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Nymox Reports Results of Prospective Cross-Over Study of Fexapotide Treatment for Prostate Cancer

On October 29, 2015 Nymox Pharmaceutical Corporation (NASDAQ:NYMX) reported that long-term randomized cross-over data from the Company’s trial of fexapotide triflutate for low grade localized prostate cancer has shown statistical significance in efficacy compared to controls (Press release, Nymox, OCT 29, 2015, View Source [SID:1234507839]).

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The study results indicate that randomized control subjects who subsequently switched to fexapotide had long-term outcomes significantly superior to control patients who did not change (cross-over) to fexapotide treatment.

These results are the initial 18 month follow-up results for the fexapotide trial for prostate cancer to be reported. The cross-over study arm of NX03-0040 consisted of 35 subjects. Based on biopsy progression the proportion of patients who progressed on biopsy and required biopsy progression-related surgery or radiotherapy in the cross-over group (0%) at 18 months was significantly less than in the control group (p<.03).

The cross-over group patients received randomized fexapotide 15 mg or 2.5 mg in a single treatment targeted toward the positive baseline cancer focus identified in initial positive biopsies. There were no cases in either of the 2 fexapotide dosage level treatment groups with biopsy progression at 18 months (p<.03).

In addition to the positive clinical progression results, the primary endpoint of the study (re-biopsy absence of tumor in the initially positive biopsy baseline area of the prostate) also reached statistical significance (p<.03) in the cross-over study. At the 18 month assessments, the post-treatment biopsy taken from the treated area of the prostate which was initially positive at baseline, showed absence of tumor (tumor presence in re-biopsy of baseline positive focus n=0) in the cross-over treated patients, which was statistically significant compared to controls (p<.03).

The Company expects to report results from its long-term NX03-0040 low grade localized prostate cancer study in the fourth quarter.

One of the major problems with current prostate treatments for localized prostate cancer (radical prostatectomy, external beam radiation, or brachytherapy) is the relatively high incidence of reported sexual dysfunction post-treatment. In 9 studies, NX-1207 treatment has been shown to have no significant adverse effect post-treatment on sexual function or testosterone levels.

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OncoSec Enrolls First Patient in Biomarker-Focused Pilot Study in Triple Negative Breast Cancer

On October 29, 2015 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that the Company has enrolled the first patient into a pilot biomarker trial of ImmunoPulse IL-12 in patients with triple negative breast cancer (TNBC) (Press release, OncoSec Medical, OCT 29, 2015, View Source [SID:1234507833]). ImmunoPulse IL-12, which employs intratumoral electroporation to enhance delivery of DNA-based interleukin-12 (IL-12), is designed to enhance tumor immunogenicity, leading to increased tumor infiltrating lymphocytes (TILs) and pro-inflammatory cytokines.

Previous studies have demonstrated that breast cancer patients whose tumors are associated with markers of inflammation, such as the presence of TILs, have better clinical outcomes. These data have initiated an effort by an international consortium to develop guidelines and recommendations for the routine evaluation of TILs for breast cancer. Further, preliminary data reported at the 2014 San Antonio Breast Cancer Symposium indicate that TNBC is responsive to cancer immunotherapies, such as anti-PD-1/PD-L1 checkpoint therapies. However, response rates in these TNBC patients, who were selected for study participation based upon TIL status, were only 18 to 33 percent.

"There is increasing evidence that breast cancer patients with tumors characterized by a ‘pro-inflammatory phenotype,’ including those with TNBC, have better responses to chemotherapy and experience longer disease-free and overall survival rates," said Mai H. Le, MD, Chief Medical Officer at OncoSec. "We anticipate that ImmunoPulse IL-12 will drive a tumor-specific inflammatory response in TNBC patients. The goal with ImmunoPulse IL-12 is to increase the number of patients who will benefit from anti-PD-1 therapy. We are very excited to be working closely with our colleagues at Stanford University to evaluate the role of ImmunoPulse IL-12 in promoting tumor immunogenicity."

