On June 25, 2019 Array BioPharma Inc. (Nasdaq: ARRY) reported that it will present updated data from the combination of BRAFTOVI (encorafenib), a BRAF inhibitor, MEKTOVI (binimetinib), a MEK inhibitor, and ERBITUX (cetuximab), an anti-EGFR antibody (BRAFTOVI Triplet), in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two lines of therapy (Press release, Array BioPharma, JUN 25, 2019, View Source [SID1234537244]). These data will be presented in an oral presentation on Saturday, July 6, at the ESMO (Free ESMO Whitepaper) 21stWorld Congress on Gastrointestinal Cancer in Barcelona, Spain.

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Oral Presentation:

Title:

BEACON CRC: A Randomized, 3-Arm, Phase 3 Study of Encorafenib and Cetuximab With or Without Binimetinib vs. the Choice of Either Irinotecan or FOLFIRI plus Cetuximab in BRAFV600E-Mutant Metastatic Colorectal Cancer

Presenter:

Scott Kopetz, M.D., Ph.D., FACP, Associate Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center

Abstract:

LBA-006

Session:

Session XX: Colorectal Cancer (Part I)

Date:

Saturday July 6, 2019

Session Time:

9:20 AM – 10:05 AM CEST (3:20 AM – 4:05 AM ET)

Location:

Auditorium A, Level 0

Following the presentation, the slides will be available as a PDF on Array’s website at www.arraybiopharma.com.

About Colorectal Cancer

Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.8 million new diagnoses in 2018. [1,2] In the U.S. alone, an estimated 140,250 patients were diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease each year. [3] BRAF mutations are estimated to occur in up to 15% of patients with mCRC and represent a poor prognosis for these patients. [4-8] The V600 mutation is the most common BRAF mutation and the risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF. [7,9] Several irinotecan and cetuximab-containing regimens, similar to the BEACON CRC control arm, have established observed historical published benchmarks in BRAFV600E-mutant mCRC patients, whose disease has progressed after one or two prior lines of therapy. Previous benchmarks include median OS of 5.9 months, median PFS of 2.0 months, and ORR of 4%. [4-6,10-15] BRAFV600E-mutant mCRC is an area of high unmet need as there are currently no FDA-approved therapies specifically indicated for patients with BRAF-mutant mCRC, and these patients derive limited benefit from available chemotherapy regimens. [16-18] For more information about BRAFV600E-mutant mCRC visit www.brafmcrc.com.

About BEACON CRC

BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of BRAFTOVI, MEKTOVI and ERBITUX in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAFV600E-mutant mCRC. Thirty patients were treated in the safety lead-in and received the triplet combination (BRAFTOVI 300 mg daily, MEKTOVI 45 mg twice daily and ERBITUX per label). Of the 30 patients, 29 had a BRAFV600 mutation. Microsatellite instability high, resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomized portion of the trial. The randomized portion of the BEACON CRC trial is designed to assess the efficacy of BRAFTOVI in combination with ERBITUX with or without MEKTOVI compared to ERBITUX and irinotecan-based therapy. 665 patients were randomized 1:1:1 to receive the triplet combination, the doublet combination (BRAFTOVI and ERBITUX) or the control arm (irinotecan-based therapy and ERBITUX). The study has been amended to include an interim analysis of endpoints including ORR. The primary overall survival endpoint is a comparison of the triplet combination to the control arm. Secondary endpoints address efficacy of the doublet combination compared to the control arm, and the triplet combination compared to the doublet therapy. Other secondary endpoints include PFS, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. The BEACON CRC trial is being conducted with support from Ono Pharmaceutical Co. Ltd., Pierre Fabre and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).

The triplet combination of BRAFTOVI, MEKTOVI and ERBITUX for the treatment of patients with BRAFV600E-mutant mCRC is investigational and not approved by the FDA.

About BRAFTOVI + MEKTOVI

BRAFTOVI is an oral small molecule BRAF kinase inhibitor and MEKTOVI is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma. In Europe, the combination is approved for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test. In Japan, the combination is approved for unresectable melanoma with a BRAF mutation.

