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SRI International to Support Anti-Cancer Vaccine Studies for NIH Center

On March 11, 2016 SRI International reported it will carry out pre-clinical studies on compounds and vaccines to determine if they can act as preventive agents against cancer under a $19.8 million contract with a National Institutes of Health center (Press release, SRI International, MAR 11, 2016, View Source [SID:1234509502]).

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The company said Thursday its biosciences division will work to examine the effectiveness of experimental vaccines and test biomarkers in an effort to parallel how the body responds to treatment.

NIH’s National Cancer Institute has awarded SRI two task orders to develop a mesothelin-based vaccine against ovarian cancer and novel models to test how preventative agents act against the disease.

"Discovery and development of cancer preventative agents is an area that is underserved, primarily because the length of required clinical trials can be resource-prohibitive for many companies," said Lidia Sambucetti, SRI Biosciences senior director for cancer biology, center for discovery technologies and principal investigator for the contract.

Sambucetti added the project aims to address this issue through the company’s biomarker discovery efforts in an effort to shorten the time of clinical trials.

SRI researchers are also working on a model to test experimental drugs to prevent ovarian cancer.

XALKORI® (crizotinib) Approved by U.S. FDA for the Treatment of Patients with ROS1-Positive Metastatic Non-Small Cell Lung Cancer

On March 11, 2016 Pfizer Inc. (NYSE:PFE) reported that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for XALKORI (crizotinib) to treat patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive (Press release, Pfizer, MAR 11, 2016, View Source [SID:1234509499]).

In 2015, the FDA granted Breakthrough Therapy and Priority Review designations for this indication. XALKORI also is indicated for patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.1

"Today’s approval of XALKORI for ROS1-positive metastatic NSCLC represents an important milestone for patients who previously had limited treatment options," said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. "As the only FDA-approved biomarker-driven therapy that includes two distinct molecular targets in metastatic NSCLC, ROS1 and ALK, XALKORI exemplifies our commitment to precision drug development and to identifying the right treatment for the right patient."

ROS1 rearrangements occur when the ROS1 gene attaches to another gene and changes the way each gene normally functions, which can contribute to cancer-cell growth. Epidemiology data suggest that ROS1 rearrangements occur in approximately one percent of NSCLC cases.2 Of the estimated 1.5 million new cases of NSCLC worldwide each year, roughly 15,000 may be driven by oncogenic ROS1 fusions.2,3,4

"The approval of crizotinib for metastatic ROS1-positive non-small cell lung cancer represents another significant step forward in biomarker-driven cancer care," said Dr. Alice Shaw, Associate Professor of Medicine at Massachusetts General Hospital and Harvard Medical School, and principal study investigator. "As with ALK-positive lung cancer, ROS1-positive lung cancer defines a distinct subset of patients for whom crizotinib is efficacious."

The approval is based on a multicenter, single-arm Phase 1 study (Study 1001) that included 50 patients with ROS1-positive metastatic NSCLC treated with 250 mg of XALKORI orally twice daily. The efficacy outcome measures in this study were objective response rate and duration of response.1

The results of this study showed that XALKORI exhibited marked anti-tumor activity in patients with ROS1-positive metastatic NSCLC, with an objective response rate of 66 percent (95% CI: 51%, 79%) by an independent radiology review. There was one complete response and 32 partial responses. The median duration of response was 18.3 months (95% CI: 12.7 months, not reached). Additionally, the safety profile of XALKORI in ROS1-positive metastatic NSCLC was generally consistent with that observed in patients with ALK-positive metastatic NSCLC.1

An FDA-approved test for the detection of ROS1 rearrangements in NSCLC is not currently available; however, laboratory developed tests are available. A companion diagnostic test is currently under development to identify patients with ROS1-positive metastatic NSCLC who may benefit from treatment with XALKORI.

Additionally, the European Medicines Agency (EMA) is reviewing an application to extend the marketing authorization of XALKORI to include the treatment of adult patients with ROS1-positive advanced NSCLC. In Europe, XALKORI is indicated for the first-line treatment of adults with ALK-positive advanced NSCLC and for the treatment of adults with previously treated ALK-positive advanced NSCLC.

