On February 14, 2018 Agilent Technologies, Inc. (NYSE: A) today reported revenue of $1.21 billion for the first-quarter ended January 31, 2018, up 14 percent year over year (up 10 percent on a core basis(2)) (Press release, Agilent, FEB 14, 2018, http://www.agilent.com/about/newsroom/presrel/2018/14feb-gp18028.html [SID1234524147]).

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On a GAAP basis, including the $533 million charge related to U.S. Tax Reform legislation, first-quarter net loss was $320 million, or $0.99 net loss per share. Last year’s first-quarter GAAP net income was $168 million, or $0.52 per share.

During the first quarter, Agilent had an adjustment related to U.S. Tax Reform of $533 million, intangible amortization of $25 million, a pension settlement gain of $5 million, transformation costs of $5 million, acquisition and integration costs of $3 million, and $3 million in other costs. Excluding these items and a tax benefit of $28 million, Agilent reported first-quarter non-GAAP net income of $216 million, or $0.66 per share(1).

"We are very pleased with our strong start to the year," said Mike McMullen, Agilent CEO and President. "The Agilent team continued our positive momentum and delivered another excellent quarter of operating results."

"Looking forward, we will keep our focus on driving sustainable above-market growth and delivering value to shareholders through the execution of our proven strategy," continued McMullen. "Overall, we are well-positioned to continue delivering excellent operating results."

First-quarter revenue of $618 million from Agilent’s Life Sciences and Applied Markets Group (LSAG) grew 14 percent year over year (up 11 percent on a core basis(2)), with broad strength across all major end markets. LSAG’s operating margin for the quarter was 25.8 percent.

First-quarter revenue of $408 million from Agilent CrossLab Group (ACG) grew 12 percent year over year (up 9 percent on a core basis(2)). Growth was strong across services and consumables. ACG’s operating margin for the quarter was 21.6 percent.

First-quarter revenue of $185 million from Agilent’s Diagnostics and Genomics Group (DGG) grew 13 percent year over year (up 8 percent on a core basis(2)) led by strong demand for pathology products and companion diagnostics services. DGG’s operating margin for the quarter was 11.7 percent.

Agilent expects second-quarter 2018 revenue in the range of $1.20 billion to $1.22 billion. Second-quarter 2018 non-GAAP earnings are expected to be in the range of $0.61 to $0.63 per share(3).

For fiscal year 2018, Agilent expects revenue of $4.885 billion to $4.905 billion and non-GAAP earnings of $2.62 to $2.68 per share(3). The guidance is based on January 31, 2018 currency exchange rates.

Conference Call

Agilent’s management will present more details about its first-quarter fiscal 2018 financial results on a conference call with investors today at 1:30 p.m. (Pacific Time). This event will be webcast live in listen-only mode. Listeners may log on at www.investor.agilent.com and select "Q1 2018 Agilent Technologies Inc. Earnings Conference Call" in the "News & Events — Calendar of Events" section. The webcast will remain available on the company’s website for 90 days.

Additional information regarding financial results can be found at www.investor.agilent.com by selecting "Financial Results" in the "Financial Information" section.

A telephone replay of the conference call will be available at approximately February 14, 2018 at 4:30 p.m. (Pacific Time) after the call and through February 21 by dialing +1 855-859-2056 (or +1 404-537-3406 from outside the United States) and entering pass code 1482568.

# # #

Financial Statements for First-Quarter Fiscal 2018

AGILENT TECHNOLOGIES, INC.
CONDENSED CONSOLIDATED STATEMENT OF OPERATIONS
(In millions, except per share amounts)
(Unaudited)
PRELIMINARY

Three Months Ended
January 31, Percent
2018 2017 Inc/(Dec)

Net revenue $ 1,211 $ 1,067 14 %

Costs and expenses:
Cost of products and services 538 493 9 %
Research and development 93 79 18 %
Selling, general and administrative 341 289 18 %
Total costs and expenses 972 861 13 %

Income from operations 239 206 16 %

Interest income 9 4 125 %
Interest expense (20 ) (20 ) —
Other income (expense), net 5 3 67 %

Income before taxes 233 193 21 %

Provision for income taxes 553 25 —

Net income (loss) $ (320 ) $ 168 —

Net income (loss) per share:
Basic $ (0.99 ) $ 0.52
Diluted $ (0.99 ) $ 0.52

Weighted average shares used in computing net income (loss) per share:
Basic 323 322
Diluted 323 326

Cash dividends declared per common share $ 0.149 $ 0.132

The preliminary income statement is estimated based on our current information.

