On June 10, 2016 Janssen-Cilag International NV reported data from the Phase 3 MMY3003 (POLLUX) trial, which show the immunotherapy daratumumab in combination with a standard of care treatment regimen, lenalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid), achieved a significant 63 percent reduction in the risk of disease progression or death (progression-free survival, or PFS) compared to lenalidomide and dexamethasone alone in patients with multiple myeloma who had received at least one prior line of therapy (Hazard Ratio [HR]=0.37; 95 percent CI (0.27-0.52), p<0.0001) (Press release, Janssen-Cilag International, JUN 10, 2016, View Source [SID:1234513203]).1 The median PFS in the daratumumab arm has not been reached, compared with a median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone.1 Additionally, daratumumab significantly increased the overall response rate (ORR) [93 percent vs. 76 percent, p<0.0001]. 1

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"Daratumumab induced deep and durable responses when combined with standard of care, more than doubling the rates of complete response or better in these previously treated patients"
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These data will be highlighted during the Press Briefing at the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) at 8:30 a.m. CEST and have been selected for inclusion in the Presidential Symposium from 4:47 – 5:00 p.m. CEST on Friday, June 10th (Abstract LB2238).

"Daratumumab induced deep and durable responses when combined with standard of care, more than doubling the rates of complete response or better in these previously treated patients," said Meletios A. Dimopoulos, MD, Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece and lead author of the abstract. "These striking results underscore the clinical benefit of a treatment plan built on daratumumab for patients with one or more prior lines of therapy."

In addition to meeting the primary endpoint of significantly improved PFS at a median follow-up of 13.5 months and significantly increasing ORR compared to lenalidomide and dexamethasone alone, daratumumab doubled rates of complete response (CR) or better [43 percent vs. 19 percent, p<0.0001], including rates of very good partial response (VGPR) or better [76 percent vs. 44 percent, p<0.0001].1 The treatment effect for daratumumab was consistent across all pre-specified subgroups.

"We’re so pleased to see daratumumab delivering consistent results across the treatment continuum in multiple myeloma. MMY3003 is the second Phase 3 study with daratumumab in combination to standard therapy, to meet its primary endpoint before the final analysis," said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. "These data will be discussed in more detail at EHA (Free EHA Whitepaper) today, and we look forward to what will be an extremely exciting medical meeting for Janssen Oncology."

Overall, the safety of the daratumumab combination therapy was consistent with the known safety profile of daratumumab monotherapy (D) and lenalidomide plus dexamethasone (Rd), respectively. Similar rates of treatment discontinuation due to TEAEs were observed (7 percent/8 percent) in both the experimental arm and the control arm.1 The most common (<25 percent) treatment-emergent adverse events (TEAEs) [DRd/Rd] were neutropenia (59 percent/43 percent), diarrhoea (43 percent/25 percent), fatigue (35 percent/28 percent), upper respiratory tract infection (32 percent/21 percent), anaemia (31 percent/35 percent), constipation (29 percent/25 percent), cough (29 percent/13 percent), thrombocytopenia (27 percent/27 percent) and muscle spasms (26 percent/19 percent).1 Most common grade 3/4 TEAEs (>10 percent) were neutropenia (52 percent/37 percent), thrombocytopenia (13 percent/14 percent) and anaemia (12 percent/20 percent).1 The rate of Grade 3/4 infections was 28 percent versus 23 percent, and the most common Grade 3/4 infections (≥5 percent) was pneumonia (8 percent/8 percent).1 Daratumumab-associated infusion-related reactions (48 percent of patients) were mostly grade 1/2 (grade 3/4: 5 percent/0 percent), and most (92 percent) occurred during the first infusion.1

