Momenta Discontinues Further Accrual of its Phase 2 Trial of Necuparanib in Patients with Pancreatic Cancer Following Planned Interim Futility Analysis

On August 4, 2016 Momenta Pharmaceuticals, Inc. (NASDAQ:MNTA), a biotechnology company specializing in the characterization and engineering of complex drugs, reported that the Company has discontinued further accrual in its Phase 2 trial evaluating necuparanib in combination with Abraxane and gemcitabine in patients with advanced metastatic pancreatic cancer (Press release, Momenta Pharmaceuticals, AUG 4, 2016, View Source [SID:1234514227]).

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The decision to discontinue enrollment into the study was based on the recommendation from the independent Data Safety Monitoring Board (DSMB) following a planned interim futility analysis conducted once 57 deaths (50% of the target number of 114 events required for trial completion) had occurred. Data were assessed from 120 randomized patients as of July 20, 2016. While no new safety signals were observed and the toxicity profile was considered manageable, the DSMB determined that necuparanib in combination with Abraxane and gemcitabine did not show a sufficient level of efficacy to warrant continued enrollment. Additionally, no new toxicities were observed that necessitate immediate discontinuation of study drug in patients currently active on protocol. The DSMB also recommended that the company consider unblinding the data to provide more information to determine how best to address ongoing patients.

"We are extremely disappointed with the outcome of the futility analysis – in particular, for those patients with pancreatic cancer where there is still so much unmet need for safe and effective therapy," said Jim Roach, M.D., Senior Vice President of Development and Chief Medical Officer of Momenta Pharmaceuticals. "We agree with the DSMB recommendations and plan to confirm the futility analysis and determine next steps for the necuparanib program."

"We are saddened that necuparanib did not produce the outcome we had hoped for in this patient population," said Craig A. Wheeler, President and Chief Executive Officer of Momenta Pharmaceuticals. "We would like to thank the investigators and their brave patients for participating in this trial as well as our staff and external advisors for their support throughout this program."

The Phase 1/2 necuparanib trial is a two-part study in patients with advanced metastatic pancreatic cancer. Part A was a Phase 1, open-label, multiple ascending dose study of necuparanib given first as a single dose and then daily in combination with Abraxane and gemcitabine; final data from Part A was reported at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting. Part B is a Phase 2, randomized, placebo-controlled, double-blind study investigating the antitumor activity of necuparanib combined with Abraxane and gemcitabine compared with placebo combined with Abraxane and gemcitabine.

About Necuparanib
Necuparanib (M402) is a novel oncology drug candidate engineered to have a broad range of effects on tumor cells. The use of heparins to treat venous thrombosis in cancer patients has generated numerous reports of antitumor activity; however, the dose of these products has been limited by their anticoagulant activity. Leveraging its experience in deciphering the structure-function relationships of complex therapeutics, Momenta engineered necuparanib from unfractionated heparin to have significantly reduced anticoagulant activity while preserving relevant antitumor properties associated with heparins.

BioCryst Reports Second Quarter 2016 Financial Results

On August 4, 2016 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported financial results for the second quarter ended June 30, 2016 (Press release, BioCryst Pharmaceuticalsa, AUG 4, 2016, View Source [SID:1234514234]).

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"We continue to make progress, and have initiated subject screening to start the APeX-1 trial evaluating our once daily oral kallikrein inhibitor BCX7353 to prevent HAE attacks," said Jon P. Stonehouse, President & Chief Executive Officer. "Our goal remains to report out initial data by year end for this trial."

Second Quarter Financial Results
For the three months ended June 30, 2016, revenues decreased to $4.8 million from $25.8 million in the second quarter of 2015. The decrease was primarily due to the one time, partial recognition of a large upfront payment from Seqirus UK Limited (Seqirus) associated with the licensing of RAPIVAB (peramivir injection) in the second quarter of 2015, as well as lower collaborative revenue associated with BCX4430 development in the second quarter of 2016.

Research and Development (R&D) expenses for the second quarter of 2016 decreased to $14 .2 million from $16.5 million in the second quarter of 2015. This decrease was primarily due to lower development costs associated with the Company’s BCX4430 program.

General and administrative (G&A) expenses for the second quarter of 2016 decreased to $2.7 million compared to $3.5 million for the second quarter of 2015, due to a general reduction of administrative expenses throughout the Company during the second quarter of 2016, as compared to the second quarter of 2015.

Interest expense, which is primarily related to Company’s non-recourse notes payable, was $1.4 million in the second quarter of 2016 and $1.3 million in the second quarter of 2015. In addition, a $3.7 million mark-to-market loss on the Company’s foreign currency hedge was recognized in the second quarter of 2016, as compared to a $796,000 mark-to-market loss in the second quarter of 2015. These gains and losses result from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement. During the second quarters of 2016 and 2015, we also realized currency gains of $811,000 and $1.5 million, respectively, from the exercise of a U.S. Dollar/Japanese yen currency option within our foreign currency hedge.

