On February 7, 2017 Galectin Therapeutics Inc. (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins, and the Providence Cancer Center reported the presentation of preclinical and early clinical data from two investigator-initiated Phase 1 clinical trials of GR-MD-02 used in combination with approved cancer immunotherapies (Filing, 8-K, Galectin Therapeutics, FEB 7, 2017, View Source [SID1234517663]). Data presented today at the 9th GTCBio Immunotherapeutics & Immunomonitoring Conference in San Diego, CA by Dr. William L. Redmond, Providence Cancer Center, has been posted.

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"Preclinical results in mouse models of multiple types of cancers show
ed important anti-tumor and increased survival effects of combining GR-MD-02 with different types of immune modulators, providing a compelling case for progressing studies into human patients with cancer" said William L. Redmond, Ph.D., Associate Member, Laboratory of Cancer Immunotherapy, and Director, Immune Monitoring Laboratory, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR. "We are pleased that our translational medicine team is conducting two phase 1 clinical trials which were initiated under the direction of principal investigator Brendan D. Curti, M.D., Director of the Providence Biotherapy Program at Providence Cancer Center."

GR-MD-02 was combined with pembrolizumab (KEYTRUDA) in patients with advanced melanoma, and this study has been expanded to patients with oral/head and neck cancer (OHN) and non small cell lung cancer (NSCLC) (View Source). Six subjects with advanced melanoma have been enrolled in the lowest dose cohort (2 mg/kg) with no safety concerns related to GR-MD-02. To date, one partial response and one mixed response has been observed. Below is a chest CT scan of the patient with a partial response showing a marked reduction in tumor size at week 12 of therapy, after 3 doses of combined GR-MD-02 and pembrolizumab.

Baseline CT Scan
Week 12 Therapy CT Scan
LOGO
GR-MD-02 was also combined with ipilimumab (Yervoy) in patients with advanced melanoma (View Source). Seven subjects treated with the lowest two dose cohorts of GR-MD-02 (1 and 2 mg/kg) have been completed with no safety signals identified due to GR-MD-02. In these low dose initial cohorts, there were no notable changes in the peripheral immune signature. Due to changes in the standard of care for metastatic melanoma (i.e., approval of KEYTRUDA), recruitment has been slowed significantly.
"We are encouraged by these early safety results and look forward to further data on the safety and efficacy of GR-MD-02 used in combination with pembrolizumab (KEYTRUDA) in patients with metastatic melanoma, OHN, or NSCLC", said Dr. Curti. "While we cannot conclude from the one partial response in the pembrolizumab study that the response was related to GR-MD-02, it provides us with a clinically relevant signal to follow as GR-MD-02 doses are escalated. We hope to report additional data in early 2018 when we anticipate a decision on progressing to phase 2. This decision will be based on the response rate of the combination of pembrolizumab with GR-MD-02 as compared to historical response rates to pembrolizumab alone."

About GR-MD-02
GR-MD-02 is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of fatty liver disease and fibrosis. Galectin-3 plays a major role in diseases that involve scarring of organs including fibrotic disorders of the liver, lung, kidney, heart and vascular system. The drug binds to galectin proteins and disrupts their function. Preclinical data in animals have shown that GR-MD-02 has robust treatment effects in reversing liver fibrosis and cirrhosis.

On February 7, 2017 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) (“Actinium” or “the Company”), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, reported that a Phase 1 clinical trial studying Actimab-M in multiple myeloma has been initiated (Press release, Actinium Pharmaceuticals, FEB 7, 2017, View Source [SID1234517653]).

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Actimab-M is comprised of the CD-33 targeting monoclonal antibody HuM-195 coupled to the alpha-particle emitter actinium 225. CD33 is an antigen found on hematopoietic cells in certain blood cancers. It is commonly associated with myeloid malignancies including AML, but recent research has shown that CD33 can also be found on malignant cells of approximately 25%-35% of all multiple myeloma patients. Furthermore, the expression of this marker increases in relapsed and refractory myeloma. In addition, it predicts for a very aggressive course of disease. This makes CD33 a potential target for the treatment of this usually fatal disease. Although treatable, multiple myeloma is currently not considered curable and almost all patients eventually relapse or become refractory to available treatments as their condition progresses. In this new trial, Actimab-M will be used in patients who have progressing disease after 3 prior multiple myeloma treatment regimens or are refractory to QUAD (Caflizomib, Lenalidomide, Pomalidomide, Dexamethason).

