BLINCYTO® (blinatumomab) Significantly Improved Overall Survival In Patients With B-Cell Precursor Acute Lymphoblastic Leukemia Compared To Chemotherapy

On March 1, 2017 Amgen (NASDAQ:AMGN) reported the New England Journal of Medicine published results from the Phase 3 TOWER study evaluating the efficacy of BLINCYTO (blinatumomab) versus standard of care (SOC) chemotherapy in high-risk adult patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), one of the most aggressive B-cell malignancies (Press release, Amgen, MAR 1, 2017, View Source [SID1234517917]). Results from the analysis showed that median overall survival (OS) was 7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO versus four months (95 percent CI: 2.9, 5.3) for SOC (hazard ratio [HR] for death=0.71; p=0.012).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The TOWER study is the confirmatory study for the Phase 2 trial that supported the U.S. Food and Drug Administration’s (FDA) accelerated approval designation for BLINCYTO in 2014.

BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct. It is the first bispecific antibody construct from Amgen’s BiTE platform, which helps the body’s immune system target cancer cells and represents an entirely new area of oncology research. BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.

"Historically, patients with relapsed or refractory ALL have a poor prognosis, with an overall survival of just four months on standard of care chemotherapy," said Max S. Topp, M.D., professor and head of Hematology, University Hospital of Wuerzburg, Germany. "Findings from this head-to-head study showed that BLINCYTO almost doubled the median overall survival from four to 7.7 months, offering these high-risk patients a much needed alternative to chemotherapy that is both innovative and effective."

The survival benefit for BLINCYTO was independent of allogeneic stem cell transplant (alloSCT), as the median OS, censored at the time of alloSCT, was 6.9 months for BLINCYTO versus 3.9 months for SOC. Improvement in OS was generally consistent regardless of age, prior salvage therapy or prior alloSCT. The magnitude of this benefit appeared greatest in earlier lines of salvage. Neutropenia and infection greater than or equal to Grade 3 appeared less frequently with BLINCYTO compared to SOC, while neurological events appeared at a similar rate between arms.

"Adults with Ph- relapsed or refractory B-cell precursor ALL are in critical need of new treatment options," said Hagop M. Kantarjian, M.D., professor and chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston. "Results from the TOWER study reinforce the potential of this single agent bispecific T cell engager immunotherapy, which helped a higher percentage of patients achieve minimal residual disease response versus standard of care chemotherapy, highlighting the depth and quality of remissions achieved."

Evaluation of key secondary endpoints showed that remission rates were also higher for BLINCYTO versus SOC. In the BLINCYTO group, 34 percent of patients achieved complete remission versus 16 percent in the SOC group. Patients receiving BLINCYTO also had a higher rate of combined complete remission or complete remission with partial or incomplete hematologic recovery (44 percent versus 25 percent).

Among patients with complete remission or complete remission with partial or incomplete hematologic recovery, 76 percent in the BLINCYTO group versus 48 percent in the SOC group achieved minimal residual disease (MRD) negative status, a measure of eradication of residual disease at the molecular level. Also among these patients, the median duration of remission was 7.3 months in the BLINCYTO group versus 4.6 months in the SOC group. For the key secondary efficacy endpoint of event-free survival, six month estimates in the BLINCYTO and chemotherapy groups were 30.7 percent and 12.5 percent, and the HR was 0.55 (95 percent CI: 0.43, 0.71), favoring BLINCYTO.

"As the first study of an immunotherapy to demonstrate overall survival benefit in adult patients with Ph- relapsed or refractory B-cell precursor ALL, TOWER represents an important advance in the understanding of this aggressive, ultra-orphan disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "As demonstrated by the data published today in the New England Journal of Medicine, BLINCYTO has proven to improve overall survival, extend remission rates and reduce minimal residual disease in these high-risk patients who previously have had limited effective options."

Safety results among subjects who received BLINCYTO were comparable to those seen in the Phase 2 studies in adult patients with Ph- relapsed or refractory B-cell precursor ALL. For the most common adverse events (greater than or equal to 10 percent incidence rate) in the BLINCYTO arm, only three events (cough, pyrexia, cytokine release syndrome) occurred at an incidence rate that was at least 5 percent higher for BLINCYTO compared to SOC chemotherapy.

ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 Adult patients diagnosed with Ph- B-cell precursor ALL are often young, with a median age at diagnosis of 34-39.3,4 Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy.5 Adults with relapsed or refractory ALL typically have a very poor prognosis, with a median OS of three to five months.6

About the TOWER Study
The TOWER study was a Phase 3, randomized, open-label study investigating the efficacy of BLINCYTO versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL. Patients were randomized in a 2:1 ratio to receive BLINCYTO (n=271) or treatment with investigator choice of one of four protocol-defined SOC chemotherapy regimens (n=134). The primary endpoint was OS. Key secondary endpoints included complete remission within 12 weeks, the combined endpoint of complete remission plus complete remission with partial or incomplete hematologic recovery and event-free survival. Other secondary endpoints included remission duration, MRD remission (<10–4), alloSCT rate and adverse event rates.

