On April 24, 2018 Mirati Therapeutics, Inc. (Nasdaq: MRTX) (the Company or Mirati), a clinical-stage targeted oncology company, reported that a progress update on its lead development programs and announced updated, positive clinical trial data for sitravatinib, a spectrum selective kinase inhibitor, and mocetinostat, a class I and IV HDAC inhibitor (Press release, Mirati, APR 24, 2018, View Source [SID1234525643]). The Company has been evaluating sitravatinib and mocetinostat in separate Phase 2 clinical trials in combination with checkpoint inhibitor therapy in non-small cell lung cancer (NSCLC) patients whose disease had progressed following prior treatment with a checkpoint inhibitor. Both clinical trials have generated encouraging preliminary data demonstrating the potential to overcome resistance to checkpoint inhibitor therapy.

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"The majority of NSCLC patients either do not respond to checkpoint inhibitor therapy or experience disease progression following treatment. These patients have limited treatment options and generally experience poor outcomes in response to standard of care chemotherapy," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer. "The preliminary data from our Phase 2 study of sitravatinib plus nivolumab continue to highlight the promise of this combination to overcome resistance to initial checkpoint inhibitor therapy and provide a meaningful treatment option for this large and underserved patient population."

Sitravatinib is being evaluated in a Phase 2 study in combination with nivolumab (OPDVIO), an anti-PD-1 checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with a checkpoint inhibitor. As of the data cutoff date of March 31, 2018:

23 patients were evaluable for response with at least one radiographic scan

Six patients achieved a Partial Response (PR) (four confirmed and two unconfirmed)

1Five of the six patients with PRs remain on study, including both patients with unconfirmed PRs; the longest treatment duration exceeds 50 weeks and is ongoing

The other patient with a PR progressed following a treatment duration that exceeded 40 weeks

19 of 23 patients demonstrated tumor reductions

To date, the combination has been well-tolerated and most adverse events (AEs) reported by investigators were Grade 1 or 2.
"The responses and duration of treatment seen with the combination of sitravatinib and a checkpoint inhibitor are very promising, notably because these patients had relapsed following prior checkpoint inhibitor therapy," said Alexander Spira, M.D., Ph.D., Director of the Virginia Cancer Specialists Research Institute. "The trial is enrolling well, and we have been pleased with the favorable tolerability of the combination."

Enrollment is accelerating, and 45 patients have been enrolled. Correlative analyses of peripheral blood and tumor tissue biomarkers are ongoing. The Company is planning to present more mature data at an oncology conference later this year. The Company expects to meet with regulatory authorities in the second half of 2018 to discuss plans for registration.

In a separate Phase 2 study, mocetinostat is being evaluated in combination with durvalumab (IMFINZI), an anti-PD-L1 checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with a checkpoint inhibitor. As of the data cutoff date of March 31, 2018:

23 patients were evaluable for response with at least one radiographic scan

Three patients achieved a PR (two confirmed and one unconfirme

All three patients with PRs remain on study; the longest treatment duration exceeds 44 weeks and is ongoing
8 of 23 patients demonstrated tumor reductions.

To date, the combination has been well-tolerated, and most AEs reported by investigators were Grade 1 or 2.
31 patients have been enrolled in this ongoing trial and the Company plans to present more mature data at an oncology conference later this year.
Mirati also provided an update on the Phase 1b expansion trial for sitravatinib as a single agent. Interim clinical data will be presented in a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 1 – 5, 2018 in Chicago, Illinois. The presentation, titled "Evaluation of the spectrum selective RTK inhibitor sitravatinib in renal cell carcinoma (RCC) refractory to anti-angiogenic therapy" will report data from patients with RCC treated with single agent sitravatinib.

In that same Phase 1b trial of single agent sitravatinib, enrollment continues in the cohorts of patients whose tumors harbor CBL, CHR4Q12 and RET genetic alterations in NSCLC and other tumor types. The Company plans to present more mature data for these patients at an oncology conference later this year.

