On October 31, 2019, Myovant Sciences Ltd. ("Myovant") and Sumitomo Dainippon Pharma Co., Ltd. ("DSP") reported that it has entered into a letter agreement (the "Letter Agreement") pursuant to which Myovant and DSP agreed to take certain actions in connection with the transactions described in the publicly announced Memorandum of Understanding entered into by Roivant Sciences Ltd. ("Roivant") and DSP, which matters have been agreed to in a Transaction Agreement dated October 31, 2019 between DSP, Roivant and other parties (the "DSP-Roivant Agreement") (Filing, 8-K, Myovant Sciences, OCT 31, 2019, View Source [SID1234550112]). Upon the closing under the DSP-Roivant Agreement (the "Closing"), DSP, or an entity that will become a subsidiary of DSP (DSP or such entity, the "Acquiring Entity"), will acquire Roivant’s ownership interest in Myovant and become a significant shareholder of Myovant (the "Transactions"). Myovant understands that Roivant has committed in the DSP-Roivant Agreement that, at or prior to the closing, Roivant will ensure that the Acquiring Entity will obtain not less than a majority of the outstanding shares of Myovant by purchasing additional Myovant shares at prices not below market trading prices and delivering such shares, or voting rights with respect thereto, to the Acquiring Entity.

The terms of the Letter Agreement provide, among other things:

1.The Myovant Board of Directors has approved the Transactions and, subject to and at or prior to the Closing, the appointment of the Acquiring Entity’s director designees to the Myovant Board as described below.

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2. At or promptly following the Closing, Myovant and DSP will enter into a secured low-interest Loan Agreement under which DSP will commit to provide Myovant a five-year term loan facility of US$350 million with a total interest rate in the single digits subject to further transfer pricing analysis and otherwise on mutually agreed terms (the "Loan Agreement").

3. The Myovant Board will (i) replace the three currently serving Roivant-selected directors with three DSP-selected directors who will be appointed to the Myovant Board, (ii) appoint two DSP-selected directors to the Nominating and Corporate Governance Committee to replace two currently serving members, and (iii) appoint one DSP-selected director to the Compensation Committee to replace one currently serving member.

4. At or prior to the Closing, the Myovant Bye-Laws will be amended to (i) remove the requirement that each of the Nominating and Corporate Governance Committee and the Compensation Committee be made up solely of Independent Directors (as defined below), provided that the Audit Committee shall continue to be made up solely of Independent Directors; and (ii) provide that the Board delegates to the Nominating and Corporate Governance Committee the right to fix the size of the Board and fill vacancies on the Board, other than three Independent Directors and their direct or indirect successors.

5. At the Closing, Myovant and the Acquiring Entity will enter into an Investor Rights Agreement that contains, among others, the following provisions:

(a) At all times that DSP and its affiliates (including the Acquiring Entity) hold 50% or more of the outstanding shares of Myovant (the "Ownership Threshold"):

(i) (A) the Myovant Board will include a minimum of three directors who each meet the definition of "independent director" as is required by New York Stock Exchange rules and who are independent of DSP and the Acquiring Entity ("Independent Directors") and at least one of whom is a financial expert, and (B) DSP has agreed that, provided that the existing Independent Directors serving on the Myovant Board continue to satisfy the requirements to serve as an independent director, the term of the current independent directors serving on the Myovant Board will continue;

(ii) the Audit Committee of the Myovant Board shall comprise the Independent Directors; the Nominating and Corporate Governance Committee shall comprise two DSP-selected directors and one Independent Director; and the Compensation Committee shall comprise two Independent Directors and one DSP-selected director;

(iii)the Bye-Law pursuant to which the Board delegates its right to the Nominating and Corporate Governance Committee will not be revised without prior written consent by DSP; and

(iv)DSP will vote its shares in connection with each election of Independent Directors in the same proportion as the shares held by shareholders other than DSP and its subsidiaries and will not, with respect to the election of Independent Directors, engage in any solicitation of proxies.

