On February 6, 2018 TapImmune Inc. (NASDAQ: TPIV), a leading clinical-stage immuno-oncology company with ongoing clinical trials in ovarian and breast cancer, reported that its President and CEO, Peter Hoang, will present at the 2018 BIO CEO & Investor Conference, held February 12-13, 2018, in New York City (Press release, TapImmune, FEB 6, 2018, View Source [SID1234523778]). He will also attend the 11th Annual European Life Sciences CEO Forum & Exhibition, held February 26-27, 2018, in Zurich, Switzerland.

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TapImmune Presentation Details:

Event: 2018 BIO CEO & Investor Conference

Date: Monday, February 12, 2018

Time: 2:30 PM (Eastern Time)

Location: New York Marriott Marquis, Odets Room

An audio webcast will be accessible via the News and Events section of the TapImmune website: View Source An archive of the audio will remain available for 90 days following the presentation.

On February 6, 2018 Array BioPharma Inc. (Nasdaq: ARRY) and Pierre Fabre reported results of the planned analysis of overall survival (OS) from the pivotal Phase 3 COLUMBUS trial in patients with BRAF-mutant melanoma (Press release, Array BioPharma, JUN 6, 2018, View Source [SID1234523750]). Treatment with the combination of encorafenib 450 mg daily and binimetinib 45 mg twice daily (COMBO450) reduced the risk of death compared to treatment with vemurafenib 960 mg daily [hazard ratio (HR) of 0.61, [95% CI 0.47, 0.79, p <0.001]. Median OS was 33.6 months for patients treated with COMBO450, compared to 16.9 months for patients treated with vemurafenib as a monotherapy.

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"Many patients with BRAF-mutant melanoma still face significant challenges managing their disease, and there remains a substantial need for well-tolerated treatments that delay disease progression and improve overall survival," said Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. "This data suggests that the combination of encorafenib and binimetinib may have the potential to become a meaningful new therapy for patients with advanced BRAF-mutant melanoma."

At the time of the planned analysis comparing COMBO450 to vemurafenib monotherapy, a preliminary analysis of OS in patients treated with 300 mg encorafenib alone daily (ENCO300), demonstrated a median OS of 23.5 months.

"We are excited to report these overall survival results from the COLUMBUS trial," said Victor Sandor, M.D., Chief Medical Officer, Array BioPharma. "This encouraging overall survival finding further validates previously reported median progression-free survival and overall response rate results, and taken together with the attractive tolerability profile, these data suggest that the combination of encorafenib with binimetinib has the potential to become a promising new treatment option for these patients."

As previously reported, the combination of encorafenib and binimetinib was generally well-tolerated. Grade 3/4 adverse events (AEs) that occurred in more than 5% of patients receiving the combination were increased gamma-glutamyltransferase (GGT) (9%), increased blood creatine phosphokinase (CK) (7%) and hypertension (6%). The incidence of selected any grade AEs of special interest, defined based on toxicities commonly associated with commercially available BRAF+MEK-inhibitor treatments for patients receiving the combination of encorafenib and binimetinib included: rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%). Full safety results of COLUMBUS Part 1 were presented at the 2016 Society for Melanoma Research Annual Congress.

The U.S. Food and Drug Administration (FDA) is currently reviewing the New Drug Applications to support use of the combination of encorafenib and binimetinib for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The FDA set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. In addition, the European Medicines Agency (EMA), as well as the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA), is reviewing the Marketing Authorization Applications for encorafenib and binimetinib.

A detailed update from the COLUMBUS trial will be presented at an upcoming medical congress.

About Melanoma
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [1, 2] There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma. [1, 3, 4]

About COLUMBUS
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of the combination of encorafenib and binimetinib compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial. Patients were randomized into two parts:

In Part 1, 577 patients were randomized 1:1:1 to receive COMBO450, ENCO300, or vemurafenib 960 mg alone. The dose of encorafenib in the combination arm is 50% higher than the single agent maximum tolerated dose of 300 mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was a median progression-free survival (mPFS) comparison of the COMBO450 arm versus vemurafenib. mPFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the mPFS of ENCO300 to that of the COMBO450 arm and a comparison of OS for the COMBO450 arm to that of vemurafenib alone. Results from Part 1 of the COLUMBUS trial previously presented at the 2016 Society for Melanoma Research Annual Congress, showed that COMBO450 more than doubled median progression free survival (mPFS) in patients with advanced BRAF-mutant melanoma, with a mPFS of 14.9 months compared with 7.3 months observed with vemurafenib [HR 0.54, (95% CI 0.41-0.71, P<0.001)]. In the secondary mPFS comparison of COMBO450 to ENCO300, ENCO300 demonstrated a mPFS of 9.6 months [HR 0.75, (95% CI 0.56-1.00, p=0.051)].
In Part 2, 344 patients were randomized 3:1 to receive encorafenib 300 mg plus binimetinib 45 mg (COMBO300) or ENCO300. Part 2 was designed to provide additional data to help evaluate the contribution of binimetinib to the combination of encorafenib and binimetinib.
As the secondary endpoint comparison of mPFS between the COMBO450 arm and ENCO300 arm in Part 1 did not achieve statistical significance, the planned analysis of OS is descriptive.

