On November 7, 2016 ArQule, Inc. (Nasdaq: ARQL) reported its financial results for the third quarter of 2016 (Press release, ArQule, NOV 7, 2016, View Source [SID1234516358]).

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For the quarter ended September 30, 2016, the Company reported a net loss of $5,817,000 or $0.08 per share, compared to a net loss of $2,354,000 or $0.04 per share, for the third quarter of 2015. For the nine-month period ended September 30, 2016, the Company reported a net loss of $15,898,000 or $0.23 per share, compared to a net loss of $10,922,000 or $0.17 per share for the nine-month period ended September 30, 2015.

At September 30, 2016, the Company had a total of $37,659,000 in cash, equivalents and marketable securities.

Key Highlights

ARQ 087, our proprietary FGFR inhibitor, is approaching completion of enrollment in the phase 2 portion of the phase 1/2 trial in intrahepatic cholangiocarcinoma (iCCA). Discussions with regulatory agencies in the U.S. and Europe are nearing completion for the design of a potential pivotal trial in iCCA. We plan to finalize the trial design by year end pending final trial results.
ARQ 531, our proprietary reversible BTK inhibitor, continues to demonstrate best-in-class potential with preclinical data to be presented at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The data, to be presented by The Ohio State University, demonstrate that ARQ 531 effectively inhibits C481S mutant BTK in patient derived cells and in a TCL1 mouse model shows efficacy superior to that of ibrutinib in Chronic Lymphocytic Leukemia (CLL). The company plans to complete preclinical studies and file an Investigational New Drug (IND) application in early 2017 to begin clinical trials with an initial focus on the fast-to-market, ibrutinib resistant C481S mutant BTK CLL population.
ARQ 092, our lead proprietary AKT inhibitor, continues to demonstrate the potential utility of targeting AKT in rare non-oncological indications and will be the focus of an oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting. The data, to be presented by The University of Illinois College of Medicine, demonstrate that in neutrophils and platelets from Sickle Cell Disease (SCD) patients in vitro and cell-cell interactions in a mouse model of SCD, ARQ 092 attenuates neutrophil-platelet interactions. The study provides evidence that ARQ 092 could be a novel therapy in treating and preventing acute vaso-occlusive complications in SCD. The data warrants further studies of ARQ 092 in SCD.
ARQ 092 phase 1 trial for Proteus syndrome continues to enroll and our collaborator, the National Institutes of Health (NIH), is in the final stages of implementing an updated enrollment protocol that will facilitate logistics for patients and their families. To date, the drug has been well tolerated, and we are looking forward to assessing full data from the initial two cohorts in the early part of next year.
ARQ 092 clinical research to be expanded into PROS (PIK3CA-Related Overgrowth Spectrum) family of rare diseases. The company received approval of its IND application from the Food and Drug Administration (FDA) in the PROS family of rare diseases, including Proteus syndrome, for a potential clinical trial.
Tivantinib METIV-HCC phase 3 trial for hepatocellular carcinoma (HCC) is scheduled to conclude in early 2017. Top-line data is expected in the first quarter of 2017.
"It is exciting to see our proprietary pipeline being pursued independently and through collaborations with the top researchers in the fields of oncology, hematology and selected rare diseases," said Paolo Pucci, Chief Executive Officer of ArQule. "We are encouraged that several projects have attracted the interest of leading scientific institutions including ARQ 531, our BTK inhibitor, which is in preclinical testing with our collaborators at The Ohio State University. ARQ 092 continues to progress in Proteus syndrome through a program that includes a phase 1 trial conducted by the NIH. In addition, we now have preclinical data for ARQ 092 in Sickle Cell Disease through the work of The University of Illinois College of Medicine. Lastly, we are pleased to have moved closer to a potential pivotal trial in an attractive fast to market opportunity for ARQ 087 in iCCA."

"Our lead proprietary drug candidate, ARQ 087, is nearing completion of the phase 2 iCCA trial," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "Encouraging discussions and positive feedback from the regulatory agencies, combined with the totality of the efficacy data we have observed in the clinical trials, has moved us closer to defining a pivotal trial design for ARQ 087 in this indication."

Revenues and Expenses

Revenues for the quarter ended September 30, 2016, were $1,223,000 compared with revenues of $2,653,000 for the quarter ended September 30, 2015. Revenues in the nine-months ended September 30, 2016 were $3,522,000 compared with revenues of $8,442,000 in the nine-months ended September 30, 2015. Revenue in the three and nine-month periods of 2016 and 2015 is comprised of revenue from the Daiichi Sankyo tivantinib development agreement and the Kyowa Hakko Kirin exclusive license agreement.