The net loss for the second quarter of 2016 was $16.3 million, or a $0.22 net loss per share, compared to net income of $4.9 million, or $0.06 net income per fully diluted share, for the second quarter 2015.

Cash, cash equivalents and investments decreased to $64.3 million at June 30, 2016, as compared to $100.9 million at December 31, 2015. Net operating cash use for the second quarter of 2016 was $15.4 million, as compared to $12.0 million for the second quarter of 2015.

Year to Date Financial Results
For the six months ended June 30, 2016, total revenues decreased to $9.6 million from $32.7 million in the first half of 2015. The decrease in revenue resulted from the recognition of approximately $21.7 million of collaborative revenue in the second quarter of 2015 associated with the RAPIVAB out-licensing transaction with Seqirus in June 2015.

R&D expenses increased to $34.7 million in the first half of 2016 from $33.6 million in the first half of 2015. The increase in 2016 R&D expense, as compared to 2015, reflects increased spending in our RAPIVAB program, somewhat offset by decreased development activity in our BCX4430 program. The majority of R&D spending was associated with the Company’s HAE development program.

G&A expenses decreased to $5.9 million for the six months ended June 30, 2016 from $7.6 million for the six months ended June 30, 2015, due primarily to lower unrestricted grants awarded to HAE patient advocacy groups, as well as a general reduction of administrative expenses in the first half of 2016.

In the first half of 2016 and 2015, interest expense was $2.9 million and $2.6 million, respectively, and was primarily related to the Company’s non-recourse notes payable. A mark-to-market loss on our foreign currency hedge of $6.4 million was recognized in the first half of 2016, compared to a mark-to-market loss of $332,000 in the first half of 2015. These gains and losses result from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement. As noted above, we also realized currency gains of $811,000 and $1.5 million from the exercise of U.S. dollar/Japanese yen currency options during the first half of 2016 and 2015, respectively.

The net loss for the six months ended June 30, 2016 increased to $39.1 million, or $0.53 per share, from $10.3 million, or $0.14 per share for the same period last year.

Corporate Update & Outlook
The APeX-1 clinical trial of BCX7353 for prophylaxis of angioedema attacks in patients with HAE has received regulatory approval in Canada and several European countries, and patient screening has commenced. We expect initial data from APeX-1 to be available by year end 2016.

A clinical pharmacology study of several dosage formulations of avoralstat is nearing completion. Cohorts of healthy volunteers have received single doses ranging from 200 mg to 2000 mg of avoralstat in tablet or suspension formulations, with no clinically significant adverse events reported. While these dosing formulations have improved total avoralstat exposure (AUC) up to approximately five-fold compared to a 500 mg dose given as soft gel capsules, the plasma concentration-time profile has not met our objectives of twice-daily dosing with drug levels at or above the target range. For that reason, we have decided to stop further development of avoralstat.

A phase 1 first-in-human study of the broad-spectrum antiviral drug BCX4430 has been completed. Study drug was administered by i.m. injection to healthy volunteers. Single doses of BCX4430 ranging from 0.3 to 10 mg/kg were administered, and daily doses of 2.5 mg/kg to 10 mg/kg were administered for 7 days. Exposure to BCX4430 was dose-proportional. BCX4430 dosing was generally safe and well-tolerated, and there were no grade 3 or 4 adverse events.

On July 5, 2016, BioCryst announced that the National Institute of Allergy and Infectious Diseases (NIAID) has provided additional funding for efficacy studies of BCX4430 in non-human primates to further assess effective dose regimens. This funding represents an increase of $5.5 million for the development of BCX4430 as a treatment for hemorrhagic fever viruses. The NIAID contract value now totals $39.5 million, if all contract options are exercised. To date, approximately $35.4 million of funding has been awarded under the contract.

About APeX-1
APeX-1 is a two part, Phase 2, randomized, double-blind, placebo-controlled proof of concept and dose ranging trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of BCX7353 as a preventative treatment to eliminate or reduce the frequency of angioedema attacks in HAE patients. Up to a total of approximately 50 eligible subjects with HAE will be enrolled in the trial.

In part 1 of APeX-1, up to 36 subjects with HAE will be randomized in a 1:1 ratio to receive an oral dose of either 350 mg of BCX7353 once daily or placebo once daily for four weeks. An interim analysis will be conducted after the first 24 subjects have completed treatment through study day 28. If a robust treatment effect is observed at the interim analysis, Part 2 of the study will be initiated. In the event the treatment effect is not well characterized with 24 subjects, a total of up to approximately 36 subjects will be enrolled in part 1. The sample size in Part 1 was kept flexible to cover a range of response options that would achieve 90% power with an alpha of 0.05, based on reduction of attack rate of at least 70% on BCX7353, placebo response rate of approximately 30%, and standard deviation of approximately 0.45 attacks per week.

To characterize dose-response in part 2 of APeX-1, 14 additional subjects with HAE will be randomized to 250mg of BCX7353 once daily (n=6), 125mg of BCX7353 once daily (n=6) or placebo (n=2).