About Encorafenib and Binimetinib
BRAF and MEK are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma and colorectal cancer. Encorafenib is a late-stage small molecule BRAF inhibitor and binimetinib is a late-stage small molecule MEK inhibitor, both of which target key enzymes in this pathway. Encorafenib and binimetinib are being studied in clinical trials in advanced cancer patients, including the Phase 3 BEACON CRC trial and the Phase 3 COLUMBUS trial.

Array BioPharma has exclusive rights to encorafenib and binimetinib in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America. Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

On February 6, 2018 Allergan plc (NYSE: AGN) reported its fourth quarter and full-year 2017 continuing operations performance (Press release, Allergan, FEB 6, 2018, View Source [SID1234523753]).

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Total fourth quarter net revenues were $4.33 billion, a 12.0 percent increase from the prior year quarter, driven by BOTOX Cosmetic, BOTOX Therapeutic, JUVÉDERM Collection, ALLODERM, CoolSculpting and new products, including VRAYLAR, NAMZARIC and VIBERZI. The increase was partially offset by lower revenues from products losing patent exclusivity, and the continuing decline in ACZONE and NAMENDA XR. For the full year 2017, Allergan reported total net revenues of $15.94 billion, a 9.4 percent increase versus the prior year, driven by continued strong growth across key therapeutic areas and key products, and the addition of Regenerative Medicine products and CoolSculpting.

"2017 was a pivotal year for Allergan and we delivered solid results. We powered strong revenue growth of our top products and in each of our regions. We acquired, integrated and grew two new businesses and continued to advance our R&D pipeline. Allergan also continued to execute our capital deployment plan by completing a $15 billion share repurchase program, instituting a dividend and paying down debt in 2017," said Brent Saunders, Chairman and CEO of Allergan. "I believe that Allergan has a strong future and I am especially proud of our Allergan colleagues who continue to be Bold for Life by delivering treatments that make a difference for patients around the world."

Fourth Quarter 2017 Performance
GAAP operating loss from continuing operations in the fourth quarter 2017 was $90.5 million, including the impact of amortization, in-process research and development (R&D) impairments and charges associated with the December 2017 restructuring program announced on January 3, 2018 (herein referred to as the "December 2017 restructuring program"). Non-GAAP adjusted operating income from continuing operations in the fourth quarter of 2017 was $2.17 billion, an increase of 16.4 percent versus the prior year quarter. Cash flow from operations for the fourth quarter of 2017 increased to approximately $2.05 billion.

Full-Year 2017 Performance
GAAP operating loss from continuing operations for the full year 2017 was $5.92 billion, compared with $1.83 billion in 2016 primarily due to impairment charges recognized in the third quarter of 2017 of $3.2 billion related to RESTASIS and $646.0 million related to ACZONE. Non-GAAP adjusted operating income from continuing operations for the full year 2017 was $7.65 billion, an increase of 5.6 percent versus prior year. GAAP Cash flow from operations for the full year of 2017 increased to approximately $5.87 billion, compared to $1.45 billion in 2016, which was negatively impacted by cash taxes paid in connection with the gain recognized on the businesses sold to Teva Pharmaceuticals Industries, Ltd ("Teva").

Operating Expenses
Total GAAP Selling, General and Administrative (SG&A) Expense was $1.27 billion for the fourth quarter 2017, compared to $1.28 billion in the prior year quarter. Included within GAAP SG&A in the fourth quarter and full year 2017 were charges related to the December 2017 restructuring program of $80.0 million. Total non-GAAP SG&A expense increased to $1.13 billion for the fourth quarter 2017, compared to $1.07 billion in the prior year period, primarily due to costs associated with the addition of the Regenerative Medicine and CoolSculpting businesses. GAAP R&D investment for the fourth quarter of 2017 was $408.2 million, compared to $913.3 million in the fourth quarter of 2016. Non-GAAP R&D investment for the fourth quarter 2017 was $405.7 million, a decrease of 4.7 percent over the prior year quarter, due to reprioritization of on R&D programs and tight expense management.

Asset Sales & Impairments, Net and In-Process R&D Impairments
The Company recorded impairment charges of $238.5 million and $456.0 million in the three months ended December 31, 2017 and 2016, respectively. The Company excludes asset sales and impairments, net and in-process research and development impairments from its Non-GAAP performance net income attributable to shareholders as well as Adjusted EBITDA and Adjusted Operating Income.

Amortization, Other Income (Expense) Net, Tax and Capitalization
Amortization expense from continuing operations for the fourth quarter 2017 was $1.92 billion, compared to $1.64 billion in the fourth quarter of 2016.

The Company’s GAAP continuing operations tax rate benefit in the fourth quarter of 2017, was primarily attributable to discrete income tax benefits recognized as a result of the Tax Cuts and Jobs Act ("TCJA"). The Company’s non-GAAP adjusted continuing operations tax rate was 11.4 percent in the fourth quarter 2017. As of December 31, 2017, Allergan had cash and marketable securities of $6.45 billion and outstanding indebtedness of $30.1 billion.

Provisional Estimates of the Impact of U.S. Tax Reform
Allergan recorded a net provisional benefit of approximately $2.8 billion related to the TCJA. This amount includes a $730 million provisional expense representing the U.S. tax payable on deemed repatriated earnings of non-U.S. subsidiaries offset by a $3.5 billion net reduction of U.S. deferred tax liabilities due to the lower enacted U.S. tax rate and the change in assertion regarding permanently reinvested earnings as a result of the transition to a territorial tax system. These provisional estimates are based on the Company’s initial analysis and current interpretation of the legislation. Given the complexity of the TCJA, anticipated guidance from the U.S. Treasury, and the potential for additional guidance from the Securities and Exchange Commission or the Financial Accounting Standards Board, these estimates may be adjusted during 2018.