The revenue decreases in the quarter ended September 30, 2016 of $0.5 million from our Daiichi Sankyo METIV-HCC trial and $1.0 million from our Kyowa Hakko Kirin JET-HCC trial were principally due to the March 2016 extension of the development period through December 31, 2016 for both programs. The revenue decreases in the nine months ended September 30, 2016 of $2.0 million from our Daiichi Sankyo METIV-HCC trial and $2.9 million from our Kyowa Hakko Kirin JET-HCC trial were also principally due to the extension of the development period through December 31, 2016.

Research and development expense in the third quarter of 2016 was $5,265,000 compared with $3,180,000 for the third quarter of 2015. The $2.1 million increase in research and development expense in the third quarter of 2016 was principally due to increased outsourced clinical and product development costs of $1.9 million and professional fees of $0.2 million.

Research and development expense in the nine-months ended September 30, 2016 was $13,800,000 compared with $11,920,000 in the nine-months ended September 30, 2015. The $1.9 million increase in research and development expense in the nine-months ended September 30, 2016 was primarily due to increased outsourced clinical and product development costs of $2.6 million and professional fees of $0.2 million, partially offset by decreased labor and related costs of $0.4 million and facility costs of $0.5 million.

General and administrative expense was $1,824,000 in the third quarter of 2016 compared with $1,839,000 in the third quarter 2015.

General and administrative expense was $5,755,000 in the nine-months ended September 30, 2016 compared with $7,802,000 in the nine-months ended September 30, 2015. General and administrative expense decreased by $2.0 million in the nine-months ended September 30, 2016 primarily due to lower facility costs of $1.6 million, labor related costs of $0.2 million and professional fees of $0.2 million.

On November 7, 2016 pSivida Corp. (NASDAQ:PSDV) (ASX:PVA), a leader in the development of sustained release drug products and technologies, reported financial results for its fiscal first quarter ended September 30, 2016 (Press release, pSivida, NOV 7, 2016, View Source [SID1234516355]). In addition, the Company’s new leadership team updated corporate objectives and anticipated product development milestone timeline.

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"Since joining the Company in mid-September, I have been working with our team to assess the impressive clinical and commercial potential of our pipeline that is largely based on pSivida’s proven Durasert sustained drug release technology, the only intraocular sustained release technology with approval of three different products," said Nancy Lurker, President & CEO. "We’ve made significant progress on a number of fronts and I’m even more excited about the potential for pSivida to make a true difference in patients’ lives while we build returns to our shareholders. Our assessment reaffirmed the clear strength and quality of clinical data from studies of our Durasert three-year treatment for posterior segment uveitis (formerly known as Medidur) and we remain focused on preparing our submission for approval of this product candidate in both the European Union and United States during 2017. We’ve also begun a thorough examination of how to most efficiently and effectively launch the Durasert three-year uveitis product in the United States while we actively explore partnership possibilities to address patients with a similar diagnosis in Europe."

"Our review also resulted in our management team deploying more focus on lower risk and nearer term market opportunities as well as a renewed emphasis on potential collaborations for our Durasert technology and implementation of improvements to our product candidate evaluations. Since joining, we have continued to advance our uveitis clinical program and have reprioritized our development programs. These now include a next generation Durasert bio-erodible shorter duration treatment for posterior segment uveitis, increased emphasis on Durasert for severe osteoarthritis (OA) of the knee in conjunction with HSS, and continued work on our Durasert tyrosine kinase inhibitor (TKI) program for Wet AMD. We also continue to pursue our Tethadur platform for large molecules," Ms. Lurker added.

Fiscal First Quarter 2017 Results

Revenue for the first fiscal quarter ended September 30, 2016 totaled $277,000 compared to $466,000 for the prior year quarter. The year-over-year decrease was primarily attributable to $157,000 of non-royalty sublicense consideration earned from Alimera in the prior-year period. Operating expenses for the three months ended September 30, 2016 totaled $7.5 million compared to $5.4 million a year earlier. The increase was primarily attributable to approximately $1.1 million of severance costs, professional fees and stock-based compensation expense related to the September CEO transition, $436,000 of costs for the previously announced U.K. restructuring and approximately $300,000 of CRO and regulatory contractor costs for our Durasert three-year uveitis product candidate. Net loss for the quarter ended September 30, 2016 was $7.2 million, or $0.21 per share, compared to net loss of $4.9 million, or $0.17 per share, for the prior year quarter.