The TOWER study is the confirmatory trial for BLINCYTO. Click here to read about the trial on ClinicalTrials.gov.

About Adult ALL
In the United States (U.S.), the incidence of adult ALL is approximately 0.9 per 100,000 persons per year.7 The incidence of adult ALL in European countries is generally between 0.6 to 0.9 per 100,000 persons per year.7 In adult ALL, approximately 75 percent is B-cell precursor ALL, of which 75-80 percent is Ph- and roughly half will be refractory to treatment or experience relapse.7 In the U.S., the incidence of adult Ph- relapsed or refractory B-cell precursor ALL was approximately 650 patients in 2015 and in the European Union (EU), the estimated incidence is approximately 1,200 patients per year.7,8

About BLINCYTO (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BLINCYTO was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

In November 2015, BLINCYTO was granted conditional marketing authorization in the EU for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.

About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

BLINCYTO U.S. Product Safety Information

Important Safety Information Regarding BLINCYTO (blinatumomab) U.S. Indication

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications
BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO as outlined in the Prescribing Information (PI).
Neurological Toxicities: Approximately 64% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to onset of any neurological toxicity was 4 days. The most common (≥ 10%) manifestations of neurological toxicity were headache, tremor, dizziness, and altered state of consciousness. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 17% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The neurological toxicity profile varied by age group. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.
Tumor Lysis Syndrome (TLS): TLS, which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Adverse Reactions

The most common adverse reactions (≥ 20%) in the safety population studied in clinical trials were pyrexia (66%), headache (34%), nausea (27%), edema (26%), hypokalemia (26%), anemia (25%), febrile neutropenia (24%), neutropenia (22%), thrombocytopenia (20%), and abdominal pain (20%). The safety population included 225 patients weighing 45 kg or more and 57 patients weighing less than 45 kg. For some adverse reactions, there were differences in the incidence rates by age subgroup.
In patients weighing greater than or equal to 45 kg, serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia (9%), pyrexia (6%), sepsis (5%), pneumonia (5%), device-related infection (4%), neutropenia (3%), tremor (3%), overdose (3%), encephalopathy (3%), infection (2%), confusion (3%) and headache (2%).
In patients weighing less than 45 kg, serious adverse reactions were reported in 51% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia (12%), febrile neutropenia (9%), cytokine release syndrome (4%), convulsion (4%), device-related infection (4%), hypoxia (4%), sepsis (4%), and overdose (4%).
U.S. Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO at www.BLINCYTO.com.

Important EU Product Safety Information

This product is subject to additional monitoring in the EU and EEA. All suspected adverse reactions should be reported in accordance with the national reporting system.

The adverse reactions described in this section were identified in the pivotal clinical study (N=189).The most serious adverse reactions that may occur during blinatumomab treatment include: infections (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%) cytokine release syndrome (0.5%), and tumor lysis syndrome (0.5%). The most common adverse reactions were: infusion-related reactions (67.2%), infections (63.0%), pyrexia (59.8%), headache (34.4%), febrile neutropenia (28%), peripheral edema (25.9%), nausea (24.3%), hypokalaemia (23.8%), constipation (20.6%), anaemia (20.1%), cough (18.5%), diarrhea (18.0%), tremor (17.5%), neutropenia (17.5%), abdominal pain (16.9%), insomnia (15.3%), fatigue (15.3%), and chills (15.3%).

Please refer to the Summary of Product Characteristics for full European prescribing information.

Merrimack Reports Fourth Quarter and Full-Year 2016 Financial Results

On March 1, 2017 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) reported its fourth quarter and full year 2016 financial results for the period ended December 31, 2016 (Press release, Merrimack, MAR 1, 2017, View Source [SID1234517915]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Key Recent Events

As announced on January 8, 2017, Merrimack entered into an asset purchase and sale agreement with Ipsen S.A. under which Merrimack will sell ONIVYDE and its generic version of doxorubicin hydrochloride (HCI) liposome injection to Ipsen for up to $1.025 billion, plus up to $33.0 million in net milestone payments retained by Merrimack pursuant to Merrimack’s license and collaboration agreement with Shire. A special meeting of Merrimack’s stockholders is scheduled for March 30, 2017 to consider and vote on the asset sale. Merrimack anticipates completing the asset sale shortly after approval of the asset sale at the special meeting.
Merrimack also announced on January 8, 2017 the conclusion of a comprehensive pipeline review by its Board of Directors, which resulted in the identification of the three most promising clinical programs to focus its development efforts on going forward: MM-121, MM-141 and MM-310.
Merrimack appointed Dr. Richard Peters as President and Chief Executive Officer, effective February 6, 2017. Dr. Peters succeeded Gary Crocker, Chairman of the Board, who was serving as Interim President and Chief Executive Officer prior to Dr. Peters’ appointment.
"This is an exciting and important time for Merrimack as we are refocusing into an earlier-stage, R&D-focused biopharmaceutical company," said Dr. Peters. "The transaction with Ipsen, once completed, will allow for the immediate return of cash to stockholders, while also providing Merrimack with an infusion of capital that we believe will fund our streamlined oncology pipeline into the second half of 2019. We are confident that our clinical stage assets have the potential to benefit cancer patients around the world and drive Merrimack’s long-term success and stockholder value creation."

