On November 3, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that data from 25 abstracts evaluating an important variety of investigational uses of the company’s portfolio of blood cancer medicines will be presented during the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 3-6, in San Diego, CA (Press release, AbbVie, NOV 3, 2016, View Source [SID1234516204]).

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!

AbbVie will present results from several studies evaluating ibrutinib, an inhibitor of Bruton’s tyrosine kinase (BTK) being developed by Pharmacyclics, an AbbVie company, and Janssen Biotech, Inc., across a number of blood cancers. AbbVie will also present data on venetoclax, a BCL-2 inhibitor, being developed by AbbVie and Genentech, a member of the Roche Group. The scientific presentations describe the potential of ibrutinib and venetoclax in multiple hematologic malignancies, including chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and acute myeloid leukemia (AML), among others. Data for elotuzumab, co-developed by Bristol-Myers Squibb and AbbVie, in MM will also be presented at the meeting.

"Every year the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting marks the opportunity to show AbbVie’s success in advancing important treatments for people impacted by cancer," said Dr. Gary Gordon, vice president, oncology development, AbbVie. "Through our work with scientists, doctors and patients, AbbVie is presenting data highlighting progress in the discovery and development of new and promising therapies to treat blood cancers."

AbbVie abstracts:

Ibrutinib

Outcomes of Ibrutinib Therapy by Age in Patients with CLL/SLL: Analyses from Phase 3 Trial Data (RESONATE and RESONATE-2); J.Woyach et al.; Abstract 2041; Poster Session; Saturday, December 3, 2016; 5:30-7:30 p.m. PST
11q Deletion (del11q) Is Not a Prognostic Factor for Adverse Outcomes for Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Treated with Ibrutinib: Pooled Data from 3 Randomized Phase 3 Studies; T. Kipps et al.; Abstract 2042; Poster Session; Saturday, December 3, 2016; 5:30-7:30 p.m. PST
Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia; S. O’Brien et al.; Abstract 233; Oral Session; Saturday, December 3, 2016; 5 p.m. PST
Updated Efficacy and Safety from the Phase 3 RESONATE-2 Study: Ibrutinib as First-Line Treatment Option in Patients 65 Years and Older with Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia; P. Barr et al.; Abstract 234; Oral Session; Saturday, December 3, 2016; 5:15 p.m. PST
Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study; A. Noy et al.; Abstract 1213; Oral Session; Monday, December 5, 2016; 6:15 p.m. PST
A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Combination with Lenalidomide and Rituximab in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL); A. Goy et al.; Abstract 473; Oral Session; Sunday, December 4, 2016; 5:30 p.m. PST
Ibrutinib Combined with Rituximab in Treatment-Naïve Patients with Follicular Lymphoma: Arm 1 + Arm 2 Results from a Multicenter, Open-Label Phase 2 Study; N. Fowler et al.; Abstract 1804; Poster Session; Saturday, December 3, 2016; 5:30-7:30 p.m. PST
Integrated and Long-Term Safety Analysis of Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL); S. Coutre et al.; Abstract 4383; Poster Session; Monday, December 5, 2016; 6-8 p.m. PST
Changes in Clinical Stage Identify Different Response Categories among Patients in iwCLL PR: Analysis of CLL Patients on the RESONATE Study; C. Moreno et al.; Abstract 4384; Poster Session; Monday, December 5, 2016; 6-8 p.m. PST
Ibrutinib Potentiated NK Cell-Mediated Cytotoxicity in Mouse Models of B-Cell Lymphomas; H. Kuo et al.; Abstract 4140; Poster Session; Monday, December 5, 2016; 6-8 p.m. PST

