On June 16, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that positive results from the pivotal QuANTUM-R phase 3 study of single agent quizartinib were presented today as a late-breaking oral presentation in the plenary program at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden (Press release, Daiichi Sankyo, JUN 16, 2018, View Source [SID1234527368]).

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QuANTUM-R study results showed that patients with relapsed/refractory acute myeloid leukemia (AML) with FLT3-ITD mutations who received single agent quizartinib had a 24 percent reduction in the risk of death compared to patients who received salvage chemotherapy (hazard ratio [HR] = 0.76, P=0.0177, 95 percent CI 0.58-0.98). The median overall survival was 6.2 months (two-sided 95 percent CI 5.3-7.2) for patients treated with quizartinib and 4.7 months (two-sided 95 percent CI 4.0-5.5) for patients treated with salvage chemotherapy. The estimated survival probability at 1 year was 27 percent for patients who received quizartinib and 20 percent for patients who received salvage chemotherapy.

"FLT3-ITD mutated AML represents a high unmet need entity as patients with this aggressive form of the disease have an overall dismal prognosis as evidenced by low response rates to current available therapies, high risk of relapse and a shorter overall survival than those without this mutation," said Jorge E. Cortes, MD, Deputy Chair of the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. "In relapsed/refractory AML with FLT3-ITD mutations, these findings represent the first reported clinical data demonstrating that a single agent can significantly improve overall survival, suggesting that quizartinib could potentially help these patients live longer. Additionally, in the study, a higher proportion of patients received a stem cell transplant in the quizartinib arm compared to the chemotherapy arm."

Secondary and key exploratory analyses including composite complete remission (CRc) are consistent and supportive of the primary analysis.

"Results of this study are consistent with previous phase 2 studies of quizartinib and demonstrate the value of targeting the FLT3-ITD driver mutation. We are encouraged by these data, which will form the basis of regulatory submissions to health authorities. If approved, quizartinib has the potential to redefine the treatment of patients with relapsed/refractory AML with FLT3-ITD mutations," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "These results also build on our understanding of this difficult-to-treat type of AML as we continue to explore the potential role of quizartinib in combination with chemotherapy and other novel mechanisms to further advance the treatment of patients with relapsed/refractory and newly-diagnosed AML with FLT3-ITD mutations."

The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program. The median treatment duration with quizartinib was 4 cycles of 28 days (97 days; range: 1-1,182 days) versus 1 cycle (range: 1-2) in the salvage chemotherapy arm. The median relative dose intensity for quizartinib was 89 percent. Incidence of treatment-emergent adverse events were comparable between patients who received single agent quizartinib (n=241) and those who received salvage chemotherapy (n=94). The most common adverse events (>30 percent, any Grade) in patients treated with quizartinib versus chemotherapy, respectively, included nausea (48 vs 42 percent), thrombocytopenia (39 vs 34 percent), fatigue (39 vs 29 percent), musculoskeletal pain (37 vs 28 percent), pyrexia (38 vs 45 percent), anemia (37 vs 32 percent), neutropenia (34 vs 26 percent), febrile neutropenia (34 vs 28 percent), vomiting (33 vs 21 percent) and hypokalemia (32 vs 28 percent). The most common adverse events Grade ≥3 (>10 percent of patients) were thrombocytopenia (35 vs 34 percent), anemia (30 vs 29 percent), neutropenia (32 vs 25 percent), febrile neutropenia (31 vs 21 percent), leukopenia (17 vs 16 percent), sepsis/septic shock (16 vs 18 percent), hypokalemia (12 vs 9 percent) and pneumonia (12 vs 9 percent). QTcF >500 msec occurred in 8 patients (3.3 percent) and 2 out of 241 patients discontinued quizartinib due to QTcF prolongation. There were no reported events of Grade 4 QTcF prolongation (Torsade de Pointe, sudden death or cardiac arrest) in the quizartinib arm.