At September 30, 2016, cash, cash equivalents and marketable securities totaled $22.5 million.

Product Candidate Program Update & Anticipated Milestones

Durasert three-year treatment for posterior segment uveitis: The Company met its enrollment target in the second uveitis Phase 3 trial of 150 patients in September. Readout of this second trial, which is required by the U.S. Food & Drug Administration for the Company’s NDA filing, is currently expected by the end of the first half of 2017. The first Phase 3 study met its primary efficacy endpoint with a p value of < 0.001 and safety data that are consistent with the known effect of ocular corticosteroid use. With regard to the planned E.U. submission for marketing authorization, management’s goal remains to submit during the first quarter of 2017. The Company was recently notified that protocol approval for a pediatric study would be required by the European regulatory authority prior to the acceptance of the application for market authorization. The protocol for the pediatric study has been submitted and the timing of its approval could move the acceptance of the market application into the second quarter of 2017.

Next Generation Durasert bio-erodible shorter duration treatment for posterior segment uveitis: The Company has initiated and prioritized a development program for a next generation Durasert bio-erodible for uveitis. The Company is initiating formulation testing now and expects to begin pre-clinical safety and PK studies of this product candidate in the first half of 2017. Management believes this product candidate will provide enhanced benefits to patients and physicians by offering a shorter delivery time period of corticosteroid and providing more flexibility to physicians with multiple Durasert dosing intervals.

Durasert implant for severe osteoarthritis (OA) of the knee: On August 1, 2016, the Hospital for Special Surgery in New York, NY and pSivida announced the opening of an IND in support of an investigator-sponsored clinical study of a Durasert implant to treat severe OA of the knee. Management believes severe OA of the knee is a large and growing condition with continued high unmet medical needs. The implant is designed to provide long-term pain relief for this condition, which, if effective, could potentially result in the delay of knee replacement surgery. The study is an open-label, single dose, safety and tolerability study of the screw implant to deliver dexamethasone, a corticosteroid previously proven to provide pain relief in knee OA. Six patients will each receive the implant in one knee. While a safety and tolerability study, change from baseline in weekly mean of pain intensity scored at rest, during activity and at night will be assessed through 24 weeks. To date two patients have received the implant and HSS expects to have all six patients implanted over the next few months.

Durasert bio-erodible TKI for Wet AMD: Management believes that pSivida’s TKI program could represent a valuable advancement to the treatment of Wet AMD. As part of the new leadership’s program assessment, it has been determined that further evaluation of additional TKIs is needed to optimize candidate selection, and management is actively pursuing a lead candidate for the clinic.

Tethadur for large molecules: The Tethadur program applies proprietary technology to achieve the sustained release of large molecules such as biologics. Recently, management narrowed its focus to silica-based technology from the earlier silicon-based technology in an effort to advance the program in a cost-effective way. Pre-clinical activities on this program are continuing.

"During the past few weeks I have had the pleasure of getting to know the people that developed pSivida’s terrific technology. With the recent additions of Dr. Dario Paggiarino and Deb Jorn, we have a talented and committed team with a singular focus to successfully bring pSivida’s products to patients and deliver greater shareholder returns," concluded Ms. Lurker.

On November 7, 2016 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) reported financial results for the third quarter 2016 and business update (Press release, Progenics Pharmaceuticals, NOV 7, 2016, View Source [SID1234516354]).

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"In recent months, we have realized $100 million in non-dilutive funding from RELISTOR, first with the $50M RELISTOR oral approval milestone in July, followed by the $50 million of proceeds from the non-recourse loan secured by future RELISTOR royalties announced today," said Mark Baker, Chief Executive Officer of Progenics. "With our strong balance sheet, we have the resources to advance our programs through key milestones. We expect to report registrational topline data, in early 2017, for our ultra-orphan radiotherapeutic candidate AZEDRA, for the treatment of pheochromocytoma and paraganglioma, rare tumors of the adrenal gland, and are beginning to build our commercial infrastructure to support a potential launch. In addition, we are continuing to advance our innovative portfolio of imaging agents and therapeutic candidates which have the potential to transform how we find, fight and follow prostate cancer."

Key Business Highlights

RELISTOR, treatment for opioid-induced constipation (partnered with Valeant Pharmaceuticals International, Inc.)