Venetoclax

M13-365: Detailed Safety Analysis of Venetoclax Combined with Rituximab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia; D. Brander et al.; Abstract 2033; Poster Session; Saturday, December 3, 2016; 5:30-7:30 p.m. PST
M14-032: Venetoclax (VEN) Monotherapy for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapsed After or Were Refractory to Ibrutinib or Idelalisib; J. Jones et al.; Abstract 637; Oral Session; Monday, December 5, 2016; 7 a.m. PST
Safety Profile of Venetoclax Monotherapy in Patients with Chronic Lymphocytic Leukemia; J. Seymour et al.; Abstract 4395; Poster Session; Monday, December 5, 2016; 6-8 p.m. PST
Attainment of Complete Remission is Significantly Associated with Longer Survival Outcomes in Relapsed/Refractory (R/R) CLL: A Meta-Analysis; V. Ektare et al.; Abstract 2045; Poster Session; Saturday, December 3, 2016; 5:30-7:30 p.m. PST
Pooled Multi-trial Analysis of Venetoclax Efficacy in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia; A. Roberts et al.; Abstract 3230; Poster Session; Sunday, December 4, 2016; 6-8 p.m. PST
M13-367: Venetoclax Monotherapy for Relapsed/Refractory Multiple Myeloma: Safety and Efficacy Results from a Phase I Study; S. Kumar et al.; Abstract 488; Oral Session; Sunday, December 4, 2016; 4:30-6 p.m. PST
M12-901: Venetoclax Combined with Bortezomib and Dexamethasone for Patients with Relapsed/Refractory Multiple Myeloma; P. Moreau et al.; Abstract 975; Oral Session; Monday, December 5, 2016; 2:45-4:15 p.m. PST
Correlative Biomarkers of Response to Venetoclax in Combination with Chemotherapy or Hypomethylating Agents in Elderly Untreated Patients with Acute Myeloid Leukemia; B. Chyla et al.; Abstract 1709; Poster Session; Saturday, December 3, 2016; 5:30-7:30 p.m. PST
M14-387: Safety and Efficacy of Venetoclax Plus Low-Dose Cytarabine in Treatment-Naïve Patients Aged >=65 Years with Acute Myeloid Leukemia (AML); A. Wei et al.; Abstract 102; Oral Session; Saturday, December 3, 2016; 9:30-11 a.m. PST
BO29337 (CONTRALTO): Phase 2 Study of Venetoclax plus Rituximab or Bendamustine+Rituximab Versus BR Alone in Relapsed/Refractory Follicular Lymphoma: Preliminary Data; Hiddemann et al.; Oral Session; Monday, December 5, 2016; 7-8:30 p.m. PST
GO28440: Results of a Phase Ib Study (GO28440) of Venetoclax with Bendamustine/Rituximab or Bendamustine/Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia; Salles et al.; Poster Session; Monday, December 5, 2016; 6-8 p.m. PST
GO27878 (CAVALLI): Results of a Phase Ib Study of Venetoclax Plus R- or G-CHOP in Patients with B-cell Non-Hodgkin Lymphoma; A. Zelenetz et al.; Poster Session; Sunday, December 4, 2016; 6-8 p.m. PST
BCL-2 Family Expression Favor t(11;14)+ Patients Amongst Molecular Subgroups of Multiple Myeloma, for Susceptibility to Single Agent Venetoclax; J. Wu et al.; Online Publication

Elotuzumab

Safety and Efficacy of Elotuzumab with Lenalidomide/Dexamethasone for Multiple Myeloma in a Japanese Subpopulation Analysis of the Phase 3 ELOQUENT-2 Trial; K. Ohashi et al.; Abstract 3315; Poster Session; Sunday, December 4, 2016; 6-8 p.m. PST
Budget Impact Analysis of Introducing Elotuzumab in Combination with Lenalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: A U.S. Payer Perspective; R. Potluri et al.; Abstract 2363; Poster Session; Saturday, December 3, 2016; 5:30-7:30 p.m. PST
The ASH (Free ASH Whitepaper) 2016 Annual Meeting abstracts are available at View Source

About IMBRUVICA (ibrutinib) in the U.S.
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.1,2 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.1

IMBRUVICA is approved to treat patients with CLL/SLL, patients with mantle cell lymphoma (MCL) who have received at least one prior therapy, and patients with Waldenström’s macroglobulinemia. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.1

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers. More than 6,000 patients have been treated with IMBRUVICA in clinical trials. Currently, 14 Phase 3 trials have been initiated with IMBRUVICA and more than 90 trials are registered on www.clinicaltrials.gov.

