On October 30, 2018 Array BioPharma Inc. (Nasdaq: ARRY) reported results for its first quarter of fiscal 2019 and provided an update on the progress of its key commercial products and clinical development programs (Press release, Array BioPharma, OCT 30, 2018, View Source [SID1234530370]).

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"We have received positive feedback from the melanoma community and our team continues to execute a robust U.S. launch of BRAFTOVI + MEKTOVI for patients with BRAF-mutant melanoma. We were also delighted BRAFTOVI + MEKTOVI received European Commission approval in September," said Ron Squarer, Chief Executive Officer. "Our BEACON CRC Phase 3 trial continues to advance and is supported by Breakthrough Therapy Designation. We look forward to the interim analysis of the BEACON CRC trial in the first half of 2019."

MELANOMA
COMMERCIAL
BRAFTOVI + MEKTOVI U.S. Approval and Launch
BRAFTOVI + MEKTOVI were available for sale beginning on July 2, 2018, and patients began receiving the combination therapy that same week.

Net product sales for the first quarter was $14 million. Array has seen strong demand for BRAFTOVI + MEKTOVI and continues to receive positive feedback from healthcare providers, payers and the melanoma community regarding the combination.

BRAFTOVI + MEKTOVI European Approval
On September 20, 2018, the European Commission approved BRAFTOVI in combination with MEKTOVI for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test. This approval is applicable to all 28 European Union member states, as well as Liechtenstein, Iceland and Norway.

COLUMBUS PHASE 3 TRIAL OVERALL SURVIVAL (OS) RESULTS PUBLISHED IN THE LANCET ONCOLOGY
Detailed OS results of the pivotal COLUMBUS trial were published online on September 12, 2018 by The Lancet Oncology.

The median OS was 33.6 months for patients treated with BRAFTOVI + MEKTOVI, compared to 16.9 months for patients treated with vemurafenib as a monotherapy. The combination reduced the risk of death compared to treatment with vemurafenib [hazard ratio (HR) of 0.61, (95% CI 0.47-0.79, p <0.0001)] in the planned analysis of OS.
Observed grade 3 or 4 adverse events seen in more than 5% of patients with BRAFTOVI + MEKTOVI were increased gamma-glutamyltransferase (9%), increased blood creatine phosphokinase (7%) and hypertension (6%). Additional safety information can be found in the manuscript and in the Important Safety Information and the full Prescribing Information for BRAFTOVI and MEKTOVI below.
COLORECTAL CANCER (CRC)
BEACON CRC PHASE 3 TRIAL
Breakthrough Therapy Designation
On August 7, 2018, Array announced that the FDA granted Breakthrough Therapy Designation to BRAFTOVI, in combination with MEKTOVI and cetuximab for the treatment of patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC) as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease. BRAFV600E-mutant mCRC patients have a mortality risk more than double that of mCRC patients without the mutation, and currently there are no therapies specifically approved for this high unmet need population. [1-6]

Regulatory Update
Following consultation with the FDA and European Medicines Agency, Array has initiated an amendment to the BEACON CRC protocol to allow for an interim analysis of trial endpoints. Should a planned analysis based primarily on confirmed overall response rate (ORR) and durability of response be supportive, the Company plans to use it to seek accelerated approval in the U.S. The interim analysis may also support regulatory submissions in other regions. The Company anticipates topline results from this analysis in the first half of 2019. This timing allows for the subset of patients required for the interim analysis of ORR to achieve a response and for the durability of responses to be appropriately evaluated.

The BEACON CRC trial continues to enroll well and Array expects to complete enrollment of the trial around the end of 2018.

ANCHOR CRC TRIAL
In October 2018, ANCHOR CRC, an international trial designed to assess the efficacy and safety of the combination of encorafenib, binimetinib and cetuximab in patients with BRAFV600E-mutant mCRC in the first-line setting, was posted to clinicaltrials.gov. This trial was designed in partnership with top global key opinion leaders and Array is excited by the potential of this combination therapy to benefit patients in the first-line setting. The ANCHOR CRC trial is being conducted in collaboration with Pierre Fabre and Ono Pharmaceutical Co.,Ltd., and with support from Merck KGaA, Darmstadt, Germany.

