On April 18, 2017 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that a publication in the journal Science provided new translational data from a clinical trial of TIL therapy for the treatment of advanced metastatic cervical cancer conducted at the Surgery Branch of the National Cancer Institute (NCI) (Press release, Lion Biotechnologies, APR 18, 2017, View Source [SID1234518616]). This trial has been supported in part by Lion under a Cooperative Research and Development Agreement (CRADA) with Dr. Steven Rosenberg, Chief of the Surgery Branch, National Cancer Institute (NCI), National Institutes of Health.

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"Based on the encouraging data we have seen thus far for TIL therapy in this indication, we have initiated a Phase 2 trial of Lion’s TIL therapy in metastatic cervical cancer to investigate the responses seen in the NCI trial in a larger number of cervical cancer patients. However, patient selection in our ongoing Phase 2 trial is not limited by the presence of HPV, as the study is designed to allow a broader patient population to be enrolled," said Maria Fardis, PhD, MBA, President and Chief Executive Officer of Lion Biotechnologies.

Data from the NCI clinical trial was previously presented at the 2014 meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. These data indicated that a single infusion of TIL therapy generated two complete and durable remissions, ongoing at 15 and 22 months at the time of presentation. A third patient was reported to have achieved a partial three-month response with a 39% reduction in tumor volume.

The new translational study published in Science further evaluated the two patients with ongoing complete remissions. These data demonstrated that the antitumor activity of these patients’ TIL targeted both viral and non-viral tumor antigens.

Dr. Christian Hinrichs, the lead investigator of the trial at NCI’s Center for Cancer Research (CCR) said, "Our research shows the importance of not only viral but also non-viral antigens in immunotherapy for cervical cancer. These findings have important implications for how we design and study new treatments for this disease."

On April 18, 2017 Johnson & Johnson (NYSE: JNJ) reported sales of $17.8 billion for the first quarter of 2017, an increase of 1.6% as compared to the first quarter of 2016 (Press release, Johnson & Johnson, APR 18, 2017, View Source [SID1234518610]).

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Operational sales results increased 2.0% and the negative impact of currency was 0.4%. Domestic sales increased 0.6%. International sales increased 2.8%, reflecting operational growth of 3.6% and a negative currency impact of 0.8%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.2%, domestic sales decreased 0.7% and international sales increased 3.4%.*

Net earnings and diluted earnings per share for the first quarter of 2017 were $4.4 billion and $1.61, respectively. First-quarter 2017 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.4 billion. First-quarter 2016 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.2 billion. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $5.0 billion and adjusted diluted earnings per share were $1.83, representing increases of 3.8% and 5.8%, respectively, as compared to the same period in 2016. * On an operational basis, adjusted diluted earnings per share also increased 7.5%.* A reconciliation of non-GAAP financial measures is included as an accompanying schedule.

"Johnson & Johnson’s first-quarter results are in line with our expectations and we are confident we will achieve the full-year financial guidance we established at the beginning of the year," said Alex Gorsky, Chairman and Chief Executive Officer. "The pending acquisition of Actelion demonstrates our ongoing commitment to bringing innovation to patients with significant unmet needs, and provides a unique opportunity for us to expand our portfolio with leading, differentiated in-market medicines and promising late-stage products. We look forward to the associates from Actelion joining the Johnson & Johnson Family of Companies."

The Company is now including the estimated impact of the Actelion transaction in its financial guidance. As such, the Company increased its sales guidance for the full-year 2017 to $75.4 billion to $76.1 billion. Additionally, the Company increased its adjusted earnings guidance for full-year 2017 to $7.00 – $7.15 per share.*

Worldwide Consumer sales of $3.2 billion for the first quarter 2017 represented an increase of 1.0% versus the prior year, consisting of an operational increase of 0.8% and a positive impact from currency of 0.2%. Domestic sales increased 4.1%; international sales decreased 1.3%, which reflected an operational decrease of 1.6% and a positive currency impact of 0.3%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales decreased 2.3%, domestic sales decreased 2.9% and international sales decreased 1.9%*.