Discontinued Operations and Continuing Operations
As a result of the divestiture of the Company’s generics business and the divestiture of the Company’s Anda Distribution business in 2016, the financial results of those businesses have been reclassified to discontinued operations for all periods presented in our consolidated financial statements up through the date of the divestitures.

Included within (loss) from discontinued operations for the three months ended December 31, 2017 was a charge to settle certain Teva related matters, net of tax of $387.4 million.

Included in segment revenues in the twelve months ended December 31, 2016 are product sales that were sold by the Anda Distribution business once the Anda Distribution business had sold the product to a third-party customer. These sales are included in segment results and are excluded from total continuing operations revenues through a reduction to Corporate revenues. Cost of sales for these products in discontinued operations is equal to our average third-party cost of sales for third-party branded products distributed by Anda Distribution.

U.S. Specialized Therapeutics net revenues in the fourth quarter of 2017 were $1.9 billion, an increase of 19.8 percent versus the prior year quarter, driven primarily by the addition of the Regenerative Medicine and CoolSculpting businesses, as well as growth in BOTOX and JUVÉDERM Collection, offset by decreased revenues in Medical Dermatology.

Eye Care
RESTASIS net revenues in the fourth quarter of 2017 were $400.3 million, an increase of 1.8 percent versus the prior year quarter.
The Glaucoma franchise experienced a modest decline with ALPHAGAN/COMBIGAN net revenues in the fourth quarter of 2017 remaining stable at $101.8 million, while LUMIGAN/GANFORT net revenues decreased 5.9 percent versus the prior year quarter to $80.9 million in the fourth quarter of 2017, primarily impacted by lower volume.
OZURDEX net revenues in the fourth quarter of 2017 increased 16.8 percent from the prior year quarter to $26.4 million, driven by continued strong demand.

Medical Aesthetics
The Facial Aesthetics franchise continues to deliver strong growth with revenues increasing 14.1 percent versus the prior year quarter.
BOTOX Cosmetic net revenues in the fourth quarter of 2017 were $228.4 million, up 14.5 percent versus the prior year quarter, reflecting continued strong demand growth.
JUVÉDERM Collection (defined as JUVÉDERM, VOLUMA and other fillers) net revenues in the fourth quarter of 2017 were $139.5 million, up 14.7 percent versus the prior year quarter, driven by continued strong demand and market share gains.
Regenerative Medicine
ALLODERM net revenues in the fourth quarter of 2017 were $97.9 million.
STRATTICE net revenues were $27.3 million in the fourth quarter of 2017.
Body Contouring
CoolSculpting net revenues (including both CoolSculpting Systems/Applicators and Consumables) in the fourth quarter of 2017 were $94.4 million.
Plastic Surgery
Breast implant net revenues in the fourth quarter of 2017 were $69.0 million, an increase of 21.5 percent versus the prior year quarter, driven by higher demand following the launch of INSPIRA breast implants.
Skin Care
SkinMedica net revenues in the fourth quarter of 2017 were $24.7 million, a decrease of 7.8 percent versus the prior year quarter, due in part to supply disruptions.

Medical Dermatology
ACZONE net revenues in the fourth quarter of 2017 were $38.0 million, a decrease of 37.9 percent versus the prior year quarter, primarily due to generic pressure on the branded acne category, the loss of exclusivity for ACZONE 5% and higher discounts for formulary coverage.
TAZORAC net revenues in the fourth quarter of 2017 were $14.1 million compared with $27.5 million in the prior year quarter, primarily due to continued generic competition.

Neurosciences & Urology
BOTOX Therapeutic net revenues in the fourth quarter of 2017 were $367.2 million, an increase of 17.1 percent versus the prior year quarter, primarily driven by continued growth in the chronic migraine, overactive bladder and adult spasticity indications.

U.S. Specialized Therapeutics gross margin for the fourth quarter of 2017 was 92.2 percent, negatively impacted by the addition of the Regenerative Medicine and CoolSculpting businesses. SG&A expenses in the segment for the fourth quarter 2017 were $387.6 million. Selling and marketing expenses in the segment for the fourth quarter 2017 were $328.8 million, an increase of 12.5 percent versus the prior year quarter mainly attributed to the addition of the Regenerative Medicine and CoolSculpting businesses, offset, in part by reduced promotional spending. General and administrative expenses at the segment level for the fourth quarter 2017 were $58.8 million, an increase of 23.0 percent versus the prior year quarter, attributed in part to the addition of the Regenerative Medicine and CoolSculpting businesses. Segment contribution for the fourth quarter 2017 remained strong at $1.35 billion, an increase of 16.7 percent versus the prior year quarter.

U.S. General Medicine net revenues in the fourth quarter 2017 were $1.5 billion, remaining stable versus the prior year quarter, driven by strong growth from LINZESS, VRAYLAR, NAMZARIC and Lo LOESTRIN, offset by lower revenues from MINASTRIN and ASACOL due to generic competition, and to the continued decline in NAMENDA XR .

