On November 5, 2015 Celgene Corporation (NASDAQ:CELG) reported net product sales of $2,313 million for the third quarter of 2015, an 18 percent increase from the same period in 2014 (Press release, Celgene, NOV 5, 2015, View Source [SID:1234508003]). The negative net impact of currency on net product sales was 2 percent. Third quarter total revenue increased 18 percent to $2,334 million compared to $1,982 million in the third quarter of 2014. Adjusted net income for the third quarter of 2015 increased 26 percent to $1,011 million compared to $806 million in the third quarter of 2014. Adjusted diluted earnings per share (EPS) in the third quarter of 2015 was $1.23 and includes a $0.04 dilutive impact related to the acquisition of Receptos, Inc. For the same period in 2014, adjusted diluted EPS was $0.97. The results of operations for Receptos, Inc. are included in the consolidated financial results from the August 27, 2015 acquisition date.

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Based on U.S. GAAP (Generally Accepted Accounting Principles), Celgene reported a third quarter of 2015 net loss of $34 million or a loss of $0.04 per diluted share. The reported GAAP net loss for the quarter primarily reflects an increase in costs related to strategic transactions including upfront collaboration expenses driven by the Juno Therapeutics collaboration, inclusive of the premium paid to acquire an equity stake, as well as expenses incurred in connection with the acquisition of Receptos. For the third quarter of 2014, net income was $508 million or $0.61 per diluted share.

"Our strong third quarter performance and acceleration of key drivers create significant momentum in our business, further advancing us toward our 2020 targets," said Bob Hugin, Chairman and Chief Executive Officer of Celgene Corporation. "The continued progress of our clinical pipeline and important strategic collaborations have us well-positioned for long-term growth."

Third Quarter 2015 Financial Highlights

Unless otherwise stated, all comparisons are for the third quarter of 2015 compared to the third quarter of 2014. The adjusted operating expense categories presented below exclude share-based employee compensation expense and upfront collaboration payments. Please see the attached Reconciliation of GAAP to Adjusted Net Income for further information.

Net Product Sales Performance

REVLIMID sales for the third quarter increased 12 percent to $1,453 million. U.S. sales of $895 million and International sales of $558 million increased 18 percent and 3 percent year-over-year, respectively. Volume was the main driver of the increase as both market share and duration trends are positive across major geographies.

POMALYST/IMNOVID sales for the third quarter were $257 million, an increase of 42 percent. U.S. sales were $150 million and International sales were $107 million, an increase of 27 percent and 69 percent, respectively. POMALYST/IMNOVID sales were driven by increased volume as both market share and duration trends are positive across major geographies.

ABRAXANE sales for the third quarter were $230 million, an 8 percent increase. U.S. sales of $145 million decreased 4 percent year-over-year and were impacted by competitive dynamics in lung cancer and breast cancer. International sales of $85 million increased 40 percent year-over-year and were positively impacted by increased volume from the ongoing launch for pancreatic cancer in Europe.

OTEZLA sales for the third quarter were $139 million, increasing 55 percent over the second quarter of 2015. U.S. sales were $129 million and International sales were $10 million. OTEZLA uptake and market share gains continued to accelerate in the third quarter in the U.S. with increased contribution from early launch countries in Europe.
All other product sales, which include THALOMID, ISTODAX, VIDAZA and an authorized generic of VIDAZA drug product in the U.S., were $234 million in the third quarter of 2015 compared to $246 million for the third quarter of 2014.

Research and Development (R&D)

Adjusted R&D expenses were $488 million for the third quarter of 2015 compared to $419 million for the third quarter of 2014. The increase was primarily due to an increase in clinical trial activity across the portfolio. On a GAAP basis, R&D expenses were $1,305 million for the third quarter of 2015 and $675 million for the same period in 2014 primarily reflecting an increase in upfront collaboration expenses driven by the Juno Therapeutics collaboration, inclusive of the premium paid to acquire an equity stake.

Selling, General, and Administrative (SG&A)

Adjusted SG&A expenses were $474 million for the third quarter of 2015 compared to $441 million for the third quarter of 2014. The increase was primarily due to investments in support of the global launches of OTEZLA in psoriasis and psoriatic arthritis and REVLIMID in newly diagnosed multiple myeloma. On a GAAP basis, SG&A expenses were $550 million for the third quarter of 2015 compared to $498 million for the same period in 2014.