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were negatively impacted by LISTERINE oral care products, baby care products, and wound care products, partially offset by growth in over-the-counter products, including domestic TYLENOL analgesics.

Worldwide Pharmaceutical sales of $8.2 billion for the first quarter 2017 represented an increase of 0.8% versus the prior year with an operational increase of 1.4% and a negative impact from currency of 0.6%. Domestic sales decreased 1.3%; international sales increased 4.1%, which reflected an operational increase of 5.6% and a negative currency impact of 1.5%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 2.2%, domestic sales decreased 0.4% and international sales increased 6.1%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by new products and the strength of core products. Strong growth in new products include DARZALEX (daratumumab), for the treatment of patients with multiple myeloma and IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer. Additional contributors to operational sales growth included STELARA (ustekinumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, and INVEGA SUSTENNA/XEPLION/TRINZA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults. Sales growth was negatively impacted by a positive adjustment of rebate accruals in the first quarter of 2016, which did not occur to the same degree in the first quarter of 2017.

During the quarter, the Company announced a definitive agreement to acquire Actelion Ltd., a leading biopharmaceutical company, for approximately $30 billion. The public tender offer for Actelion has been declared successful based on the number of shares tendered and regulatory approval has been obtained in six of seven jurisdictions in which the company filed for such approval, with antitrust approval from the European Commission pending. The transaction is expected to close in the second quarter of 2017, subject to the satisfaction of remaining closing conditions.

Also in the quarter, the Committee for Medicinal Products for Human Use of the European Medicines Agency issued a positive opinion recommending broadening the existing marketing authorization for DARZALEX (daratumumab) for use in combination with lenalidomide and dexamethasone; or bortezomib and dexamethasone, for the treatment of multiple myeloma in patients who have received at least one prior therapy. A supplemental New Drug Application was submitted to the U.S. Food and Drug Administration for IMBRUVICA (ibrutinib) for the treatment of chronic Graft-Versus-Host Disease after failure of one or more lines of systemic therapy.

In April, subsequent to the quarter, a marketing authorization application was submitted to the European Medicines Agency for ZYTIGA (abiraterone acetate) to expand the existing indication to include treatment of men with newly diagnosed high-risk metastatic hormone sensitive prostate cancer.

Worldwide Medical Devices sales of $6.3 billion for the first quarter 2017 represented an increase of 3.0% versus the prior year consisting of an operational increase of 3.4% and a negative currency impact of 0.4%. Domestic sales increased 2.2%; international sales increased 3.8%, which reflected an operational increase of 4.7% and a negative currency impact of 0.9%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.7%, domestic sales decreased 0.2% and international sales increased 3.7%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by electrophysiology products in the Cardiovascular business; ACUVUE contact lenses in the Vision Care business and endocutters in the Advanced Surgery business, partially offset by declines in the Diabetes Care business.

During the quarter, the company completed the acquisition of Abbott Medical Optics, a wholly-owned subsidiary of Abbott and global leader in ophthalmic surgery, for approximately $4.3 billion.

Additionally, the acquisitions of Megadyne Medical Products, Inc., a privately held medical device company that develops, manufactures and markets electrosurgical tools, and Torax Medical Inc., a privately held medical device company that manufactures and markets the LINX Reflux Management System for the surgical treatment of gastroesophageal reflux disease, were completed.

In April, subsequent to the quarter, the acquisition of Neuravi Limited, a privately held medical device company that develops and markets medical devices for neurointerventional therapy, was completed.

On April 18, 2017 XOMA Corporation (Nasdaq:XOMA), a pioneer in the discovery and development of therapeutic antibodies, reported the presentation of positive data from pre-clinical studies investigating the activity of its anti-PTH1R antagonist monoclonal antibody (mAb) (Press release, Xoma, APR 18, 2017, View Source [SID1234518611]). The antibody is a potential first-in-class therapeutic agent for the treatment of hyperparathyroidism (HPT) and humoral hypercalcemia of malignancy (HHM). These presentations were made at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) and the Endocrine Society (ENDO) annual meetings.