IMMUNO-ONCOLOGY COLLABORATIONS
TRIALS ADVANCING WITH BRISTOL-MYERS SQUIBB, MERCK AND PFIZER
Array is developing binimetinib in combination with PD-1/PD-L1 checkpoint inhibitors and previously announced separate, strategic collaborations with Bristol-Myers Squibb, Merck and Pfizer. Each collaboration is pursuing a different rationally designed clinical approach in several solid tumor populations including metastatic colorectal cancer patients with microsatellite stable tumors (BMS and Merck), and patients with non-small cell lung and pancreatic cancer (Pfizer). These approaches are characterized by their focus on earlier lines of therapy and the addition of a third regimen.

FINANCIAL HIGHLIGHTS

First Quarter of Fiscal 2019 Compared to First Quarter of Fiscal 2018

Net Product Sales for BRAFTOVI + MEKTOVI for the first quarter of fiscal 2019 was $14.0 million. The Company has seen strong demand for BRAFTOVI + MEKTOVI during the quarter and continues to receive positive feedback from the melanoma community.
Total Revenue for the first quarter of fiscal 2019 increased by $27.2 million compared to the same quarter of fiscal 2018. The increase was primarily due to new product sales and increased milestone revenue from Pierre Fabre and Loxo Oncology, which was partially offset by reduced reimbursement revenue from Novartis as those underlying trials continue to decrease and certain reimbursement limits are met.
Cost of Goods Sold related to our product revenues was $0.2 million which represents 1.4% of net sales. The Company expects the percentage of net sales in subsequent quarters to increase as the initial launch inventory was mostly expensed prior to approval.
Research and development expense for proprietary programs increased by $2.3 million, compared to the first quarter of fiscal 2018. The increase was primarily driven by activities related to the BEACON CRC trial, which was partially offset by lower activity on the Novartis transitioned studies.
Selling, General and Administrative increased by $12.8 million compared to first quarter of fiscal 2018, primarily driven by commercialization activities for the BRAFTOVI and MEKTOVI launch.
Net loss for the first quarter of fiscal 2019 was $24.8 million, or ($0.12) per share, compared to $38.0 million, or ($0.22) per share, for the same quarter in fiscal 2018. The decrease in net loss was primarily due to new product sales and increased milestone revenue from Pierre Fabre and Loxo Oncology, which was partially offset by reduced reimbursement revenue from Novartis.
Cash, cash equivalents and marketable securities as of September 30, 2018 were $415 million.
CONFERENCE CALL INFORMATION
Array will hold a conference call on Tuesday, October 30, 2018, at 9:00 a.m. Eastern Time to discuss these results and provide an update on the progress of its key commercial products and clinical development programs. Ron Squarer, Chief Executive Officer, will lead the call.

Date:

Tuesday, October 30, 2018

Time:

9:00 a.m. Eastern Time

Toll-Free:

(844) 464-3927

Toll:

(765) 507-2598

Pass Code:

5559328

Webcast, including Replay and Conference Call Slides:
View Source

About BRAF-mutant Metastatic Melanoma
Melanoma develops when unrepaired DNA damage to skin cells triggers mutations that may lead them to multiply and form malignant tumors. Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [7,8] There are a variety of gene mutations that can lead to metastatic melanoma. The most common genetic mutation in metastatic melanoma is BRAF. 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. [7,9-11]

About BRAFTOVI + MEKTOVI
BRAFTOVI is an oral small molecule BRAF kinase inhibitor and MEKTOVI is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma. In Europe, the combination is approved for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test.

The Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA) are currently reviewing the Marketing Authorization Applications for BRAFTOVI and MEKTOVI submitted by Pierre Fabre, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) is currently reviewing the Manufacturing and Marketing Approval applications submitted by Ono Pharmaceutical Co, Ltd.

Indications and Usage
BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) are kinase inhibitors indicated for use in combination for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.

Limitations of Use: BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma.

BRAFTOVI + MEKTOVI Important Safety Information
The information below applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted.

Warnings and Precautions New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous malignancies can occur. In the COLUMBUS trial, cutaneous squamous cell carcinoma, including keratoacanthoma, occurred in 2.6% and basal cell carcinoma occurred in 1.6% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies.

Tumor Promotion in BRAF Wild-Type Tumors: Confirm evidence of BRAFV600E or BRAFV600Kmutation prior to initiating BRAFTOVI.

Cardiomyopathy: In the COLUMBUS trial, cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients. Cardiomyopathy resolved in 87% of patients. Assess left ventricular ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal.

Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE occurred in 6% of patients, including 3.1% of patients who developed pulmonary embolism.

Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in 19% of patients and ≥Grade 3 hemorrhage occurred in 3.2% of patients. Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients.

Ocular Toxicities: In the COLUMBUS trial, serous retinopathy occurred in 20% of patients; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. In patients with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of patients experienced retinal vein occlusion (RVO). Permanently discontinue MEKTOVI in patients with documented RVO. In COLUMBUS, uveitis, including iritis and iridocyclitis, was reported in 4% of patients. Assess for visual symptoms at each visit. Perform ophthalmic evaluation at regular intervals and for any visual disturbances.

Interstitial Lung Disease (ILD): ILD, including pneumonitis, occurred in 0.3% of patients with BRAFmutation-positive melanoma across multiple clinical trials. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD.

Hepatotoxicity: In the COLUMBUS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 6% for alanine aminotransferase (ALT) and 2.6% for aspartate aminotransferase (AST). Monitor liver laboratory tests before and during treatment and as clinically indicated.

Rhabdomyolysis: In the COLUMBUS trial, elevation of laboratory values of serum creatine phosphokinase (CPK) occurred in 58% of patients. Rhabdomyolysis was reported in 0.1% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Monitor CPK periodically and as clinically indicated.

QTc Prolongation: In the COLUMBUS trial, an increase in QTcF to >500 ms was measured in 0.5% (1/192) of patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms.

Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause fetal harm when administered to pregnant women. Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI + MEKTOVI.

Adverse Reactions
The most common adverse reactions (≥20%, all Grades, in the COLUMBUS trial) were: fatigue, nausea, diarrhea, vomiting, abdominal pain, arthralgia, myopathy, hyperkeratosis, rash, headache, constipation, visual impairment, serous retinopathy.

In the COLUMBUS trial, the most common laboratory abnormalities (≥20%, all Grades) included: increased creatinine, increased CPK, increased gamma glutamyl transferase, anemia, increased ALT, hyperglycemia, increased AST, and increased alkaline phosphatase.

Drug interactions
Avoid concomitant use of strong or moderate CYP3A4 inhibitors or inducers and sensitive CYP3A4 substrates with BRAFTOVI. Modify BRAFTOVI dose if concomitant use of strong or moderate CYP3A4 inhibitors cannot be avoided.

Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information [12,13]. You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Array at 1-844-Rx-Array (1-844-792-7729).

About COLUMBUS
The COLUMBUS trial (NCT01909453) is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of BRAFTOVI (encorafenib) in combination with MEKTOVI (binimetinib) compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. The primary endpoint of the trial was PFS; all secondary efficacy analyses, including the prospectively planned analysis of OS, are descriptive in nature. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial.

About Colorectal Cancer
Worldwide, colorectal cancer 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. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer. [14] 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. [15] In the U.S., BRAF mutations are estimated to occur in 10% to 15% of patients with colorectal cancer and represent a poor prognosis for these patients. [5,6,16,17] The risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF. [18] Several irinotecan and cetuximab-containing regimens, similar to the BEACON CRC control arm, have established clinical activity benchmarks in BRAFV600E-mutant mCRC patients, whose disease has progressed after one or two prior lines of therapy. These benchmarks include ORR of 4% to 8% ,mPFS of 1.8 to 2.5 months and median OS of 4 to 6 months. [1-6,19]

About BEACON CRC
BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of BRAFTOVI, MEKTOVI and cetuximab in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAFV600E-mutant mCRC. Thirty patients were treated in the safety lead-in and received the triplet combination (BRAFTOVI 300 mg daily, MEKTOVI 45 mg twice daily and cetuximab per label). Of the 30 patients, 29 had a BRAFV600E mutation. 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 BRAFTOVI in combination with cetuximab with or without MEKTOVI compared to cetuximab and irinotecan-based therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet combination, doublet combination (BRAFTOVI and cetuximab) or the control arm (irinotecan-based therapy and cetuximab). The study has been amended to include an interim analysis of endpoints including ORR. The primary overall survival endpoint is a comparison of the triplet combination 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, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. The BEACON CRC trial is being conducted with support from Ono Pharmaceutical Co., Pierre Fabre and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).

On October 30, 2018 Amgen (NASDAQ:AMGN) reported financial results for the third quarter of 2018 (Press release, Amgen, OCT 30, 2018, View Source [SID1234530368]). Key results include:

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Total revenues increased 2 percent versus the third quarter of 2017 to $5.9 billion.

