On December 11, 2017 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported the presentation of comprehensive dose-ranging data from two Phase 1b/2 studies of ALXN1210, the Company’s investigational long-acting C5 complement inhibitor, in patients with paroxysmal nocturnal hemoglobinuria (PNH), a chronic, progressive, debilitating and potentially life-threatening ultra-rare blood disorder characterized by complement-mediated hemolysis.1,2 Treatment with ALXN1210 for up to eight months resulted in rapid and sustained reduction of plasma lactate dehydrogenase (LDH) levels, a direct marker of hemolysis, with reductions in mean LDH levels from Baseline (BL) ranging from 73% to 88%. ALXN1210 was generally well tolerated with a safety profile that is consistent with that seen historically in patients with complement inhibition (Press release, Alexion, DEC 11, 2017, View Source [SID1234522523]). The data were presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in Atlanta. All patients from the Phase 1b study and from Cohorts 1, 2, and 3 of the Phase 2 study have been successfully transitioned to the Phase 3 dosing regimen, after which plasma LDH levels have remained suppressed.

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"It is encouraging to see rapid and sustained reduction in plasma LDH levels in these dose optimization studies," said Alexander Röth, M.D. from the Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany and an investigator in the Phase 1b/2 studies. "These comprehensive results provide robust preliminary evidence for the efficacy and safety of ALXN1210 as a future treatment for patients with PNH."

"The strength of these data and exposure-response analyses, along with the totality of data for ALXN1210 and discussions with global regulators, allowed us to determine an eight-week, weight-based dosing regimen that targets complete C5 inhibition and rapid and sustained suppression of LDH," said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. "We have completed enrollment in our two multinational Phase 3 PNH studies, with nearly 450 patients enrolled, and expect data from these studies in the second quarter of 2018."

Optimization of Dose Regimen for ALXN1210, a Novel Complement C5 Inhibitor, in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results of Two Phase 1b/2 Studies 3

The researchers presented results from two open-label Phase 1b/2 studies designed to provide dose ranging data to optimize the dosing regimen for the Phase 3 development of ALXN1210 as a treatment for patients with PNH based on exposure-response assessments. The studies included a total of 39 adult patients with PNH (Study 103, n=13; Study 201, n=26) who were naïve to complement inhibition. The primary efficacy endpoint was the change from BL in mean plasma LDH levels to day 169 in Study 103 and day 253 in Study 201. The secondary efficacy endpoints were changes from BL in free hemoglobin, haptoglobin, and reticulocytes. Post hoc efficacy analyses evaluated the proportion of patients achieving LDH levels within the normal range and the incidence of breakthrough hemolysis (days 29-253). LDH BL was defined as the average of values at screening, prior to the first ALXN1210 infusion. For other parameters, BL was defined as the most recent value prior to the first infusion. Study 103 evaluated two escalating intravenous (IV) dosing regimens of ALXN1210, and Study 201 evaluated four IV regimens with different doses and intervals. The results demonstrated exposure-response relationships, and further substantiate and extend previously presented results.4,5,6,7

