On November 5, 2015 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported its third quarter 2015 financial results and ongoing progress with its pipeline, including duvelisib, an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, and IPI-549, an oral immuno-oncology development candidate that selectively inhibits PI3K-gamma (Press release, Infinity Pharmaceuticals, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107548 [SID:1234508033]). Infinity also announced today that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the investigation of duvelisib for the treatment of patients with follicular lymphoma (FL) who have received at least two prior therapies. Earlier this year, Infinity received Fast Track designation for the investigation of duvelisib for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Infinity is conducting registration-focused trials evaluating the safety and efficacy of duvelisib, including DYNAMO, a Phase 2 study in patients with refractory indolent non-Hodgkin lymphoma (iNHL), and DUO, a Phase 3 study in patients with relapsed/refractory CLL.

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"The quarter was marked by important clinical development progress for duvelisib, particularly the completion of patient enrollment in DYNAMO. We are also pleased to have recently received Fast Track designation for the investigation of duvelisib for the treatment of follicular lymphoma in patients who have received at least two prior therapies, which complements our Fast Track designation in CLL and supports our belief in the potential of duvelisib to help fill important medical needs," stated Adelene Perkins, Infinity’s chair, president and chief executive officer. "We are making strong progress toward the completion of patient enrollment in DUO and expect to complete enrollment this quarter. We look forward to completing our regulatory requirements expeditiously to leverage the Fast Track opportunities as we pursue parallel registration paths within iNHL and CLL."

In addition to the DYNAMO and DUO studies, Infinity is conducting CONTEMPO, a Phase 1b/2 study in treatment-naive FL patients, and SYNCHRONY, a Phase 1b study in CLL patients whose disease is refractory to or has relapsed while receiving a Bruton’s tyrosine kinase (BTK) inhibitor. Infinity expects three additional clinical studies to begin this year, including the first clinical study of duvelisib in combination with venetoclax, AbbVie’s first-in-class investigational B-cell lymphoma-2 (BCL-2) selective inhibitor. Infinity and AbbVie are jointly developing duvelisib in oncology.

"At Infinity, our mission is to build a company and a community that can sustainably discover, develop and deliver first-in-class and best-in-class medicines to patients. The recent expansion of our pipeline into solid tumors with the addition of IPI-549 represents an important step toward fulfilling our mission. We are planning to initiate a Phase 1 study of IPI-549 in patients with solid tumors in the first quarter of 2016," Ms. Perkins continued.

In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 has the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring an anti-tumor immune response when used in combination with other immunotherapies such as checkpoint inhibitors.

Recent highlights include the following:

Duvelisib Program

Duvelisib granted Fast Track designation for the treatment of patients with FL: Infinity reported that the FDA granted Fast Track designation for the investigation of duvelisib for the treatment of patients with FL who have received at least two prior therapies. The FDA established the Fast Track designation process to facilitate the development and expedite the review of investigational medicines intended to treat serious or life-threatening conditions and that demonstrate the potential to address an unmet medical need.

Duvelisib data to be presented at ASH (Free ASH Whitepaper) Annual Meeting: Infinity reported that three duvelisib abstracts have been accepted for presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2015 Annual Meeting, which is being held December 5 – 8 in Orlando, Florida. Presentations will include data from preclinical and translational research conducted in collaboration with The Feinstein Institute for Medical Research demonstrating that inhibition of PI3K-delta and PI3K-gamma affect B-cell growth and survival through both direct effects on CLL cells as well as by disrupting the tumor microenvironment. Additionally, clinical data from two investigator-sponsored studies in patients with hematologic malignancies will be presented. The three poster presentations are as follows:

Saturday, December 5, 2015, 5:30 p.m. – 7:30 p.m. ET
Title: Dual inhibition of PI3K-delta and gamma by duvelisib (IPI-145) impairs CLL B- and T-cell migration, survival and proliferation in a murine xenograft model using primary chronic lymphocytic leukemia cells (Abstract #1753)
Lead Author: Shih-Shih Chen, Ph.D., The Feinstein Institute for Medical Research

Monday, December 7, 2015, 6:00 p.m. – 8:00 p.m. ET
Title: Preliminary results of a Phase Ib study of duvelisib in combination with FCR (dFCR) in previously untreated, younger patients with CLL (Abstract #4158)
Lead Author: Matthew Davids, M.D., Dana-Farber Cancer Institute

Title: Combination trial of duvelisib (IPI-145) with bendamustine, rituximab or bendamustine/rituximab in patients with lymphoma or chronic lymphocytic leukemia (Abstract #3928)
Lead Author: Ian Flinn, M.D., Sarah Cannon Research Institute

Target enrollment in DYNAMO reached: In September, Infinity announced it had reached target enrollment in DYNAMO, a global, Phase 2 open-label, single-arm, monotherapy study of duvelisib (25 mg BID) in approximately 120 patients with iNHL whose disease is refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint is overall response rate. Topline data from the study are anticipated in the third quarter of 2016. The enrollment milestone triggered a $130 million milestone payment from AbbVie.

BRAVURA study announced: In October, Infinity announced plans to initiate BRAVURA, a Phase 3, double-blind, placebo-controlled study in patients with relapsed iNHL, in the fourth quarter of 2015. BRAVURA is designed to evaluate the safety and efficacy of duvelisib plus rituximab and bendamustine (RB) compared to placebo plus RB in approximately 600 patients. The primary endpoint is progression-free survival. Infinity is planning to meet with the FDA to ascertain that BRAVURA can serve as a confirmatory study if DYNAMO supports an accelerated approval.