(b)Until such time as DSP or its subsidiaries hold less than 35% of the outstanding shares of Myovant and its subsidiaries, Myovant will not be permitted to take or commit to taking the following actions without prior approval of the Independent Directors:

(i)participation in specified "related-party transactions" between Myovant and DSP or any affiliate of DSP including use of DSPs commercial infrastructure (other than pursuant to the Loan Agreement in accordance with its terms);

(ii)any amendment of Myovant’s Certificate of Incorporation, Memorandum of Association, Committee Charters or Bye-Laws that would remove the Independent Directors, cause the appointment of any member of the Audit Committee who is not an Independent Director or change the right of the Independent Directors to approve the "related-party transactions"; or

(iii) making any modification of or causing Myovant to waive any rights under the Loan Agreement or the Investor Rights Agreement to expand DSP’s or the Acquiring Entity’s, as the case may be, rights thereunder.

6. A standstill provision, which provides that until such time as DSP or its subsidiaries hold less than 35% of the outstanding shares of Myovant, any transaction proposed by DSP or its controlled affiliates that would cause DSP or its subsidiaries to hold beneficial ownership of greater than 60% of the outstanding voting power of Myovant must be either:

(a)(i) made on a confidential basis to the Independent Directors; provided that after the three-year anniversary of the Closing, this requirement will only require a period of confidential discussions with the Independent Directors prior to making a public announcement thereof and shall except disclosures that are required by law;

(ii)until the three-year anniversary of the Closing, subject to approval by a majority of the Independent Directors; and

(iii)subject to a non-waivable condition requiring approval or acceptance by the holders of a majority of the Myovant shares voting and that are not beneficially owned by DSP or its affiliates;

or

(beffected under the circumstances set forth in a specified section of Myovant’s Bye-Laws having to do with third-party acquisition proposals.

7.Myovant has agreed, until the Closing, to reasonably assist and reasonably cooperate with Roivant in complying with the interim operating covenants contained in the DSP-Roivant Agreement that relate to Myovant, in which Roivant has agreed, among other things, to cause Myovant to (a) afford to DSP reasonable access to its offices, properties, employees and business and financial records, (b) furnish to DSP such additional information concerning its assets, properties, operations and businesses as DSP may reasonably request, and (c) conduct its business in the ordinary course, including refraining from taking a list of actions without DSP’s consent, including (subject to certain limitations) but not limited to incurrence of additional indebtedness, issuance of equity securities, granting of liens, and sales of assets.

On October 31, 2019 Oncolytics Biotech Inc. (NASDAQ:ONCY)(TSX:ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reorted an update on its partner, Adlai Nortye’s, clinical progress and approval by the National Medical Products Administration (NMPA) of China for initiating a phase 3 clinical trial for pelareorep (Press release, Oncolytics Biotech, OCT 31, 2019, View Source [SID1234550111]).

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"We congratulate Adlai on this significant regulatory and business achievement that paves the way for pelareorep’s development in the world’s second largest pharmaceutical market," said Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development. "Since the consummation of this partnership almost two years ago, we’ve been very happy with how Adlai is progressing the development of pelareorep in China, the second largest and rapidly growing pharmaceutical market in the world."

The phase 3 study, initially based on positive results from the randomized phase 2 metastatic breast cancer study IND-213, will be finalized based on data from Oncolytics’ AWARE-1 breast cancer study in combination with Roche’s Tecentriq and BRACELET-1 metastatic breast cancer study in combination with Pfizer’s and Merck KGaA’s Bavencio. These studies provide valuable biomarker data that will help define enrollment criteria to include patients most likely to respond to treatment with pelareorep and increase the likelihood of a positive clinical outcome in this important phase 3 registrational study.

