On November 3, 2016 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported financial results for the three and nine months ended September 30, 2016, and provided an operating forecast and program updates (Press release, Ligand, NOV 3, 2016, View Source [SID1234516346]). Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time to discuss this announcement and answer questions.

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"Our solid third quarter financial performance is highlighted by all-time high royalty revenues. In addition, we had a very active quarter with new licensings further increasing our portfolio of partnered assets," said John Higgins, Chief Executive Officer of Ligand. "Novartis continues to make excellent progress with growing sales, expanding indications and entering new geographies with Promacta. Amgen is focused on growing Kyprolis, and Spectrum’s product Evomela is showing good momentum in sales growth following its launch earlier this year. Also, recent positive clinical and regulatory milestones were achieved with a few of our more important portfolio programs, notably for programs or technologies licensed to Retrophin, Lundbeck and Melinta. We also initiated a Phase 2 clinical trial with LGD-6972 for the treatment of type 2 diabetes mellitus."

Ligand is in the process of evaluating certain deferred tax assets (DTA) recorded in the third quarter of 2015. Ligand is reviewing the amount of net operating loss carryforwards recorded as a result of capitalized R&D expenses associated with two acquisitions accounted for in 2010. As a result, the amount of DTA Ligand recorded in connection with the release of its valuation allowance could be reduced by approximately 10% of the $217 million DTA booked in the third quarter of 2015. The impact of the reduction would reduce the one-time DTA gain and would reduce GAAP net income for that period by the same amount. The balance sheet for the third quarter of 2015 and every subsequent period would reflect the reduction in DTA. The 2015 GAAP net income and earnings per share, which would be impacted by the reduction in DTA, are not available at this time, but will be reported in Ligand’s Form 10-Q for the third quarter of 2016, which will include Ligand’s conclusion regarding the reduction in DTA. The GAAP and adjusted net income and EPS figures for the three and nine month periods ended September 30, 2016 would be unaffected by the changes.

Third Quarter 2016 Financial Results

Total revenues for the third quarter of 2016 were $21.6 million, compared with $17.7 million for the same period in 2015. Royalty revenues were $15.7 million, compared with $9.8 million for the same period in 2015 primarily due to higher royalties from Promacta and Kyprolis. Material sales were $4.2 million, compared with $6.0 million for the same period in 2015 due to timing of Captisol purchases for use in clinical trials and commercial products. License and milestone revenues were $1.7 million, compared with $1.9 million for the same period in 2015.

Cost of goods sold was $1.0 million for the third quarter of 2016, compared with $1.3 million for the same period in 2015 due to the timing and mix of Captisol sales. Amortization of intangibles was $2.7 million, compared with $0.6 million for the same period in 2015 due primarily to additional amortization of intangibles related to the acquisition of OMT. Research and development expense was $6.3 million, compared with $1.9 million for the same period of 2015 as a result of the addition of OMT-related expenses, timing of spending on internal development programs and non-cash stock-based compensation expense. General and administrative expense was $6.3 million, compared with $5.0 million for the same period in 2015 due to costs associated with OMT and non-cash stock-based compensation expense.

GAAP net income for the third quarter of 2016 was $0.6 million, or $0.03 per share. Adjusted net income for the third quarter of 2016 was $13.5 million, or $0.62 per diluted share, compared with adjusted net income for the same period in 2015 of $12.0 million, or $0.57 per diluted share. See "Adjusted Financial Measures" and the accompanying table below for the adjusted calculations and reconciliation to comparable GAAP financial measures.

As of September 30, 2016, Ligand had cash, cash equivalents and short-term investments of $124.1 million.

Year-to-Date Financial Results

Total revenues for the nine months ended September 30, 2016 were $70.8 million, compared with $50.7 million for the same period in 2015. Royalty revenues were $39.8 million, compared with $26.6 million for the same period in 2015 primarily due to higher royalties from Promacta and Kyprolis. Material sales were $13.5 million, compared with $20.5 million for the same period in 2015 due to timing of Captisol purchases for use in clinical trials and commercial products. License and milestone revenues were $17.5 million, compared with $3.6 million for the same period in 2015 due to the addition of OmniAb revenue as of January 2016 and the timing of milestones and upfront license fees.

Cost of goods sold was $2.7 million for the nine months ended September 30, 2016, compared with $4.9 million for the same period in 2015 due to the timing and mix of Captisol sales. Amortization of intangibles was $7.9 million, compared with $1.8 million for the same period in 2015 due primarily to additional amortization of intangibles related to the acquisition of OMT. Research and development expense was $14.8 million, compared with $8.7 million for the same period of 2015 as a result of timing of spending on internal development programs and non-cash stock-based compensation expense. General and administrative expense was $20.0 million, compared with $18.2 million for the same period in 2015 due to costs associated with OMT and non-cash stock-based compensation expense.

GAAP net income for the nine months ended September 30, 2016 was $1.5 million, or $0.07 per diluted share. Adjusted net income for the nine months ended September 30, 2016 was $45.3 million, or $2.09 per diluted share, compared with adjusted net income for the same period in 2015 of $57.3 million, or $2.75 per diluted share.

Revised Financial Forecast

The Company is revising expectations for full-year 2016 total revenues to be between $110 million and $114 million, and adjusted earnings per diluted share to be between $3.37 and $3.44. This compares to previous Company expectations for full-year 2016 total revenues to be between $115 million and $119 million, and adjusted earnings per diluted share to be between $3.41 and $3.46. The revised outlook for total revenues reflects expected lower sales for Captisol due to timing of certain regulatory and clinical events. The Company expects total revenues for the fourth quarter of 2016 to be between $39 million and $43 million, including approximately $19 million in royalty revenues. Fourth quarter adjusted earnings per diluted share is expected to be between $1.29 and $1.36. For 2017, we are maintaining our previously disclosed guidance of greater than $160 million of revenue and greater than $5.03 of adjusted earnings per diluted share.

