Oncternal Therapeutics Announces Presentation of ROR1 CAR-T Preclinical Data at 2020 ASCO-SITC Clinical Immuno-Oncology Symposium

On February 6, 2020 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of preclinical data from its ROR1 chimeric antigen receptor T cell (CAR-T) program at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) – Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting in Orlando, Florida (Press release, Oncternal Therapeutics, FEB 6, 2020, View Source [SID1234553949]). A copy of the poster presentation is available online at www.oncternal.com.

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In preclinical studies, anti-ROR1 CAR-T constructs were evaluated in an animal model of human leukemia. A single dose of anti-ROR1 CAR T-cells expanded in treated animals and the chimeric T cells trafficked to the disease sites. By week four, leukemia cells were cleared from major tissue reservoirs, including bone marrow, kidneys and spleen. CAR-T cell-treated animals survived longer than 90 days compared to 21 days for animals in control groups. The CAR-T cells were highly active and detected in mouse tissues more than two months after injection.

This research effort was led by Professor Thomas J. Kipps, M.D., Ph.D., and Charles Prussack, Pharm.D., Ph.D., at the University of California San Diego (UC San Diego) under a research grant from the California Institute of Regenerative Medicine (CIRM).

"It is exciting to see the potent preclinical activity of the ROR1 CAR-T cell therapy and its selectivity in targeting tumors," said Thomas Kipps, M.D., Ph.D., Professor of Medicine, Evelyn and Edwin Tasch Chair in Cancer Research, and Deputy Director of Research Operations at the UC San Diego Moores Cancer Center. "This CAR-T cell product utilizes the ROR1 binding domain derived from cirmtuzumab (UC-961), a clinical stage antibody that is currently being evaluated in patients with hematological malignancies and solid tumors. The challenges of CAR-T therapies include patient relapses due to the loss of target antigen and safety issues due to targeting of normal cells expressing the antigen. Harnessing cirmtuzumab’s specificity for ROR1 expressed on cancer cells has the potential to improve CAR-T efficacy and safety, and address the high unmet medical need for treating patients with aggressive cancers."

"We are encouraged by the preclinical results of this ROR1 CAR-T program and look forward to advancing it to clinical testing, initially for treating patients with hematological cancers, potentially in the fourth quarter of this year," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.

About ROR1 CAR-T

Oncternal Therapeutics is developing a ROR1-targeting (Receptor tyrosine kinase-like Orphan Receptor 1) chimeric antigen receptor T cell therapy (CAR-T) as a potential treatment for patients with aggressive hematological malignancies or solid tumors, in collaboration with the UC San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). The Company’s CAR-T program is based on the binding domain of cirmtuzumab, which is an investigational, potentially first-in-class monoclonal antibody targeting ROR1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of patients with chronic lymphocytic leukemia, or CLL, or mantle cell lymphoma, or MCL, and in an investigator-initiated Phase 1 clinical trial in combination with paclitaxel for the treatment of women with metastatic or unresectable breast cancer.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Because the epitope of ROR1 recognized by cirmtuzumab appears to be restricted to tumor cells, a cirmtuzumab-based CAR-T may be selective in distinguishing cancer from normal tissues. Cirmtuzumab and ROR1 CAR-T cell therapy have not been approved by the U.S. Food and Drug Administration for any indication.

MEI Pharma Reports Fiscal Second-Quarter 2020 Results and Operational Highlights

On February 6, 2020 MEI Pharma, Inc. (NASDAQ: MEIP) ("MEI"), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported results for its second quarter ended December 31, 2019 (Press release, MEI Pharma, FEB 6, 2020, View Source [SID1234553965]).

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"We’re off to a good start in calendar year 2020. Our pipeline of clinical oncology candidates continues to advance, and the successful equity offering this past December gives us added resources to execute on our clinical strategy through key value-creating inflection points," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "We have several important milestones across our pipeline in 2020 including completing enrollment in the ME-401 TIDAL study, data updates from the Phase 1b study of ME-401 administered as a monotherapy and in combination with other agents to treat patients with B-cell malignancies, one year survival data from the Phase 2 pracinostat study in patients with MDS, and voruciclib updates in patients with AML and B-cell malignancies."

Dr. Gold added, "We remain very encouraged by the ME-401 clinical program; the maturing data on the intermittent dosing schedule in the Phase 1b study continue to demonstrate high overall response rates and durable responses, and the intermittent schedule also continues to be well tolerated. Based on the strength of the data set from these intermittent schedule patients, the TIDAL study was amended to consolidate the remaining study enrollment into the intermittent dosing arm. We expect to complete enrollment in the TIDAL study this summer and plan a submission for accelerated approval with the FDA based on the results of this study."

Recent Highlights

In December 2019, the Company completed a public offering of common stock resulting in net proceeds to the Company of approximately $48.5 million.
In December 2019, the Company amended the study protocol for TIDAL (Trials of PI3K DeltA in Non-Hodgkin’s Lymphoma), the Phase 2 trial evaluating ME-401 in patients with relapsed or refractory follicular lymphoma ("FL"). TIDAL is intended to support an accelerated approval marketing application with the FDA.
The amendment consolidates the remaining enrollment into the dosing arm in which patients receive ME-401 administered on the intermittent schedule ("IS").
The amendment was prompted by maturing data from the Phase 1b trial of ME-401 demonstrating that the IS regimen is as active as the continuous daily dosing regimen, is associated with durable responses to date, and is also associated with improved tolerability.
Approximately 120 patients will be enrolled in the IS arm and completion of enrollment is expected to complete in the summer of 2020.
In October 2019, the Company reported updated data from the ongoing Phase 1b study of ME-401, an investigational selective oral inhibitor of phosphatidylinositol 3-kinase ("PI3K") delta. The data demonstrate:
Overall response rates of 78% in relapsed or refractory FL and 89% in r/r chronic lymphocytic leukemia or small lymphocytic lymphoma ("CLL/SLL").
Rates of Grade 3 adverse events of special interest related to ME-401 exposure were observed in <10% of patients dosed on an IS.
Median duration of response was not reached in patients with FL or CLL/SLL on the IS regimen. Median follow-up for FL and CLL/SLL patients was 9.2 months (range 3.4-20.7 months) and 7.4 months (range 2.6-14.7 months), respectively.
Fiscal Second-Quarter Fiscal Year 2020 Financial Results

As of December 31, 2019, MEI had $103.9 million in cash, cash equivalents and short-term investments, with no outstanding debt.
For the quarter ended December 31, 2019, cash used in operations was $10.5 million, compared to $7.2 million for 2018.
Research and development expenses were $8.3 million for the quarter ended December 31, 2019, compared to $9.1 million for 2018. The decrease was primarily related to decreased drug manufacturing costs associated with ME-401.
General and administrative expenses were $4.2 million for the quarter ended December 31, 2019, compared to $3.8 million for 2018. The increase primarily relates to increased headcount and increased professional services expenses to support our activities.
Revenue was $1.0 million for the quarter ended December 31, 2019, compared to revenue of $2.0 million for the quarter ended December 31, 2018. Revenue resulted from the recognition of fees allocated to research and development activities related to the Helsinn and Kyowa Kirin License Agreements. During the quarter ended December 31, 2018, revenue also included $0.9 million from transfer of the license to Kyowa Kirin.
Net loss was $20.2 million, or $0.26 per share, for the quarter ended December 31, 2019, compared to net income of $12.0 million, or $0.17 per share for 2018. Net loss increased primarily as a result of a non-cash expense in the current quarter and a non-cash gain in the prior quarter related to changes in the fair value of the warrant liability associated with the May 2018 financing. The Company had 105,998,677 shares of common stock outstanding as of December 31, 2019, compared with 71,131,486 shares as of December 31, 2018.
The adjusted net loss for the quarter ended December 31, 2019, excluding a non-cash expense related to changes in the fair value of the warrants (a non-GAAP measure), was $11.8 million, compared to an adjusted net loss of $11.4 million for 2018.

Sanofi delivers strong 2019 business EPS growth of 6.8% at CER

On February 6, 2020 Fourth-quarter 2019 sales performance(3) driven by Dupixent and Vaccines (Press release, Sanofi, FEB 6, 2020, View Source [SID1234553981]).

Net sales were €9,608 million, up 6.8% on a reported basis and 4.7%(3) at CER.

Dupixent (global sales €679 million, up 135%) the largest growth contributor, drove Sanofi Genzyme GBU sales up 19.7%.

Vaccines sales increased 22.0%, reflecting majority of U.S. influenza vaccine shipments in Q4.

CHC sales down 5.2%, mainly due to Zantac voluntary recall, non-core divestments and changing regulatory requirements.

Primary Care GBU sales declined 8.7% due to lower sales in Diabetes and Established Products.

Lower China sales (down 21.0%) due to anticipated price and inventory adjustments on Plavix and Avapro in the channel.

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Full-year 2019 sales growth of 3.6% at CER/CS(4) and business EPS growth of 6.8% at CER

Net sales were €36,126 million, up 4.8% on a reported basis and 2.8% at CER (up 3.6% at CER/CS(4)).

Dupixent sales reached €2,074 million, on track with ambition to achieve more than €10 billion peak sales.

Vaccines sales increased 9.3% to €5,731 million, supporting expected mid-to-high single digit CAGR from 2018 to 2025.

Business operating income margin improved 1.2 percentage points to 27.0%, trending towards objective of 30% by 2022.

Q4 2019 business EPS(1) up 17.3% at CER to €1.34.

Full-year 2019 business EPS of €5.99 up 6.8% at CER.

Full-year 2019 IFRS EPS of €2.24 (down 35.1%(2)), reflecting a €3.6 billion impairment charge mainly related to Eloctate.

Board proposes annual dividend of €3.15, the 26th consecutive increase in dividend.