Oncolytics and Adlai Nortye entered into an $86.6 million regional licensing agreement in November 2017, providing Adlai with exclusive development and commercialization rights to pelareorep in China, Hong Kong, Macau, Singapore, South Korea and Taiwan. To date Oncolytics has received $5 million in up front payments and is eligible for $81.6 million in milestone payments.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On October 31, 2019 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported it has concluded an End-of-Phase II Meeting with the U.S. Food and Drug Administration (FDA) regarding its recently completed Phase II study of Namodenoson in the treatment of hepatocellular cancer (HCC), the most common form of liver cancer (Press release, Can-Fite BioPharma, OCT 31, 2019, View Source [SID1234550100]). The purpose of the meeting was to review the Phase II study data with the FDA and to present Can-Fite’s proposed Phase III study design to the regulatory agency.

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The FDA agreed with Can-Fite’s proposed pivotal Phase III trial design to support a New Drug Application (NDA) submission and approval. The Phase III study will enroll patients with advanced HCC, with underlying Child Pugh B7 (CPB7) cirrhosis, whose cancer has progressed on first line therapy. This design leverages the previously announced Phase II trial data, which showed promising efficacy signals in this population. The FDA’s guidance will be incorporated into the Phase III study’s final protocol.

"Namodenoson is a novel approach to treating advanced liver cancer with an orally bioavailable drug specifically targeting the tumor cells, a unique mechanism that contributes to the favorable safety profile. We are very pleased with this outcome from our meeting with the FDA. With the FDA’s guidance, we plan to now finalize our Phase III study protocol for this unmet advanced liver cancer indication," stated Dr. Michael Silverman, Can-Fite’s Medical Director.

Can-Fite’s completed Phase II liver cancer study found that Namodenoson increased overall survival in HCC patients with CPB7 cirrhosis, the largest subpopulation of the study, even though the Phase II study did not achieve its primary endpoint of overall survival in the whole population.

DelveInsight estimates the HCC drug market will reach $3.8 billion in 2027 in the G8 countries. According to the American Cancer Society, in the U.S. liver cancer incidence has tripled since 1980, with an estimated 42,000 cases diagnosed and 32,000 deaths annually. Incidence of liver cancer is much higher in other countries, with more than 800,000 diagnoses and 700,000 deaths estimated globally each year.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being developed as a second line treatment for hepatocellular carcinoma, with a recently completed Phase II trial and planned Phase III trial in this indication. The drug is currently in an ongoing Phase II trial as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On October 31, 2019 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the third quarter 2019 and reviewed recent business highlights (Press release, Alnylam, OCT 31, 2019, View Source [SID1234550103]).

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"In the third quarter of 2019 and recent period we saw strong execution on the global commercialization of ONPATTRO. For the rest of the year and beyond, we expect steady and continued growth in patients on ONPATTRO therapy through improved disease awareness, new patient finding, expansion in global markets – such as our recent launch in Japan and NDA filing in Brazil – and the potential for future label expansion in hereditary and wild-type ATTR cardiomyopathy through our recently initiated APOLLO-B Phase 3 study. We’re also pleased to have received a Priority Review and Accelerated Assessment for givosiran from the FDA and EMA, respectively, and we are preparing for the potential launch of our second RNAi therapeutic in the coming months, assuming positive regulatory reviews," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "While executing on our commercial objectives, we also made excellent progress on our late stage pipeline, including positive Phase 3 results for inclisiran announced by our partner, The Medicines Company, representing what we believe is a landmark event for Alnylam and for the entire field of RNAi therapeutics. In the final months of 2019, we aim to extend this encouraging track record with pivotal data from our lumasiran program, continued enrollment in our HELIOS-A Phase 3 trial and initiation of the HELIOS-B Phase 3 study with vutrisiran. Each of these anticipated milestones will bring us closer to achieving our Alnylam 2020 goals of building a multi-product, global biopharma company with a deep clinical pipeline to fuel future growth and a robust product engine for sustainable and organic innovation, a profile rarely achieved in our industry."