About XALKORI (crizotinib)

XALKORI is a kinase inhibitor indicated in the U.S. for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test, and for the treatment of patients with metastatic NSCLC whose tumors are ROS1-positive. XALKORI was the first ALK inhibitor approved in the U.S. and has been used to treat more than 8,000 patients to date.5

XALKORI Important Safety Information

Hepatotoxicity: Drug-induced hepatotoxicity with fatal outcome occurred in 0.1% of patients treated with XALKORI across clinical trials (n=1719). Transaminase elevations generally occurred within the first 2 months. Monitor with liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 2 months of treatment, then once a month and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations. Permanently discontinue for ALT/AST elevation >3 times ULN with concurrent total bilirubin elevation >1.5 times ULN (in the absence of cholestasis or hemolysis); otherwise, temporarily suspend and dose-reduce XALKORI as indicated.

Interstitial Lung Disease (Pneumonitis): Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur. Across clinical trials (n=1719), 2.9% of XALKORI-treated patients had any grade ILD, 1.0% had Grade 3/4, and 0.5% had fatal ILD. ILD generally occurred within 3 months after initiation of treatment. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Exclude other potential causes and permanently discontinue XALKORI in patients with drug-related ILD/pneumonitis.

QT Interval Prolongation: QTc prolongation can occur. Across clinical trials (n=1616), 2.1% of patients had QTcF (corrected QT by the Fridericia method) ≥500 ms and 5.0% had an increase from baseline QTcF ≥60 ms by automated machine-read evaluation of ECGs. Avoid use in patients with congenital long QT syndrome. Monitor with ECGs and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. Permanently discontinue XALKORI in patients who develop QTc >500 ms or ≥60 ms change from baseline with Torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia. Withhold XALKORI in patients who develop QTc >500 ms on at least 2 separate ECGs until recovery to a QTc ≤480 ms, then resume at a reduced dose.

Bradycardia: Symptomatic bradycardia can occur. Across clinical trials, bradycardia occurred in 12.7% of patients treated with XALKORI (n=1719. Avoid use in combination with other agents known to cause bradycardia. Monitor heart rate and blood pressure regularly. In cases of symptomatic bradycardia that is not life-threatening, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, re-evaluate the use of concomitant medications, and adjust the dose of XALKORI. Permanently discontinue for life-threatening bradycardia due to XALKORI; however, if associated with concomitant medications known to cause bradycardia or hypotension, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm. If concomitant medications can be adjusted or discontinued, restart XALKORI at 250 mg once daily with frequent monitoring.

Severe Visual Loss: Across clinical trials, the incidence of Grade 4 visual field defect with vision loss was 0.2% (n=1719). Discontinue XALKORI in patients with new onset of severe visual loss (best corrected vision less than 20/200 in one or both eyes). Perform an ophthalmological evaluation. There is insufficient information to characterize the risks of resumption of XALKORI in patients with a severe visual loss; a decision to resume should consider the potential benefits to the patient.

Vision Disorders: Most commonly visual impairment, photopsia, blurred vision or vitreous floaters, occurred in 63.1% of 1719 patients. The majority (95%) of these patients had Grade 1 visual adverse reactions. 0.8% of patients had Grade 3 and 0.2% had Grade 4 visual impairment. The majority of patients on the XALKORI arms in Studies 1 and 2 (>50%) reported visual disturbances which occurred at a frequency of 4-7 days each week, lasted up to 1 minute, and had mild or no impact on daily activities.

Embryo-Fetal Toxicity: XALKORI can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to the fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 45 days (females) or 90 days (males) respectively, following the final dose of XALKORI.

ROS1-positive Metastatic NSCLC: Safety was evaluated in 50 patients with ROS1-positive metastatic NSCLC from a single-arm study, and was generally consistent with the safety profile of XALKORI evaluated in patients with ALK-positive metastatic NSCLC. Vision disorders occurred in 92% of patients in the ROS1 study; 90% of patients had Grade 1 vision disorders and 2% had Grade 2.