Array has exclusive rights to BRAFTOVI and MEKTOVI in the U.S. and Canada. Array has granted Ono Pharmaceutical Co. Ltd., exclusive rights to commercialize both products in Japan and South Korea, Medison exclusive rights to commercialize both products in Israel and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Latin American and Asia (excluding Japan and South Korea).

BRAFTOVI + MEKTOVI have received regulatory approval in the United States, European Union, Australia and Japan. The Swiss Medicines Agency (Swissmedic) is currently reviewing the Marketing Authorization Applications for BRAFTOVI and MEKTOVI submitted by Pierre Fabre.

Indications and Usage

BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) are kinase inhibitors indicated for use in combination for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.

Limitations of Use: BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma.

BRAFTOVI + MEKTOVI Important Safety Information

The information below applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted. See full Prescribing Information for BRAFTOVI and for MEKTOVI for dose modifications for adverse reactions.

Warnings and Precautions

New Primary Malignancies: Cutaneous and non-cutaneous malignancies can occur. In the COLUMBUS trial, cutaneous squamous cell carcinoma, including keratoacanthoma, occurred in 2.6% and basal cell carcinoma occurred in 1.6% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Dose modification is not recommended for new primary cutaneous malignancies. Based on its mechanism of action, BRAFTOVI may promote malignancies associated with activation of RAS through mutation or other mechanisms. Monitor patients receiving BRAFTOVI for signs and symptoms of non-cutaneous malignancies. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies.

Tumor Promotion in BRAF Wild-Type Tumors: Confirm evidence of BRAFV600E or V600Kmutation prior to initiating BRAFTOVI.

Cardiomyopathy, manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients. In the COLUMBUS trial, cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients. Cardiomyopathy resolved in 87% of patients. Assess left ventricular ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. Safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal. Patients with cardiovascular risk factors should be monitored closely.

Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE occurred in 6% of patients, including 3.1% of patients who developed pulmonary embolism.

Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in 19% of patients and ≥ Grade 3 hemorrhage occurred in 3.2% of patients. Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients. The most frequent hemorrhagic events were gastrointestinal, including rectal hemorrhage (4.2%), hematochezia (3.1%), and hemorrhoidal hemorrhage (1%).

Ocular Toxicities: In the COLUMBUS trial, serous retinopathy occurred in 20% of patients; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. RVO is a known class-related adverse reaction of MEK inhibitors and may occur in patients treated with MEKTOVI in combination with encorafenib. In patients with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of patients experienced retinal vein occlusion (RVO). The safety of MEKTOVI has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. Perform ophthalmological evaluation for patient-reported acute vision loss or other visual disturbance within 24 hours. Permanently discontinue MEKTOVI in patients with documented RVO. In COLUMBUS, uveitis, including iritis and iridocyclitis was reported in 4% of patients. Assess for visual symptoms at each visit. Perform ophthalmological evaluation at regular intervals and for any visual disturbances, and to follow new or persistent ophthalmologic findings.

Interstitial Lung Disease (ILD): ILD, including pneumonitis occurred in 0.3% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD.

Hepatotoxicity: In the COLUMBUS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 6% for alanine aminotransferase (ALT) and 2.6% for aspartate aminotransferase (AST), and 0.5% for alkaline phosphatase. Monitor liver laboratory tests before and during treatment and as clinically indicated.

Rhabdomyolysis: In the COLUMBUS trial, elevation of laboratory values of serum creatine phosphokinase (CPK) occurred in 58% of patients. Rhabdomyolysis was reported in 0.1% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Monitor CPK and creatinine levels prior to initiating MEKTOVI, periodically during treatment, and as clinically indicated.

QTc Prolongation: BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients. In the COLUMBUS trial, an increase in QTcF to > 500 ms was measured in 0.5% (1/192) of patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc > 500 ms.

Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause fetal harm when administered to pregnant women. BRAFTOVI can render hormonal contraceptives ineffective. Non-hormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI + MEKTOVI.

Adverse Reactions

The most common adverse reactions (≥20%, all Grades, in the COLUMBUS trial): were fatigue, nausea, diarrhea, vomiting, abdominal pain, arthralgia, myopathy, hyperkeratosis, rash, headache, constipation, visual impairment, serous retinopathy.