Product sales grew 1 percent globally. New and recently launched products including Repatha (evolocumab), Prolia (denosumab), KYPROLIS (carfilzomib) and XGEVA (denosumab) showed double-digit growth.

GAAP earnings per share (EPS) increased 4 percent to $2.86 driven by higher total revenues, a lower tax rate and lower weighted-average shares outstanding.

GAAP operating income decreased 5 percent to $2.3 billion and GAAP operating margin decreased 2.5 percentage points to 42.2 percent.

Non-GAAP EPS increased 13 percent to $3.69 driven by higher total revenues, a lower tax rate and lower weighted-average shares outstanding.

Non-GAAP operating income decreased 2 percent to $3.0 billion and non-GAAP operating margin decreased 1.7 percentage points to 53.9 percent.

2018 EPS guidance revised to $12.23-$12.55 on a GAAP basis and $14.00-$14.25 on a non-GAAP basis; total revenues guidance revised to $23.2-$23.5 billion.

The Company generated $3.1 billion of free cash flow in the third quarter of 2018 versus $3.3 billion in the third quarter of 2017.

Product Sales Performance

Total product sales increased 1 percent for the third quarter of 2018 versus the third quarter of 2017.

Repatha sales increased 35 percent driven primarily by higher unit demand, offset partially by lower net selling price.

Prolia sales increased 15 percent driven by higher unit demand.

KYPROLIS sales increased 12 percent driven by higher unit demand, offset partially by lower net selling price.

XGEVA sales increased 12 percent driven by higher unit demand.

BLINCYTO (blinatumomab) sales increased 12 percent driven by higher unit demand.

Nplate (romiplostim) sales increased 11 percent driven by higher unit demand.

Vectibix (panitumumab) sales increased 8 percent driven by higher unit demand, offset partially by lower net selling price.

Parsabiv (etelcalcetide) was launched in the U.S. in the first quarter of 2018 and sales grew 40 percent sequentially in the third quarter.

Aimovig (erenumab-aooe) was launched in the U.S. in the second quarter of 2018 and generated $22 million in sales in the third quarter.

EPOGEN (epoetin alfa) sales decreased 5 percent driven by lower net selling price.

Enbrel (etanercept) sales decreased 5 percent driven by lower unit demand and, to a lesser extent, lower net selling price, offset partially by favorable changes in accounting estimates.

Neulasta (pegfilgrastim) sales decreased 6 percent driven by lower net selling price, lower unit demand and favorable prior-period changes in accounting estimates.

Aranesp (darbepoetin alfa) sales decreased 8 percent driven primarily by the impact of competition on unit demand.

Sensipar/Mimpara (cinacalcet) sales decreased 11 percent driven primarily by lower unit demand, which was due to continued adoption of Parsabiv in the U.S.

NEUPOGEN (filgrastim) sales decreased 38 percent driven by lower unit demand and, to a lesser extent, lower net selling price, which the Company believes is a function of competition.

Operating Expense, Operating Margin and Tax Rate Analysis
On a GAAP basis:

Total Operating Expenses increased 7 percent. All expense categories reflect savings from our transformation and process improvement efforts. Cost of Sales margin increased by 0.6 points due to higher manufacturing costs and higher acquisition-related intangibles amortization, offset partially by lower royalty cost and the favorable comparison to Hurricane Maria-related charges in Q3 2017. Research & Development (R&D) increased 6 percent driven by spending in late and early-stage programs, offset partially by decreased spending to support marketed products. Selling, General & Administrative (SG&A) expenses increased 11 percent due to investments in product launches and marketed product support. Other operating expenses increased primarily due to higher impairment-related charges associated with intangible assets acquired in business combinations.

Operating Margin decreased by 2.5 percentage points to 42.2 percent.

Tax Rate decreased by 3.9 percentage points due to the impacts of U.S. corporate tax reform.
On a non-GAAP basis:

Total Operating Expenses increased 7 percent. All expense categories reflect savings from our transformation and process improvement efforts. Cost of Sales margin increased by 0.3 points due to higher manufacturing cost, offset partially by lower royalty cost and the favorable comparison to Hurricane Maria-related charges in Q3 2017. R&D increased 6 percent driven by spending in late and early-stage programs, offset partially by decreased spending to support marketed products. SG&A expenses increased 11 percent due to investments in product launches and marketed product support.