Adverse Reactions: Safety was evaluated in a phase 3 study in previously untreated patients with ALK-positive metastatic NSCLC randomized to XALKORI (n=171) or chemotherapy (n=169). Serious adverse events were reported in 34% of patients treated with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary embolism (2.9%). Fatal adverse events in XALKORI-treated patients occurred in 2.3% of patients, consisting of septic shock, acute respiratory failure, and diabetic ketoacidosis. Common adverse reactions (all grades) occurring in ≥25% and more commonly (≥5%) in patients treated with XALKORI vs chemotherapy were vision disorder (71% vs 10%), diarrhea (61% vs 13%), edema (49% vs 12%), vomiting (46% vs 36%), constipation (43% vs 30%), upper respiratory infection (32% vs 12%), dysgeusia (26% vs 5%), and abdominal pain (26% vs 12%). Grade 3/4 reactions occurring at a ≥2% higher incidence with XALKORI vs chemotherapy were QT prolongation (2% vs 0%), and constipation (2% vs 0%). In patients treated with XALKORI vs chemotherapy, the following occurred: elevation of ALT (any grade [79% vs 33%] or Grade 3/4 [15% vs 2%]); elevation of AST (any grade [66% vs 28%] or Grade 3/4 [8% vs 1%]); neutropenia (any grade [52% vs 59%] or Grade 3/4 [11% vs 16%]); lymphopenia (any grade [48% vs 53%] or Grade 3/4 [7% vs 13%]); hypophosphatemia (any grade [32% vs 21%] or Grade 3/4 [10% vs 6%]). In patients treated with XALKORI vs chemotherapy, renal cysts occurred (5% vs 1%). Nausea (56%), decreased appetite (30%), fatigue (29%), and neuropathy (21%) also occurred in patients taking XALKORI.

Drug Interactions: Exercise caution with concomitant use of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may increase plasma concentrations of crizotinib. Avoid concomitant use of strong CYP3A inducers and inhibitors. Avoid concomitant use of CYP3A substrates with narrow therapeutic range in patients taking XALKORI. If concomitant use of CYP3A substrates with narrow therapeutic range is required in patients taking XALKORI, dose reductions of the CYP3A substrates may be required due to adverse reactions.

Lactation: Because of the potential for adverse reactions in breastfed infants, advise females not to breast feed during treatment with XALKORI and for 45 days after the final dose.

Hepatic Impairment: XALKORI has not been studied in patients with hepatic impairment. As crizotinib is extensively metabolized in the liver, hepatic impairment is likely to increase plasma crizotinib concentrations. Use caution in patients with hepatic impairment.

Renal Impairment: Administer XALKORI at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment (CLcr <30 mL/min) not requiring dialysis. No starting dose adjustment is needed for patients with mild and moderate renal impairment.

For more information and full Prescribing Information, visit www.XALKORI.com (link is external).

20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)]

(Filing, Annual, BioLineRx, 2015, MAR 10, 2016, View Source [SID:1234509467])

8-K – Current report

On March 10, 2016 SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) reported financial results for the quarter and year ended December 31, 2015 (Filing, Q4/Annual, SciClone Pharmaceuticals, 2015, MAR 10, 2016, View Source [SID:1234509495]).

· Revenues: Revenues for the full year 2015 were $157.3 million, compared to $134.8 million for the full year of 2014. In the fourth quarter of 2015, revenues were $42.9 million, compared to $41.4 million for the same period in 2014.

· GAAP Diluted EPS: GAAP diluted earnings per share for the full year 2015 were $0.56, compared to $0.48 for the full year of 2014. In the fourth quarter of 2015, GAAP diluted earnings per share were $0.24, compared to $0.07 for the same period in 2014.

· Non-GAAP Diluted EPS: Non-GAAP diluted earnings per share for the full year 2015 were $1.00, compared to $0.75 for the full year of 2014. In the fourth quarter of 2015, non-GAAP diluted earnings per share were $0.30, compared to $0.29 for the same period in 2014.