“I am very excited to lead in the development of this novel and promising approach,” said Dr. M. Yair Levy of Texas Oncology – Baylor Charles A. Sammons Cancer Center. “Relapsed and refractory multiple myeloma is an area of high unmet medical need that we hope to address with Actimab-M. Myeloma is a very radiosensitive cancer, and does not present with the neutropenia and thrombocytopenia of AML. I would expect tolerability of this treatment to be better in this disease. Based on my previous experience with Actimab-A in AML and my research in the area of multiple myeloma, I believe that this targeted treatment could prove efficacious and be a part of our growing armamentarium against this disease.”

Sandesh Seth, Executive Chairman of Actinium Pharmaceuticals said, “We are incredibly excited to see the initiation of this trial for Actimab-M in multiple myeloma. Not only does this mark the beginning of the expansion of our clinical pipeline beyond AML, it also demonstrates the broad applicability of our radioimmunotherapy technologies that we intend to progress into new indications and patient populations. Further, this reinforces Actinium’s commitment to developing therapies for patients with unmet needs. We look forward to providing updates as this trial progresses.”

About Multiple Myeloma

Multiple Myeloma is a blood cancer characterized by malignant transformation of the type of white blood cells called plasmocytes. These cells accumulate in the bone marrow and eventually lead to serious bone and kidney damage. Multiple Myeloma is the second most commonly diagnosed blood cancer after Non-Hodgkin Lymphoma with estimated about 30,000 new cases per year in the US. Almost 100,000 people in the US currently live with the disease. Average age at diagnosis is 70, and only 2% of cases occur in people younger than 40 years. There is currently no cure for Multiple Myeloma, although a number of drugs have been approved for treatment of the disease. However, most patients eventually stop responding to available treatments, which results in a high unmet medical need for relapsed and refractory forms of the disease.

About Actimab-M

Actimab-M is comprised of the anti-CD33 monoclonal antibody HuM-195 coupled to actinium 225, an alpha-particle emitting radioisotope, and is the same construct of Actinium’s Actimab-A, which is currently being studied in a Phase 2 clinical trial in patients newly diagnosed with acute myeloid leukemia (AML) who are over the age of 60. Actimab-A is being studied in AML at fractionated doses of 2.0 μCi/Kg administered via infusion on day 1 and day 7 as a single cycle while Actimab-M is being studied in multiple myeloma as a single infusion up to 1.0 μCi/Kg for up to 8 cycles not to exceed 4.0 μCi/Kg total per patient. The Phase 1 trial for Actimab-M is a multicenter, open label, dose-escalation study. Patients will be administered a starting dose level of 0.5 μCi/Kg of Actimab-M via infusion on day 1 of each cycle for up to 8 cycles with each cycle lasting 42 days. If this dose level is deemed safe, a second dose level of 1.0 μCi/kg will be explored for up to 4 cycles also of 42 days per cycle. Total dose received per patient is not to exceed 4.0 μCi/kg. In the event of dose limiting toxicities (DLTs) at the 0.5 μCi/Kg dose level, a dose level of 0.25 μCi/Kg will be explored. The Phase 1 trial will estimate maximum tolerated dose (MTD), assess adverse events, measure response rates (objective response rate, complete response rate, stringent complete response rate, very good partial response rate and partial response rate) as well as progression free survival (PFS) and overall survival (OS).

On February 7, 2017 Gilead Sciences, Inc. (Nasdaq: GILD) reported its results of operations for the fourth quarter and full year 2016 (Press release, Gilead Sciences, FEB 7, 2017, View Source [SID1234517656]).

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Total revenues for the fourth quarter of 2016 were $7.3 billion, compared to $8.5 billion for the same period in 2015. Net income for the fourth quarter of 2016 was $3.1 billion, or $2.34 per diluted share, compared to $4.7 billion, or $3.18 per diluted share for the same period in 2015. Non-GAAP net income, which excludes amounts related to acquisition-related, up-front collaboration, stock-based compensation and other expenses, for the fourth quarter of 2016 was $3.6 billion, or $2.70 per diluted share, compared to $4.9 billion, or $3.32 per diluted share for the same period in 2015.