Page 1

AGILENT TECHNOLOGIES, INC.
CONDENSED CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME (LOSS)
(In millions)
(Unaudited)
PRELIMINARY

Three Months Ended
January 31,
2018 2017

Net income (loss) $ (320 ) $ 168

Other comprehensive income (loss), net of tax:

Unrealized gain (loss) on derivative instruments (7 ) 1
Foreign currency translation 79 (3 )
Net defined benefit pension cost and post retirement plan costs:
Change in actuarial net loss 6 17
Change in net prior service benefit (1 ) (1 )
Other comprehensive income 77 14

Total comprehensive income (loss) $ (243 ) $ 182

The preliminary statement of comprehensive income is estimated based on our current information.

Page 2

AGILENT TECHNOLOGIES, INC.
CONDENSED CONSOLIDATED BALANCE SHEET
(In millions, except par value and share amounts)
(Unaudited)
PRELIMINARY

January 31, October 31,
2018 2017
ASSETS

Current assets:
Cash and cash equivalents $ 2,887 $ 2,678
Accounts receivable, net 751 724
Inventory 608 575
Other current assets 151 192
Total current assets 4,397 4,169

Property, plant and equipment, net 792 757
Goodwill 2,633 2,607
Other intangible assets, net 341 361
Long-term investments 140 138
Other assets 395 394
Total assets $ 8,698 $ 8,426

LIABILITIES AND EQUITY

Current liabilities:
Accounts payable $ 292 $ 305
Employee compensation and benefits 221 276
Deferred revenue 321 291
Short-term debt 345 210
Other accrued liabilities 182 181
Total current liabilities 1,361 1,263

Long-term debt 1,800 1,801
Retirement and post-retirement benefits 241 234
Other long-term liabilities 770 293
Total liabilities 4,172 3,591

Total Equity:
Stockholders’ equity:
Preferred stock; $0.01 par value; 125 million shares authorized; none issued and outstanding

— —
Common stock; $0.01 par value, 2 billion shares authorized; 323 million shares at January 31, 2018 and 322 million shares at October 31, 2017, issued

3 3
Treasury stock at cost; 37 thousand shares at January 31, 2018 and zero shares at October 31, 2017

(3 ) —
Additional paid-in-capital 5,320 5,300
Accumulated deficit (529 ) (126 )
Accumulated other comprehensive loss (269 ) (346 )
Total stockholders’ equity 4,522 4,831
Non-controlling interest 4 4
Total equity 4,526 4,835
Total liabilities and equity $ 8,698 $ 8,426

The preliminary balance sheet is estimated based on our current information.

Page 3

AGILENT TECHNOLOGIES, INC.
CONDENSED CONSOLIDATED STATEMENT OF CASH FLOWS
(In millions)
(Unaudited)
PRELIMINARY

Three Months Ended
January 31, January 31,
2018 2017
Cash flows from operating activities:
Net income (loss) $ (320 ) $ 168

Adjustments to reconcile net income (loss) to net cash provided by (used in) operating activities:
Depreciation and amortization 51 55
Share-based compensation 31 20
Excess and obsolete inventory related charges 5 7
Other non-cash expenses, net 1 2
Changes in assets and liabilities:
Accounts receivable, net (5 ) (31 )
Inventory (34 ) (26 )
Accounts payable (3 ) 9
Employee compensation and benefits (62 ) (43 )
Change in assets and liabilities due to Tax Reform 533 —
Other assets and liabilities 18 (45 )
Net cash provided by operating activities (a) 215 116

