On April 26, 2016 Baxter International Inc. (NYSE:BAX) reported results for the first quarter of 2016, and also increased its earnings per share outlook for full-year 2016 (Press release, Baxter International, APR 26, 2016, View Source [SID:1234511410]). First quarter worldwide sales totaled $2.4 billion, an increase of 4 percent on a constant currency basis as compared to the prior year period. On a reported basis, sales declined 1 point as foreign exchange negatively impacted sales by five percentage points in the quarter.

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"We are off to a strong start in 2016, with first quarter results exceeding our expectations," said José (Joe) E. Almeida, chairman and chief executive officer. "Our new strategic framework focused on portfolio optimization, operational excellence and capital allocation is driving improved performance throughout the organization and is reflected in our increased financial outlook for the year. We are confident our strategy positions the company for sustainable growth and value creation for all our stakeholders."

During the quarter, Baxter achieved a number of operational, pipeline and commercial milestones in support of its strategy to accelerate profitable growth, including:

U.S. launch of ready-to-use VANCOMYCIN injection in 0.9% Sodium Chloride (Normal Saline) in 500 mg, 750 mg and 1 gram presentations. Baxter is the only manufacturer to offer VANCOMYCIN in a premixed presentation, which uses the company’s proprietary frozen GALAXY container technology. With this launch, Baxter now supplies VANCOMYCIN in both saline and dextrose presentations, providing additional therapy options for a critical antibiotic that has appeared periodically on the FDA Drug Shortage list. In addition, Baxter has now submitted to the FDA for review the third of the nine molecules expected to launch over the next several years.
CE marking for the expanded indication of HEMOPATCH in the European Union for tissue sealing and dura replacement in addition to hemostasis. The advanced surgical patch now has one of the broadest indications available for advanced surgical patches in Europe.
Japanese approval for the expanded use of our flowable hemostat FLOSEAL to include endoscopic surgery.
Marketing authorization in United Kingdom and Denmark, the initial of 20 country approvals sought in 2016 for NUMETA G13E, the only triple-chamber, commercially prepared parenteral nutrition system approved to meet the critical needs of vulnerable neonatal patients.
Enrollment of the first patient in the U.S. clinical trial for VIVIA, an investigational home hemodialysis (HD) system. The trial is designed to study more frequent, extended duration nocturnal home HD therapy (High Dose HD).
Retirement of approximately $3.7 billion of gross debt through utilization of a portion of the retained stake in Baxalta Incorporated (Baxalta) through two debt-for-equity exchanges. At the end of the quarter, Baxter held approximately 30.5 million Baxalta shares and currently intends to utilize this remaining equity through a contribution to its U.S. qualified pension plan and an equity-for-equity exchange. While subject to regulatory approval, both of these transactions are currently expected to be completed during the second quarter.
Financial Results

During the quarter, Baxter reported income from continuing operations of $3.4 billion, or $6.13 per diluted share, on a GAAP (Generally Accepted Accounting Principles) basis. These results included an after-tax net gain of approximately $3.3 billion from the disposition of shares the company retained following the spin-off of Baxalta in July 2015. Partially offsetting these results were net after-tax special items totaling $109 million (or $0.20 per diluted share) primarily related to debt extinguishment, intangible asset amortization, Baxalta related spin-off costs and certain business optimization initiatives.

On an adjusted basis, excluding special items, Baxter’s first quarter income from continuing operations totaled $199 million, or $0.36 per diluted share, exceeding the company’s previously-issued guidance of $0.28 to $0.30 per diluted share.

Sales within the United States advanced 5 percent to $992 million, while international sales totaled $1.4 billion, representing a 4 percent increase on a constant currency basis, and a 5 percent decline on a reported basis. There was no impact on Baxter’s total sales growth in the quarter from U.S. cyclophosphamide.

By business, Hospital Products sales of $1.5 billion increased 4 percent on a constant currency basis and declined 1 percent on a reported basis. Hospital Products performance in the quarter benefited from strong sales of Baxter’s next-generation SIGMA SPECTRUM infusion pump and IV solutions in the United States as well as increased demand for the company’s injectable drug compounding services.

Baxter’s Renal Products sales totaled $898 million, representing a 5 percent increase on a constant currency basis, and a 2 percent decline on a reported basis. Increased demand for peritoneal dialysis products and continuous renal replacement therapies contributed to sales growth in the quarter.