FRESCO study announced: In October, Infinity announced plans to initiate FRESCO, a Phase 2 study in patients with relapsed/refractory FL, in the fourth quarter of 2015. FRESCO is designed to evaluate the safety and efficacy of duvelisib plus rituximab versus rituximab in combination with chemotherapy in approximately 200 patients. The primary endpoint is progression-free survival.

IPI-549 Program

IPI-549 expected to enter Phase 1 clinical development in the first quarter of 2016: In September, Infinity announced the expansion of its pipeline with IPI-549, an oral immuno-oncology development candidate that selectively inhibits PI3K-gamma. At the CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper), Infinity researchers reported preclinical data demonstrating the potential of IPI-549 to disrupt the immune-suppressive tumor microenvironment and enable a heightened anti-tumor immune response. Research also showed that IPI-549 demonstrated dose-dependent, single-agent, anti-tumor activity in multiple solid tumor models, including murine models of lung, colon and breast cancer. Additionally, mice treated with IPI-549 in combination with checkpoint inhibitors showed greater tumor growth inhibition than either treatment as a monotherapy.
In the first quarter of 2016, Infinity expects to begin a Phase 1 clinical study of IPI-549 in patients with selected solid tumors, including non-small cell lung cancer and melanoma. The study will evaluate IPI-549 as a monotherapy as well as in combination with an anti–PD-1 antibody therapy.

Corporate Updates

Senior management team augmented: In October, William Bertrand joined Infinity as executive vice president, general counsel. Prior to Infinity, Mr. Bertrand held various roles of increasing responsibility at Salix Pharmaceuticals, Inc. and most recently served as senior vice president, general manager responsible for the Salix commercial business as well as its transition and integration into Valeant Pharmaceuticals International, Inc. From 2001 to 2013, Mr. Bertrand held positions of increasing responsibility at MedImmune, Inc., serving as its first and only general counsel from 2003 to 2013, prior to and following its sale to AstraZeneca PLC in 2008. Prior to MedImmune, Mr. Bertrand served as associate general counsel at Pharmacia Corporation. He earned a B.S. in Biology from Wayne State University and a J.D. from the University of Wisconsin-Madison.

Third Quarter 2015 Financial Results

At September 30, 2015, Infinity had total cash, cash equivalents and available-for-sale securities of $163.0 million, compared to $199.5 million at June 30, 2015, which does not include the $130 milestone payment received from AbbVie in November 2015.
Total revenue during the third quarter of 2015 was $90.7 million, compared to $160.6 million in the third quarter of 2014.
Revenue included a $75.2 million license fee associated with the $130 million milestone payment from AbbVie for the completion of patient enrollment in DYNAMO and $15.5 million in research and development (R&D) services. R&D services revenue for the third quarter of 2015 was composed of $9.8 million associated with the $130 million milestone payment and $5.7 million associated with the $275 million upfront payment from AbbVie received in September 2014. Revenue during the third quarter of 2014 was composed of $159.1 million license fee and $1.5 million in R&D services, both of which related to the $275 million upfront milestone from AbbVie. Infinity will recognize the remainder of the $130 million milestone payment and $275 million upfront payment over the period in which R&D services will be provided.

R&D expense for the third quarter of 2015 was $37.7 million, compared to $44.9 million for the third quarter of 2014. The decrease in R&D expense for the third quarter of 2015 compared to the same period in 2014 was primarily due to a $5.0 million option fee payment to Takeda in the third quarter of 2014 as well as lower clinical development expenses for duvelisib.

General and administrative (G&A) expense was $9.8 million for the third quarter of 2015, compared to $8.0 million for the same period in 2014. The increase in G&A expense was primarily related to the continued build-out of the company’s commercial capabilities and the functional support related to those activities.

Net income for the third quarter of 2015 was $42.5 million, or a basic earnings per common share of $0.85 and a diluted earnings per common share of $0.84. Net income for the third quarter of 2014 was $103.2 million, or a basic earnings per common share of $2.08 and a diluted earnings per common share of $2.03.
2015 Financial Guidance

The company’s 2015 financial outlook is as follows:

Revenue: Infinity expects revenue to range from $100 million to $120 million.
Net Loss: Infinity expects net loss for 2015 to range from $125 million to $145 million.
Cash and Investments: Infinity expects to end 2015 with a year-end cash and investments balance ranging from $230 million to $250 million. This anticipated year-end cash and investments balance includes the $130 million milestone payment from AbbVie associated with the completion of patient enrollment in DYNAMO.
Conference Call Information
Infinity will host a conference call today at 4:30 p.m. ET to discuss these financial results and company updates. A live webcast of the conference call can be accessed in the "Investors/Media" section of Infinity’s website at www.infi.com. To participate in the conference call, please dial 1-877-316-5293 (domestic) or 1-631-291-4526 (international) five minutes prior to start time. The conference ID number is 60777175. An archived version of the webcast will be available on Infinity’s website for 30 days.

About Duvelisib
Duvelisib is an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, two proteins with predominantly non-overlapping roles known to support the growth and survival of malignant B-cells.i Preclinical data suggest that PI3K-delta signaling can lead to the proliferation of malignant B-cells, and both PI3K-gamma and PI3K-delta play a role in the formation and maintenance of the supportive tumor microenvironment.ii Duvelisib is the only investigational PI3K-delta,gamma inhibitor in Phase 3 clinical development and has the potential to be a first-in-class treatment for certain types of hematologic malignancies, or blood cancers. AbbVie and Infinity Pharmaceuticals, Inc. are jointly developing duvelisib in oncology.

