando, FL.

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"We look forward to presenting further insights into isatuximab, including efficacy and safety data in patients 75 years of age and older, who generally experience poorer outcomes than those who are younger. In addition, we are detailing new results on depth of response, which is associated with long-term progression-free and overall survival," said Dietmar Berger, Head of Global Development at Sanofi. "These data advance our understanding of multiple myeloma, a difficult-to-treat disease with significant patient need."

The ICARIA-MM clinical trial serves as the basis of a Biologic License Application for isatuximab, which is currently under review by the U.S. Food and Drug Administration (FDA) with a target action date for a decision of April 30, 2020. The clinical trial is among a number of ongoing pivotal studies to evaluate the potential role of isatuximab in multiple standard-of-care treatment regimens for multiple myeloma. A Marketing Authorization Application for isatuximab was also accepted for review by the European Medicines Agency (EMA) in the second quarter of 2019.

Key Sanofi data being presented at ASH (Free ASH Whitepaper) include:

Efficacy of Isatuximab with Pomalidomide and Dexamethasone in Elderly Patients with Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis (Dr. Fredrik Schjesvold; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)
Depth of Response and Response Kinetics in the ICARIA-MM Study of Isatuximab/Pomalidomide/Dexamethasone in Relapsed/Refractory Multiple Myeloma (Dr. Cyrille Hulin; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)
Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma Treated with Isatuximab plus Pomalidomide and Dexamethasone: ICARIA-MM Study (Katherine Houghton; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)
Evaluating Isatuximab Interference with Monoclonal Protein Detection By Immuno-Capture and Liquid Chromatography Coupled to High Resolution Mass Spectrometry in the Pivotal Phase 3 Multiple Myeloma Trial, ICARIA-MM (Dr. Greg Finn; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)
The Relationship Between Baseline Biomarkers and Efficacy of Isatuximab in Combination with Pomalidomide and Dexamethasone in RRMM: Insights from Phase 1 and Phase 3 studies (Dr. Paul Richardson; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)
Exposure-response Analyses and Disease Modeling for Selection and Confirmation of Optimal Dosing Regimen of Isatuximab in Combination Treatment in Patients with Multiple Myeloma (Dr. Fatiha Rachedi; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)

In addition, new Phase 2 results in smoldering multiple myeloma will be presented (Investigator-Sponsored Study):

A Multicenter Phase II Single Arm Trial of Isatuximab in Patients with High Risk Smoldering Multiple Myeloma (Dr. Elisabet E. Manasanch; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)

About ICARIA-MM and isatuximab

ICARIA-MM is a pivotal Phase 3 randomized, open-label, multi-center trial evaluating isatuximab in combination with pomalidomide and dexamethasone (pom-dex) versus pom-dex alone in patients with relapsed/refractory multiple myeloma (RRMM). The study enrolled 307 patients with RRMM across 96 centers spanning 24 countries. Overall, patients had received a median of three prior lines of anti-myeloma therapy, including at least two consecutive cycles of lenalidomide and a proteasome inhibitor given alone or in combination.

During the trial, isatuximab was administered through an intravenous infusion at a dose of 10mg/kg once weekly for four weeks, then every other week for 28-day cycles in combination with standard doses of pom-dex for the duration of treatment.

Isatuximab targets a specific epitope on the CD38 receptor and is designed to trigger multiple, distinct mechanisms of action that are believed to directly promote programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and cell surface receptors, making it a potential target for antibody-based agents such as isatuximab. The clinical significance of these findings is under investigation.

Isatuximab is an investigational agent and its safety and efficacy have not been evaluated by the U.S. FDA, the EMA, or any other regulatory authority.

On November 6, 2019 Sanofi reported New clinical data from oncology and rare blood disorders portfolios and pipelines will be featured, including four oral presentations and 18 posters, at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition from December 7-10 in Orlando, FL (Press release, Sanofi Genzyme, NOV 6, 2019, View Source [SID1234550545]).

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"Blood cancers and rare blood disorders account for some of the most challenging diseases to treat, and patients often have limited therapeutic options," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "Drawing upon our deep expertise in hematology, and one of the industry’s more robust research and development programs actively working to address numerous hematologic conditions, we are excited to present new data at ASH (Free ASH Whitepaper) that we believe demonstrate our commitment to advancing science and improving the lives of patients we serve."