The primary efficacy endpoint of APeX-1 is the number of angioedema attacks; attack rate per week, counts of attacks, proportion of subjects with no attacks, and number of attack-free days will be analyzed. Efficacy analyses will be conducted for HAE attacks reported over the entire dosing interval (Days 1 through 28) and during the dosing period in which plasma concentrations of BCX7353 should be at steady-state conditions (Days 8 through 28). Secondary efficacy endpoints include severity and duration of angioedema attacks, and measures of health-related quality of life. Safety will be characterized through evaluation of adverse events and laboratory testing. Pharmacokinetics and pharmacodynamic effects will be assessed through measurement of plasma drug levels and kallikrein inhibition.

About BCX7353
Discovered by BioCryst, BCX7353 is a novel, once-daily, selective inhibitor of plasma kallikrein in development for the prevention of angioedema attacks in patients diagnosed with HAE. By inhibiting plasma kallikrein, BCX7353 suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients. BCX7353 has been generally safe and well tolerated in clinical pharmacology studies that have enrolled 117 healthy volunteers, 46 receiving single doses of up to 1000 mg, and 71 receiving once-daily doses of up to 500 mg for 7 days and 350 mg for 14 days. In the second week of study, approximately 4-5% of healthy volunteers administered daily doses of ‘7353 for at least 7 days developed a drug-related skin rash that resolved within a few days.

Financial Outlook for 2016
Based upon development plans and our awarded government contracts, BioCryst expects its 2016 net operating cash use to be in the range of $55 to $75 million, and its 2016 operating expenses to be in the range of $78 to $98 million. Our operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the Company’s stock, as well as by the vesting of the Company’s outstanding performance-based stock options.

Navidea Reports Second Quarter 2016 Financial Results

On August 4, 2016 Navidea Biopharmaceuticals, Inc. (NYSE MKT:NAVB), reported financial results for the second quarter of 2016. Navidea reported total revenue for the second quarter of 2016 of $5.4 million, including Lymphoseek (technetium Tc 99m tilmanocept) injection sales revenue of $4.2 million (Press release, Navidea Biopharmaceuticals, AUG 4, 2016, View Source;p=RssLanding&cat=news&id=2192878 [SID:1234514255]). The net loss from operations was $580,000 and the net loss attributable to common stockholders was $6.7 million.

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"Despite the significant disruption in our organization during the first half of 2016 caused by legal and financial challenges, we remain committed to advancing our Lymphoseek commercial efforts, expanding our Manocept platform to other larger immunodiagnostic and immunotherapeutic indications, and controlling our operating expenses" said Jed Latkin, interim Chief Operating Officer and Chief Financial Officer at Navidea. "Despite the disruptions caused by CRG’s (Capital Royalty Partners II L.P.) actions we are confident that the technology we are developing and our lead commercial product, Lymphoseek, provide Navidea and its shareholders with significant unrealized value. Given the advanced state of our technology, continued growth of Lymphoseek in the U.S. and the impending launch in Europe, we believe we will be successful in seeking a replacement financing arrangement for the CRG debt. We believe we have significant claims for damages against CRG that we intend to pursue. Finally our Macrophage Therapeutics subsidiary has made great strides towards demonstrating the breadth of the technology’s potential to develop innovative immunotherapies."

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

Commercial

Achieved sequential quarter-on-quarter Lymphoseek revenue growth of 12% and continued improvement in key performance indicators;
Reported investigator-initiated study results demonstrating beneficial performance characteristics of Lymphoseek and positive comparative results versus commonly-used, non-receptor-targeted imaging agents in breast cancer presented by Emory University School of Medicine and University of California San Diego (UCSD) at the 2016 Society of Nuclear Medicine and Molecular Imaging annual meeting; and
Continued to progress our development efforts to meet the projected Q4 launch of Lymphoseek in Europe by our partner, Norgine BV.
Lymphoseek Lifecycle Management

Continued market development clinical activities with Navidea’s and investigator-initiated studies in cervical cancer, pediatric solid tumors, anal-rectal cancer, endometrial cancer, and for further confirmation of workflow efficiency compared to sulfur colloid, which are supported in large part by National Institutes of Health (NIH) grant funding; and
Received Western Institutional Review Board (WIRB) approval of several Lymphoseek investigational protocols including anal-rectal cancer sentinel lymph node detection, imaging in Kaposi sarcoma (KS) and intravenous (IV) administration in rheumatoid arthritis (RA).
Immunodiagnostic & Immunotherapeutic Development Pipeline

Rheumatoid Arthritis Immunodiagnostic Indication
Received IRB approval at University of California, San Francisco and from WIRB for the RA subcutaneous administration clinical trial protocol;
Expect patient enrollment in the subcutaneous injection trial to begin shortly;
Awarded Part 2 grant funding of $1.1 million from our previously announced RA grant;
Completed cardiovascular disease imaging study with Massachusetts General Hospital, manuscripts being prepared for publication;
Expect to begin grant-funded Phase 1/2 evaluation of Lymphoseek – IV in KS patients in the second half of 2016;
Received $1.8 million grant to support the development of Manocept immunotherapeutic program in KS; and
Successfully completed a number of preclinical studies of Manocept in animal models of nonalcoholic steatohepatitis (NASH), arthritis, asthma, neuro-inflammation and tumor-associated macrophage (TAM) depletion in two cancer models. Both MT1000 class and MT2000 class molecules demonstrated their predicted activity in animal testing.
Operational & Financial