Central Nervous System
NAMENDA XR net revenues in the fourth quarter of 2017 were $97.8 million, a decrease of 30.7 percent versus the prior year quarter, driven primarily by lower demand and generic pressure.
NAMZARIC net revenues in the fourth quarter of 2017 increased to $36.8 million from $19.5 million in the prior year quarter driven by increased demand.
VRAYLAR net revenues in the fourth quarter of 2017 were $87.7 million, compared with $43.2 million in the prior year quarter, driven by continued strong demand growth.
VIIBRYD/FETZIMA net revenues in the fourth quarter of 2017 were $89.0 million, compared with $89.7 million in the prior year quarter.
SAPHRIS net revenues in the fourth quarter of 2017 were $37.7 million, a decrease of 12.7 percent versus the prior year quarter, primarily due to lower demand.

Gastrointestinal
LINZESS net revenues in the fourth quarter of 2017 were $194.8 million, an increase of 12.2 percent versus the prior year quarter, driven by continued strong demand growth.
VIBERZI net revenues in the fourth quarter of 2017 were $42.9 million, an increase of 12.9 percent versus the prior year quarter, driven by higher average selling prices.
ASACOL/DELZICOL net revenues in the fourth quarter of 2017 were $42.8 million, a decrease of 32.0 percent versus the prior year quarter, impacted by generic entry for ASACOL HD and a decline in demand for DELZICOL.
ZENPEP net revenues in the fourth quarter of 2017 were $58.5 million, an increase of 5.2 percent versus the prior year quarter, driven by higher average selling prices.
CARAFATE/SULCRATE net revenues in the fourth quarter of 2017 were $59.2 million, a decrease of 3.4 percent versus the prior year quarter.

Women’s Health
Lo LOESTRIN net revenues in the fourth quarter of 2017 were $126.5 million, an increase of 17.7 percent versus the prior year quarter, driven by strong demand growth and higher average selling prices. Lo LOESTRIN remains the number one prescribed branded oral contraceptive.
ESTRACE Cream net revenues in the fourth quarter were $101.5 million, compared to $103.0 million in the prior year quarter.
MINASTRIN 24 net revenues in the fourth quarter of 2017 were $5.3 million, compared to $78.4 million in the prior year quarter, impacted by loss of patent exclusivity for MINASTRIN 24 in March 2017.
TAYTULLA net revenues were $27.4 million in the fourth quarter of 2017 following the launch of this new oral contraceptive soft gel product in November 2016.
Anti-Infectives
TEFLARO net revenues in the fourth quarter of 2017 were $29.2 million, a decrease of 7.9 percent versus the prior year quarter, primarily impacted by generic pressure in the category.
AVYCAZ net revenues in the fourth quarter of 2017 were $18.5 million versus $9.2 million in the fourth quarter of 2016, when product supply was disrupted.
DALVANCE net revenues in the fourth quarter of 2017 were $13.0 million compared to $12.6 million in the prior year quarter.

Diversified Brands and Other Products
Diversified Brands net revenues in the fourth quarter of 2017 were $319.4 million, a decrease of 2.6 percent versus the prior year quarter.
Within Diversified Brands, BYSTOLIC/BYVALSON net revenues in the fourth quarter of 2017 were $157.5 million, compared to $159.8 million in the prior year quarter.

U.S. General Medicine gross margin for the fourth quarter of 2017 increased to 85.5 percent. SG&A expenses in the segment were $293.4 million in the fourth quarter of 2017. Selling and marketing expenses in the segment were $245.8 million, a decrease of 13.1 percent versus the prior year quarter, due to a decrease in promotional expenses and sales force reductions due to previous restructurings. General and administrative expenses were $47.6 million, an increase of 1.9 percent versus the prior year quarter. Segment contribution for the fourth quarter 2017 was $1.01 billion.

International net revenues in the fourth quarter of 2017 were $915.9 million, an increase of 16.8 percent versus the prior year quarter excluding foreign exchange impact, driven by growth in Facial Aesthetics, BOTOX Therapeutic, Eye Care and the addition of CoolSculpting.

Medical Aesthetics
Facial Aesthetics
BOTOX Cosmetic net revenues in the fourth quarter of 2017 were $155.0 million, an increase of 20.1 percent versus the prior year quarter excluding foreign exchange impact, driven by continued strong growth across all regions.
JUVÉDERM Collection net revenues in the fourth quarter of 2017 were $154.7 million, an increase of 27.8 percent versus the prior year quarter excluding foreign exchange impact, reflecting continued strong demand growth across all regions.
Plastic Surgery
Breast implant net revenues in the fourth quarter of 2017 were $40.1 million, an increase of 2.4 percent versus the prior year quarter, excluding foreign exchange impact.

Body Contouring
CoolSculpting net revenues (including both CoolSculpting Systems/Applicators and Consumables) in the fourth quarter of 2017 were $27.0 million.

Eye Care
LUMIGAN/GANFORT and ALPHAGAN/COMBIGAN net revenues in the fourth quarter of 2017 were $99.7 million and $46.7 million, respectively, reflecting continued stable performance.
OZURDEX net revenues in the fourth quarter of 2017 were $60.9 million, up 17.4 percent versus the prior year quarter excluding foreign exchange impact, reflecting continued strong demand across all regions.
OPTIVE net revenues in the fourth quarter of 2017 were $30.6 million, up 11.1 percent versus the prior year quarter excluding foreign exchange impact, reflecting strong demand in Europe and Latin America/Canada.