Announced Food and Drug Administration (FDA) Approval and Commercial Launch of Oral RELISTOR for the Treatment of Opioid Induced Constipation in Adults with Chronic Non-Cancer Pain. The approval triggered a $50 million milestone payment on July 25 from Progenics’ commercialization partner, Valeant, as well as subsequent royalties and the potential of up to $200 million in sales milestones.

RELISTOR (SC and Oral) Net Sales for the Third of 2016 Totaled $22.1 million. The third quarter 2016 sales, as reported to Progenics by Valeant, translated to $3.3 million in royalty revenue for the quarter.
AZEDRA, Ultra-orphan radiotherapeutic candidate

AZEDRA Topline Results Expected First Quarter 2017. In early 2017, Progenics expects to report topline results from its ongoing registrational trial of AZEDRA. If the AZEDRA trial meets the endpoints of the Special Protocol Assessment (SPA), Progenics expects to submit a New Drug Application (NDA) to the FDA during the first half of 2017.
PSMA-Targeted Prostate Cancer Pipeline

Enrollment in Pivotal Phase 3 Study of 1404 is Ongoing. The study will enroll up to 450 patients with newly-diagnosed or low-grade prostate cancer who are candidates for active surveillance. Progenics plans for an interim analysis by the end of this year, to assess futility and evaluate the need for a sample size re-estimation, remain unchanged.

On Track to Initiate Phase 2/3 Trial of PyL Imaging Agent. Progenics remains on-track to initiate a Phase 2/3 trial of PyL by year-end. The study is designed to assess the diagnostic accuracy of PyL PET/CT imaging in patients with high risk and/or metastatic prostate cancer.

PyL Research Access ProgramTM. At the recent Prostate Cancer Foundation Scientific Retreat, Progenics announced a new PyL research access program that will make limited doses of PyL available to researchers beginning January 1, 2017. Progenics will be able to use the data generated from the access program to support its registration efforts for PyL and advance the development of algorithms designed to analyze and interpret the scans.

Company Remains On-Track to Initiate a Phase 1 Trial of 1095 in the Fourth Quarter of 2016. The Phase 1 Study of 1095, a PSMA-Targeted Therapeutic for Metastatic Prostate Cancer, will be conducted at Memorial Sloan Kettering Cancer Center.
Corporate

Announced $50 Million RELISTOR Royalty-Backed Non-Dilutive Debt Financing with HealthCare Royalty Partners. In a separate press release issued today, Progenics announced that it has entered into a $50 million non-recourse, term loan agreement secured by and to be repaid from royalties on future sales of RELISTOR. Any future sales milestones received under Valeant agreement are excluded from the transaction and would not be used to repay interest or principal on the loan. Progenics and HealthCare Royalty Partners may mutually elect to include a second tranche of an additional $50 million within twelve months of the closing date.

Appointed Biopharmaceutical Industry Veteran Bryce V. Tenbarge as Vice President of Commercial. Mr. Tenbarge brings to Progenics over fifteen years of experience in biopharmaceutical marketing, most recently as Vice President of Marketing and Commercialization at Celldex Therapeutics.
Third Quarter 2016 Financial Results

Third quarter revenue totaled $53.9 million, up from $1.4 million in the third quarter of 2015, reflecting RELISTOR royalty income of $3.3 million compared to $1.2 million in the corresponding period of 2015. Valeant’s reported net sales include a non-recurring favorable sales return adjustment and launch of oral RELISTOR. The increase in revenue was primarily attributable to milestone revenue of $50 million for the July 19 approval of RELISTOR Tablets.

Third quarter and year-to-date research and development expenses increased by $2.8 million and $6.7 million, respectively, compared to the corresponding prior year periods, resulting from higher clinical trial and contract manufacturing expenses for 1404, AZEDRA, PyL and 1095. Third quarter general and administrative expenses increased by $2.6 million compared to the corresponding prior year period, primarily attributable to an accrual for front pay compensation related to litigation with a former employee, and higher consulting and market research expenses. Year-to-date general and administrative expenses increased by $4.2 million compared to the corresponding period in 2015, primarily due to higher depreciation expense as a result of a reduction in the remaining useful lives of our leasehold improvements at our Tarrytown, NY location, and higher compensation, consulting and market research expenses. Progenics also recorded a non-cash charge of $0.6 million in the third quarter related to an increase in the fair value estimate of the contingent consideration liability.