About the QuANTUM-R Study

QuANTUM-R is a pivotal, global, phase 3, open-label randomized study that enrolled 367 patients with FLT3-ITD-mutated AML who were refractory to or in relapse following (with duration of remission of six months or less) standard first-line AML therapy with or without hematopoietic stem cell transplantation (HSCT). Patients were randomized in a 2:1 ratio to receive either single agent oral quizartinib (60 mg, with 30 mg lead-in) or salvage chemotherapy. The primary objective of the study was to determine whether single agent quizartinib prolonged overall survival compared to salvage chemotherapy.

About Quizartinib

Quizartinib, the lead investigational agent in the AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective FLT3 inhibitor currently in global phase 3 development for relapsed/refractory (QuANTUM-R) and newly-diagnosed (QuANTUM-First) AML with FLT3-ITD mutations, and phase 2 development for relapsed/refractory AML with FLT3-ITD mutations in Japan.

Quizartinib has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory AML. Quizartinib also has been granted Orphan Drug designation by the FDA and European Medicines Agency (EMA) for the treatment of AML. Quizartinib is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Acute Myeloid Leukemia with FLT3-ITD Mutations

AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells.1 The five-year survival rate of AML reported from 2005 to 2011 was approximately 26 percent, which was the lowest of all leukemias.1

FLT3 gene mutations are one of the most common genetic abnormalities in AML.2 The FLT3-ITD mutation is the most common FLT3 mutation, affecting approximately one in four patients with AML.3,4,5,6 Patients with FLT3-ITD-mutated AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapseand a higher likelihood of relapse following HSCT as compared to those without this mutation.7,8

On June 15, 2018 Novartis reported results from a new comparison study showing that Jakavi(ruxolitinib)-treated patients with polycythemia vera (PV), who were resistant or intolerant to hydroxyurea (HU), had a significantly reduced risk of thrombosis (blood clots) and death compared to PV patients who received best available therapy[1] (Press release, Novartis, JUN 15, 2018, View Source [SID1234527352]). The study findings are based on a comparison of patients in the Phase III RESPONSE Jakavi clinical trial and the real-world Spanish GEMFIN patient registry. PV is a rare and incurable blood cancer associated with an overproduction of blood cells that can cause serious cardiovascular complications, such as blood clots, stroke and heart attack[4].

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The new findings were presented at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden.

"When you can complement clinical trial data with real-world experiences, it can provide valuable insight into how treatments affect patients in their day-to-day lives," said lead study investigator, Alberto Alvarez-Larran, MD, Hematology Department, Hospital Clinic, Barcelona, Spain. "This latest research supports the use of Jakavi to help people with polycythemia vera gain better control of their disease when hydroxyurea is not an option."

Additional Jakavi data presented at the EHA (Free EHA Whitepaper) Annual Congress includes efficacy and safety analyses of the largest expanded access trial of myelofibrosis (MF) patients treated with Jakavi to date (JUMP). An efficacy analysis showed that patients with lower-risk MF achieved spleen size reductions when treated with Jakavi, with most patients (82.1%) achieving a >=50% reduction at any time[2],[3]. A separate analysis identified factors that may lead to a greater spleen response in patients with MF treated with Jakavi, including treating earlier in the course of the disease and at a higher dose (>=10 mg BID)[5].

"With limited treatment options, patients with myeloproliferative neoplasms (MPNs) often struggle to keep their disease under control," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "The research conducted by Novartis teams and our physician partners in both PV and MF is helping to clarify how Jakavi can help relieve disease burden for patients."

Additionally, 48-week data from the EXPAND study support Jakavi 10 mg BID as a starting dose in patients with MF with low platelet counts, providing important information in a patient population at an increased risk of bleeding and serious complications[5]. Nearly one-third of patients in the study treated with Jakavi achieved a >=50% reduction in spleen size at week 48 (31.8% of patients [7/22] with a platelet count of 75 to 99 x 109/L and 35.7% [5/14] of patients with a platelet count of 50 to 74 x 109/L)[5].

About the PV Real-World Comparison Study
The new data presented at EHA (Free EHA Whitepaper) compares overall survival and thrombosis (blood clots) rates using data from patients treated in the Jakavi arm of the RESPONSE trial and patients treated in a real-world setting with best available therapy (BAT) from the Grupo Español de Enfermedades Mieloproliferativas Crónicas Filadelfia Negativas (GEMFIN) registry[1].