About the MMY3003 (POLLUX) Trial1

The MMY3003 (POLLUX) trial is a Phase 3, multinational, open-label, randomised, multicentre, active-controlled study in 569 patients with multiple myeloma who received a median of one prior line of therapy. Patients were randomised to receive either daratumumab combined with lenalidomide and dexamethasone, or lenalidomide and dexamethasone alone. Participants were treated until disease progression, unacceptable toxicity or if they had other reasons to discontinue the study. Nineteen percent of patients received three or more prior lines of therapy. Eighty-six percent of patients received prior treatment with proteasome inhibitor (PI); 55 percent received prior treatment with an immunomodulatory agent (including 18 percent with lenalidomide); and 44 percent received prior treatment with a PI and immunomodulatory agent. Twenty-seven percent of patients were refractory to their last line of prior therapy; 18 percent were refractory to a PI; and none were refractory to lenalidomide.

On May 20, 2016, the MMY3003 trial was stopped early after meeting its primary endpoint of significantly improved PFS in a pre-planned interim analysis. Based on the recommendation of an Independent Data Monitoring Committee (IDMC), patients in the control treatment arm were offered the option to receive daratumumab following confirmed disease progression.

About Daratumumab

Daratumumab is a first-in-class biologic targeting CD38, a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.2-4Daratumumab induces rapid tumour cell death through apoptosis (programmed cell death)5,6 and multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).5,7,8 Daratumumab has also demonstrated immunomodulatory effects that contribute to tumour cell death via a decrease in immune suppressive cells including T-regs and myeloid-derived suppressor cells.5,9 Five Phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed. For more information, please see www.clinicaltrials.gov.

In May 2016, daratumumab was conditionally approved by the European Commission for monotherapy of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.5 Daratumumab was approved under an accelerated assessment, a process reserved for medicinal products expected to be of major public health interest, particularly from the point of view of therapeutic innovation.10

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.11,12 Refractory cancer occurs when a patient’s disease is resistant to treatment or in the case of multiple myeloma, patients progress within 60 days of their last therapy.13,14 Relapsed cancer means the disease has returned after a period of initial, partial or complete remission.15 Accounting for approximately one percent of all cancers and 15 percent to 20 percent of haematologic malignancies worldwide,16 multiple myeloma is designated as an orphan disease in both Europe and the US. Globally, it is estimated that 124,225 people were diagnosed, and 87,084 died from the disease in 2015.17,18 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections.12 Patients who relapse after treatment with standard therapies (including PIs or immunomodulatory agents) typically have poor prognoses and few remaining options.19

On June 10, 2016 Syros Pharmaceuticals reported that SY-1425, its potent and selective retinoic acid receptor alpha (RARα) agonist, was observed to inhibit the growth of cancer cells and prolong survival in an in vivo model of acute myeloid leukemia (AML) with a novel RARA biomarker discovered by the Company (Press release, Syros Pharmaceuticals, JUN 10, 2016, View Source [SID:1234513202]). Syros also announced that SY-1365, its first-in-class potent and selective cyclin-dependent kinase 7 (CDK7) inhibitor, was observed to selectively kill acute leukemia cells over non-cancerous cells and induce complete tumor regression and a significant survival benefit in in vivo models of AML. These data are being presented this week at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark.

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"The presentations at EHA (Free EHA Whitepaper) highlight the potential of our gene control platform to systematically analyze the non-coding, regulatory region of the genome to advance a new wave of medicines designed to control the expression of disease-causing genes"
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"The presentations at EHA (Free EHA Whitepaper) highlight the potential of our gene control platform to systematically analyze the non-coding, regulatory region of the genome to advance a new wave of medicines designed to control the expression of disease-causing genes," said Nancy Simonian, MD, Chief Executive Officer of Syros. "By pioneering the understanding of this previously unexploited region of the genome, we believe we can identify novel disease drivers in specific patient populations and develop drugs that influence multiple disease-driving genes to provide patients with a more profound and durable benefit than many of today’s targeted therapies. Based on these strong preclinical data, we are currently advancing SY-1425 into a Phase 2 trial in genomically defined subsets of relapsed or refractory AML and relapsed high-risk MDS patients and plan to advance SY-1365 into a clinical trial for acute leukemia in the first half of 2017."