Reduced cash used in operations by over 87% for the first half of 2016 compared to the first half of 2015; and
Continued partnering/divestiture efforts for the Company’s investigational imaging agent, NAV4694, for the detection of amyloid plaques in Alzheimer’s disease.
CRG litigation update

As previously reported, on April 7, 2016, Navidea received a notice from CRG pursuant to the Term Loan Agreement, dated May 8, 2015 which claimed that certain Events of Default, unrelated to repayment terms, had occurred under the Loan Agreement. CRG commenced a state court action in Harris County, Texas District Court against the Company on that same date. By letter dated May 31, 2016, CRG declared all of the Company’s obligations under the Loan Agreement and all other loan documents to be immediately due and payable in the amount of $56,157,240.69. The Company disputes the total amount claimed to be due and owing, and contends CRG’s acceleration of the maturity of the loan was improper. On July 13, 2016, a hearing was held in the District Court of Harris County, Texas with respect to CRG’s application for a temporary injunction seeking to restrain Navidea from operating or using new accounts without having first entered into a blocked account control and/or pledge collateral account control agreement with CRG for any such new account. At the conclusion of the temporary injunction hearing, the Court ordered the parties to mediation and stayed any ruling on CRG’s request for injunctive relief until after mediation has been completed. The parties participated in a mediation on July 20, 2016, but did not reach a settlement. The district judge in the Texas case has since recused herself from the case, and the case has been reassigned to a different Harris County District Court. The district court did not issue a ruling on the application for temporary injunction prior to the judge’s recusal from the case, and no hearing or other matter is currently set in the Texas court case.

Concurrently with the Texas court case, CRG previously sent a notice to Cardinal Health demanding that all monies owing to Navidea be sent directly to CRG. In response, Cardinal filed an interpleader action in Ohio, pursuant to which the Ohio court initially ruled that 50% of the monies should be sent to Navidea, and 50% should be placed into the registry of the Court pending a determination of the parties’ rights to the funds. The court has since ruled that 75% of the Cardinal payments should be sent to Navidea and 25% should be deposited into the registry of the court up until the deposit in the registry of the court equals $1 million, which will serve as a bond pending a determination on the merits of the case, and then Navidea will receive 100% of the Cardinal payments pending further order by the Court in the Ohio case.

The Company reiterates its firmly-held position that the alleged claims by CRG do not constitute Events of Default under the Loan Agreement and will vigorously defend against such claims. The Company also contends CRG’s wrongful conduct has caused harm to the Company and it will pursue its counterclaims against CRG seeking all remedies and other relief it may be entitled to under the law.

The Company is also continuing to explore alternative financing arrangements in order to refinance the CRG debt. The Company believes that the actions of CRG are a violation of the Loan Agreement and, as a result, CRG is in breach of the Loan Agreement, not the Company. The Company believes that its best course of action is to refinance the CRG debt and pursue its claims for damages.

Financials

Total revenues for the quarter ended June 30, 2016 were $5.4 million compared to $2.9 million in the second quarter of last year. Second quarter 2016 product revenues recognized from the sale of Lymphoseek were $4.2 million, compared to $3.8 million in the first quarter of 2016 and $2.0 million in the second quarter of 2015. During the second quarter of 2016, the Company also reported $1.2 million in grant, licensing and other revenue. For the six months ended June 30, 2016, Navidea’s total revenue was $10.1 million compared to $5.0 million for the same period in 2015, an increase of 103%. The primary driver of this increase was revenues recognized from the sale of Lymphoseek which exceeded $8.0 million for the six months ended June 30, 2016 compared to $3.8 million for the same period last year.

Gross margins on Lymphoseek product sales grew to 87% for the second quarter of 2016 compared to 83% for the second quarter of 2015, primarily due to inventory written off in 2015 related to a production issue.

Research and development (R&D) expenses for the second quarter of 2016 were $2.5 million, compared to $2.3 million in the second quarter of last year. R&D expenses were $5.2 million for the six months ended June 30, 2016 compared to $6.3 million in the same period of 2015. The net decreases in year-to-date R&D expenses were primarily a result of decreased headcount costs coupled with decreased project costs related to the Company’s neuro assets, offset by increased project costs related to the Company’s Manocept and Lymphoseek programs. Selling, general and administrative (SG&A) expenses for the second quarter of 2016 were $2.9 million, compared to $4.0 million in the second quarter of last year. SG&A expenses were $7.0 million for the six months ended June 30, 2016, compared to $9.5 million for the same period in 2015. The net decrease in year-to-date SG&A expenses was due primarily to decreased headcount coupled with decreased costs related to contracted medical science liaisons, commercialization costs for Lymphoseek and NAV4694 and license fees, offset by increases in commercial headcount costs related to the addition of our internal sales force coupled with increased legal and professional services. Total operating expenses were $5.4 million for the second quarter of 2016, compared to $6.3 million in the second quarter of last year. Operating expenses were $12.2 million for the six months ended June 30, 2016, compared to $15.8 million for the same period in 2015.