Patient Access to IMBRUVICA
AbbVie and Janssen strive to make access to IMBRUVICA easy by helping patients understand their insurance benefits for IMBRUVICA. The YOU&i Support Program is a personalized program that includes information on access and affordability, nurse call support and resources for patients being treated with IMBRUVICA. This includes the YOU&i Instant Savings program, which provides co-pay support to eligible commercially insured IMBRUVICA patients. Patients can access the program by contacting 1-877-877-3536, option 1 or by visiting View Source

The YOU&i Instant Savings program is not available for patients enrolled in Medicare or Medicaid. For a list of patient support organizations that may be able to provide financial support please visit: View Source

U.S. IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (?20%) in patients with B-cell malignancies (MCL, CLL/SLL, and WM) were neutropenia* (64%), thrombocytopenia* (63%), diarrhea (43%), anemia* (41%), musculoskeletal pain (30%), rash (29%), nausea (29%), bruising (29%), fatigue (27%), hemorrhage (21%), and pyrexia (21%).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

The most common Grade 3 or 4 non-hematologic adverse reactions (?5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.

Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see full U.S. Prescribing Information: View Source

About Venclexta (venetoclax) in the U.S.
Venclexta (venetoclax) is an oral B-cell lymphoma-2 (BCL-2) inhibitor indicated in the U.S. for the treatment of patients with relapsed/refractory CLL with 17p deletion, as detected by an FDA-approved test.3 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.3 Venclexta is designed to selectively inhibit the BCL-2 protein.3 Venclexta was developed in collaboration with Genentech and Roche.

Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory and first-line CLL, along with early phase studies in several cancers.

Venetoclax is under evaluation by health authorities in multiple countries, and is currently approved in Argentina, Puerto Rico and Canada.

On November 3, 2016 Navidea Biopharmaceuticals (NYSE MKT:NAVB) reported financial results for the quarter ending September 30, 2016 (Press release, Navidea Biopharmaceuticals, NOV 3, 2016, View Source;p=RssLanding&cat=news&id=2219021 [SID1234516230]). Navidea reported total revenue for the third quarter of 2016 of $8.5 million, including Lymphoseek (technetium Tc 99m tilmanocept) injection sales revenue of $6.7 million. The income from operations was $3.4 million and the net loss attributable to common stockholders was $59,000.

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!

"We ended the third quarter with a clear plan for Navidea’s future. With our previously announced Letter of Intent with Cardinal Health, Inc., we believe that we have successfully identified an arrangement to extinguish the CRG (Capital Royalty Partners II L.P) debt and to focus Navidea on several attractive development efforts outside of lymphatic mapping, lymph node biopsy and the diagnosis of metastatic spread to lymph nodes for the staging of cancer in North America. The contemplated transaction with Cardinal Health, as well as the impending launch of Lymphoseek in Europe by our partner SpePharm AG (Norgine BV), should provide additional income for many years to come," said Dr. Michael Goldberg, Navidea President and CEO. "Our focus moving forward will be on expansion and development of Manocept-based diagnostic markets initially in rheumatoid arthritis and cardiovascular disease, as well as developing our immunotherapeutic platform with a strong preclinical pipeline for cancer, autoimmune, inflammatory and infectious diseases."

Specific events and milestones achieved since the beginning of the third quarter include the following:

Operational & Financial

Entered into Letter of Intent with Cardinal Health, Inc. for the sale of Lymphoseek in North America;
Operating activities provided cash of $1.3 million during the first nine months of 2016, compared to $14.9 million cash used in operations during the same period in 2015;
Reduced cash used in operations by over 100% for the first nine months of 2016 compared to the same period of 2015; and
Appointed Michael M. Goldberg, M.D. President and Chief Executive Officer, and Eric K. Rowinsky, M.D. Chairman of the Board.
Commercial

Achieved sequential quarter-on-quarter Lymphoseek sales revenue growth;
Earned a $500,000 milestone payment from Cardinal Health with the sale of the 100,000th Lymphoseek dose;
Received positive opinion in Europe for new Lymphoseek reduced-mass vial enabling a single injection per vial and triggering a $500,000 milestone payment by our partner, Norgine BV; and
Continued to support the projected Q4 launch of Lymphoseek in Europe by Norgine BV.
Immunodiagnostic & Immunotherapeutic Development Pipeline

Received both Institutional Review Board at University of California, San Francisco and Western Institutional Review Board approvals for a tilmanocept subcutaneous administration clinical trial protocol in rheumatoid arthritis, allowing subject enrollment to begin. To date, 17 of 18 patients have been dosed and imaged;
Received Institutional Review Board approval for a tilmanocept clinical trial protocol in Kaposi Sarcoma which is supported by an NIH grant;
Clinical trial results of tilmanocept in cardiovascular disease from Massachusetts General Hospital have been submitted for publication; and
Completed a number of additional preclinical animal studies and initiated additional studies with the MT 1000 and MT 2000 class of compounds.
Financials

"We are pleased with our financial performance despite the significant disruption in our organization caused by the ongoing litigation with CRG. Our results demonstrate our commitment to our commercial efforts and controlling our operating expenses," said Jed Latkin, interim Chief Operating Officer and Chief Financial Officer at Navidea.