Botox Therapeutic
BOTOX Therapeutic net revenues in the fourth quarter of 2017 were $96.9 million, an increase of 11.2 percent versus the prior year quarter excluding foreign exchange impact, reflecting strong demand in Europe and Latin America/Canada.

International gross margin for the fourth quarter of 2017 was 85.0 percent. SG&A expenses in the segment were $274.7 million in the fourth quarter of 2017. Selling and marketing expenses in the segment were $240.6 million, an increase of 11.2 percent versus prior year excluding foreign exchange impact, in line with higher sales and the addition of CoolSculpting. General and administrative expenses were $34.1 million, an increase of 5.9 percent versus the prior year quarter excluding foreign exchange impact. Segment contribution was $504.1 million.

Corporate Function
Included within our corporate function are shared costs, including above site and unallocated costs associated with running our global manufacturing facilities, corporate general and administrative expenses and corporate initiatives.

Pipeline Update
Allergan R&D continues to deliver on its pipeline. Key development highlights included:

U.S. and International Branded Product Approvals
Allergan received approval from the U.S. Food and Drug Administration (FDA) for the use of VRAYLAR (cariprazine) for the maintenance treatment of adults with schizophrenia. VRAYLAR is also approved in the U.S. for the treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
Allergan received FDA approval for AVYCAZ (ceftazidime and avibactam) for the treatment of patients with hospital-acquired bacterial pneumonia and ventilator-associated Bacterial Pneumonia (HABP/VABP). This marks the third approved indication for AVYCAZ, in addition to complicated intra-abdominal infections and complicated urinary tract infections.
Allergan’s CoolSculpting treatment received clearance from the FDA for the improved appearance of lax tissue in conjunction with submental fat, or double chin, treatments. CoolSculpting is also FDA-cleared in the U.S. for the treatment of visible fat bulges in the submental area, thigh, abdomen and flank, along with bra fat, back fat, underneath the buttocks and upper arm.
Allergan received an Imported Drugs License (IDL) from the Chinese Food and Drug Administration (CFDA) to market Ozurdex (dexamethasone intravitreal implant 0.7 mg) for the treatment of adult patients with macular edema following either Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO).
Allergan received approval from the FDA for BOTOX Cosmetic for the temporary improvement in the appearance of moderate to severe forehead lines associated with frontalis muscle activity in adults. This marks the third approved indication for BOTOX Cosmetic, in addition to crow’s feet and glabellar lines.

Regulatory Milestones & Clinical Updates

Allergan announced that the FDA has accepted a New Drug Application (NDA) for Seysara (sarecycline) for the treatment of moderate to severe acne vulgaris in patients 9 years of age and older.
Allergan announced that VISTABEL (botulinum toxin type A) received a Positive Opinion from the Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) for the temporary improvement in the appearance of moderate to severe forehead lines in adults when the severity of the facial lines has an important psychological impact. This is an important step toward VISTABEL securing national licenses in the 28 countries of the European Union as well as Norway and Iceland.
Allergan announced positive topline results for a phase 3 study of cariprazine for the treatment of adults with major depressive episodes associated with bipolar I disorder (bipolar I depression). This is the second positive pivotal trial of cariprazine for this investigational use. The Company plans to submit a supplemental New Drug Application (sNDA) to the FDA in the 2nd half of 2018.

Fourth Quarter and Full-Year 2017 Conference Call and Webcast Details
Allergan will host a conference call and webcast today, Tuesday, February 6, at 8:30 a.m. Eastern Time to discuss its fourth quarter and full-year 2017 results. The dial-in number to access the call is U.S./Canada (877) 251-7980, International (706) 643-1573, and the conference ID is 67779395. A taped replay of the conference call will also be available beginning approximately two hours after the call’s conclusion, and will remain available through 11:30 p.m. Eastern Time on March 6, 2018. The replay may be accessed by dialing (855) 859-2056 and entering the conference ID 67779395. From international locations, the replay may be accessed by dialing (404) 537-3406 and entering the same conference ID.

To access the live webcast, please visit Allergan’s Investor Relations Web site at View Source A replay of the webcast will also be available.

On February 6, 2018 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company"), reported that the Company is initiating a new clinical trial that will study Actimab-A in combination with CLAG-M for patients with relapsed or refractory acute myeloid leukemia (AML) (Press release, Actinium Pharmaceuticals, FEB 6, 2018, View Source [SID1234523752]). CLAG-M is a salvage chemotherapy regimen that consists of cladribine, cytarabine, and filgrastim with mitoxantrone for patients with relapsed or refractory AML. The combination trial will be a Phase 1, dose-escalation study that will be conducted at the Medical College of Wisconsin by principal investigator Dr. Ehab Atallah.

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Dr. Mark Berger, Actinium’s Chief Medical Officer said, "Relapsed and refractory AML patients unfortunately have limited treatment options that have little clinical benefit for patients. Actimab-A is ideally suited to be studied in combination with other therapeutic modalities like CLAG-M given its potency and minimal extramedullary toxicities. We are optimistic that this novel combination will demonstrate Actimab-A’ s key strengths through higher response rates, a greater number of patients successfully receiving a bone marrow transplant and ultimately, survival. Further, it will demonstrate the value of using Actimab-A in combinations as we believe that combination therapies will be the next wave in the treatment of patients with AML just as combinations of regimen’s approved in multiple myeloma over the past three or four years have become for patients with that disease."