About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

Duvelisib and IPI-549 are investigational compounds and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On November 5, 2015 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for its quarter ended September 30, 2015, and provided an update on the Company’s clinical development programs for 2015 (Press release, Clovis Oncology, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107598 [SID:1234508032]).

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"We are entering a new phase at Clovis, transitioning into becoming a commercial biopharmaceutical company," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Our U.S. commercial organization, including the sales force, is now fully in place. This team is highly experienced, enthusiastic and ready to go, following our U.S. launch meeting last week. We are now fully prepared to launch rociletinib upon a potential U.S. approval and we are actively building our E.U. commercial organization in preparation for a late 2016 launch in Europe. Additionally, having advanced our rucaparib NDA submission timeline to Q2 2016, we are planning for a potential U.S. launch of rucaparib for advanced ovarian cancer by the end of 2016. We are very enthusiastic about the prospect of having our commercial organization support sales for both rociletinib and rucaparib."

Third Quarter 2015 Financial Results

Net loss attributable to common shareholders was $98.6 million ($2.62 per share) for the third quarter of 2015 and $233.3 million ($6.62 per share) for the first nine months of 2015, compared to a net loss of $39.6 million ($1.17 per share) and $105.1 million ($3.10 per share) for the comparable periods of 2014.

Research and development expenses totaled $76.1 million for the third quarter of 2015 and $193.3 million for the first nine months of 2015, compared to $35.0 million and $87.6 million for the comparable periods in 2014. The increase in expenses for both the three- and nine-month periods is due to the significantly expanded clinical development activities for rociletinib and rucaparib, increased launch planning activities for rociletinib and increased personnel-related expenses associated with the hiring of additional staff to support the Company’s expanded activities.

General and administrative expenses totaled $8.3 million for the third quarter of 2015 and $22.3 million for the first nine months of 2015, compared to $5.3 million and $15.9 million for the comparable periods in 2014. The year over year increase is primarily due to higher share-based compensation and personnel expense for employees engaged in general and administrative activities, increased facility costs and higher professional service fees.

Acquired in-process research and development expenses totaled $12.0 million for both the third quarter of 2015 and the first nine months of 2015. There was no acquired in-process research and development expense for the third quarter of 2014 and $8.8 million for the first nine months of 2014. During the third quarter of 2015, the Company made milestone payments totaling $12.0 million to Celgene Corporation upon acceptance of the NDA and MAA submissions for rociletinib by the FDA and EMA, respectively.

Share-based compensation expense totaled $12.4 million for the third quarter of 2015 and $29.5 million for the first nine months of 2015.

Clovis had $605.9 million in cash, cash equivalents and available-for-sale securities and approximately 38.3 million outstanding shares of common stock as of September 30, 2015. Our net cash used in operations for the third quarter of 2015 was $71.7 million and $177.4 million for the first nine months of 2015, including $12.0 million in rociletinib milestone payments. In July 2015, the Company raised net proceeds of $298.5 million through an offering of 4.1 million shares of common stock.

2015 Key Milestones and Objectives

Highlights of planned or completed objectives for each product follows:

Rociletinib

Rociletinib is an investigational therapy for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation. The U.S. Food and Drug Administration (FDA) has accepted Clovis’ New Drug Application (NDA) for rociletinib and has granted it priority review status with a Prescription Drug User Fee Act (PDUFA) action date of March 30, 2016. In addition, the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for rociletinib.

The U.S. commercial and medical affairs organizations are now in place and efforts are currently underway to build out the E.U. commercial organization.

Rociletinib was the subject of several posters and presentations during the third quarter, including updates of data from the TIGER-X study in EGFR mutant, T790M-positive patients with a history of CNS involvement, as well as EGFR mutant, T790M-negative patients as determined by tissue as well as plasma testing. Posters and presentations for all Clovis products in development presented during the third quarter may be viewed at View Source

Rucaparib

During the third quarter, updated findings from ARIEL2 and Study 10, two ongoing studies evaluating the safety and activity of rucaparib in advanced ovarian cancer patients were presented at the 18th ECCO – 40th ESMO (Free ESMO Whitepaper) European Cancer Congress. Data from these studies demonstrated encouraging activity and safety in women with advanced, platinum-sensitive ovarian cancer with tissue BRCA (gBRCA and sBRCA) mutations. In addition, these data demonstrated that the application of Clovis’ proprietary BRCA-like tumor DNA signature to Foundation Medicine’s companion diagnostic assay successfully predicts the population of BRCA-like patients that are not gBRCA or sBRCA that respond to rucaparib therapy. Highlights of the data presented included the following (all response rates RECIST):

Data from ARIEL2 in 40 evaluable BRCA-mutant patients demonstrated an ORR of 75%, a median PFS of 12.8 months and a median duration of response of 9.5 months
Complete responses (CRs) observed in 15% of patients
Data from ARIEL2 in 77 evaluable patients with the BRCA-like signature demonstrated an ORR of 36%, a median PFS of 5.7 months and a median duration of response of 8.2 months
Data from Study 10 in 39 evaluable germline BRCA-mutant patients demonstrated an ORR of 67%, a disease control rate (DCR) of 87%, and median duration of response of 6.6 months
CRs observed in 8% of patients in this group
Rucaparib is well-tolerated with a manageable safety profile; the grade 3/4 treatment-related adverse events (AEs) observed in >15% of patients treated with the recommended 600mg BID dose were anemia/decreased hemoglobin (19%) in ARIEL2, and fatigue/asthenia (21%), and anemia (26%) in Study 10
Based on these compelling data, Clovis intends to submit an NDA to the FDA for rucaparib as treatment for advanced ovarian cancer patients with a tissue BRCA mutation in the second quarter of 2016, with the intention, pending data, to follow with a supplemental NDA for advanced ovarian cancer patients with a BRCA-like mutation. During the quarter, Clovis completed enrollment of the mutant BRCA population that will serve as the basis of its planned NDA submission.