MRTX849, the Company’s small molecule mutation-selective KRAS G12C inhibitor, continues to advance towards a planned Investigational New Drug (IND) submission in the fourth quarter of 2018, with the potential to generate early proof-of-concept clinical data in 2019.

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About Sitravatinib

Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being tested in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in NSCLC patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.

Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion trial enrolling patients whose tumors harbor CBL, CHR4Q12 and RET genetic alterations in NSCLC and other solid tumors.

About Mocetinostat

Mocetinostat is a selective Class I and IV HDAC inhibitor. Inhibition of histone acetylation is predicted to enhance the recognition of tumor cells by anti-tumor T cells and reverse immunosuppressive factors in the tumor microenvironment. The Company is conducting a Phase 2 study of mocetinostat in combination with durvalumab (IMFINZI), an anti-PD-L1 checkpoint inhibitor, in NSCLC patients who have experienced disease progression following prior treatment with a checkpoint inhibitor.

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 complete regression of KRAS G12C-positive human tumors implanted in mice. IND-enabling preclinical studies are underway, and an IND submission is expected in the fourth quarter of 2018, with early clinical proof-of-concept anticipated in 2019.

On April 24, 2018 Amgen (NASDAQ:AMGN) reported financial results for the first quarter of 2018 (Press release, Amgen, APR 24, 2018, View Source;p=RssLanding&cat=news&id=2344288 [SID1234525627]).

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Key results include:
Total revenues increased 2 percent versus the first quarter of 2017 to $5.6 billion.
Product sales grew 3 percent globally. All new and recently launched products including Repatha (evolocumab), KYPROLIS (carfilzomib), Prolia (denosumab) and XGEVA (denosumab) showed double-digit growth.
GAAP earnings per share (EPS) increased 16 percent to $3.25 driven by higher product sales, a lower tax rate and lower weighted-average shares outstanding.
GAAP operating income increased 5 percent to $2.7 billion and GAAP operating margin increased 1.2 percentage points to 51.0 percent.
Non-GAAP EPS increased 10 percent to $3.47 driven by higher product sales, a lower tax rate and lower weighted-average shares outstanding.
Non-GAAP operating income increased 1 percent to $3.0 billion and non-GAAP operating margin decreased 0.7 percentage points to 56.9 percent.
2018 EPS guidance revised to $11.30-$12.28 on a GAAP basis and $12.80-$13.70 on a non-GAAP basis; total revenues guidance revised to $21.9-$22.8 billion.
The Company generated $2.6 billion of free cash flow in the first quarter versus $2.2 billion in the first quarter of 2017.

Product Sales Performance

Total product sales increased 3 percent for the first quarter of 2018 versus the first quarter of 2017.
Repatha sales increased 151 percent driven primarily by higher unit demand.
BLINCYTO (blinatumomab) sales increased 44 percent driven by higher unit demand.
Sensipar/Mimpara (cinacalcet) sales increased 18 percent driven primarily by higher unit demand.
KYPROLIS sales increased 17 percent driven primarily by higher unit demand.
Prolia sales increased 16 percent driven primarily by higher unit demand.
Nplate (romiplostim) sales increased 16 percent driven by higher unit demand.
Vectibix (panitumumab) sales increased 15 percent driven primarily by higher unit demand.
XGEVA sales increased 11 percent driven primarily by higher unit demand.
Parsabiv (etelcalcetide) sales increased driven by our U.S. launch.
Neulasta (pegfilgrastim) sales decreased 5 percent driven by lower unit demand from continued declines in the use of myelosuppressive chemotherapy regimens and from favorable prior year changes in accounting estimates, offset partially by favorable changes in net selling price and inventory.
Enbrel (etanercept) sales decreased 6 percent driven primarily by lower unit demand and, to a lesser extent, lower net selling price and favorable prior year changes in accounting estimates, offset partially by favorable changes in inventory.
EPOGEN (epoetin alfa) sales decreased 10 percent driven primarily by unfavorable changes in net selling price and lower unit demand.
Aranesp (darbepoetin alfa) sales decreased 11 percent driven primarily by the impact of competition on unit demand.
NEUPOGEN (filgrastim) sales decreased 30 percent driven primarily by the impact of competition on unit demand.