Actinium will host a conference call on Tuesday, February 13, 2018 at 4:30 PM ET that will be led by Dr. Mark Berger, Actinium’s Chief Medical Officer and Dr. Atallah.

Webcast Registration: View Source
U.S. Participant Dial-in: (646) 402-9440
U.S./Canada Toll Free Dial-in: (855) 698-6739
Conference ID: 2540

Sandesh Seth, Actinium’s Chairman and CEO said, "This latest clinical initiative is especially exciting as it further demonstrates that we are building the industry leading CD33 Program. We the only company with multi-disease, multi-indication clinical trials with our ongoing Actimab-A, Actimab-M and planned Actimab-MDS studies and this latest initiative has the potential of extending the addressable patient population for Actimab-A. This is a viable approach for Actimab-A as we begin to strategize and implement the next phase of Actimab-A’s development. In doing so, we expect to maximize the value of our CD33 program and increase its synergies for potential partners and collaborators. Further, this initiative is aligned with Actinium’s core strategy of improving access and outcomes to transplants and one we are excited to embark on."

Actimab-A is Actinium’s lead drug candidate from its CD33 program and is an Antibody Radio-Conjugate (ARC) that is comprised of the CD33 targeting antibody lintuzumab and actinium-225, an alpha-emitting radioisotope. Actimab-A is currently being studied in Phase 2 clinical trial in patients that are newly diagnosed with AML who are over the age of 60 that are ineligible for intense chemotherapy, also known as unfit patients. The Company expects to complete patient enrollment of the Phase 2 trial in the first half of 2018 and report top line data results in the second half of 2018. The Company is also developing Actimab-M and Actimab-MDS, which are also CD33 actinium-225 ARCs. Actimab-M is being studied in a Phase 1 investigator-initiated trial for patients with refractory multiple myeloma. The Phase 1 Actimab-M trial is expected to complete enrollment and report top like data in the second half of 2018. Actimab-MDS is expected to begin a Phase 2 clinical trial in the second half of 2018 following a pre-IND meeting with the FDA in the first half of 2018. Actimab-MDS is intended to bridge patients with high-risk myelodysplastic syndrome (MDS) that have a p53 genetic mutation to a bone marrow transplant via targeted myeloablation.

On February 6, 2018 Array BioPharma Inc. (Nasdaq: ARRY) reported results for its second quarter of fiscal 2018 and provided an update on the progress of its key clinical development programs (Press release, Array BioPharma, FEB 6, 2018, View Source [SID1234523740]).

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COLUMBUS PHASE 3 TRIAL

Treatment with the combination of encorafenib 450 mg daily and binimetinib 45 mg twice daily (COMBO450) reduced the risk of death compared to treatment with vemurafenib 960 mg daily [hazard ratio (HR) of 0.61, (95% CI 0.47, 0.79, p<0.001)] in patients with BRAF-mutant melanoma in the Phase 3 COLUMBUS trial.

Phase 3 trial showed mOS of 33.6 months for patients treated with COMBO450, compared to 16.9 months for patients treated with vemurafenib as a monotherapy.
As previously announced, the combination of encorafenib and binimetinib was generally well-tolerated. Grade 3/4 adverse events (AEs) that occurred in more than 5% of patients receiving the combination were increased gamma-glutamyltransferase (GGT) (9%), increased blood creatine phosphokinase (CK) (7%) and hypertension (6%). The incidence of selected any grade AEs of special interest, defined based on toxicities commonly associated with commercially available BRAF+MEK-inhibitor treatments for patients receiving the combination of encorafenib and binimetinib included: rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%). Full safety results of COLUMBUS Part 1 were presented at the 2016 Society for Melanoma Research Annual Congress.

The FDA:

Continues review of Array’s New Drug Applications (NDAs) to support use of the encorafenib and binimetinib combination for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma
Set a target action date under Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications
Informed Array that, based on its preliminary review of the applications, it has not identified any potential review issues, and that it is not currently planning to hold an advisory committee meeting to discuss these NDAs
The regulatory submissions were based on findings from the pivotal Phase 3 COLUMBUS trial.

“We believe the strength of the COLUMBUS data, with a remarkable median overall survival of 33.6 months and median progression-free survival of 14.9 months, highlights the potential of the encorafenib and binimetinib combination for patients with BRAF-mutant melanoma,” said Ron Squarer, Chief Executive Officer. “These data, together with our impressive, recently presented results in BRAF-mutant colorectal cancer, and our strong cash balance, position us well to advance our innovative therapies for patients with cancer.”

BEACON CRC PHASE 3 TRIAL

Updated results from the 30 patient safety lead-in of the Phase 3 BEACON CRC trial evaluating the triplet combination of encorafenib, binimetinib and cetuximab, an EGFR antagonist, in patients with BRAF-mutant CRC whose disease has progressed after one or two prior regimens were presented at the ASCO (Free ASCO Whitepaper) 2018 Gastrointestinal Cancers Symposium.