Net income attributable to Progenics for the quarter was $36.3 million or $0.52 per diluted share, compared to a net loss of $10.0 million or $0.14 per diluted share in the corresponding 2015 period. Progenics ended the quarter with cash and cash equivalents of $98.9 million, an increase of $24.8 million compared to cash and cash equivalents as of December 31, 2015.

On November 7, 2016 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that new data investigating the use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in patients with previously treated advanced urothelial cancer will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 31st Annual Meeting, Nov. 9-13 (Press release, Merck & Co, NOV 7, 2016, View Source [SID1234516353]). Data on overall survival (OS) and progression-free survival (PFS) from the phase 3 KEYNOTE-045 study – investigating KEYTRUDA compared to investigator’s choice chemotherapy in patients with metastatic or locally advanced or unresectable urothelial cancer that has recurred or progressed following platinum-based chemotherapy – will be presented for the first time; these data were accepted as a late-breaking abstract. In addition, results from three different studies exploring the utility of various biomarkers for KEYTRUDA will be presented at the meeting.

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KEYTRUDA Data at SITC (Free SITC Whitepaper) 2016

Below is a select listing of the KEYTRUDA abstracts accepted at SITC (Free SITC Whitepaper) 2016; abstracts are available on the meeting website .

Late-Breaking Oral Presentation, Location: Maryland Ballroom

(Abstract #470) KEYNOTE-045: open-label, phase 3 study of pembrolizumab versus investigator’s choice of paclitaxel, docetaxel, or vinflunine for previously treated advanced urothelial cancer.
Session Time: Saturday, Nov. 12, 11:15 a.m. – 12:00 p.m. ET
Presentation Time: 11:45 a.m. – 12:00 p.m. ET
Poster Presentations, Location: Prince George’s Exhibition Hall AB

(Abstract #61) Association between microsatellite instability and clinical response across tumor types in the phase 1b KEYNOTE-012 and KEYNOTE-028 studies of pembrolizumab in PD-L1-expressing advanced solid tumors.
Session Time: Friday, Nov. 11, 12:15 p.m. – 1:30 p.m. ET
(Abstract #72) An immune-related gene expression profile delineates features of the tumor microenvironment required for clinical response to PD-1 blockade.
Session Time: Saturday, Nov. 12, 11:45 a.m. – 1:00 p.m. ET
(Abstract #73) Tumor mutational load and T cell inflamed microenvironment are independent determinants of response to pembrolizumab.
Session Time: Friday, Nov. 11, 12:15 p.m. – 1:30 p.m. ET
The KEYTRUDA (pembrolizumab) clinical development program includes more than 30 tumor types in more than 360 clinical trials, including nearly 200 trials that combine KEYTRUDA with other cancer treatments. For genitourinary cancers, Merck has the largest immuno-oncology clinical development program in bladder cancer, with 27 trials underway involving KEYTRUDA as monotherapy and in combination, including four registration-enabling studies.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA (pembrolizumab) is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA (pembrolizumab) can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA (pembrolizumab) occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA (pembrolizumab) is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 360 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On November 7, 2016 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported financial results for the third quarter ended September 30, 2016 (Press release, BioCryst Pharmaceuticalsa, NOV 7, 2016, View Source [SID1234516352]).

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"Our company’s primary focus is on the execution of the APeX-1 trial of BCX7353," said Jon P. Stonehouse, President & Chief Executive Officer. "The screening success rate in APeX-1 has been high, approximately 90%, similar to our previous studies in HAE. We are pleased that subject screening has gained momentum recently. As of last Friday, 19 subjects have been screened, of whom 16 have been randomized. Based on our current number of randomized patients, we are modifying our projection for reporting the results of part one to the first quarter of 2017."

Third Quarter Financial Results
For the three months ended September 30, 2016, revenues decreased to $7.8 million from $11.0 million in the third quarter of 2015, largely due to decreased RAPIVAB product sales associated with the transition of RAPIVAB commercialization to the Company’s partner, Seqirus UK Limited (Seqirus), as well as a decrease in collaborative revenue associated with galidesivir (formerly BCX4430) development, which is funded by U.S. Government contracts. This decrease was offset by a large increase in RAPIACTA royalties from government stockpiling sales by the Company’s commercial partner in Japan, Shionogi & Co. Ltd.