SY-1425 for Novel Genomically Defined Subsets of AML and MDS Patients
The data on SY-1425, which will be detailed in an oral presentation Sunday at EHA (Free EHA Whitepaper), shows that a biomarker for a highly specialized regulatory region of non-coding DNA, known as a super-enhancer, that is associated with the RARA gene is predictive of response to treatment with SY-1425 in AML cell lines and a patient-derived xenograft (PDX) model of AML. Treatment with SY-1425 was observed to inhibit cancer growth and prolong survival in a PDX model of AML with the RARA biomarker but not in a model of AML without the biomarker. Syros found the biomarker in approximately 25 percent of AML and myelodysplastic syndrome (MDS) patient tissue samples analyzed. Highlights of the data include:

Greatly reduced tumor burden in the blood, bone marrow and spleen in a PDX mouse model with the RARA biomarker treated with SY-1425 compared to untreated mice; by contrast, no effect was seen in a PDX model of AML without the biomarker.
Prolonged survival with 100 percent of mice with the RARA biomarker treated with SY-1425 alive at the end of the 35-day study; by contrast, none of the untreated mice survived beyond 25 days; notably, no survival benefit was seen in a PDX model of AML without the biomarker.
No anti-tumor or survival benefit seen with ATRA, a less potent and non-selective retinoid, in a PDX model with the RARA biomarker.
Differentiation of AML cells with the RARA biomarker treated with SY-1425.
Using its gene control platform, Syros identified subsets of AML and MDS patients whose tumors have the RARA super-enhancer. The super-enhancer is believed to lead to over-production of the RARα transcription factor, locking cells in an immature, undifferentiated and proliferative state. Treatment with SY-1425 inhibits cancer growth by promoting differentiation of AML cells with the RARA super-enhancer. Syros is on track to initiate a Phase 2 clinical trial of SY-1425 in mid-2016 in subsets of relapsed or refractory AML and relapsed high-risk MDS patients with the RARA biomarker.

CDK7 Inhibition as a Novel Treatment Strategy for Acute Leukemia
In the preclinical studies being presented Saturday at EHA (Free EHA Whitepaper), SY-1365 was observed to preferentially kill AML and acute lymphoblastic leukemia (ALL) cells over non-cancerous cells and induce tumor regression and significantly prolong survival in models of AML. Highlights of the in vitro and in vivo data include:

Complete tumor regression, which was maintained through the end of the 38-day study, in 100 percent of treated mice in a cell-line derived xenograft model of AML.
Strong survival benefit, with treated mice surviving up to 7-1/2 weeks beyond untreated mice in a PDX model of treatment-resistant AML.
Robust, sustained and dose-dependent apoptosis in AML and ALL cells treated with SY-1365 while not inducing apoptosis in non-cancerous cells.
Potent and selective inhibition of CDK7, with only six other kinases exhibiting greater than 90 percent binding when profiled across a panel of 468 kinases at a concentration of 1μM; notably, SY-1365 was not observed to significantly bind to members of the CDK family involved in cell cycle.
Minimal effect on blood cell counts, including white blood cells, lymphocytes, neutrophils and reticulocytes, in an in vivo model, demonstrating a more favorable profile than a non-selective CDK inhibitor.
Reduced expression of cancer-contributing genes associated with super-enhancers, including oncogenic transcription factors MYB and MYC, in an AML cell line.
Synergistic activity when combined with other targeted agents in AML, including Flt3, Bcl-2 and pan-Brd inhibitors.
Certain cancers, including AML and ALL, are dependent on high and constant expression of transcription factors for their growth and survival and have been shown to be particularly responsive to selective inhibition of CDK7. Syros has generated several selective CDK7 inhibitors, which have been observed to delay tumor progression in in vivo models of additional transcriptionally addicted cancers, including MYCN-amplified neuroblastoma, small cell lung cancer and triple negative breast cancer. Syros selected SY-1365 as its development candidate based on its strong preclinical efficacy and safety and plans to begin a Phase 1/2 clinical trial of SY-1365 in acute leukemia in the first half of 2017.