Significant R&D advances and regulatory milestones


SAR442168, a BTK inhibitor, achieved proof of concept in relapsing multiple sclerosis; phase 3 program to be initiated mid-2020.

Dupixent submitted to FDA (priority review) and EMA as first biologic for children aged 6-11 years with atopic dermatitis.

Dupixent phase 3 pivotal studies initiated in bullous pemphigoid, chronic spontaneous urticaria and prurigo nodularis.

Dupixent efficacy and safety further supported by 3-year data from OLE (Open Label Extension) study.

Fluzone High-Dose Quadrivalent approved in the U.S.

Sutimlimab demonstrated positive phase 3 results in cold agglutinin disease.

SAR408701, an anti-CEACAM5 antibody-drug conjugate, entered into phase 3 in non-small cell lung cancer.

Olipudase demonstrated positive pivotal topline data in adult and pediatric patients with acid sphingomyelinase deficiency.

Successful completion of Synthorx acquisition enhances Sanofi’s position as an emerging leader in oncology and immunology.

2020 financial outlook

Sanofi expects 2020 business EPS(1) to grow around 5%(5) at CER, barring unforeseen major adverse events. Applying average January 2020 exchange rates, the positive currency impact on 2020 business EPS is estimated to be around 1%.

Sanofi Chief Executive Officer, Paul Hudson, commented:

"I am encouraged by the fourth quarter results which position Sanofi to deliver on our new strategic priorities. The acceleration in sales performance was mainly driven by the impressive growth of Dupixent, our transformative medicine for type 2 inflammatory diseases and by our differentiated Vaccines portfolio. At the same time, our sharpened focus on operating and financial efficiencies helped us to deliver margin expansion and significant cash flow improvement. We are making great progress in our ambition to transform Sanofi R&D and I am particularly excited by the positive proof of concept data for our BTK inhibitor, a potentially practice changing therapy for multiple sclerosis, announced today. There is increasing momentum across the entire Sanofi organization and I am confident we will achieve the long-term growth aspirations and margin targets we set out at our Capital Markets Day".

In order to facilitate an understanding of operational performance, Sanofi comments on the business net income statement. Business net income is a non-GAAP financial measure (see Appendix 11 for definitions). The consolidated income statement for Q4 2019 is provided in Appendix 3 and a reconciliation of reported IFRS net income to business net income is set forth in Appendix 4; (2) Q4 2019 and full-year 2019 included impairment charge of €1,581 million and €3,604 million, respectively, mainly related to Eloctate; (3) Changes in net sales are expressed at constant exchange rates (CER) unless otherwise indicated (see Appendix 11); (4) Constant Structure: Adjusted for divestment of European generics business and sales of Bioverativ products to SOBI; (5) Base for business EPS growth is €5.97, reflecting 2 cents impact from IFRS 16 (see appendix 11).

Investor Relations: (+) 33 1 53 77 45 45 – E-mail: [email protected] – Media Relations: (+) 33 1 53 77 46 46 – E-mail: [email protected]

Website: www.sanofi.com

2019 fourth-quarter and full-year Sanofi sales

Unless otherwise indicated, all percentage changes in sales in this press release are stated at CER(6).

In the fourth quarter of 2019, Company sales were €9,608 million, up 6.8% on a reported basis. Exchange rate movements had a positive effect of 2.1 percentage points, mainly driven by the strength of the U.S. dollar and the Japanese yen. At CER, Company sales increased 4.7%. Full-year 2019 Company sales reached €36,126 million, up 4.8% on a reported basis. Exchange rate movements had a favorable effect of 2.0 percentage points. At CER, Company sales were up 2.8%.

Global Business Units

At its Capital Markets Day in December 2019, Sanofi announced plans for a new GBU organization(7) which will include three core GBUs, Specialty Care, General Medicines and Vaccines together with a standalone Consumer Healthcare business. The General Medicines GBU will be created from two existing GBUs, Primary Care and China & Emerging Markets. Each GBU will include its respective Emerging Markets sales contribution.

Olivier Charmeil has been appointed to lead the General Medicines GBU. Olivier is one of Sanofi’s most seasoned business leaders. He will draw on his recent experience leading the China & Emerging Markets GBU to engage with customers and markets and ensure that our combined Diabetes, Cardiovascular and Established Products business drives growth and deliver for patients around the world.

Alongside the GBU reorganization, Sanofi will implement changes in the configuration of its Executive Committee. This leadership committee will now include, in addition to the four GBU Heads, the global Heads of R&D, Industrial Affairs, Finance, Human Resources and Legal, together with the Chief Digital Officer. A leaner configuration will foster agility and speed in decision-making, in line with the fourth priority of the company’s new strategy ("Reinvent How We Work").

The table below presents sales by Global Business Unit (GBU).

Net Sales by GBU

(€ million)

Q4 2019
Change

at CER

2019
Change

at CER

Sanofi Genzyme (Specialty Care)(a)

2,525 +19.7 % 9,195 +22.4 %(c)
Primary Care(a)

2,325 -8.7 % 9,076 -14.8 %(d)
China & Emerging Markets(b)

1,698 -1.9 % 7,437 +6.4 %
Total Pharmaceuticals

6,548 +2.4 % 25,708 +2.2 %
Consumer Healthcare (CHC)

1,152 -5.2 % 4,687 -0.8 %
Sanofi Pasteur (Vaccines)

1,908 +22.0 % 5,731 +9.3 %
Total net sales

9,608 +4.7 % 36,126 +2.8 %(e)

(a)
Does not include China & Emerging Markets sales – see definition page 9; (b) Includes Emerging Markets sales for Primary Care and Specialty Care; (c) +19.3% at CS – Adjusted for Bioverativ acquisition and sales of Bioverativ products to SOBI – see page 5; (d) -10.9% at CS; (e) +3.6% at CS – Adjusted for Bioverativ and sales of Bioverativ products to SOBI and disposal of European Generics business.

Global Franchises

The tables below present fourth-quarter and full-year 2019 sales by global franchise, including Emerging Markets sales, to facilitate comparisons. Appendix 1 provides a reconciliation of sales by GBU and franchise.

Net sales by Franchise

(€ million)

Q4 2019
Change

at CER


Developed

Markets


Change

at CER


Emerging

Markets


Change

at CER

Specialty Care franchises

2,830 +18.9 % 2,525 +19.7 % 305 +12.8 %
Rare Disease

815 +1.6 % 661 +0.8 % 154 +5.3 %
Multiple Sclerosis

540 -3.0 % 517 -3.8 % 23 +21.1 %
Oncology

441 +11.4 % 333 +12.6 % 108 +7.9 %
Immunology

733 +128.6 % 721 +126.2 % 12 ns
Rare Blood Disorder

301 -0.7 % 293 -2.4 % 8 ns
Primary Care franchises

3,718 -7.2 % 2,325 -8.7 % 1,393 -4.7 %
Established Rx Products

2,276 -6.3 % 1,299 -4.0 % 977 -9.3 %
Diabetes

1,268 -9.2 % 861 -15.5 % 407 +7.4 %
Cardiovascular

174 -4.5 % 165 -5.8 % 9 +33.3 %
Consumer Healthcare

1,152 -5.2 % 727 -9.4 % 425 +3.0 %
Vaccines

1,908 +22.0 % 1,356 +25.5 % 552 +14.2 %
Total net sales

9,608 +4.7 % 6,933 +5.9 % 2,675 +1.8 %

(6)
See Appendix 11 for definitions of financial indicators. (7) subject to consultation with social partners and works councils.

2

Net sales by Franchise

(€ million)

2019
Change

at CER


Developed

Markets


Change

at CER


Emerging

Markets


Change

at CER

Specialty Care franchises

10,431 +22.7 %(1) 9,195 +22.4 % 1,236 +24.4 %
Rare Disease

3,165 +6.5 % 2,551 +2.6 % 614 +24.0 %
Multiple Sclerosis

2,160 +1.8 % 2,080 +1.3 % 80 +14.7 %
Oncology

1,695 +10.6 % 1,205 +8.3 % 490 +16.7 %
Immunology

2,259 +148.1 % 2,228 +146.1 % 31 ns
Rare Blood Disorder

1,152 +22.0 %(2) 1,131 +20.0 %(3) 21 ns
Primary Care franchises

15,277 -8.2 %(4) 9,076 -14.8 %(5) 6,201 +3.3 %
Established Rx Products(6)

9,559 -8.3 %(7) 5,088 -15.0 %(8) 4,471 +0.6 %
Diabetes

5,113 -8.2 % 3,412 -15.6 % 1,701 +10.3 %
Cardiovascular

605 -4.6 % 576 -6.4 % 29 +55.6 %
Consumer Healthcare

4,687 -0.8 % 3,035 -3.6 % 1,652 +4.7 %
Vaccines

5,731 +9.3 % 3,906 +3.4 % 1,825 +24.0 %
Total net sales

36,126 +2.8 %(9) 25,212 +0.4 %(10) 10,914 +8.7 %

(1)
+19.9 % at CS- Adjusted for Bioverativ and sales of products to SOBI – see page 5; (2) +0.8% at CS- see page 5; (3) -0.8% at CS -see page 5; (4) -5.5% at CS;

(5)
-10.9% at CS; (6) including Generics; (7) -4.1% at CS; (8) -7.9% at CS; (9) +3.6% at CS- Adjusted for Bioverativ and sales of Bioverativ products to SOBI and disposal of European Generics business;(10) +1.5% at CS – Adjusted for Bioverativ and sales of Bioverativ products to SOBI and disposal of European Generics business.

Pharmaceuticals

Fourth-quarter Pharmaceutical sales were up 2.4% to €6,548 million, mainly driven by Dupixent which was partially offset by Diabetes and Established Rx Products. Full-year 2019 sales for Pharmaceuticals increased 2.2% (up 3.3% at CS) to €25,708 million, reflecting the disposal of the European generics business at the end of the third quarter of 2018.