The adjusted net income per diluted share guidance excludes non-cash stock-based compensation expense, non-cash debt-related costs, amortization related to acquisitions, changes in contingent liabilities, non-cash net losses of Viking Therapeutics equity, mark-to-market adjustment for amounts owed to licensors, fair value adjustments to Viking Therapeutics convertible note receivable and warrants, non-cash tax benefit (expense), unissued shares relating to the Senior Convertible Note and adjustments for discontinued operations, net of non-cash tax expense.

Third Quarter 2016 and Recent Business Highlights

Portfolio Program Progress

Promacta/Revolade

Novartis announced Q3 2016 net sales of Promacta (eltrombopag) of $168 million, a $51 million or 44% increase over Q3 2015. Novartis also announced that Promacta is now approved in more than 100 countries.
Kyprolis (carfilzomib), an Amgen Product Utilizing Captisol

On September 27, 2016, Amgen announced top-line results of the Phase 3 CLARION trial, which evaluated an investigational regimen of Kyprolis (carfilzomib), melphalan and prednisone (KMP) versus Velcade (bortezomib), melphalan and prednisone (VMP) for 54 weeks in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem-cell transplant. The trial did not meet the primary endpoint of superiority in progression-free survival (PFS). A Phase 3 study evaluating Kyprolis in combination with lenalidomide plus dexamethasone (KRd) versus Velcade in combination with lenalidomide plus dexamethasone (VRd) in newly diagnosed multiple myeloma patients called ENDURANCE, an investigator-sponsored study, is underway independently by the ECOG-ACRIN Cancer Research Group.
In July 2016, Amgen announced that the European Commission approved an extended indication for Kyprolis (carfilzomib), to be used in combination with dexamethasone alone, for adult patients with multiple myeloma who have received at least one prior therapy. Also, Ono Pharmaceuticals, holder of Kyprolis (carfilzomib) marketing rights in Japan, announced approval in Japan for treatment of patients with relapsed or refractory multiple myeloma.
Additional Pipeline and Partner Developments

Retrophin announced positive top-line results from the Phase 2 DUET study of sparsentan for the treatment of focal segmental glomerulosclerosis. The study achieved statistical significance in the primary efficacy endpoint for the overall sparsentan treatment group, demonstrating a greater than two-fold reduction of proteinuria compared to irbesartan after the eight-week, double-blind treatment period. Additional data from the Phase 2 DUET study of sparsentan for the treatment of focal segmental glomerulosclerosis will be presented at the late-breaking High-Impact Clinical Trials oral session at the American Society of Nephrology (ASN) Kidney Week 2016.
Lundbeck announced FDA approval of Carnexiv (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Ligand earned a $1.25 million milestone payment upon approval and is entitled to receive a royalty of 2.75% on net sales of Carnexiv.
Melinta Therapeutics announced that it has submitted NDAs to the FDA for approval of IV and oral Baxdela (delafloxacin) for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). With the submission, Ligand earned a $1.5 million milestone payment. If approved, Ligand is entitled to receive a 2.5% royalty on net sales of the IV formulation of Baxdela and an additional $1.5 million approval milestone payment. Baxdela was the subject of several poster presentations at IDWeek 2016, held October 26-30 at the New Orleans Ernest N. Morial Convention Center.
The FDA granted orphan designation to Merck’s Noxafil for treatment of invasive aspergillosis.
Viking Therapeutics announced the first patient has been dosed in the company’s Phase 2 clinical trial of VK2809 in patients with primary hypercholesterolemia and non-alcoholic fatty liver disease.
Viking Therapeutics announced positive top-line results from a proof-of-concept study of VK0214 in a mouse model of X-linked adrenoleukodystrophy (X-ALD), showing VK0214 rapidly reduced plasma very long chain fatty acid levels by more than 25% in treated animals compared with vehicle controls (p<0.01). Detailed study results were presented at the 86th Annual Meeting of the American Thyroid Association.
Aldeyra Therapeutics announced plans for ADX-102 (formerly NS2) for the first-ever vehicle-controlled Phase 3 clinical trial in noninfectious anterior uveitis, as well as a Phase 3 clinical trial in Sjögren-Larsson Syndrome. Aldeyra also announced the expected advancement of ADX-102 to a Phase 2b clinical trial in allergic conjunctivitis and the addition of a clinical program in dry eye syndrome.
Eli Lilly presented data on Prexasertib (LY2606368) demonstrating activity in patients with BRCA wild type sporadic high-grade serous ovarian cancer at the European Society for Medical Oncology 2016 Congress.
Merrimack Pharmaceuticals announced the FDA granted seribantumab (MM-121) Fast Track designation for development in patients with heregulin-positive, locally advanced or metastatic non-small cell lung cancer whose disease has progressed following immunotherapy.
Lubris BioPharma announced positive results of a clinical trial that showed recombinant human lubricin demonstrated significant improvement in both signs and symptoms of dry eye disease compared to sodium hyaluronate (HA). Results were published in the September issue of The Ocular Surface.
Opthea announced that the Phase 1 dose-escalation study of OPT-302 met its primary objective demonstrating safety and tolerability as monotherapy and in combination with the current wet AMD standard of care Lucentis. Opthea is recruiting patients for its Phase 2a dose-expansion trial and expects data by the end of 2016.
New Licensing Deals