Melinda L. Telli, MD, Assistant Professor of Medicine (Oncology) and Irene Wapnir, MD, Professor of Surgery (General Surgery), are leading this clinical trial at Stanford University Medical Center. Approximately 10 patients are planned for enrollment into this trial. The primary objective of the study is to evaluate the potential of ImmunoPulse IL-12 to promote a pro-inflammatory molecular and histological signature in tumor samples obtained from study participants. Secondary objectives include: evaluation of safety and tolerability; evaluation of local ablative effect (% necrosis); and description of other evidence of anti-tumor activity.

To learn more about the trial, visit www.oncosec.com. Additional details can also be found at www.clinicaltrials.gov.

About Triple Negative Breast Cancer (TNBC)
Breast cancer cells that test negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-) means the cancer is triple negative.1 Approximately 15-20 percent of US breast cancer cases are triple negative breast cancer (TNBC),2 which disproportionately affects younger women as well as African-American women, followed by Hispanic women.3

TNBC remains a poor-prognosis breast cancer subtype, with limited treatment options for patients with advanced, recurrent disease. In the recurrent disease setting, chemotherapy remains the standard of care, and median survival is approximately 13 months from the time of disease recurrence.4

Emerging evidence shows immunotherapy options may play an important role in the treatment paradigm for TNBC. Preliminary data demonstrated the anti-PD-1 antibody, pembrolizumab, led to an objective response in approximately 18 percent of TNBC patients;5 the anti-PD-L1 antibody, MPDL3280A, achieved an objective response in 33 percent of patients.6 There is increasing evidence that tumors need TILs for anti-PD-1/PD-L1 therapies to be most effective. Data also show TILs promote better responses to chemotherapy and improve clinical outcomes in breast cancer, including TNBC.7-12

Igenica Biotherapeutics Enters Into a Strategic Oncology Research Agreement with MedImmune

On October 28, 2015 – Igenica Biotherapeutics, Inc., a company focused on the discovery and development of innovative antibody-based therapies for the treatment of cancer, reported that it has entered into an oncology research agreement with MedImmune, the global biologics research and development arm of AstraZeneca (NYSE: AZN) (Press release, Igenica, OCT 28, 2015, View Source [SID1234519302]). Igenica and MedImmune will evaluate the potential of antibody-drug conjugates (ADCs) targeting Surface Antigen in Leukemia (SAIL), a novel cell surface protein with high prevalence of expression in a variety of hematologic malignancies and several solid tumors. Preclinical data have supported the selective targeting of tumors expressing SAIL with ADCs.

Under the agreement, Igenica will contribute its proprietary anti-SAIL antibodies, including IGN786, and its proprietary SNAP ADC drug linker, and MedImmune will provide its proprietary anti-tumor payload. Igenica and MedImmune will then jointly investigate the resulting novel ADC in preclinical studies.

MedImmune will receive an option to an exclusive worldwide license to anti-SAIL antibodies and antibody-drug conjugates resulting from the collaboration. Igenica will receive an exclusive option fee and, if MedImmune exercises its option, is also eligible to receive an upfront license fee, clinical, regulatory and commercialization milestones, and royalties on net sales. MedImmune will fund all development and commercialization costs under a license agreement.

"We are pleased to collaborate with MedImmune, a leading biotechnology company, to build on our pioneering research," commented John Celebi, Chief Business Officer, Igenica. "This agreement provides a strong opportunity to realize the potential value of IGN786 and complements our strategy focused on targeting drugs to block the immunosuppressive activities of immune cells in the tumor microenvironment to reinvigorate or activate de novo anti-tumor responses."

"We look forward to working with Igenica Biotherapeutics on developing a novel antibody-drug conjugate in hematology," said Ronald Herbst, Vice President, Oncology Research & Development, MedImmune. "Developing next generation antibody-drug conjugates is a key strategic area for us, and we are committed to advancing our pipeline in this area both externally and internally."