For the year ended December 31, 2015, SciClone reported revenues of $157.3 million, a 17% increase compared to $134.8 million for the same period last year. ZADAXIN revenues were $146.1 million for the year ended December 2015, a $20.0 million or 16% increase, compared to $126.1 million last year. Promotion services revenues were $2.9 million for the year ended December 31, 2015, a $0.1 million or 4% increase, compared to $2.8 million last year. Revenues in the fourth quarter of 2015 were $42.9 million, a $1.4 million or 3% increase, compared to $41.4 million for the same period in 2014. ZADAXIN revenues were $40.2 million in the fourth quarter of 2015, a $1.2 million or 3% increase, compared to $39.0 million for the same period in 2014. Promotion services revenues were $0.9 million for the fourth quarter of 2015, a $0.2 million or 29% increase, compared to $0.7 million in the same period in 2014.

On a GAAP basis, SciClone reported net income for the year ended December 31, 2015 of $29.5 million, or $0.59 and $0.56 per share on a basic and diluted basis, respectively, after deducting $10.8 million in settlement expense for the US Securities and Exchange Commission (SEC) investigation recorded in the second quarter of 2015, compared with net income of $25.2 million, or $0.49 and $0.48 on a basic and diluted basis, respectively, for the same period in 2014. SciClone’s net income in the fourth quarter of 2015 was $12.5 million, or $0.25 and $0.24 per share on a basic and diluted

basis, respectively, compared to net income of approximately $3.5 million, or $0.07 per share on a basic and diluted basis for the same period in 2014.

As previously disclosed, in February 2016, SciClone entered into a settlement agreement with the SEC that fully resolved the SEC’s investigation. Under the terms of the settlement agreement, SciClone paid a total of $12.8 million, including disgorgement, prejudgment interest, and a penalty. The payment is in line with the charges SciClone previously recorded and disclosed in its Form 10-Q filed with the SEC on August 10, 2015. As part of the agreement, the Company neither admits nor denies it engaged in any wrongdoing. The Department of Justice (DOJ) has also completed its related investigation and has declined to pursue any action.

SciClone reported non-GAAP net income for the year ended December 31, 2015 of $52.2 million, or $1.05 and $1.00 per share on a basic and diluted basis, respectively, compared with non-GAAP net income of $39.7 million, or $0.77 and $0.75 on a basic and diluted basis, respectively, for the prior year. SciClone’s non-GAAP net income in the fourth quarter of 2015 was $15.5 million, or $0.31 and $0.30 per share on a basic and diluted basis, respectively, compared with non-GAAP net income of $15.4 million, or $0.30 and $0.29 per share on a basic and diluted basis, respectively, for the same period of the prior year.

Friedhelm Blobel, PhD, SciClone’s Chief Executive Officer commented: "We are very pleased with our overall 2015 financial results, including the continuing success and growth of ZADAXIN, as well as the full resolution of the SEC and DOJ investigations. These important accomplishments position us well to continue our growth trajectory in 2016. We are especially pleased with the continued strong demand for ZADAXIN, which grew 16% over the prior year and thus clearly faster than its generic competitors, and remains a major growth driver for our company. DC Bead continues to gain traction in the marketplace, supported by successful implementation of academic marketing strategies, as does our overall oncology portfolio and our promoted products."

"Despite macro-economic variables, the China pharmaceutical market grew about 8% to 9% in 2015, still significantly outpacing Western market growth rates, and continuing to represent meaningful opportunities for SciClone to continue to expand our business. The extensive regulatory reforms underway in China are showing signs of increasing the speed and efficiency of drug reviews and approvals. We anticipate that this trend will continue, and have a beneficial impact on our ability to advance our development portfolio."

"We are looking forward to conducting a full review of strategic alternatives with the goal of maximizing shareholder value. We continue to believe that SciClone represents a unique opportunity in the China pharma market, and that our commercial experience, reputation for high quality products, industry-leading compliance and partner-of-choice status should translate into opportunities to benefit our stakeholders."

For the year ended December 31, 2015, SciClone reported sales and marketing (S&M) expenses of $54.0 million, compared with $48.5 million for last year. For the fourth quarter of 2015, S&M expenses were $14.9 million, compared with $13.5 million for the same period in 2014. The increase in S&M for the fourth quarter of 2015, compared to the same period in 2014, related to increases in our sales and marketing efforts for ZADAXIN and DC Bead.