Fourth Quarter and Full Year 2016 Financial Results

The following summarizes Merrimack’s financial results from the year ended December 31, 2016:

Aggregate research and development and selling, general and administrative expenses for the year ended December 31, 2016, when calculated in accordance with GAAP, were $241.6 million. This amount includes $35.5 million of milestone payments made to PharmaEngine. This corresponds to aggregate research and development and selling, general and administrative expenses, excluding milestone payments to PharmaEngine, a non-GAAP financial measure, of $206.1 million for the year ended December 31, 2016. As a result of Merrimack’s various cost control measures, these amounts are within the lowered GAAP and non-GAAP guidance ranges previously provided by Merrimack;
Product revenues from the commercial sale of ONIVYDE, net of discounts, allowances and reserves, were $53.1 million for the year ended December 31, 2016, compared to $4.3 million for the year ended December 31, 2015;
License and collaboration revenues were $87.1 million for the year ended December 31, 2016, compared to $85.0 million for the year ended December 31, 2015. This amount includes $40.0 million of substantive milestones achieved during the year ended December 31, 2016 under Merrimack’s license and collaboration agreement with Shire, compared to $20.0 million of substantive milestones achieved under this collaboration during the year ended December 31, 2015;
Restructuring expenses were $5.9 million for the year ended December 31, 2016 and were related to the previously-announced 22% reduction in headcount that occurred in October 2016 as part of a major corporate restructuring with the objective of prioritizing Merrimack’s research and development on a focused set of systems biology-derived oncology products and strengthening its financing runway;
Interest expense was $43.6 million for the year ended December 31, 2016, compared to $19.2 million for the year ended December 31, 2015. This $24.4 million increase was primarily due to a $14.6 million one-time, non-cash loss related to the conversion of an aggregate principal amount of $64.2 million of Merrimack’s convertible notes in April 2016 as well as interest incurred on its senior secured notes that were issued in December 2015; and
Net loss attributable to Merrimack for the year ended December 31, 2016 was $151.7 million, or $1.21 per share, compared to a net loss attributable to Merrimack of $148.0 million, or $1.33 per share, for the year ended December 31, 2015.
The following summarizes Merrimack’s financial results from the quarter ended December 31, 2016:

Product revenues from the commercial sale of ONIVYDE, net of discounts, allowances and reserves, were $15.8 million for the quarter ended December 31, 2016, compared to $14.5 million for the quarter ended September 30, 2016. This represents an increase of $1.3 million, or 9%, over the prior quarter;
License and collaboration revenues were $44.1 million for the quarter ended December 31, 2016, compared to $12.4 million for the quarter ended September 30, 2016. This $31.7 million increase is primarily due to the achievement of $30.0 million of substantive milestones during the fourth quarter under Merrimack’s license and collaboration agreement with Shire;
Aggregate research and development and selling, general and administrative expenses for the quarter ended December 31, 2016, when calculated in accordance with GAAP, were $79.2 million compared to $50.1 million for the quarter ended September 30, 2016. This represents an increase of $29.1 million, or 58%. The majority of this increase was related to $25.5 million of milestone payments owed to PharmaEngine in the fourth quarter of 2016;
Restructuring expenses were $5.0 million for the quarter ended December 31, 2016; and
Net loss attributable to Merrimack for the quarter ended December 31, 2016 was $32.4 million, or $0.25 per share, compared to a net loss attributable to Merrimack of $30.1 million, or $0.23 per share, for the quarter ended September 30, 2016.
A table reconciling aggregate research and development and selling, general and administrative expenses, excluding milestone payments to PharmaEngine, a non-GAAP financial measure, to aggregate research and development and selling, general and administrative expenses calculated in accordance with GAAP is included at the end of this press release.

2017 Financial Outlook

Upon the closing of the asset sale, Merrimack will receive a $575.0 million upfront cash payment from Ipsen (subject to a working capital adjustment as provided in the asset purchase and sale agreement). Merrimack expects to use these proceeds to declare and pay a special cash dividend of at least $200.0 million to stockholders and use an additional $195.1 million to redeem its senior secured notes. Additionally, if the asset sale is consummated and certain milestones are met with Shire, Merrimack expects to receive up to an aggregate of $33.0 million in net milestone payments in 2017. Merrimack believes that these potential cash inflows, along with the completion of the headcount reduction and refocused research and development efforts that were announced in January 2017, will provide financial resources sufficient to fund its operations into the second half of 2019.