Cash, Cash Equivalents, and Marketable Securities

In the third quarter of 2015, Celgene purchased approximately 7.1 million of its shares at a total cost of approximately $815 million. As of September 30, 2015, the Company had approximately $4.3 billion remaining under the stock repurchase program.

During the third quarter of 2015, Celgene issued an aggregate of $8 billion in senior unsecured notes in tranches of three-, five-, seven-, ten- and thirty-years. The Company used the net proceeds from the offering primarily to finance the acquisition of Receptos, Inc. as well as for general corporate purposes.

Operating cash flow was $285 million in the third quarter of 2015. Celgene ended the quarter with approximately $7.5 billion in cash, cash equivalents and marketable securities.

2015 Guidance for REVLIMID and ABRAXANE Updated

Total net product sales are expected to be in the range of $9.0 billion to $9.5 billion
REVLIMID net sales are expected to be approximately $5.8 billion, an increase from the previous range of $5.6 billion to $5.7 billion

ABRAXANE net sales are expected to be in the range of $950 million to $1.0 billion, a decrease from the previous range of $1.0 billion to $1.25 billion
Adjusted 2015 operating margin remains unchanged at approximately 52 percent; GAAP operating margin is expected to be approximately 25.2 percent, lowered from approximately 36.4 percent
Adjusted diluted EPS is expected to be in the range of $4.75 to $4.85
GAAP diluted EPS is expected to be in the range of $2.02 to $2.24, a decrease from the previous range of $2.17 to $2.46
Product and Pipeline Updates

Hematology

In October, VIDAZA was approved by the European Commission for the treatment of adult patients aged 65 years or older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplantation. A positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) was granted in September. VIDAZA will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

A Supplementary New Drug Application was filed with the U.S. Food and Drug Administration for the expanded indication of REVLIMID for the treatment of non-del 5q lower risk myelodysplastic syndromes (MDS). The Prescription Drug User Fee Act date for the submission is April 16, 2016.

American Society of Hematology Meeting

At the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December, data presentations expected include:

Data from the phase III cooperative group SWOG S0777 trial comparing REVLIMID, bortezomib, and dexamethasone versus REVLIMID and dexamethasone in patients with newly diagnosed multiple myeloma not intended for immediate autologous stem cell transplant
Data on REVLIMID in novel combinations including elotuzumab, ixazomib and PD-1/PD-L1 compounds in multiple myeloma
Data from phase II trials of luspatercept in beta-thalassemia and MDS
Data from a phase I/II trial AG-221 in patients with IDH2-mutated AML
Data from a phase I trial of AG-120 in advanced hematologic malignancies
Data from phase I/II trials of ACY-1215 in relapsed and/or refractory multiple myeloma

Oncology

At the 2015 San Antonio Breast Cancer Symposium annual meeting in December, data presentations expected include:

Updated data from the GEPARSepto phase III trial with ABRAXANE in neoadjuvant breast cancer
Data from the WSG-ADAPT TN phase II trial comparing ABRAXANE in combination with carboplatin to gemcitabine in triple-negative breast cancer
Updated data from a phase I trial with atezolizumab in combination with ABRAXANE in triple-negative breast cancer

Inflammation & Immunology (I&I)

On August 27, 2015, Celgene completed the acquisition of Receptos, Inc. for approximately $7.1 billion, net of cash and marketable securities acquired. The acquisition of Receptos, Inc. enhances the Company’s I&I portfolio, further diversifies the expected revenue beginning in 2019, and builds upon the Company’s growing expertise in inflammatory bowel disease. The transaction adds ozanimod, a novel, potentially best-in-class, oral, selective sphingosine 1-phosphate 1 and 5 receptor modulator to the Company’s deep and diverse pipeline of potential disease-altering medicines and investigational compounds. Phase III trials with ozanimod in moderate-to-severe ulcerative colitis and relapsing multiple sclerosis are ongoing with data from these trials expected beginning in 2017.

Maintenance data from the phase II TOUCHSTONE trial with ozanimod in moderate-to-severe ulcerative colitis were presented in October at both the American College of Gastroenterology and the United European Gastroenterology: Week annual meetings. In the trial, a significantly greater proportion of patients that continued on to the ozanimod maintenance phase achieved or maintained clinical remission at 32 weeks compared with those on placebo. In addition at 32 weeks, both the high- and low-dose ozanimod arms were statistically significant compared to placebo for clinical response and mucosal healing. In phase II trials, ozanimod had a well-tolerated safety profile.