Navidea’s net loss from operations for the quarter ended June 30, 2016 was $580,000 compared to $3.8 million for the same period in 2015. For the six months ended June 30, 2016, Navidea’s net loss from operations was $3.1 million compared to a net loss from operations of $11.6 million for the same period in 2015. Navidea’s net loss attributable to common stockholders for the quarter ended June 30, 2016 was $6.7 million, or $0.04 per share, compared to $9.7 million, or $0.06 per share, for the same period in 2015. For the six months ended June 30, 2016, Navidea’s net loss attributable to common stockholders was $10.4 million, or $0.07 per share, compared to a net loss attributable to common stockholders of $17.0 million, or $0.11 per share, for the same period in 2015. Net losses attributable to common stockholders include fees paid to CRG (which the Company is disputing in court), the interest expense on our outstanding debt, as well as significant non-cash charges. For the six-month periods ended June 30, 2016 and June 30, 2015, net loss attributable to common stockholders included $7.2 million and $5.4 million, respectively, in interest, debt-related fees, losses on extinguishment of debt, and changes in the fair value of financial instruments.

Navidea ended the quarter with $1.7 million in cash, $501,000 of which was restricted related to the CRG debt.

Regeneron Reports Second Quarter 2016 Financial and Operating Results

On August 4, 2016 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the second quarter of 2016 and provided a business update (Press release, Regeneron, AUG 4, 2016, View Source [SID:1234514303]).

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Financial Highlights

($ in millions, except per share data)

Three Months Ended
June 30,

2016

2015*

% Change
EYLEA U.S. net product sales

$
831

$
655

27
%
Total revenues

$
1,213

$
999

21
%
GAAP net income

$
196

$
195

1
%
GAAP net income per share – diluted

$
1.69

$
1.69


%
Non-GAAP net income(2)

$
329

$
265

24
%
Non-GAAP net income per share – diluted(2)

$
2.82

$
2.27

24
%

* See Table 3 of this press release for an explanation of revisions made to 2015 non-GAAP amounts previously reported.

"In the first half of this year, EYLEA continued to demonstrate strong sales growth, and Praluent sales made steady progress as healthcare providers become more familiar with this new therapeutic class and learn to navigate payer utilization management criteria," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "In the second half of the year, for sarilumab in rheumatoid arthritis, we look forward to the upcoming U.S. regulatory decision and potential launch. We also recently completed a U.S. regulatory submission for dupilumab for the treatment of atopic dermatitis and are working to bring this breakthrough therapy to patients as soon as possible."

Business Highlights

Marketed Product Update

EYLEA (aflibercept) Injection for Intravitreal Injection

In the second quarter of 2016, net sales of EYLEA in the United States increased 27% to $831 million from $655 million in the second quarter of 2015. Overall distributor inventory levels remained within the Company’s one- to two-week targeted range.
Bayer commercializes EYLEA outside the United States. In the second quarter of 2016, net sales of EYLEA outside of the United States(1) were $486 million, compared to $338 million in the second quarter of 2015. In the second quarter of 2016, Regeneron recognized $167 million from its share of net profit from EYLEA sales outside the United States, compared to $107 million in the second quarter of 2015.
Praluent (alirocumab) Injection for the Treatment of Elevated Low-Density Lipoprotein (LDL) Cholesterol

In the second quarter of 2016, global net sales of Praluent were $24 million. Product sales for Praluent are recorded by Sanofi, and the Company shares in any profits or losses from the commercialization of Praluent. Praluent was launched in the United States in the third quarter of 2015 and in certain countries in the European Union commencing in the fourth quarter of 2015.
In the second quarter of 2016, the U.S. Food and Drug Administration (FDA) accepted for review a supplemental Biologics License Application (sBLA) for a monthly dosing regimen of Praluent, with a target action date of January 24, 2017.
In July 2016, the Japanese Ministry of Health, Labour and Welfare granted marketing and manufacturing authorization for Praluent for the treatment of uncontrolled LDL cholesterol, in certain adult patients with hypercholesterolemia at high cardiovascular risk.
The ODYSSEY OUTCOMES trial remains ongoing, and is assessing the potential of Praluent to demonstrate cardiovascular benefit.
Pipeline Progress
Regeneron has fifteen product candidates in clinical development. These consist of EYLEA and fourteen fully human monoclonal antibodies generated using the Company’s VelocImmune technology, including four in collaboration with Sanofi. In addition to EYLEA and Praluent, highlights from the antibody pipeline include:

Sarilumab, the Company’s antibody targeting IL-6R for rheumatoid arthritis, is currently being studied in the global Phase 3 SARIL-RA program.