On June 10, 2016 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported that interim data were presented from a Phase 1/2 study of ALXN1210, an investigational, highly innovative longer-acting anti-C5 antibody, in patients with paroxysmal nocturnal hemoglobinuria (PNH), a debilitating, ultra-rare blood disorder characterized by complement-mediated hemolysis (destruction of red blood cells) (Press release, Alexion, JUN 10, 2016, View Source [SID:1234513201]).1 In this study, once-monthly dosing of ALXN1210 achieved rapid and sustained reductions in mean levels of lactate dehydrogenase (LDH), a marker of hemolysis, in 100 percent of treated patients, which were observed through up to five once-monthly dosing intervals. Researchers also reported that, at this time, 80 percent of patients who required at least 1 blood transfusion in the 12 months prior to treatment with ALXN1210 did not require transfusions while on treatment.2 These findings were presented in a late-breaking poster at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark.

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In a separate late-breaking poster at EHA (Free EHA Whitepaper), additional interim results were presented from a Phase 2 trial evaluating ALXN1007, a novel anti-inflammatory antibody targeting complement protein C5a, in patients with acute graft-versus-host disease of the lower GI tract (GI-GVHD). Acute GI-GVHD is a severe and life-threatening rare autoimmune disease that can occur as a complication of stem cell or bone marrow transplantation.3,4,5 The study showed an overall 28-day response rate—defined as improvement from diagnosis in any organ by ≥1 stage, without progression in any other organ and no need for additional therapy—of 77 percent in ALXN1007-treated patients.6

"Alexion has more than 20 years of experience in complement research and discovery, and we are pleased to have late-breaking data from two of our highly innovative, investigational complement inhibitors, ALXN1210 and ALXN1007, presented at EHA (Free EHA Whitepaper)," said Martin Mackay, Ph.D., Executive Vice President and Global Head of R&D at Alexion. "Interim results from the Phase 1/2 study of ALXN1210 in patients with PNH showed rapid, complete, and sustained complement inhibition, as measured by reductions in LDH levels, with a once-monthly dosing regimen in all treated patients. A Phase 2 study is ongoing to evaluate the safety and efficacy of ALXN1210 in additional dosing cohorts evaluating longer dosing intervals."

ALXN1210, a Long-Acting C5 Inhibitor, Results in Rapid and Sustained Reduction of LDH with a Monthly Dosing Interval in Patients with PNH: Preliminary Data from a Dose-Escalation Study (Abstract LB2247) 2

In a poster session, interim results were presented from a Phase 1/2, open-label, 24-week dose-escalating study of ALXN1210 in patients with PNH. The primary efficacy endpoint was the percent change in LDH levels from baseline; other efficacy endpoints included change in blood transfusion requirements and change in hematologic parameters from baseline. Patients with PNH (aged 18 and older; n=13) with mean LDH levels ≥3 times the upper limit of normal and who were complement inhibitor-naïve were separated into two study cohorts. Patients in Cohort 1 (n=6) received either 400 mg or 600 mg induction doses of ALXN1210, followed by a 900 mg maintenance dose once-monthly. Patients in Cohort 2 (n=7) received 600 mg and 900 mg induction doses of ALXN1210, followed by an 1,800 mg maintenance dose once-monthly.