Study 201 Study 103
LDH at Protocol-Specified Endpointa Cohort 1
1000 mg q4w
n=6
Cohort 2
1600 mg q6w
n=6
Cohort 3
2400 mg q8w
n=7
Cohort 4
5400 mg q12w
n=7
Cohort 1
900 mg q4w
n=6
Cohort 2
1800 mg q4w
n=7
% LDH reduction from BL, mean (SD)b 72.9 (12.1) 77.8 (6.5) 85.0 (4.4) 87.6 (6.9) 86.0 (3.2) 84.7 (3.8)
LDH levels, U/L, mean (SD) 230.0 (44.0) 266.0 (54.3) 306.1 (130.7) 276.4 (196.9) 232.0 (82.3) 227.9 (50.6)
LDH normalization (D29-D253)c
LDH normalized, n/N (%) 5/6 (83) 3/6 (50) 4/7 (57) 5/7 (71) 4/6 (67) 6/7 (86)
LDH >1.5 x ULN, n/N (%) 4/6 (67) 3/6 (50) 2/7 (29) 3/7(43) 2/6 (33) 1/7 (14)
LDH >2 x ULN, n/N (%) 2/6 (33) 1/6 (17) 2/7 (29) 1/7 (14) 1/6 (17) 0/7 (0)
Breakthrough hemolysis (D29-253)d
Incidence of breakthrough hemolysis through day 253, n/N (%) 2/6 (33.3) 1/6 (16.7) 2/7 (28.6) 1/7 (14.3) 1/6 (16.7) 0/7 (0)
BL: baseline; SD: standard deviation; D: day; LDH: lactate dehydrogenase; ULN: upper limit of normal
q4w: every 4 weeks; q6w: every 6 weeks; q8w: every 8 weeks; q12w: every 12 weeks
a LDH parameters at protocol-specified endpoint: Study 103, day 169/24 weeks; Study 201, day 253/36 weeks.
b Primary efficacy endpoint.
c Patients meeting each parameter at least once after day 29 through day 253.
d Defined as at least 1 symptom or sign of intravascular hemolysis (fatigue, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL and hemoglobin< baseline hemoglobin], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) within ±7 days of an elevated LDH ≥2 x ULN after prior LDH reduction to <1.5 x ULN on therapy.

The most frequent related treatment-emergent adverse event (TEAE) was headache. No patient stopped treatment or withdrew from the studies, and there were no deaths. Two patients in Study 201 experienced meningococcal infections but recovered completely and continued receiving ALXN1210. Meningococcal infections are a known risk with terminal complement inhibition, and specific risk-management plans have been in place for ten years for Soliris (eculizumab) to minimize the risk for patients.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating and potentially life-threatening ultra-rare blood disorder that can strike men and women of all races, backgrounds, and ages without warning, with an average age of onset in the early 30s.1,2,8 PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.2 In patients with PNH, chronic, uncontrolled activation of the complement system, a component of the body’s immune system, results in hemolysis (the destruction of red blood cells)9, which in turn can result in progressive anemia, fatigue, dark urine and shortness of breath.10,11,12 The most devastating consequence of chronic hemolysis is thrombosis (the formation of blood clots), which can damage vital organs and cause premature death.13 Historically, it had been estimated that one in three patients with PNH did not survive more than five years from the time of diagnosis.2 PNH is more common among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).14,15,16 In certain patients with thrombosis of unknown origin, PNH may be an underlying cause.9

About ALXN1210

ALXN1210 is an innovative, long-acting C5 inhibitor discovered and developed by Alexion that works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system that, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). In early studies, ALXN1210 demonstrated rapid, complete, and sustained reduction of free C5 levels, as well as rapid and sustained reduction of plasma lactate dehydrogenase (LDH) levels, a direct marker of hemolysis (the destruction of red blood cells).4,5,6,7 ALXN1210 is currently being evaluated in Phase 3 clinical studies as a potential treatment for patients PNH and aHUS, administered intravenously every eight weeks. In addition, Alexion plans to initiate a single, pharmacokinetics (PK)-based Phase 3 clinical study of ALXN1210 delivered subcutaneously once per week as a potential treatment for patients with PNH and aHUS.

ALXN1210 has received Orphan Drug Designation (ODD) for the intravenous treatment of patients with PNH in the U.S. and EU, and for the subcutaneous treatment of patients with aHUS in the U.S.

About Soliris (eculizumab)

Soliris is a first-in-class complement inhibitor that works by inhibiting the C5 protein in the terminal part of the complement cascade, a part of the immune system that, when activated in an uncontrolled manner, plays a role in severe rare and ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). Soliris is approved in the U.S., EU, Japan, and other countries as the first and only treatment for patients with PNH and aHUS, in the EU as the first and only treatment of refractory generalized MG (gMG) in adults who are anti-AchR antibody-positive, and in the U.S. for the treatment of adult patients with gMG who are anti-AchR antibody-positive. Alexion’s new drug application in Japan for Soliris as a treatment for patients with anti-AchR antibody-positive refractory gMG has been accepted for review by the Japanese Ministry of Health, Labour, and Welfare (MHLW). Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS).