The phase III SUNBEAM trial with ozanimod in relapsing multiple sclerosis (RMS) completed enrollment ahead of schedule in October. In addition to the ongoing phase III trials with ozanimod in RMS and moderate-to-severe ulcerative colitis, a phase II proof-of-concept trial in moderate-to-severe Crohn’s disease initiated this quarter.

The phase III registration program with GED-0301 in patients with active Crohn’s disease is initiating. The registration-enabling endoscopy trial with GED-0301 in patients with active Crohn’s disease is ongoing and expected to complete enrollment by year-end. A phase II trial with GED-0301 in moderate-to-severe ulcerative colitis is expected to begin by year-end.

One-year data from the phase III LIBERATE (PSOR-010) trial evaluating OTEZLA or injectable etanercept versus placebo in patients with moderate-to-severe plaque psoriasis were presented at the European Academy of Dermatology and Venereology meeting in October. Improvements in PASI scores and disease-related quality of life observed at week 16 were maintained at week 52 in patients randomized to OTEZLA at baseline and in patients who switched from etanercept to OTEZLA at week 16.

Research and Early Development

The previously announced acquisition of Quanticel Pharmaceuticals, Inc. closed in October 2015. Celgene now has access to Quanticel’s proprietary platform for the single-cell genomic analysis of human cancer, as well as Quanticel’s programs that target specific epigenetic modifiers, which are expected to advance Celgene’s pipeline of innovative cancer therapies. Multiple drug candidates from Quanticel are expected to enter into clinical development beginning in early 2016. Celgene acquired Quanticel for $100 million in cash and up to an additional $385 million in contingent payments.

Management Update

Perry Karsen, Chief Executive Officer of Celgene Cellular Therapeutics (CCT), is retiring at the end of 2015. Mr. Karsen’s time with Celgene spanned over 10 years. He served as CEO of CCT since May 2013 and was also Chief Operations Officer from July 2010 until July 2014 and from 2004 to 2009 was Senior Vice President and Head of Worldwide Business Development. Mr. Karsen was instrumental in the acquisition of Pharmion in 2008 which brought VIDAZA to our portfolio of products.

Third Quarter 2015 Conference Call and Webcast Information

Celgene will host a conference call to discuss the third quarter of 2015 operational and financial performance on Thursday, November 5, 2015, at 9 a.m. ET. The conference call will be available by webcast at www.celgene.com. An audio replay of the call will be available from noon November 5, 2015, until midnight ET November 12, 2015. To access the replay in the U.S., dial 1-855-859-2056; outside the U.S. dial 404-537-3406. The participant passcode is 52827642.

On November 5, 2015 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies, reported that data from its ongoing clinical studies of LentiGlobin BB305 in beta-thalassemia major and severe sickle cell disease (SCD) will be highlighted in oral and poster presentations at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Filing, 8-K, bluebird bio, NOV 5, 2015, View Source [SID:1234508002]). The company will also present preclinical data from its lead oncology program, bb2121, in three posters at ASH (Free ASH Whitepaper). bluebird bio is developing bb2121 as an anti-BCMA oncology therapy in collaboration with Celgene Corporation. Preliminary data from all six of these abstracts will become available on the ASH (Free ASH Whitepaper) conference web site at 9:00 a.m. ET today.

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"Our expanding clinical experience with LentiGlobin continues to show promising clinical benefit in patients with beta-thalassemia major and severe sickle cell disease," said David Davidson, M.D., chief medical officer, bluebird bio. "We are pleased to see a median HbAT87Q level of 5.2 g/dL in the seven Northstar patients with beta-thalassemia major of all genotypes followed for six months or more, as this represents a substantial proportion of their total hemoglobin. It is exciting that transfusion independence has been achieved in all of our patients with beta‑thalassemia major with non-β0/β0 genotypes followed for at least six months in Northstar and HGB-205. Varying degrees of transfusion reduction have been observed in patients with β0/β0 genotypes. As would be expected, longer follow-up is required to assess the extent of HbAT87Q production and the impact on transfusion requirements in these patients with β0/β0 genotypes since they produce no functional beta-globin at baseline. Turning to sickle cell disease, our first treated patient is producing increased levels of HbAT87Q since we last reported on this study in June. HbAT87Q represented 48 percent of total hemoglobin at nine months post-infusion, and the patient remains transfusion independent without sickle cell-related adverse events as of the data cut-off. These results support the transformative potential of gene therapy, and we look forward to sharing more data at ASH (Free ASH Whitepaper)."