Third Quarter 2019 and Recent Significant Corporate Highlights

Commercial Performance in Third Quarter 2019

Achieved global net product revenues for the third quarter of 2019 of $46.1 million for ONPATTRO.
Attained over 600 patients worldwide on commercial ONPATTRO treatment since launch.
Continued global expansion with receipt of regulatory approval for ONPATTRO in Switzerland, and initiation of commercial launches in Japan and Canada.
Continued progress with market access efforts across the CEMEA region (Canada, Europe, Middle East, and Africa).
Following favorable ratings from health technology assessment agencies, achieved reimbursement approvals in the United Kingdom, Belgium, and Germany.
Received recognition for ONPATTRO as an innovative biotechnology medicine through award of the prestigious Prix Galien in The Netherlands and Italy and nominations for the Prix Galien in additional countries, including France, Germany, and the U.S.
Late Stage R&D Highlights

Advanced patisiran (the non-proprietary name for ONPATTRO), an intravenously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis.
Initiated the APOLLO-B Phase 3 study in ATTR amyloidosis patients with cardiomyopathy.
Filed a marketing authorization application with the Brazilian Health Regulatory Agency (ANVISA) for the treatment of hereditary ATTR amyloidosis with polyneuropathy.
Advanced vutrisiran, a subcutaneously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis.
Continued enrollment in the HELIOS-A Phase 3 study in hereditary ATTR amyloidosis patients with polyneuropathy.
Aligned with regulatory agencies on the design of the HELIOS-B Phase 3 study in patients with hereditary or wild-type ATTR amyloidosis with cardiomyopathy, and are on track to initiate the study in late 2019.
Advanced givosiran, an investigational RNAi therapeutic in development for the treatment of acute hepatic porphyria (AHP).
Received Priority Review from the U.S. Food and Drug Administration (FDA) for the givosiran New Drug Application (NDA). The FDA set an action date of February 4, 2020 under the Prescription Drug User Fee Act (PDUFA), and the agency has indicated that it is not currently planning an advisory committee meeting as part of the NDA review.
Completed submission of a Marketing Authorization Application (MAA) under an Accelerated Assessment to the European Medicines Agency (EMA).
Presented new clinical results at the 2019 International Congress on Porphyrins and Porphyrias.
Advanced lumasiran, an investigational RNAi therapeutic in development for the treatment of primary hyperoxaluria type 1 (PH1).
The Company remains on track to report topline results from the ILLUMINATE-A Phase 3 study in late 2019.
Continued enrollment in ILLUMINATE-B, a global Phase 3 pediatric study of lumasiran in PH1 patients under six years of age.
Presented new clinical results on the pediatric cohort of patients from the Phase 1/2 study at the International Pediatric Nephrology Association (IPNA) 2019 Annual Meeting.
Alnylam’s partner, The Medicines Company, reported positive results from Phase 3 studies with inclisiran, an investigational RNAi therapeutic in development for the treatment of hypercholesterolemia, including:
Positive complete results from the ORION-11 Phase 3 study in patients with atherosclerotic cardiovascular disease (ASCVD) (ex-U.S.), presented at the European Society of Cardiology’s ESC Congress 2019.
Positive topline results from the ORION-9 Phase 3 study in patients with heterozygous familial hypercholesterolemia (HeFH).
Positive topline results from the ORION-10 Phase 3 study in patients with ASCVD (U.S.-based).
Additional Business Updates

Received recognition as the world’s #1 biopharma employer from Science magazine based on more than 7,500 responses to its annual survey of the biotech and pharmaceutical industry.
Entered into a U.S. gastroenterologist disease education and post-approval promotional agreement with Ironwood Pharmaceuticals for the investigational RNAi therapeutic givosiran, to augment Alnylam’s broader education and commercial activities.
Announced the +myFamily program as part of the existing collaboration with 23andMe to offer free 23andMe Health + Ancestry kits to first-degree family members of 23andMe customers with a detected TTR variant.
Announced the appointment of Jeff Poulton as Executive Vice President, Chief Financial Officer.
Upcoming Events

In late 2019, Alnylam intends to:

Continue global expansion of ONPATTRO.
Prepare for the potential launch of givosiran in the U.S. and Europe, assuming regulatory approvals.
Initiate the HELIOS-B Phase 3 study of vutrisiran in hereditary and wild-type ATTR amyloidosis patients with cardiomyopathy.
Report topline results from the ILLUMINATE-A Phase 3 study of lumasiran.
Initiate the ILLUMINATE-C Phase 3 study of lumasiran in PH1 patients with severe renal impairment.
Present a review of its R&D and commercial activities at the Company’s R&D Day on November 22 in New York City.
In addition, The Medicines Company plans to report complete results from the ORION-9 and 10 Phase 3 studies of inclisiran at the American Heart Association Scientific Sessions 2019, taking place November 16 – 18 in Philadelphia. The Medicines Company also plans to file an NDA for inclisiran by year-end 2019.