Total revenues for the quarter ended September 30, 2016 were $8.5 million compared to $4.0 million in the third quarter of last year. Third quarter 2016 product revenues recognized from the sale of Lymphoseek were $6.7 million, compared to $4.2 million in the second quarter of 2016 and $3.0 million in the third quarter of 2015. During the third quarter of 2016, the Company also reported $1.8 million in licensing, grant and other revenue. For the nine months ended September 30, 2016, Navidea’s total revenue was $18.6 million compared to $9.0 million for the same period in 2015, an increase of 108%. The primary driver of this increase was revenues recognized by Navidea from the sale of Lymphoseek which exceeded $14.7 million for the nine months ended September 30, 2016 compared to $6.8 million for the same period last year. Third quarter 2016 revenue from the sale of Lymphoseek included $2.0 million of inventory purchases by Cardinal Health and $500,000 of additional revenue from a milestone related to the sale of the 100,000th Lymphoseek dose by Cardinal Health.

Third quarter 2016 margins also remained above 80%, contributing to a total gross profit of $7.6 million for the quarter, compared to $3.5 million for the same period last year. For the nine months ended September 30, 2016, total gross profit rose to $16.6 million versus $7.7 million for the same period last year, an increase of 115%. The increases in total gross profit in the third quarter and first nine months of 2016 was primarily due to $2.0 million of inventory purchases by Cardinal Health, a $500,000 milestone related to the sale of the 100,000th Lymphoseek dose by Cardinal Health, and receipt of a $500,000 milestone payment, and recognition of the remaining $500,000 of the upfront license fee received from SpePharm related to the positive regulatory opinion on a reduced-mass vial in Europe.

Research and development (R&D) expenses for the third quarter of 2016 were $1.3 million, compared to $3.9 million in the third quarter of last year. R&D expenses were $6.5 million for the nine months ended September 30, 2016 compared to $10.2 million in the same period of 2015. The net decreases in year-to-date R&D expenses were primarily a result of decreased headcount costs coupled with decreased project costs related to the Company’s neuro assets and Lymphoseek, offset by increased project costs related to the Company’s therapeutic programs. Selling, general and administrative (SG&A) expenses for the third quarter of 2016 were $2.9 million, compared to $3.9 million in the third quarter of last year. SG&A expenses were $9.9 million for the nine months ended September 30, 2016, compared to $13.5 million for the same period in 2015. The net decrease in year-to-date SG&A expenses was due primarily to decreased headcount coupled with decreased costs related to business development consulting services, contracted medical science liaisons, commercialization costs for Lymphoseek, license fees and investor relations, offset by increases in commercial and medical headcount costs related to the addition of our internal sales force and medical science liaisons coupled with increased legal and professional services. Total operating expenses were $4.2 million for the third quarter of 2016, compared to $7.8 million in the third quarter of last year. Operating expenses were $16.4 million for the nine months ended September 30, 2016, compared to $23.7 million for the same period in 2015.

Navidea’s income from operations for the quarter ended September 30, 2016 was $3.4 million compared to a loss from operations of $4.3 million for the same period in 2015. For the nine months ended September 30, 2016, Navidea’s income from operations was $210,000 compared to a loss from operations of $15.9 million for the same period in 2015. Navidea’s net loss attributable to common stockholders for the quarter ended September 30, 2016 was $59,000, or $0.00 per share, compared to net loss attributable to common stockholders of $8.1 million, or $0.05 per share, for the same period in 2015. For the nine months ended September 30, 2016, Navidea’s net loss attributable to common stockholders was $10.4 million, or $0.07 per share, compared to a net loss attributable to common stockholders of $25.1 million, or $0.17 per share, for the same period in 2015. Net losses attributable to common stockholders include fees paid to CRG (which the Company is disputing in court), the interest expense on our outstanding debt, as well as significant non-cash charges. For the nine-month periods ended September 30, 2016 and September 30, 2015, net loss attributable to common stockholders included $10.6 million and $9.1 million, respectively, in interest, debt-related fees, losses on extinguishment of debt, and changes in the fair value of financial instruments.