Cash flows from investing activities:
Investments in property, plant and equipment (60 ) (32 )
Payment to acquire cost method investments (1 ) —
Proceeds from divestitures — 1
Acquisition of businesses and intangible assets, net of cash acquired (6 ) (70 )
Net cash used in investing activities (67 ) (101 )

Cash flows from financing activities:
Issuance of common stock under employee stock plans 25 18
Payment of taxes related to net share settlement of equity awards (28 ) (12 )
Payment of dividends (48 ) (42 )
Proceeds from debt and revolving credit facility 274 131
Repayment of debt and revolving credit facility (139 ) (42 )
Treasury stock repurchases (47 ) (111 )
Net cash provided by (used in) financing activities 37 (58 )

Effect of exchange rate movements 24 (5 )

Net increase (decrease) in cash and cash equivalents 209 (48 )

Cash and cash equivalents at beginning of period 2,678 2,289

Cash and cash equivalents at end of period $ 2,887 $ 2,241

(a) Cash payments included in operating activities:
Income tax payments, net $ 32 $ 27
Interest payments $ 29 $ 29

The preliminary cash flow is estimated based on our current information.

Page 4

AGILENT TECHNOLOGIES, INC.
NON-GAAP NET INCOME AND DILUTED EPS RECONCILIATIONS
(In millions, except per share amounts)
(Unaudited)
PRELIMINARY

Three Months Ended
January 31,
2018
Diluted
EPS

2017
Diluted
EPS

GAAP net (loss) income $ (320 ) $ (0.99 ) (b) $ 168 $ 0.52
Non-GAAP adjustments:
Intangible amortization 25 0.08 31 0.10
Transformational initiatives 5 0.02 2 0.01
Acquisition and integration costs 3 0.01 16 0.05
Pension settlement gain (5 ) (0.02 ) (32 ) (0.11 )
NASD site costs 2 0.01 — —
Special compliance costs 1 — — —
Other — — 2 0.01
Adjustment for Tax Reform

533 1.63 — —
Adjustment for taxes (a) (28 ) (0.08 ) (15 ) (0.05 )
Non-GAAP net income $ 216 $ 0.66 (c) $ 172 $ 0.53

(a) The adjustment for taxes excludes tax benefits that management believes are not directly related to on-going operations and which are either isolated or cannot be expected to occur again with any regularity or predictability. For the three months ended January 31, 2018, management uses a non-GAAP effective tax rate of 18.0%. In the same periods last year, management used a non-GAAP effective tax rate of 19.0%.

(b) GAAP diluted net loss per share was computed using 323 million weighted average diluted shares which excludes from consideration the anti-dilutive effects of all potential common shares outstanding.

(c) Non-GAAP diluted net income per share was computed using 327 million weighted average diluted shares which includes the dilutive effects of potential common shares outstanding.

We provide non-GAAP net income and non-GAAP net income per share amounts in order to provide meaningful supplemental information regarding our operational performance and our prospects for the future. These supplemental measures exclude, among other things, charges related to amortization of intangibles, transformational initiatives, acquisition and integration costs, pension settlement gain, NASD site costs, special compliance costs, and adjustment for Tax Reform.

Transformational initiatives include expenses associated with targeted cost reduction activities such as manufacturing transfers, small site consolidations, legal entity and other business reorganizations, insourcing or outsourcing of activities. Such costs may include move and relocation costs, one-time termination benefits and other one-time reorganization costs. Included in this category are also expenses associated with the post-separation resizing of the IT infrastructure and streamlining of IT system as well as company programs to transform our product lifecycle management (PLM) system and financial systems.

Acquisition and Integration costs include all incremental expenses incurred to effect a business combination. Such acquisition costs may include advisory, legal, accounting, valuation, and other professional or consulting fees. Such integration costs may include expenses directly related to integration of business and facility operations, the transfer of assets and intellectual property, information technology systems and infrastructure and other employee-related costs.

Pension settlement gain resulted from transfer of the substitutional portion of our Japanese pension plan to the government.

NASD site costs include all the costs related to the expansion of our manufacturing of nucleic acid active pharmaceutical ingredients incurred prior to the commencement of commercial manufacturing.