Financial Results for the Quarter Ended September 30, 2019

"Having recently joined Alnylam as CFO, I have been very impressed by the strong commercial execution of the organization, building on the Company’s heritage of scientific excellence and R&D success. Notably, we finished the third quarter with over 600 patients on commercial ONPATTRO and generated $46.1 million in global net product revenues with strong growth contributions from both our U.S. and international markets," said Jeff Poulton, Chief Financial Officer of Alnylam. "As we look towards 2020 and beyond, our balance sheet remains strong, supporting further investment in both commercial and R&D programs to drive near- and long-term growth, which we believe will bring us closer to achieving a self-sustainable financial profile for the future."

Cash and Investments
At September 30, 2019, Alnylam had cash, cash equivalents and marketable debt securities, and restricted investments, excluding equity securities, of $1.74 billion, as compared to $1.13 billion at December 31, 2018.

GAAP and Non-GAAP Net Loss
The net loss according to accounting principles generally accepted in the U.S. (GAAP) for the third quarter of 2019 was $208.5 million, or $1.92 per share on both a basic and diluted basis, as compared to a net loss of $245.3 million, or $2.43 per share on both a basic and diluted basis, for the same period in the previous year.

The non-GAAP net loss for the third quarter of 2019 was $162.5 million, or $1.50 per share on both a basic and diluted basis, as compared to a non-GAAP net loss of $157.3 million, or $1.56 per share on both a basic and diluted basis, for the same period in the previous year.

Reconciling items between GAAP and non-GAAP net loss for the third quarter of 2019 and 2018 include stock-based compensation expense. See "Use of Non-GAAP Financial Measures" below for a description of non-GAAP financial measures and a reconciliation between GAAP and non-GAAP net loss appearing later in this press release.

ONPATTRO Revenues, Net
Net product revenues from sales of ONPATTRO were $46.1 million in the third quarter of 2019, as compared to net product revenues of $0.5 million for the same period in the previous year.

Net Revenues from Collaborators
Net revenues from collaborators were $24.0 million in the third quarter of 2019, primarily related to $15.3 million in revenue from the Regeneron collaboration, as compared to $1.6 million in the third quarter of 2018.

GAAP and Non-GAAP Research and Development Expenses
GAAP research and development (R&D) expenses were $160.8 million in the third quarter of 2019, as compared to $139.9 million in the third quarter of 2018.

Non-GAAP R&D expenses were $138.1 million in the third quarter of 2019, as compared to $94.2 million in the third quarter of 2018. Non-GAAP R&D expenses exclude stock-based compensation expense. A reconciliation between GAAP and non-GAAP R&D expenses appears later in this press release.

GAAP and Non-GAAP Selling, General and Administrative Expenses
GAAP selling, general and administrative (SG&A) expenses were $120.4 million in the third quarter of 2019, as compared to $116.5 million in the third quarter of 2018.

Non-GAAP SG&A expenses were $97.1 million in the third quarter of 2019, as compared to $74.4 million in the third quarter of 2018. Non-GAAP SG&A expenses exclude stock-based compensation expense. A reconciliation between GAAP and non-GAAP SG&A expenses appears later in this press release.

2019 Financial Guidance
Alnylam reiterates its expectations for 2019 non-GAAP R&D expenses to be in the range of $550 to $575 million and non-GAAP SG&A expenses to be in the range of $390 to $400 million. Both non-GAAP R&D and non-GAAP SG&A expenses exclude stock-based compensation expenses.

The Company expects its current cash, cash equivalents, and marketable debt securities will support company operations for multiple years based upon its current operating plan.