In December 2015, the FDA accepted for review a Biologics License Application (BLA) for sarilumab, with a target action date of October 30, 2016.
In July 2016, the European Medicines Agency (EMA) accepted for review the Marketing Authorization Application (MAA) for sarilumab.
Dupilumab, the Company’s antibody that blocks signaling of IL-4 and IL-13, is currently being studied in atopic dermatitis, asthma, nasal polyps, and eosinophilic esophagitis.

A BLA for atopic dermatitis was recently submitted to the FDA.
In April 2016, the Company and Sanofi reported that the Phase 3 LIBERTY AD SOLO 1 and SOLO 2 trials evaluating dupilumab in adult patients with inadequately controlled moderate-to-severe atopic dermatitis met their primary endpoints.
In June 2016, the Company and Sanofi reported that the Phase 3 LIBERTY AD CHRONOS trial evaluating dupilumab with topical corticosteroids in adult patients with inadequately controlled moderate-to-severe atopic dermatitis met its primary and key secondary endpoints.
Fasinumab, the Company’s antibody targeting Nerve Growth Factor (NGF), is currently being studied in patients with pain due to osteoarthritis (Phase 3) and chronic low back pain (Phase 2b/3).

In May 2016, the Company reported top-line results from a Phase 2/3 study evaluating fasinumab in patients with moderate-to-severe osteoarthritis pain of the hip or knee who have a history of inadequate pain relief or intolerance to current analgesic therapies. The study met its primary endpoint at 16 weeks.
REGN2810, an antibody to programmed cell death protein 1 (PD-1), entered a potentially pivotal clinical study for the treatment of advanced cutaneous squamous cell carcinoma in the second quarter of 2016.

Evinacumab is an antibody to Angptl-3. In May 2016, the Company reported positive interim results from an ongoing proof-of-concept study in patients with homozygous familial hypercholesterolemia (HoFH).

REGN3470-3471-3479 is a combination of antibodies to Ebola virus. A Phase 1 clinical study in healthy volunteers was initiated in the second quarter of 2016. In addition, in the second quarter of 2016, the FDA granted orphan-drug designation to REGN3470-3471-3479 for the treatment of Ebola virus infection.

REGN2477 is an antibody to Activin A being developed for Fibrodysplasia Ossificans Progressiva (FOP). A Phase 1 clinical study was initiated in the second quarter of 2016 in healthy volunteers.

Select Upcoming 2016 Milestones

Clinical Programs
Milestones
REGN2176-3 (PDGFR-beta Antibody co-formulated with aflibercept)
Report results from Phase 2 study
Praluent
Data Monitoring Committee interim analysis of ODYSSEY OUTCOMES trial
Ongoing launch in additional countries
Sarilumab (IL-6R Antibody)
FDA target action date of October 30, 2016
File for additional regulatory approvals outside the United States
Dupilumab (IL-4R Antibody)
FDA to provide target action date related to BLA submission for atopic dermatitis in the United States
Complete patient enrollment in Phase 3 asthma trial
Initiate Phase 3 study in pediatric patients in atopic dermatitis

Business Development Update

In April 2016, the Company and Intellia Therapeutics, Inc. entered into a license and collaboration agreement to advance CRISPR/Cas gene-editing technology for in vivo therapeutic development. In addition to the discovery, development and commercialization of new therapies, the companies will focus on technology development of the CRISPR/Cas platform. In May 2016, Intellia completed an initial public offering of its common stock and the Company purchased $50.0 million of Intellia common stock in a concurrent private placement.
In July 2016, the Company and Adicet Bio, Inc. entered into a license and collaboration agreement to develop next-generation engineered immune-cell therapeutics with fully human chimeric antigen receptors and T-cell receptors directed to disease-specific cell surface antigens in order to enable the precise engagement and killing of tumor cells.
Second Quarter 2016 Financial Results

Product Revenues: Net product sales were $834 million in the second quarter of 2016, compared to $658 million in the second quarter of 2015. EYLEA net product sales in the United States were $831 million in the second quarter of 2016, compared to $655 million in the second quarter of 2015.

Total Revenues: Total revenues, which include product revenues described above, increased by 21% to $1,213 million in the second quarter of 2016, compared to $999 million in the second quarter of 2015. Total revenues also include Sanofi and Bayer collaboration revenues of $355 million in the second quarter of 2016, compared to $329 million in the second quarter of 2015. Collaboration revenues in the second quarter of 2016 increased primarily due to an increase in the Company’s net profit from commercialization of EYLEA outside the United States and reimbursement of the Company’s research and development expenses and amortization of up-front payments received in connection with the Company’s July 2015 immuno-oncology collaboration with Sanofi, partly offset by lower reimbursement of the Company’s research and development expenses and an increase in the Company’s share of losses primarily from the commercialization of Praluent under the Company’s antibody collaboration with Sanofi.

Refer to Table 4 for a summary of collaboration revenue.