"The three accepted oncology abstracts represent the great progress we have made building our immuno-oncology business," said Rob Ross, M.D., head of oncology, bluebird bio. "These posters describe the encouraging pre-clinical data supporting the development of bb2121 in multiple myeloma, including our robust manufacturing platform, and key scientific insights into engineering more potent CARs that are applicable across our planned oncology portfolio."

LentiGlobin Presentations

Update of Results from the Northstar Study (HGB-204): A Phase 1/2 Study of Gene Therapy for Beta-Thalassemia Major via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector (LentiGlobin BB305 Drug Product) (Abstract #201)

Presenter: Mark C. Walters, M.D., UCSF Benioff Children’s Hospital, Oakland, CA

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-off:

· Seven subjects have been monitored for at least six months post-infusion: three of the β0/β0 genotype and four of the non-β0/β0 genotype.

· The median level of HbAT87Q expression among these seven subjects is 5.2 g/dL (range 1.9 to 8.2 g/dL), with total hemoglobin ranging from 8.5 to 11.1 g/dL at last visit.

· All four non-β0/β0 subjects have been transfusion-free for at least 90 days, with a median of 287 days transfusion-free (range: 171 to 396 days).

· Two of the β0/β0 subjects have received a single transfusion post-discharge, and one remains transfusion-dependent.

· All subjects engrafted.

· The safety profile was consistent with autologous transplantation. No Grade 3 or higher drug-product related adverse events have been observed, and there is no evidence of clonal dominance after a median follow-up of 198 days (range: 65 to 492 days).

Outcomes of Gene Therapy for Severe Sickle Disease and Beta-Thalassemia Major via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector (Abstract #202)

Presenter: Marina Cavazzana, M.D., Ph.D., Hôpital Universitaire Necker – Enfants Malades, Paris, France

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· The subject with severe SCD is producing approximately 51.5% anti-sickling hemoglobin (48 percent HbAT87Q, 1.8 percent HbF, 1.7 percent HbA2) at nine months post-infusion.

· The subject with severe SCD remains free of transfusions.

· The subject with severe SCD has not had a post-treatment hospitalization for a disease-related event despite ceasing chronic transfusions on Day +88.

· Both subjects with beta-thalassemia major have remained transfusion-free for at least 15 months post‑infusion, with consistent expression of HbAT87Q – both subjects are β0/βE genotype.

· One additional subject with beta-thalassemia major had one month follow-up post-infusion.

· No subject has experienced a drug product-related adverse event, and there is no evidence of clonal dominance.

Initial Results from Study HGB-206: A Phase 1 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the LentiGlobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease (Abstract #3233)

Presenter: John F. Tisdale, M.D., National Institutes of Health, Bethesda, MD

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· LentiGlobin BB305 drug product has been manufactured for 2 subjects with severe SCD and 1 subject has been infused.

· The safety profile has been consistent with autologous transplantation, with no Grade 3 or higher drug product-related adverse events.

bb2121 Presentations

Manufacturing an Enhanced CAR T Cell Product by Inhibition of the PI3K/Akt Pathway During T Cell Expansion Results in Improved In Vivo Efficacy of Anti-BCMA CAR T Cells (Abstract #1893)

Presenter: Molly Perkins, D.Phil., bluebird bio, Cambridge, MA

Date: Saturday, December 5, 2015

Abstract Results, as of July 31st Data Cut-Off:

· In an in vivo aggressive lymphoma model, mice treated with anti-BCMA CAR T cells cultured with IL-2 and an inhibitor of PI3K experienced complete and long-term tumor regression; mice treated with anti-BCMA CAR T cells cultured only with IL-2 experienced no effect on tumor growth and succumbed to the tumors within two weeks after treatment; anti-BCMA CAR T cells grown in IL-7 and IL-15 also did not affect tumor growth.

· In an in vivo multiple myeloma model, mice received a single administration of anti-BCMA CAR T cells cultured under various conditions; all treatment groups demonstrated tumor regression regardless of culture conditions. In a model of tumor relapse, two weeks after tumor clearance, surviving mice were re-challenged with the same multiple myeloma model on the opposite flank; only animals that had been treated with anti-BCMA CAR T cells cultured with the PI3K inhibitor were able to resist subsequent tumor challenge.