In the previously reported Phase III RESPONSE trial, the high rate of crossover from BAT to Jakavi precluded the comparison of overall survival and thrombosis rates. RESPONSE was a global, open-label study that included patients with PV resistant to or intolerant of hydroxyurea, who were randomized 1:1 to receive either Jakavi (starting dose of 10 mg twice daily) or BAT, which was defined as investigator-selected monotherapy or observation only. The GEMFIN registry patients in the real-world BAT group had resistance or intolerance to hydroxyurea according to the modified European Leukemia Net criteria and received hydroxyurea (44%), busulfan (10%), radioactive phosphorus (2%), interferon (6%), anagrelide (12%), other therapy (11%) or no cytoreductive therapy (26%). Some patients were also treated with multiple therapies[1].

In the GEMFIN study, patients treated with Jakavi had a significantly prolonged overall survival (HR=0.28 [0.11-0.72]) and a lower risk of blood clots (HR=0.21 [0.06-0.76]) when compared to real-world patients treated with BAT[1].

About the JUMP Study
JUMP is an expanded access Phase IIIb study designed to further evaluate the safety and efficacy of Jakavi in MF. It includes the largest cohort of patients with MF treated with Jakavi, 2,233, to date. The study provided access to Jakavi for patients who had no access to the treatment outside of a clinical trial and included 60 patients who were determined to have DIPSS low-risk disease[2],[3].

About the EXPAND Study
EXPAND is an open-label, Phase Ib, dose-finding study in patients with MF with baseline platelet counts of 50 to 99 x 109/L. Results presented at EHA (Free EHA Whitepaper) are from the 48-week follow- period[5].

The study evaluated 10 mg BID as a safe starting dose of Jakavi. The key secondary endpoints are safety and efficacy, including proportion of patients achieving >=50% of reduction in spleen size. Safety findings were also consistent with previous studies of Jakavi[5].

About Myelofibrosis and Polycythemia Vera
Myelofibrosis (MF) and polycythemia vera (PV) are part of a group of related and rare blood cancers called myeloproliferative neoplasms (MPNs) in which bone marrow cells responsible for the body’s blood cells develop and function abnormally[4],[6].

In patients with MF, the bone marrow can no longer produce enough normal blood cells, causing the spleen to enlarge. MF affects approximately one in every 100,000 people[6].

PV is associated with an overproduction of blood cells that can cause serious cardiovascular complications if left inadequately controlled, such as blood clots, stroke and heart attack. PV affects up to three per 100,000 people globally each year[4].

About Jakavi
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Jakavi is approved in 101 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 75 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Jakavi is marketed in the United States by Incyte Corporation as Jakafi for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea and for the treatment of patients with intermediate or high-risk MF.

The recommended starting dose of Jakavi in PV is 10 mg given orally twice daily. The recommended starting dose of Jakavi in MF is 15 mg given orally twice daily for patients with a platelet count between 100,000 cubic millimeters (mm[3]) and 200,000 mm[3], and 20 mg twice daily for patients with a platelet count of >200,000 mm[3]. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for MF and PV patients with platelet counts between 50,000/mm[3] and <100,000/mm[3]. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously[7].

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation. The safety and efficacy profile of Jakavi has not yet been established outside the approved indications.

Jakavi Important Safety Information for Treatment of Myelofibrosis (MF) and Polycythemia Vera (PV)
Jakavi can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with any hepatic impairment or severe renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended, and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed. Progressive multifocal leukoencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. Hepatitis B viral load (HBV-DNA titer) increases have been reported in patients with chronic HBV infections. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines. Non-melanoma skin cancer (NMSC) has been reported in Jakavi treated patients. Periodic skin examination is recommended. Very common adverse reactions in MF (>10%) include urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, alanine aminotransferase increased, aspartate aminotransferase increased, bruising and weight gain. Common adverse reactions in MF (1 to 10%) include herpes zoster and flatulence. Uncommon adverse reactions in MF include tuberculosis. Very common adverse reactions in PV (>10%) include anemia, thrombocytopenia, hypercholesterolemia, hypertriglyceridemia, dizziness, alanine aminotransferase increased and aspartate aminotransferase increased. Common adverse reactions in PV (1 to 10%) include urinary tract infections, herpes zoster, weight gain, constipation and hypertension.