In the COLUMBUS trial, the most common laboratory abnormalities (≥20%, all Grades): included increased creatinine, increased CPK, increased gamma glutamyl transferase, anemia, increased ALT, hyperglycemia, increased AST, and increased alkaline phosphatase.

Drug Interactions

Avoid concomitant use of strong or moderate CYP3A4 inhibitors or inducers and sensitive CYP3A4 substrates with BRAFTOVI. Modify BRAFTOVI dose if concomitant use of strong or moderate CYP3A4 inhibitors cannot be avoided. Avoid co-administration of BRAFTOVI with medicinal products with a known potential to prolong QT/QTc interval.

Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information. [19-20] You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Array at 1-844-Rx-Array (1-844-792-7729).

On June 25, 2019 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that it has completed the rights offering period and will be extending the subscription period until 5:00 PM Eastern time on July 12, 2019, unless further extended by the Company (Press release, DelMar Pharmaceuticals, JUN 25, 2019, View Source [SID1234537260]).

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Under the rights offering, DelMar distributed one non-transferable subscription right for each share of common stock and each participating warrant held on the record date. The subscription rights are exercisable for up to an aggregate of $1.9 million of units with aggregate participation to be allocated among holders, subject to certain participation rights, on a pro rata basis if in excess of that threshold.

All record holders of rights that wish to participate in the rights offering must deliver a properly completed and signed subscription rights statement, together with payment of the subscription price for both basic subscription rights and any over subscription privilege election for delivery no later than 5:00 PM Eastern Time on July 12, 2019 to the Subscription Agent:

By mail:

By hand or overnight courier:

Broadridge Corporate Issuer Solutions, Inc.

Attn: BCIS Re-Organization Dept.

P.O. Box 1317

Brentwood, New York 11717-0693

(888) 789-8409 (toll free)

Broadridge Corporate Issuer Solutions, Inc.

Attn: BCIS IWS

51 Mercedes Way

Edgewood, New York 11717

(888) 789-8409 (toll free)

If exercising subscription rights through a broker, dealer, bank or other nominee, rights holders should promptly contact their nominee and submit subscription documents and payment for the units subscribed for in accordance with the instructions and within the time period provided by such nominee. The broker, dealer, bank or other nominee may establish a deadline before July 12, 2019, by which instructions to exercise subscription rights, along with the required subscription payment, must be received.

Each subscription right entitles the holder to purchase one unit, at a subscription price of $1,000 per unit, consisting of one share of Series C Convertible Preferred Stock with a stated value of $1,000 (and immediately convertible into shares of DelMar’s common stock) and warrants to purchase DelMar’s common stock. The Series C Convertible Preferred Stock conversion price is $3.10 and each unit consists of 209 warrants to purchase DelMar’s common stock at an exercise price of $3.10 per share. The warrants are exercisable for five (5) years after the date of issuance and shall be redeemable as described in the preliminary and final prospectus, when available.

Holders who fully exercise their basic subscription rights will be entitled, if available, to subscribe for an additional amount of units that are not purchased by other holders, on a pro rata basis and subject to the $1.9 million aggregate offering threshold and other ownership limitations.

DelMar has engaged Maxim Group LLC and Dawson James Securities Inc. as co-dealer-managers in the rights offering. Questions about the rights offering or requests for copies of the preliminary and final prospectuses, when available, may be directed to Maxim Group LLC at 405 Lexington Avenue, New York, NY 10174, Attention Syndicate Department, or via email at [email protected] or telephone at (212) 895-3745.

A registration statement relating to these securities has been filed with the Securities and Exchange Commission (the "SEC") and became effective on May 28, 2019, and is available on the SEC’s website located at View Source Additionally, a post-effective amendment to the registration statement was filed on June 10, 2019 for pricing and other adjustments discussed above.

Any subscriptions received prior to the effective date of the post-effective amendment will be deemed to be revoked. Such subscriptions will not be processed by Broadridge Corporate Issuer Solutions, Inc., or by the Depository Trust Company, and any monetary payments received in respect of such subscriptions will be returned to the applicable holder upon the expiration date of the offering. Any subscription materials received following such effective date will be deemed to be for subscriptions pursuant to the revised terms of the rights offering described in the Company’s post-effective amendment to its initial registration statement.