Advancing the understanding of multiple myeloma in difficult-to-treat populations

Isatuximab: In the area of multiple myeloma, analyses from the pivotal ICARIA-MM trial for isatuximab, an investigational anti-CD38 monoclonal antibody, will highlight depth of response and associated long-term outcomes (abstract #3185), health-related quality of life (abstract #1850), and outcomes in an elderly patient population (abstract #1893). The ICARIA-MM clinical trial serves as the basis of a Biologic License Application for isatuximab for the treatment of relapsed/refractory multiple myeloma, which is currently under review by the U.S. Food and Drug Administration with a target action date for a decision of April 30, 2020. A Marketing Authorization Application for isatuximab was also accepted for review by the European Medicines Agency in the second quarter of 2019. Read more about our oncology data at ASH (Free ASH Whitepaper).

Striving to address unmet needs for people with rare blood disorders

Cold Agglutinin Disease and Immune Thrombocytopenic Purpura: New analyses of transfusion practices in the U.S. (abstract #3559) and mortality risks associated with cold agglutinin disease (CAD) (abstract #4790) will underscore the seriousness of this rare and debilitating hemolytic anemia. Sutimlimab, an investigational monoclonal antibody designed to inhibit C1s, is being investigated as a potential first-in-class treatment for CAD in two pivotal Phase 3 studies. An oral presentation on sutimlimab will also explore its potential in immune thrombocytopenic purpura (ITP) patients without adequate response to two or more prior therapies (abstract #898). ITP represents a second indication being investigated for sutimlimab.

Hemophilia: Final data from a Phase 1 study (abstract #625) of BIVV001 (rFVIIIFc-VWF-XTEN) evaluating the safety and pharmacokinetics of repeated dosing will be shared in an oral presentation. BIVV001 is the first and only investigational von Willebrand (VWF)-independent factor VIII therapy that is designed to provide high sustained factor activity and extend protection from bleeds with once weekly dosing for people with hemophilia A. A Phase 3 study of BIVV001 is expected to be initiated by year-end. BIVV001 is being developed in collaboration with Sobi.

Additional analysis of the ongoing Phase 2 open-label extension study (abstract #1138) of fitusiran, a potential first-in-class, once-monthly, fixed-dose subcutaneously administered RNA interference therapeutic targeting antithrombin (AT) will also be shared. Fitusiran is the first and only monthly investigational therapy in Phase 3 development for the treatment of both hemophilia A and B, with and without inhibitors.

Hemoglobinopathies: New pre-clinical and clinical research on our pipeline of investigational, zinc finger nuclease ex vivo gene-edited cell therapies for sickle cell disease (BIVV003) and beta thalassemia (ST-400) will be shared in multiple presentations. BIVV003 and ST-400 are being developed in collaboration with Sangamo Therapeutics, Inc.

Acquired Thrombotic Thrombocytopenic Purpura; Additional presentations include results from studies on Cablivi (caplacizumab-yhdp), our first-in-class approved treatment, in combination with plasma exchange and immunosuppressive therapy, for adult patients with acquired thrombotic thrombocytopenic purpura (aTTP).

Oncology Poster Presentations:

Isatuximab

Efficacy of Isatuximab with Pomalidomide and Dexamethasone in Elderly Patients with Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis (Dr. Fredrik Schjesvold; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)

Depth of Response and Response Kinetics in the ICARIA-MM Study of Isatuximab/Pomalidomide/Dexamethasone in Relapsed/Refractory Multiple Myeloma (Dr. Cyrille Hulin; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)

Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma Treated with Isatuximab plus Pomalidomide and Dexamethasone: ICARIA-MM Study (Katherine Houghton; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)

Exposure-response Analyses and Disease Modeling for Selection and Confirmation of Optimal Dosing Regimen of Isatuximab in Combination Treatment in Patients with Multiple Myeloma (Dr. Fatiha Rachedi; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)

The Relationship Between Baseline Biomarkers and Efficacy of Isatuximab in Combination with Pomalidomide and Dexamethasone in RRMM: Insights from Phase 1 and Phase 3 studies (Dr. Paul Richardson; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)

Evaluating Isatuximab Interference with Monoclonal Protein Detection By Immuno-Capture and Liquid Chromatography Coupled to High Resolution Mass Spectrometry in the Pivotal Phase 3 Multiple Myeloma Trial, ICARIAMM (Dr. Greg Finn; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)

Rare Blood Disorders Oral and Poster Presentations:

Cold Agglutinin Disease and Immune Thrombocytopenic Purpura

Inhibition of the Classical Pathway of Complement With Sutimlimab in Chronic Immune Thrombocytopenic Purpura Patients Without Adequate Response to Two or More Prior Therapies – #898 – Monday, December 9, 2019, 6:15 PM – 7:45 PM (ET) – Oral Presentation – Room W307

Cold Agglutinin Disease Transfusion Practices in the United States: An Electronic Medical Record–Based Analysis – #3559 – Monday, December 9, 2019, 6:00 PM – 8:00 PM (ET)

Mortality Among Patients With Cold Agglutinin Disease in the United States: An Electronic Medical Record (EMR)–Based Analysis – #4790 (abstract only)

Hemophilia

Phase 1 Repeat Dosing with BIVV001: The First Investigational Factor VIII Product to Break through the Von Willebrand Factor–Imposed Half-Life Ceiling – #625 –Monday, December 9, 2019 10:30 AM – 12:00 PM (ET) – Oral presentation – Room W415A

Cryo-EM Structure of BIVV001 Reveals Coagulation Factor VIII-Von Willebrand Factor D’D3 Interaction Mode – #94- Saturday, December 7, 2019, 9:30 AM – 11:00 AM (ET) – Oral presentation – Room W414AB

Fitusiran, an RNAi Therapeutic Targeting Antithrombin to Restore Hemostatic Balance in Patients with Hemophilia A or B with or without Inhibitors: Management of Acute Bleeding Events – #1138 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET)

Patients’ and Caregivers’ Preferences for Different Hemophilia A Treatment Attributes – #2122 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET)

Acquired Thrombotic Thrombocytopenic Purpura

Safety of Caplacizumab in Patients Without Documented Severe ADAMTS13 Deficiency During the HERCULES Study – #1093 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET)

Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Baseline Disease Severity #2366 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)

Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Initial Immunosuppression Regimen – #2365 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)

Narratives of Patients with Fatal Outcomes During the Phase 2 TITAN and Phase 3 HERCULES Studies – #4908 (abstract only)

Sickle Cell Disease and Beta Thalassemia

Genetic Activation of NRF2 By KEAP1 Inhibition Induces Fetal Hemoglobin Expression and Triggers Anti-Oxidant Stress Response in Erythroid Cells – #210 – Saturday, December 7, 2019, 2:00 PM – 3:30 PM (ET) – Oral Presentation – Room W414B

Zinc Finger Nuclease-Mediated Disruption of the BCL11A Erythroid Enhancer Results in Enriched Biallelic Editing, increased Fetal Hemoglobin, and Reduced Sickling in Erythroid Cells Derived from Sickle Cell Disease Patients – #974 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET) – Joint with Sangamo

MetAP2 Inhibition Modifies Hemoglobin S (HbS) to Delay Polymerization and Improve Blood Flow in Sickle Cell Disease – #2260 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)

Differential Efficacy of Anti-Sickling and Anti-Inflammatory Mechanisms in a Fluorescent Intravital Microscopy Dorsal Skinfold Vaso-occlusion Model in Sickle Cell Disease Townes Mice, #2264 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)

Characterization of a genetically engineered HUDEP2 cell line harboring a sickle cell disease mutation as a potential research tool for preclinical Sickle Cell Disease Drug Discovery – #3559 – Monday, December 9, 2019, 6:00 PM – 8:00 PM (ET)

Preliminary Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia – #3544 – Monday, December 9, 2019, 6:00 – 8:00 PM (ET) – Joint with Sangamo

Identification of Novel Variants Associated with Fetal Hemoglobin Levels in Healthy Donors (the INTERVAL study) – #2243 – Sunday, December 8, 201, 6:00 PM – 8:00 PM (ET)

Rare Disease Presentations:

Gaucher Disease

Response to Oral Eliglustat in Adults with Gaucher Disease Type 1: Results from 4 Completed Clinical Trials – #4859 (abstract only)

About isatuximab

Isatuximab, an investigational anti-CD38 monoclonal antibody, targets a specific epitope on the CD38 receptor and is designed to trigger multiple, mechanisms of action that are believed to directly promote programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and cell surface receptors, making it a potential target for antibody-based therapeutics such as isatuximab.

Isatuximab is an investigational agent and its safety and efficacy have not been evaluated by the U.S. FDA, the European Medicines Agency, or any other regulatory authority.