Lucitanib

A Phase 2 program is ongoing to explore lucitanib in multiple indications, including a U.S. study in patients with treatment-refractory FGF-aberrant breast cancer and a global study in patients with advanced lung cancer with FGFR1 amplification, both of which are currently enrolling patients. In parallel with these Clovis-sponsored studies, a Servier-sponsored Phase 2 study of lucitanib in patients with advanced breast cancer is underway to identify the population of patients most likely to benefit from lucitanib therapy.

Management Update

Erle Mast, Clovis’ Executive Vice President, Chief Financial Officer and Clovis co-founder, has announced his plan to retire effective March 31, 2016. The Company is initiating a search for Erle’s successor, and intends to recruit a candidate prior to his departure date to enable a transition period during the first quarter.

"With great regret we announce today that Erle Mast, Chief Financial Officer and a co-founder of Clovis, and importantly, my friend and colleague for more than 14 years, has informed us of his plans to retire on March 31, 2016," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "While I am very sorry to see him go, I certainly understand his decision and can only add how much I have enjoyed working with him and appreciate all that he has done for Clovis. Obviously, we are confident that we will be able to recruit a highly qualified individual as a new CFO and appreciate very much Erle giving sufficient notice to allow a smooth transition."

On November 5, 2015 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company"), a specialty biopharmaceutical company engaged in developing and commercializing novel treatments in oncology, endocrinology and women’s health, reported financial and operating results as at and for the third quarter ended September 30, 2015 (Filing, 6-K, AEterna Zentaris, NOV 5, 2015, View Source [SID:1234508029]).

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Commenting on third quarter results and the Company’s prospects, David A. Dodd, Chairman, President and Chief Executive Officer of the Company, stated, "Despite our continued progress in transforming the Company, the price of our common shares remained under intense pressure during the third quarter as a result of the exercise of Series B Common Share Purchase Warrants ("Series B Warrants"). At the beginning of the quarter, 26,812,308 Series B Warrants were outstanding. We finished the quarter with 6,880,170. As a result of the agreements we reached with the major holders of the Series B Warrants on November 1, only approximately 0.8 million Series B Warrants will remain outstanding, representing approximately 2.7% of the number originally issued. While the dilution caused by the Series B Warrants is substantially ended, we find it necessary to ask our fellow shareholders to approve another share consolidation. We believe that a share consolidation will permit our common shares to remain listed on The Nasdaq Capital Market, which will permit us to raise capital again on reasonable terms, further supporting our focus on developing a profitable, growth-oriented pharmaceutical business."

Commenting on the Company’s lead oncology compound, Mr. Dodd stated, "Our confidence in the commercial potential of Zoptrex, which is the brand name we selected for zoptarelin doxorubicin, was enhanced by the announcement during the third quarter of the results of an investigator sponsored Phase 2 clinical study of Zoptrex in men with in castration- and taxane-resistant prostate cancer. Zoptrex achieved its primary endpoint and demonstrated good tolerability during this early-stage study. The primary endpoint was Clinical Benefit, defined as remaining progression-free by RECIST and Prostate Specific Antigen after treatment for 12+ weeks. Shortly after quarter end, we received very encouraging news regarding Zoptrex when, following a comprehensive review of the final interim efficacy and safety data, the DSMB recommended that we continue the ZoptEC Phase 3 clinical study to its conclusion. We look forward to the successful completion of the clinical development of ZoptrexTM for our initial indication over the next year."

Continuing with his commentary, Mr. Dodd stated, "During the third quarter, we made progress promoting Saizen, a leading product in the $1.6 billion US market for the treatment of growth hormone deficiency in children and adults. Our recently commenced promotional efforts for Saizen show promise and support our belief that detailing this product will contribute to our commercial success. In addition, year-over-year new prescription growth for EstroGel in our territories increased significantly, compared to its market which is currently flat or declining. Our commercial operation, while not yet a meaningful contributor to our financial results, is an important investment we are making in the transformation of the Company. This demonstrated, effective commercial operation will position us to build our portfolio by in-licensing products. We intend to continue with this investment in parallel with our efforts to successfully in-license products."

Concluding, Mr. Dodd addressed the Company’s earlier stage development efforts as follows: "We also made significant progress with respect to our pipeline of internally developed products, selecting an optimized Erk-inhibitor compound for further development. We are looking for other parties to assist us with the further development of the compound because we believe it could represent an important new category of cancer therapy."

Third Quarter Financial Highlights
Research and development ("R&D") costs were $4.1 million for the three-month period ended September 30, 2015, as compared to $6.1 million for the same period in 2014. A substantial portion of this decrease is mainly due to the realization of cost savings in connection with the Company’s global resource optimization program, as well as to the weakening, in 2015, of the euro against the US dollar. The decrease was partly offset by higher costs associated with the Company’s ZoptEC and Macrilen Phase 3 trials.
Selling expenses were $1.7 million for the three-month period ended September 30, 2015, as compared to $0.9 million for the same period in 2014. This increase is mainly attributable to the implementation of our promotional activities associated with EstroGel, which commenced in late 2014. We also expanded the size of our contracted sales force from 19 to 23 sales representatives during the quarter in order to support our promotional efforts associated with Saizen.