Specialty Care franchises

Immunology franchise

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Dupixent

679 +135.4 % 2,074 +151.6 %
Kevzara

54 +67.7 % 185 +114.5 %
Total Immunology

733 +128.6 % 2,259 +148.1 %
Dupixent (collaboration with Regeneron) generated sales of €679 million in the fourth quarter (up 135%). In the U.S., Dupixent sales of €545 million (up 135%) were driven by continued growth in atopic dermatitis which benefited from increased penetration in adult patients and launch in the adolescent age group (12 to 17 years of age) in March, together with rapid uptake in asthma and launch in chronic rhinosinusitis with nasal polyposis (CRSwNP, approved in June). In the U.S., Dupixent NBRx and TRx more than doubled in the quarter compared to the fourth quarter of 2018, growing at 108% and 117%, respectively. Fourth-quarter sales of Dupixent in Europe rose to €64 million (up 117%) following additional launches while sales in Japan were €46 million (versus €13 million in the fourth quarter of 2018). Full-year 2019 Dupixent sales increased 152% to €2,074 million. Dupixent is now launched in 34 countries for adult atopic dermatitis; among these, Dupixent is also launched in adolescent atopic dermatitis in 10 countries, in asthma in 8 countries and in CRSwNP in 4 countries. Potentially as many as 89 additional country launches are planned across these indications for 2020.

Kevzara (collaboration with Regeneron) sales were €54 million (up 68%) in the fourth quarter, of which €34 million was generated in the U.S. (up 39%). Full-year 2019 Kevzara sales increased 114% to €185 million.

Multiple Sclerosis franchise

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Aubagio

482 +5.4 % 1,879 +10.0 %
Lemtrada

58 -41.7 % 281 -31.6 %
Total Multiple Sclerosis

540 -3.0 % 2,160 +1.8 %

3

Fourth-quarter Multiple Sclerosis (MS) sales decreased 3.0% to €540 million. Over the period, Aubagio sales growth in the U.S. was more than offset by lower Lemtrada sales. Full-year 2019 MS sales increased 1.8% to €2,160 million.

Fourth-quarter Aubagio sales increased 5.4% to €482 million, driven by the U.S. performance (up 7.1% to €343 million). Full-year 2019 Aubagio sales increased 10.0% to €1,879 million. As of January 1, Aubagio was excluded from the national formulary at ESI, which covers roughly 14% of total commercial lives in the US. Contracted access positions for Aubagio remain strong for other national health plans and national PBMs.

In the fourth quarter, Lemtrada sales decreased 42% to €58 million due to lower sales in the U.S. (down 29% to €34 million) and in Europe (down 57% to €16 million), reflecting increased global competition and the update to the EU label. Full-year 2019 Lemtrada sales decreased 32% to €281 million.

Oncology franchise

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Jevtana

128 +9.6 % 484 +11.1 %
Thymoglobulin

89 +12.8 % 354 +16.5 %
Eloxatin

42 -4.7 % 203 +10.4 %
Mozobil

55 +12.8 % 198 +11.7 %
Taxotere

42 +10.5 % 173 +3.0 %
Zaltrap

26 +8.7 % 97 +4.4 %
Others

59 +29.5 % 186 +9.1 %
Total Oncology

441 +11.4 % 1,695 +10.6 %
Fourth-quarter Oncology sales increased 11.4% to €441 million driven by the U.S. (up 18.4% to €174 million) and Europe (up 15.7% to €102 million). Full-year 2019 Oncology sales increased 10.6% to €1,695 million.

Fourth-quarter Jevtana sales increased 9.6% to €128 million driven by the U.S. and by publication of the results of the CARD study in metastatic castration-resistant prostate cancer at ESMO (Free ESMO Whitepaper) (European Society for Medical Oncology) in September 2019. Full-year 2019 Jevtana sales were up 11.1% to €484 million. In the fourth quarter, Thymoglobulin sales increased 12.8% to €89 million, driven by the U.S. 2019 sales of Thymoglobulin increased 16.5% to €354 million.

Libtayo (collaboration with Regeneron) approved for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation had ex-U.S. sales of €12 million and €16 million in the fourth quarter and full-year 2019, respectively. In 2019 Libtayo was launched in 7 countries outside the U.S. and there are 13 additional country launches planned by the end of 2020. U.S. Libtayo sales are reported by Regeneron.

Rare Disease franchise

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Myozyme / Lumizyme

238 +4.4 % 918 +8.3 %
Fabrazyme

215 +2.4 % 813 +5.3 %
Cerezyme

177 -6.8 % 708 +2.7 %
Aldurazyme

54 0.0 % 224 +9.2 %
Cerdelga

55 +22.7 % 206 +26.4 %
Others Rare Disease

76 +1.4 % 296 +0.7 %
Total Rare Disease

815 +1.6 % 3,165 +6.5 %
In the fourth quarter, Rare Disease sales increased 1.6% to €815 million against a high base for comparison. This performance was driven by Emerging Markets (up 5.3% to €154 million) and the U.S. (up 2.7% to €309 million). In Europe, over the period, sales were flat at €263 million. Full-year 2019 Rare Disease sales increased 6.5% to €3,165 million.

Fourth-quarter Gaucher (Cerezyme and Cerdelga) sales decreased 1.3% to €232 million, impacted by Cerezyme sales phasing effects in Emerging Markets which offset strong Cerdelga performance. Fourth-quarter Cerdelga sales increased 22.7% to €55 million, with sales up 18.8% in Europe (to €20 million) and up 19.2% in the U.S. (to €31 million). Full-year 2019 Gaucher sales were €914 million, up 7.0%.

4

Fourth-quarter Pompe (Myozyme/Lumizyme) sales grew 4.4% to €238 million, driven by the U.S. (up 7.6% to €88 million) and Emerging Markets (up 16.7% to €41 million) and supported by positive trends in naïve patient accrual. Full-year 2019 Myozyme/Lumizyme sales increased 8.3% to €918 million.

Fourth-quarter Fabry (Fabrazyme) sales grew 2.4% to €215 million, driven by Emerging Markets (up 15.4% to €29 million) and Europe (up 6.7% to €48 million). Over the period, U.S. sales decreased 1.0% to €106 million. Full-year 2019 Fabrazyme sales were up 5.3% to €813 million.

Rare Blood Disorder franchise

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Eloctate

177 -12.8 % 684 +6.6 %*
Alprolix

108 +9.5 % 412 +37.2 %**
Cablivi

16 ns 56 ns
Total Rare Blood Disorder

301 -0.7 % 1,152 +22.0 %***

*
-11.6% at CS in 2019 – see footnote 8; **+12.4% at CS in 2019 – see footnote 8; *** +0.8% at CS in 2019 – see footnote 8

Bioverativ was consolidated in Sanofi’s Financial Statements from March 9, 2018. Fourth-quarter sales of the Rare Blood Disorder franchise were €301 million, down 0.7%. Fourth-quarter U.S. sales were €210 million, down 13.6%. Non U.S. sales were €91 million with Japan as the primary contributor. Full-year 2019 sales of the Rare Blood Disorder franchise were €1,152 million, up 0.8% at CS(8).

Eloctate sales were €177 million in the fourth quarter, down 12.8%. In the U.S., sales of the product decreased 25.6% to €123 million, reflecting ongoing competitive pressure. In the Rest of the World region, fourth-quarter Eloctate sales increased 35.3% to €47 million. Full-year 2019 Eloctate sales were €684 million, down 11.6% at CS(8).

Alprolix sales were €108 million in the fourth quarter, up 9.5%. In the U.S., sales of the product decreased 1.3% to €77 million, related to shipment timing. In the Rest of the World region, Alprolix sales increased 47.4% to €30 million due to growth in product sales to SOBI. Full-year 2019 Alprolix sales were €412 million, up 12.4% at CS(8).

Cablivi for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP) generated fourth-quarter sales of €16 million. The number of patients treated with Cablivi increased over 30% compared to the third quarter to approximately 150 patients. Sales were sequentially lower primarily due to price adjustments in Europe and increased assistance program participations in the U.S. In the U.S., where Cablivi was launched in April, sales were €10 million. In Europe, the product is commercially available in Germany, Denmark, Austria, Belgium and the Netherlands. Cablivi has a temporary license to be sold in France. Full-year 2019 Cablivi sales were €56 million.

Primary Care franchises

Cardiovascular franchise

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Praluent

75 -11.0 % 258 -3.8 %
Multaq

99 +1.1 % 347 -5.1 %
Total cardiovascular franchise

174 -4.5 % 605 -4.6 %
Fourth-quarter Praluent (collaboration with Regeneron) sales decreased 11.0% to €75 million, reflecting lower sales in the U.S. (down 26.9% to €39 million) which were impacted by significantly higher rebates. In Europe, Praluent sales increased 4.3% to €24 million despite the suspension of sales in Germany in August following the Regional Court of Dusseldorf ruling in the ongoing patent litigation. Full-year 2019 Praluent sales decreased 3.8% to €258 million.

In December 2019, Sanofi and Regeneron announced their intent to simplify their antibody collaboration for Kevzara and Praluent by restructuring into a royalty-based agreement. Under the proposed restructuring, Sanofi is expected to gain sole global rights to Kevzara and sole ex-U.S. rights to Praluent. Regeneron is expected to gain sole U.S. rights to Praluent. Under the proposed terms of the agreement, each party will be solely responsible for funding development and commercialization expenses in their respective territories. These changes are expected to increase efficiency and streamline operations for the products. Completion of the agreement is expected to be finalized in the first quarter of 2020.