For the year ended December 31, 2015, SciClone reported research and development (R&D) expenses of $12.3 million, which included $7.5 million in upfront and milestone payments related to new in-license arrangements, primarily with Theravance Biopharma, Inc., compared with $14.6 million for last year, which included $11.0 million in upfront payments under our in-license arrangement primarily related to The Medicines Company for two cardiovascular products, Angiomax (bivalirudin) and Cleviprex (clevidipine). R&D expenses for the three months ended December 31, 2015 were $3.6 million which included $2.0 million in milestone payments under our in-license arrangements, compared with $11.6 million for the same period last year, which included $11.0 million in upfront payments as noted above which were recorded in the fourth quarter of 2014.

For the year ended December 31, 2015, SciClone reported general and administrative (G&A) expenses of $27.9 million, compared with $22.7 million for last year. For the fourth quarter of 2015, G&A expenses were $6.5 million, compared with $5.3 million for the same period in 2014, an increase of $1.2 million primarily related to our China entity restructuring, higher professional consulting fees for business development strategy, higher stock-based compensation expense, and lower credits to bad debt expense for recovery of previously written-off accounts receivable.

As of December 31, 2015, cash, cash equivalents and short-term investments totaled $101.4 million excluding the $12.8 million of restricted cash held in escrow as of December 31, 2015 for the SEC settlement which was released and paid in February 2016, compared to $86.3 million as of December 31, 2014.

SciClone has had a share repurchase program under which its Board of Directors had authorized $80.5 million, of which approximately $78.1 million had been utilized through December 31, 2015. The share repurchase program expired on December 31, 2015 and is currently under strategic review by the Board.

SciClone has presented non-GAAP information above as the Company believes this non-GAAP information is useful for investors, taken in conjunction with SciClone’s GAAP financial statements, because management uses such information internally for its operating, budgeting and financial planning purposes. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of SciClone’s operating results as reported under GAAP. The non-GAAP calculations and reconciliation are provided in the accompanying table titled "Reconciliation of GAAP to Non-GAAP Net Income."

In light of the strategic review underway at SciClone, the Company does not plan to provide revenue and earnings per share guidance for 2016.

OncoMed Pharmaceuticals Announces Full Year and Fourth Quarter 2015 Financial Results and 2016 Guidance

On March 10, 2016 OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage company developing novel cancer stem cell (CSC) and immuno-oncology therapeutics, reported financial results for the year and quarter ended December 31, 2015 and provided 2016 guidance (Press release, OncoMed, MAR 10, 2016, View Source [SID:1234509493]). As of December 31, 2015, pro-forma cash and marketable securities totaled $227.3 million, exceeding the company’s 2015 guidance of year-end cash of greater than $120 million. Full-year cash expense was $101.1 million, in line with the 2015 cash expense guidance of $100-$110 million.

2016 Financial Guidance
For the full year 2016, based on its current plans and expectations, OncoMed anticipates total cash expenses in the range of approximately $110-$120 million. OncoMed projects a 2016 year-end cash balance of more than $100 million, before considering the receipt of any potential collaboration milestones or opt-in payments. Potential milestone and opt-in payments over the course of 2016, 2017, and 2018 total over $270 million. Existing cash is anticipated to fund company operations for at least two years, without taking into account potential future milestones or payments from partners. This is an increase from the 1.5 years of cash guidance announced in January 2016 and is the result of pipeline and budget prioritization and careful fiscal management.

"Having extended our runway to greater than two years cash — without taking into account potential milestones over the course of those two years — OncoMed is well positioned to execute on plan and continue to build value through the advancement and growth of our research and development pipeline," said Paul J. Hastings, Chairman and Chief Executive Officer. "We have a number of things to look forward to in 2016, including the advancement of three randomized Phase 2 trials, data from several earlier-stage clinical programs, and two new immuno-oncology programs moving toward IND filings in late 2016/early 2017."

Key 2016 Milestones and Anticipated Events
Demcizumab (anti-DLL4, OMP-21M18)

Initiate a Phase 1b trial of demcizumab plus anti-PD-1 (pembrolizumab) in solid tumor patients in the first quarter.

Present updated survival data from the demcizumab Phase 1b non-small cell lung cancer (NSCLC) trial mid-year, contingent upon abstract acceptance.