The estimated mPFS at the time of analysis was 8 months in 29 patients with BRAFV600E-mutant CRC.
The confirmed overall response rate (ORR) was 48% with 3 complete responses in patients with BRAFV600E-mutant CRC. Further, the ORR was 62% in the 16 patients who received only one prior line of therapy.
These data represent improvements compared to several separate historical published standard of care benchmarks for this population which range between 4% to 8% ORR and 1.8 and 2.5 months mPFS.
The triplet combination was generally well-tolerated. Two patients discontinued treatment due to AEs with only one of these considered related to treatment. The most common grade 3 or 4 AEs seen in at least 10% of patients were fatigue, urinary tract infection, increased aspartate aminotransferase (AST) and increased blood CK.
Enrollment in the randomized portion of BEACON CRC is ongoing. BRAF mutations are estimated to occur in 10% to 15% of patients with CRC and represent a poor prognosis for these patients.
“Media progression-free survival of 8 months in the BEACON CRC safety lead-in represents an exciting result relative to historical benchmarks and is an encouraging signal for the success of the randomized portion of this trial,” said Victor Sandor, M.D., Chief Medical Officer.

Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

IMMUNO-ONCOLOGY COLLABORATIONS: TRIAL ADVANCING WITH BRISTOL-MYERS SQUIBB, TRIAL INITIATED WITH MERCK AND NEW COLLABORATION ANNOUNCED WITH PFIZER
Array is developing binimetinib in combination with PD-1 / PD-L1 checkpoint inhibitors. We have announced separate, strategic collaborations with Bristol-Myers Squibb, Merck and Pfizer, but in each case, are pursuing a unique trial design to explore different clinical approaches.

Bristol-Myers Squibb

The clinical trial with Bristol-Myers Squibb continues to advance and is designed to investigate the safety, tolerability and efficacy of binimetinib in combination with nivolumab (anti-PD-1 therapy), with and without ipilimumab (CTLA-4 antibody), in patients with advanced metastatic microsatellite stable (MSS) CRC and the presence of a RAS mutation who have received one or two prior regimens.
The trial is jointly supported by Array and Bristol-Myers Squibb and sponsored by Array.
Merck

The clinical trial with Merck is designed to investigate the safety, tolerability and efficacy of binimetinib in combination with pembrolizumab (anti-PD-1 therapy), with and without FOLFOX or FOLFIRI (chemotherapy) in patients with CRC whose tumors are not microsatellite instability-high (MSI-H).
After establishing combinability in separate Phase 1 cohorts, the trial will enroll expansion cohorts of 1st and 2nd-line CRC patients onto these novel triplet combinations to determine effectiveness.
The trial will be sponsored and funded by Merck, with Array providing binimetinib supply.
Pfizer

The clinical trial with Pfizer is designed to investigate the safety, tolerability and efficacy of several novel anti-cancer combinations, including binimetinib, avelumab (anti-PD-L1 therapy) and talazoparib (PARP inhibitor) across various tumor types.
The multi-arm Phase 1b clinical trial is designed to establish recommended doses of different regimens combining the drugs.
Initially, the focus will be in non-small cell lung cancer (NSCLC) and pancreatic cancer, with additional indications being explored at a later stage.
The study is expected to begin by the third quarter of 2018, and results will be used to determine optimal approaches to further clinical development of these combinations.
The trial will be sponsored and funded by Pfizer, with Array providing binimetinib supply.
NEW SUBSIDIARY FORMED TO ADVANCE ARRY-797
Array formed a wholly-owned subsidiary, Yarra Therapuetics, LLC, to further develop and commercialize therapeutics targeted towards rare diseases, including ARRY-797, an oral, selective p38 mitogen-activated protein kinase inhibitor. A Phase 3 trial of ARRY-797 in patients with LMNA A/C-related dilated cardiomyopathy is planned to begin this quarter. LMNA A/C-related dilated cardiomyopathy is a rare, degenerative cardiovascular disease caused by mutations in the LMNA gene and characterized by a poor prognosis.

FINANCIAL HIGHLIGHTS
Novartis Financial Commitment
Novartis continues to substantially fund all ongoing trials with encorafenib and binimetinib that were active or planned as of the close of the Novartis Agreements in 2015, including the COLUMBUS Phase 3 trial. Reimbursement revenue from Novartis was approximately $88.5 million for the 12 months ended December 31, 2017, of which $22.4 million was recorded in the quarter ended December 31, 2017. Total revenue and upfront payment collected from Novartis since the start of the 2015 agreement is $348.7 million.

Second Quarter of Fiscal 2018 Compared to First Quarter of Fiscal 2018 (Sequential Quarters Comparison)

Revenue for the second quarter of fiscal 2018 was $42.2 million, compared to $29.7 million for the prior quarter. The increase was primarily due to recognition of the remaining $7.9 million deferral of the Asahi Kasei Pharma upfront payment resulting from completion of all remaining material obligations under the Collaboration and License Agreement, as well as higher Novartis reimbursement revenue.
Cost of partnered programs for the second quarter of fiscal 2018 was $13.7 million, compared to $11.8 million for the prior quarter. The increase was primarily due to higher costs incurred for the BEACON CRC trial as it continues to advance, as well as additional resources engaged on collaborations.
Research and development expense was $42.6 million, compared to $41.4 million in the prior quarter. The increase was driven by costs related to the increased activity on Novartis transitioned studies, and is partially offset by the non-recurring expense related to commercial and clinical supply from the previous quarter.
Loss from Operations for the quarter was $25.7 million, compared to a loss from operations of $35.5 million in the previous quarter. The decrease in net loss was primarily due to increased revenue, which was partially offset by increased research and development.
Net loss for the second quarter was $34.1 million, or ($0.17) per share, compared to $38.0 million, or ($0.22) per share, in the prior quarter.
Cash, Cash Equivalents and Marketable Securities as of December 31, 2017 were $420 million.
Second Quarter of Fiscal 2018 Compared to Second Quarter of Fiscal 2017 (Prior Year Comparison)