General and administrative expenses were $1.9 million for the three-month period ended September 30, 2015, as compared to $2.8 million for the same period in 2014. General and administrative expenses were lower in the current-year quarter mainly due to the realization of costs savings in connection with the Company’s global resource optimization program.

Net finance costs were $7.9 million for the three-month period ended September 30, 2015, as compared to net finance costs of $1.8 million for the same period in 2014. The increase in net finance costs of $6.1 million is mainly related to the change in the estimated fair value of the Company’s warrant liability.

Net loss for the three-month period ended September 30, 2015 was $15.3 million or $0.07 per basic and diluted share, as compared to $11.3 million or $0.20 per basic and diluted share for the same period in 2014. This increase is predominantly due to higher comparative net finance costs and to higher comparative selling expenses, partially offset by lower comparative R&D costs.

At the opening of the third quarter, the Company had 139.9 million issued and outstanding common shares. On September 30 and November 4, 2015, the Company had 492.5 million and 632.7 million issued and outstanding common shares, respectively. The increase in the Company’s outstanding shares during the quarter and subsequent to quarter-end through November 4, 2015, results from the issuance of 492.8 million common shares upon the alternate cashless exercise of Series B Warrants.

Cash and cash equivalents were $38.3 million as at September 30, 2015, compared to $34.9 million as at December 31, 2014.

On November 5, 2015 Johnson & Johnson reported that at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, Janssen Research & Development, LLC will present new data for both approved and investigational oncology and cardiovascular compounds across 10 disease areas (Press release, Johnson & Johnson, NOV 5, 2015, View Source [SID:1234508028]). More than 40 abstracts from company-sponsored studies have been accepted for presentation, including 17 oral presentations, the largest presence of company data to date. Oral presentations from five Janssen brands across two therapeutic areas will be presented at the meeting, including ibrutinib, daratumumab, siltuximab, imetelstat and rivaroxaban. Data and posters from bortezomib, decitabine and JNJ56022473 (formerly CSL362) will be presented as well.

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"The depth and breadth of data presented at ASH (Free ASH Whitepaper) 2015 demonstrate our deep passion for developing transformational medical solutions to treat and prevent disease in novel ways, with the goal of radically improving health for patients in need," said William N. Hait, M.D., Ph.D., Global Head, ​Janssen Research & Development, LLC.

Ibrutinib will be featured in 23 presentations sponsored by either Janssen or its collaboration partner, Pharmacyclics, seven of which are orals. Presentations include data evaluating its use as a single agent and in combination with other therapies across several disease states. IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

Daratumumab will be featured in 10 presentations sponsored or supported by Janssen, three of which are orals. The company will present data evaluating the fully human anti-CD38 monoclonal antibody as a single agent and in combination with standard therapies in multiple myeloma patients who are relapsed or refractory to standard therapies.

Siltuximab will be featured in one presentation sponsored by Janssen, reporting data from a Phase 2 study assessing the economic burden of relapsed or refractory multiple myeloma.

Imetelstat will be featured in two oral presentations sponsored by either Janssen or its licensing and collaboration partner, Geron Corporation.

Rivaroxaban will be featured in four oral presentations on anticoagulant use in venous thromboembolic disease sponsored by Janssen Pharmaceuticals, Inc. and its development partner for this medicine, Bayer HealthCare.

Ibrutinib Oral Presentations:

Chronic Lymphocytic Leukemia

Results from the International, Randomized Phase 3 Study of Ibrutinib Versus Chlorambucil in Patients 65 Years and Older with Treatment-Naïve CLL/SLL (RESONATE-2TM). (Abstract 495)
Outcome of Ibrutinib Treatment by Baseline Genetic Features in Patients with Relapsed or Refractory CLL/SLL With del17p in the RESONATE-17 Study. (Abstract 833)
Ibrutinib Plus Bendamustine/Rituximab (BR) is Associated with Greater Reductions in Fatigue Than Placebo Plus BR Among Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia and Fatigue. (Abstract 267)

Mantle Cell Lymphoma

Ibrutinib vs Temsirolimus: Results From a Phase 3, International, Randomized, Open-Label, Multicenter Study in Patients With Previously Treated Mantle Cell Lymphoma (MCL). (Abstract 469)

Multiple Myeloma

Combination Treatment with the Bruton’s Tyrosine Kinase Inhibitor Ibrutinib and Carfilzomib in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma: Initial Results from a Multicenter Phase 1/2b Study. (Abstract 377)

Diffuse Large B-cell Lymphoma

The Role of PIM1 in Ibrutinib-Resistant ABC Subtype of Diffuse Large B-Cell Lymphoma. (Abstract 699)

Follicular Lymphoma

Ibrutinib Plus Rituximab in Treatment-Naïve Patients with Follicular Lymphoma: Results from a Multicenter, Phase 2 Study. (Abstract 470)

Daratumumab Oral Presentations:

Multiple Myeloma

Clinical Efficacy of Daratumumab Monotherapy in Patients with Heavily Pretreated Relapsed or Refractory Multiple Myeloma. (Abstract 29)
Daratumumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma: Updated Results of a Phase 1/2 Study (GEN503). (Abstract 507)
Open-label, Multicenter, Phase 1b Study of Daratumumab in Combination with Pomalidomide and Dexamethasone in Patients with at Least 2 Lines of Prior Therapy and Relapsed or Relapsed and Refractory Multiple Myeloma. (Abstract 508)

Siltuximab Oral Presentation:

Multiple Myeloma

Economic Burden of Relapsed or Refractory Multiple Myeloma: Results from an International Trial. (Abstract 875)

Imetelstat Oral Presentations:

Telomerase Inhibitor Imetelstat Therapy in Refractory Anemia with Ring Sideroblasts with or without Thrombocytosis. (Abstract 55)
Dynamics of Mutations in Patients with ET Treated with Imetelstat. (Abstract 57)

Rivaroxaban Oral Presentations:

Deep Vein Thrombosis and Pulmonary Embolism

Safe and Effective Use of Rivaroxaban for Treatment of Cancer-Associated Venous Thromboembolic Disease: A Quality Improvement Initiative. (Abstract 431)
Current Practice Patterns and Patient Persistence on Anticoagulant Treatments for Cancer-Associated Thrombosis. (Abstract 626)
Xalia, a Non-Interventional Study Comparing Rivaroxaban with Standard Anticoagulation for Initial and Long-Term Therapy in Deep Vein Thrombosis. (Abstract 894)
Validation of the Inhospital Mortality for Pulmonary Embolism Using Claims Data (IMPACT) Prediction Rule within an All-Payer Inpatient Administrative Claims Database. (Abstract 747)

About IMBRUVICA (ibrutinib)

IMBRUVICA was one of the first therapies to receive U.S. approval after having received the FDA’s Breakthrough Therapy Designation. IMBRUVICA works by blocking a specific protein called Bruton’s tyrosine kinase (BTK).1 The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread.1, 2 IMBRUVICA targets and blocks BTK, inhibiting cancer cell survival and spread.1 For more information, visit www.IMBRUVICA.com.

Additional Information about IMBRUVICA

INDICATIONS

IMBRUVICA is indicated to treat people with:

Chronic lymphocytic leukemia (CLL) who have received at least one prior therapy
Chronic lymphocytic leukemia (CLL) with 17p deletion
Waldenström’s macroglobulinemia (WM)
Mantle cell lymphoma (MCL) who have received at least one prior therapy
Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

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

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

Infections – Fatal and non-fatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Monitor patients for fever and infections and evaluate promptly.

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

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

Second Primary Malignancies – Other malignancies (range, 5 to 14%) including non-skin carcinomas (range, 1 to 3%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4 to 11%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been reported with IMBRUVICA therapy. Monitor patients closely and take appropriate precautions in patients at risk for tumor lysis syndrome (e.g., high tumor burden).

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

ADVERSE REACTIONS

The most common adverse reactions (≥25%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%, 52%, 43%), neutropenia* (47%, 51%, 44%), diarrhea (51%, 48%, 37%), anemia* (41%, 36%, 13%), fatigue (41%, 28%, 21%), musculoskeletal pain (37%, 28%†, NA‡), bruising (30%, 12%†, 16%†), nausea (31%, 26%, 21%), upper respiratory tract infection (34%, 16%, 19%), and rash (25%, 24%†, 22%†).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).
†Includes multiple ADR terms.
‡Not applicable; no associated ADRs.

The most common Grade 3 or 4 non-hematological adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).
Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse events.
Approximately 5% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse events. Most frequent adverse events leading to discontinuation were infections, subdural hematomas, and diarrhea in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

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

CYP3A Inducers – Avoid co-administration with strong CYP3A inducers.

SPECIFIC POPULATIONS

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

Please see full Prescribing Information: View Source

About Daratumumab
Daratumumab is an investigational human monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through multiple immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity, as well as via induction of apoptosis.3, 4, 5 Five Phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin lymphoma. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

About SYLVANT (siltuximab)
SYLVANT is an anti-interleukin-6 (IL-6) chimeric monoclonal antibody that binds to human IL-6.6 IL-6 is a multifunctional cytokine produced by various cells such as T cells, B cells, monocytes, fibroblasts and endothelial cells. Dysregulated overproduction of IL-6 from activated B cells in affected lymph nodes has been implicated in the pathogenesis of, or mechanism causing, MCD.7 Information about ongoing studies with siltuximab can be found at www.clinicaltrials.gov.

Additional Information about SYLVANT

INDICATION

SYLVANT (siltuximab) is indicated for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Limitation of Use. SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL‐6 in a nonclinical study.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS – Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.

Concurrent Active Severe Infections – Do not administer to patients with severe infections until the infection resolves. SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute phase reactants such as C-reactive protein (CRP). Monitor patients closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT until the infection resolves.

Vaccinations – Do not administer live vaccines to patients receiving SYLVANT because interleukin-6 (IL-6) inhibition may interfere with the normal immune response to new antigens.

Infusion Related Reactions and Hypersensitivity – Stop the infusion if the patient develops signs of anaphylaxis. Discontinue further therapy.

Stop the infusion if the patient develops mild to moderate infusion reactions. If the reaction resolves, the infusion may be restarted at a lower infusion rate. Consider medicating with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT if the patient does not tolerate the infusion following these interventions. [see Adverse Reactions (6)].

Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.

Gastrointestinal (GI) Perforation – Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated with or suggestive of GI perforation.

Adverse Reactions – The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.

Drug Interactions – Cytochrome P450 (CYP450) Substrates – Upon initiation or discontinuation of SYLVANT, in patients being treated with CYP450 substrates with narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).

For more information on SYLVANT, including the full prescribing information, visit www.SYLVANT.com.

About Imetelstat
Janssen entered into an exclusive worldwide license and collaboration agreement with Geron Corporation (Nasdaq: GERN) in November 2014 to develop and commercialize imetelstat, an investigational telomerase inhibitor. Imetelstat is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Imetelstat has not been approved for marketing by any regulatory authority.