· These data suggest that inhibition of PI3K during ex vivo expansion may generate a superior anti-BCMA CAR T cell product for clinical use; this approach could potentially be used in manufacture of other anti-tumor CAR therapies.

A Novel and Highly Potent CAR T Cell Drug Product for Treatment of BCMA-Expressing Hematological Malignancies (Abstract #3094)

Presenter: Alena Chekmasova, Ph.D., bluebird bio, Cambridge, MA

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· bluebird bio has developed a chimeric antigen receptor (CAR) targeting BCMA (bb2121) that consists of extracellular single chain variable fragment scFv antigen recognition domain derived from antibodies to BCMA linked to CD137 (4-1BB) co-stimulatory and CD3zeta chain signaling domains.

· Based on receptor density quantification bb2121 can recognize tumor cells expressing less than 800 BCMA molecules per cell.

· In a BCMA+ MM xenograph model, treatment with bb2121 resulted in rapid and sustained elimination of the tumors and 100 percent survival.

Characterization of Lentiviral Vector Derived Anti-BCMA CAR T Cells Reveals Key Parameters for Robust Manufacturing of Cell-Based Gene Therapies for Multiple Myeloma (Abstract #3243)

Presenter: Graham W.J. Lilley, M.Sc., bluebird bio, Cambridge, MA

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· Successful personalized medicine will require robust and reproducible cell manufacturing. A series of experiments were conducted to determine whether variations in anti-BCMA CAR surface expression resulted in changes in the activity of CAR T cells.

· The potency of the final drug product was shown to be independent of total anti-BCMA CAR expression on the cell surface.

· T cells transduced with varying MOIs to yield different amounts of CAR surface expression were diluted with donor-matched untransduced cells to achieve a uniform population of T cells containing 26 + 4 percent anti-BCMA CAR T cells. When exposed to tumor, these CAR T cell populations exhibited no difference in cytotoxicity against BCMA-expressing cells. All T cell productions easily achieved a level of anti-BCMA CAR expression that resulted in potent anti-BCMA activity.

· These data show that our manufacturing platform has been optimized to overcome significant challenges associated with personalized medicine by reducing the effects of variability while maintaining potency in autologous cellular drug product manufacturing.

On November 5, 2015 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported financial results for the third quarter ended September 30, 2015 (Filing, 8-K, BioCryst Pharmaceuticals, NOV 5, 2015, View Source [SID:1234508001]).

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"The completion of enrollment of our OPuS-2 trial of avoralstat and the successful outcome of the Phase 1 healthy volunteer study of BCX7353 have positioned both programs to reach important value creating events in 2016. We expect to initiate the APeX-1 (Angioedema ProphylaXis) proof of concept trial of BCX7353 in HAE patients and to report OPuS-2 results by early 2016," said Jon P. Stonehouse, President & Chief Executive Officer of BioCryst. "These oral kallikrein inhibitors have the potential to revolutionize HAE treatment, providing patients the ability to lead normal lives."

Third Quarter Financial Results

For the three months ended September 30, 2015, revenues increased to $11.0 million from $3.2 million in the third quarter of 2014. The increase was the result of higher levels of product and collaboration revenue associated with the sale of RAPIVAB (peramivir injection) and the Seqirus, formerly bioCSL, out-licensing transaction, as well as increased collaboration revenue associated with BCX4430 development as a medical counter measure for Ebola virus and other filovirus diseases.

Research and development (R&D) expenses for the quarter increased to $20.1 million from $13.0 million in the third quarter of 2014. The increase in 2015 R&D expenses was primarily due to the advancement of the Company’s hereditary angioedema (HAE) programs, and to a lesser extent, higher expenses associated with two discovery-stage rare disease projects.

Selling, general and administrative (SG&A) expenses for the third quarter 2015 increased to $2.7 million from $1.8 million in 2014. This increase was due primarily to the initiation of activities in preparation for commercialization of the Company’s HAE product candidates, and to a lesser extent, commercial expenses associated with RAPIVAB.

In the third quarter of both 2015 and 2014, interest expense was $1.2 million and related to non-recourse notes payable. In addition, a mark-to-market loss on our foreign currency hedge of $460,000 was recognized in the third quarter of 2015, compared to a gain of $4.1 million in the third quarter of 2014. These gains and losses resulted from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement. During the third quarter of 2015, we 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 2015 was $14.6 million, or $0.20 per share, as compared to a net loss of $8.7 million, or $0.12 per share, for the third quarter of 2014.