Please see full Prescribing Information available at www.jakavi.com.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

On June 15, 2018 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported positive long-term outcomes including durable remissions and encouraging safety findings from two Phase 2 studies of tab-cel (tabelecleucel), Atara’s most advanced off-the-shelf T-cell immunotherapy (Press release, Atara Biotherapeutics, JUN 15, 2018, View Source [SID1234527345]). These single center, open-label studies enrolled patients with Epstein-Barr virus associated post-transplant lymphoproliferative disorder (EBV+ PTLD) following allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT) who failed first-line therapy. Atara and its collaborating investigators at Memorial Sloan Kettering Cancer Center (MSK) reported the Phase 2 results in a poster presentation at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), being held in Stockholm, Sweden, June 14-17, 2018.

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"Tab-cel demonstrated durable remissions and an encouraging safety profile after substantial follow-up time for patients with EBV-associated lymphomas who have limited treatment options and often experience poor outcomes," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "No patient who responded to tab‑cel in these studies died of EBV+ PTLD after treatment with this off-the-shelf, allogeneic T-cell immunotherapy. We are progressing two tab-cel Phase 3 clinical studies to confirm the Phase 2 findings in patients with EBV+ PTLD following HCT and SOT who have failed first line therapy."

Overall Survival (OS)

One- and three-year OS for tab-cel treated patients with EBV+ PTLD following HCT who failed rituximab (n=35) was 68% and 55%, respectively. Median OS was not reached after 23.3 months of follow-up in this patient group. The expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16 to 56 days.1,2
In patients with EBV+ PTLD following SOT who failed rituximab, the one- and three-year OS after treatment with tab-cel (n=14) was 64% and 43%, respectively. Median survival in this patient group was 21.3 months, which compares favorably to the expected 12- to 13-month median survival in patients with EBV+ PTLD following SOT who fail to achieve a complete response to first-line therapy with single-agent rituximab.3
None of the EBV+ PTLD patients who had complete or partial responses (CR or PR) after treatment with tab-cel died of EBV+ PTLD. Two-year OS for these responding patients was 83% and 86% following HCT (n=24) and SOT (n=7), respectively.
Overall response rates (ORR)

Tab-cel was associated with durable ORR (CR plus PR) of 69% and 50% in patients with EBV+ PTLD following HCT and SOT, respectively, who have failed rituximab.
Safety

Tab-cel was generally well-tolerated. Safety findings were consistent with previous reports of these studies with no new signals noted with additional follow up.
Atara anticipates results from the first tab-cel Phase 3 study and submission of an EU conditional marketing authorization application in the first half of 2019.

Details for the poster presentation at the EHA (Free EHA Whitepaper) Congress are as follows:

Abstract PF401: Long Term Outcomes of Tabelecleucel (Allogeneic Third-Party EBV-Targeted Cytotoxic T Lymphocytes) for Rituximab-Refractory Post-Transplant EBV+ Lymphomas: A Single Center Experience
Session Title: Gene therapy, cellular immunotherapy and vaccination – Clinical
Presentation Date & Time: Friday, June 15; 5:30 p.m. to 7:00 p.m. CEST
Authors:Susan Prockop, Ekaterina Doubrovina, Amy Feng, Guenther Koehne, Parastoo Dahi, Esperanza Papadopoulos, Craig Sauter, Stephanie Suser, Willis Navarro, Akshay Sudhindra, Richard O’Reilly
Location: Poster area, Älvsjö building, Stockholm International Fairs and Congress Centre (Stockholmsmässan)

About EBV+ PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas, and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) represents a life-threatening condition. Median overall survival in patients with EBV+ PTLD following HCT who have failed rituximab-based first line therapy is 16-56 days. In EBV+ PTLD following SOT, patients failing rituximab experience increased chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+ PTLD following SOT is 36% and 0%, respectively.