Financial Outlook

Based on the company’s strong first quarter performance, Baxter is raising its financial outlook for full-year 2016. Baxter now expects constant currency sales growth for full-year 2016 of approximately 3 percent, or approximately 4 percent after adjusting for increased U.S. competition for cyclophosphamide. On a reported basis, including the impact of foreign exchange, Baxter now expects sales to increase approximately 1 percent as compared to previous guidance of a decline of approximately 1 percent. In addition, the company now expects earnings from continuing operations, before special items, of $1.59 to $1.67 per diluted share for the full year as compared to previous guidance of $1.46 to $1.54 per diluted share.

For the second quarter, the company expects constant currency sales growth of approximately 4 percent, and on a reported basis, sales growth of approximately 2 percent. Baxter expects earnings from continuing operations, before special items, of $0.38 to $0.40 per diluted share for the second quarter of 2016.

The earnings guidance for the second quarter and full-year 2016 excludes approximately $1.94 and $8.01, respectively, per diluted share of realized gains related to the planned use of the Baxalta retained stake; $0.05 and $0.21, respectively, per diluted share of intangible asset amortization expense; an estimated $0.08 to $0.09 and $0.30 to $0.34, respectively, per diluted share related to business optimization and Baxalta separation-related expense activities; and $0.11 per diluted share of debt extinguishment loss and product related reserve adjustments for full-year 2016. These estimates are based on information reasonably available at the time of this release and future events or new information may result in different actual results. Reconciling for the inclusion of these items results in GAAP earnings of $2.18 to $2.21 per share for the second quarter of 2016 and $8.94 to $9.06 per diluted share for full-year 2016.

On April 26, 2016 Tokai Pharmaceuticals Inc. (NASDAQ: TKAI), a biopharmaceutical company focused on developing and commercializing innovative therapies for prostate cancer and other hormonally driven diseases, reported an oral presentation on galeterone at the 2016 American Urological Association (AUA) Annual Meeting in San Diego (Press release, Tokai Pharmaceuticals, APR 26, 2016, View Source;p=RssLanding&cat=news&id=2161338 [SID:1234511407]). Galeterone, Tokai’s lead product candidate, is being developed for the treatment of men with metastatic castration-resistant prostate cancer.

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The presentation, titled "Galeterone shows anti-tumor activity in multiple pre-clinical models that express androgen receptor splice variants, supporting correlative patient data seen in ARMOR2" (abstract number PD32-07), will be presented on Sunday, May 8, from 4:30 – 4:40 p.m. PDT in room 30DE, as part of the session, "Prostate Cancer: Advanced (including Drug Therapy) III." The presenting author is Vincent C.O. Njar, Ph.D., Professor of Medicinal Chemistry and Pharmacology, Department of Pharmacology; Head of the Medicinal Chemistry Section, Center for Biomolecular Therapeutics; and Member of the Marlene and Stewart Greenebaum Cancer Center at the University of Maryland School of Medicine, Baltimore. Dr. Njar is a co-inventor of galeterone.

Additional information, including the presentation schedule and full abstracts, may be found at www.aua2016.org. A copy of the presentation will be available on the "Publications & Presentations" page of Tokai’s website, www.tokaipharmaceuticals.com.

About Galeterone
Galeterone is an oral small molecule that utilizes the established pathways, including CYP17 enzyme and androgen receptor inhibition, of the current second-generation hormonal therapies abiraterone and enzalutamide. Galeterone also introduces a distinct third mechanism – androgen receptor degradation – that decreases the sensitivity of androgen receptors to androgen activity, thus leading to reductions in tumor growth. Tokai is developing galeterone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). ARMOR3-SV, the company’s pivotal Phase 3 study of galeterone in treatment-naive mCRPC patients whose prostate tumors express the AR-V7 splice variant, is evaluating whether administration of galeterone results in a statistically significant increase in radiographic progression-free survival as compared to enzalutamide. Tokai is also evaluating galeterone in mCRPC patients who have shown resistance following treatment with second-generation hormonal agents. Tokai has worldwide development and commercialization rights to galeterone.