Cash, cash equivalents and investments totaled $119.7 million at September 30, 2015, compared to $114.0 million at December 31, 2014. Net operating cash use for the third quarter of 2015 was $12.3 million, as compared to $8.0 million in the third quarter of 2014. Net operating cash use for the first nine months of 2015 was $28.1 million, as compared to $19.8 million for the 2014 period.

Year to Date Financial Results

For the nine months ended September 30, 2015, total revenues increased to $43.7 million from $8.2 million in the same period of 2014. The increase in 2015 was primarily due to revenue recognition of $21.7 million associated with the upfront payment from the Seqirus out-licensing transaction, RAPIVAB product revenue, and increased collaboration revenue associated with BCX4430 development.

R&D expenses increased to $53.7 million for the first nine months of 2015 from $33.3 million in the same period of 2014. The increase in 2015 expenses was primarily due to increased spending associated with the Company’s HAE development programs, and to a lesser extent, higher BCX4430 development costs and discovery activity on two rare disease projects.

SG&A expenses increased to $10.3 million for the nine months ended September 30, 2015 from $5.4 million for the nine months ended September 30, 2014. The increase was primarily associated with the initiation of a commercial organization in preparation for commercialization of the Company’s HAE drug candidates, unrestricted grants awarded to the U.S. and international HAE patient advocacy groups, as well as deal-related expenses associated with the Seqirus out-licensing transaction.

In the first nine months of 2015 and 2014, interest expense was $3.9 million and $3.7 million, respectively, and related to the non-recourse notes payable. In addition, a mark-to-market loss on our foreign currency hedge of $793,000 was recognized in the first nine months of 2015, compared to a gain of $732,000 in the same period of 2014. These gains and losses result from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement. We also realized a currency hedge gain of $1.7 million from the exercise of a U.S. Dollar/Japanese yen currency option.

The net loss for the nine months ended September 30, 2015 decreased to $24.9 million, or $0.34 per share, compared to a net loss of $33.5 million, or $0.52 per share, for the same period in 2014.

Clinical Development Update & Outlook

BioCryst recently announced that the OPuS-2 (Oral ProphylaxiS-2) clinical trial of avoralstat completed enrollment of approximately 100 HAE patients, and the Company expects to report results in early Q1 2016.

BioCryst also announced that the randomized, placebo-controlled, Phase 1 clinical trial of orally-administered BCX7353 in healthy volunteers successfully met all of its objectives. Oral BCX7353 was generally safe and well tolerated at all doses up to 500 mg once-daily for 7 days and 350 mg once-daily for 14 days in healthy volunteers, and no dose-limiting toxicity was identified. There were no serious adverse events (AEs) and most AEs were mild. The safety, tolerability, drug exposure and on-target plasma kallikrein inhibition results strongly support advancing the development program into the (APeX-1) Phase 2 proof of concept clinical trial of BCX7353 in HAE patients.

The APeX-1 (Angioedema ProphylaXis) Phase 2, four week dose ranging trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of BCX7353 as a preventative treatment to reduce or eliminate attacks in HAE patients is expected to begin by early 2016, with results expected mid-2016.

On October 27, The Japanese Ministry of Health Labor & Welfare (MHLW) announced that BioCryst’s BCX7353 was one of six products designated under MLHW’s new "Sakigake" fast track review system. The Sakigake Designation System promotes R&D in Japan, aiming at early market availability for innovative pharmaceutical products. This designation provides for additional interactions with the regulatory agency in Japan (PMDA) from early development through filing, prioritized development and review, and introduction of the product as soon as possible to address a serious unmet medical need.

Financial Outlook for 2015

Based upon current trends, assumptions, and development plans, BioCryst expects its 2015 net operating cash use to be in the range of $8 to $18 million, upon adjusting the Company’s previously predicted range for the first nine months of operations and including the favorable impact of the Seqirus transaction. In addition, BioCryst continues to expect its operating expenses to be within the range of $75 to $95 million. Our operating expense range excludes equity-based compensation expense due to the difficulty in accurately projecting this expense, as it is significantly impacted by the volatility and price of the Company’s stock, as well as vesting of the Company’s outstanding performance-based stock options.

