On January 8, 2018 PTC Therapeutics, Inc. (NASDAQ: PTCT) today provided a corporate update, which will be detailed as part of the company’s presentation at the 36th Annual J.P. Morgan Healthcare Conference on Wednesday, January 10th at 2:30 pm PT (Press release, PTC Therapeutics, JAN 8, 2018, View Source [SID1234525048]). Stuart W. Peltz, Ph.D., PTC’s Chief Executive Officer, will highlight the company’s 20-year commitment to bring best-in-class therapies to patients affected by rare disorders, the company’s 2018 strategic priorities, preliminary 2017 financial results and 2018 financial guidance. The presentation will be webcast live on the Events and Presentations page under the investors section of PTC Therapeutics’ website at www.ptcbio.com.

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Preliminary 2017 Unaudited Financial Results

PTC expects to report Translarna (ataluren) net product revenue for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) of approximately $145 million for 2017, an increase of 78% over the prior year. This strong performance, which achieves the upper end of the company’s guidance for the full year 2017, reflects the rapid uptake and the high unmet need in this community. PTC continues to be pleased by the greater than 90% compliance rate of patients on therapy.
PTC expects to report EMFLAZA (deflazacort) net product revenue for the treatment of Duchenne muscular dystrophy (DMD) of approximately $29 million for 2017, 16% higher than the upper end of the company’s guidance for the full year 2017.
PTC expects to report year-end cash and cash equivalents of approximately $191 million.
2018 Guidance

PTC anticipates full-year net product revenues to be between $260 and $295 million. PTC anticipates Translarna net product revenue for the full year 2018 to be between $170 and $185 million. PTC projects a 5-year (12/31/17-12/31/22) compound annual growth rate of 15% representing continued strong growth year-over-year of Translarna in existing countries and in expansion into new territories. PTC anticipates EMFLAZA net product revenue for the full year 2018 to be between $90 and $110 million.
PTC anticipates GAAP R&D and SG&A expense for the full year 2018 to be between $280 and $290 million.
PTC anticipates Non-GAAP R&D and SG&A expense for the full year 2018 to be between $250 and $260 million, excluding estimated non-cash, stock-based compensation expense of approximately $30 million.
Corporate Highlights

Successful commercial launch of EMFLAZA for the treatment of Duchenne muscular dystrophy. PTC has established programs with the goal of ensuring that all eligible patients will have access to EMFLAZA regardless of financial or insurance status. PTC is committed to improving the standard of care for all Duchenne patients.
Continued strong growth of Translarna product revenue outside US in nonsense mutation Duchenne patients. PTC plans continued growth in Translarna ex-US business by increasing penetration in current countries, expanding into new geographies, and pursuing opportunities for label expansion.
As part of the US FDA appeal process for the Translarna NDA, a meeting is scheduled at the request of the Office of New Drugs and PTC plans to provide an update in the first quarter.
The SUNFISH trial in the spinal muscular atrophy (SMA) program transitioned to the pivotal portion in 2017 with FIREFISH anticipated to transition to the pivotal stage in the coming months. Survival data from FIREFISH study in Type 1 SMA patients will be presented at the upcoming SMA Europe International Scientific Congress in Krakow. The SMA program is a joint collaboration with Roche and the SMA Foundation.
PTC continues to expand its innovative pipeline with internal research programs in the company’s next generation readthrough platform, alternative splicing platform and key developments in oncology with two DHODH inhibitor compounds.
PTC to host an analyst day in the upcoming months to provide an update on its growing pipeline.
Non-GAAP Financial Measures:
In this press release, the unaudited financial results and financial guidance of PTC are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, non-GAAP financial measures exclude non-cash, stock-based compensation expense. This non-GAAP financial measure is provided as a complement to results reported in GAAP because management uses this non-GAAP financial measure when assessing and identifying operational trends. In management’s opinion, this non-GAAP financial measure is useful to investors and other users of PTC’s financial statements by providing greater transparency into the operating performance at PTC and the company’s future outlook. Quantitative reconciliations of these non-GAAP financial measures to GAAP financial measures are included in the table below.