Navidea ended the quarter with $4.3 million in cash, $3.5 million of which was restricted related to the CRG debt.

On November 3, 2016 NantKwest Inc. (Nasdaq:NK), a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases, reporteded several presentations at the upcoming 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA, December 3-6, 2016 (Press release, NantKwest, NOV 3, 2016, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2220144 [SID1234516468]).

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!

"As these presentations demonstrate, since our IPO in July 2016, NantKwest continues to make significant progress in our preclinical and clinical development efforts," said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest. "We are honored to present these results at the upcoming annual ASH (Free ASH Whitepaper) meeting and remain focused on bringing our novel, natural killer cell based therapies to the routine clinical cancer setting for a broad range of cancer types."

Presentation Summaries

Combination Therapy with Daratumumab and CAR-NK Targeting CS1 for Multiple Myeloma

Abstract #1342, View Source
Presenter: Yibo Zhang, PhD, Comprehensive Cancer Center, Ohio State University, Columbus, OH
Saturday, December 3, 2016, 5:30 – 7:30 PM, Hall GH
This poster will review the combination of Daratumumab and CS1.taNK therapy targeting two different tumor-associated antigens, both with potent efficacy in multiple myeloma, which may have synergistic effects.

Phase 1 Clinical Trial of Adoptive Immunotherapy Using "Off-The-Shelf" Activated Natural Killer Cells (aNK) in Patients with Refractory/Relapsed Acute Myeloid Leukemia

Abstract #1649, View Source
Presenter: Michael Boyiadzis, MD, MHSc, University of Pittsburgh Medical Center, UPMC Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA
Saturday, December 3, 2016, 5:30 – 7:30 PM, Hall GH
This poster will review a Phase I clinical trial of the safety and efficacy of "off-the-shelf" aNK cell therapy in heavily pretreated patients with refractory/relapsed AML

CD19 Target Activated Natural Killer (CD19.taNK) Cellular Therapy: A Novel Immunotherapeutic Approach to the Treatment of Non-Hodgkin Lymphoma (NHL)

Abstract #4174, View Source
Presenter: Ravi Dashnamoorthy, PhD, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA
Monday, December 4, 2016, 6:00 – 8:00PM, Hall GH
This poster will review the potent single agent anti-tumor activity against a range of NHL cell and ongoing activity into the biological mechanisms of activity of CD19.taNK therapy and potential combination therapy approaches.

On November 3, 2016 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported business highlights and financial results for the third quarter ended September 30, 2016 (Filing, Q3, Agios Pharmaceuticals, 2016, NOV 3, 2016, View Source [SID1234516180]).

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!

"We have made significant progress during 2016, establishing proof of concept with our lead pyruvate kinase-R (PKR) activator, executing late-stage clinical development for both of our lead isocitrate dehydrogenase (IDH) mutant inhibitors in hematologic malignancies and strengthening our balance sheet through our recent financing," said David Schenkein, M.D., chief executive officer at Agios. "As we head into year end, we are focused on supporting the enasidenib NDA submission with our partner Celgene and planning for our next steps in clinical development for our PKR and IDH portfolios based on data we will present at a number of upcoming medical meetings this quarter."

THIRD QUARTER 2016 HIGHLIGHTS & UPDATES
IDH Mutant Inhibitors in Hematologic Malignancies:
In September, Agios and Celgene announced plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration for enasidenib (AG-221) in relapsed and/or refractory (R/R) acute myeloid leukemia (AML) with an IDH2 mutation by year-end. The NDA will be based on data from an ongoing Phase 1/2 trial in patients with relapsed and/or refractory AML and other advanced hematologic malignancies with an IDH2 mutation.

Agios plans to explore a similar regulatory path for AG-120, its wholly owned, first-in-class, oral, potent inhibitor of mutant IDH1, which could lead to a NDA submission in 2017 in the U.S.