Use of Non-GAAP Financial Measures
This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and non-recurring gains outside the ordinary course of the Company’s business. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.

The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in the press release are stock-based compensation expense, a gain on the change in fair value of a liability obligation, and a gain on litigation settlement. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. The Company has excluded the impact of a gain on the change in fair value of a liability obligation and the gain on litigation settlement because the Company believes these items are one-time events occurring outside the ordinary course of the Company’s business.

The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between GAAP and non-GAAP measures is provided later in this press release.

The Company does not provide in this press release a reconciliation of its estimated 2019 non-GAAP R&D and non-GAAP SG&A expense guidance to the comparable GAAP measures because it is not able to estimate 2019 stock-based compensation expense without unreasonable efforts. The Company’s stock-based compensation expense is subject to significant fluctuations from period to period due to variability in the probability of performance-based vesting events for stock options and restricted stock units and changes in the Company’s stock price which materially impact the recognition, timing of expense and fair value of these awards. In addition, the Company believes such reconciliations for its 2019 financial guidance would imply a degree of precision that would be confusing or misleading to investors.

Conference Call Information
Management will provide an update on the Company and discuss third quarter 2019 results as well as expectations for the future via conference call on Thursday, October 31, 2019 at 8:30 am ET. To access the call, please dial 866-548-4713 (domestic) or +1-323-794-2093 (international) five minutes prior to the start time and refer to conference ID 2198008. A replay of the call will be available beginning at 11:30 am ET on the day of the call. To access the replay, please dial 888-203-1112 (domestic) or +1-719-457-0820 (international) and refer to conference ID 2198008.

About ONPATTRO (patisiran)
ONPATTRO is an RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union and Switzerland for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. Based on Nobel Prize-winning science, ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR) for the treatment of hereditary ATTR amyloidosis. It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. ONPATTRO blocks the production of TTR in the liver, reducing its accumulation in the body’s tissues in order to halt or slow down the progression of the disease.

ONPATTRO Important Safety Information

Infusion-Related Reactions
Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In a controlled clinical study, 19 percent of ONPATTRO-treated patients experienced IRRs, compared to 9 percent of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions
The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory-tract infections (29 percent) and infusion-related reactions (19 percent).

For additional information about ONPATTRO, please see the full Prescribing Information.

About LNP Technology
Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

On October 31, 2019 Celgene Corporation (NASDAQ: CELG) reported third quarter 2019 total revenue of $4,520 million, a 16 percent increase compared to $3,892 million in the third quarter of 2018 (Press release, Celgene, OCT 31, 2019, View Source [SID1234550102]).

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Based on U.S. GAAP (Generally Accepted Accounting Principles), Celgene reported net income of $1,691 million and diluted earnings per share (EPS) of $2.32 for the third quarter of 2019. For the third quarter of 2018, GAAP net income was $1,082 million and diluted EPS was $1.50.

Adjusted net income for the third quarter of 2019 increased 33 percent to $2,184 million compared to $1,645 million in the third quarter of 2018. For the same period, adjusted diluted EPS increased 31 percent to $2.99 from $2.29.

"Across functions and around the world, our teams delivered outstanding third quarter results," said Mark J. Alles, Chairman and Chief Executive Officer of Celgene Corporation. "We are continuing to advance multiple high-potential medicines toward regulatory approvals and look forward to closing the Bristol-Myers Squibb transaction by the end of the year."

Third Quarter 2019 Financial Highlights

Unless otherwise stated, all comparisons are for the third quarter of 2019 compared to the third quarter of 2018. The adjusted operating expense categories presented below exclude share-based employee compensation expense and collaboration-related upfront expense. Please see the attached Use of Non-GAAP Financial Measures and Reconciliation of GAAP to Adjusted Net Income 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.

Net Product Sales Performance

·REVLIMID sales for the third quarter were $2,770 million, an increase of 13 percent year-over-year. U.S. sales were $1,902 million and international sales were $868 million, an increase of 14 percent and 11 percent year-over-year, respectively. REVLIMID sales growth was driven primarily by the adoption of triplet therapy for myeloma resulting in increases in treatment duration and market share.