Soliris has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU, Japan, and many other countries, for the treatment of patients with aHUS in the U.S., EU, and many other countries, for the treatment of patients with MG in the U.S. and EU, and for the treatment of patients with refractory gMG in Japan. Alexion and Soliris have received some of the pharmaceutical industry’s highest honors for the medical innovation in complement inhibition: the Prix Galien USA (2008, Best Biotechnology Product) and France (2009, Rare Disease Treatment).

For more information on Soliris, please see full prescribing information for Soliris, including BOXED WARNING regarding risk of serious meningococcal infection, available at www.soliris.net

Important Soliris Safety Information

The U.S. prescribing information for Soliris includes the following warnings and precautions: Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current Centers for Disease Control (CDC)’s Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with meningococcal vaccines at least two weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected. Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Patients may have increased susceptibility to infections, especially with encapsulated bacteria. Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions.

In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis, back pain and nausea. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, and pyrexia. In patients with gMG who are anti-AchR antibody-positive, the most frequently reported adverse reaction observed with Soliris treatment in the placebo-controlled clinical study (≥10%) was musculoskeletal pain.

On December 11, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported initial clinical data from its ongoing Phase 2 trial of SY-1425, its first-in-class oral, selective retinoic acid receptor alpha (RARα) agonist, in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (Press release, Syros Pharmaceuticals, DEC 11, 2017, View Source [SID1234522519]). The data are being presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"I’m encouraged with the single-agent activity and tolerability of SY-1425 in difficult-to-treat leukemia and MDS patients who have few treatment options," said Joseph G. Jurcic, Professor of Medicine at Columbia University Medical Center and Director of the Hematologic Malignancies Section of the Division of Hematology/Oncology. "We saw improved blood counts and reduced blast counts in conjunction with differentiation of cancer cells in genomically defined patients. These data, along with the mechanistic and preclinical data supporting combinations with azacitidine and with daratumumab, suggest SY-1425 could be a meaningful combination agent with the potential to address a substantial unmet need for patients with AML and MDS."

"The biologic and clinical activity seen in patients selected by our proprietary RARA and IRF8 biomarkers provide validation of our platform’s ability to enrich for patients most likely to respond to gene control therapies," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "These data support continued development of SY-1425 in combination,

which will be our focus going forward. Our preclinical data showing the tumor-killing activity of SY-1425 in combination with azacitidine and with daratumumab support the ongoing development of SY-1425 in combination with these therapies, and we plan to present initial clinical data on these two combinations in 2018."

Data from the Ongoing Phase 2 Clinical Trial

The ongoing Phase 2 clinical trial of SY-1425 is assessing the safety and efficacy as both a single agent and a combination agent in AML and MDS patients who are positive for either the RARA or IRF8 biomarkers, or both. The data being presented at ASH (Free ASH Whitepaper) are from two of the five cohorts in the ongoing trial. As of the data cutoff at the end of October 2017, 58 patients had been treated with SY-1425 in two single-agent cohorts, consisting of 29 patients in the relapsed or refractory AML and higher-risk MDS cohort and 29 patients in the lower-risk transfusion-dependent MDS cohort.

The relapsed or refractory AML and higher-risk MDS cohort had a median age of 72 years with more than half the patients having poor risk cytogenetics and 45% having two or more prior therapies, and the lower-risk MDS cohort had a median age of 76 years. Target enrollment has been reached in both cohorts.

Initial Safety Data

· Chronic daily dosing of SY-1425 administered at 6 mg/m2 orally divided in two doses was generally well-tolerated, with a median treatment duration of 80 days, and patients treated up to eight months and remaining on study.
· The majority of adverse events (AEs) were Grade 1 or Grade 2.
· Across all grades and causality, the most commonly reported AEs included hypertriglyceridemia (36%), fatigue (31%), and dermatologic effects (28%).
· The most common Grade 3 or 4 AE was hypertriglyceridemia (16%).