Special compliance costs include costs associated with transforming our processes to implement new regulations such as the EU’s General Data Protection Regulation (GDPR), revenue recognition and certain tax reporting requirements.

Other includes certain legal costs and settlements in addition to other miscellaneous adjustments.

Adjustment for Tax Reform primarily consists of an estimated provision of $480 million for U.S. transition tax and correlative items on deemed repatriated earnings of non-U.S. subsidiaries and an estimated provision of $53 million associated with the decrease in the U.S. corporate tax rate from 35% to 21% and its impact on our U.S. deferred tax assets and liabilities. The taxes payable associated with the transition tax, net of tax attributes, on deemed repatriation of foreign earnings is approximately $440 million, payable over 8 years. The final impact of Tax Reform may differ materially from these estimates, due to, among other things, changes in interpretations, analysis and assumptions made, additional guidance that may be issued, and actions that we may undertake.

Our management uses non-GAAP measures to evaluate the performance of our core businesses, to estimate future core performance and to compensate employees. Since management finds this measure to be useful, we believe that our investors benefit from seeing our results "through the eyes" of management in addition to seeing our GAAP results. This information facilitates our management’s internal comparisons to our historical operating results as well as to the operating results of our competitors.

Our management recognizes that items such as amortization of intangibles can have a material impact on our cash flows and/or our net income. Our GAAP financial statements including our statement of cash flows portray those effects. Although we believe it is useful for investors to see core performance free of special items, investors should understand that the excluded items are actual expenses that may impact the cash available to us for other uses. To gain a complete picture of all effects on the company’s profit and loss from any and all events, management does (and investors should) rely upon the GAAP income statement. The non-GAAP numbers focus instead upon the core business of the company, which is only a subset, albeit a critical one, of the company’s performance.

Readers are reminded that non-GAAP numbers are merely a supplement to, and not a replacement for, GAAP financial measures. They should be read in conjunction with the GAAP financial measures. It should be noted as well that our non-GAAP information may be different from the non-GAAP information provided by other companies.

The preliminary non-GAAP net income and diluted EPS reconciliation is estimated based on our current information.

Page 5

AGILENT TECHNOLOGIES, INC.
SEGMENT INFORMATION
(In millions, except where noted)
(Unaudited)

PRELIMINARY

Life Sciences and Applied Markets Group
Q1’18 Q1’17
Revenue $ 618 $ 540
Gross Margin, % 61.8 % 59.6 %
Income from Operations $ 159 $ 126
Operating margin, % 25.8 % 23.4 %

Diagnostics and Genomics Group
Q1’18 Q1’17
Revenue $ 185 $ 164
Gross Margin, % 54.4 % 54.8 %
Income from Operations $ 22 $ 23
Operating margin, % 11.7 % 14.3 %

Agilent CrossLab Group
Q1’18 Q1’17
Revenue $ 408 $ 363
Gross Margin, % 50.6 % 48.5 %
Income from Operations $ 88 $ 74
Operating margin, % 21.6 % 20.3 %

Income from operations reflect the results of our reportable segments under Agilent’s management reporting system which are not necessarily in conformity with GAAP financial measures. Income from operations of our reporting segments exclude, among other things, charges related to amortization of intangibles, business exit and divestiture costs, transformational initiatives, acquisition and integration costs, pension settlement gain, NASD site costs, and special compliance costs.

Readers are reminded that non-GAAP numbers are merely a supplement to, and not a replacement for, GAAP financial measures. They should be read in conjunction with the GAAP financial measures. It should be noted as well that our non-GAAP information may be different from the non-GAAP information provided by other companies.

The preliminary segment information is estimated based on our current information.