All patients showed rapid reductions in mean LDH levels at Day 8 (the first evaluable time point of the study), which were sustained for up to five once-monthly dosing intervals. At the most recent evaluable time point, the mean percentage reduction in LDH levels from baseline was 85.4 percent in Cohort 1 (Day 148) and 86.0 percent in Cohort 2 (Day 85). Among five patients with one or more transfusions in the year prior to the study, only one patient, from Cohort 1, required a transfusion during treatment with ALXN1210. This patient received two units of packed red blood cells (RBC) while receiving ALXN1210, compared to 12 units of RBC in the six months prior to ALXN1210. In addition, mean levels of hemoglobin, another direct marker of intravascular hemolysis, were improved or stable in both cohorts.

"PNH is a devastating, ultra-rare blood disorder caused by uncontrolled activation of complement, putting patients at risk for severe and life-threatening consequences," said lead author Jong-Wook Lee, M.D., of The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, Korea. "The interim data presented at EHA (Free EHA Whitepaper) suggest that treatment with ALXN1210 results in effective blockade of complement-mediated hemolysis and reduces transfusion requirements in patients with PNH. All patients achieved rapid decreases in LDH levels that were sustained through extended, once-monthly dosing intervals, consistent with the longer half-life of ALXN1210."

No serious adverse events or study withdrawals were observed in either patient cohort. The most common treatment-related adverse events were headache and upper respiratory tract infection (each occurring in 3 patients), which resolved during ongoing treatment with ALXN1210.

Phase 2A Study of ALXN1007, A Novel C5a Inhibitor, in Subjects with Newly Diagnosed Acute Graft-Versus-Host Disease (GVHD) Involving the Lower Gastrointestinal Tract (Abstract LB2269) 6

In a poster session, additional interim results were presented from an ongoing Phase 2, open-label study of ALXN1007 in patients with newly diagnosed acute GI-GVHD. The primary efficacy endpoint is the overall acute GVHD response rate at Day 28. Other efficacy endpoints include complete GI-GVHD response rate at Day 28 and Day 56. Patients were treated once-weekly with 10 mg/kg of ALXN1007 for eight weeks in combination with methylprednisolone or equivalent, with one year of follow-up.

At both Day 28 and Day 56, the overall acute GVHD response rate was 77 percent in 13 evaluable patients. Complete GI-GVHD response rates at Days 28 and 56 were 69 percent and 77 percent, respectively. Additionally, at Day 180, the non-relapse mortality rate from causes other than the underlying malignancy was 12.5 percent, and the overall survival rate was 69.2 percent, among 13 evaluable patients.

The study also evaluated the degree of C5a inhibition relative to PK and acute GI-GVHD response suggesting that higher doses and frequency may be needed to optimize C5a inhibition and maximize clinical response. The trial protocol was subsequently amended to evaluate an ALXN1007 dose of 20 mg/kg weekly and twice-weekly.

Two patients (13 percent) experienced serious treatment-related adverse events and one patient had a grade 2 infusion-related reaction. There were no grade 3 or higher non-serious adverse events related to treatment with ALXN1007. One patient withdrew from the study due to a treatment-emergent adverse event (relapse of T-cell lymphoma). Six deaths were reported, none of which were considered related to treatment with ALXN1007.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is an ultra-rare blood disorder in which chronic, uncontrolled activation of complement, a component of the normal immune system, results in hemolysis (destruction of the patient’s red blood cells). PNH strikes people of all ages, with an average age of onset in the early 30s.1 Approximately 10 percent of all patients first develop symptoms at 21 years of age or younger.7 PNH develops without warning and can occur in men and women of all races, backgrounds and ages. PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.8 In the period of time before Soliris (eculizumab) was available, it had been estimated that approximately one-third of patients with PNH did not survive more than five years from the time of diagnosis.1 PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).9,10,11 In patients with thrombosis of unknown origin, PNH may be an underlying cause.1

About ALXN1210

ALXN1210 is a highly innovative, longer-acting C5 antibody being evaluated by Alexion for the treatment of patients with PNH. In early studies, ALXN1210 has demonstrated rapid, complete, and sustained reduction of free C5 activity and a terminal half-life of more than 30 days, which may facilitate a monthly or longer dosing interval.12 Alexion is conducting two clinical studies of ALXN1210 in patients with PNH—a Phase 1/2 dose-escalating study and an open-label, multi-dose Phase 2 study.