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The PTH1R receptor is part of the B GPCR family and is the primary receptor of two ligands, parathyroid hormone (PTH) and parathyroid related protein (PTHrP). Hypercalcemia can occur when elevated levels of PTH, as seen in primary HPT, or elevated levels of PTHrP, as seen in HHM, lead to excessive activation of the PTH1R receptor. A potent and long-acting receptor antagonist could reverse hypercalcemia in all these conditions.

"Consistent with our new strategy, we are seeking partners with a deep commitment to and an expertise in drug development who are interested in licensing this first-in-class antibody and taking it through the clinical development process," said Jim Neal, Chief Executive Officer of XOMA. "There is a real need for better therapies that address hypercalcemia induced by hyperparathyroidism, and we are encouraged by these data, which demonstrate the efficacy of our anti-PTH1R approach as a potential treatment for patients suffering from HPT and HHM."

Data presented at the AACR (Free AACR Whitepaper) and ENDO conferences between April 1-4, 2017 showed:

PTH1R antagonism in vitro by the anti-PTH1R mAb translated to potent in vivo activity
XOMA’s anti-PTH1R antagonist mAb has the potential to become a first-in-class therapy for HHM, as the data demonstrated it ameliorated hypercalcemia and associated morbidities in pre-clinical models
XOMA’s antibody libraries enabled the discovery of functional antibodies against a very complex target — i.e. the G-Protein Coupled PTH1Receptor
A high affinity fully human mAb to PTH1R has been selected and characterized
Proprietary antibody engineering resulted in antibodies with improved potency and manufacturing characteristics
"While hyperparathyroidism is a classic endocrine disorder, HHM spans both endocrine and oncology specialties. HHM is a life-threatening complication of many advanced cancers and is caused by tumor secretion of the PTH1R ligand, PTH-related peptide, which causes high calcium. Since current treatments often fall short of correcting hypercalcemia and many cancer patients die from such high calcium and associated metabolic complications, PTH1R antibodies could prove beneficial for the treatment of this devastating condition," said John Wysolmerski, MD, Professor of Medicine and Associate Section Chief for Research in the Section of Endocrinology and Metabolism, Yale School of Medicine.

The complete presentations can be found online at www.xoma.com/content/pipeline/publications.htm.

About XOMA’s PTH1R Monoclonal Antibodies Program
XOMA has developed unique functional antibody antagonists targeting PTH1R, a G-protein-coupled receptor involved in the regulation of calcium metabolism. These antibodies have shown promising efficacy in in vivo studies and potentially could address high unmet medical needs, including primary hyperparathyroidism (PHPT) and humoral hypercalcemia of malignancy (HHM). Some secondary and tertiary HPT cases are additionally challenging to manage via current pharmacological approaches and may be well-addressed by XOMA’s anti-PTH1R antibody.

On April 18, 2017 Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) reported a collaboration and license agreement with Suzhou Ribo Life Science Co., Ltd. (Ribo) to develop and commercialize RNA-targeted therapeutics in China (Press release, Ionis Pharmaceuticals, APR 18, 2017, View Source [SID1234518609]). Ionis granted Ribo a license for the right to commercialize in China two Ionis Generation 2+ antisense drugs in metabolic disease and cancer and an option to license a third pre-specified Generation 2+ antisense drug. In addition, Ribo will be responsible for conducting a multi-year research and drug discovery program to identify drugs that utilize Ionis’ ssRNAi technology. Ionis will receive an undisclosed up-front payment and equity in Ribo. Ionis retains the rights to develop and commercialize ssRNAi technology and all drugs under the collaboration outside of China.