GLYCOMIMETICS REPORTS FOURTH QUARTER AND YEAR-END 2016 RESULTS

On March 1, 2017 GlycoMimetics, Inc. (NASDAQ: GLYC) reported progress on its clinical development programs and its financial results for the fourth quarter and year ended December 31, 2016 (Filing, Q4/Annual, GlycoMimetics, 2016, MAR 1, 2017, View Source [SID1234517911]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In 2016, GlycoMimetics made significant progress across its clinical pipeline, perhaps most significantly in the maturing data from our study of GMI-1271, an E-selectin antagonist, in acute myeloid leukemia (AML). Starting early in the year, continuing mid-year at the European Hematology Association (EHA) (Free EHA Whitepaper), and finally, in December at the 58th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, we presented results from the Phase 2 portions of this study, in both newly diagnosed and relapsed/refractory patients. The ongoing trial is expected to complete enrollment in the first half of this year. Importantly the data to date suggest a very real potential for bringing a differentiated commercial product to this vastly underserved market.

Beyond this program, we initiated two new trials in 2016, a Phase 1 clinical trial of GMI-1271 in multiple myeloma (MM), and a Phase 1 clinical trial of our next drug candidate GMI-1359, a dual antagonist of both E-selectin and CXCR4, in healthy volunteers. These accomplishments position us for significant news flow in 2017. In addition, the Phase 3 trial of rivipansel being conducted by Pfizer continues to enroll sickle cell patients with the goal of completion of enrollment in the second half of 2018," said Rachel King, GlycoMimetics’ Chief Executive Officer.

Key Operational Highlights for the Fourth Quarter of 2016:

·

At the ASH (Free ASH Whitepaper) Annual Meeting in San Diego held in December 2016, GlycoMimetics presented results from its Phase 1/2 clinical trial of GMI-1271, in which high rates of remission and favorable tolerability were observed among AML patients in both arms of the trial. In the Phase 1/2 clinical trial, clinicians are studying the use of GMI-1271 along with chemotherapy. For a total of 33 study participants with relapsed or refractory disease in one arm of the trial, the complete response (CR) rate was 45 percent. For 11 newly diagnosed study participants 60 or more years of age in the




second arm of the trial, the CR rate was 73 percent. All study participants evaluated as of the ASH (Free ASH Whitepaper) meeting who had responded had complete remissions; there were no patients observed who responded with incomplete count recoveries. In addition, in elderly, newly diagnosed patients evaluated as of the date of the ASH (Free ASH Whitepaper) meeting, the 60-day mortality rate was zero for those receiving intensive induction chemotherapy plus GMI-1271.

·

GlycoMimetics continues to recruit and dose patients in the Phase 2 portion of its clinical study evaluating GMI-1271 in AML in both newly diagnosed and relapsed/refractory patients at eight active sites in the United States, Ireland and Australia. GMI-1271 has received fast track designation from the US Food & Drug Administration (FDA) for the treatment of AML, and GlycoMimetics plans to continue to engage with the FDA to discuss clinical and manufacturing planning as the program progresses.

·

GlycoMimetics continues enrollment in a Phase 1 clinical trial of GMI-1271 for MM, which enrolled the first patient in September 2016. The multi-center, open-label dose escalation trial, which has begun in Ireland, is designed to measure the efficacy, safety and pharmacokinetics of GMI-1271 in combination with chemotherapy among patients who have been diagnosed with MM and have not responded well to standard chemotherapy.

·

GlycoMimetics completed dosing in a Phase 1 clinical trial of GMI-1359 in healthy volunteers. GMI-1359 is a small molecule drug candidate that simultaneously inhibits both E-selectin and CXCR4. In this first-in-human trial, volunteer participants received a single injection of GMI-1359 and were evaluated for safety, tolerability, pharmacokinetics and pharmacodynamics over 16 days. The randomized, double-blind escalating dose study was conducted at a single site in the United States.

Fourth Quarter 2016 Financial Results:

·

Cash position: As of December 31, 2016, GlycoMimetics had cash and cash equivalents of $40.0 million as compared to $46.8 million as of December 31, 2015.

·

Revenue: The company’s revenue for the year ended December 31, 2016 was not material. The revenue recorded in the year ended December 31, 2015 was due to a $20.0 million non-refundable milestone payment from Pfizer triggered upon the dosing of the first patient in the Phase 3 clinical trial of rivipansel. There were no milestone or royalty payments from Pfizer during the year ended December 31, 2016.






·

R&D Expenses: The company’s research and development expenses decreased to $6.1 million for the quarter ended December 31, 2016 as compared to $7.0 million for the fourth quarter of 2015. Research and development expenses similarly decreased by $1.8 million to $23.3 million for the year ended December 31, 2016, from $25.1 million in the year ended December 31, 2015. During the year ended December 31, 2016, there was an increase in the costs associated with the clinical development for GMI-1271 and GMI-1359, offset by a year-over-year decrease in expenses related to manufacturing and process development for GMI-1271.