Complete enrollment in the Phase 2 YOSEMITE clinical trial of demcizumab plus Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with first-line pancreatic cancer by year end. Data from this study are expected to be available in the first half of 2017.

Continue enrollment in the Phase 2 DENALI clinical trial of demcizumab plus carboplatin and pemetrexed in patients with first-line non-squamous NSCLC. Data from the Phase 2 DENALI trial are anticipated in late 2017-2018.

Data from YOSEMITE or DENALI trials could trigger a potential Celgene opt-in, leading to an as-yet undisclosed opt-in payment and the Phase 3 co-development and co-commercialization of demcizumab in the U.S.

Tarextumab (anti-Notch2/3, OMP-59R5)

Complete enrollment in the Phase 2 PINNACLE clinical trial of tarextumab plus platinum chemotherapy and etoposide in subjects with first-line extensive-stage small cell lung cancer by year end. Data from this study are expected to be available in early 2017. Data from PINNACLE could support an opt-in decision from GlaxoSmithKline (GSK) for the tarextumab program in the first half of 2017, resulting in a $25 million milestone payment to OncoMed, and the advancement of the program to a fully funded randomized Phase 3 trial funded and conducted by GSK.

Wnt Programs – Vantictumab (anti-Fzd7, OMP-18R5) and Ipafricept (Fzd8-Fc, OMP-54F28)

Present opt-in packages to Bayer for both vantictumab and ipafricept by late 2016/early 2017. Bayer can elect to exercise its option for vantictumab and/or ipafricept at any time through completion of the Phase 1b clinical trials. OncoMed could receive a total of $40 million with the potential opt-in by Bayer of these two programs, and the programs could be advanced to randomized Phase 2 clinical trials by Bayer.

Present clinical Phase 1b data from the vantictumab breast cancer and pancreatic cancer trials in 2016, contingent upon abstract acceptance.

Present clinical Phase 1b data from the ipafricept ovarian cancer and pancreatic cancer trials in 2016, contingent upon abstract acceptance.

Brontictuzumab (anti-Notch1, OMP-52M51)

Initiate Phase 1b clinical trial of brontictuzumab combined with chemotherapy in colorectal cancer patients including an expansion cohort of biomarker-selected patients. GSK and OncoMed have agreed to share out-of-pocket costs for the Phase 1b clinical trial and are currently in discussions to potentially extend GSK’s option through the end of the Phase 1b clinical trial. Currently, GSK may exercise its option for brontictuzumab at the end of Phase 1a or Phase 2 clinical trials.

Anti-DLL4/VEGF Bispecific (OMP-305B83)

Present data from the Phase 1a dose-escalation clinical trials of anti-DLL4/VEGF bispecific in the second half of the year, contingent upon dose-escalation and abstract acceptance.

In coordination with our partner, Celgene, initiate at least one Phase 1b anti-DLL4/VEGF bispecific clinical trial in combination with standard of care.

Completion of Phase 1b could trigger a potential Celgene opt-in, resulting in an as-yet undisclosed opt-in payment from Celgene and the potential co-development and co-commercialization of the program in the U.S.

Anti-RSPO3 (OMP-131R10)

Present data from the Phase 1a/b dose-escalation clinical trial of anti-RSPO3 in the second half of the year, contingent upon dose-escalation and abstract acceptance.

Completion of the Phase 1a/1b trial and delivery of the data could trigger a potential Celgene opt-in, resulting in an as-yet undisclosed opt-in payment from Celgene and the potential co-development and co-commercialization of the program in the U.S.

Immuno-Oncology Programs

Advance the immuno-oncology product candidate that is part of OncoMed’s collaboration with Celgene (IO#2) and OncoMed’s wholly owned GITRL-Fc program toward at least one Investigational New Drug (IND) application filing by the end of 2016. Both programs are currently advancing in IND-enabling preclinical studies.

OncoMed reiterated that over the course of the next three years (2016, 2017 and 2018), the company may be eligible to receive more than $270 million in potential opt-in and milestone payments from its partners: over $168 million from its collaboration with Celgene, $60 million from Bayer and over $43 million from GSK. OncoMed is eligible for more than $5 billion in total potential milestone and option payments from its collaboration agreements with Celgene, Bayer, and GSK. To date, OncoMed has received over $450 million from its existing partners.