(8)
Growth comparing 2019 sales versus full 2018 sales at CER. Sales of products to SOBI were initially recorded in "other revenues" in H1 2018 and in sales from H2 2018; the H1 2018 reclassification was reflected in Q3 2018. H1 2018 and Q3 2018 sales were adjusted accordingly for calculation of CS. Unaudited data.

5

Diabetes franchise

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Lantus

729 -17.2 % 3,012 -17.0 %
Toujeo

234 +8.5 % 883 +3.2 %
Total glargine

963 -12.2 % 3,895 -13.2 %
Amaryl

79 0.0 % 334 -2.1 %
Apidra

88 -2.2 % 344 -3.6 %
Admelog

56 -1.8 % 250 +155.9 %
Soliqua

39 +40.7 % 122 +60.3 %
Insuman

20 -13.0 % 82 -7.7 %
Total Diabetes

1,268 -9.2 % 5,113 -8.2 %
In the fourth quarter, global Diabetes sales decreased 9.2% to €1,268 million, due to lower glargine (Lantus and Toujeo) sales in the U.S. Fourth-quarter U.S. Diabetes sales were down 20.5% to €454 million, reflecting the increased contribution to the coverage gap related to Medicare Part D and a continued decline in average U.S. glargine net prices. Fourth-quarter sales in Emerging Markets increased 7.4% to €407 million. Fourth-quarter sales in Europe decreased 4.4% to €305 million despite Toujeo growth. Full-year 2019 global Diabetes sales decreased 8.2% to €5,113 million. Broad U.S. payer coverage for key Diabetes brands is expected to be largely maintained in 2020.

In the fourth quarter, Lantus sales were €729 million, down 17.2%. In the U.S., Lantus sales decreased 26.9% to €286 million, mainly reflecting lower average net price and the increased contribution to the coverage gap related to Medicare Part D. In Europe, fourth-quarter Lantus sales were €146 million, down 13.1% due to biosimilar glargine competition and patients switching to Toujeo. In Emerging Markets, fourth-quarter Lantus sales were stable at €244 million reflecting lower sales in the Middle-East. Full-year 2019 Lantus sales decreased 17.0% to €3,012 million.

On January 28, 2020, Sanofi’s petition for rehearing the Court of Appeals for the Federal Circuit decision affirming the December 2018 PTAB decisions invalidating the Lantus formulation patents was denied. Mylan currently does not have FDA approval for either its vial or pen product.

Fourth-quarter Toujeo sales increased 8.5% to €234 million. In the U.S., fourth-quarter Toujeo sales were €77 million, down 7.4% mainly reflecting lower average net price and the increased contribution to the coverage gap related to Medicare Part D. In Europe and Emerging Markets, fourth-quarter Toujeo sales were €87 million (up 14.3%) and €48 million (up 48.4%), respectively. Full-year 2019 Toujeo sales increased 3.2% to €883 million.

Fourth-quarter and full-year 2019 Amaryl sales were €79 million (stable) and €334 million (down 2.1%), respectively. In China, the second wave of the nationwide VBP (volume-based procurement) program includes glimepiride in 2020 and Sanofi has opted not to bid with Amaryl. In China, Amaryl sales were €136 million (up 3.1%) in 2019. Sanofi expects sales of Amaryl in China to decline significantly in 2020 due to the extended VBP program.

Fourth-quarter Apidra sales decreased 2.2% to €88 million. Lower sales in the U.S. (down 47.1% to €10 million) offset growth in Emerging Markets (up 20.7% to €34 million). Full-year 2019 Apidra sales were €344 million, down 3.6%.

Admelog (insulin lispro injection) generated sales of €56 million (down 1.8%) in the fourth quarter. Admelog sales in the U.S. were €52 million, down 7.4% due to the WAC price adjustment of -44% which took effect on July 1, 2019. Full-year 2019 Admelog sales were €250 million versus €93 million in 2018. Sanofi expects lower Admelog sales in 2020 due to the full-year impact of the U.S. WAC price adjustment.

Fourth-quarter and full-year 2019 Soliqua 100/33 (insulin glargine 100 Units/mL & lixisenatide 33 mcg/mL injection) and Suliqua sales increased 41% (to €39 million) and 60% (to €122 million), respectively.

6

Established Rx Products

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Lovenox

335 -4.0 % 1,359 -7.4 %
Plavix

212 -36.9 % 1,334 -8.8 %
Aprovel/Avapro

131 -15.2 % 674 +2.0 %
Synvisc /Synvisc-One

81 -1.2 % 309 -5.1 %
Renvela/Renagel

82 -15.6 % 311 -26.5 %
Myslee/Ambien/Stilnox

56 -6.8 % 219 -7.8 %
Allegra

28 0.0 % 128 -2.4 %
Generics

271 -0.4 % 1,075 -27.9 %
Other

1,080 +2.7 % 4,150 -1.8 %
Total Established Rx Products

2,276 -6.3 % 9,559 -8.3 %
In the fourth quarter, Established Rx Products sales decreased 6.3% to €2,276 million, primarily reflecting the decline in Plavix and Aprovel family sales in China due to net price adjustments and inventory reduction in the channel following the nationwide implementation of the VBP program in December. Full-year 2019 Established Rx Products sales decreased 8.3% to €9,559 million (down 4.1% at CS) reflecting divestment of the European generics business at the end of the third quarter of 2018.

Fourth-quarter Lovenox sales decreased 4.0% to €335 million, reflecting lower Mature Markets sales (down 14.4% to €197 million) due to biosimilar competition in several countries in Europe. In Emerging Markets, Lovenox sales grew 16.2% to €138 million. Full-year 2019 Lovenox sales were down 7.4% to €1,359 million.

In the fourth quarter, Plavix sales were down 36.9% to €212 million, primarily reflecting the decrease in China (sales down 69.1% to €55 million) due to net price adjustments and inventory reduction in the channel following the nationwide implementation of the VBP program in December. In Japan, Plavix sales decreased 21.1% to €32 million due to a price reduction in October 2019. Full-year 2019 Plavix sales decreased 8.8% to €1,334 million.

Fourth-quarter Aprovel/Avapro sales were down 15.2% to €131 million, primarily reflecting the decrease in China (sales down 40.6% to €40 million) due to net price adjustments and inventory reduction in the channel following nationwide implementation of the VBP program in December. Full-year 2019 Aprovel/Avapro sales increased 2.0% to €674 million.

As previously announced, Sanofi expects sales of Plavix and the Aprovel family in China to decline by around 50% in 2020 due to implementation of the VBP program.

Fourth-quarter Renvela/Renagel (sevelamer) sales decreased 15.6% to €82 million, due to generic competition in the U.S. (down 40.4% to €35 million) and despite growth in China. Full-year 2019 Renvela/Renagel sales decreased 26.5% to €311 million.

In the fourth quarter, Generics sales decreased 0.4% to €271 million, including stable sales in Emerging Markets (at €172 million). Full-year 2019 Generics sales were €1,075 million, down 27.9% (up 3.9% at CS), reflecting the divestment of the European generics business at the end of the third quarter of 2018.

7

Consumer Healthcare

CHC sales by geography and category are provided in Appendix 1.

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Allergy Cough & Cold

281 +1.9 % 1,179 +2.2 %
of which Allegra

95 +16.3 % 436 +6.1 %
of which Mucosolvan

28 -6.7 % 99 -10.9 %
of which Xyzal

12 +10.0 % 51 +17.1 %
Pain

329 -2.4 % 1,259 +1.3 %
of which Doliprane

95 -3.1 % 324 -3.0 %
of which Buscopan

50 +8.2 % 189 +7.7 %
Digestive

227 -13.3 % 1,004 0.0 %
of which Dulcolax

54 -3.6 % 225 +2.8 %
of which Enterogermina

53 +10.6 % 222 +20.2 %
of which Essentiale

49 -2.1 % 190 +5.6 %
of which Zantac

-5 ns 78 -42.5 %
Nutritionals

165 -7.5 % 657 -4.1 %
Other

150 -7.5 % 588 -8.2 %
of which Gold Bond

64 -9.0 % 213 -4.3 %
Total Consumer Healthcare

1,152 -5.2 % 4,687 -0.8 %
In the fourth quarter, Consumer Healthcare (CHC) sales decreased 5.2% to €1,152 million. Over half of the decline was related to the voluntary recall of Zantac. In addition, divestments of non-core products and product suspensions due to changing regulatory requirements impacted sales performance. These factors are expected to have a dampening effect on CHC performance through the first half of 2020. Full-year 2019 CHC sales decreased 0.8% to €4,687 million.

In September 2019, the U.S. Food and Drug Administration (FDA) and Health Canada issued public statements alerting that some ranitidine medicines, including Zantac OTC, could contain NDMA at low levels and asked manufacturers to conduct testing. Evaluations are ongoing on both drug substance (active ingredient) and finished drug product. Due to inconsistencies in preliminary test results of the active ingredient used in the U.S. and Canadian products, Sanofi decided to conduct the voluntary recall in the U.S. and Canada in October 2019.

In Europe, fourth-quarter CHC sales decreased 11.7% to €325 million, impacted by changing regulatory requirements as well as divestments of non-strategic brands. Full-year 2019 CHC sales in Europe were down 6.4% to €1,311 million.

In the U.S., fourth-quarter CHC sales decreased 12.8% to €246 million, reflecting the impact of the Zantac recall. In the fourth quarter, Zantac sales were -€3m compared to €31 million in the fourth quarter of 2018, reflecting the recall as well as additional provisions for returns. Full-year 2019 CHC sales in the U.S. were down 3.6% to €1,086 million.

In Emerging Markets, fourth-quarter CHC sales increased 3.0% to €425 million, driven by performance in Asia. Full-year 2019 CHC sales in Emerging Markets increased 4.7% to €1,652 million.