PTC Therapeutics, Inc.

Reconciliation of Projected GAAP to Non-GAAP Full Year 2018 R&D and SG&A Expense (In thousands)

Low End of Range

High End of Range

Projected GAAP R&D and SG&A expense

280,000

290,000

Less: projected non-cash stock-based compensation expense

30,000

30,000

Total projected non-GAAP R&D and SG&A expense

$

250,000

$

260,000

Preliminary 2017 Financial Results:
PTC is currently in the process of finalizing its financial results for the 2017 fiscal year. The above information is based on preliminary unaudited information and management estimates for the full year 2017, subject to the completion of PTC’s financial closing procedures. In addition, the above information is subject to revision as PTC completes its financial closing procedures for fiscal 2017.

On January 8, 2018 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported key 2018 priorities in conjunction with its presentation at the 36th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Agios Pharmaceuticals, JAN 8, 2018, View Source [SID1234522985]). The presentation will outline how Agios’ clinical and research programs have the potential to provide meaningful benefit to a large number of patients. The company will webcast its presentation today at 9:30 a.m. PT (12:30 p.m. ET) at investor.agios.com.

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"We presented a significant amount of clinical data across our portfolio in 2017, including data supporting the approval of our first internally discovered medicine, which proves that our research and development engine has the ability to deliver important precision medicines from a discovery in the lab to patients as an approved drug," said David Schenkein, M.D., chief executive officer at Agios. "We are very pleased with the early launch performance of IDHIFA and expect to repeat this success with ivosidenib upon FDA approval in 2018, while continuing our label expansion opportunities for frontline AML and solid tumors and bringing our next drug candidate targeting genetically defined cancers, AG-270, into the clinic. In rare genetic diseases, AG-348 has demonstrated proof of concept in pyruvate kinase deficiency and in addition to beginning pivotal trials in this disease, we are exploring the utility of PK activation in other anemias, starting with a Phase 2 study in thalassemia."

The company plans to achieve the following key milestones in 2018:

Cancer:

Potential FDA approval and commercialization of ivosidenib for relapsed/refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) mutation in the United States in the second half of 2018.

Plan to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for ivosidenib for IDH1m R/R AML in the fourth quarter of 2018.

Support with Celgene an intergroup sponsored, global, registration-enabling Phase 3 trial combining ivosidenib or enasidenib and standard induction (7+3) and consolidation chemotherapy with a primary endpoint of event free survival (EFS) in frontline AML patients with an IDH1 or IDH2 mutation in the fourth quarter of 2018.

Initiate a perioperative ‘window’ trial with ivosidenib and AG-881 in low-grade glioma to further investigate their effects on brain tumor tissue in the first half of 2018.

Initiate a Phase 1 dose-escalation trial for AG-270, a first-in-class methionine adenosyltransferase 2a (MAT2A) inhibitor, in methylthioadenosine phosphorylase (MTAP)-deleted tumors in the first quarter of 2018.
Rare Genetic Diseases:

Initiate two global pivotal trials for AG-348 in PK deficiency:

ACTIVATE-T: A single arm trial of approximately 20 regularly transfused patients is expected to initiate in the first quarter of 2018.

ACTIVATE: A 1:1 randomized, placebo-controlled trial of 80 patients who do not receive regular transfusions is expected to initiate in the second quarter of 2018.

Initiate a global registry for adult and pediatric patients with PK deficiency (PEAK) in the first quarter of 2018 to increase understanding of the long-term disease burden of this chronic anemia.

Initiate a Phase 2 proof of concept trial of AG-348 in thalassemia in the fourth quarter of 2018.
Research:

Submit an investigational new drug (IND) application for our latest development candidate, an inhibitor of the metabolic enzyme dihydroorotate dehydrogenase (DHODH) for the treatment of hematologic malignancies in the fourth quarter of 2018.
The company plans to host an analyst day in the first half of 2018 to review Agios’ commercial readiness and broad clinical development programs and highlight the depth of the research portfolio across oncology, rare genetic disease and metabolic immuno-oncology.