·POMALYST/IMNOVID sales for the third quarter were $664 million, an increase of 29 percent year-over-year. U.S. sales were $469 million and international sales were $195 million, an increase of 31 percent and 25 percent year-over-year, respectively. POMALYST/IMNOVID sales growth was driven primarily by the adoption of triplet therapy for myeloma resulting in increases in treatment duration and market share.

·OTEZLA sales for the third quarter were $547 million, an increase of 27 percent year-over-year. U.S. sales were $445 million and international sales were $102 million, an increase of 28 percent and 21 percent year-over-year, respectively. OTEZLA sales growth in the U.S. was driven by increase in demand, while international sales were driven by continued uptake in key markets.

·ABRAXANE sales for the third quarter were $318 million, an increase of 10 percent year-over-year. U.S. sales were $206 million and international sales were $112 million, an increase of 18 percent and a decrease of 2 percent year-over-year, respectively. ABRAXANE sales growth was driven primarily by increased demand due to immuno-oncology (IO) combinations in non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC).

·In the third quarter, all other product sales, which include INREBIC, IDHIFA, THALOMID, ISTODAX, VIDAZA and an authorized generic version of VIDAZA drug product primarily sold in the U.S., were $219 million compared to $208 million in the third quarter of 2018.

Research and Development (R&D)

On a GAAP basis, R&D expenses were $1,167 million for the third quarter of 2019 compared to $1,081 million for the same period in 2018. Adjusted R&D expenses were $928 million for the third quarter of 2019 compared to $948 million for the third quarter of 2018. The decrease in adjusted R&D expense was driven by reductions in expenses related to certain collaboration arrangements and regulatory submission-related work on multiple programs. Additional R&D expenses (only included on a GAAP basis) increased in 2019, as outlined in the attached Reconciliation of GAAP to Adjusted Net Income.

Selling, General and Administrative (SG&A)

On a GAAP basis, SG&A expenses were $781 million for the third quarter of 2019 compared to $746 million for the same period in 2018. Adjusted SG&A expenses were $700 million for the third quarter of 2019 compared to $642 million for the third quarter of 2018. The increase was driven primarily by increased pre-launch marketing-related expenses. Additional SG&A expense (only included on a GAAP basis) decreased in 2019, as outlined in the attached Reconciliation of GAAP to Adjusted Net Income.

Cash, Cash Equivalents, Marketable Debt Securities and Publicly-Traded Equity Securities

Operating cash flow was $2.2 billion in the third quarter of 2019, compared to $1.9 billion for the third quarter of 2018. Celgene ended the quarter with approximately $10.9 billion in cash, cash equivalents, marketable debt securities and publicly-traded equity securities.

Portfolio Updates

·INREBIC (fedratinib):

·In August, Celgene announced that the U.S. Food and Drug Administration (FDA) approved INREBIC (fedratinib) for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis

·The Marketing Authorization Application (MAA) submission in the European Union is planned by year-end 2019

·Luspatercept1:

·The U.S. FDA accepted the Biologics License Application (BLA) for luspatercept for the treatment of anemia in adult patients with beta-thalassemia who require regular red blood cell (RBC) transfusions and set a Prescription Drug User Fee Act (PDUFA) date of December 4, 2019

·The U.S. FDA accepted the BLA for luspatercept for the treatment of adult patients with very low to intermediate-risk myelodysplastic syndromes (MDS)-associated anemia who have ring sideroblasts and require regular RBC transfusions and set a PDUFA date of April 4, 2020

·The MAA for luspatercept for the treatment of adult patients with beta-thalassemia and MDS has been accepted for review by the European Medicines Agency (EMA)

·Liso-cel (JCAR017):

·The BLA submission for liso-cel in patients with relapsed or refractory large B-cell lymphoma after at least 2 prior therapies is on-track for the fourth quarter of 2019

·Ide-cel (bb2121)2:

·An update from the pivotal KarMMa trial in patients with relapsed and/or refractory multiple myeloma (RRMM) is expected by year-end 2019. The BLA submission for ide-cel in 4L+ multiple myeloma is expected in the first half of 2020

·The phase II KarMMa-2 and phase III KarMMa-3 trials in patients with 2L and 3L+ multiple myeloma, respectively, are continuing to enroll

·Initiation of a newly diagnosed multiple myeloma (NDMM) trial is planned for the fourth quarter of 2019

·CC-486:

·In September, Celgene announced that the phase III QUAZAR AML-001 trial evaluating CC-486 as maintenance therapy in patients with newly diagnosed acute myeloid leukemia (AML) who achieved first complete response (CR) or complete response with incomplete blood count recovery (CRi) with induction chemotherapy met the primary endpoint of prolonged overall survival (OS). Celgene plans regulatory submissions beginning in the first half of 2020. Data from QUAZAR AML-001 will be presented at a future medical meeting

·Ozanimod:

·The U.S. FDA accepted the New Drug Application (NDA) for ozanimod for the treatment of patients with relapsing forms of multiple sclerosis (RMS) and set a PDUFA date of March 25, 2020

·The EMA accepted the MAA for ozanimod for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). A regulatory decision is expected in the first half of 2020

·Data from the phase III TRUE NORTH trial in patients with ulcerative colitis (UC) is expected in mid-2020

·At the 61st ASH (Free ASH Whitepaper) annual meeting in December, select anticipated data presentations include:

·Data from the pivotal TRANSCEND NHL-001 trial evaluating liso-cel in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL), which includes diffuse large B-cell lymphoma (DLBCL);

·Updated data, including minimal residual disease (MRD), from the ongoing phase I/II TRANSCEND CLL-004 trial evaluating liso-cel in a heavily pretreated patient population with high-risk chronic lymphocytic leukemia (CLL);

·Initial results from the phase II PILOT trial evaluating liso-cel as second-line treatment in patients with transplant noneligible (TNE) relapsed and/or refractory NHL;

·Data from the outpatient treatment of liso-cel in multiple ongoing clinical trials in patients with relapsed/refractory B-cell NHL;

·Initial data from the phase II trial evaluating luspatercept in patients with myelofibrosis;

·Updated data from the phase I trial evaluating bb21217 in patients with RRMM;

·First clinical data from a phase I trial evaluating CC-93269, a T cell bispecific antibody targeting B-cell maturation antigen (BCMA) in patients with RRMM; and,

·First clinical data from a phase I trial evaluating CELMoD agent CC-90009 in patients with relapsed or refractory AML

1 In collaboration with Acceleron Pharma

2 In collaboration with bluebird bio

Transaction Update

·In June, Bristol-Myers Squibb announced the planned divestiture of OTEZLA (apremilast) in light of concerns raised by the U.S. Federal Trade Commission ("FTC"). In August, Celgene entered into an agreement with Amgen under which Amgen would acquire the OTEZLA (apremilast) product line and related intellectual property, including any patents that primarily cover apremilast, and other specified assets and liabilities related to the OTEZLA (apremilast) product line for $13.4 billion in cash (the "OTEZLA Divestiture"), which represents an important step towards completion of the pending merger between Bristol-Myers Squibb and Celgene. The closing of the OTEZLA Divestiture is contingent on Bristol-Myers Squibb and Celgene entering into a consent decree with the Federal Trade Commission (FTC) in connection with their pending merger, the closing of the pending merger between Bristol-Myers Squibb and Celgene, and the satisfaction of other customary closing conditions. The pending merger between Bristol-Myers Squibb and Celgene is expected to close by the end of 2019, subject to the FTC’s acceptance of a consent order and the satisfaction of customary closing conditions.

Third Quarter 2019 Earnings Information

Due to the pending transaction with Bristol-Myers Squibb, Celgene is not hosting a conference call in conjunction with its third-quarter 2019 earnings release and does not expect to do so for future quarters. Please direct any questions regarding this press release to Celgene Investor Relations or Celgene Communications.