Full year 2016 total revenues were $30.4 billion, compared to $32.6 billion for 2015. Net income for 2016 was $13.5 billion, or $9.94 per diluted share, compared to $18.1 billion, or $11.91 per diluted share for 2015. Non-GAAP net income for 2016, which excludes amounts related to acquisition-related, up-front collaboration, stock-based compensation and other expenses, was $15.7 billion, or $11.57 per diluted share, compared to $19.2 billion, or $12.61 per diluted share for 2015.

Three Months Ended Twelve Months Ended
December 31, December 31,
(In millions, except per share amounts) 2016 2015 2016 2015
Product sales $ 7,216 $ 8,409 $ 29,953 $ 32,151
Royalty, contract and other revenues 104 97 437 488
Total revenues $ 7,320 $ 8,506 $ 30,390 $ 32,639

Net income attributable to Gilead $ 3,108 $ 4,683 $ 13,501 $ 18,108
Non-GAAP net income* $ 3,585 $ 4,889 $ 15,713 $ 19,174

Diluted earnings per share $ 2.34 $ 3.18 $ 9.94 $ 11.91
Non-GAAP diluted earnings per share* $ 2.70 $ 3.32 $ 11.57 $ 12.61
* Non-GAAP net income and non-GAAP diluted earnings per share exclude acquisition-related, up-front collaboration, stock-based compensation and other expenses. A reconciliation between GAAP and non-GAAP financial information is provided in the tables on pages 7 and 8.

Product Sales

Total product sales for the fourth quarter of 2016 were $7.2 billion, compared to $8.4 billion for the same period in 2015. Product sales for the fourth quarter of 2016 were $4.9 billion in the United States, $1.4 billion in Europe, $314 million in Japan and $556 million in other locations. Product sales for the fourth quarter of 2015 were $4.8 billion in the United States, $1.7 billion in Europe, $1.4 billion in Japan and $565 million in other locations.

Total product sales during 2016 were $30.0 billion, compared to $32.2 billion in 2015. For 2016, product sales were $19.3 billion in the United States, $6.1 billion in Europe, $2.5 billion in Japan and $2.1 billion in other locations. For 2015, product sales were $21.2 billion in the United States, $7.2 billion in Europe, $1.9 billion in Japan and $1.9 billion in other locations.

Antiviral Product Sales

Antiviral product sales, which include sales of our HIV and other antiviral products and our chronic hepatitis C (HCV) products, were $6.6 billion for the fourth quarter of 2016, compared to $7.9 billion for the same period in 2015. For 2016, antiviral product sales were $27.7 billion, compared to $30.2 billion in 2015.

HIV and other antiviral product sales for the fourth quarter of 2016 were $3.4 billion, compared to $3.0 billion for the same period in 2015 and $12.9 billion for the full year 2016, compared to $11.1 billion in 2015. The increases were primarily due to the continued uptake of our tenofovir alafenamide (TAF)-based products, Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg), Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) and Odefsey (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg), partially offset by decreases in sales of tenofovir disoproxil fumarate (TDF)-based products.
HCV product sales, which consist of Harvoni (ledipasvir 90 mg/sofosbuvir 400 mg), Sovaldi (sofosbuvir 400 mg) and Epclusa (sofosbuvir 400 mg/velpatasvir 100 mg), were $3.2 billion for the fourth quarter of 2016, compared to $4.9 billion for the same period in 2015 and $14.8 billion for the full year 2016, compared to $19.1 billion in 2015. The declines were due to lower sales of Harvoni and Sovaldi, partially offset by sales of Epclusa, which was launched in 2016 across various locations.
Other Product Sales

Other product sales, which include Letairis (ambrisentan), Ranexa (ranolazine) and AmBisome (amphotericin B for liposome injection), were $621 million for the fourth quarter of 2016, compared to $523 million for the same period in 2015. For 2016, other product sales were $2.2 billion, compared to $1.9 billion in 2015.

Operating Expenses

Three Months Ended Twelve Months Ended
December 31, December 31,
(In millions) 2016 2015 2016 2015
Research and development (R&D) expenses $ 1,208 $ 757 $ 5,098 $ 3,014
Non-GAAP R&D expenses* $ 959 $ 779 $ 3,749 $ 2,845

Selling, general and administrative (SG&A) expenses $ 992 $ 1,066 $ 3,398 $ 3,426
Non-GAAP SG&A expenses* $ 938 $ 1,013 $ 3,194 $ 3,224
* Non-GAAP R&D and SG&A expenses exclude acquisition-related, up-front collaboration, stock-based compensation and other expenses. A reconciliation between GAAP and non-GAAP financial information is provided in the tables on pages 7 and 8.