The company also highlighted key 2017 achievements:

Collaborated with Celgene to achieve the U.S. Food and Drug Administration (FDA) full approval and subsequent launch of IDHIFA (enasidenib) for the treatment of adult patients with R/R AML with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA approved diagnostic test.

Submitted a new drug application (NDA) to the FDA for ivosidenib for the treatment of patients with R/R AML with an IDH1 mutation.

Initiated a global, registration-enabling Phase 3 study (AGILE) combining ivosidenib and VIDAZA in newly diagnosed AML patients with an IDH1 mutation ineligible for intensive chemotherapy.

Finalized two global, pivotal trial designs evaluating AG-348 in adults with pyruvate kinase (PK) deficiency.

Achieved FDA clearance of an IND application for AG-270, a MAT2A inhibitor, targeting MTAP-deleted tumors.
2017 Year-End Cash and Updated Guidance

Agios ended 2017 with approximately $568 million of cash, cash equivalents and marketable securities. Based on its expanded clinical and research programs announced today, the company now expects that its existing cash, cash equivalents and marketable securities as of December 31, 2017, together with anticipated interest income, anticipated expense reimbursements, and royalty payments under our collaboration agreements, but excluding any additional program-specific milestone payments, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through the end of third quarter of 2019.

Presentation at 36th Annual J.P. Morgan Healthcare Conference

Agios will webcast its corporate presentation from the 36th Annual J.P. Morgan Healthcare Conference in San Francisco on Monday, January 8, 2018 at 9:30 a.m. PT (12:30 p.m. ET). A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.

On January 8, 2018 AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) reported a business update, including preliminary unaudited fourth quarter and full year 2017 financial results and 2018 financial guidance (Press release, AMAG Pharmaceuticals, JAN 8, 2018, View Source [SID1234522984]). The company will present further details at the 36th Annual J.P. Morgan Healthcare Conference in San Francisco on Tuesday, January 9, 2018 at 10:00 a.m. PT (1:00 p.m. ET). A live audio webcast of the presentation and following breakout session will be accessible through the Investors section of AMAG’s website at www.amagpharma.com.

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William Heiden, AMAG’s president and chief executive officer, said, "Over the last few years we have transformed AMAG from a one product company into a company with five marketed products and two additional products in development. Today we are reporting double-digit revenue growth in 2017 of more than $600 million, along with strong bottom-line cash generation. Throughout the year, we also achieved many important goals that will be key to our long-term success, including the establishment of our new 200-person women’s health commercial team, the launch of Intrarosa (prasterone), a novel women’s health product, and the filing of supplemental new drug applications to extend our Makena and Feraheme brands."

"Our flexible operating plan supports the 2018 top-line revenue and adjusted EBITDA guidance ranges provided today, which incorporate the opportunities and key risks across our product portfolio. 2018 promises to be an exciting year for AMAG with many key value drivers ahead of us, including potential FDA approvals of the Makena subcutaneous auto-injector and the Feraheme broad label, as well as building on the successful launch of Intrarosa, with approximately 20,000 total prescriptions already written by more than 4,200 healthcare providers since our July 2017 launch," Mr. Heiden concluded.

Preliminary Fourth Quarter and Full Year 2017 Financial Results (unaudited)
Fourth Quarter 2017
AMAG expects total GAAP revenue for the fourth quarter of 2017 to be between $155 million and $162 million, representing approximately 5% growth over the same period in 2016. This includes Makena (hydroxyprogesterone caproate injection) net product sales of between $97 million and $102 million, Feraheme (ferumoxytol) injection and MuGard net product sales of between $26 million and $28 million, Intrarosa (launched in July 2017) net product sales of approximately $2 million, and Cord Blood Registry (CBR) service revenue of approximately $30 million.