About IGN786 and SAIL
IGN786 is a humanized monoclonal antibody that binds to SAIL, a cell surface protein with high prevalence of expression in a variety of hematologic malignancies and several solid tumors. Igenica was the first to describe the biological properties of human SAIL and elucidate its potential as an antibody-drug conjugate approach (Blood Cancer Journal (2015) 5, e316). Preclinical data with IGN786 have supported the selective targeting of tumors expressing SAIL with antibody-drug conjugates.

Amgen’s Third Quarter 2015 Revenues Increased 14 Percent To $5.7 Billion And Adjusted Earnings Per Share (EPS) Increased 18 Percent To $2.72

On October 28, 2015 Amgen (NASDAQ:AMGN) reported financial results for the third quarter of 2015. Key results include:

Total revenues increased 14 percent versus the third quarter of 2014 to $5,723 million, with 14 percent product sales growth driven primarily by Enbrel (etanercept), Sensipar (cinacalcet), Neulasta (pegfilgrastim), Prolia (denosumab), XGEVA (denosumab) and Kyprolis (carfilzomib) (Press release, Amgen, OCT 28, 2015, View Source;p=RssLanding&cat=news&id=2103603 [SID:1234507905]). Unfavorable changes in foreign exchange rates impacted total revenue and product sales growth by 2 percentage points.

Adjusted EPS grew 18 percent versus the third quarter of 2014 to $2.72 driven by higher revenues and higher operating margins. Adjusted operating income increased 19 percent to $2,686 million and adjusted operating margin improved by 2 percentage points to 49 percent.

GAAP EPS were $2.44 compared to $1.61 and GAAP operating income was $2,339 million compared to $1,466 million. The prior year was negatively impacted by charges for the restructuring plan announced in the third quarter of 2014.

The Company generated $2.7 billion of free cash flow compared to $2.6 billion in the third quarter of 2014.

"We delivered record revenues, adjusted earnings and cash flow in the third quarter, while improving our operating margins and investing in six exciting new product launches," said Robert A. Bradway, chairman and chief executive officer. "With several innovative medicines still in development, we are well on the way to achieving our long-term objectives for shareholders and patients alike."

Third Quarter 2015 Product Sales Performance

Total product sales increased 14 percent for the third quarter of 2015 versus the third quarter of 2014. The increase was driven primarily by ENBREL, Sensipar, Neulasta, Prolia, XGEVA and Kyprolis. Growth for the quarter was due to net selling price, low inventory levels in the prior year period and higher unit demand.

ENBREL sales increased 30 percent year-over-year driven by net selling price and low inventory levels in the prior year period, offset partially by the impact of competition.

Neulasta sales increased 6 percent year-over-year driven by net selling price and favorable changes in inventory levels.
Aranesp (darbepoetin alfa) sales increased 4 percent year-over-year driven by higher unit demand, including a shift in dialysis customer purchases from EPOGEN (epoetin alfa), offset partially by net selling price and unfavorable changes in foreign exchange rates.

EPOGEN sales decreased 6 percent year-over-year driven by the impact of competition and the shift to Aranesp, offset partially by favorable changes in inventory levels and net selling price.

XGEVA sales increased 19 percent year-over-year driven primarily by higher unit demand.

Sensipar/Mimpara sales increased 29 percent year-over-year driven by low inventory levels in the prior year period, net selling price and higher unit demand.

Prolia sales increased 25 percent year-over-year driven by higher unit demand.

NEUPOGEN (filgrastim) sales decreased 5 percent year-over-year driven primarily by the impact of competition in the United States (U.S.).

Kyprolis sales increased 46 percent year-over-year driven by higher unit demand.

Nplate (romiplostim) sales increased 15 percent year-over-year driven by higher unit demand.

Vectibix (panitumumab) sales decreased 4 percent year-over-year driven by unfavorable changes in foreign exchange rates. Strong unit growth continued in the U.S. and Europe.