Corporate:
In September, Agios completed an underwritten public offering of common stock for 3,876,403 shares at the offering price of $44.50 per share, resulting in gross proceeds of approximately $173 million.

Agios recently announced the appointment of Andrew Hirsch to chief financial officer. Mr. Hirsch has more than 20 years of experience in a range of strategic and operating roles. He most recently served as president and chief executive officer of BIND Therapeutics. Prior to joining BIND, he was chief financial officer at Avila Therapeutics until its acquisition by Celgene and held roles of increasing responsibility during his nearly 10-year tenure at Biogen.

UPCOMING MEDICAL MEETING PRESENTATIONS

• First data from the expansion phase of the ongoing Phase 1 study of AG-120 in advanced IDH1 mutant positive chondrosarcoma at the Connective Tissue Oncology Society (CTOS) Annual Meeting on November 10, 2016 in Lisbon, Portugal.

• Preliminary data from the expansion phase of the ongoing Phase 1 study of AG-120 in advanced IDH1 mutant positive low-grade glioma at the Society for NeuroOncology (SNO) Annual Meeting on November 18, 2016 in Scottsdale, AZ.

• Updated data from the AG-348 Phase 2 DRIVE-PK study, the AG-519 Phase 1 healthy volunteer study, the Natural History Study of pyruvate kinase deficiency (PKD), and new AG-348 metabolic data in PKD patients at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 3-6, 2016 in San Diego, CA.

• Updated follow-up and molecular data from the completed dose escalation portion of the AG-120 Phase 1 study in R/R AML at ASH (Free ASH Whitepaper).

ADDITIONAL 2016 EXPECTED MILESTONES
IDH Mutant Inhibitors in Hematologic Malignancies:

• Complete enrollment of the 125-patient expansion cohort for the Phase 1 study of AG-120 in patients with R/R AML
IDH Mutant Inhibitors in Solid Tumors:

• Initiate a randomized study of AG-120 in IDH1 mutant positive cholangiocarcinoma

Cancer Metabolism Research:

• Initiate preclinical development activities for the first molecule in a program focused on MTAP (methylthioadenosine phosphorylase) deleted cancers
Rare Genetic Metabolic Disorders:

• Provide a development strategy update for our PKR activator program, including molecule selection

• Outline the clinical development plans for our PKR activators in beta-thalassemia

THIRD QUARTER 2016 FINANCIAL RESULTS
Cash, cash equivalents and marketable securities as of September 30, 2016 were $622.6 million, compared to $375.9 million as of December 31, 2015. The increase in cash was driven by cash received from Celgene totaling $251.5 million, which includes a $200 million upfront payment from the May 2016 collaboration agreement, $25 million related to initiation of the enasidenib Phase 3 IDHENTIFY study and $26.5 million of program funding related to our collaboration agreements, and net proceeds of $162.1 million received from the company’s September 2016 public offering. These items were offset by a decrease in cash related to expenditures to fund operating activities of $161.7 million and purchases of fixed assets, net of reimbursements, of $4.3 million during the nine months ended September 30, 2016.

Collaboration revenue was $9.0 million for the quarter ended September 30, 2016, compared to $5.5 million for the comparable period in 2015.

Research and development (R&D) expense was $60.6 million, including $7.9 million of stock-based compensation expense, for the quarter ended September 30, 2016, compared to $36.0 million, including $4.9 million in stock-based compensation expense, for the quarter ended September 30, 2015. The increase in R&D expense was primarily due to increased costs to support advancement of the company’s lead investigational medicines toward later-stage development. Celgene is responsible for all development costs for enasidenib and certain development costs for AG-881 and reimburses the company for development costs incurred for these investigational medicines.

General and administrative (G&A) expense was $11.9 million, including $4.2 million of stock-based compensation expense, for the quarter ended September 30, 2016, compared to $9.9 million, including $4.5 million of stock-based compensation expense, for the quarter ended September 30, 2015. The increase in G&A expense was largely due to increased headcount and other professional expenses to support growing operations.

Net loss for the quarter ended September 30, 2016 was $62.8 million, compared to a net loss of $40.3 million for the comparable period in 2015.