AMGEN REPORTS THIRD QUARTER 2018 FINANCIAL RESULTS

Operating Margin decreased by 1.7 percentage points to 53.9 percent.

Tax Rate decreased by 6.4 percentage points due to the impacts of U.S. corporate tax reform

Cash Flow and Balance Sheet

The Company generated $3.1 billion of free cash flow in the third quarter of 2018 versus $3.3 billion in the third quarter of 2017 with the decrease driven by timing of tax payments.

The Company’s third quarter 2018 dividend of $1.32 per share was declared on July 31, 2018, was paid on Sept. 7, 2018, to all stockholders of record as of Aug. 17, 2018.

During the third quarter, the Company repurchased 8.7 million shares of common stock at a total cost of $1.7 billion. At the end of the third quarter, the Company had $3.7 billion remaining under its stock repurchase authorization.

AMGEN REPORTS THIRD QUARTER 2018 FINANCIAL RESULTS
Page 5

2018 Guidance
For the full year 2018, the Company now expects:

Total revenues in the range of $23.2 billion to $23.5 billion.

Previously, the Company expected total revenues in the range of $22.5 billion to $23.2 billion.

On a GAAP basis, EPS in the range of $12.23 to $12.55 and a tax rate in the range of 12.5 percent to 13.5 percent.

Previously, the Company expected GAAP EPS in the range of $11.83 to $12.62. Tax rate guidance is unchanged.

On a non-GAAP basis, EPS in the range of $14.00 to $14.25 and a tax rate in the range of 13.5 percent to 14.5 percent.

Previously, the Company expected non-GAAP EPS in the range of $13.30 to $14.00. Tax rate guidance is unchanged.

Capital expenditures to be approximately $700 million.

Third Quarter Product and Pipeline Update
The Company provided the following updates on selected product and pipeline programs:
KYPROLIS

In October, the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application to expand the Prescribing Information to include a once-weekly dosing option for KYPROLIS (20/70 mg/m2) in combination with dexamethasone for patients with relapsed or refractory multiple myeloma.
BLINCYTO

In September, the Japanese Ministry of Health, Labour and Welfare granted marketing approval for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

In August, the European Commission (EC) approved an expanded indication for BLINCYTO as monotherapy for the treatment of pediatric patients aged one year or older with Philadelphia chromosome-negative CD19 positive B-cell precursor ALL, which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
Aimovig

In July, the EC approved Aimovig for the prevention of migraine in adults experiencing four or more migraine days per month.
Repatha

In July, the National Drug Administration of China approved Repatha for the treatment of adults and adolescents over 12 years old with homozygous familial hypercholesterolemia.
Tezepelumab

In September, the FDA granted Breakthrough Therapy Designation for tezepelumab in patients with severe asthma without an eosinophilic phenotype.

Aimovig is developed in collaboration with Novartis.
Tezepelumab is developed in collaboration with AstraZeneca.

AMGEN REPORTS THIRD QUARTER 2018 FINANCIAL RESULTS

Non-GAAP Financial Measures
In this news release, management has presented its operating results for the third quarters of 2018 and 2017, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2018 EPS and tax rate guidance in accordance with GAAP and on a 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. Reconciliations for these non-GAAP financial measures to the most directly comparable GAAP financial measures are included in the news release. Management has also presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the third quarters of 2018 and 2017. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP.
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 ongoing business activities by facilitating comparisons of results of ongoing business operations among current, past and future periods. 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 news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. 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

On October 30, 2018 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported that it will report financial results for the third quarter ending September 30, 2018 on Wednesday, November 7, 2018, before the U.S. financial markets open (Press release, Alnylam, OCT 30, 2018, View Source;p=RssLanding&cat=news&id=2374231 [SID1234530367]).

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Management will provide an update on the Company and discuss third quarter 2018 results as well as expectations for the future via conference call on Wednesday, November 7, 2018 at 8:30 am ET. To access the call, please dial 800-667-5617 (domestic) or 334-323-0509 (international) five minutes prior to the start time and refer to conference ID 7650424. A replay of the call will be available beginning at 11:30 am ET on the day of the call. To access the replay, please dial 888-203-1112 (domestic) or 719-457-0820 (international) and refer to conference ID 7650424.