In the Rest of the World, fourth-quarter CHC sales increased 2.7% to €156 million, driven by the strong performance of Allegra in Japan.

Vaccines

Net sales (€ million) Q4 2019
Change

at CER

2019
Change

at CER

Polio/Pertussis/Hib vaccines (incl. Hexaxim / Hexyon, Pentacel, Pentaxim and Imovax)

443 -13.7 % 1,946 +9.8 %
Influenza vaccines (incl. Vaxigrip, Fluzone HD, Fluzone & Flublok)

1,039 +69.1 % 1,891 +7.3 %
Meningitis/Pneumo vaccines (incl. Menactra)

124 -6.1 % 682 +8.4 %
Adult Booster vaccines (incl. Adacel )

147 +6.7 % 563 +16.2 %
Travel and other endemic vaccines

123 -7.7 % 539 +8.4 %
Other vaccines

32 +6.5 % 110 +13.8 %
Total Vaccines

1,908 +22.0 % 5,731 +9.3 %

8

Fourth-quarter Vaccines sales increased 22.0% to €1,908 million as the majority of U.S. influenza vaccines shipments occurred in the quarter, reflecting the delay in strain selection by the WHO at the beginning of the year. As a consequence, U.S. fourth-quarter Vaccines sales were up 33.1% to €1,002 million. In Europe and Emerging Markets, fourth-quarter Vaccines sales were up 15.1% (to €275 million) and up 14.2% (to €552 million), respectively, also driven by influenza vaccines performance. Full-year 2019 Vaccines sales were up 9.3% to €5,731 million.

In the fourth quarter, Polio/Pertussis/Hib (PPH) vaccines sales decreased 13.7% to €443 million, reflecting unfavorable delivery phasing of Hexaxim in Emerging Markets. Fourth-quarter Emerging Markets PPH vaccines sales were down 16.4% to €243 million. In the U.S., PPH vaccines sales were up 3.9% to €110 million in the fourth quarter driven by Pentacel. In Europe, over the period, PPH vaccines sales were down 9.6% to €75 million due to unfavorable delivery phasing on pediatric vaccines. Full-year 2019 PPH vaccines sales were up 9.8% to €1,946 million.

Influenza vaccines sales increased 69.1% to €1,039 million in the fourth quarter, as the majority of U.S. influenza vaccines shipments occurred in the quarter (up 65.7% to €705 million). U.S. performance also benefited from successful influenza differentiation strategy. Over the period, influenza vaccines sales in Europe (up 40.9% to €130 million) and in Emerging Markets (up 139% to €163 million) benefited from further quadrivalent vaccines penetration as well as an increase in vaccination coverage rates. Full-year 2019 influenza vaccines sales increased 7.3% to €1,891 million. U.S. influenza vaccines sales were stable (up 0.2%) in 2019 as a result of reserves for estimated higher returns, reflecting the later timing of supply compared with the previous year.

Fourth-quarter Menactra sales decreased 5.4% to €124 million, reflecting order phasing in the U.S. and continued expansion in Emerging markets. Full-year 2019 Menactra sales increased 8.6% to €682 million.

Fourth-quarter Travel and other endemic vaccines sales were €123 million, down 7.7%, reflecting lower rabies vaccines sales. Full-year 2019 Travel and other endemic vaccines sales were up 8.4% to €539 million.

Fourth-quarter Adult Booster vaccines sales were up 6.7% to €147 million, driven by performance in Europe (up 18.2% to €39 million) and Emerging Markets (up 50.0% to €27 million). In the US., over the period, Adult Booster vaccines were down 5.3% to €74 million, reflecting delivery phasing for Adacel. Full-year 2019 Adult Booster vaccines sales increased 16.2% to €563 million.

Company sales by geographic region

Sanofi sales (€ million)

Q4 2019

Change
at CER

2019

Change

at CER

United States

3,684

+11.8 %

12,756

+5.0

%

Emerging Markets(a)

2,675 +1.8 % 10,914 +8.7 %
of which Asia

883 -9.0 % 4,393 +8.5 %
of which Latin America

744 +7.5 % 2,734 +11.2 %
of which Africa, Middle East

634 +3.2 % 2,307 +1.7 %
of which Eurasia(b)

360 +19.8 % 1,312 +17.2 %
Europe(c)

2,344 0.0 % 8,852 -6.1 %
Rest of the World(d)

905 +0.6 % 3,604 +2.8 %
of which Japan

455 +0.5 % 1,908 +4.6 %

Total Sanofi sales

9,608

+4.7

%

36,126

+2.8

%

(a)
World excluding U.S., Canada, Western & Eastern Europe (except Eurasia), Japan, South Korea, Australia, New Zealand and Puerto Rico

Russia, Ukraine, Georgia, Belarus, Armenia and Turkey

Western Europe + Eastern Europe except Eurasia

Japan, South Korea, Canada, Australia, New Zealand, Puerto Rico

Fourth-quarter sales in the U.S. increased 11.8% to €3,684 million, reflecting strong Dupixent performance and quarterly phasing of influenza vaccines shipments. Full-year 2019 U.S. sales increased 5.0% to €12,756 million.

Fourth-quarter sales in Emerging Markets rose 1.8% to €2,675 million as growth in Vaccines (up 14.2%) and Diabetes (up 7.4%) was largely offset by lower sales of Established Rx Products (down 9.3%). In Asia, fourth-quarter sales were down 9.0% to €883 million, due to lower sales in China (down 21.0% to €453 million), mainly reflecting the impact of the VBP program. In Latin America, fourth-quarter sales increased 7.5% to €744 million driven by Mexico performance. Fourth-quarter sales in Brazil were up 2.4% to €249 million. In Africa and the Middle East region, fourth-quarter sales were up 3.2% to €634 million, mainly reflecting order phasing. Fourth-quarter sales in the Eurasia region increased 19.8% to €360 million, supported by strong growth in Turkey. Fourth-quarter sales in Russia were €168 million, up 1.3%. In Emerging Markets, full-year 2019 sales increased 8.7% to €10,914 million. In 2019, sales in China, Brazil and Russia were €2,704 million (up 8.8%), €1,013 million (up 1.6%) and €673 million (up 9.1%), respectively.

Fourth-quarter sales in Europe were stable at €2,344 million. Over the period, Dupixent and Vaccines performance were offset by lower Lovenox, Lemtrada, Lantus and CHC sales. In Europe, full-year 2019 sales decreased 6.1% (-1.3% at CS) to €8,852 million, reflecting divestment of the European generics business at the end of the third quarter of 2018.

Sales in Japan increased 0.5% to €455 million in the fourth quarter, driven by Dupixent which offset lower sales of Plavix and Vaccines. In Japan, full-year 2019 sales increased 4.6% to €1,908 million.

R&D update

Consult Appendix 9 for full overview of Sanofi’s R&D pipeline
Regulatory update

Regulatory updates since October 31, 2019 include the following:

In November, Dupixent (collaboration with Regeneron) was submitted to the FDA in children 6 to 11 years with moderate-to-severe atopic dermatitis.The FDA has granted a priority review and set a PDUFA date of May 26, 2020. Dupixent was also submitted for the same indication in the European Union in January.

In November, the FDA approved a supplemental NDA expanding the indication for Toujeo in the United States to include the treatment of pediatric patients 6 years and older with diabetes.

In November, the FDA approved a supplemental Biologics License Application for Fluzone High-Dose Quadrivalent (influenza vaccine) for use in adults 65 years of age and older.

In December, the China National Medical Products Administration (NMPA) approved Praluent for the treatment of adult patients with primary hypercholesterolaemia or mixed dyslipidemia and for the treatment of adult patients with established atherosclerotic cardiovascular disease to reduce myocardial infarction, stroke or unstable angina requiring hospitalization.

In December, the China National Medical Products Administration (NMPA) approved Fabrazyme as a long term enzyme replacement therapy in patients with confirmed diagnosis of Fabry disease.

In January, the European Commission approved the expansion of the indication for Toujeo in the European Union to include the treatment of diabetes in adolescents and children (6 years and older).

At the beginning of February 2020, the R&D pipeline contained 91 projects, including 38 new molecular entities in clinical development (or that have been submitted to the regulatory authorities). 39 projects are in phase 3 or have been submitted to the regulatory authorities for approval.

Portfolio update

Phase 3:

data from the OLE (Open Label Extension) study of Dupixent supporting the long term efficacy and safety profile were presented at the Maui Dermatology Conference in January.

Positive results of a pivotal phase 3 open-label, single-arm trial evaluating the safety and efficacy of sutimlimab in people with primary cold agglutinin disease (CAD) were presented at the Late Breaking Abstracts Session of the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper). This study met its primary and secondary endpoints.
from the EDITION JUNIOR phase 3 trial, evaluating Toujeo in children and adolescents with type 1 diabetes, were presented at the International Society for Pediatric and Adolescent Diabetes Annual Conference.

SAR408701, an anti-CEACAM5 antibody-drug conjugate, entered into phase 3 in second and third line non-small cell lung cancer (NSCLC).

Dupixent entered into phase 3 in bullous pemphigoid, chronic spontaneous urticaria and prurigo nodularis.

BIVV001 (recombinant coagulation factor VIII Fc) entered into phase 3 in hemophilia A.

Phase 2

BTK inhibitor, SAR442168, met the primary endpoint in a proof of concept trial in relapsing multiple sclerosis, with detailed results expected to be presented at an upcoming medical meeting in Q2 2020.

Olipudase alfa, a recombinant human acid sphingomyelinase, demonstrated positive results in two separate clinical trials evaluating olipudase alfa for the treatment of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. Olipudase alfa is the first and only investigational enzyme replacement therapy in late-stage development for the treatment of ASMD. No treatments are currently approved for ASMD.