AGILENT TECHNOLOGIES, INC.
RECONCILIATIONS OF REVENUE BY SEGMENT EXCLUDING
ACQUISITIONS, DIVESTITURES AND THE IMPACT OF CURRENCY ADJUSTMENTS (CORE)
(in millions)
(Unaudited)
PRELIMINARY

Year-over-Year

GAAP
Year-over-Year
GAAP Revenue by Segment

Q1’18 Q1’17 % Change

Life Sciences and Applied Markets Group $ 618 $ 540 14 %

Diagnostics and Genomics Group 185 164 13 %

Agilent CrossLab Group 408 363 12 %

Agilent $ 1,211 $ 1,067 14 %

Non-GAAP
(excluding Acquisitions & Divestitures)

Currency
Adjustments

Currency
Adjustments

Currency-Adjusted (a)
Year-over-Year Year-over-Year
Non GAAP Revenue by Segment

Q1’18 Q1’17 % Change Q1’18 Q1’17 Q1’18 Q1’17 % Change

Life Sciences and Applied Markets Group $ 616 $ 539 14 % $ (3 ) $ (17 ) $ 619 $ 556 11 %

Diagnostics and Genomics Group 182 163 12 % (1 ) (7 ) 183 170 8 %

Agilent CrossLab Group 408 363 12 % (3 ) (15 ) 411 378 9 %

Agilent (Core) $ 1,206 $ 1,065 13 % $ (7 ) $ (39 ) $ 1,213 $ 1,104 10 %

(a) We compare the year-over-year change in revenue excluding the effect of recent acquisitions and divestitures and foreign currency rate fluctuations to assess the performance of our underlying business. To determine the impact of currency fluctuations, current and prior year period results for entities reporting in currencies other than United States dollars are converted into United States dollars at the actual exchange rate in effect during the last month of the current period.

The preliminary reconciliation of GAAP revenue adjusted for recent acquisitions and divestitures and impact of currency is estimated based on our current information.

On February 14, 2018 NanOlogy, a clinical-stage pharmaceutical development company and affiliate of DFB Pharmaceuticals, reported the first patient in a Phase 1/2 clinical trial of a submicron particle paclitaxel topical anhydrous ointment for the treatment of cutaneous metastases (Press release, NanOlogy, FEB 14, 2018, View Source [SID1234523975]). The open label dose escalating trial of three different strengths of the product will be followed by dose confirmation to evaluate safety. NanOlogy has licensed the topical formulation for use in oncology from DFB Soria, which is owned and operated by DFB.

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Because no other topical treatment options exist for many patients suffering from cutaneous metastases, the company says it will seek to gain FDA fast track status if the results of this trial are successful.

Separately, Soria has completed enrollment in a Phase 2 actinic keratosis clinical trial that is evaluating different strengths of the topical formulation for safety and efficacy. Results from the randomized, double-blind, placebo-controlled trial are expected in April; preliminary blinded observations are promising.

On February 14, 2018 Heat Biologics, Inc. ("Heat") (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported that its abstract highlighting interim results of its Phase 2 study on HS-110 (viagenpumatucel-L) and nivolumab (Opdivo) combination therapy in the treatment of advanced non-small cell lung cancer (NSCLC), has been accepted as a scientific poster presentation during the 2018 Keystone Symposia Conference XI: Immunological Memory: Innate, Adaptive and Beyond, February 25 – March 1, 2018 in Austin (Press release, Heat Biologics, FEB 14, 2018, View Source [SID1234523971]).

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The poster presentation details are as follows:

Title: "Correlation of Adaptive Immune Response with Clinical Response after Treatment with Viagenpumatucel-L and Nivolumab in Previously Treated Non-Small Cell Lung Cancer (NSCLC) Patients"
Session Date/Time: February 27, 2018, 7:30 p.m. – 10 p.m. CT
Authors: Lori McDermott, MSc; Vamsidhar Velcheti, MD; Roger B. Cohen, MD; Jeff Hutchins, PhD; Daniel Morgensztern, MD
In addition, Heat will be hosting an analyst and investor event in New York City on February 28, 2018, at 8 a.m. ET, to discuss these results. Event details and webcast information to be provided prior to the event.

On February 14, 2018 Athenex, Inc. (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported early completion of patient enrollment for both Phase III clinical studies of KX2-391 Ointment for actinic keratosis indications months ahead of schedule (Press release, Athenex, FEB 14, 2018, View Source;p=RssLanding&cat=news&id=2332390 [SID1234523964]).