About tab-cel (tabelecleucel; formerly known as ATA129)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. Atara also received positive regulatory feedback from Health Canada in September 2017 supporting the submission of tab-cel for an expedited approval pathway. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara is planning a Phase 1/2 study in NPC. Tab-cel is also available to eligible patients with EBV-associated hematologic and solid tumors through an ongoing multicenter expanded access protocol clinical study, positive interim results of which were presented in December 2017 at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

On June 15, 2018 Molecular Partners AG (SIX: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported that the company will present updated preliminary results from the ongoing Phase 2 study of its lead proprietary oncology drug MP0250 at the 23th Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm (Press release, Molecular Partners, JUN 15, 2018, View Source [SID1234527337]).

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The ongoing, open label Phase 2 clinical study[1] is examining the safety and efficacy of MP0250 in combination with bortezomib (Velcade) and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) who have failed at least two lines of standard therapies, including bortezomib and an IMiD. The study is being performed at nine centers in Germany, Poland and Italy.

In the first of two cohorts, patients received MP0250 at 8mg/kg every 3 weeks (corresponding to 66% of the recommended dose) in combination with standard doses of bortezomib and dexamethasone.

All patients had been pretreated with at least two lines of therapy, including an IMiD and bortezomib. 50% of those patients were considered proteasome refractory. At the data cutoff on May 21, 2018, five of eight evaluable patients achieved an objective response (4 patients with PR/partial response; 1 patient with VGPR/very good partial response). Responses were durable, with median time on treatment for responding patients of 22.5 weeks and the longest response still ongoing at 41 weeks.

Main adverse events were consistent with the known side effect profile of VEGF-targeting agents and of Velcade, respectively: thrombocytopenia (4 out of 8 patients), hypertension (3 out of 8 patients) and upper respiratory infection (3 out of 8 patients).

"We are very encouraged by the initial activity and the safety profile of MP0250 in combination with bortezomib and dexamethasone, even at the low dose of MP0250. We have started the treatment of the first two patients with the higher dose of 12 mg/kg which may be even more effective," said Andreas Harstrick, Chief Medical Officer of Molecular Partners.

Patrick Amstutz, CEO of Molecular Partners added: "These results further substantiate our development plans in multiple myeloma as well as the launch of our additional phase 1b/2 study of MP0250 in combination with osimertinib in EGFR-mutated NSCLC."

The ongoing Phase study of MP0250 in multiple myeloma is currently recruiting patients at the higher dose of 12mg/kg q3weeks. Overall, a total of at least 40 patients are planned to be treated. Additional safety and efficacy data are expected by the end of 2018.

An additional phase 1b/2 study will evaluate MP0250 in combination with osimertinib in patients with EGFR-mutated NSCLC pretreated with osimertinib (Tagrisso). The study is conducted in the US and is open for patient enrollment[2].

Full details on the Molecular Partners’ poster presentation today, from 5.30 to 7.00pm CET, at EHA (Free EHA Whitepaper) Stockholm can be found on the conference website. Following its presentation at EHA (Free EHA Whitepaper), the poster will also be available one the Molecular Partners website.

[1] ClinicalTrials.gov identifier NCT03136653

[2] ClinicalTrials.gov identifier NCT03418532

*DARPin is a registered trademark owned by Molecular Partners AG.

Financial Calendar
August 30, 2018 – Publication of 2018 Half-year Results
November 01, 2018 – Q3 2018 Management Statement
View Source

About MP0250
MP0250 is a multi-DARPin candidate targeting simultaneously VEGF and HGF, two prominent escape pathways, and has the potential to reverse resistance that has built to standard of care cancer therapies. Increases in VEGF and HGF are associated with disease progression in multiple myeloma and have been linked to poor prognosis. They are known to be able to stimulate neovascularization, bone destruction, and myeloma proliferation, migration, and adhesion in the bone marrow.

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.
With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in Phase 3, in partnership with Allergan.
Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in Phase 1 clinical development for the treatment of solid tumors and in Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has moved into Phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.