Initial Clinical Activity Data

As of the data cutoff, 48 patients were evaluable for response assessment, including 23 patients in the relapsed or refractory AML and higher-risk MDS cohort and 25 patients in the lower-risk transfusion-dependent MDS cohort.

· Ten of the 23 (43%) evaluable relapsed or refractory AML and higher-risk MDS patients and two of the 25 (8%) evaluable transfusion-dependent lower-risk MDS patients had evidence of clinical activity, including:.

· Nine with improvements in hematological parameters. Of those, four achieved hematological improvement lasting at least eight weeks, as defined by Revised International Working Group (IWG) criteria.
· Five with reductions in bone marrow blasts. Of those, one relapsed or refractory higher-risk MDS patient achieved a marrow complete response as defined by IWG criteria. The patient had been on treatment 238 days and remained on treatment as of the data cutoff.

· 13 of the 23 (57%) evaluable relapsed or refractory AML and higher-risk MDS patients had stable disease.
· 11 of 13 (85%) of patients with pre- and post-treatment immunophenotyping samples showed increased expression of CD38, a marker of cell differentiation, on bone marrow blasts after one 28-day cycle of treatment.
· No patients with lower-risk MDS achieved transfusion independence.

Additionally, myeloid cell differentiation in the bone marrow, as measured by morphologic evaluation, FISH analysis and immunophenotyping, was observed, consistent with the underlying mechanism of action of SY-1425 as a differentiating agent. The induction of CD38 observed in bone marrow blasts from patients treated with SY-1425 supports the combination cohort with daratumumab recently added to the Phase 2 trial.

As presented at the European School of Haematology’s 4th International Conference on Acute Myeloid Leukemia in October 2017, approximately 40% of 201 patients screened for the clinical trial as of the end of August 2017 were biomarker-positive, including approximately one-third of relapsed or refractory AML and higher-risk MDS patients. In blood samples taken from patients upon screening and treated ex vivo with SY-1425, a positive biomarker status was significantly correlated with SY-1425 induced myeloid cell differentiation, supporting the predictive value of the biomarker test for patient selection.

Preclinical Combination Data for SY-1425

SY-1425 has shown synergistic tumor-killing activity in combination with azacitidine, a standard-of-care therapy in AML and MDS, as well as with daratumumab, an anti-CD38 antibody approved to treat multiple myeloma, in preclinical models of RARA biomarker-positive AML. In combination with azacitidine, SY-1425 demonstrated greater clearance of tumor cells in bone marrow and other tissues and greater depth and duration of tumor response, compared to either azacitidine or SY-1425 alone. In combination with daratumumab, SY-1425 triggered robust immune cell-mediated tumor death. Notably, AML cells do not normally express high levels of CD38. Syros has shown that by inducing CD38 expression, SY-1425 sensitizes biomarker-positive AML models to the tumor-killing effects of daratumumab.

Clinical Development Plans for SY-1425

Syros plans to focus its ongoing Phase 2 clinical trial on assessing the safety and efficacy of SY-1425 in combination with other therapies. Syros is continuing to enroll patients in a cohort evaluating SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy. Syros recently added a cohort in relapsed or refractory AML and higher-risk MDS patients to evaluate SY-1425 in combination with daratumumab and expects to begin enrolling patients in that cohort in early 2018. All patients enrolled or to be enrolled in the trial are prospectively selected using the Company’s RARA or IRF8 biomarkers. Syros expects to report initial clinical data from each combination cohort in 2018. Syros does not plan to pursue further development of SY-1425 as a single agent and is stopping enrollment in the single-agent cohort in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

Additional details about the trial can be found using the identifier NCT02807558 at www.clinicaltrials.gov.

Investor Event and Webcast Information

Syros will host an investor event on Monday, December 11 beginning at 12:00 p.m. ET in Atlanta to discuss the initial SY-1425 clinical data presented at ASH (Free ASH Whitepaper). The event can be accessed by dialing 866-595-4538 (domestic) or 636-812-6496 (international) and providing the passcode 8887999. A live webcast will also be available and can be accessed under "Events & Presentations" in the Investors section of the Company’s website at View Source A replay of the webcast will be available approximately two hours after the event and will be available for 30 days following the event.