SAR439859, a selective estrogen receptor degrader (SERD), has entered into a pivotal phase 2 study in second and third line metastatic breast cancer as a monotherapy, a phase 2 study to enable examination in the adjuvant setting, and a phase 1 combination with palbociclib.

Phase 1

A candidate vaccine for Yellow Fever entered into phase 1.

THOR-707, an engineered "not-alpha" IL-2, entered into phase 1 for the treatment of solid tumors, with the acquisition of Synthorx.

SAR441000, an mRNA-based intratumoral immunotherapy, entered into phase1 in combination with PD-1.

Synthorx

On January 23, Sanofi announced the completion of its acquisition of Synthorx, enhancing Sanofi’s position as an emerging leader in the area of oncology and immunology. Through the acquisition Sanofi gained access to THOR-707 and an innovative platform that complements the company’s oncology and immunology research.

Sustainable performance update

Sanofi’s leadership in water management was recently recognized by CDP in its rating upgrade to A- from B. CDP is a global non-profit organization that drives companies and governments to reduce greenhouse gas emissions, safeguard water resources.

Sanofi considers water as a sustainable renewable resource and believes that shortages of water could become a major obstacle to public health involving diseases associated with lack of access to safe drinking water, inadequate sanitation and poor hygiene. Consequently the company has implemented a dedicated program to reduce water consumption and promote its reuse. Sanofi has already exceeded its 2020 target to reduce water consumption.

2019 fourth-quarter and full-year 2019 financial results(9)

Business Net Income(9)

In the fourth quarter of 2019, Sanofi generated net sales of €9,608 million, an increase of 6.8% (up 4.7% at CER). Full-year 2019 sales were €36,126 million, up 4.8% on a reported basis (up 2.8% at CER).

Fourth-quarter other revenues increased 24.3% (up 20.4% at CER) to €409 million, reflecting the VaxServe sales contribution of non-Sanofi products (€358 million, up 32.4% at CER). Full-year 2019 other revenues increased 24.0% (up 18.0% at CER) to €1,505 million, driven by the VaxServe sales contribution of non-Sanofi products (€1,273 million, up 26.3% at CER) and the consolidation of collaboration revenues from Swedish Orphan Biovitrum AB (SOBI).

Fourth-quarter Gross Profit increased 6.0% to €6,562 million (up 3.8% at CER). The gross margin ratio decreased 0.5 percentage points to 68.3% (68.2% at CER) versus the fourth quarter of 2018. The negative impact from net price adjustments of inventory in the channel in China, products and geographical mix in CHC, U.S. Diabetes net price evolution and Vaccines more than offset the favorable impact from Dupixent growth. In the fourth quarter of 2019, the gross margin ratio of segments were 72.8% for Pharmaceuticals (up 0.7 percentage points), 64.5% for CHC (down 1.5 percentage points) and 60.1% for Vaccines (down 0.3 percentage points). Full-year 2019 Gross Profit increased 5.3% to €25,657 million (up 3.1% at CER). In 2019, the gross margin ratio increased 0.3 percentage points to 71.0% (70.8% at CER) versus 2018.

Research and Development (R&D) expenses increased 0.5% to €1,687 million in the fourth quarter of 2019. At CER, R&D expenses decreased 0.7% reflecting smart spending initiatives as well as portfolio prioritization. In the fourth quarter, the ratio of R&D to sales decreased 1.1 percentage points to 17.6% compared to the fourth quarter of 2018. In 2019, R&D expenses increased 2.2% to €6,022 million (up 0.2% at CER). In 2019, the ratio of R&D to sales was 0.4 percentage points lower at 16.7% compared to 2018.

Fourth-quarter selling general and administrative expenses (SG&A) increased 0.1% to €2,724 million. At CER, SG&A expenses were down 1.4%, reflecting a decrease in general expenses which more than offset increased investments in Specialty Care and Vaccines. In the fourth quarter, the ratio of SG&A to sales decreased 1.8 percentage points to 28.4% compared to the fourth quarter of 2018. In 2019, SG&A expenses increased 0.5% to €9,880 million (down 1.4% at CER). In 2019, the ratio of SG&A to sales was 1.2 percentage points lower at 27.3% compared to 2018.

Fourth-quarter operating expenses were €4,411 million, an increase of 0.3% and a decrease of 1.2% at CER. Full-year 2019 operating expenses were €15,902 million, an increase of 1.1% and down 0.8% at CER.

Fourth-quarter other current operating income net of expenses was -€70 million versus -€148 million in the fourth quarter of 2018. In the fourth quarter of 2019, this line included an expense of €241 million (versus an expense of €65 million in the fourth quarter of 2018) corresponding to the share of profit to Regeneron of the monoclonal antibodies Alliance, reimbursement of development costs by Regeneron and the reimbursement of commercialization-related expenses incurred by Regeneron. In the fourth quarter of 2019, this line also included a one-time income due to a legislation change related to supplementary pension plans in France. In the fourth quarter of 2018, the "other current operating income net of expenses" line also included charges related to a legal contingency provision as well as a capital gain on an associate company and other accruals, which in aggregate represented a net charge of €72 million. In 2019, other current operating income net of expenses was -€382 million versus -€64 million in 2018. The full-year 2019 expense associated with the monoclonal antibodies Alliance with Regeneron was €681 million, which compared with an expense of €211 million in 2018 (see appendix 7 for further details).

The share of profit from associates was €119 million in the fourth quarter versus €121 million in 2018, mainly reflecting the share of profit in Regeneron. In 2019, the share of profit from associates was broadly stable at €420 million versus €423 million in 2018.

In the fourth quarter, non-controlling interests were -€8 million versus -€22 million in prior period, reflecting the end of non-controlling interests related to the Alliance with Bristol-Myers Squibb on Plavix and Avapro. In 2019, non-controlling interests were -€35 million versus -€106 million for 2018.

See Appendix 3 for 2019 fourth-quarter consolidated income statement; see Appendix 11 for definitions of financial indicators, and Appendix 4 for reconciliation of IFRS net income reported to business net income.

Fourth-quarter business operating income increased 26.0% to €2,192 million. At CER, business operating income increased 20.9%. The ratio of business operating income to net sales increased 3.5 percentage points to 22.8% versus the fourth quarter of 2018. Over the period, the business operating income ratio of segments were 28.7% for Pharmaceuticals (up 1.6 percentage points), 27.3% for CHC (down 1.7 percentage points) and 37.6% for Vaccines (up 1.5 percentage points). In 2019, business operating income was €9,758 million, up 9.8% (up 7.1% at CER). In 2019, the ratio of business operating income to net sales increased 1.2 percentage points to 27.0%.

Net financial expenses were -€63 million in the fourth quarter versus -€60 million in the same period of 2018, reflecting lower cost of net debt. The fourth quarter of 2018 included a gain of €22 million in the market value of a financial investment. Full-year 2019 net financial expenses were -€264 million versus -€271 million in 2018.

Fourth-quarter and full-year 2019 effective tax rate were 22.1% and 22.0%, respectively. Sanofi expects its effective tax rate to be around 22% in 2020.

Fourth-quarter business net income(9) increased 23.5% to €1,684 million and increased 18.4% at CER. The ratio of business net income to net sales increased 2.3 percentage points to 17.5% versus the fourth quarter of 2018. In 2019, business net income(9) increased 9.8% to €7,489 million and increased 7.0% at CER. The ratio of business net income to net sales increased 0.9 percentage points to 20.7% versus 2018.

In the fourth quarter of 2019, business earnings per share(9) (EPS) increased 21.8% to €1.34 on a reported basis and 17.3% at CER. The average number of shares outstanding was 1,253.1 million versus 1,245.6 million in the fourth quarter of 2018.

In 2019, business earnings per share(9) was €5.99, up 9.5% on a reported basis and up 6.8% at CER. The average number of shares outstanding was 1,249.9 million in 2019 versus 1,247.1 million in 2018.

Reconciliation of IFRS net income reported to business net income (see Appendix 4)

In 2019, the IFRS net income was €2,806 million. The main items excluded from the business net income were:

An amortization charge of €2,146 million related to fair value remeasurement on intangible assets of acquired companies (primarily Genzyme: €727 million, Bioverativ: €488 million, Boehringer Ingelheim CHC business: €240 million, Aventis: €197 million) and to acquired intangible assets (licenses/products: €102 million). An amortization charge of €510 million related to fair value remeasurement on intangible assets of acquired companies (primarily Genzyme: €177 million, Bioverativ: €108 million, Boehringer Ingelheim CHC business: €56 million, Aventis: €44 million) and to acquired intangible assets (licenses/products: €22 million) was recorded in the fourth quarter. These items have no cash impact on the Company.

An impairment of intangible assets of €3,604 million mainly related to Eloctate (€2,803 million due to revision of sales projections), Zantac (€352 million), sotagliflozin and Lemtrada. The fourth quarter included an impairment of intangible assets of €1,581 million of which €1,194 million related to Eloctate and €169 million to Zantac.

Restructuring costs and similar items of €1,062 million (of which €158 million in the fourth quarter) mainly related to streamlining initiatives in Japan, Europe and the U.S.

An income of €238 million mainly reflecting a decrease of Bayer contingent considerations linked to Lemtrada (an income of €214 million of which €74 million in the fourth quarter), a contingent price adjustment on the disposal of SP MSD (€192 million) and a fair value remeasurement on the CVR price (a charge of €49 million of which €32 million in the fourth quarter).

A net income of €327 million (of which a charge of €67 million in the fourth quarter) mainly related to litigation.

A €1,866 million tax effect arising from the items listed above, mainly comprising €1,409 million of deferred taxes generated by amortization and impairments of intangible assets and €311 million associated with restructuring costs and similar items. The fourth quarter tax effect was €587 million, including €503 million of deferred taxes generated by amortization and impairments of intangible assets and €64 million associated with restructuring costs and similar items (see Appendix 4).