Third Quarter Operating Expense, Operating Margin and Tax Rate Analysis, on an Adjusted Basis

Operating Expenses increased 10 percent. Operating expense growth was reduced by 3 percentage points due to changes in foreign exchange rates.

Cost of Sales margin improved 2.2 points driven by net selling prices, lower royalty expense and manufacturing efficiencies.

Research & Development (R&D) expenses increased 11 percent driven by upfront payments related to the Company’s recent deal activity and increased support for launch products, offset partially by savings from transformation and process improvement efforts.

Selling, General & Administrative expenses increased 17 percent driven primarily by investments in new product launches and ENBREL-related payments, offset partially by savings from transformation and process improvement efforts.

Operating Margin improved by 2 percentage points to 49 percent.

Tax Rate increased 0.9 percentage points to 18.0 percent primarily due to changes in the geographic mix of earnings.

Cash Flow and Balance Sheet Discussion

The Company generated $2.7 billion of free cash flow in the third quarter of 2015 versus $2.6 billion in the third quarter of 2014.
The Company’s fourth quarter 2015 dividend of $0.79 per share declared on Oct. 14, 2015, will be paid on Dec. 7, 2015, to all stockholders of record as of the close of business on Nov. 16, 2015.

During the third quarter, the Company repurchased 4.6 million shares of common stock at a total cost of $0.7 billion.

2015 Guidance

For the full year 2015, the Company now expects:

Total revenues in the range of $21.4 billion to $21.6 billion and adjusted EPS in the range of $9.95 to $10.10. Previously, the Company expected total revenues in the range of $21.1 billion to $21.4 billion and adjusted EPS in the range of $9.55 to $9.80.
Adjusted tax rate to be in the range of 18 percent to 19 percent. This excludes the benefit of the federal R&D tax credit, which has not yet been extended for 2015.
Capital expenditures to be approximately $700 million.
2016 Preliminary Guidance

For the full year 2016, the Company expects:

Total revenues in the range of $21.7 billion to $22.3 billion and adjusted EPS in the range of $10.35 to $10.75.
Adjusted tax rate to be in the range of 20.5 percent to 21.5 percent, excluding the federal R&D tax credit.
Capital expenditures to be approximately $700 million.
Dividend planned to be increased 27 percent to $1.00 per share in the first quarter of 2016.
Share repurchases of $2 billion to $3 billion in 2016. In October 2015, the Company’s Board of Directors approved an increase in the remaining share repurchase authorization for an aggregate authorization of $5 billion.

Third Quarter Product and Pipeline Update

Repatha

In August, the U.S. Food and Drug Administration (FDA) approved Repatha as an adjunct to diet and maximally tolerated statin therapy for treatment of adults with heterozygous familial hypercholesterolemia (FH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Repatha is also indicated as an adjunct to diet and other LDL-lowering therapies for the treatment of patients with homozygous FH who require additional lowering of LDL-C. The effect of Repatha on cardiovascular morbidity and mortality has not been determined.

The requisite number of events in the event driven Phase 3 cardiovascular outcomes study is expected to accrue by mid-2016, with top-line data expected in H2 2016.

A supplemental Biologics License Application for a monthly administration single-dosing option was submitted to FDA and has received a Prescription Drug User Fee Act target action date of July 10, 2016.

Omecamtiv mecarbil

Phase 2 data in patients with chronic heart failure showed statistically significant improvements in several pre-specified measures of cardiac function.

Kyprolis

In the EU, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending marketing authorization for Kyprolis in combination for the treatment of relapsed multiple myeloma based on data from the Phase 3 ASPIRE study.

FDA granted priority review to the supplemental New Drug Application submitted in the U.S. based on data from the Phase 3 ENDEAVOR study.

BLINCYTO (blinatumomab)

The CHMP issued a positive opinion recommending marketing authorization for the treatment of Philadelphia chromosome-negative B-precursor relapsed or refractory acute lymphoblastic leukemia.

IMLYGIC

The FDA approved IMLYGIC for the local treatment of unresectable cutaneous, subcutaneous and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases.