About Graft-Versus-Host Disease of the Lower GI tract (GI-GVHD)

GI-GVHD is an immune-mediated disease that affects 10 to 12 percent of patients who receive an allogeneic hematopoietic stem cell transplant.3,4 Patients with severe, acute GI-GVHD have a 30 to 40 percent mortality rate within the first six months post-transplant.13 There are no approved treatments for GI-GVHD.

About ALXN1007

ALXN1007 is a novel anti-inflammatory antibody targeting complement protein C5a being evaluated in a Phase 2 trial for patients with acute GI-GVHD.

About Soliris (eculizumab)

Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. Soliris is approved in the U.S. (2007), European Union (2007), Japan (2010) and other countries as the first and only treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. PNH is a debilitating, ultra-rare and life-threatening blood disorder, characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is also approved in the U.S. (2011), European Union (2011), Japan (2013) and other countries as the first and only treatment for patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, or TMA (blood clots in small vessels). aHUS is a debilitating, ultra-rare and life-threatening genetic disorder characterized by complement-mediated TMA. Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). For the breakthrough medical innovation in complement inhibition, Alexion and Soliris have received some of the pharmaceutical industry’s highest honors: the Prix Galien USA (2008, Best Biotechnology Product) and France (2009, Rare Disease Treatment).

More information, including the full U.S. prescribing information, on Soliris is available at www.soliris.net.

Important Safety Information

The U.S. product label for Soliris includes a boxed warning: "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 [see Warnings and Precautions (5.1)]. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with a meningococcal vaccine 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. [See Warnings and Precautions (5.1) for additional guidance on the management of the risk of 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 [see Warnings and Precautions (5.2)]. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747)."

In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis (runny nose), back pain and nausea. 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. 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. Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). Please see full prescribing information for Soliris, including BOXED WARNING regarding risk of serious meningococcal infection.

On June 10, 2016 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported that the United States District Court for the District of Delaware has ruled in favor of Teva in the Company’s patent infringement lawsuit against Hetero USA, Inc., InnoPharma Inc., Hospira Inc., Sagent Pharmaceuticals Inc., and Accord Healthcare Inc., regarding Teva’s TREANDA (bendamustine hydrochloride) for Injection (Filing, 6-K, Teva, JUN 10, 2016, View Source [SID:1234513199]).

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At trial, the defendants alleged that certain claims of U.S. Patents 8,436,190; 8,609,863; 8,791,270; and 8,895,756, listed in the Orange Book for TREANDA, are invalid. The defendants had previously stipulated to infringement of certain claims of these patents. Today the court issued a ruling affirming the validity of the relevant claims of all four patents. As a result, we expect that the court will enter an order enjoining the defendants from launching their respective generic versions of TREANDA until patent expiry in 2026.

"Teva is very pleased that the court has upheld the validity of its patents for the lyophilized formulation of TREANDA," said Rob Koremans, M.D., President and CEO of Teva Global Specialty Medicines. "This ruling is a testament to the strength of Teva’s intellectual property and commitment to defending our bendamustine franchise."

On June 10, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX) reported data presented during the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) being held in Copenhagen, Denmark (Press release, TG Therapeutics, JUN 10, 2016, View Source [SID:1234513197]). These presentations include long term follow-up data of TGR-1202, the Company’s once daily PI3K delta inhibitor, both alone and in combination with TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, as well as data presented for the first time from a Phase I/Ib study of TGR-1202 in combination with ibrutinib in patients with relapsed/refractory CLL or MCL.