(Shionogi).
Research and Development (R&D) expenses for the third quarter of 2016 decreased to $14.1 million from $20.1 million in the third quarter of 2015. This decrease was related to the discontinuation of avoralstat development activities subsequent to OPuS-2 during the summer.
General and Administrative (G&A) expenses for the third quarter of 2016 were $2.8 million, and were consistent with $2.7 million for the third quarter of 2015.
Interest expense, which is currently and primarily related to the Company’s non-recourse notes payable, was $1.5 million in the third quarter of 2016 and $1.2 million in the third quarter of 2015. In addition, a $931,000 mark-to-market loss on the Company’s foreign currency hedge was recognized in the third quarter of 2016, as compared to a $460,000 mark-to-market loss in the third quarter of 2015. These losses resulted from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of the Company’s underlying hedge arrangement. During the third quarter of 2015, the Company also realized a currency hedge gain of $108,000 from the exercise of a U.S. Dollar/Japanese yen currency option.
The net loss for the third quarter of 2016 was $11.5 million, or a $0.16 net loss per share as compared to a net loss of $14.6 million, or $0.20 net loss per share, for the third quarter 2015.
Cash, cash equivalents and investments decreased to $68.7 million at September 30, 2016, as compared to $100.9 million at December 31, 2015. Net operating cash use for the third quarter of 2016 was $15.0 million, as compared to $12.3 million for the third quarter of 2015. In September 2016, we closed a $23 million senior credit facility, which provided net proceeds to the Company that exceeded cash utilized for operations in the third quarter, thereby increasing the Company’s total cash and investments from June 30, 2016. The senior credit facility was fully funded at closing and bears a variable interest rate based upon LIBOR, currently at 8.5%; an interest-only payment period through fiscal 2017; and scheduled principal and interest payments starting in January 2018 and for the following 40 months. Proceeds from the facility are forecasted to extend the Company’s cash runway into the first quarter of 2018 based upon current operating plans. The Company has the option to repay the facility at any time prior to the scheduled principal repayment schedule.
Year to Date Financial Results
For the nine months ended September 30, 2016, total revenues decreased to $17.4 million, from $43.7 million in the first nine months 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 to Seqirus, no longer recording product sales in 2016 associated with the Seqirus transaction, as well as a decrease in collaborative revenue associated with galidesivir development.
R&D expenses decreased to $48.9 million in the nine months of 2016 from $53.7 million in the first nine months of 2015. The decrease in 2016 R&D expense, as compared to 2015, reflects the discontinuation of avoralstat development as well as reduced spending on the galidesivir program.
G&A expenses decreased to $8.7 million for the nine months ended September 30, 2016 from $10.3 million for the nine months ended September 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 nine months of 2016 and 2015, interest expense was $4.4 million and $3.9 million, respectively, and was primarily related to the Company’s non-recourse notes payable. A mark-to-market loss on the Company’s foreign currency hedge of $7.4 million was recognized in the first nine months of 2016, compared to a mark-to-market loss of $793,000 in the first nine months 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 the Company’s underlying hedge arrangement. During the second quarters of 2016 and 2015, we also realized currency gains of $811,000 and $1.7 million, respectively, from the exercise of a U.S. Dollar/Japanese yen currency option within the Company’s foreign currency hedge.
The net loss for the nine months ended September 30, 2016 increased to $50.6 million, or $0.69 per share, from $24.9 million, or $0.34 per share for the same period last year.
Corporate Update & Outlook
In August, BioCryst announced that it dosed the first subject in the APeX-1 clinical trial of BCX7353 for the oral treatment of hereditary angioedema (HAE). The goal of the APeX-1 trial is to reduce or eliminate angioedema attacks in patients with HAE. Results from
APeX-1 are expected in the first quarter of 2017.

On September 7, BioCryst announced positive results from a proof-of-concept study of its broad spectrum antiviral, galidesivir, (formerly BCX4430), for the delayed treatment of Ebola virus infection in rhesus macaques.

On September 26, the Company announced that it closed a $23 million Senior Credit Facility with Midcap Financial.

On October 29, galidesivir nonclinical results from a Zika virus infection model were presented in a late-breaker scientific session at IDWeek by Dr. James B. Whitney, PhD, Assistant Professor of Medicine, Harvard Medical School, and Principal Investigator in the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston. Galidesivir dosing in rhesus macaques was well-tolerated and offered significant protection against Zika virus infection.
Financial Outlook for 2016
Based upon development plans and the Company’s awarded government contracts, BioCryst continues to expect its 2016 net operating cash use to be in the range of $55 to $75 million, and has revised its 2016 operating expenses to be in the range of $68 to $80 million, which reflects a reduction from the previous forecasted range of $78 to $98 million. BioCryst’s 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 the vesting of the Company’s outstanding performance-based stock options.