AMAG expects total fourth quarter 2017 total non-GAAP revenue to be between $156 million and $163 million, which reflects a $1.4 million purchase accounting adjustment related to CBR deferred revenue.

For the fourth quarter of 2017, AMAG expects an operating loss of between $6 million and $16 million and adjusted EBITDA of between $58 million and $68 million.1

Full Year 2017
AMAG expects 2017 total GAAP revenue to be between $607 million and $614 million, representing 15% growth over 2016. This includes Makena net product sales of between $385 million and $390 million, Feraheme and MuGard net product sales of between $106 million and $108 million, Intrarosa net product sales of approximately $2 million, and CBR service revenue of approximately $114 million.

AMAG expects 2017 total non-GAAP revenue to be between $613 million and $620 million, which reflects a $5.5 million purchase accounting adjustment related to CBR deferred revenue.

For the full year of 2017, AMAG expects an operating loss of between $292 million and $302 million (due primarily to a third quarter non-cash accounting charge) and adjusted EBITDA of between $220 million and $230 million, the higher end of the guidance range.

In 2017, AMAG reduced total debt by approximately 20%, extended average debt maturities, and repurchased and retired approximately 1.4 million shares in the fourth quarter at an average price of $14.27 per share.

The company ended 2017 with approximately $329 million in cash and investments and total debt (principal amount outstanding) of approximately $815 million. In late February 2018, the company expects to report final financial results for the fourth quarter and audited results for full year of 2017.

2018 Financial Guidance
The company is providing the following financial guidance for 2018. This guidance encompasses management’s current assumptions about the potential impact of multiple opportunities and risks across AMAG’s product portfolio, including various potential outcomes of the pending FDA submissions for the Makena subcutaneous auto-injector and the Feraheme label expansion, as well as the entrance of generics to compete with the Makena intramuscular formulation in 2018.

$ in millions 2018 GAAP Guidance 2018 Non-GAAP Guidance
Total revenue $500 – $560 $500 – $560
Operating loss ($147) – ($117) N/A
Adjusted EBITDA N/A $100 – $130

2018 Key Dates and Priorities
•
February 2, 2018: PDUFA date for the expansion of the Feraheme label beyond the current chronic kidney disease (CKD) indication to include all eligible adult patients with iron deficiency anemia (IDA); prepare for first quarter 2018 potential approval and subsequent launch;
•
February 3, 2018: loss of Makena orphan drug exclusivity – While the company is currently ready with a partner to launch its own authorized generic to the intramuscular formulation (IM) as early as February, the company believes that a generic competitor may not enter the market until later in 2018;
•
February 14, 2018: PDUFA date for Makena subcutaneous auto-injector; prepare for first quarter 2018 potential approval and subsequent launch;
•
First quarter 2018: submit bremelanotide new drug application to FDA;
•
Continue to broaden awareness and drive prescriptions of Intrarosa
‒
Increase formulary coverage (65% unrestricted commercial lives covered anticipated by month end);
‒
Increase the number of healthcare professional prescribers (from ~4,200 achieved in 2017);
‒
Increase the number of total prescriptions written (from ~20,000 in 2017);
‒
Increase market share (from year-end weekly NRx share of 2.6%);
‒
Launch digital-to-direct consumer campaign in first half of 2018;
•
Expand CBR first time enrollments; and
•
Further diversify product portfolio through disciplined business development.

"In 2017, we delivered strong top-line and adjusted EBITDA results while investing aggressively in the products that will drive our future growth. We also improved our liability profile so that our balance sheet is better aligned with our evolving business strategy. Finally, we have managed and will continue to manage our expenses carefully to maintain operational flexibility," said Ted Myles, AMAG’s chief financial officer. "​We are guiding to continued positive adjusted EBITDA generation​ in 2018, and with $329 million of cash on hand as of December 31, 2017, ​we are in a strong position to continue to invest in our current products, while remaining active in the search for additional asset acquisitions or licensing transactions that provide durable, long-term growth."