On December 11, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment; TecDAX, OTC: MPSYY) reported clinical data from the ongoing phase 2 clinical trial (L-MIND) evaluating MOR208 in combination with lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). DLBCL is the most frequent type of malignant lymphoma worldwide and accounts for approximately 30% of all non-Hodgkin lymphomas. Data will be reported in a poster presentation (available for download) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia/USA. MOR208 is an investigational Fc-engineered monoclonal antibody directed against CD19 (Press release, MorphoSys, DEC 11, 2017, View Source [SID1234522518]).

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The data presented at ASH (Free ASH Whitepaper) formed the basis for the Breakthrough Therapy designation recently awarded by the FDA for MOR208, in combination with lenalidomide, for the treatment of non-transplant eligible patients with R/R DLBCL.

At data cut-off (June 13, 2017), 51 patients had been enrolled in the study, of whom 44 were evaluable for efficacy assessments. Preliminary data show an objective response in 23 out of 44 patients (ORR: 52%), 19 (83%) of whom show ongoing responses. Complete remission was seen in 14 out of 44 patients (CR: 32%). The median time to response was 1.8 months, the median time to complete response was 2.3 months. The preliminary median progression-free survival (PFS) based on Kaplan Meier calculation was 11.3 months.

No unexpected toxicities were observed for the treatment combination and no infusion-related reactions were reported for MOR208. The most frequent adverse events with a toxicity grading of 3 or higher were neutropenia, thrombocytopenia, and leukopenia, observed in 35%, 10%, and 8% of patients, respectively. Pneumonia and hypokalemia were reported for 10% and 8% of the patients. To date, 45% of patients required a reduction of their lenalidomide dose, from a starting dose of 25mg daily.

The trial has recently completed patient recruitment as required by the study protocol. To date, 81 patients have been enrolled.

"We are very encouraged by the updated clinical trial results from the ongoing L-MIND trial, especially the complete responses and the duration of responses we have seen so far. DLBCL is a very aggressive lymphoma. In particular, those patients with relapsed or refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplantation are in need of more therapeutic options. Based on the FDA Breakthrough Therapy designation we recently obtained, we intend to develop MOR208 together with lenalidomide as a potential new treatment option for this patient group as quickly as possible," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG.

The L-MIND trial (Lenalidomide plus MOR208 in DLBCL) is a single-arm, open-label, multicenter study of MOR208 in combination with lenalidomide. The trial is enrolling patients with relapsed or refractory DLBCL after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy (e.g. rituximab). Patients could not be candidates for high-dose chemotherapy and autologous stem cell transplantation. Patients enrolled had a median age of 74 years.

Details of the MOR208 presentation at ASH (Free ASH Whitepaper) 2017:

Abstract #4123; Poster III

Single-Arm Phase II Study of MOR208 Combined with Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: L-Mind

The poster will be presented during the session #626 "Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials" on Monday, December 11, 2017, 6:00pm-8:00pm EST (Dec. 12, 2017, 0:00am-2:00am CET), in the Georgia World Congress Center, Bldg A, Lvl 1, Hall A2.

In addition to the presentation, the abstract has been published online in the December 8, 2017 supplemental volume of Blood. Additional information can be found at www.hematology.org, including the abstract.

MorphoSys will hold an investor & analyst conference call after the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2017 on December 12, 2017, 11:00am EST(5:00pm CET).

Dial in:
Germany: +49 89 2444 32975
United Kingdom: +44 20 3003 2666
USA: +1 202 204 1514
The presentation slides and webcast link will be available at www.morphosys.com/conference-calls. A slide-synchronized audio replay of the conference will also be available at the corporate website following the live event.

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an investigational Fc-enhanced monoclonal antibody directed against CD19, a prominent marker present on the surface of B-cells. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. Furthermore, MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys AG is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) was started in March 2016 and is designed to investigate the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL. The phase 2/3 B-MIND study was started in August 2016 and transitioned into its phase 3 pivotal part in June 2017 following a recommendation of the IDMC based on the available data from the phase 2 initial safety evaluation. The B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Furthermore, MOR208 is currently being clinically investigated in combination with idelalisib or venetoclax in patients with relapsed/refractory CLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib).