Ligand announced worldwide license agreements with Gilead Sciences, F-Star Biotechnology Limited and TeneoBio to use certain or all of the OmniAb platform technologies to discover fully human antibodies. Ligand is eligible to receive annual access payments, sublicensing fees, milestone payments and royalties on future net sales of any antibodies discovered under these licenses.
Ligand announced licensing rights to four programs to Seelos Therapeutics including aplindore for the treatment of various CNS disorders, a CRTH2 antagonist for the treatment of respiratory disorders, a Captisol-enabled acetaminophen program for pain and fever management and an H3 receptor antagonist program for the treatment of narcolepsy. Ligand is entitled to receive milestones and net sales royalties ranging from 4% to 10% for the various programs licensed.
Ligand announced a license agreement for its LTP technology with Nucorion Pharmaceuticals, a venture-funded biotechnology company focused on developing anti-cancer and anti-viral agents initially directed to China, of which Ligand is a minority shareholder. Three initial programs fall under the license: NUC-202, a targeted anticancer analog for the treatment of hepatocellular carcinoma; NUC-404, a targeted nucleotide analog for the treatment of hepatitis B; and NUC-101, a targeted nucleotide analog for the treatment of hepatitis C. Ligand is eligible to receive milestones in addition to royalties ranging from 5% to 9% on future net sales of any approved program.
Internal Glucagon Receptor Antagonist (GRA) Program

Ligand announced initiation of a Phase 2 clinical trial with LGD-6972 for the treatment of type 2 diabetes mellitus (T2DM). The randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of LGD-6972, as an adjunct to diet and exercise, in subjects with T2DM whose blood glucose levels are inadequately controlled with metformin. Results from two Phase 1 clinical trials with LGD-6972 were published online in the August 2016 issue of the journal Diabetes, Obesity and Metabolism.
Adjusted Financial Measures

The adjusted financial measures discussed above and in the tables below for the three and nine months ended September 30, 2016 and 2015 exclude non-cash stock-based compensation expense, non-cash debt-related costs, amortization related to acquisitions, changes in contingent liabilities, non-cash net losses of Viking Therapeutics equity, mark-to-market adjustment for amounts owed to licensors, fair value adjustments to Viking Therapeutics convertible note receivable and warrants, non-cash tax benefit (expense), unissued shares relating to the Senior Convertible Note and adjustments for discontinued operations, net of non-cash tax expense.

Management has presented net income and net income per share on an adjusted basis. Ligand believes the presentation of adjusted financial measures provides useful supplementary information to investors and reflects amounts that are more closely aligned with the cash profits for the period. Ligand uses these adjusted financial measures in connection with its own budgeting and financial planning. These adjusted financial measures are in addition to, and not a substitute for, or superior to, measures of financial performance prepared in conformity with GAAP.

On November 3, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported that new data for duvelisib, an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2016 Annual Meeting, being held December 3-6, 2016 in San Diego (Press release, Verastem, NOV 3, 2016, View Source;p=RssLanding&cat=news&id=2219237 [SID1234516338]).
Data from DYNAMO, a Phase 2 monotherapy study evaluating the efficacy and safety of duvelisib in relapsed/refractory iNHL, will be presented in an oral session. Updated data from CONTEMPO, a Phase 1b/2 study evaluating duvelisib in combination with rituximab or obinutuzmab in treatment-naïve follicular lymphoma patients, and preclinical research on the role of Focal Adhesion Kinase (FAK) inhibition in AML, will be presented in a poster session.
Details for the presentations at ASH (Free ASH Whitepaper) are below:
Oral Presentation
Title: DYNAMO: A phase 2 study demonstrating the clinical activity of duvelisib in patients with relapsed refractory indolent non-Hodgkin lymphoma
Lead Author: Ian Flinn, M.D., Ph.D., Director, Hematologic Malignancies Program, Sarah Cannon Research Institute
Abstract Number: 1218
Location: San Diego Convention Center, Ballroom 20BC
Date and Time: Monday, December 5, 2016, 7:30 – 7:45 pm PT
The full abstract can be viewed here.
Poster Presentations
Title: Preliminary results in first-line treatment of follicular lymphoma with the oral dual PI3K-delta,gamma inhibitor, duvelisib, in combination with rituximab or obinutuzumab
Lead Author: Carla Casulo, M.D., Assistant Professor, Wilmot Cancer Institute, University of Rochester
Abstract Number: 2979
Location: San Diego Convention Center, Hall GH
Date and Time: Sunday, December 4, 2016, 6:00 – 8:00 pm PT
The full abstract can be viewed here.
Title: Inhibition of FAK Exerts Anti-Leukemic Activity and Potentiates ABT-199-Induced Apoptosis in AML
Lead Author: Bing Carter, Ph.D.., Associate Professor, Department of Leukemia – Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Abstract Number: 1574
Location: San Diego Convention Center, Hall GH
Date and Time: Saturday, December 3, 2016, 5:30 – 7:30 pm PT
The full abstract can be viewed here.
About the Tumor Microenvironment
The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T cells, myeloid-derived suppressor cells, M2 tumor-associated macrophages, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib, defactinib, VS-4718 and VS-5584 also target the tumor microenvironment as a mechanism of action to potentially improve a patient’s response to therapy.
About Duvelisib
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes that are known to help support the growth and survival of malignant B cells and T cells. PI3K signaling may lead to the proliferation of malignant B cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)4, and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL) that achieved its primary endpoint of overall response rate upon topline analysis of efficacy data5. Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T cell lymphoma.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

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On November 3, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported operating results for third-quarter 2016 and provided an update on the Company’s marketed product and development programs (Press release, TESARO, NOV 3, 2016, View Source [SID1234516336]).