Webcast Information
A live audio webcast of the company’s presentation and the following breakout session, along with the accompanying slide presentation at the 36th Annual J.P. Morgan Healthcare Conference, will be accessible through the Investors section of the company’s website at www.amagpharma.com on January 9, 2018 at 10:00 a.m. P.T. (1:00 p.m. E.T.). Following the conference, the webcast will be archived on the company’s website until February 9, 2018.

Use of Non-GAAP Financial Measures
AMAG has presented certain non-GAAP financial measures, including non-GAAP revenue and non-GAAP adjusted EBITDA (earnings before income taxes, depreciation and amortization). These non-GAAP financial measures exclude certain amounts, revenue, expenses or income, from the corresponding financial measures determined in accordance with accounting principles generally accepted in the U.S. (GAAP). Management believes this non-GAAP information is useful for investors, taken in conjunction with AMAG’s GAAP financial statements, because it provides greater transparency regarding AMAG’s operating performance. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of AMAG’s operating results as reported under GAAP, not as a substitute for GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures are included in the tables at the conclusion of this press release.

On January 8, 2018 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that it has achieved a milestone for the first Investigational New Drug (IND) application to the U.S. Food and Drug Administration by Bristol-Myers Squibb Company (BMS) (NYSE:BMY) for a therapeutic candidate under the immune checkpoint pathway discovery collaboration between the companies (Press release, Five Prime Therapeutics, JAN 8, 2018, View Source [SID1234522980]). The first clinical candidate from the collaboration is a fully-human monoclonal antibody targeting TIM-3 (T-cell immunoglobulin and mucin domain-3), an immune checkpoint receptor that is known to limit the duration and magnitude of T-cell responses1. This first IND application triggers a $5 million milestone payment to Five Prime.

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"We are excited to see Bristol-Myers Squibb file an IND for the first innovative immuno-oncology therapeutic candidate to advance to the clinic under our immuno-oncology discovery collaboration," said Bryan Irving, Ph.D. Senior Vice President, Research at Five Prime. "TIM-3 is thought to inhibit the response of T cells and other crucial immune cell types, so blocking this checkpoint pathway could be a promising component of an immuno-oncology strategy to treat a variety of tumors."

Under the terms of the discovery collaboration agreement, BMS has exclusive, worldwide rights to develop and commercialize products directed toward certain protein targets in three checkpoint pathways. Five Prime is eligible to receive up to $300 million in future development, regulatory and sales-based milestone payments for each collaboration target, including TIM-3. Five Prime is also eligible to receive tiered royalties starting from mid-single-digit increasing to low-double-digit percentages of global net sales of each product commercialized by BMS.

In addition, BMS has exercised its option to further extend the research term of the collaboration between the companies for the discovery, development and commercialization of immuno-oncology (I-O) therapies directed toward targets in two additional undisclosed immune checkpoint pathways. BMS has elected to extend the research term to March 2019 and will provide additional funding to Five Prime for the extended term. This is the second extension to the original collaboration term under the agreement that was established in March 2014.

BMS will continue to utilize Five Prime’s discovery capabilities to advance the immune checkpoint programs, including to identify and select drug candidates for preclinical development. Drug candidates developed against targets in these pathways may be studied either as single agents or in combination with approved BMS immuno-oncology therapies or others in development.

On January 8, 2018 Celgene Corporation (NASDAQ:CELG) reported a business update as well as its preliminary 2017 unaudited results and financial guidance for 2018 at the 36th Annual J.P. Morgan Healthcare Conference (Press release, Celgene, JAN 8, 2018, View Source [SID1234522979]). Based on U.S. Generally Accepted Accounting Principles (GAAP), GAAP diluted earnings per share (EPS) for the full-year of 2017 is expected to be in the range of $3.64 to $4.19, a 57 percent year-over-year increase based on the mid-point of the range. Full year 2017 GAAP operating margin is expected to be approximately 36 percent, an increase from 28 percent in the prior year, primarily due to increased product sales. For the fourth quarter 2017, GAAP EPS is expected to be in the range of ($0.09) to $0.46, a 65 percent year-over-year decrease based on the mid-point of the range. Fourth quarter 2017 GAAP operating margin is expected to be approximately 34 percent, an increase from 31 percent in the prior year, primarily due to increased product sales.