About XARELTO (rivaroxaban)
XARELTO works by blocking the blood clotting Factor Xa. XARELTO does not require routine blood monitoring. XARELTO has a broad indication profile and is approved for six indications that include:

To reduce the risk of strokes and blood clots in patients with atrial fibrillation not caused by a heart valve problem. For patients currently well managed on warfarin, there is limited information on how XARELTO and warfarin compare in reducing the risk of stroke.
To treat patients with deep vein thrombosis (DVT).
To treat patients with pulmonary embolism (PE).
To reduce the risk of recurrence of DVT or PE following an initial six-month treatment for acute venous thromboembolism.
To reduce the risk of blood clots in the legs and lungs of patients who have just had knee replacement surgery.
To reduce the risk of blood clots in the legs and lungs of patients who have just had hip replacement surgery.

IMPORTANT SAFETY INFORMATION

WARNING: (A) PREMATURE DISCONTINUATION OF XARELTO INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA

A. PREMATURE DISCONTINUATION OF XARELTO INCREASES THE RISK OF THROMBOTIC EVENTS
Premature discontinuation of any oral anticoagulant, including XARELTO, increases the risk of thrombotic events. If anticoagulation with XARELTO is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
B. SPINAL/EPIDURAL HEMATOMA

Epidural or spinal hematomas have occurred in patients treated with XARELTO who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:
Use of indwelling epidural catheters
Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants, see Drug Interactions
A history of traumatic or repeated epidural or spinal punctures
A history of spinal deformity or spinal surgery <
Optimal timing between the administration of XARELTO and neuraxial procedures is not known
Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.
Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

CONTRAINDICATIONS

Active pathological bleeding
Severe hypersensitivity reaction to XARELTO (eg, anaphylactic reactions)

WARNINGS AND PRECAUTIONS

Increased Risk of Thrombotic Events After Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including XARELTO, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from XARELTO to warfarin in clinical trials in atrial fibrillation patients. If XARELTO is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

Risk of Bleeding: XARELTO increases the risk of bleeding and can cause serious or fatal bleeding. Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement. Discontinue XARELTO in patients with active pathological hemorrhage.

A specific antidote for rivaroxaban is not available. Because of high plasma protein binding, rivaroxaban is not expected to be dialyzable.

Concomitant use of other drugs affecting hemostasis increases the risk of bleeding. These include aspirin, P2Y12 platelet inhibitors, other antithrombotic agents, fibrinolytic therapy, and NSAIDs.

Spinal/Epidural Anesthesia or Puncture: When neuraxial anesthesia (spinal/epidural anesthesia) or spinal puncture is employed, patients treated with anticoagulant agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. To reduce the potential risk of bleeding associated with the concurrent use of rivaroxaban and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of rivaroxaban. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. An epidural catheter should not be removed earlier than 18 hours after the last administration of XARELTO. The next XARELTO dose is not to be administered earlier than 6 hours after the removal of the catheter. If traumatic puncture occurs, the administration of XARELTO is to be delayed for 24 hours. Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture, monitor frequently to detect any signs or symptoms of neurological impairment, such as midline back pain, sensory and motor deficits (numbness, tingling, or weakness in lower limbs), or bowel and/or bladder dysfunction. Instruct patients to immediately report if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae.
Use in Patients With Renal Impairment:

Nonvalvular Atrial Fibrillation: Avoid the use of XARELTO in patients with creatinine clearance (CrCl) <15 mL/min, since drug exposure is increased. Discontinue XARELTO in patients who develop acute renal failure while on XARELTO.

Treatment of Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and Reduction in the Risk of Recurrence of DVT and of PE: Avoid the use of XARELTO in patients with CrCl <30 mL/min due to an expected increase in rivaroxaban exposure and pharmacodynamic effects in this patient population.

Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery: Avoid the use of XARELTO in patients with CrCl <30 mL/min due to an expected increase in rivaroxaban exposure and pharmacodynamic effects in this patient population. Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with CrCl 30 to 50 mL/min. Patients who develop acute renal failure while on XARELTO should discontinue the treatment.

Use in Patients With Hepatic Impairment: No clinical data are available for patients with severe hepatic impairment. Avoid use of XARELTO in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy, since drug exposure and bleeding risk may be increased.

Use With P-gp and Strong CYP3A4 Inhibitors or Inducers: Avoid concomitant use of XARELTO with combined P-gp and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan). Avoid concomitant use of XARELTO with drugs that are P-gp and strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s wort).

Risk of Pregnancy-Related Hemorrhage: In pregnant women, XARELTO should be used only if the potential benefit justifies the potential risk to the mother and fetus. XARELTO dosing in pregnancy has not been studied. The anticoagulant effect of XARELTO cannot be monitored with standard laboratory testing and is not readily reversed. Promptly evaluate any signs or symptoms suggesting blood loss (eg, a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress).

Patients With Prosthetic Heart Valves: The safety and efficacy of XARELTO have not been studied in patients with prosthetic heart valves. Therefore, use of XARELTO is not recommended in these patients.

Acute PE in Hemodynamically Unstable Patients/Patients Who Require Thrombolysis or Pulmonary Embolectomy: Initiation of XARELTO is not recommended acutely as an alternative to unfractionated heparin in patients with pulmonary embolism who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.

DRUG INTERACTIONS

Avoid concomitant use of XARELTO with other anticoagulants due to increased bleeding risk, unless benefit outweighs risk. Promptly evaluate any signs or symptoms of blood loss if patients are treated concomitantly with aspirin, other platelet aggregation inhibitors, or NSAIDs.

XARELTO should not be used in patients with CrCl 15 to 80 mL/min who are receiving concomitant combined P-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk.