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"We are very pleased to have submitted regulatory applications for niraparib in both the United States and in Europe for the maintenance treatment of patients with platinum-sensitive, recurrent ovarian cancer who are in response to platinum-based chemotherapy. Pre-launch activities are well underway in support of four potential product launches in 2017, including VARUBI IV and niraparib in the U.S and VARUBI oral and niraparib in Europe," said Lonnie Moulder, CEO of TESARO. "The recent ESMO (Free ESMO Whitepaper) 2016 Congress was very gratifying for TESARO, highlighted by the presentation of the landmark niraparib NOVA trial results during a Presidential Symposium by Dr. Mansoor Raza Mirza. We look forward to advancing our comprehensive ovarian cancer clinical program and expanding niraparib development into other tumor types in 2017."

Recent Business Highlights

The U.S. launch of VARUBI continues, and unit volume increased by 14% for the third quarter compared to the second quarter. For the month of September, VARUBI achieved a 28% market share in the oral NK-1 market in the U.S.
TESARO officially opened its international commercial headquarters in Zug, Switzerland on October 11.
Earlier this week, the rolling submission of a New Drug Application (NDA) for niraparib to the U.S. Food and Drug Administration (FDA) was completed for the maintenance treatment of patients with recurrent, platinum-sensitive ovarian cancer who are in response to platinum-based chemotherapy. The indication proposed in the niraparib NDA provides for the use of niraparib regardless of tumor biomarker status, and it is anticipated that the BRACAnalysis CDx and myChoice HRD tests would be available to physicians as complementary diagnostics.
The Marketing Authorisation Application (MAA) for niraparib has been submitted to and accepted for review by the European Medicines Agency (EMA) for the maintenance treatment of patients with recurrent, platinum-sensitive ovarian cancer who are in response to platinum-based chemotherapy.
The niraparib Phase 3 ENGOT-OV16/NOVA clinical trial results were presented at the Presidential Symposium at the ESMO (Free ESMO Whitepaper) 2016 Congress by Dr. Mansoor Raza Mirza, M.D., Medical Director of the Nordic Society of Gynecologic Oncology (NSGO) and principal investigator. These data were simultaneously published in the New England Journal of Medicine.
Planning is underway to support initiation of an Early Access Program (EAP) for niraparib in the United States and Europe.
Janssen initiated a Phase 2 clinical trial with niraparib in monotherapy in men with metastatic castration resistant prostate cancer (mCRPC) and recently began a Phase 1 safety and pharmacokinetics study of niraparib plus apalutamide (ARN-509).
Enrollment continues in the PRIMA trial for patients with first-line ovarian cancer, the QUADRA trial of niraparib for the treatment of patients with ovarian cancer who have received three or more prior lines of chemotherapy, and in the BRAVO trial for patients with germline BRCA-mutated, metastatic breast cancer.
Enrollment continues in the TOPACIO trial of niraparib plus KEYTRUDA (pembrolizumab) in patients with ovarian cancer or with triple negative breast cancer and in the AVANOVA trial of niraparib plus bevacizumab in patients with ovarian cancer.
TESARO and Zai Lab (Shanghai) Co., Ltd. announced a collaboration to support the development and commercialization of niraparib for patients in China and the potential to advance two immuno-oncology programs outside of China.
The Phase 1 dose escalation study of TSR-022, an anti-TIM-3 antibody candidate, was initiated in July, and the Phase 1 trial of TSR-042, an anti-PD-1 antibody candidate, continues to enroll.
Third Quarter 2016 Financial Results

TESARO reported a net loss of $101.2 million, or ($1.98) per share, for the third quarter of 2016, compared to a net loss of $66.6 million, or ($1.66) per share, for the third quarter of 2015.

Net product revenue for the third quarter of 2016 totaled $2.8 million and included sales of VARUBI from specialty pharmacy customers to patients and from specialty distributors to providers that were made during the third quarter, as well as sales from specialty distributors to providers that occurred in the second quarter of 2016. License, collaboration and other revenue for the third quarter of 2016 totaled $0.9 million and included amortization of milestone payments and shipments of clinical materials under our license agreements with Hengrui and Janssen.

Research and development expenses increased to $60.8 million for the third quarter of 2016, compared to $40.1 million for the third quarter of 2015, driven primarily by higher costs related to the ongoing registration trials of niraparib, manufacturing costs associated with niraparib, and the initiation of clinical studies for our immuno-oncology portfolio, in addition to increased headcount.

Selling, general and administrative expenses increased to $37.7 million for the third quarter of 2016, compared to $22.8 million for the third quarter of 2015, primarily due to higher commercial headcount, including the establishment of a U.S. field sales organization in August 2015, commercial activities in support of the launch of VARUBI, costs associated with the establishment of our international headquarters, and higher professional service fees.

Operating expenses, as described above, include total non-cash, stock-based compensation expense of $12.9 million for the third quarter of 2016, compared to $8.1 million for the third quarter of 2015.

As of September 30, 2016, TESARO had approximately $647 million in cash and cash equivalents, which includes the $409 million in net proceeds from a follow-on offering of 5.3 million shares of common stock that was completed in July 2016. For the quarter ended September 30, 2016, TESARO had approximately 51.2 million shares outstanding on a weighted average basis.

In anticipation of four product launches in 2017, TESARO will continue to invest in pre-launch inventory manufacturing, development of supply chain capabilities and capacity, and expansion of European and targeted U.S. commercial operations, in addition to making milestone payments for regulatory submissions. As a result of these investments, the Company expects its cash and cash equivalents balance to decline by approximately $100 million during the fourth quarter of 2016.