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Ionis Pharmaceuticals

"The need for new medicines in China is growing rapidly, especially for metabolic diseases and certain genetically-defined cancers," said Brett Monia, senior vice president of drug discovery and franchise leader for oncology and rare diseases at Ionis Pharmaceuticals. "Ribo is the ideal partner for us in China. Ribo has made excellent progress in its RNAi therapeutic programs and we believe we will benefit from their drug development and regulatory expertise in China. We believe that our partnership with Ribo maximizes the value of our drugs in this collaboration by leveraging the clinical data generated in China to support the overall global development plan for each drug."

"We are committed to advancing new RNA-targeted therapeutics, like RNAi and antisense, to patients with high unmet medical need in China," said Liang Zicai, founder and Chairman of Ribo. "Ionis has made significant breakthroughs showing that chemically modified single-stranded oligonucleotides can activate the RNAi pathway. We believe that this work is the foundation for a robust drug discovery platform that takes advantage of using single-stranded RNA-like antisense drugs that harness the power of the RNAi pathway. We are excited by the opportunity to contribute our expertise and resources to advancing this promising technology."

Following the identification of a development candidate, Ribo may exercise its option to license each drug by paying Ionis a license fee. For each drug that Ribo licenses, Ribo will be responsible for all development and commercialization activities and costs in China. Ionis is eligible to receive development, regulatory and commercial milestone payments as each drug advances. In addition, Ionis is eligible to receive royalties on net sales of each drug.

Ribo will provide Ionis a royalty-free license to the data and intellectual property created under the collaboration.

ABOUT RNAi AND ssRNAi
As it is known to occur in nature, the RNAi pathway is mediated by short double-stranded RNA oligonucleotides called "small interfering RNAs" or "siRNAs." To date, efforts aimed at harnessing this pathway to silence disease-causing proteins have used double-stranded siRNAs. Double-stranded siRNA drugs require complex formulations or special conjugates to achieve sufficient delivery for systemic activity. This requirement has severely limited the development of safe and effective drugs that work through the RNAi pathway. In contrast, single-stranded RNA-like antisense drugs can be administered subcutaneously and distribute to tissues without the need for complex formulations or special conjugates. Using its expertise in oligonucleotide chemistry and design, Ionis has discovered strategies for designing single-stranded oligonucleotides that act through the RNAi mechanism. With further development, these chemically modified, single-stranded, RNA-like oligonucleotides have the potential for improved properties for systemic administration while harnessing the advantages of the RNAi mechanism.

On April 18, 2017 Argos Therapeutics Inc. (Nasdaq:ARGS), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis precision immunotherapy technology platform, reported interim results from its randomized, active controlled, open-label, multi-center Phase 3 ADAPT trial of Rocapuldencel-T in combination with sunitinib/standard-of-care for the treatment of newly diagnosed metastatic renal cell carcinoma (mRCC) (Press release, Argos Therapeutics, APR 18, 2017, View Source [SID1234518608]). The Company also provided perspective on its decision to continue the trial.

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A total of 462 patients were enrolled in the ADAPT study and randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib (combination arm) vs. sunitinib monotherapy (control arm). For both arms, the protocol permits switching to other standard-of-care treatments for mRCC for reasons such as intolerance to therapy or disease progression. The primary efficacy endpoint for the study is a statistically significant improvement in overall survival, with secondary efficacy endpoints evaluated to date of progression-free survival, objective response rate and disease control rate, and an exploratory efficacy endpoint of immune response. The trial was opened in January 2013 and completed enrollment in July 2015 at 107 sites across North America, Europe and Israel.

The most recent interim analysis was conducted by the Independent Data Monitoring Committee (IDMC) in February 2017 (data cut-off as of February 3, 2017) after 75% of the targeted number of 290 events (deaths) for the analysis of the primary endpoint of overall survival had occurred. In accordance with the statistical analysis plan, median overall survival was estimated using the Kaplan-Meier method. At the time of the interim analysis, the estimated median overall survival for the combination arm was 27.7 months (95% Confidence Interval (CI): 23.0, 35.9) compared to 32.4 months (95% CI: 22.5, -) for the control arm. The hazard ratio was 1.10 (95% CI: 0.83, 1.46), which was greater than the pre-defined futility boundary for the final interim analysis of 0.98. As a result, the IDMC recommended that the study be discontinued for futility. The IDMC concluded that the study was unlikely to demonstrate a statistically significant improvement in overall survival in the combination arm, utilizing the intent-to-treat population, the primary endpoint of the study. The IDMC also noted that Rocapuldencel-T was generally well-tolerated in the trial.