See Appendix 3 for 2019 fourth-quarter consolidated income statement; see Appendix 11 for definitions of financial indicators, and Appendix 4 for reconciliation of IFRS net income reported to business net income.

An expense of €165 million net of tax (of which €71 million In the fourth quarter) related to restructuring costs of associates and joint ventures and expenses arising from the impact of acquisitions on associates and joint ventures.

Capital Allocation

In 2019, Free Cash Flow (see definition on Appendix 11) increased 48.6% to €6,026 million, after net changes in working capital (-€580 million), capital expenditures (-€1,405 million) and other asset acquisitions1 (-€576 million) net of disposal proceeds1 (€490 million), and payments related to restructuring and similar items (-€1,142 million). Over the period, the dividend paid by Sanofi was €3,834 million and proceeds from disposals2 were €672 million. As a consequence, net debt decreased from €17,628 million at December 31, 2018, to €15,107 million at December 31, 2019 (amount net of €9,427 million cash and cash equivalents).

Bristol-Myers Squibb Reports Fourth Quarter and Full Year Financial Results for 2019

On February 6, 2020 -Bristol-Myers Squibb Company (NYSE:BMY) reported results for the fourth quarter and full year of 2019, which highlight continued strong sales and robust operating performance, along with the ongoing advancement of the company’s pipeline (Press release, Bristol-Myers Squibb, FEB 6, 2020, View Source [SID1234553914]).

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"By all measures, 2019 was a transformative year for Bristol-Myers Squibb as we progressed our strategy through the acquisition of Celgene, delivered strong operational and financial performance, and continued to drive important science for patients," said Giovanni Caforio, M.D., chairman and chief executive officer, Bristol-Myers Squibb. "With an expanded portfolio of high-performing brands, eight potential commercial launch opportunities, a deep and broad early pipeline, and the financial flexibility to continue to invest in innovation, the company enters 2020 uniquely positioned to transform patients’ lives through science and create long-term sustainable growth."

Fourth Quarter

$ amounts in millions, except per share amounts

*Includes Celgene results from November 20, 2019 through December 31, 2019.

FOURTH QUARTER FINANCIAL RESULTS

All comparisons are made versus the same period in 2018 unless otherwise stated.

Bristol-Myers Squibb posted fourth quarter revenues of $7.9 billion, an increase of 33%, primarily due to the Celgene acquisition (closed on November 20, 2019). Revenues increased 34% when adjusted for foreign exchange impact.
U.S. revenues increased 42% to $4.8 billion in the quarter. International revenues increased 21% to $3.2 billion in the quarter. When adjusted for foreign exchange impact, international revenues increased 23%.
Gross margin as a percentage of revenue decreased from 72.0% to 68.6% in the quarter primarily due to unwinding of inventory purchase price accounting adjustments, partially offset by product mix.
Marketing, selling and administrative expenses increased 30% to $1.7 billion in the quarter primarily due to $400 million costs associated with the Celgene acquisition.
Research and development expenses increased 52% to $2.1 billion in the quarter primarily due $500 million related to the Celgene acquisition.
Amortization of acquired intangible assets was $1.1 billion in the quarter primarily due to the Celgene acquisition.
Income taxes were $931 million despite pre-tax loss of $129 million in the current quarter primarily due to the Otezla (apremilast) divestiture, certain non-deductible expenses and purchase price adjustments. The effective tax rate was 23.1% in the same period a year ago.
The company reported net loss attributable to Bristol-Myers Squibb of $1.1 billion, or $0.55 per share, in the fourth quarter, compared to net earnings of $1.2 billion, or $0.71 per share, for the same period a year ago. The results in the current quarter include costs and expenses resulting from purchase price accounting, contingent value right fair value adjustments and other acquisition and integration expenses.
The company reported non-GAAP net earnings attributable to Bristol-Myers Squibb of $2.4 billion, or $1.22 per share, in the fourth quarter, compared to net earnings of $1.5 billion, or $0.94 per share, for the same period a year ago. A discussion of the non-GAAP financial measures is included under the "Use of Non-GAAP Financial Information" section.
Cash, cash equivalents and marketable debt securities were $16.2 billion and debt was $46.7 billion as of December 31, 2019.
ACQUISITION OF CELGENE CORPORATION

In November, the company announced the completion of its acquisition of Celgene Corporation following the receipt of regulatory approval from all government authorities required by the merger agreement. (link)
As announced in August 2019, in connection with the regulatory approval process of the acquisition of Celgene, Celgene entered into an agreement to divest the global rights to Otezla to Amgen Inc. for $13.4 billion in cash. On November 21, 2019, the Otezla divestiture was completed.
Otezla is a trademark of Amgen Inc.

FOURTH QUARTER PRODUCT AND PIPELINE UPDATE

Product Revenue Highlights

Global product revenue increases in the fourth quarter of 2019, as compared to the fourth quarter of 2018, drove revenue increases.

Product

Quarter Ended
December 31, 2019

* Represents product revenues for Celgene products only from November 20, 2019, which was the date of the closing of the acquisition, through December 31, 2019. See "Worldwide Product Revenue," which is available on bms.com/investors, for information on the revenue for these products and other products of the company and Celgene presented on a quarterly basis for 2018 and 2019.

Oncology

Opdivo

Regulatory

In January, the company announced that the U.S. Food and Drug Administration (U.S. FDA) has accepted for priority review its supplemental Biologics License Application (sBLA) for Opdivo plus Yervoy for the first-line treatment of patients with metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations with an FDA action date of May 15, 2020.
In January, the company announced that it has withdrawn its European application for Opdivo (nivolumab) plus Yervoy (ipilimumab) for the first-line treatment of advanced non-small cell lung cancer (NSCLC).
In November, the company announced that the U.S. FDA accepted its sBLA and granted Breakthrough Therapy Designation for Opdivo plus Yervoy for the treatment of patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib with an FDA action date of March 10, 2020.
Clinical

In November, the company announced results from CheckMate -915, a randomized Phase 3 study evaluating Opdivo plus Yervoy versus Opdivo alone for the adjuvant treatment of patients who have had a complete surgical removal of stage IIIb/c/d or stage IV (no evidence of disease) melanoma. The study did not meet one of its co-primary endpoints of recurrence-free survival (RFS) in patients whose tumors expressed PD-L1 <1%. The study will continue to assess the other co-primary endpoint of RFS in the intent-to-treat population. (link)
Cardiovascular

Eliquis

Clinical

In November, the company and its alliance partner Pfizer announced the initiation of a new randomized, controlled study, GUARD-AF (ReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals). (link)
Immunology

Orencia

Regulatory

In December, the company announced that the U.S. FDA granted Breakthrough Therapy Designation for Orencia (abatacept) for the prevention of moderate to severe acute graft-versus-host disease in hematopoietic stem cell transplants from unrelated donors.
Clinical

In November, at the 2019 American College of Rheumatology and Association of Rheumatology Professionals Annual Meeting, the company announced new data from the randomized Phase IIIb Assessing Very Early Rheumatoid arthritis Treatment (AVERT)-2 trial exploring de-escalation of therapy in early, seropositive rheumatoid arthritis patients who achieved sustained Simplified Disease Activity Index remission following induction with Orencia and methotrexate. (link)
Hematology

Conferences

In December, at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the company announced important new data and analysis from its hematology portfolio:

QUAZAR AML-001: a study evaluating investigational agent CC-486 as maintenance therapy in a broad population of patients with front-line, newly diagnosed acute myeloid leukemia who have achieved complete remission with intensive induction chemotherapy. (link)
TRANSCEND NHL 001: an evaluation of lisocabtagene maraleucel (liso-cel) in patients with in relapsed/refractory large B-cell lymphomas. (link)
TRANSCEND CLL 004: a study evaluating liso-cel in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. (link)
PILOT: a study evaluating liso-cel in second-line patients with relapsed or refractory large B-cell non-Hodgkin’s lymphoma patients who were ineligible for high-dose chemotherapy and hematopoietic stem cell transplant. (link)
An analysis of patients with relapsed/refractory large B-cell non-Hodgkin lymphoma who received liso-cel in the outpatient setting across three studies. (link)
The following data were also presented at the ASH (Free ASH Whitepaper) Annual Meeting by the company and its partners:

The company and its partner Acceleron Pharma Inc. presented data evaluating Reblozyl in patients with anemia associated with a range of serious and rare blood diseases. Data included the initial results from a Phase 2 study in myelofibrosis-associated anemia, and long-term results from two pivotal Phase 3 studies—the MEDALIST study in adult patients with anemia associated with very low to intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts and require red blood cell (RBC) transfusions, and the BELIEVE study in adult patients with anemia associated with beta thalassemia who require regular RBC transfusions. (link)
The company and its partner bluebird bio, Inc. presented updated safety and efficacy results from the ongoing Phase 1 study, CRB-402, evaluating bb21217, an investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapy being studied in patients with relapsed/refractory multiple myeloma. (link)
The company and its alliance partner Pfizer announced results from retrospective real-world data analyses reporting outcomes on the safety and effectiveness of Eliquis (apixaban) compared to low molecular weight heparin or warfarin for the treatment of venous thromboembolism in patients with active cancer. (link )
Revlimid

Regulatory

In December, the company announced that the European Commission approved a new indication for Revlimid (lenalidomide), in combination with rituximab, for the treatment of adult patients with previously treated follicular lymphoma.
Reblozyl

Regulatory

In November, Celgene and partner Acceleron Pharma Inc. announced the FDA approved Reblozyl for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions. The company is also seeking approval of Reblozyl for the treatment of anemia in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts and require red blood cell (RBC) transfusions and has an FDA action date of April 4, 2020.
Clinical