Corporate Objectives

The following is a summary of TESARO’s key objectives:

VARUBI (rolapitant):

Achieve #1 market share position within the oral NK-1 receptor antagonist market by year-end 2016 in the U.S.;
Launch VARUBI IV into the U.S. market in 1H 2017, pending FDA approval;
Establish a European commercial organization; and
Launch VARUBI oral in Europe in 1H 2017, pending EMA approval.
Niraparib:

Continue commercial preparations in support of the launches of niraparib in the U.S. in 1H 2017 and Europe in 2H 2017, pending regulatory approvals;
Report QUADRA data in 2H 2017;
Report Phase 3 BRAVO data in 2H 2017;
Finalize a potential lung cancer registration strategy and initiate development program in 1H 2017; and
Determine the potential registration strategy for niraparib plus an anti-PD-1 antibody in ovarian cancer and triple-negative breast cancer in 2H 2017.
Immuno-Oncology Portfolio:

Identify a dose and schedule for TSR-042 (anti-PD-1 antibody) by the end of 2016;
Select at least one bispecific antibody clinical candidate by the end of 2016;
Identify the first clinical candidate within the MD Anderson collaboration in 1H 2017;
Initiate a Phase 1 study of TSR-033 (anti-LAG-3 antibody) in 1H 2017;
Finalize the TSR-042 registration strategy and initiate a registration program in 1H 2017; and
Initiate a Phase 1 clinical trial of TSR-022 in combination with an anti-PD-1 antibody in mid-2017.

On November 3, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that it will present a total of 16 company-sponsored abstracts at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place in San Diego from December 3 to 6, 2016 (Press release, Takeda, NOV 3, 2016, View Source [SID1234516333]). Takeda’s presentations at this year’s meeting will feature Phase 3 and earlier-stage data from clinical studies across the company’s broad hematology-oncology portfolio.

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"Even as we convene at ASH (Free ASH Whitepaper) to discuss the latest innovations in hematology, we recognize that there is still a need for additional effective, convenient and sustainable therapies that address the issues impacting patients and their families on a daily basis," said Christophe Bianchi MD, President, Takeda Global Oncology Business Unit. "The data we are presenting this year illustrate our enduring commitment to the development and evaluation of therapies that may transform patient care across various types of complex and refractory blood cancers – lymphoma, multiple myeloma, myelodysplastic syndromes and more. From our Phase 3 NINLARO and ADCETRIS programs to our earliest preclinical studies, we hope to continue to make strides toward fulfilling unmet needs and providing additional treatment options for patients with hematologic malignancies in the future."

Takeda will present on a wide range of topics, including full data from the Phase 3 ALCANZA study of ADCETRIS in CD30-positive cutaneous T-cell lymphoma, as well as 5-year overall survival data for the pivotal Phase 2 study of ADCETRIS in systemic Anaplastic Large Cell Lymphoma (sALCL) in partnership with Seattle Genetics for the first time. The company also plans to share new data from a post-hoc biomarker analysis for the Phase 3 TOURMALINE-MM1 trial, exploring the association between expression of the c-MYC gene and improved progression-free survival in patients with relapsed and/or refractory multiple myeloma receiving a regimen of NINLARO plus lenalidomide and dexamethasone versus the placebo regimen.

In addition to investigational data for NINLARO and ADCETRIS, several presentations on findings from clinical studies will highlight the scope of Takeda’s research and development organization. The company will share analyses on pevonedistat, a first-in-class selective inhibitor of the NEDD8-activating enzymes in a clinical trial for myelodysplastic syndromes and acute myeloid leukemia. This inhibitor disrupts cullin-ring ligase mediated protein turnover leading to apoptosis in cancer cells. Further, Takeda will present findings from studies of TAK-659, an investigational dual inhibitor of SYK and FLT-3 kinases, for the treatment of various types of lymphoma and acute myeloid leukemia.

Among the 16 Takeda-sponsored abstracts accepted for presentation during ASH (Free ASH Whitepaper) 2016, selected highlights include:

Note: all times listed are in Pacific Standard Time

ADCETRIS (brentuximab vedotin):

Brentuximab Vedotin Demonstrates Significantly Superior Clinical Outcomes in Patients with CD30-Expressing Cutaneous T-Cell Lymphoma Versus Physician’s Choice (Methotrexate or Bexarotene): The Phase 3 Alcanza Study. Abstract 182. Oral presentation. Saturday, December 3, 2:15 p.m., Room 6AB. (San Diego Convention Center)
Five-Year Survival Data from a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma. Abstract 4144. Monday, December 5, 6:00 – 8:00 p.m., Hall GH.* (San Diego Convention Center)
*Presentation by Seattle Genetics

NINLARO (ixazomib) capsules:

Higher c-MYC Expression Is Associated with Ixazomib-Lenalidomide-Dexamethasone (IRd) Progression-Free Survival (PFS) Benefit Versus Placebo-Rd: Biomarker Analysis of the Phase 3 Tourmaline-MM1 Study in Relapsed/Refractory Multiple Myeloma (RRMM). Abstract 243. Oral presentation. Saturday, December 3, 4:30 p.m., Seaport Ballroom ABCD. (Manchester Grand Hyatt San Diego)
Longer Time to Best Response and Depth of Response Are Associated with Improved Duration of Best Achieved Response and Progression-Free Survival (PFS): Post-Hoc Analysis of Phase 3 Tourmaline-MM1 Trial in Relapsed/Refractory Multiple Myeloma (RRMM). Abstract 2134. Saturday, December 3, 5:30-7:30 p.m., Hall GH. (San Diego Convention Center)
Phase 2 Study of the All-Oral Combination of Ixazomib Plus Cyclophosphamide and Low-Dose Dexamethasone (ICd) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM). Abstract 3327. Sunday, December 4, 6:00 -8:00 p.m., Hall GH. (San Diego Convention Center)
Pipeline:

Results of a Clinical Study of Pevonedistat (Pev), a First-in-Class NEDD8-Activating Enzyme (NAE) Inhibitor, Combined with Azacitidine (Aza) in Older Patients (Pts) with Acute Myeloid Leukemia (AML). Abstract 98. Oral presentation. Saturday, December 3, 9:45 a.m., Grand Hall A. (Manchester Grand Hyatt San Diego)
A Phase 1b/2 Study of TAK-659, an Investigational Dual SYK and FLT-3 Inhibitor, in Patients (Pts) with Relapsed or Refractory Acute Myelogenous Leukemia (R/R AML). Abstract 2834, Sunday, December 4, 6:00 -8:00 p.m., Hall GH. (San Diego Convention Center)
Updated Results from a Phase 1 Study of TAK-659, an Investigational and Reversible SYK Inhibitor, in Patients (Pts) with Advanced Solid Tumor or Lymphoma Malignancies. Abstract 624. Oral presentation. Monday, December 5, 8:15 a.m., Room 6B. (San Diego Convention Center)
For more information, the ASH (Free ASH Whitepaper) program is available here: View Source

About NINLAROTM (ixazomib) capsules

NINLAROTM (ixazomib) is an oral proteasome inhibitor which is also being studied across the continuum of multiple myeloma treatment settings as well as in relapsed or refractory systemic light-chain (AL) amyloidosis. It was the first oral proteasome inhibitor to enter Phase 3 clinical trials and to receive approval. NINLARO was approved by the U.S. Food and Drug Administration (FDA) in November 2015 following a priority review. In the U.S., NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory systemic light-chain (AL) amyloidosis, a related ultra orphan disease, in 2014.

The comprehensive ixazomib clinical development program, TOURMALINE, further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. TOURMALINE includes a total of five ongoing pivotal trials – four, which together are investigating every major multiple myeloma patient population, and one in light-chain amyloidosis:

TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT; this study is currently enrolling
TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis; this study is currently enrolling
In addition to the TOURMALINE program, ixazomib is being evaluated in multiple therapeutic combinations for various patient populations in investigator initiated studies globally.

NINLAROTM (ixazomib) capsules: Global Important Safety Information

SPECIAL WARNINGS AND PRECAUTIONS

Thrombocytopenia has been reported with NINLARO (28% vs. 14% in the NINLARO and placebo regimens, respectively) with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. It did not result in an increase in hemorrhagic events or platelet transfusions. Monitor platelet counts at least monthly during treatment with NINLARO and consider more frequent monitoring during the first three cycles. Manage with dose modifications and platelet transfusions as per standard medical guidelines.

Gastrointestinal toxicities have been reported in the NINLARO and placebo regimens respectively, such as diarrhea (42% vs. 36%), constipation (34% vs. 25%), nausea (26% vs. 21%), and vomiting (22% vs. 11%), occasionally requiring use of antiemetic and anti-diarrheal medications, and supportive care.

Peripheral neuropathy was reported with NINLARO (28% vs. 21% in the NINLARO and placebo regimens, respectively). The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.
Peripheral edema was reported with NINLARO (25% vs. 18% in the NINLARO and placebo regimens, respectively). Evaluate patients for underlying causes and provide supportive care, as necessary. Adjust the dose of dexamethasone per its prescribing information or the dose of NINLARO for severe symptoms.

Cutaneous reactions occurred in 19% of patients in the NINLARO regimen compared to 11% of patients in the placebo regimen. The most common type of rash reported in both regimens was maculo-papular and macular rash. Manage rash with supportive care, dose modification or discontinuation.

Hepatotoxicity, drug-induced liver injury, hepatocellular injury, hepatic steatosis, and hepatitis cholestatic have been uncommonly reported with NINLARO. Monitor hepatic enzymes regularly and adjust dose for Grade 3 or 4 symptoms.

Pregnancy- NINLARO can cause fetal harm. Advise male and females patients of reproductive potential to use contraceptive measures during treatment and for an additional 90 days after the final dose of NINLARO. Women of childbearing potential should avoid becoming pregnant while taking NINLARO due to potential hazard to the fetus. Women using hormonal contraceptives should use an additional barrier method of contraception.

Lactation- It is not known whether NINLARO or its metabolites are excreted in human milk. There could be potential adverse events in nursing infants and therefore breastfeeding should be discontinued.

SPECIAL PATIENT POPULATIONS

Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.

Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease (ESRD) requiring dialysis. NINLARO is not dialyzable and, therefore, can be administered without regard to the timing of dialysis.

DRUG INTERACTIONS

Co-administration of strong CYP3A inducers with NINLARO is not recommended.

ADVERSE REACTIONS

The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen, and greater than in the placebo regimen, were diarrhea (42% vs. 36%), constipation (34% vs. 25%), thrombocytopenia (28% vs. 14%), peripheral neuropathy (28% vs. 21%), nausea (26% vs. 21%), peripheral edema (25% vs. 18%), vomiting (22% vs. 11%), and back pain (21% vs. 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.

For US Prescribing Information: View Source

For Canada Product Monograph: View Source

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing proprietary technology by Seattle Genetics. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). In January 2016, the European Commission approved a Type II variation to include data on the retreatment of adult patients with Hodgkin lymphoma or sALCL who previously responded to ADCETRIS and who later relapse. In June 2016, the European Commission extended the current conditional approval of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT. ADCETRIS has received marketing authorization by regulatory authorities in 65 countries. See important safety information below.

ADCETRIS is being evaluated broadly in more than 45 ongoing clinical trials, including the Phase 3 ALCANZA trial in CD30-positive cutaneous T cell lymphoma (CTCL) and two additional Phase 3 studies, one in frontline classical Hodgkin lymphoma (ECHELON-1) and one in frontline CD30-positive mature T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) Global Important Safety Information

Active Ingredient: brentuximab vedotin

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

INDICATIONS

ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL):

1. following autologous stem cell transplant (ASCT) or

2. following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option.

ADCETRIS is indicated for the treatment of adult patients with CD30+ HL at increased risk of relapse or progression following ASCT.

ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. In addition, combined use of ADCETRIS with bleomycin is contraindicated as it causes pulmonary toxicity.

SPECIAL WARNINGS & PRECAUTIONS

Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in PML and death can occur in patients treated with ADCETRIS. PML has been reported in patients who received ADCETRIS after receiving multiple prior chemotherapy regimens.

Patients should be closely monitored for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain, and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. ADCETRIS dosing should be held for any suspected case of PML and should be permanently discontinued if a diagnosis of PML is confirmed.

Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. ADCETRIS should be held for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.

Pulmonary Toxicity: Cases of pulmonary toxicity, some with fatal outcomes, have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. New or worsening pulmonary symptoms should be promptly evaluated and treated appropriately.

Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Patients should be carefully monitored during treatment for emergence of possible serious and opportunistic infections.

Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have occurred with ADCETRIS. Patients should be carefully monitored during and after an infusion. If anaphylaxis occurs, administration of ADCETRIS should be immediately and permanently discontinued and appropriate medical therapy should be administered. If an IRR occurs, the infusion should be interrupted and appropriate medical management instituted. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. IRRs are more frequent and more severe in patients with antibodies to ADCETRIS.

Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS. These patients should be monitored closely and managed according to best medical practice.

Peripheral neuropathy (PN): ADCETRIS treatment may cause PN, both sensory and motor. ADCETRIS-induced PN is typically cumulative and reversible in most cases. Patients should be monitored for symptoms of PN, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay and a dose reduction or discontinuation of ADCETRIS.

Hematological toxicities: Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (equal to or greater than one week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose.

Febrile neutropenia: Febrile neutropenia has been reported. Patients should be monitored closely for fever and managed according to best medical practice if febrile neutropenia develops.

Stevens-Johnson syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have been reported. If SJS or TEN occurs, treatment with ADCETRIS should be discontinued and appropriate medical therapy should be administered.

Gastrointestinal (GI) Complications: GI complications, some with fatal outcomes, including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, have been reported. New or worsening GI symptoms should be promptly evaluated and treated appropriately.

Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Liver function should be tested prior to treatment initiation and routinely monitored in patients receiving ADCETRIS. Patients experiencing hepatotoxicity may require a delay, dose modification, or discontinuation of ADCETRIS.

Hyperglycemia: Hyperglycemia has been reported during trials in patients with an elevated body mass index (BMI) with or without a history of diabetes mellitus. However, any patient who experiences an event of hyperglycemia should have their serum glucose closely monitored. Anti-diabetic treatment should be administered as appropriate.

Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations. The recommended starting dose in patients with hepatic impairment or severe renal impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with renal or hepatic impairment should be closely monitored for adverse events.

Sodium content in excipients: This medicinal product contains a maximum of 2.1 mmol (or 47 mg) of sodium per dose. To be taken into consideration for patients on a controlled sodium diet.

INTERACTIONS

Patients who are receiving a strong CYP3A4 and P-gp inhibitor, concomitantly with ADCETRIS may have an increased risk of neutropenia and should be closely monitored. Co-administration of ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of ADCETRIS but it appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. ADCETRIS is not expected to alter the exposure to drugs that are metabolized by CYP3A4 enzymes.

PREGNANCY: Women of childbearing potential should be using two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. There are no data from the use of ADCETRIS in pregnant women, although studies in animals have shown reproductive toxicity. ADCETRIS should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus. If a pregnant woman needs to be treated, she should be clearly advised on the potential risk to the fetus.

LACTATION (breast-feeding): There are no data as to whether ADCETRIS or its metabolites are excreted in human milk, therefore a risk to the newborn/infant cannot be excluded. With the potential risk, a decision should be made whether to discontinue breast-feeding or discontinue/abstain from therapy with ADCETRIS.

FERTILITY: In nonclinical studies, ADCETRIS treatment has resulted in testicular toxicity, and may alter male fertility. Men being treated with this medicine are advised not to father a child during treatment and for up to 6 months following the last dose.

ADVERSE REACTIONS

Serious adverse drug reactions were: pneumonia, acute respiratory distress syndrome, headache, neutropenia, thrombocytopenia, constipation, diarrhea, vomiting, nausea, pyrexia, peripheral motor neuropathy, peripheral sensory neuropathy, hyperglycemia, demyelinating polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome.

In the clinical studies of ADCETRIS, adverse reactions defined as very common (≥1/10) were: infection, upper respiratory tract infection, neutropenia, PN (sensory and motor), cough, dyspneoa, diarrhea, nausea, vomiting, constipation, abdominal pain, alopecia, pruritus, myalgia, arthralgia, fatigue, chills, pyrexia, infusion-related reactions and weight decreased. Adverse reactions defined as common (≥1/100 to <1/10) were: Sepsis/septic shock, herpes zoster, pneumonia, herpes simplex, anemia, thrombocytopenia, hyperglycemia, dizziness, demyelinating polyneuropathy, ALT/AST increased, rash, and back pain.

On November 3, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported financial results for the third quarter ended September 30, 2016. Loss from operations for the three months ended September 30, 2016 was $8.5 million (Press release, Sunesis, NOV 3, 2016, View Source;p=RssLanding&cat=news&id=2219049 [SID1234516331]). As of September 30, 2016, cash, cash equivalents and marketable securities totaled $24.3 million.

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"Since the beginning of the third quarter we have made significant progress in advancing both our vosaroxin and BTK inhibitor programs. In addition, in October, we secured the financial resources from leading life sciences investors which will help us reach several potential value inflection points," said Daniel Swisher, Chief Executive Officer of Sunesis. "The potential milestones include a marketing authorization decision on vosaroxin in Europe, the potential for a corresponding partnership and product launch in this territory, and the initiation and prosecution of a Phase 1B/2 study of SNS-062, our differentiated, non-covalent BTK-inhibitor, in patients with B-cell malignancies."