Research and Development (R&D) Expenses: GAAP R&D expenses were $560 million in the second quarter of 2016, compared to $390 million in the second quarter of 2015. The higher R&D expenses in the second quarter of 2016 were principally due to the $75 million up-front payment made in connection with the April 2016 license and collaboration agreement with Intellia, higher development costs primarily related to fasinumab and REGN2810, and higher headcount to support the Company’s increased R&D activities, partly offset by lower development costs primarily related to dupilumab. In addition, in the second quarter of 2016, R&D-related non-cash share-based compensation expense was $79 million, compared to $60 million in the second quarter of 2015.

Selling, General, and Administrative (SG&A) Expenses: GAAP SG&A expenses were $292 million in the second quarter of 2016, compared to $175 million in the second quarter of 2015. The increase was primarily due to higher commercialization-related expenses in connection with EYLEA and Praluent, and higher headcount. In addition, in the second quarter of 2016, SG&A-related non-cash share-based compensation expense was $48 million, compared to $32 million in the second quarter of 2015.

Cost of Goods Sold (COGS): GAAP COGS was $41 million in the second quarter of 2016, compared to $61 million in the second quarter of 2015. COGS primarily consists of royalties as well as costs in connection with producing U.S. EYLEA commercial supplies, and various start-up costs in connection with the Company’s Limerick, Ireland commercial manufacturing facility. COGS decreased principally due to a decrease in royalties since the Company’s obligation to pay Genentech based on sales of EYLEA ended in May 2016.

Income Tax Expense: In the second quarter of 2016, GAAP income tax expense was $96 million and the effective tax rate was 32.9%, compared to $133 million and 40.7% in the second quarter of 2015. The effective tax rate for the second quarter of 2016 was positively impacted, compared to the U.S. federal statutory rate, by the tax benefit associated with stock-based compensation, the domestic manufacturing deduction, and the federal tax credit for increased research activities, partly offset by the negative impact of losses incurred in foreign jurisdictions with rates lower than the federal statutory rate and the non-tax deductible Branded Prescription Drug Fee. As described in Table 3 of this press release, the Company adopted Accounting Standards Update 2016-09 (ASU 2016-09), Compensation – Stock Compensation, Improvements to Employee Share-Based Payment Accounting, during the second quarter of 2016. ASU 2016-09 requires companies to recognize all excess tax benefits and tax deficiencies in connection with stock-based compensation as income tax expense or benefit in the income statement (previously, excess tax benefits were recognized in additional paid-in capital on the balance sheet).

GAAP and Non-GAAP Net Income: The Company reported GAAP net income of $196 million, or $1.88 per basic share and $1.69 per diluted share, in the second quarter of 2016, compared to GAAP net income of $195 million, or $1.89 per basic share and $1.69 per diluted share, in the second quarter of 2015.

The Company reported non-GAAP net income of $329 million, or $3.15 per basic share and $2.82 per diluted share, in the second quarter of 2016, compared to non-GAAP net income of $265 million, or $2.58 per basic share and $2.27 per diluted share, in the second quarter of 2015.

A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

2016 Financial Guidance(3)

The Company’s updated full year 2016 financial guidance consists of the following components:

EYLEA U.S. net product sales
20% – 25% growth over 2015 (reaffirmed)
Sanofi reimbursement of Regeneron commercialization-related expenses
$310 million – $340 million
(previously $320 million – $370 million)
Non-GAAP unreimbursed R&D(2) (4)
$970 million – $1.01 billion
(previously $875 million – $950 million)
Non-GAAP SG&A(2) (4)
$980 million – $1.02 billion
(previously $925 million – $1.0 billion)
Effective tax rate
33% – 41%
Capital expenditures
$480 million – $530 million
(previously $550 million – $625 million)

(1)
Regeneron records net product sales of EYLEA in the United States. Outside the United States, EYLEA net product sales comprise sales by Bayer in countries other than Japan and sales by Santen Pharmaceutical Co., Ltd. in Japan under a co-promotion agreement with an affiliate of Bayer. The Company recognizes its share of the profits (including a percentage on sales in Japan) from EYLEA sales outside the United States within "Bayer collaboration revenue" in its Statements of Operations.

(2)
This press release uses non-GAAP net income, non-GAAP net income per share, non-GAAP unreimbursed R&D, and non-GAAP SG&A, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"). These non-GAAP financial measures are computed by excluding certain non-cash and other items from the related GAAP financial measure. Non-GAAP adjustments also include the income tax effect of reconciling items.

The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company’s control, such as the Company’s stock price on the dates share-based grants are issued. Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company’s core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company’s non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by Regeneron should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP. A reconciliation of the Company’s historical GAAP to non-GAAP results is included in Table 3 of this press release.

(3)
The Company’s 2016 financial guidance does not assume the completion of any significant business development transactions not completed as of the date of this press release.

