On October 30, 2018 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted oncology company, reported that it has submitted an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to initiate a Phase 1/2 trial with the initial goal to evaluate safety, tolerability and pharmacokinetics of the Company’s KRAS G12C inhibitor, MRTX849, in patients with advanced solid tumors (Press release, Mirati, OCT 30, 2018, View Source [SID1234530351]). The trial will utilize an accelerated titration design with single patient cohorts and intra-patient dose escalation to rapidly achieve an active dose level for MRTX849. Phase 2 expansion cohorts will enroll patients whose tumors are driven by KRAS G12C positive mutations. The Phase 2 portion of the trial in patients with non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) may provide proof of concept and the basis for accelerated approval.

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"MRTX849, is a potent, highly selective inhibitor of G12C positive mutations. These mutations occur in large patient populations with NSCLC and CRC tumors, and are also present in patients with other solid tumors, such as pancreatic cancer. We submitted the IND on October 29th, 2018 and plan to begin enrolling patients soon after FDA approval is received. The trial is designed to enable early clinical efficacy data in 2019," said Charles Baum, M.D., Ph.D., President and Chief Executive Officer, Mirati Therapeutics, Inc. "KRAS has long been one of the most difficult targets in all of oncology and this program has the potential to be a breakthrough for patients with G12C positive mutations."

"KRAS has been an elusive target for researchers for more than 30 years. It’s exciting to see an IND filing that would potentially provide a therapy for patients with G12C mutations, which were once considered undruggable and who have had no viable treatment options," said Channing J. Der, Ph.D., the Sarah Graham Kenan Professor of Pharmacology at the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center.

About MRTX849

MRTX849 is an orally-available small molecule that potently and selectively inhibits a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MTRX849 has demonstrated broad-spectrum tumor regression in a large cohort of KRAS G12C-positive pre-clinical in-vivo human tumor models. MRTX849 demonstrated complete regression of tumors in a subset of models at well-tolerated dose levels. Early proof-of-concept clinical data is anticipated in 2019.

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 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, reported that it will host a conference call on Monday, November 5, 2018 at 5pm ET to discuss third quarter 2018 financial results and provide a corporate update (Press release, Ultragenyx Pharmaceutical, OCT 30, 2018, http://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-host-conference-call-third-quarter-2018-financial [SID1234530387]).

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The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call by phone, dial 855-797-6910 (USA) or 262-912-6260 (international) and enter the passcode 1290627. The replay of the call will be available for one year.

On October 30, 2018 Castle Biosciences, Inc., the skin cancer diagnostics company providing molecular diagnostics to improve cancer management decisions, reported the presentation of data highlighting how the accuracy of the DecisionDx-Melanoma gene expression profile (GEP) test in patients with Stage II and IIIA melanoma can improve adjuvant clinical trial design at the 2018 Society for Melanoma Research International Congress held in Manchester, England from October 24-27 (Press release, Castle Biosciences, OCT 30, 2018, View Source [SID1234530427]).

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The study titled, "Implications of a 31-gene expression profile test for cutaneous melanoma on AJCC-based risk assessment and adjuvant therapy trial design," was presented as a poster at the meeting.

Study Background

The adjuvant treatment setting for melanoma has experienced significant advances in recent years. While therapies provide clear benefits for a subset of melanoma patients, they also can be associated with significant adverse effects. Accurate assessment of individual patient risk is increasingly important to guide treatment decisions, especially for those with no evidence of disease.
The analysis focused on the use of the DecisionDx-Melanoma test to inform which Stage II and IIIA melanoma patients are at high risk of recurrence and could benefit from adjuvant therapy. Adjuvant therapy trials are being considered or underway for Stage II and Stage IIIA patients, but recurrence rates in this population make trials in this population challenging.
The study assessed whether the DecisionDx-Melanoma test could have a role in patient selection for future adjuvant therapy clinical trials, and evaluated the potential cost savings associated with patient enrollment based on risk assessment.
Study Details and Key Findings

The DecisionDx-Melanoma test was previously validated in a cohort of 690 patients from 18 centers to accurately predict 5-year risk of recurrence for patients with melanoma (Class 1A lowest risk; Class 2B highest risk).
This analysis included a subset of 173 patients who had Stage II or IIIA melanoma (restaged using American Joint Committee on Cancer [AJCC] 8th edition).
Patients in the Stage II-IIIA cohort who had a Class 1A DecisionDx-Melanoma test result had a 5-year melanoma-specific survival (MSS) rate of 100%, similar to the risk of patients with Stage 1A melanoma. Stage II-IIIA patients who had a Class 2B result had an MSS of 85%, similar to a Stage IIIB risk.
Similarly, 5-year recurrence-free survival for patients in the Stage II-IIIA cohort who had a Class 2B DecisionDx-Melanoma test result was 39% and distant metastasis-free survival was 54%, significantly lower than those for patients with a Class 1A result.
Study results showed that using the DecisionDx-Melanoma test to select patients for a clinical trial, sample size could be reduced by 36% with an overall reduction in trial costs if enrollment focused on patients with a high risk of recurrence as determined by a DecisionDx-Melanoma Class 2B result.
"Optimization of adjuvant clinical trial enrollment for melanoma is increasingly important given the adverse effects that are associated with current targeted and immune checkpoint therapies," said Sancy Leachman M.D., Ph.D., Professor and chair, Department of Dermatology and Director, Melanoma Research Program, Oregon Health & Science University. "These data support application of the DecisionDx-Melanoma test to identify Stage II-IIIA patients who are at higher risk for recurrence and metastasis and are therefore appropriate candidates for adjuvant therapy consideration in a clinical trial."

The poster is available on the www.SkinMelanoma.com website.

About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in multi-center and single-center studies. More information about the test and disease can be found at www.SkinMelanoma.com.

On October 30, 2018 NewLink Genetics Corporation (NASDAQ:NLNK), a clinical stage biopharmaceutical company focused on developing novel immuno-oncology therapeutic candidates, reported it will present at the Stifel 2018 Healthcare Conference (Press release, NewLink Genetics, OCT 30, 2018, View Source [SID1234530682]). The conference is being held on November 13 – 14 at the Lotte New York Palace Hotel in New York City, New York.

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NewLink’s management will participate in an analyst-led fireside chat Tuesday, November 13, 2018 from 11:45 AM – 12:25 PM ET and will be available for one-on-one meetings with investors who are registered to attend the conference.

A live webcast of the conference presentation will be available on the Company’s website at www.newlinkgenetics.com in the "Investors & Media" section under "Events & Presentations".