A live audio webcast of the call will be available on the Investors section of the Company’s website, www.alnylam.com. An archived webcast will be available on the Alnylam website approximately two hours after the event.

On October 30, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported financial results for the third quarter ended September 30, 2018 (Press release, Aduro Biotech, OCT 30, 2018, View Source;p=RssLanding&cat=news&id=2374236 [SID1234530366]). Net loss for the third quarter of 2018 was $23.1 million, or $0.29 per share, and for the nine months ended September 30, 2018 net loss was $69.0 million, or $0.88 per share, compared to net loss of $24.5 million, or $0.33 per share, and net loss of $65.7 million, or $0.92 per share, respectively, for the same periods in 2017.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Cash, cash equivalents and marketable securities totaled $278.6 million at September 30, 2018, compared to $349.7 million at December 31, 2017.

"Our strong cash position enables us to advance our lead STING agonist, ADU-S100, and novel anti-APRIL antibody, BION-1301, toward maturing data from ongoing clinical studies. We look forward to presenting preliminary data on ADU-S100 at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in Washington, D.C.," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro.

Revenue was $3.1 million for the third quarter of 2018 and $12.3 million for the nine months ended September 30, 2018, compared to $3.8 million and $13.5 million, respectively, for the same periods in 2017. The decrease in revenue for both periods was primarily due to the adoption of the ASC 606 accounting standard on January 1, 2018, which resulted in a change in revenue recognition methodology for our Novartis collaboration revenue.

Research and development expenses were $18.7 million for the third quarter of 2018 and $58.2 million for the nine months ended September 30, 2018, compared to $24.5 million and $66.5 million, respectively, for the same periods in 2017. The decrease in research and development expenses for both periods was primarily due to lower expenses for our antibody programs, including contingent consideration and contract manufacturing related to ADU-1604 and BION-1301, respectively.

General and administrative expenses were $9.1 million for the third quarter of 2018 and $27.0 million for the nine months ended September 30, 2018, compared to $8.5 million and $25.0 million, respectively, for the same periods in 2017. The increase in general and administrative expenses for both periods was primarily due to outside professional services and consulting costs as well as higher stock-based compensation expense.

On October 30, 2018 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) reported that the next stage of development for its CD33 ARC (Antibody Radiation Conjugate) Ac-225-Lintuzumab program, after successful completion of the Actimab-A phase 2 trial in Acute Myeloid Leukemia (AML), will incorporate two key initiatives; a pivotal trial pathway for its Actimab-MDS program for Myelodysplastic Syndromes (MDS), and also in two combination trials with Venetoclax for AML (Press release, Actinium Pharmaceuticals, OCT 30, 2018, View Source [SID1234530365]). Actinium’s development strategy for its CD33 program is being informed by: clinical data from 4 trials totaling over 100 patients including the recent Actimab-A Phase 2 trial in AML; positive interactions with the FDA regarding its Actimab-MDS trial; company research findings regarding potential synergy with Venetoclax; support from leading physicians; and attractiveness of the targeted indications given the unmet medical need and potential of its differentiated ARC modality in combination with chemotherapy.

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Actinium highlighted the outcome of its successful discussions with the FDA for the Actimab-MDS program, which resulted in guidance for an accelerated pathway to a pivotal trial after a short dose finding Phase 1 portion. Actinium’s initial proposal to the FDA was to conduct a larger Phase 2 trial prior to a pivotal trial in patients with a TP53 mutation, however, the company was encouraged by the FDA to expand the trial to include all high-risk patients with poor or very poor and complex cytogenetics. The program will use the ARC Ac-225-lintuzumab for targeted conditioning in combination with a reduced intensity dose of fludarabine and melphalan prior to a BMT or Bone Marrow Transplant in patients with high-risk Myelodysplastic Syndrome (MDS).

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "In our studies to date, we’ve seen that Ac-225 – Lintuzumab can achieve remissions with minimal extramedullary toxicities even in patients progressing to AML from MDS. Typically, high-risk MDS patients undergoing a BMT do poorly with standard conditioning resulting in poor outcomes. The goal of the Actimab-MDS program is to use our ARC AC-225 – Lintuzumab to target cells of the myeloid lineage including progenitor cells in combination with reduced intensity conditioning with the goal of achieving improved conditioning and BMT outcomes, as successful BMT is the only potentially curative treatment option for these patients. We are building on the data we already have from our CD33 program and we are excited to have a quicker pathway to a pivotal trial that targets a larger patient population than originally envisaged."