·

G&A Expenses: The company’s general and administrative expenses increased to $2.3 million for the quarter ended December 31, 2016 as compared to $2.0 million for the fourth quarter of 2015. General and administrative expenses for the year ended December 31, 2016 increased to $8.7 million as compared to $7.8 million in the prior year. These increases were primarily due to increased labor-related costs and stock-based compensation expense.
·
Shares Outstanding: Shares outstanding as of December 31, 2016 were 23,250,023.

About GMI-1271

GMI-1271 is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. Preclinical research points to the drug’s potential role in moving cancerous cells out of the protective environment of the bone marrow where they hide and escape the effects of chemotherapy. In preclinical studies using animal models of AML, the results of which were presented at ASH (Free ASH Whitepaper) meetings, GMI-1271 was also associated with a reduction of chemotherapy-induced neutropenia and chemotherapy-induced mucositis.

Eagle Pharmaceuticals, Inc. Reports Fourth Quarter and Full Year 2016 Results

On March 1, 2017 Eagle Pharmaceuticals, Inc. (“Eagle” or “the Company”) (Nasdaq:EGRX) reported its financial results for the three- and twelve-months ended December 31, 2016 (Press release, Eagle Pharmaceuticals, MAR 1, 2017, View Source [SID1234517910]). Highlights of and subsequent to the fourth quarter of 2016 include:

Business Highlights:

Bendeka total market share rose to 92%, as of February 24, 2017;
Bendeka achieves $500 million in cumulative sales, triggering $25 million sales milestone from Teva in Q1 2017;
Eight new patents allowed by the U.S. Patent and Trademark Office for Eagle’s Bendeka portfolio bringing the total to 14 issued or allowed, with 11 issued to-date and ten listed in the Orange Book;
The Centers for Medicare & Medicaid Services (CMS) established a unique J-Code (J9034) for Bendeka effective January 1, 2017 triggering a $40 million milestone payment from Teva in Q4 2016;
Ryanodex sales increased to $3.9 million during the fourth quarter;
Completed NDA submission for Ryanodex for Exertional Heat Stroke (EHS) and requested Priority Review;
NDA for Pemetrexed Injection for non-small cell lung cancer and mesothelioma accepted for filing; PDUFA target date of October 30, 2017;
Entered the biologics sector with the acquisition of Arsia Therapeutics, now renamed Eagle Biologics;
Board member, David Pernock, joined Eagle management as President and Chief Commercial Officer; and,
At year end, Eagle had purchased $37 million in Eagle common stock as part of its $75 million Share Repurchase Program. Since commencing the program authorized in August 2016, Eagle has purchased more than 722,000 shares totaling approximately $48 million.
Financial Highlights:

Fourth Quarter

Total revenue for the fourth quarter of 2016 grew 346% to $81.1 million;
Product sales increased to $9.1 million compared to $2.9 million in Q4 2015;
Royalty income increased to $32.0 million compared to $0.3 million in Q4 2015;
License and other income increased to $40.0 million compared to $15 million in Q4 2015;
$52.9 million in total operating expenses during the quarter included approximately $15.6 million related to accelerated and non-recurring expenses; including $12.3 million related to R&D and $3.3 million in accelerated Sales and Marketing expense related to Ryanodex for EHS marketing activities:
R&D expense increased to $16.7 million compared to $8.8 in Q4 2015, which included $12.3 million related to accelerated and non-recurring expenses;
Sales & Marketing expense increased to $17.4 million compared to $5.6 in Q4 2015, which included $3.3 million related to accelerated spending as referenced above;
A tax benefit of $29 million was recorded during the fourth quarter driven by our reversal of the valuation allowance against the Company’s net deferred tax asset;
Q4 2016 income before income tax benefit was $28.3 million; and,
Q4 2016 net income was $57.3 million, or $3.75 per basic and $3.52 per diluted share, compared to net income of $1.2 million, or $0.08 per basic and $0.07 per diluted share in Q4 2015.
Full Year 2016

2016 revenue grew 186% to $189.5 million compared to $66.2 million in 2015;
Product sales increased to $40.6 million in 2016 compared to $13.0 million in 2015;
Royalty income increased to $99.0 million in 2016 compared to $8.3 million in 2015;
License and other income increased $49.8 million in 2016 compared to $45 million in 2015;
Full Year 2016 income before income tax benefit was $53.4 million;
Full Year 2016 net income was $81.5 million, or $5.24 per basic and $4.96 per diluted share, compared to net income of $2.6 million, or $0.17 per basic and $0.16 per diluted share in 2015; and,
Cash and cash equivalents were $52.8 million and accounts receivable were $42.2 million as of December 31, 2016.
“In 2016, we significantly enhanced Eagle’s long term value and we continue to see momentum in our business. Bendeka, for which we receive a 25% royalty, grew to 92% of the bendamustine market and has exceeded $500 million in cumulative sales since its launch in January 2016. With ten Orange-Book listed and fourteen total issued or allowed patents protecting Bendeka from 2026 through 2033, we believe the product will have a very long lifecycle,” stated Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