On November 5, 2015 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing targeted agents and molecular diagnostics to treat the underlying mechanisms of cancer, reported that preclinical data for its lead investigational anticancer therapeutic APTO-253 will be presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 5-8, 2015, in Orlando, FL (Filing, 6-K, Aptose Biosciences, NOV 5, 2015, View Source [SID:1234508000]).

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Researchers from the Knight Cancer Institute at Oregon Health & Science University (OHSU) will present data demonstrating the ability of APTO-253 to kill acute myeloid leukemia (AML) cells in the majority of patient samples, with a trend toward correlation with baseline KLF4 expression level. Moreover, APTO-253 demonstrated enhanced killing ability of AML cells in patient samples when combined with either the BET inhibitor JQ1 or with the FLT3 inhibitor quizartinib. The studies were led by OHSU Knight Cancer Institute researcher Jeffrey Tyner, Ph.D., an assistant professor in the Department of Cell, Developmental & Cancer Biology in the OHSU School of Medicine. Beat AML is a collaborative research initiative spearheaded by the OHSU Knight Cancer Institute and The Leukemia & Lymphoma Society.

"These findings further support the ability of APTO-253, a first-in-class KLF4 inducer, to serve as a targeted treatment for AML," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "Indeed, this emboldens our clinical efforts to develop APTO-253 for use as a single agent and in combination therapies to treat AML and other hematologic malignancies and achieve favorable outcomes with lesser side effects."

The abstract is also available in the online edition of Blood, the official Journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) and on the ASH (Free ASH Whitepaper) conference website:

Abstract Details

Title: "Broad Activity of Apto-253 in AML and Other Hematologic Malignancies Correlates with KLF4 Expression Level"
Date/Time: Saturday, December 5, 2015, 5:30-7:30 p.m.
Location: Orange County Convention Center, Hall A
Abstract #: 83676
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I

Additional Abstract

An additional abstract describingthe favorable pharmacokinetics and safety profile of APTO-253 was accepted for publication in the ASH (Free ASH Whitepaper) online conference materials, in the December 3 edition of Blood and in the ASH (Free ASH Whitepaper) and Blood abstract archive.

Title: "Clinical Pharmacokinetics of APTO-253 Support its Use as a Novel Agent for the Treatment of Relapsed or Refractory Hematologic Malignancies"
Abstract #: 4934
Location: Publication

About APTO-253

APTO-253 is a clinical-stage small molecule targeted agent that acts through induction of the innate tumor suppressor gene Krüppel-like factor 4 (KLF4). Suppression of KLF4 gene expression has been reported as a key driver in the leukemogenesis of AML and subsets of other hematologic diseases. Aptose researchers have reported the ability of APTO-253 to upregulate KLF4 expression and induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved therapies for AML or myelodysplastic syndromes (MDS).

At last year’s ASH (Free ASH Whitepaper) meeting, Aptose presented data that demonstrated APTO-253’s robust safety profile and potent activity as a single agent and administered in combination with the chemotherapeutic drug azacitadine. In a prior single-agent, Phase 1 clinical study, APTO-253 demonstrated antitumor activity and a robust safety profile in patients with solid tumors.

APTO-253 is currently being evaluated in an ongoing open-label, single-agent, dose-escalating Phase 1b clinical trial in patients with relapsed or refractory hematologic malignancies, including AML and high-risk MDS.

On November 05, 2015 TG Therapeutics, Inc. (Nasdaq:TGTX) reported that updated data for TG-1101 (ublituximab), the Company’s novel, glycoengineered anti-CD20 monoclonal antibody, and TGR-1202, the Company’s next generation PI3K delta inhibitor, has been selected for presentation at the upcoming 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper), to be held December 5-8, 2015, at the Orange County Convention Center in Orlando, Florida (Press release, TG Therapeutics, NOV 5, 2015, View Source [SID:1234507999]).