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Adjusted EPS is expected to be approximately $7.44 for the full year of 2017, a 25 percent year-over-year increase. Full year 2017 adjusted operating margin is expected to be 58.1 percent, an increase of 310 basis points (bps) year-over-year. For the fourth quarter of 2017, adjusted EPS is expected to be approximately $2.00, a 24 percent year-over-year increase. Fourth quarter 2017 adjusted operating margin is expected to be 55.3 percent, a decrease of 70 bps year-over-year.

"2017 was a strong year for Celgene as we delivered excellent top- and bottom-line growth and achieved critical milestones across our hematology, oncology, inflammation and immunology franchises," said Mark J. Alles, Chief Executive Officer of Celgene. "We are executing on a strategy to achieve our 2020 targets, accelerate portfolio diversification and expand our pipeline of innovative therapies."

Preliminary Q4 and FY 2017 Net Product Sales and Total Revenue are expected to be (Unaudited, in millions):

Q4 2017

Y/Y%

FY 2017

Y/Y%

REVLIMID $2,188 21% $8,187 17%
POMALYST/IMNOVID $442 17% $1,614 23%
OTEZLA $371 22% $1,279 26%
ABRAXANE $251 (6)% $992 2%
Total Revenue $3,483 17% $13,003 16%

Certain activities involved in determining the audited results for the fiscal year ended December 31, 2017 are in-process and could result in the final reported audited results being different from the unaudited results noted in this press release. The ranges of our estimated GAAP diluted earnings per share for the quarter and year ended December 31, 2017 include an estimated financial statement impact of between approximately $800 million and approximately $1,300 million related to the Tax Cuts and Jobs Act ("Tax Act"), which was enacted on December 22, 2017. Our estimate of the impact of the Tax Act is based on currently available information and interpretation of its provisions. Our actual results may materially differ from our current estimate due to, among other things, further guidance that may be issued by U.S. tax authorities or regulatory bodies and/or changes in interpretations and assumptions we have preliminarily made. We will continue to analyze the Tax Act to finalize its financial statement impact, including the mandatory deemed repatriation of foreign earnings, re-measurement of deferred taxes and certain other provisions of the Tax Act. We anticipate finalizing our preliminary analysis and the impact on our December 31, 2017 financial statements by the time we announce our financial results currently anticipated on January 25, 2018. Additionally, please see the attached Use of Non-GAAP Financial Measures and Reconciliation of Estimated/Projected GAAP to Adjusted (Non-GAAP) Measures for further information relevant to the interpretation of adjusted financial measures and reconciliations of these adjusted financial measures to the most comparable GAAP measures, respectively, for each of 2017 and 2018.

Celgene Expects Volume-Driven Product Sales and Earnings Growth in 2018

In 2018, total revenue is expected to be approximately $14.4 billion to $14.8 billion, a 12 percent increase year-over-year, based on the mid-point of the range. Based on GAAP, EPS for the full-year 2018 is expected to be in the range of $6.58 to $6.95, excluding the impact of any strategic transactions, impairments, loss contingencies, changes in the fair value of equity investments and non-operating tax adjustments that have not yet occurred. For the full-year 2018, adjusted diluted EPS is expected to be in the range of $8.70 to $8.90, an 18 percent increase year-over-year, based on the mid-point of the range.

Year-over-Year

Change

Total Revenue $14.4B to $14.8B 12%*
REVLIMID Net Product Sales Approximately $9.4B 15%
POMALYST/ IMNOVID Net Product Sales Approximately $1.9B 18%
OTEZLA Net Product Sales Approximately $1.5B 17%
ABRAXANE Net Product Sales Approximately $1.0B 1%
GAAP diluted EPS $6.58 to $6.95 N/M**
Adjusted diluted EPS $8.70 to $8.90 18%*
GAAP operating margin Approximately 46.5% N/M**
Adjusted operating margin Approximately 60.0% ~ +200 bps
Weighted average diluted shares 775M -34M
Adjusted Tax Rate ~18% ~ +200 bps
*Year-over-year percentage change based on the mid-point of the range.