Revenue for the second quarter of fiscal 2018 decreased $2.3 million compared to the same quarter of fiscal 2017. The decrease was primarily due to decreased reimbursement revenue for the Novartis transitioned studies, which was partially offset by revenue from new and expanded collaborations.
Cost of partnered programs increased $4.7 million compared to the second quarter of fiscal 2017. The increase was primarily due to higher costs incurred for the BEACON CRC trial, as well as more resources engaged on collaborations.
Research and development expense decreased $3.9 million, compared to the second quarter of fiscal 2017. The decrease was due to expenses associated with the Novartis transitioned studies.
Net loss for the second quarter of fiscal 2018 was $34.1 million, or ($0.17) per share, compared to $23.3 million, or ($0.14) per share, for the same quarter in fiscal 2017. The increase in net loss was primarily due to a decrease in reimbursement revenue from Novartis and one-time costs to convert and extinguish Array’s convertible debt.
CONFERENCE CALL INFORMATION
Array will hold a conference call on Tuesday, February 6, 2018 at 9:00 a.m. Eastern Time to discuss these results and provide an update on the progress of its key clinical development programs. Ron Squarer, Chief Executive Officer, will lead the call.

Webcast, including Replay and Conference Call Slides:
View Source

About COLUMBUS
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of the combination of encorafenib and binimetinib compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial. Patients were randomized into two parts:

In Part 1, 577 patients were randomized 1:1:1 to receive COMBO450, ENCO300, or vemurafenib 960 mg alone. The dose of encorafenib in the combination arm is 50% higher than the single agent maximum tolerated dose of 300 mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was an mPFS comparison of the COMBO450 arm versus vemurafenib. mPFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the mPFS of ENCO300 to that of the COMBO450 arm and a comparison of OS for the COMBO450 arm to that of vemurafenib alone. Results from Part 1 of the COLUMBUS trial previously presented at the 2016 Society for Melanoma Research Annual Congress, showed that COMBO450 more than doubled mPFS)\ in patients with advanced BRAF-mutant melanoma, with a mPFS of 14.9 months compared with 7.3 months observed with vemurafenib [HR 0.54, (95% CI 0.41-0.71, p<0.001)]. In the secondary mPFS comparison of COMBO450 to ENCO300, ENCO300 demonstrated a mPFS of 9.6 months [HR 0.75, (95% CI 0.56-1.00, p=0.051)].
In Part 2, 344 patients were randomized 3:1 to receive encorafenib 300 mg plus binimetinib 45 mg (COMBO300) or ENCO300. Part 2 was designed to provide additional data to help evaluate the contribution of binimetinib to the combination of encorafenib and binimetinib.
As the secondary endpoint comparison of mPFS between the COMBO450 arm and ENCO300 arm in Part 1 did not achieve statistical significance, the planned analysis of mOS is descriptive.

About Melanoma
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [1, 2] There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma. [1, 3, 4]

About BEACON CRC
BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of encorafenib, binimetinib and cetuximab in patients with BRAF-mutant metastatic CRC whose disease has progressed after one or two prior regimens. Thirty patients were treated in the safety lead-in and received the triplet combination of encorafenib 300 mg daily, binimetinib 45 mg twice daily and cetuximab per label. Of the 30 patients, 29 had a BRAFV600E mutation. Microsatellite instability-high (MSI-H), resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomized portion of the trial.

The randomized portion of the BEACON CRC trial is designed to assess the efficacy of encorafenib in combination with cetuximab with or without binimetinib compared to cetuximab and irinotecan-based therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet combination, doublet combination (encorafenib and cetuximab) or the control arm (irinotecan-based therapy and cetuximab). The primary endpoint of the trial is mOS of the triplet combination compared to the control arm. Secondary endpoints address efficacy of the doublet combination compared to the control arm, and the triplet combination compared to the doublet therapy. Other secondary endpoints include PFS, ORR, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial will be conducted at over 250 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed in 2018.

BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAF-mutant advanced CRC. Phase 2 trial results were presented at the 2016 ASCO (Free ASCO Whitepaper) annual meeting. [5] In the doublet arm of encorafenib and cetuximab, mOS exceeded one year, which is more than double several separate historical published standard of care benchmarks for this population. [5-11] Further, the ORR was 22% and the mPFS was 4.2 months. [5] Historical published ORR and mPFS benchmarks in this patient population using standard of care regimens range between 4% to 8% and 1.8 and 2.5 months, respectively. [9-12]

About Colorectal Cancer
Worldwide, CRC is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. [13] Of these, nearly 750,000 were diagnosed in men, and 614,000 in women. [14] Globally in 2012, approximately 694,000 deaths were attributed to CRC. [13] In the U.S. alone, an estimated 140,250 patients will be diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease. [13] In the U.S., BRAF mutations are estimated to occur in 10% to 15% of patients with CRC and represent a poor prognosis for these patients. [7, 8, 16, 17] Based on recent prospective historical data, the prevalence of MSI-H in tumors from patients with metastatic BRAF-mutant CRC ranged from 14% in a recent Phase 1b/2 trial (NCT01719380) (Array, data on file) to 18% in a recent Southwestern Oncology Group (SWOG) randomized Phase 2 trial. [11]