On December 11, 2017 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on the development of potentially curative therapeutics using the CRISPR technology, and its collaborator, Novartis, reported initial data from their research collaboration on genome-edited human hematopoietic stem cells (Press release, Intellia Therapeutics, DEC 11, 2017, View Source [SID1234522514]). These data showed successful ex vivo editing of the erythroid specific enhancer of BCL11A, a gene associated with prevention of sickle cell disease, and the ability of these cells to stably engraft in mice while maintaining their desired properties.

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These data were presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in the platform presentation session: Hemoglobinopathies, Excluding Thalassemia – Basic and Translational Science: Sickle Cell Disease – Hematopoiesis and Fetal Hemoglobin Augmentation. In the presented studies, the companies:

Achieved approximately 80-95 percent target site modification in human hematopoietic stem and progenitor CD34+ cells following electroporation of ribonucleoprotein (RNP) composed of Cas9 and a guide RNA (gRNA), selected for efficacy and potency;

Demonstrated an approximately 40 percent reduction in BCL11A mRNA with a corresponding two-fold increase in γ-globin transcript and 30-40 percent more fetal hemoglobin-positive cells above background. Similar decreases in BCL11A mRNA and increases in γ-globin transcipt were observed when sickle cell disease-derived cells from patient donors were edited;

Achieved engraftment over 16 weeks following transplantation of edited human bone marrow CD34+ cells into immune compromised mice, while maintaining editing levels in engrafted cells; and

Observed no off-target events in CD34+ cells edited with the selected gRNA, as measured by targeted next generation sequencing of sites identified through in silico prediction and based on an unbiased, genome-wide, oligo-insertion detection method.
"We are pleased to be reporting data from studies generated through Intellia’s collaboration with Novartis, demonstrating successful ex vivo CRISPR/Cas9 editing in hematopoietic stem cells," said John Leonard, M.D., executive vice president, Research & Development, Intellia Therapeutics. "These results are significant as we have shown high levels of editing as well as increased production of fetal hemoglobin to clinically relevant levels, which could potentially ameliorate sickle cell disease in affected patients. We are very encouraged to present this progress given that sickle cell disease is a serious condition that currently has limited treatment options."

About Sickle Cell Disease

Sickle cell disease is a life-threatening, hereditary disorder that impacts approximately 30 million people worldwide. The disease results from a single amino acid change in the β-globin gene, which causes polymerization of hemoglobin and the deformation of red blood cells, leading to vaso-occlusion, severe pain crisis and multi-organ dysfunction. The average life expectancy in the developed world is 40 to 60 years. About 80 percent of sickle cell disease cases are believed to occur in sub-Saharan Africa.

On December 11, 2017 Integra LifeSciences Holdings Corporation (NASDAQ:IART), a leading global medical technology company, reported it will host an Investor Day meeting with analysts and institutional investors in New York City, beginning at 8:00 a.m. EST. Members of Integra’s executive leadership team will discuss the company’s financial performance and outlook (Press release, Integra LifeSciences, DEC 11, 2017, View Source [SID1234522512]).

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Highlights of today’s conference include:

• Reaffirming 2017 financial guidance as provided on October 26, 2017, including:

Full-year 2017 revenue in the range of $1.165 billion to $1.175 billion, which includes about 4% organic growth

Full-year 2017 adjusted earnings per share in the range of $1.83 to $1.87
• Providing 2018 preliminary revenue estimate in the range of $1.46 billion to $1.48 billion, which includes about 5% organic growth

• Reaffirming 2018 adjusted earnings per share in the range of $2.25 to $2.35, consistent with preliminary estimates provided on October 26, 2017

• Establishing five-year financial targets of approximately $2 billion in revenue and an adjusted EBITDA margin range of 28% to 30%

The company will host a livestream of the presentation and conference materials are available through the Investors section of Integra’s website at www.integralife.com. A replay of the conference will be archived on the company website.