**Not meaningful as the 2018 measures exclude the impact of any strategic transactions, impairments, loss contingencies, changes in the fair value of equity investments and non-operating tax adjustments that have not yet occurred.

Reaffirming Expected 2020 Long-term Financial Targets

2020 total revenue range of $19.0 billion to $20.0 billion
Adjusted Diluted EPS to exceed $12.50
2018 Expected Operational Milestones

Hematology & Oncology

Regulatory Submissions

Submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for REVLIMID in combination with bortezomib and dexamethasone (RVd) in patients with newly diagnosed multiple myeloma (NDMM)
Submission of a New Drug Application (NDA) to the FDA for fedratinib in myelofibrosis
Trial Initiations

Initiate the pivotal program with CC-122 in non-Hodgkin lymphoma (NHL)
Initiate the pivotal program with BGB-A317 (tislelizumab) in non-small cell lung cancer (NSCLC)
Initiate a phase III trial with bb2121 in third-line plus multiple myeloma in collaboration with bluebird bio
Initiate a phase III trial with JCAR017 in transplant-eligible second-line diffuse large B-cell lymphoma (DLBCL) in collaboration with Juno Therapeutics
Initiate the phase III COMMANDS trial with luspatercept in first-line, lower-risk myelodysplastic syndromes (MDS)
Clinical Data

Data from the phase III AUGMENT trial with REVLIMID in combination with rituximab in patients with relapsed and/or refractory follicular lymphoma (FL)
Data from the phase III ROBUST trial with REVLIMID in patients with first-line ABC-subtype DLBCL
Data from the phase III apact trial with ABRAXANE as adjuvant therapy in patients with surgically resected pancreatic cancer
Data from the phase III QUAZAR AML-001 trial with CC-486 as maintenance therapy in post-induction acute myeloid leukemia (AML)
Data from the phase III OPTIMISMM trial with POMALYST in combination with bortezomib and dexamethasone (PVd) in second-line multiple myeloma
Data from the phase III MEDALIST trial with luspatercept in patients with ring sideroblast-positive (RS+) MDS in collaboration with Acceleron Pharma
Data from the phase III BELIEVE trial with luspatercept in patients with beta-thalassemia in collaboration with Acceleron Pharma
Data from phase I/II trial with CC-220 in relapsed and/or refractory multiple myeloma (RRMM)
Trial Enrollment

Complete enrollment in the pivotal KarMMa trial with bb2121 in RRMM in collaboration with bluebird bio
Complete enrollment in the pivotal TRANSCEND WORLD trial with JCAR017 in third-line DLBCL in collaboration with Juno Therapeutics
Inflammation and Immunology

Regulatory Submissions/Decisions

FDA decision on the submission of an NDA for ozanimod in patients with relapsing multiple sclerosis (RMS)
FDA decision on the submission of an sNDA for OTEZLA once-daily formulation
Submission of an sNDA for OTEZLA in Behçet’s disease
Submission of a Marketing Authorization Application (MAA) for ozanimod in RMS
Trial Initiations

Initiate a phase III trial with OTEZLA in ulcerative colitis
Initiate a phase III trial with OTEZLA in mild-to-moderate psoriasis
Initiate a phase III trial with ozanimod in secondary progressive multiple sclerosis (SPMS)
Clinical Data

Data from a phase III trial with OTEZLA in scalp psoriasis
Data from a phase II trial with OTEZLA in ulcerative colitis to be presented at a medical meeting in the first quarter of 2018

Trial Enrollment

Complete enrollment in the phase III TRUE NORTH trial with ozanimod in ulcerative colitis
Research and Early Development

File at least 5 Investigational New Drug (IND) or Clinical Trial Applications (CTA) for novel assets