Full Year and Fourth Quarter 2015 Financial Results
Pro-forma cash, cash equivalents and short-term investments at the end of 2015 totaled $227.3 million, including a $70.0 million safety milestone related to the demcizumab program from Celgene, compared to $232.0 million as of December 31, 2014. The cash decrease was driven by increased spending related to pipeline development, partially offset by a recaptured tax payment associated with the Celgene collaboration 2013 upfront payment, and the achievement of milestone revenues from collaborative partnerships.

Revenues for the full year 2015 totaled $25.9 million compared to $39.6 million in 2014. OncoMed achieved the $70.0 million safety milestone for demcizumab from Celgene, which was recorded as deferred revenue and will be amortized over the performance period. The year-over-year decrease was primarily due to the recognition of an $11.0 million development milestone in 2014 related to the tarextumab "ALPINE" clinical trial.

Fourth quarter 2015 recognized revenues decreased to $6.8 million compared to $8.5 million for the fourth quarter of 2014. The decrease was due to revisions to the estimated periods of performance, which extended the amortization of upfront payments for the company’s GSK and Bayer collaborations. In the fourth quarter 2015, OncoMed achieved a $2.5 million milestone from Celgene for the candidate designation of a novel undisclosed immuno-oncology program as well as the $70.0 million safety milestone for demcizumab which was recorded as deferred revenue and will be amortized over the performance period. In the fourth quarter 2014, OncoMed received a $2.5 million milestone from Celgene for the candidate designation of anti-RSPO3 (OMP-131R10).

Research and development (R&D) expenses for the full year ended December 31, 2015 were $92.9 million compared with $76.4 million for the year ended December 31, 2014. For the fourth quarter of 2015, R&D expenses were $26.7 million compared to $20.6 million for the fourth quarter of 2014. Increases in R&D expenditures for the full year and fourth quarter were primarily attributable to increased personnel expenses, as well as increased program costs associated with the advancement of OncoMed’s clinical-stage product candidates and preclinical pipeline.

General and administrative (G&A) expenses for the years ended December 31, 2015 and 2014 were $18.6 million and $13.8 million, respectively. For the fourth quarter of 2015 G&A expenses were $5.0 million compared to $3.6 million for the fourth quarter of 2014. Higher full-year and fourth quarter costs for 2015 were primarily attributable to increased personnel expenses, including an increase in headcount and stock-based compensation, higher legal patent expenses, and financial expenses related to the S-3 shelf registration filing in June 2015.

Net loss for the year ended December 31, 2015 was $85.4 million ($2.84 per share), compared to $50.0 million ($1.69 per share) for the year ended December 31, 2014. Non-GAAP net loss for the year ended December 31, 2015 was $21.4 million ($0.71 per share), compared to $78.1 million ($2.63 per share) for the year ended December 31, 2014. Net loss for the fourth quarter of 2015 was $24.8 million ($0.82 per share) compared to $15.1 million ($0.50 per share) for the same period of 2014. Non-GAAP net income was $45.3 million ($1.50 per share) compared to non-GAAP net loss of $18.9 million ($0.63 per share) for the same period of 2014. The change in net loss for the year and fourth quarter were primarily due to increases in operational expenses and lower milestone revenues. Non-GAAP net income was attributable to the Celgene $70.0 million safety milestone.

Recent Highlights
Demcizumab (anti-DLL4, OMP-21M18)

In December 2015, OncoMed received a $70.0 million safety-related milestone from Celgene based on an analysis of the OncoMed Phase 1b and blinded interim Phase 2 clinical trial safety data that were available at that time.
Data from the pancreatic, non-small cell lung and ovarian cancer clinical trials showed no demcizumab-related Grade 3 or higher cardio-pulmonary toxicities among 155 patients treated with truncated dosing. Of those, 68 patients had received at least two cycles of demcizumab at the Phase 2 dose or higher and had been followed for at least 100 days.
In January 2016, OncoMed presented updated Phase 1b survival data for demcizumab in combination with Abraxane plus gemcitabine in previously untreated pancreatic cancer patients at the Gastrointestinal Cancer Symposium (ASCO GI).
In 32 previously untreated patients, the updated Kaplan-Meier estimated median progression-free survival was 7.1 months and median overall survival was 12.7 months for the patients who received the demcizumab-gemcitabine-Abraxane combination.
OncoMed has completed enrollment of the Phase 1b clinical trial in advanced ovarian cancer patients and as part of budget and pipeline prioritization, and will not conduct the Phase 2 portion of that clinical trial at this time.