"The European regulatory review of vosaroxin has now resumed, following our response to the Day 120 List of Questions, and we look forward to receiving the EMA Day 180 List of Outstanding Issues before year-end. We were also pleased to present Phase 1A Healthy Volunteer Study results demonstrating a favorable safety, pharmacokinetic and pharmacodynamic profile for SNS-062 at the ESH Conference on New Concepts in B-Cell Malignancies in September."

Third Quarter 2016 and Recent Highlights

Submission of Responses to the EMA Day 120 List of Questions for the Marketing Authorization Application for Vosaroxin. In October, Sunesis announced that it submitted its responses to European Medicines Agency (EMA) Day 120 List of Questions issued by the Committee for Medicinal Products for Human Use (CHMP) as part of the centralized review process of the Marketing Authorization Application (MAA) for vosaroxin based on data from the VALOR trial, as a treatment for relapsed/refractory acute myeloid leukemia (AML) in patients aged 60 years and older. Sunesis expects to receive the EMA Day 180 List of Outstanding Issues before year-end.

Presentation of Dose Escalation Results from the Phase 1A Healthy Volunteer Study Evaluating Oral Non-Covalent BTK inhibitor SNS-062. In September, Sunesis announced results from the Company’s Phase 1A study in healthy volunteers evaluating oral non-covalent BTK inhibitor SNS-062. The study demonstrated a favorable safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile for SNS-062 in healthy subjects. The results were presented on Saturday, September 10th at the European School of Haematology’s (ESH) 2nd International Conference on New Concepts in B-Cell Malignancies at the Estoril Congress Centre in Estoril, Portugal. The presentation, titled "A Phase 1A Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the Noncovalent Bruton Tyrosine Kinase (BTK) Inhibitor SNS-062 in Healthy Subjects: Preliminary Results" is available on the Sunesis website at www.sunesis.com.

Completion of $25.9 million Financing. In October, Sunesis announced the completion of an equity financing with net proceeds of $25.9 million. The financing attracted participation from leading biotechnology investors.

Announced Publication in "Drugs" Detailing Molecular and Pharmacologic Properties of Vosaroxin. In August, Sunesis announced the publication of an article detailing the molecular and pharmacologic properties of vosaroxin as a new therapeutic for acute myeloid leukemia (AML) in the journal Drugs. Vosaroxin is the first quinolone-based topoisomerase II inhibitor studied in clinical trials in oncology. The article, titled "Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative Vosaroxin: A New Therapeutic for Acute Myeloid Leukemia," is available online and appeared in the September 2016 print issue of Drugs. The authors describe how the unique chemical and pharmacologic characteristics of vosaroxin may contribute to the efficacy and safety profile observed in Sunesis’ Phase 3 VALOR trial in first relapsed or refractory AML.
Financial Highlights

Cash, cash equivalents and marketable securities totaled $24.3 million as of September 30, 2016, as compared to $46.4 million as of December 31, 2015. The decrease of $22.1 million was primarily due to $28.9 million of net cash used in operating activities, $8.0 million of payments against notes payable, partially offset by $14.8 million in net loan proceeds. An additional $25.9 million in net proceeds was raised in the October 2016 equity financing, resulting in pro-forma September 30, 2016 cash, cash equivalents and marketable securities of $50.2 million. This capital is expected to be sufficient to fund operations into 2018.

Revenue for the three and nine months ended September 30, 2016 was $0.6 million and $1.9 million as compared to $0.7 million and $2.4 million for the same periods in 2015. The decrease between the periods was primarily due to the extension of the amortization period of our deferred revenue.

Research and development expense was $5.3 million and $18.1 million for the three and nine months ended September 30, 2016 as compared to $5.3 million and $16.1 million for the same periods in 2015. The increase of $2.0 million between the comparable nine month periods was primarily due to an increase in professional services, clinical trials and medical affairs expenses.

General and administrative expense was $3.9 million and $12.2 million for the three and nine months ended September 30, 2016 as compared to $4.0 million and $14.3 million for the same periods in 2015. The decrease of $0.1 million between the comparable three month periods was primarily due to a decrease in personnel expenses. The decrease of $2.1 million between the comparable nine month periods was primarily due to decrease in outside service costs.

Interest expense was $0.5 million and $1.2 million for the three and nine months ended September 30, 2016 as compared to $0.2 million and $0.7 million for the same periods in 2015. The increases in the 2016 periods were primarily due to the increase in the notes payable.

Net other income was nil and $0.1 million for the three and nine months ended September 30, 2016 as compared to net other income of $1.8 million and $3.6 million for the same period in 2015. The decrease in net other income is related to the quarterly re-valuation of warrant liabilities.

Cash used in operating activities was $29.0 million for the nine months ended September 30, 2016, as compared to $29.5 million for the same period in 2015. Net cash used in the 2016 period resulted primarily from the net loss of $29.5 million and changes in operating assets and liabilities of $3.6 million, including the payment of a final fee of $1.2 million under the Oxford Loan Agreement, partially offset by net adjustments for non-cash items of $4.1 million. Net cash used in the 2015 period resulted primarily from the net loss of $25.1 million and changes in operating assets and liabilities of $5.6 million, partially offset by net adjustments for non-cash items of $1.2 million.

Sunesis reported loss from operations of $8.5 million and $28.4 million for the three and nine months ended September 30, 2016 as compared to $8.6 million and $28.0 million for the same periods in 2015. Net loss was $9.0 million and $29.5 million for the three and nine months ended September 30, 2016, as compared to $7.0 million and $25.1 million for the same periods in 2015.