“With our Ryanodex for Exertional Heat Stroke and Pemetrexed NDAs now submitted to the FDA, and our continued work with fulvestrant and a potential third indication for Ryanodex for Ecstasy and methamphetamine intoxication, 2017 will be an important year for Eagle. We anticipate an FDA decision on these NDA submissions this year and are scaling our commercial organization to prepare for our first self-launched commercial product, if approved. David Pernock will lead our commercial efforts to build an internal sales organization allowing us to maximize the potential of these and future opportunities. And importantly, with multiple additional pipeline products, which we plan to discuss as the year progresses, we continue to focus on developing improved injectables for patients,” added Tarriff.

“During the fourth quarter, we took advantage of our growing cash position to accelerate our research and development spend and buy back additional Eagle shares. We will continue to evaluate opportunities throughout the year to drive additional value for our shareholders,” concluded Tarriff.

Fourth Quarter 2016 Financial Results

Total revenue for the three months ended December 31, 2016 was $81.1 million, as compared to $18.2 million for the three months ended December 31, 2015. A summary of total revenue is outlined below:

Three Months Ended December 31,
2016 2015

Revenue:
Product sales $ 9,080 $ 2,869
Royalty income 32,015 312
License and other income 40,046 15,000
Total revenue

81,141 18,181

Product sales increased to $9.1 million on net product sales in Bendeka, Ryanodex, docetaxel injection non-alcohol formulation, and Argatroban. Royalty income increased to $32.0 million, as a result of the launch of Bendeka in January 2016. License and other income increased to $40.0 million due to the milestone payment from Teva triggered by the CMS decision to issue a unique J-code for Bendeka.

Research and development expenses increased by $7.9 million to $16.7 million in the three months ended December 31, 2016, compared to $8.8 million in the prior year quarter. The increase was largely due to Eagle’s decision to accelerate development spending for molecules in our pipeline and additional non-recurring expenses. $12.3 million of the $16.7 million in R&D spend during the quarter was due to non-recurring expenses and those Eagle opted to accelerate.

SG&A expenses increased $11.8 million to $17.4 million in the fourth quarter of 2016 compared to $5.6 million in the three months ended December 31, 2015. Sales and marketing pre-launch related expenses accounted for the bulk of the increase as the Company prepares for the commercial launch of Ryanodex for EHS, if approved.

A tax benefit of $29 million was recorded during the fourth quarter driven by our reversal of the valuation allowance against the Company’s net deferred tax asset (primarily net operating losses). Based on current profitability and expected future profits we believe it is likely that these tax benefits will be utilized.

Net income for the fourth quarter was $57.3 million, or $3.75 per basic share and $3.52 per diluted share, compared to net income of $1.2 million, or $0.08 per basic and $0.07 per diluted share in the three months ended December 31, 2015, due to the factors discussed above.

Full Year 2016 Financial Results

Total revenue for the year ended December 31, 2016 was $189.5 million, as compared to $66.2 million for the year ended December 31, 2015. A summary of total revenue is outlined below:

Year Ended December 31,
2016 2015

Revenue:
Product sales $ 40,646 $ 12,968
Royalty income 99,040 8,259
License and other income 49,796 45,000
Total revenue 189,482 66,227

The $27.7 million increase in product sales in 2016 was driven by the launch of Bendeka and growth of Ryanodex sales. Royalty income increased by $90.8 million to $99.0 million in 2016 from $8.3 million in 2015, due to the launch of Bendeka. License and other income reflects payments received for achieving certain contractual milestones in connection with the Company’s licensing agreement with Teva.

Cost of product sales increased by $26.6 million to $34.3 million in 2016, from $7.8 million in 2015, due to the launch of Bendeka and inventory write downs. Cost of royalty increased by $13.1 million to $21.0 million in 2016, from $7.9 million in 2015 due to the launch of Bendeka.

R&D expense increased by $2.4 million in 2016 to $30.3 million compared to $27.9 million in 2015 as a result of development efforts to advance multiple product candidates, as well as $5.1 million in development spending for its fulvestrant formulation, which the Company elected to accelerate in Q4 2016.

SG&A expenses increased by $32.1 million to $52.3 million in 2016, compared to $20.2 million in 2015. This increase is related to the growth in the commercial organization, prelaunch expenses, staff additions and professional fees incurred to support expansion of the Company.

Included in operating expenses in 2016 is approximately $10 million related to stock-based compensation, a 140% increase over the same period in 2015. We estimate stock-based compensation will increase to approximately $15.5 million in 2017.

For the full year, the Company recorded a net tax benefit of $28 million. Included in this amount was a reversal of a valuation allowance which had been carried against the Company’s net deferred tax assets (primarily net operating losses).

Net income for the year ended December 31, 2016 was $81.5 million or $5.24 per basic and $4.96 per diluted share as compared to net income of $2.6 million or $0.17 per basic and $0.16 per diluted share for the year ended December 31, 2015, as a result of the factors discussed above.