USE IN SPECIFIC POPULATIONS

Pregnancy Category C: XARELTO should be used during pregnancy only if the potential benefit justifies the potential risk to mother and fetus. There are no adequate or well-controlled studies of XARELTO in pregnant women, and dosing for pregnant women has not been established. Use XARELTO with caution in pregnant patients because of the potential for pregnancy-related hemorrhage and/or emergent delivery with an anticoagulant that is not readily reversible. The anticoagulant effect of XARELTO cannot be reliably monitored with standard laboratory testing.

Labor and Delivery: Safety and effectiveness of XARELTO during labor and delivery have not been studied in clinical trials.

Nursing Mothers: It is not known if rivaroxaban is excreted in human milk.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Females of Reproductive Potential: Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician.
OVERDOSAGE

Discontinue XARELTO and initiate appropriate therapy if bleeding complications associated with overdosage occur. A specific antidote for rivaroxaban is not available. The use of activated charcoal to reduce absorption in case of XARELTO overdose may be considered. Due to the high plasma protein binding, rivaroxaban is not expected to be dialyzable.

ADVERSE REACTIONS IN CLINICAL STUDIES

The most common adverse reactions with XARELTO were bleeding complications.

On November 5, 2015 CTI BioPharma Corp. (NASDAQ and MTA: CTIC) reported financial results for the third quarter ended September 30, 2015 (Press release, CTI BioPharma, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107565 [SID:1234508027]).

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"We are focused on preparing our NDA submission for pacritinib and are on track to submit our application to the FDA this quarter," said James A. Bianco, M.D., CTI BioPharma’s President and CEO. "We also remain committed to completing the second Phase 3 trial of pacritinib, PERSIST-2, which we believe could serve as a post-approval confirmatory trial in the event our NDA application is accepted and approved under accelerated approval. Additionally, we look forward to upcoming data presentations of pacritinib and tosedostat studies at the ASH (Free ASH Whitepaper) Annual Meeting in December."

Third Quarter 2015 and Recent Highlights

In September 2015, announced plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) with partner Baxalta Inc. for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R for the treatment of patients with myelofibrosis, in the fourth quarter of 2015 and to request accelerated approval for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (< 50,000/uL) for whom there are no approved drugs. Priority review of the application will be requested at the time of NDA submission.
In September 2015, completed registered direct offering resulting in net proceeds of approximately $15.1 million and in October 2015, completed underwritten public offering resulting in net proceeds of approximately $46.5 million.
In November 2015, announced the upcoming presentations of data highlighting pacritinib and tosedostat at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) to be held December 5-8, 2015, in Orlando, FL.

Third Quarter 2015 Financial Results

Total revenues for the third quarter and the nine months ended September 30, 2015 were $1.0 million and $4.8 million, respectively, compared to $39.5 million and $42.3 million for the same periods in 2014. The decrease in total revenue is primarily due to recognition of milestone payments in 2014, specifically a $20.0 million development milestone payment received from Baxalta for completion of enrollment in the PERSIST-1 Phase 3 clinical trial of pacritinib and $17.3 million from an upfront payment under the PIXUVRI collaboration agreement with Servier. Net product revenues of PIXUVRI for the third quarter and the nine months ended September 30, 2015 were $0.7 million and $2.4 million, respectively, compared to $2.0 million and $4.4 million for the same periods in 2014. The decrease in net product sales was primarily related to the pricing and volume variances between the periods presented as well as the decline in average exchange rate of the euro for our euro-denominated sales.

The non-GAAP operating loss, which excludes non-cash share-based compensation expense, for the third quarter and nine months ended September 30, 2015 was $26.1 million and $77.5 million, respectively, compared to non-GAAP operating income of $11.3 million and a non-GAAP operating loss of $29.8 million for the same periods in 2014. The GAAP operating loss for the third quarter and nine months ended September 30, 2015 was $32.0 million and $90.5 million, respectively, compared to a GAAP operating income of $7.5 million and operating loss of $46.9 million for the same period in 2014. The increase in operating loss for the nine-month period is predominantly associated with the Phase 3 development program for pacritinib and the PIX306 post-authorization Phase 3 trial for PIXUVRI as well as the milestone and the upfront payments received in the 2014 periods as mentioned above. Non-cash share-based compensation expense for the third quarter and nine months ended September 30, 2015 was $5.9 million and $13.0 million, respectively, compared to $3.8 million and $17.0 million for the same periods in 2014. For information on CTI BioPharma’s use of the aforementioned non-GAAP measure and a reconciliation of such measure to GAAP operating loss, see the section below entitled "Non-GAAP Financial Measures."

Net loss for the third quarter of 2015 was $32.6 million, or $(0.19) per share, compared to a net income of $4.6 million, or $0.03 per share, for the same period in 2014. Net loss for the first nine months of 2015 was $93.8 million, or $(0.54) per share, compared to a net loss of $51.8 million, or $(0.36) per share, for the same period in 2014.

As of September 30, 2015, cash and cash equivalents totaled $46.4 million, compared to $70.9 million as of December 31, 2014. Subsequent to September 30, 2015, we received approximately $46.5 million in net proceeds from an underwritten public offering in October 2015.

2015 Financial Outlook

CTI BioPharma now expects total revenues for 2015 will be approximately $30 million to $45 million, which are primarily based upon updated current expectations regarding license and contract revenues under the agreements with Baxalta and Teva and net product sales from PIXUVRI commercial operations. Non-GAAP operating loss for 2015 will be approximately $75 million to $85 million, which excludes non-cash share-based compensation expense. These financial projections are primarily based on our current expectations regarding patient enrollment, NDA submission timing and other factors previously outlined in the Company’s fourth quarter and full year 2014 financial results press release.