As previously reported, notwithstanding the IDMC recommendation, the Company determined to continue to conduct the trial pending further review and analysis of the data and discussions with the FDA. This determination was made after discussion of the results of the interim analysis with the ADAPT trial principal investigators, Robert Figlin, MD (Cedars Sinai) and Christopher Wood, MD (MD Anderson Cancer Center). In making this determination, Argos considered, among other factors, the degree of maturity of the data set, the mechanism of action of Rocapuldencel-T, which involves the induction of long-term memory immune responses, and the IDMC’s assessment of the safety profile of Rocapuldencel-T. Of note, at the time of the IDMC’s February interim analysis, the median duration of follow-up was 20.0 months and more than half the patients in both treatment groups were still alive.

Subsequent to the IDMC meeting, to explore the hypothesis that longer follow-up time may provide useful information to identify a potential beneficial effect of Rocapuldencel-T, the Company conducted a post-hoc subgroup analysis of overall survival in the first third of patients enrolled in the study (n=154). In these patients, for whom generally the longest follow-up data was available, the estimated median overall survival for the combination arm was 30.1 months (95% CI: 23.3, -) compared to 22.2 months (95% CI: 17.2, -) for the control arm. The hazard ratio in this post-hoc subgroup analysis was 0.88 (95% CI: 0.56, 1.36).

In addition, also subsequent to the IDMC meeting, the Company began conducting a pre-defined analysis of immune responses, an exploratory efficacy endpoint, using multi-parametric flow cytometry. Data available as of March 31, 2017 included 109 of the 190 samples from patients in the combination arm, with analysis of the remaining samples ongoing. Samples were collected from patients in the combination arm enrolled at US sites who provided consent for immune monitoring. Of the 109 subjects for whom this analysis was completed, 96 (88%) met the criterion for inclusion in the pre-defined subgroup of immune responders, suggesting that Rocapuldencel-T is having its intended effect of stimulating an immune response in the majority of patients. Immune responders are defined as patients who have an increase of more than two standard deviations from the patient-specific baseline in the number of memory T cells (CD8+/CD28+/CD45RA-) at one or more time points. Of note, median overall survival at the time of the February interim analysis had not yet been reached in the subgroup of immune responders (95% CI: 30.1, -). Additionally, consistent with the mechanism of action of Rocapuldencel-T, a statistically significant correlation was observed between the increase from baseline in the number of Rocapuldencel-T-induced memory T cells (CD8+/CD28+/CD45RA-) and overall survival in patients for whom immune response data has been analyzed and who received at least seven doses of Rocapuldencel-T (including both immune responders and non-responders, n=72).

The Company continues to analyze the data from the trial and plans to meet with the FDA in May 2017, but currently believes based on the data it has reviewed that the trial should be continued until completion. Based on these analyses and discussions, the Company will make a determination as to the next steps for the Rocapuldencel-T clinical program.

About the Arcelis Technology Platform

Arcelis is a precision immunotherapy technology that captures both mutated and variant antigens that are specific to each patient’s individual disease. It is designed to overcome immunosuppression by producing a specifically targeted, durable memory T cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to the treatment of a wide range of different cancers and infectious diseases, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized immunotherapies. The Arcelis process uses only a small disease sample or biopsy as the source of disease-specific antigens, and the patient’s own dendritic cells, which are optimized from cells collected by a single leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease-specific antigens. These activated, antigen-loaded dendritic cells are then formulated with the patient’s plasma, and administered via intradermal injection as an individualized immunotherapy.