About Sutimlimab

Sutimlimab is a C1s inhibitor that received breakthrough therapy designation and is currently being investigated for the treatment of CAD in Phase 3 clinical trials. A humanized, monoclonal antibody, sutimlimab is designed to target C1s, a serine protease within the C1-complex in the classical complement pathway of the immune system, which directly impacts the central mechanism of hemolysis in CAD. Similarly, the classical complement pathway has been shown to contribute to the physiopathology of immune thrombocytopenic purpura (ITP). With a unique mechanism of action and high target specificity, sutimlimab is designed to selectively inhibit disease processes by upstream blockade of the classical complement pathway while maintaining activity of the alternative and lectin complement pathways, which are important for immune surveillance and other functions.

Sutimlimab has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.

About BIVV001

BIVV001 (rFVIIIFc-VWF-XTEN) is a novel and investigational recombinant factor VIII therapy that is designed to provide high sustained factor activity and extend protection from bleeds with prophylaxis dosing of once weekly for people with hemophilia A. BIVV001 builds on the company’s innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation. BIVV001 was granted orphan drug designation by the Food and Drug Administration in August 2017 and the European Commission in June 2019. BIVV001 is being developed in collaboration with Sobi.

BIVV001 has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.

About Fitusiran

Fitusiran is potential first-in-class investigational, once-monthly, subcutaneously administered RNA interference therapeutic targeting antithrombin (AT) in development for the treatment of hemophilia A and B, with and without inhibitors. Fitusiran also has the potential to be used for rare bleeding disorders. Fitusiran is designed to lower levels of AT with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding. Fitusiran utilizes Alnylam’s ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability. The clinical significance of this technology is under investigation.

Fitusiran has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.

About BIVV003

BIVV003 is an investigational ex vivo gene-edited cell therapy for the treatment of people with sickle cell disease being developed in collaboration with Sangamo Therapeutics, Inc. BIVV003 is a non-viral cell therapy that involves gene editing of a patient’s own hematopoietic stem cells (HSCs) using zinc finger nuclease (ZFN) technology to address underlying disease pathophysiology. A Phase 1/2 clinical trial to assess the safety, tolerability, and efficacy of BIVV003 in adults with sickle cell disease has been initiated. Sanofi and Sangamo collaborate on a similar second program, ST-400, an investigational ex vivo gene-edited cell therapy, for the treatment of adults with beta-thalassemia. The safety, efficacy and tolerability ST-400 is currently being evaluated in a Phase 1 /2 clinical trial.

BIVV003 has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.

About Cablivi

Cablivi should be administered upon initiation of plasma exchange therapy, and in combination with immunosuppressive therapy, based on a diagnosis of aTTP. Cablivi is first administered as an 11 mg intravenous injection prior to plasma exchange, followed by an 11 mg subcutaneous injection after completion of plasma exchange on day 1. During the daily plasma exchange period and 30 days following daily plasma exchange, patients will take daily 11 mg subcutaneous injections. If after the initial treatment symptoms of the underlying disease are unresolved the treatment can be further extended for a maximum of 28 days. Subcutaneous injection can by administered by a patient/caregiver following proper training.

Cablivi was developed by Ablynx, which was acquired by Sanofi in 2018. Cablivi was approved in the European Union in August 2018 and in the United States in February 2019. Cablivi is part of the company’s rare blood disorders franchise within Sanofi Genzyme, the specialty care global business unit of Sanofi.

CABLIVI IMPORTANT SAFETY INFORMATION

What is CABLIVI?

CABLIVI (caplacizumab-yhdp) is a prescription medicine used for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

Who should not take CABLIVI?

Do not take CABLIVI if you’ve had an allergic reaction to caplacizumab-yhdp or to any of the ingredients in CABLIVI.

What should I tell my healthcare team before starting CABLIVI?

Tell your doctor if you have a medical condition including if you have a bleeding disorder. Tell your doctor about any medicines you take.

Talk to your doctor before scheduling any surgery, medical or dental procedure.

What are the possible side effects of CABLIVI?

CABLIVI can cause severe bleeding. In clinical studies, severe bleeding adverse reactions of nosebleed, bleeding from the gums, bleeding in the stomach or intestines, and bleeding from the uterus were each reported in 1% of subjects. Contact your doctor immediately if excessive bleeding or bruising occur.

You may have a higher risk of bleeding if you have a bleeding disorder (i.e Hemophilia) or if you take other medicines that increase your risk of bleeding such as anti-coagulants.

CABLIVI should be stopped for 7 days before surgery or any medical or dental procedure. Talk to your doctor before you stop taking CABLIVI.

The most common side effects include nosebleed, headache and bleeding gums.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of CABLIVI. Call your doctor for medical advice about side effects.