Tarextumab (anti-Notch2/3, OMP-59R5)

In January 2016, OncoMed discontinued dosing of the ALPINE randomized Phase 2 clinical trial of tarextumab with Abraxane plus gemcitabine in advanced first-line pancreatic cancer.

A pre-planned data safety monitoring board (DSMB) analysis indicated a statistically significant worsening of response rate and progression-free survival (PFS) in the treatment arm in the overall intent-to-treat population, as well as a negative trend in each Notch biomarker subgroup and a strong trend to lack of benefit in the treatment arm for overall survival (OS), regardless of Notch biomarker levels. OncoMed conducted its own exploratory analysis of the unblinded Phase 2 data and confirmed key findings by the DSMB regarding futility of the ALPINE trial. Post-hoc, exploratory analyses conducted by OncoMed revealed subgroups of patients with decreased survival and a subgroup which appears to exhibit improved survival with tarextumab treatment.

In February 2016, OncoMed determined it would continue the "PINNACLE" Phase 2 trial of tarextumab in small cell lung cancer following a review of unblinded safety and efficacy data from both the ALPINE and PINNACLE studies by the U.S. Food and Drug Administration (FDA) and the PINNACLE DSMB. The PINNACLE study remains blinded to OncoMed, investigators and patients. Data from the Phase 2 PINNACLE trial are anticipated in 2017.

In February 2016, OncoMed presented updated survival data from the Phase 1b clinical trial of tarextumab plus chemotherapy in small cell lung cancer at the 16th Annual Targeted Therapies of Lung Cancer Meeting.

These data showed an apparent correlation between doses of tarextumab and duration of response. In 15 patients who received higher doses of tarextumab (at or above 12.5 mg/kg every three weeks) in combination with standard-of-care therapy, median PFS of 5.8 months and median OS of 16 months were observed.

Wnt Programs – Vantictumab (anti-Fzd7, OMP-18R5) and Ipafricept (Fzd8-Fc, OMP-54F28)

In November 2015, OncoMed and Bayer amended their agreement to enroll up to 12 additional subjects in the ongoing Phase 1b clinical trial of vantictumab in breast cancer and up to 12 additional subjects in the ongoing Phase 1b clinical trial of ipafricept in ovarian cancer. Bayer has agreed to reimburse OncoMed for all out-of-pocket expenses to support this additional patient enrollment.

In February 2016, OncoMed agreed with Bayer to discontinue two of the six ongoing Phase 1b trials of vantictumab and ipafricept due to changing standard-of-care paradigms and to better focus enrollment efforts and resource allocation. OncoMed expects to close out the Phase 1b trials of vantictumab in NSCLC and of ipafricept in hepatocellular carcinoma in the first half of 2016.

Non-GAAP Financial Measures
To supplement OncoMed’s financial results presented on a GAAP basis, OncoMed uses non-GAAP measures of net income and net loss and earnings per share that exclude non-cash expenses related to stock-based compensation expense, depreciation and amortization and deferred rent adjustment, and include deferred revenue. OncoMed management uses these non-GAAP financial measures to monitor and evaluate its operating results and trends on an ongoing basis, and internally for operating, budgeting and financial planning purposes. OncoMed management believes that these non-GAAP measures help investors better evaluate the company’s past financial performance and potential future results. Non-GAAP measures should not be considered in isolation or as a substitute for comparable GAAP accounting and investors should read them in conjunction with the company’s financial statements prepared in accordance with GAAP. The non-GAAP measures of net income and net loss and earnings per share may be different from, and not directly comparable to, similarly titled measures used by other companies. A description of the non-GAAP calculations and reconciliation to comparable GAAP financial measures is provided in the accompanying table entitled "Reconciliation of Non-GAAP Financial Measures."