JNJ-63709178, a bispecific antibody that targets CD3 and CD123, was created under a collaboration between Genmab and Janssen using Genmab’s DuoBody technology (Company Pipeline, Genmab, APR 26, 2016, View Source [SID:1234511406]). JNJ-63709178 is being investigated in a Phase I clinical study to treat relapsed or refractory acute myeloid leukemia and is the second bispecific antibody created with the DuoBody technology to be added to Genmab’s pipeline.

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On April 26, 2016 Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, reported that the first patient in China has been enrolled in its ongoing global Phase III OPTIMA Study evaluating ThermoDox, Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin, in combination with radiofrequency ablation standardized to 45 minutes (sRFA) versus sRFA alone to treat newly diagnosed patients with primary liver cancer, also known as hepatocellular carcinoma (HCC) (Press release, Celsion, APR 26, 2016, View Source [SID:1234511405]).

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The pivotal, double-blind, placebo-controlled OPTIMA Study is expected to enroll up to 550 patients globally, and has been successfully enrolling patients at 50 clinical sites in 12 different countries in North America, Europe and Asia Pacific. In December 2015, the Company announced that it had received a Clinical Trial Application (CTA) approval from the China Food and Drug Administration (CFDA) to conduct the OPTIMA Study at up to 20 additional clinical sites in China. The Company aims to enroll more than 200 patients in the China territory, the minimum number required by the CFDA to file a New Drug Application (NDA), assuming positive clinical results.

"The enrollment of the first patient in China represents a significant milestone for the OPTIMA program," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "With the growing incidence of primary liver cancer in China, representing approximately 50% of the 850,000 cases diagnosed annually, this country is an important element of our global registration and commercialization strategy for ThermoDox, and we are committed to driving patient enrollment in this region as we execute our OPTIMA study."

"Survival data from the subgroup analysis in the HEAT study underscore the potential of ThermoDox in combination with sRFA to serve as a potentially curative treatment in primary liver cancer, where very limited treatment options currently exist," said Dr. Nicholas Borys, Celsion’s chief medical officer. "We look forward to working with our colleagues in China and the global research team to further explore ThermoDox in this setting."

The primary endpoint for the OPTIMA Study is overall survival (OS). The statistical plan calls for two preplanned interim efficacy analyses by an independent Data Monitoring Committee (iDMC). The design of the OPTIMA Study is supported by a retrospective analysis of a large subgroup of 285 patients in the Company’s previous 701 patient HEAT Study in primary liver cancer. In a subgroup of 285 HEAT Study participants, ThermoDox plus standardized RFA demonstrated a statistically significant improvement in survival of over two years compared to standardized RFA alone. In this large subgroup, the median overall survival in the ThermoDox plus standardized RFA arm was approximately 80 months (6 ½ years), which is considered a curative treatment for HCC.

Anti-tumor cellular immunotherapies that implement a suicide gene system can limit potential undesirable effects. In a haplo-identical bone marrow transplant clinical trial, over 90% of iCaspase-9-expressing cells were eradicated after AP1903 exposure, and signs of graft-versus-host disease disappeared. Nevertheless, low numbers of genetically-modified T cells survived this treatment. We studied genetically-modified cell lines (GMCL) that carried a dual iCaspase-9/ΔCD19 DNA construct (ΔCD19=truncated CD19). With AP1903 exposure, a low percentage of cells (1.47%±0.67%; n=5 replications) persisted in-vitro. Repeated exposures to increasing AP1903 doses generated low (GMCLLR) and high AP1903-responders (GMCLHR), which expressed different levels of surface ΔCD19and intracellular iCaspase-9. Compared to GMCLHR, GMCLLR exhibited higher methylation of 5′-long-terminal repeat (LTR) promoters, both in the number of sequences with at least one methylated CpG (16 vs 51.5%, respectively) and in the number of CpG islands (1.2 vs 8.9%, respectively). Four days of 5-azacytidine exposure reduced methylation and increased ΔCD19 and iCaspase-9 expression. Interestingly, LTR demethylation restored GMCLLR sensitivity to AP1903 by 24.3-fold (1.8 vs 43.8%) without affecting GMCLHR. We showed that 5’LTR-methylation inhibited transgene expression and caused AP1903 hypo-responsiveness. Treating with a hypomethylating agent restored AP1903 sensitivity. This approach can be applied in further clinical trials to improve iCaspase-9 response if low response is detected.Gene Therapy accepted article preview online, 25 April 2016. doi:10.1038/gt.2016.39.

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