Liquidity

As of December 31, 2016, the Company had $52.8 million in cash and cash equivalents; $42.2 million in receivables, with approximately $31.1 million due from Teva; and no debt.

Expense Guidance

2017 R&D expense is expected to be in the range of $31 – $35 million
2017 SG&A expense is expected to be in the range of $65 – $68 million

Eagle Pharmaceuticals, Inc. Reports Fourth Quarter and Full Year 2016 Results

On March 1, 2017 Eagle Pharmaceuticals, Inc. ("Eagle" or "the Company") (Nasdaq:EGRX) reported its financial results for the three- and twelve-months ended December 31, 2016 (Press release, Eagle Pharmaceuticals, MAR 1, 2017, View Source [SID1234517910]). Highlights of and subsequent to the fourth quarter of 2016 include:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Business Highlights:

Bendeka total market share rose to 92%, as of February 24, 2017;
Bendeka achieves $500 million in cumulative sales, triggering $25 million sales milestone from Teva in Q1 2017;
Eight new patents allowed by the U.S. Patent and Trademark Office for Eagle’s Bendeka portfolio bringing the total to 14 issued or allowed, with 11 issued to-date and ten listed in the Orange Book;
The Centers for Medicare & Medicaid Services (CMS) established a unique J-Code (J9034) for Bendeka effective January 1, 2017 triggering a $40 million milestone payment from Teva in Q4 2016;
Ryanodex sales increased to $3.9 million during the fourth quarter;
Completed NDA submission for Ryanodex for Exertional Heat Stroke (EHS) and requested Priority Review;
NDA for Pemetrexed Injection for non-small cell lung cancer and mesothelioma accepted for filing; PDUFA target date of October 30, 2017;
Entered the biologics sector with the acquisition of Arsia Therapeutics, now renamed Eagle Biologics;
Board member, David Pernock, joined Eagle management as President and Chief Commercial Officer; and,
At year end, Eagle had purchased $37 million in Eagle common stock as part of its $75 million Share Repurchase Program. Since commencing the program authorized in August 2016, Eagle has purchased more than 722,000 shares totaling approximately $48 million.
Financial Highlights:

Fourth Quarter

Total revenue for the fourth quarter of 2016 grew 346% to $81.1 million;
Product sales increased to $9.1 million compared to $2.9 million in Q4 2015;
Royalty income increased to $32.0 million compared to $0.3 million in Q4 2015;
License and other income increased to $40.0 million compared to $15 million in Q4 2015;
$52.9 million in total operating expenses during the quarter included approximately $15.6 million related to accelerated and non-recurring expenses; including $12.3 million related to R&D and $3.3 million in accelerated Sales and Marketing expense related to Ryanodex for EHS marketing activities:
R&D expense increased to $16.7 million compared to $8.8 in Q4 2015, which included $12.3 million related to accelerated and non-recurring expenses;
Sales & Marketing expense increased to $17.4 million compared to $5.6 in Q4 2015, which included $3.3 million related to accelerated spending as referenced above;
A tax benefit of $29 million was recorded during the fourth quarter driven by our reversal of the valuation allowance against the Company’s net deferred tax asset;
Q4 2016 income before income tax benefit was $28.3 million; and,
Q4 2016 net income was $57.3 million, or $3.75 per basic and $3.52 per diluted share, compared to net income of $1.2 million, or $0.08 per basic and $0.07 per diluted share in Q4 2015.
Full Year 2016

2016 revenue grew 186% to $189.5 million compared to $66.2 million in 2015;
Product sales increased to $40.6 million in 2016 compared to $13.0 million in 2015;
Royalty income increased to $99.0 million in 2016 compared to $8.3 million in 2015;
License and other income increased $49.8 million in 2016 compared to $45 million in 2015;
Full Year 2016 income before income tax benefit was $53.4 million;
Full Year 2016 net income was $81.5 million, or $5.24 per basic and $4.96 per diluted share, compared to net income of $2.6 million, or $0.17 per basic and $0.16 per diluted share in 2015; and,
Cash and cash equivalents were $52.8 million and accounts receivable were $42.2 million as of December 31, 2016.
"In 2016, we significantly enhanced Eagle’s long term value and we continue to see momentum in our business. Bendeka, for which we receive a 25% royalty, grew to 92% of the bendamustine market and has exceeded $500 million in cumulative sales since its launch in January 2016. With ten Orange-Book listed and fourteen total issued or allowed patents protecting Bendeka from 2026 through 2033, we believe the product will have a very long lifecycle," stated Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

"With our Ryanodex for Exertional Heat Stroke and Pemetrexed NDAs now submitted to the FDA, and our continued work with fulvestrant and a potential third indication for Ryanodex for Ecstasy and methamphetamine intoxication, 2017 will be an important year for Eagle. We anticipate an FDA decision on these NDA submissions this year and are scaling our commercial organization to prepare for our first self-launched commercial product, if approved. David Pernock will lead our commercial efforts to build an internal sales organization allowing us to maximize the potential of these and future opportunities. And importantly, with multiple additional pipeline products, which we plan to discuss as the year progresses, we continue to focus on developing improved injectables for patients," added Tarriff.