On June 15, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment; TecDAX; Nasdaq: MOR) reported the presentation of clinical data from the exploratory phase 2 COSMOS trial (Press release, MorphoSys, JUN 15, 2018, View Source [SID1234527338]). The trial evaluates MorphoSys’s proprietary hemato-oncological drug candidate MOR208 in combination with the cancer drug idelalisib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), who progressed on or were intolerant to ibrutinib therapy. Data will be presented in a poster presentation on June 15, 2018, at the 23rd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Stockholm/Sweden. MOR208 is an investigational Fc-enhanced humanized monoclonal antibody directed against CD19 in clinical development for the treatment of B cell malignancies.

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"Patients with CLL after failure of ibrutinib therapy are in need of more therapeutic options. We are encouraged by the initial and, for the most part, still ongoing responses observed in this heavily pretreated patient population in our exploratory trial with MOR208 plus idelalisib," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "Overall, this shows the potential medical application of MOR208 in additional B cell malignancies. The data shows that MOR208 may be combined with other cancer drugs used in hematological malignancies, including PI3K inhibitors. We look forward to the upcoming results from the second cohort of MOR208 plus venetoclax of our ongoing COSMOS study which we expect later this year."

COSMOS is a phase 2, two-cohort, open-label, multicenter study evaluating the preliminary safety and efficacy of MOR208 combined with idelalisib (cohort A) or venetoclax (cohort B) in patients with r/r CLL/SLL previously treated with Bruton’s Tyrosine Kinase inhibitor (BTKi) ibrutinib.

Data presented at EHA (Free EHA Whitepaper) 2018 comprise preliminary safety and efficacy data on all 11 patients enrolled into cohort A (cut-off date: January 29, 2018). Patients enrolled had received a median of five prior treatment lines (range: 2-9 prior lines). Nine out of the eleven patients enrolled (82%) had discontinued prior ibrutinib treatment due to progressive disease and two patients (18%) due to toxicity.

The most common treatment-emerging adverse events (TEAEs) of grade 3 or higher were hematologic, with neutropenia observed for four patients (36%) and anemia for three patients (27%) being the most common reported events. Ten treatment-emergent serious adverse events (SAEs) were reported in five patients (45%) none of them being fatal. All except one of the six treatment-related SAEs reported for three patients (27%) were suspected to idelalisib.

According to the preliminary efficacy analysis conducted by the investigators, overall response rate (ORR) was 82%, including one complete response (CR, 9%) confirmed by bone marrow biopsy and eight partial responses (PR, 73%). In addition, two patients (18%) showed stable disease. The median observation time was 4.2 months. At the time of data-cut off, six patients continued treatment. One patient with a very good partial response according to response criteria was taken off the study to receive stem cell transplantation. Two previously responding patients had to discontinue the study due to progressive disease. Two patients (one PR, one stable disease SD) discontinued due to adverse events.

Details about the poster presentation on MOR208 at EHA (Free EHA Whitepaper) 2018:

Abstract Code: PF350

Two-cohort, phase II study in R/R CLL (COSMOS): First preliminary safety and efficacy results of MOR208 treatment in combination with idelalisib in patients who discontinued prior ibrutinib therapy

The poster will be presented during the session "Chronic lymphocytic leukemia and related disorders – Clinical" on Friday, June 15, 2018 5:30-7:00 pm CEST (11:30am-1:00pm EDT), in the poster area at the Stockholmsmässan in Stockholm.

In addition, the corresponding abstract will be on display on the E-poster screens at the conference from Friday, June 15, 2018, 9:30 am CEST (3:30 am EDT) to Sunday, June 17, 2018, 1:00 pm CEST (7:00 am EDT).

Additional information can be found at www.ehaweb.org, including the abstract.

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 humanized Fc-engineered monoclonal antibody directed against CD19. 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. 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 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) is investigating the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the FDA granted Breakthrough Therapy Designation for MOR208 plus lenalidomide in this patient population. The pivotal phase 2/3 B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. In addition, MOR208 is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.