Actinium’s two combination trials with Venetoclax, a BCL-2 inhibitor that was jointly developed by AbbVie and Genentech, will leverage Actimab-A’s unique and differentiated mechanism of action to explore synergies between the two agents for patients with relapsed or refractory AML. Venetoclax is an approved drug for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) and a supplemental New Drug Application (NDA) has been submitted to the FDA for patients newly diagnosed with AML. The first proposed study will evaluate Actimab-A in combination with Venetoclax and will be led by Dr. Gary Schiller, Director, Hematology/Stem Cell Transplantation at UCLA Medical center. The second study will evaluate Actimab-A in combination with Venetoclax and hypomethylating agents and will be conducted in collaboration with Dr. Hagop Kantarjian and Dr. Tapan Kadia of the MD Anderson Cancer Center. The company is pursuing these combination trials with Actimab-A and Venetoclax on the basis of internal preclinical studies which have demonstrated a synergistic effect between these two agents that is supported by a mechanistic rational. Specifically, patients with AML have high levels of MCL-1, a protein that mediates resistance to Venetoclax, which is known to be depleted by DNA damage caused by external radiation treatment. Preclinical studies have demonstrated that MCL-1 is effectively depleted by DNA damage caused by external radiation and Actinium believes that Actimab-A’s targeted radiation mechanism will therefore lead to a greater effect of Actimab-A plus Venetoclax, as demonstrated in the Company’s preclinical work.

Dr. Berger added, "Many therapeutic advances in oncology, and also in AML, have been the result of combination therapies. We are excited to be advancing our Actimab-A program in combination with Venetoclax, which has the potential to lead the next evolution of AML therapy, in collaboration with top thought leaders from leading medical institutions. As indicated by our collaborators during the CD33 Update webinar, while results with Venetoclax in patients with AML are encouraging, there remains a high unmet need for durable responses and curative outcomes. We believe Actimab-A can be used in combination with Venetoclax to improve patient outcomes, which is based on a strong scientific rationale supporting the combination as well as preclinical and clinical data. Our proposed trials with these combinations demonstrate the strong investigator interest we have seen for working with Ac-225 – Lintuzumab as an Antibody Radiation Conjugate is a new therapeutic modality for patients with radiation sensitive cancers such as AML, MDS and Multiple Myeloma that has the potential to improve their outcomes."

Sandesh Seth, Actinium’s Chairman and Chief Executive Officer said, "Having a clear and relatively quick pathway to a pivotal trial for Actimab-MDS materially strengthens our targeted conditioning pipeline. It also enhances our outlook for building a business focused on developing and launching multiple products for targeted conditioning prior to BMT or CAR-T that can improve both patient access and outcomes due to their superior safety and efficacy balance compared to non-targeted chemotherapy that is current standard of care. With the solid progress of the Iomab-B Phase 3 trial for BMT, the recent launch of the Iomab-ACT program for CAR-T and the solid impetus for a near-term Actimab-MDS pivotal trial, our pipeline prospects for targeted conditioning have never been better."

Mr. Seth added, "The Actimab-A trial which was recently closed has been a big success as it has provided the foundation for the near-pivotal Actimab-MDS program in an area where there is high unmet need, no competing development programs by other companies and a larger patient population than originally envisaged. Additionally, our combination trials with Venetoclax and Actimab-A are very exciting as we have the opportunity to validate our preclinical research showing superiority of the combination in two highly relevant clinical settings where the unmet medical need continues to be high. Based on these recent developments, our CD33 Program has evolved much beyond the narrow AML focused CD33 programs in the industry due to the versatility of our ARC technology. The ARC approach has allowed us to expand into other radiation sensitive diseases such as multiple myeloma and MDS, and into targeted conditioning using high doses of the ARC as well as therapeutic combinations at lower ARC doses which allow incorporation of targeted radiation as another modality to treat highly radiation sensitive cancers."

"In addition," said Mr. Seth, "from a strategic perspective, the Actimab-MDS targeted conditioning trial strengthens our go-it-alone outlook. However, the other CD33 program developments including combination trials increase its attractiveness to potential collaborators and are expected to provide our company with attractive optionality going forward, as the period between now and 2019 are expected to yield several valuable clinical milestones and data readouts. We look forward to providing updates as value in this program continues to build.".