During the fourth quarter of 2016, compared to the same period in 2015:

R&D expenses and non-GAAP R&D expenses* increased primarily due to the overall progression of Gilead’s clinical studies, including ongoing milestone payments.
R&D expenses for the fourth quarter of 2016 also include an impairment charge related to in-process R&D (IPR&D).
For 2016 compared to 2015:

R&D expenses and non-GAAP R&D expenses* increased primarily due to the overall progression of Gilead’s clinical studies, including ongoing milestone payments, and Gilead’s purchase of a U.S. Food and Drug Administration (FDA) priority review voucher.
R&D expenses for 2016 also include up-front collaboration expenses related to Gilead’s license and collaboration agreement with Galapagos NV, purchase of Nimbus Apollo, Inc. and impairment charges related to IPR&D.
SG&A expenses and non-GAAP SG&A expenses* decreased primarily due to lower branded prescription drug fee expense, partially offset by higher costs to support Gilead’s product launches and the geographic expansion of its business.
Cash, Cash Equivalents and Marketable Securities

As of December 31, 2016, Gilead had $32.4 billion of cash, cash equivalents and marketable securities, compared to $26.2 billion as of December 31, 2015, primarily due to the issuance of $5.0 billion aggregate principal amount of senior unsecured notes in September 2016. During 2016, Gilead generated $16.7 billion in operating cash flow, utilized $11.0 billion to repurchase 123 million shares of its stock and paid cash dividends of $2.5 billion.

Full Year 2017 Guidance

Gilead provided its full year 2017 guidance:

(In millions, except percentages and per share amounts) Provided
February 7, 2017
Net Product Sales $22,500 – $24,500
Non-HCV Product Sales $15,000 – $15,500
HCV Product Sales $7,500 – $9,000
Non-GAAP*
Product Gross Margin 86% – 88%
R&D Expenses $3,100 – $3,400
SG&A Expenses $3,100 – $3,400
Effective Tax Rate 25.0% – 28.0%
Diluted EPS Impact of Acquisition-related, Up-front Collaboration, Stock-Based Compensation and Other Expenses $0.84 – $0.91
* Non-GAAP product gross margin, R&D and SG&A expenses and effective tax rate exclude acquisition-related, up-front collaboration, stock-based compensation and other expenses. A reconciliation between GAAP and non-GAAP full year 2017 guidance is provided in the tables on page 9.

Corporate Highlights

Announced the promotion of James R. Meyers to Executive Vice President, Worldwide Commercial Operations, in November 2016.
Product & Pipeline Updates announced by Gilead during the Fourth Quarter of 2016 include:

Antiviral and Liver Diseases Programs

Announced that FDA and Japanese Ministry of Health, Labour and Welfare approved Vemlidy (tenofovir alafenamide) 25mg, a once-daily treatment for adults with chronic hepatitis B virus (HBV) infection with compensated liver disease. Additionally, the Committee for Medicinal Products for Human Use, the scientific committee of the European Medicines Agency, adopted a positive opinion on Gilead’s Marketing Authorization Application for Vemlidy.
Announced the submission of a New Drug Application (NDA) to FDA for an investigational, once-daily single-tablet regimen containing sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg for the treatment of direct-acting antiviral (DAA)-experienced HCV-infected patients. The data submitted in the NDA support the use of the regimen for 12 weeks in DAA-experienced patients with genotype 1 to 6 HCV infection without cirrhosis or with compensated cirrhosis.
Announced positive results from an open-label Phase 2 trial evaluating the investigational apoptosis signal-regulating kinase 1 inhibitor selonsertib (formerly GS-4997) alone or in combination with the monoclonal antibody simtuzumab in patients with nonalcoholic steatohepatitis and moderate to severe liver fibrosis (fibrosis stages F2 or F3). The data demonstrate regression in fibrosis that was, in parallel, associated with reductions in other measures of liver injury in patients treated with selonsertib for 24 weeks. These data were presented in a late-breaking abstract session at the Liver Meeting 2016.
Announced positive two-year (96-week) data from a Phase 3 study and 48-week data from two Phase 3b studies evaluating the safety and efficacy of switching virologically suppressed HIV-1-infected patients from regimens containing Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) to regimens containing Descovy. Results demonstrated regimens containing Descovy to be statistically non-inferior to regimens containing Truvada, with improvements in certain renal and bone laboratory parameters among patients receiving Descovy-based regimens.