"During the fourth quarter, we took advantage of our growing cash position to accelerate our research and development spend and buy back additional Eagle shares. We will continue to evaluate opportunities throughout the year to drive additional value for our shareholders," concluded Tarriff.

Fourth Quarter 2016 Financial Results

Total revenue for the three months ended December 31, 2016 was $81.1 million, as compared to $18.2 million for the three months ended December 31, 2015. A summary of total revenue is outlined below:


Three Months Ended December 31,
2016 2015

Revenue:
Product sales $ 9,080 $ 2,869
Royalty income 32,015 312
License and other income 40,046 15,000
Total revenue

81,141 18,181

Product sales increased to $9.1 million on net product sales in Bendeka, Ryanodex, docetaxel injection non-alcohol formulation, and Argatroban. Royalty income increased to $32.0 million, as a result of the launch of Bendeka in January 2016. License and other income increased to $40.0 million due to the milestone payment from Teva triggered by the CMS decision to issue a unique J-code for Bendeka.

Research and development expenses increased by $7.9 million to $16.7 million in the three months ended December 31, 2016, compared to $8.8 million in the prior year quarter. The increase was largely due to Eagle’s decision to accelerate development spending for molecules in our pipeline and additional non-recurring expenses. $12.3 million of the $16.7 million in R&D spend during the quarter was due to non-recurring expenses and those Eagle opted to accelerate.

SG&A expenses increased $11.8 million to $17.4 million in the fourth quarter of 2016 compared to $5.6 million in the three months ended December 31, 2015. Sales and marketing pre-launch related expenses accounted for the bulk of the increase as the Company prepares for the commercial launch of Ryanodex for EHS, if approved.

A tax benefit of $29 million was recorded during the fourth quarter driven by our reversal of the valuation allowance against the Company’s net deferred tax asset (primarily net operating losses). Based on current profitability and expected future profits we believe it is likely that these tax benefits will be utilized.

Net income for the fourth quarter was $57.3 million, or $3.75 per basic share and $3.52 per diluted share, compared to net income of $1.2 million, or $0.08 per basic and $0.07 per diluted share in the three months ended December 31, 2015, due to the factors discussed above.

Full Year 2016 Financial Results

Total revenue for the year ended December 31, 2016 was $189.5 million, as compared to $66.2 million for the year ended December 31, 2015. A summary of total revenue is outlined below:


Year Ended December 31,
2016 2015

Revenue:
Product sales $ 40,646 $ 12,968
Royalty income 99,040 8,259
License and other income 49,796 45,000
Total revenue 189,482 66,227

The $27.7 million increase in product sales in 2016 was driven by the launch of Bendeka and growth of Ryanodex sales. Royalty income increased by $90.8 million to $99.0 million in 2016 from $8.3 million in 2015, due to the launch of Bendeka. License and other income reflects payments received for achieving certain contractual milestones in connection with the Company’s licensing agreement with Teva.

Cost of product sales increased by $26.6 million to $34.3 million in 2016, from $7.8 million in 2015, due to the launch of Bendeka and inventory write downs. Cost of royalty increased by $13.1 million to $21.0 million in 2016, from $7.9 million in 2015 due to the launch of Bendeka.

R&D expense increased by $2.4 million in 2016 to $30.3 million compared to $27.9 million in 2015 as a result of development efforts to advance multiple product candidates, as well as $5.1 million in development spending for its fulvestrant formulation, which the Company elected to accelerate in Q4 2016.

SG&A expenses increased by $32.1 million to $52.3 million in 2016, compared to $20.2 million in 2015. This increase is related to the growth in the commercial organization, prelaunch expenses, staff additions and professional fees incurred to support expansion of the Company.

Included in operating expenses in 2016 is approximately $10 million related to stock-based compensation, a 140% increase over the same period in 2015. We estimate stock-based compensation will increase to approximately $15.5 million in 2017.

For the full year, the Company recorded a net tax benefit of $28 million. Included in this amount was a reversal of a valuation allowance which had been carried against the Company’s net deferred tax assets (primarily net operating losses).

Net income for the year ended December 31, 2016 was $81.5 million or $5.24 per basic and $4.96 per diluted share as compared to net income of $2.6 million or $0.17 per basic and $0.16 per diluted share for the year ended December 31, 2015, as a result of the factors discussed above.

Liquidity

As of December 31, 2016, the Company had $52.8 million in cash and cash equivalents; $42.2 million in receivables, with approximately $31.1 million due from Teva; and no debt.

Expense Guidance

2017 R&D expense is expected to be in the range of $31 – $35 million
2017 SG&A expense is expected to be in the range of $65 – $68 million