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Michael S. Weiss, Executive Chairman and Interim Chief Executive Officer of TG Therapeutics, stated "We are very excited to be able to provide updates on our key Phase 1 and 2 clinical studies for TG-1101 and TGR-1202 at the upcoming ASH (Free ASH Whitepaper) conference. With patients now on once-daily TGR-1202 for durations of over 2.5 years, we and our investigators continue to believe that TGR-1202 has a differentiated safety profile in comparison to other PI3K delta inhibitors and continues to pair nicely with TG-1101 in our proprietary "TG-1303" regimen, which we believe exhibits best-in-class attributes that not only supports our recently announced Phase 3 UNITY-CLL study, but provides a safe and highly active backbone for building novel triple and potentially quad therapies. We are also excited to report data from the first triple therapy of TGR-1202 plus chemotherapy plus a glycoengineered anti-CD20 monoclonal antibody (obinutuzumab) which appeared to be well tolerated with a high level of activity in both front-line CLL patients and patients refractory to BTK inhibitors. We believe these data further support our UNITY-CLL study and also provide a nice comparison to TG-1303, especially from a safety standpoint. Finally, there will be one pre-clinical oral presentation that elucidates a very novel and exciting mechanism of TGR-1202, that is unique to TGR-1202 as opposed to other PI3K delta inhibitors and could have broad ranging implications for certain combinations in both liquid and solid tumors," stated Michael S. Weiss, the Company’s Executive Chairman and Interim CEO. He continued, "We are looking forward to sharing the full datasets for these presentations in a few weeks, which will contain more detailed data and additional patients than included in the abstracts."

Presentations on TG-1101 and TGR-1202 at the ASH (Free ASH Whitepaper) meeting include the following:

Clinical Posters:

Title: Ublituximab + TGR-1202 Demonstrates Activity and Favorable Safety Profile in Relapsed/Refractory B-Cell NHL and High-Risk CLL: Phase I Results
Abstract Number: 1538
Session: 624. Lymphoma: Therapy with Biologic Agents, excluding Pre-Clinical Models: Poster I
Date and Time: Saturday, December 5, 2015; 5:30 PM- 7:30 PM ET
Location: Orange County Convention Center, Hall A
Presenter: Matthew Lunning, DO

Title: A Phase I Trial of TGR-1202, a Next Generation Once Daily PI3K-Delta Inhibitor in Combination with Obinutuzumab Plus Chlorambucil, in Patients with Chronic Lymphocytic Leukemia
Abstract Number: 2942
Session: 642. CLL: Therapy, excluding Transplantation: Poster II
Date and Time: Sunday, December 6, 2015; 6:00 PM-8:00 PM ET
Location: Orange County Convention Center, Hall A
Presenter: Daruka Mahadevan, MD, PhD

Title: Ublituximab (TG-1101), A Novel Glycoengineered Anti-CD20 Monoclonal Antibody, in Combination With Ibrutinib is Highly Active in Patients With Relapsed And/Or Refractory Mantle Cell Lymphoma; Results of a Phase II Trial
Abstract Number: 3980
Session: 624. Lymphoma: Therapy with Biologic Agents, excluding Pre-Clinical Models: Poster III
Date and Time: Monday, December 7, 2015; 6:00 PM- 8:00 PM ET
Location: Orange County Convention Center, Hall A
Presenter: Kathryn Kolibaba, MD

Title: TGR-1202, a Novel Once Daily PI3K-Delta Inhibitor, Demonstrates Clinical Activity with a Favorable Safety Profile in Patients with CLL and B-Cell Lymphoma
Abstract Number: 4154
Session: 642. CLL: Therapy, excluding Transplantation: Poster III
Date and Time: Monday, December 7, 2015; 6:00 PM- 8:00 PM ET
Location: Orange County Convention Center, Hall A
Presenter: Owen O’Connor, MD, PhD

Non-Clinical Oral Presentation:

Title: Disruption of the mTOR-eIF4F Axis By Selectively Targeting PI3Kdelta and Proteasome Potently Inhibits Cap Dependent Translation of c-Myc in Aggressive Lymphomas
Abstract Number: 593
Oral Session: 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Novel Therapies and Targets in Lymphoma
Date and Time: Monday, December 7, 2015; 10:30 AM – 12:00 PM ET
Presentation Time: 11:30 AM ET
Location: Orange County Convention Center, Tangerine 1 (WF1)
Presenter: Changchun Deng, MD, PhD

A copy of the above referenced abstracts can be viewed online through the ASH (Free ASH Whitepaper) meeting website at www.hematology.org.

TG Therapeutics will also host a reception on Monday, December 7th, 2015 beginning at 7:45pm ET, with featured presentations beginning promptly at 8:00pm ET. The event will take place at the Hyatt Regency Orlando. This event will be webcast live and will be available on the Events page, under the Investors & Media tab, of the Company’s website at www.tgtherapeutics.com.