In January, the company and its partner Acceleron Pharma Inc. announced that the New England Journal of Medicine published results from MEDALIST, the pivotal Phase 3 study evaluating the use of Reblozyl to treat anemia in patients with very low- to intermediate-risk MDS who have ring sideroblasts and require RBC transfusions, and who had failed, were intolerant to, or ineligible for/unlikely to respond to treatment with erythropoiesis-stimulating agents. (link)
ide-cel

Clinical

In December, the company and its partner bluebird bio, Inc. announced that KarMMa, a pivotal, open-label, single arm, multicenter, Phase 2 study evaluating ide-cel (bb2121) in patients with R/RMM, met its primary endpoint and key secondary endpoint. (link)
liso-cel

Regulatory

In December, the company announced the submission of its Biologics License Application (BLA) to the U.S. FDA for liso-cel, its autologous anti-CD19 CAR T-cell immunotherapy for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after at least two prior therapies.
BUSINESS DEVELOPMENT UPDATE

In February, the company and its partner BioMotiv announced the launch of Anteros Pharmaceuticals, a biotechnology company focused on developing a new class of drugs for fibrotic and other inflammatory diseases, as part of its strategic partnership agreement.
In January, the company and its partner Nektar Therapeutics announced that the companies amended the strategic collaboration agreement for bempegaldesleukin plus Opdivo.
In January, the company announced that it completed the divestiture of its oral solid, biologics, and sterile product manufacturing and packaging facility in Anagni, Italy, to Catalent Inc.
CAPITAL ALLOCATION

Bristol-Myers Squibb maintains a balanced approach to capital allocation focused on future business development and sourcing external innovation as a priority, de-leveraging in the near term to maintain strong investment grade credit ratings and less than 1.5x debt/EBITDA by 2023, planning for annual dividend increases, subject to board approval, and disciplined share repurchases.

In that context, the company reported its board of directors approved an increase of $5 billion to the share repurchase authorization for the company’s common stock. This is incremental to the current share repurchase program announced in October 2016 under which the company has approximately $1 billion remaining and increases the company’s total outstanding share repurchase authorization under the company’s share repurchase program to approximately $6 billion.

The specific timing and number of shares repurchased will be determined by the company’s management at its discretion and will vary based on market conditions, securities law limitations and other factors. The share repurchase program does not obligate the company to repurchase any specific number of shares, does not have a specific expiration date and may be suspended or discontinued at any time. The repurchases may be effected through a combination of one or more open market repurchases, privately negotiated transactions, transactions structured through investment banking institutions and other derivative transactions.

FINANCIAL GUIDANCE

Bristol-Myers Squibb is providing 2020 GAAP EPS guidance range of $0.75 to $0.95 and non-GAAP EPS guidance range of $6.00 to $6.20. In addition, the company is providing for 2021, a non-GAAP EPS guidance range of $7.15 to $7.45. Both GAAP and non-GAAP guidance for 2020 and non-GAAP guidance for 2021 includes the impact of the Celgene acquisition and the Otezla divestiture and assume current exchange rates. Key 2020 GAAP and non-GAAP line-item guidance assumptions are:

The financial guidance excludes the impact of any potential future strategic acquisitions and divestitures and any specified items that have not yet been identified and quantified. The 2020 and 2021 non-GAAP EPS guidance further excludes other specified items as discussed under "Use of Non-GAAP Financial Information." A reconciliation of non-GAAP financial measures to the most comparable GAAP measure and the reasons why management believes the use of these measures is important are provided in supplemental materials available on the company’s website. For 2021 non-GAAP EPS guidance, there is no reliable or reasonably estimable comparable GAAP measure as discussed below. The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Company and Conference Call Information

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook, and Instagram.

There will be a conference call on February 6 at 8:30 a.m. ET during which company executives will review financial information and address inquiries from investors and analysts. Investors and the general public are invited to listen to a live webcast of the call at View Source or by calling the U.S. toll free 888-204-4368 or international 786-789-4797, confirmation code: 5605395. Materials related to the call will be available at the same website prior to the conference call. A replay of the call will be available beginning at 11:45 a.m. ET on February 6, 2019 through 11:45 a.m. ET on February 20, 2020. The replay will also be available through View Source or by calling the U.S. toll free 888-203-1112 or international 719-457-0820, confirmation code: 5605395.

Use of Non-GAAP Financial Information

This earnings release contains non-GAAP financial measures, including non-GAAP earnings and related EPS information that are adjusted to exclude certain costs, expenses, gains and losses and other specified items that are evaluated on an individual basis. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are available on the company’s website at www.bms.com .

These non-GAAP items are adjusted after considering their quantitative and qualitative aspects and typically have one or more of the following characteristics, such as being highly variable, difficult to project, unusual in nature, significant to the results of a particular period or not indicative of future operating results. Similar charges or gains were recognized in prior periods and will likely reoccur in future periods, including amortization of acquired intangible assets beginning in the fourth quarter of 2019, including product rights that generate a significant portion of our ongoing revenue, unwind of inventory fair value adjustments, acquisition and integration expenses, restructuring costs, accelerated depreciation and impairment of property, plant and equipment and intangible assets, R&D charges or other income resulting from up-front or contingent milestone payments in connection with the acquisition or licensing of third-party intellectual property rights, costs of acquiring a priority review voucher, divestiture gains or losses, stock compensation resulting from accelerated vesting of Celgene awards, certain retention-related compensation charges related to the Celgene acquisition, pension, legal and other contractual settlement charges, interest expense on the notes issued in May 2019 prior to our acquisition of Celgene and interest income earned on the net proceeds of those notes and amortization of fair value adjustments of debt assumed from Celgene, among other items. Deferred and current income taxes attributed to these items are also adjusted for considering their individual impact to the overall tax expense, deductibility and jurisdictional tax rates. This earnings release also provides international revenues excluding the impact of foreign exchange.

Non-GAAP information is intended to portray the results of the company’s baseline performance, supplement or enhance management, analysts and investors overall understanding of the company’s underlying financial performance and facilitate comparisons among current, past and future periods. For example, non-GAAP earnings and EPS information is an indication of the company’s baseline performance before items that are considered by us to not be reflective of the company’s ongoing results. In addition, this information is among the primary indicators that we use as a basis for evaluating performance, allocating resources, setting incentive compensation targets and planning and forecasting for future periods. This information is not intended to be considered in isolation or as a substitute for net earnings or diluted EPS prepared in accordance with GAAP and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure.

Amortization of acquired intangible assets were previously included in non-GAAP earnings and EPS information. These amounts have become significant to the financial results subsequent to the Celgene acquisition and as a result, have been excluded in the non-GAAP results to better reflect our core operating performance. Comparable prior period non-GAAP results have not been revised to include this adjustment as the related amounts were insignificant ($97 million in 2018).

In connection with presenting our outlook, we are also providing non-GAAP EPS guidance for 2021. There is no reliable or reasonably estimable comparable GAAP measure for this because we are not able to reliably predict the impact of specified items beyond the next twelve months. As a result, the reconciliation of this non-GAAP measure to the most directly comparable GAAP measure is not available without unreasonable effort. In addition, the company believes such a reconciliation would imply a degree of precision and certainty that could be confusing to investors. The variability of the specified items may have a significant and unpredictable impact on our future GAAP results.

Website Information

We routinely post important information for investors on our website, BMS.com, in the "Investors" section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, SEC filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document.

$500,000 Research Grant to Combat Cancer Treatment Resistance Awarded by ALK Positive and GO2 Foundation

On February 6, 2020 ALK Positive (a patient-led group of 1,900+ lung cancer patients and caregivers in 50+ countries) and GO2 Foundation for Lung Cancer (a global lung cancer advocacy and education organization) are reported awarding a two-year, $500,000 Research Collaboration Grant to two renowned lung cancer researchers dedicated to overcoming treatment resistance (Press release, Bonnie J Addario Lung Cancer Foundation, FEB 6, 2020, View Source [SID1234553934]).

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This grant funds research to help break down barriers to successful lung cancer treatment and to identify new treatments. A 2019 partnership between ALK Positive and the GO2 Foundation raised the funds for this grant.

Patients with ALK+ lung cancer benefit from targeted therapy medications but drug resistance ultimately limits this benefit: most patients develop progressive disease within one to three years of treatment.

Dr. Trever Bivona, associate professor of medicine at the University of California – San Francisco, and Dr. Christine Lovly, associate professor of medicine, Vanderbilt University Medical Center, are receiving the grant for their project, "Transforming ALK+ lung cancer into a chronic or curable condition by combating drug resistance." Drs. Bivona and Lovly are recognized lung cancer experts. The study will explore if new combinations of targeted therapies can delay or prevent treatment resistance.

"ALK Positive is grateful to GO2 Foundation for their efforts in coordinating this partnership. The fundraising efforts of the ALK Positive members and their supporters have been extraordinary, and we are hopeful this project will make significant strides in accomplishing our mission to ‘improve the life expectancy and quality of life for all ALK-positive patients worldwide’," said Gina Hollenbeck, the group’s president.

"One of the greatest barriers to surviving lung cancer is treatment resistance. This grant will help overcome this significant obstacle, give patients hope, and help to achieve the goal of making lung cancer a chronically-managed disease," said Bonnie J. Addario, co-founder and board chair of the GO2 Foundation. "Lung cancer is truly leading the way to make research personal. This is an example of how patients, advocates and researchers are putting their heads together to create new, game-changing research."

"I am honored to work alongside the ALK Positive community on this effort to accelerate our understanding of resistance and to find new ways to fight it," said Bivona. "At a time when we are making great strides in the treatment of lung cancer, yet research funding is lacking, we are deeply appreciative of this funding from members of ALK Positive," said Lovly.