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Michael S. Weiss, the Company’s Executive Chairman and Interim CEO commented on the data, "EHA is a great opportunity to showcase to the European hematology community the exciting data for TGR-1202 and for the combination of TGR-1202 plus TG-1101 that we recently presented at ASCO (Free ASCO Whitepaper). We were also excited to present for the first time, the safety and preliminary activity of the all oral combination of TGR-1202 and the BTK inhibitor, ibrutinib, by Dr. Matthew Davids and the team from Dana-Farber. We were pleased to report today that the data demonstrates that TGR-1202 at our Phase 3 dose of 800 mg plus full dose ibrutinib appears safe, well-tolerated and produced high response rates, especially in patients with advanced CLL, including one complete response, a depth of response not generally observed with either agent alone. We thank all the investigators involved and look forward to continued enrollment in the combination of TGR-1202 plus ibrutinib, as well as the ongoing triplet combinations with TGR-1202 and TG-1101 in combination with either ibrutinib, bendamustine or pembrolizumab."

The following summarizes the posters presented yesterday and today during the EHA (Free EHA Whitepaper) meeting:

E-Poster Title: Preliminary results of a Phase I/Ib study of ibrutinib in combination with TGR-1202 in patients with relapsed/refractory CLL or MCL

This poster includes data from patients with relapsed or refractory CLL or mantle cell lymphoma (MCL), all of whom were treated with TGR-1202 in combination with ibrutinib. A total of 27 patients were evaluable for safety, 17 patients with CLL and 10 with MCL, and 21 evaluable for efficacy, 11 patients with CLL and 10 with MCL (6 CLL patients were too early for assessment). CLL patients had a median of 2 prior lines of therapy (range 1-6), with 2 patients receiving prior ibrutinib and 2 receiving prior PI3K inhibitors. MCL patients had a median of 3 prior lines of therapy (range 2-5), with 2 patients also receiving prior ibrutinib.

Highlights from this poster include:

82% (9/11) ORR in patients with CLL, with 1 patient achieving a CR confirmed by a negative bone marrow and several other patients approaching a CR radiographically
60% (6/10) ORR in patients with MCL, with clinical benefit observed in two additional patients
The combination was well tolerated with no DLTs observed up to the highest dose tested (800 mg TGR-1202 + full dose ibrutinib) with the toxicity profile being comparable to the additive toxicity of the two agents given individually
In addition to the above E-Poster, the Company is also presenting integrated analysis data from 165 patients with relapsed or refractory hematologic malignancies, which has been previously presented during the ASCO (Free ASCO Whitepaper) conference earlier this week. The data has been separated into two posters evaluating patients with CLL and then patients with NHL.

Long-term follow-up of the next generation PI3K-delta inhibitor TGR-1202 demonstrates safety and high response rates in CLL: Integrated-analysis of TGR-1202 monotherapy and combined with ublituximab (Abstract P207)

Long-term follow-up of the next generation PI3Kδ inhibitor TGR-1202 demonstrates safety and high response rates in NHL: Integrated-analysis of TGR-1202 monotherapy and combined with ublituximab (Abstract P315)

Updated information from the presentations at ASCO (Free ASCO Whitepaper) earlier this week include:

Median Progression Free Survival (PFS) for TGR-1202 monotherapy was 24 months, while median PFS and DOR were not reached for TGR-1202 plus TG-1101 with median follow-up of 10.5 months, supporting our ongoing UNITY-CLL registration Phase 3 trial

Median DOR of 12.1 months observed in DLBCL patients treated with TGR-1202 plus TG-1101, providing a strong rationale for our UNITY-DLBCL registration program

Median DOR not reached in iNHL patients treated with TGR-1202 plus TG-1102 with a median follow-up of 15.8 months, further supporting our UNITY-iNHL registration directed trial, planned to launch by YE 2016
POSTER PRESENTATION DETAILS

A copy of the above mentioned poster presentations are available on the Company’s website at www.tgtherapeutics.com, located on the Publications Page, within the Pipeline section.