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Actinic keratosis is a common skin condition that is induced through ultra-violet light damage, resulting in patches of thick, scaly, or crusty skin. Left untreated, the lesions have risk of progression to squamous cell carcinoma and consequently treatment by a dermatologist is recommended. Actinic keratosis is the most common pre-cancerous condition in dermatology and it affects more than 55 million Americans. Actinic keratosis constitutes between 14-29% of dermatologist visits in the USA.1

KX2-391, also known as KX-01, is a dual Src kinase and tubulin polymerization inhibitor and a first-in-class topical treatment of actinic keratosis. Phase I and Phase II clinical studies showed excellent efficacy and safety results. After the FDA end of Phase II meeting, two randomized double-blind controlled Phase III trials totaling 600 patients were initiated in September 2017 in the United States and completed patient recruitment in February 2018.

Dr. Rudolf Kwan, Athenex’s Chief Medical Officer, commented, "KX2-391 ointment, given its excellent clinical efficacy and safety profile compared to existing medical therapy, has the potential to change the paradigm of topical therapy for actinic keratosis. We are delighted to see that our investigators and patients are also seeing the potential of this new treatment as indicated by the rapid completion of patient enrollment in around four months which is extremely fast, and three months ahead of our original schedule. Such rapid patient recruitment rates in clinical trials underscores the excitement of the clinical and scientific communities."

Dr. Johnson Lau, Athenex’s Chief Executive Officer and Chairman of the Board, stated, "This excellent milestone highlights the quality of our clinical team members and operation. Our previous commitment to build an internal clinical operation will also ensure that the clinical trial monitoring and management, database management, and biostatistics will not be dependent on outside vendors. As such, we are confident that all aspects of treatment, follow up, monitoring, and database will be completed on time. We are now expecting topline data to be available in third quarter of 2018. We also look forward to presenting our Phase II data to the public in the upcoming American Academy of Dermatology meeting on February 17, 2018."

As previously announced on December 11, 2017, Athenex and Almirall, a leading skin-health focused global pharmaceutical company and one of the leaders in the field of actinic keratosis treatment, entered into a License Agreement in which Athenex granted Almirall an exclusive license under the Athenex Intellectual Property to research, develop and commercialize KX2-391 in the United States of America and European countries, including Russia. Athenex will receive an upfront fee and near-term payments of up to USD $55 million, and additional indications milestones payment and a royalty payment starting at 15% based on annual net sales, with incremental increases in royalty rates with increased sales. Athenex retains certain co-promotion rights in the USA and retains the rights for other parts of the world including Canada, Central and South America, Japan, Asia and China, Australia and New Zealand, and Africa including South Africa. Almirall will employ its expertise to support the development in Europe and also to commercialize the product in the defined territories. Milestones were established to encourage the joint effort of Athenex and Almirall to develop additional indications and additional formulations.

Peter Guenter, Chief Executive Officer at Almirall, said, "We are impressed by the Athenex team in their execution of drug development. KX2-391, given its efficacy and very good safety profile compared to existing medical therapies, has the potential to change the standard of care for actinic keratosis, as well as expand the market since many patients remain undiagnosed or untreated. Almirall’s experience in Europe, currently as leaders in actinic keratosis, and our presence in the United States will help to develop and commercialize this product. We are now expecting top line Phase III data to be available in the third quarter of 2018. We also look forward to the presentation of the Phase II data to the public in the upcoming American Academy of Dermatology meeting on February 17, 2018."

References
1. E. Stockfleth et al. Physician perceptions and experience of current treatment in actinic keratosis. JEADV 2015, 29, 298–306

On February 14, 2018 Amgen (NASDAQ:AMGN) reported that the Oncologic Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) will review data supporting the BLINCYTO (blinatumomab) supplemental Biologics License Application (sBLA) for the treatment of patients with minimal residual disease (MRD)-positive B-cell precursor acute lymphoblastic leukemia (ALL) at a meeting on March 7, 2018 (Press release, Amgen, FEB 14, 2018, View Source;p=RssLanding&cat=news&id=2332494 [SID1234523963]).

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MRD refers to the presence of a small amount of detectible cancer cells that remain in the patient after treatment.