(4)
A reconciliation of full year 2016 non-GAAP to GAAP financial guidance is included below:

Projected Range
(In millions)

Low

High
GAAP unreimbursed R&D (5)

$
1,390

$
1,450

R&D: Non-cash share-based compensation expense

(320)

(340)

R&D: Upfront payments related to license and
collaboration agreements

(100)

(100)

Non-GAAP unreimbursed R&D

$
970

$
1,010

GAAP SG&A

$
1,205

$
1,275

SG&A: Non-cash share-based compensation expense

(225)

(255)

Non-GAAP SG&A

$
980

$
1,020

(5)
Unreimbursed R&D represents R&D expenses reduced by R&D expense reimbursements from the Company’s collaborators and/or customers.

Stemline Therapeutics Reports Second Quarter 2016 Financial Results and Highlights Recent Clinical Progress

On August 4, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported financial results for the quarter ended June 30, 2016 (Press release, Stemline Therapeutics, AUG 4, 2016, View Source [SID:1234514305]). Clinical highlights and milestones include:

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SL-401 in blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Oral presentations of Phase 2 clinical trial results of SL-401 in patients with BPDCN delivered at annual meetings of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Hematology Association (EHA) (Free EHA Whitepaper).
SL-401 efficacy and safety data continue to be positive with increasing treatment duration, drug exposure, and patient enrollment.
As of July 2016, 29 BPDCN patients have received SL-401, including 26 adults (16 first-line and 10 relapsed/refractory) and 3 pediatric compassionate use patients.
SL-401 continues to maintain high overall response rates (ORR) in both first-line (>90% ORR) and relapsed/refractory adult BPDCN (>50% ORR). Notably, a relapsed/refractory BPDCN patient was recently bridged to stem cell transplant (SCT) following a major response to SL-401.
Response duration, progression free and overall survival data continue to mature and trend favorably. Multiple patients remain progression free after receiving ongoing SL-401 treatment (up to 12+ months [16+ cycles], ongoing) or experiencing a major response on SL-401 and proceeding to SCT (up to 16+ months, ongoing).
Further clinical and regulatory updates expected this year.
SL-401 in additional malignancies

Completed lead-in, dose escalation stage of Phase 2 trial in patients with acute myeloid leukemia (AML) in remission with high relapse risk including minimal residual disease (MRD). There were no unexpected side effects and no dose limiting toxicities. The expansion stage is currently enrolling MRD+ AML patients at 12 ug/kg.
Patients are currently enrolling in the lead-in, dose escalation stage of a Phase 2 trial in advanced, high risk myeloproliferative neoplasms (MPN). The first two dosing cohorts have been cleared with no unexpected side effects and no dose limiting toxicities. Patients are currently enrolling in the third dosing cohort, 12 ug/kg.
Patients are currently enrolling in a Phase 1/2 trial in relapsed or refractory multiple myeloma with SL-401 in combination with pomalidomide and dexamethasone (POM+DEX); the first combination trial of SL-401 with another agent. No unexpected side effects and no dose limiting toxicities have been observed with the combination to date. Enrollment continues.
Further clinical updates expected later this year from these trials.
SL-701

Phase 2 trial of SL-701 in combination with bevacizumab in adult patients with second-line GBM currently enrolling patients.
Trial updates expected later this year.
SL-801

Phase 1 trial of SL-801 in patients with advanced solid tumors currently enrolling. The first and second dosing cohorts have cleared, and the third cohort is currently enrolling.
Trial updates expected later this year and on into next year.
Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "We are making substantial progress across our entire clinical pipeline this year. A key highlight of the quarter was the high profile oral presentations of positive results from our ongoing Phase 2 potentially pivotal trial of SL-401 in BPDCN at both the ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) annual meetings." Dr. Bergstein continued, "The efficacy and safety data from this trial continue to be strong with increasing treatment duration and patient exposure. We look forward to additional clinical and regulatory updates this year, including more clarity around our registration pathway and timeline."

Dr. Bergstein concluded, "As we continue to build upon our compelling data in BPDCN, we also look forward to further updates later this year regarding our multiple enrolling trials with SL-401 in additional hematologic cancers, SL-701 in brain cancer, and SL-801 in advanced solid tumors. Importantly, our strong cash position provides us with the resources to reach important milestones across all of our programs this year and beyond."

Second Quarter 2016 Financial Results Review
Stemline ended the second quarter of 2016 with $81.2 million in cash, cash equivalents and investments, as compared to $87.8 million as of March 31, 2016, which reflects a cash burn of $6.6 million for the quarter.

For the second quarter of 2016, Stemline had a net loss of $9.3 million, or $0.52 per share, compared with a net loss of $10.2 million, or $0.58 per share, for the same period in 2015.

Research and development expenses were $6.9 million for the second quarter of 2016, which reflects a decrease of $1.3 million, or 16%, compared with $8.2 million for the second quarter of 2015. The lower expenses year over year were primarily attributable to an increase in costs in the prior year relating to clinical site startup expenses and initiation of clinical trial activities.

General and administrative expenses were $2.9 million for the second quarter of 2016, which reflects an increase of $0.7 million, or 33%, compared with $2.2 million for the second quarter of 2015. The increase in expense year over year was primarily attributable to higher non-cash stock based compensation and payroll costs relating to employees.