UPDATED FINANCIAL GUIDANCE FOR THE FULL YEAR 2016
As a result of the recent financing, Agios now expects to end 2016 with more than $550 million of cash, cash equivalents and marketable securities. The anticipated year-end 2016 cash position does not include any additional program-specific milestone payments from Celgene. Based on its current operating plans, the company expects that its existing cash, cash equivalents and marketable securities as of September 30, 2016, together with anticipated interest income, and anticipated expense reimbursements under our collaboration agreements with Celgene, but excluding any additional program-specific milestone payments from Celgene, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2018.

On November 3, 2016 Argos Therapeutics Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis technology platform, reported the publication of a Case Report in the Kidney Cancer Journal which details the clinical outcomes of two patients with intermediate risk metastatic renal cell carcinoma who had participated in a Phase 2 clinical trial of the company’s investigational immunotherapy AGS-003 in combination with sunitinib (Press release, Argos Therapeutics, NOV 3, 2016, View Source [SID1234516205]). These patients have obtained long-term control of metastatic disease that is ongoing seven years after initiation of treatment.

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!

"Our report discusses truly remarkable cases from a Phase 2 study, where two intermediate risk mRCC patients have sustained an immune response to their disease for many years," said lead author Gautam Jha, MD, medical oncologist at the University of Minnesota. "Perhaps most importantly, we have observed an increase in the number of effector memory T-cells associated with improved Overall Survival (OS) in 14 patients who received at least 5 doses of AGS-003. Considering AGS-003 is well-tolerated without significant additional side effects over single agent sunitinib, this investigational therapy remains promising for patients with advanced kidney cancer."

In the open-label Phase 2 clinical trial, 21 patients with newly-diagnosed, intermediate and poor risk mRCC were treated with AGS-003 plus sunitinib as a first-line therapy. Results demonstrated a median Progression Free Survival (PFS) of 11.2 months and median OS of 30.2 months for all patients. Five patients in the trial survived for more than five years, and two patients have maintained durable immune responses for seven years. According to the International mRCC Database Consortium, similar unfavorable risk mRCC patients have an expected OS of only 14.7 months. In addition, follow-up analysis of these Phase 2 data, approximately two years after database lock, demonstrated a median OS of 61.9 months for the intermediate risk patients in the study compared with 20.7 months for similar patients in the International mRCC Database Consortium.

Argos designed AGS-003 to capture the mutated and variant antigens that are unique to each patient’s tumor to induce a robust targeted immune response. This individualized immunotherapy is created using a small tumor sample and the patient’s own dendritic cells collected in a leukapheresis procedure. RNA is isolated from the tumor sample and used to program dendritic cells to target disease-specific antigens. Activated, antigen-loaded dendritic cells are then formulated with the patient’s plasma, and administered via intradermal injection as an individualized immunotherapy.

"By capturing the array of known, unknown, and mutated antigens present in an individual patient’s specific cancer, AGS-003 appears to elicit a broad, individualized anti-tumor immune response," said Lee F. Allen, MD, PhD, chief medical officer of Argos. "We remain focused on aggressively advancing our development program through late-stage clinical research, and continue to be encouraged by the long-term outcomes from the Phase 2 study."

Argos is currently evaluating AGS-003 in combination with standard-of-care targeted therapy in the pivotal ADAPT Phase 3 clinical trial for the treatment of mRCC. Enrollment in this 462-patient study was initiated in February 2013 and completed in July 2015. The Independent Data Monitoring Committee (IDMC) for this study most recently recommended continuation of the study following a meeting in June 2016, with the next IDMC meeting planned for February 2017. In addition, AGS-003 is being studied in Phase 2 investigator-initiated clinical trials as neoadjuvant therapy for RCC and for the treatment of non-small cell lung cancer (NSCLC).

To read the full report in the Kidney Cancer Journal, visit View Source

About the Arcelis Technology Platform
Arcelis is a precision immunotherapy technology that captures both mutated and variant antigens that are specific to each patient’s individual disease. It is designed to overcome immunosuppression by producing a specifically targeted, durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to the treatment of a wide range of different cancers and infectious diseases, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized immunotherapies. The Arcelis process uses only a small disease sample or biopsy as the source of disease-specific antigens, and the patient’s own dendritic cells, which are optimized from cells collected by a leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease-specific antigens. These activated, antigen-loaded dendritic cells are then formulated with the patient’s plasma, and administered via intradermal injection as an individualized immunotherapy.