Operating Expense, Operating Margin and Tax Rate Analysis

On a GAAP basis:

Total Operating Expenses decreased 2 percent, with all expense categories reflecting savings from our transformation and process improvement efforts. Cost of Sales margin improved by 1.5 percentage points driven primarily by lower royalties and a reduction in amortization of intangible assets, offset partially by increasing manufacturing costs. Research & Development (R&D) expenses were flat. Selling, General & Administrative (SG&A) expenses increased 6 percent due to investments in product launches and marketed product support.
Operating Margin improved by 1.2 percentage points to 51.0 percent.
Tax Rate decreased by 4.0 percentage points due to the impacts of U.S. corporate tax reform.
On a non-GAAP basis:

Total Operating Expenses increased 2 percent, with all expense categories reflecting savings from our transformation and process improvement efforts. Cost of Sales margin improved by 0.4 percentage points driven primarily by lower royalties, offset partially by increasing manufacturing costs. R&D expenses were flat. SG&A expenses increased 6 percent due to investments in product launches and marketed product support.
Operating Margin decreased by 0.7 percentage points to 56.9 percent.
Tax Rate decreased by 4.8 percentage points due to the impacts of U.S. corporate tax reform.

Cash Flow and Balance Sheet

The Company generated $2.6 billion of free cash flow in the first quarter of 2018 versus $2.2 billion in the first quarter of 2017 driven by higher net income.
The Company’s second quarter 2018 dividend of $1.32 per share declared on March 7, 2018, will be paid on June 8, 2018, to all stockholders of record as of May 17, 2018.
During the first quarter, the Company repurchased 56.4 million shares of common stock at a total cost of $10.8 billion.

2018 Guidance

For the full year 2018, the Company now expects:

Total revenues in the range of $21.9 billion to $22.8 billion.
Previously, the Company expected total revenues in the range of $21.8 billion to $22.8 billion.
On a GAAP basis, EPS in the range of $11.30 to $12.28 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 $11.18 to $12.36, and a tax rate in the range of 13 percent to 14 percent.
On a non-GAAP basis, EPS in the range of $12.80 to $13.70 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 $12.60 to $13.70, and a tax rate in the range of 14 percent to 15 percent.
Capital expenditures to be approximately $750 million.

The Company provided the following updates on selected product and pipeline programs:

Repatha

In March, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to include a new indication for adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels.
Neulasta

In February, the CHMP adopted a positive opinion recommending a label variation for Neulasta to include the Neulasta Onpro Kit.
XGEVA

In April, the European Commission approved an expanded indication for the prevention of skeletal-related events in adults with advanced malignancies involving bone. The indication now covers patients with bone metastases from solid tumors and those with multiple myeloma.
BLINCYTO

In March, the U.S. Food and Drug Administration (FDA) approved BLINCYTO for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1 percent. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival.
KANJINTI (ABP 980)

In March, the CHMP adopted a positive opinion for the marketing authorization of KANJINTI, a biosimilar to Herceptin (trastuzumab) for the treatment of the same three types of cancer as Herceptin is approved for in the European Union, including HER2-positive metastatic breast cancer, HER2-positive early breast cancer and HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction.
EVENITY, Aimovig and KANJINTI trade names provisionally approved by FDA
EVENITY is developed in collaboration with UCB globally, as well as our joint venture partner Astellas in Japan
Aimovig is developed in collaboration with Novartis
Herceptin is a registered trademark of Genentech

Non-GAAP Financial Measures
In this news release, management has presented its operating results for the first 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 first 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 April 24, 2018 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO FR0010095596), a biotechnology company specializing in the development of innovative drugs in oncology, notably against rare or resistant forms of cancer, reported the initiation of DRIIV (DNA Repair Inhibitor administered IntraVenously) phase I clinical trial of AsiDNA, its "first-in-class" DNA repair inhibitor (Press release, Onxeo, APR 24, 2018, View Source [SID1234525644]). The aim of the study is to assess AsiDNA safety profile and identify its optimal clinical dose, as well as determine its active dose at the tumor level, in patients with advanced solid cancer.