"After achieving remission, the presence of MRD is the strongest prognostic factor for relapse in acute lymphoblastic leukemia. However, today up to half of patients remain MRD-positive after induction treatments and receive limited clinical benefit from treatments like chemotherapy or stem cell transplantation as a result of failure to identify and treat this residual disease," said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "Currently there are no approved therapies for patients with MRD-positive ALL, representing a significant unmet need. This sBLA for BLINCYTO is the first application to ever be submitted for an MRD positive indication, and we look forward to discussing the supporting data with members of the Committee."

The Committee will review results from clinical studies in support of this potential new indication, including results from the Phase 2 BLAST study evaluating patients with B-cell precursor ALL and persistent or recurrent MRD after at least three cycles of intensive chemotherapy.

BLINCYTO is the first-and-only approved bispecific CD19-directed CD3 T cell engager (BiTE) immunotherapy. It is also the first bispecific antibody construct from Amgen’s BiTE platform, which helps the body’s immune system target cancer cells and represents an entirely new area of oncology research.

The sBLA for BLINCYTO was accepted by the FDA for priority review, and a Prescription Drug User Fee Act (PDUFA) target action date of March 29, 2018 has been set.

About BLINCYTO (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. BLINCYTO was granted breakthrough therapy and priority review designations by the FDA in 2014 for the treatment of relapsed or refractory B-cell precursor ALL in adults and children, and is now approved in the U.S. for this indication.

In November 2015, BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. Additional regulatory applications for BLINCYTO are underway and have been submitted to health authorities worldwide.

About the BLAST Study
The BLAST study is the largest prospective trial in patients with MRD-positive ALL. It is an open-label, multicenter, confirmatory single-arm, Phase 2 study evaluating the efficacy, safety and tolerability of BLINCYTO in adult patients with MRD-positive B-cell precursor ALL in complete hematologic remission after three or more cycles of intensive chemotherapy treatments and a presence of MRD. Patients received continuous IV infusion of 15 μg/m2/d for four weeks, followed by two weeks off. Patients received up to four cycles of treatment, or could undergo a hematopoietic stem cell transplantation (HSCT) at any time after the first cycle, if eligible. The primary endpoint was the rate of complete MRD response within the first treatment cycle. The key secondary endpoint was relapse-free survival at 18 months. Additional secondary endpoints include incidence and severity of adverse events, overall survival (OS), time to hematological remission and duration of complete MRD response. Results from the BLAST study were presented at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper) in 2015.

About ALL and MRD
ALL is a rare and rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children.1,2 Many adult patients with ALL relapse, often within one year of their diagnosis, from which the median survival is only 4 to 8 months.3 Poor outcomes have been observed in patients who relapse after achieving a complete response but have persistent MRD, with 5-year OS rates as high as 75 percent for patients that achieve MRD-negative status, compared with 33 percent among patients that remain MRD-positive.4 In pediatric patients, MRD-positive status after treatment is associated with a 15-times higher risk of relapse compared with those with undetectable residual disease.5

About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to bridge T cells to tumor cells, using the patient’s own immune system to eradicate their cancer. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

BLINCYTO U.S. Product Safety Information

Indication and Important Safety Information, including Boxed WARNINGS, for BLINCYTO (blinatumomab) for injection, for intravenous use

INDICATION

BLINCYTO is indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications
BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO as outlined in the Prescribing Information (PI).
Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.
Tumor Lysis Syndrome (TLS): TLS, which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Risk of Serious Adverse Reactions in Pediatric Patients due to Benzyl Alcohol Preservative: Serious and fatal adverse reactions including "gasping syndrome," which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol-preserved drugs including BLINCYTO (with preservative). When prescribing BLINCYTO (with preservative) for pediatric patients, consider combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO solution for infusion with preservative contain benzyl alcohol and are not recommended for use in any patients weighing < 22 kg.
Adverse Reactions

The most common adverse reactions in Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL (TOWER Study) (≥ 20%) in the BLINCYTO arm were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia.
Adverse reactions that were observed more frequently (≥ 10%) in the pediatric population compared to the adult population were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).
Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO.

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