The CHMP issued a positive opinion recommending marketing authorization for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease.
Etelcalcetide (AMG 416)

A New Drug Application was submitted in the U.S. and a Marketing Authorization Application was submitted in the EU for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on hemodialysis therapy.

Non-GAAP Financial Measures
In this news release, management has presented its operating results for the third quarters of 2015 and 2014 in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on an adjusted (or non-GAAP) basis. In addition, management has presented its full year 2015 and 2016 EPS and tax rate guidance in accordance with GAAP and on an adjusted (or non-GAAP) basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, restructuring and certain other items from the related GAAP financial measures. Management has also presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the third quarters of 2015 and 2014. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. Reconciliations for these non-GAAP financial measures to the most directly comparable GAAP financial measures are included in the news release.

The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor’s overall understanding of the financial performance and prospects for the future of the Company’s core business activities by facilitating comparisons of results of core business operations among current, past and future periods. In addition, the Company believes that excluding the non-cash amortization of intangible assets, including developed product technology rights, acquired in business combinations treats those assets as if the Company had developed them internally in the past, and thus provides a supplemental measure of profitability in which the Company’s acquired intellectual property is treated in a comparable manner to its internally developed intellectual property. The Company believes that FCF provides a further measure of the Company’s liquidity.

The Company uses the non-GAAP financial measures set forth in the press release in connection with its own budgeting and financial planning. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP.

FDA approves Yervoy to reduce the risk of melanoma returning after surgery

On October 28, 2015 The U.S. Food and Drug Administration reported that it has expanded the approved use of Yervoy (ipilimumab) to include a new use as adjuvant therapy for patients with stage III melanoma, to lower the risk that the melanoma will return following surgery (Press release, , OCT 28, 2015, View Source [SID:1234507834]).

Melanoma, the most aggressive type of skin cancer, is the leading cause of death from skin cancer. Melanoma is more likely to spread to other parts of the body than other forms of skin cancer and has been on the rise over the past several decades, according to the National Cancer Institute, with an estimated 73,870 new cases and 9,940 deaths from the disease this year. In stage III melanoma, the cancer has reached one or more lymph nodes. Patients with stage III melanoma are generally treated by surgery to remove the melanoma skin lesions and the nearby lymph nodes.

"Today’s approval of Yervoy extends its use to patients who are at high risk of developing recurrence of melanoma after surgery," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. "This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer."

Yervoy, administered intravenously, was originally approved in 2011 to treat late-stage melanoma that cannot be removed by surgery. Yervoy is a monoclonal antibody that blocks a molecule known as CTLA-4 (cytotoxic T-lymphocyte antigen). CTLA-4 may play a role in slowing down or turning off the body’s immune system, and affects its ability to fight off cancerous cells. Yervoy may work by allowing the body’s immune system to recognize, target and attack cells in melanoma tumors.

The safety and effectiveness of Yervoy for this new use were studied in 951 patients who received Yervoy or a placebo as adjuvant therapy following complete surgical removal of melanoma. The study measured the amount of time after treatment it took for the cancer to come back ("recurrence-free survival") and overall survival. Forty-nine percent of participants taking Yervoy had their cancer return after an average of 26 months, compared to 62 percent of those receiving a placebo, whose cancer returned after an average of 17 months. The analysis of overall survival data has not yet occurred.

The most common side effects of Yervoy in this study were rash, diarrhea, fatigue, itching, headache, weight loss and nausea. Yervoy can also cause autoimmune disease in the digestive system, liver, skin, nervous system (which would each require treatment with corticosteroids), as well as in the hormone-producing glands (which requires life-long hormone replacement therapy). Women who are pregnant should not take Yervoy because it may cause harm to a developing fetus.

Due to the potential for fatal immune-mediated adverse reactions and unusual severe side effects with Yervoy, the label includes a Boxed Warning. A Medication Guide will also be provided to patients to inform them about the therapy’s potential side effects.