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First patient has been enrolled and dosed with AsiDNA.

AsiDNA has a unique and innovative mechanism of action that inhibits the repair of tumor DNA damages through a decoy process by activating the enzymes involved in the signaling and repairing of tumor DNA lesions and harnessing them, thus making them unable to repair the tumor damages, which leads to the mitotic death of the cell.

The DRIIV study is being conducted at three of the most prestigious centers in France and Belgium and interim results are expected in the second half of 2018.

"The DNA-damage response approach to cancer treatment is a highly compelling approach which has been already validated with the approval of PARP inhibitors, which belongs to the same general class of DDR. AsiDNA has a unique mechanism of action and the potential to provide patients with an attractive therapeutic option. I look forward to further evaluating AsiDNA in this important clinical trial," said Professor Christophe Le Tourneau of the Institut Curie in Paris, principal investigator of DRIIV.

"The initiation of DRIIV represents a significant milestone in the development of this unique asset and in enhancing the therapeutic potential of AsiDNA," said Judith Greciet, CEO of Onxeo. "Importantly, while AsiDNA has previously shown clinical activity when injected directly into the tumor, demonstrating similar activity via systemic administration will provide the opportunity to target a vast range of cancers. We look forward to evaluating AsiDNA in this phase I clinical trial in order to establish the clinical benefit of this promising product candidate when administered systemically, which represents a strong value catalyst for this key asset."

Olivier de Beaumont, Chief Medical Officer of Onxeo, added, "Thanks to the pre-clinical data generated to date, we have established the optimal clinical trial protocol for this phase I study and we look forward to conducting the DRIIV study with experienced oncology investigators. DRIIV is the first step in men that will enable us to effectively characterize AsiDNA’s safety profile and determine the optimal clinical dose in order to further develop AsiDNA, whether combined with other anticancer agents or as a monotherapy."

On April 24, 2018 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported that William G. Rice, Ph.D., Chairman, President and Chief Executive Officer, and Gregory K. Chow, Senior Vice President and Chief Financial Officer, will participate at the Bloom Burton & Co. Healthcare Conference on Wednesday, May 2, 2018 at 1:30 p.m. EDT (Press release, Aptose Biosciences, APR 24, 2018, View Source;p=RssLanding&cat=news&id=2344129 [SID1234525628]):

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Time: 1:30 p.m. EDT
Date: Wednesday, May 2, 2018
Location: Sheraton Centre Toronto Hotel, Toronto, Canada
Live webcast: View Source
The audio webcast can also be accessed through the Aptose website at www.aptose.com and will be archived shortly after the live event and available for 90 days.

On April 24, 2018 Perrigo Company plc (NYSE; TASE: PRGO) reported that it will release its first quarter calendar year 2018 financial results on Tuesday, May 8, 2018 (Press release, Perrigo Company, APR 24, 2018, View Source [SID1234525645]). The Company will host a conference call beginning at 8:30 a.m. (EDT).

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The conference call will be available live via webcast to interested parties in the investor relations section of the Perrigo website at View Source or by phone at 877-248-9413, International 973-582-2737, and reference ID #6366917. A taped replay of the call will be available beginning at approximately 12:00 p.m. (EDT) Tuesday, May 8, until midnight Day, May 18, 2018. To listen to the replay, dial 800-585-8367, International 404-537-3406, and use access code 6366917.

The Company also announced that it will present at the Deutsche Bank 43rd Annual Healthcare Conference at 1:30 PM EDT on Wednesday, May 9, 2018. Interested parties can access the presentation webcast at View Source.