The rights offering is being made only by means of a written prospectus. A copy of the prospectus for the rights offering may be obtained, when available, from Maxim Group LLC, 405 Lexington Avenue, New York, NY 10174, Attention Syndicate Department, email: [email protected] or telephone (212) 895-3745. Investors may also obtain these documents at no cost by visiting the SEC’s website at View Source

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On June 25, 2019 Dune Medical Devices reported that it has reached another milestone in their MarginProbe Post Approval Study (PAS) as Johns Hopkins Hospital and Moffitt Cancer Center complete their patient enrollments for the trial (Press release, Dune Medical Devices, JUN 25, 2019, http://www.dunemedical.com/prestigious-cancer-centers-johns-hopkins-and-moffitt-complete-patient-enrollment-in-post-approval-study-for-marginprobe-transforming-the-standard-of-care-for-breast-cancer-patients/ [SID1234537245]). This PAS, required by the FDA, seeks to substantiate the vast body of data produced since MarginProbe’s original approval, demonstrating its effectiveness at intraoperatively identifying positive margins and subsequent effects on reducing re-excision rates while maintaining cosmetic outcomes after surgery.

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Dr. Mehran Habibi, Medical Director of the Johns Hopkins Breast Center, and Dr. Susan Hoover, Surgical Oncologist for Moffitt Cancer Center’s Department of Breast Oncology, are the participating Principal Investigators (PI) for their respective centers in the trial. Johns Hopkins and Moffitt are the number one and number two highest enrolling centers in the study. Dr. Habibi, the Lead PI of the trial, will be working closely with Dr. Hoover to develop a publication cadence for this meaningful and relevant work.

"Johns Hopkins is continuously pursuing the newest technology and advancements in breast cancer diagnosis and treatment," Dr. Habibi explained. "Participating in this study has allowed us to face the challenge of positive margin rates after lumpectomy head-on."

Dr. Hoover has also spoken out about Moffitt Cancer Center’s efforts to stay on top of the latest technology for both breast cancer screening and treatment.

"Moffitt is a thought leader in the world of breast disease. We are in constant motion striving to stay ahead of the latest innovations in breast cancer in order to go beyond the current standard of care for our patients," said Dr. Hoover. "With MarginProbe’s ability to identify positive margins in real-time and potentially lower re-excision rates, participating in this Post-Approval Study put us one step closer to accomplishing this goal."

Johns Hopkins and Moffitt now join Pinnacle Health Cancer Institute, Summit Medical Group, and Northshore University HealthSystem as sites which have completed enrollment in the study. The three sites will follow each patient for six months as required in the next phase of the study. To date, over 300 of the study’s 440 patients have been enrolled. Six additional cancer centers across the country will continue accruing patients until August 2019 when enrollment is anticipated to be complete.

The adoption of MarginProbe by major cancer centers such as Johns Hopkins and Moffitt speaks volumes for the device’s credibility and efficacy, as well as the role it plays in improving the healthcare experience for patients. Nearly 200,000 women receive lumpectomy surgery annually, which precedes a period of uncertainty while awaiting final pathology results. A pathology report indicating a positive margin subjects patients to further surgery and a prolonged treatment timeline. Acceptance of MarginProbe as a Standard of Care will provide significantly more women with the peace of mind that their cancer was fully removed during one procedure, and the ability to complete their treatment plan returning them back to their normal life.

The MarginProbe device utilizes radiofrequency spectroscopy to characterize and differentiate cancerous versus healthy tissue, giving surgeons the ability to identify microscopic residual cancer and DCIS in real-time, removing additional tissue if needed. MarginProbe provides greater confidence for both the surgeon and the patient that all of the cancer is successfully removed in the first surgery and reduces the likelihood of costly, burdensome additional surgeries.

For a list of cancer centers currently enrolling patients in the MarginProbe post-approval trial, please visit www.clinicaltrials.govand search "MarginProbe".

On June 25, 2019 I-Mab Biopharma ("I-Mab"), a clinical stage biotech company exclusively focusing on discovery and development of innovative biologics in immuno-oncology and autoimmune diseases, reported on June 24, 2019, that the first patient has been dosed in a Phase I clinical trial of TJC4 (Press release, I-Mab Biopharma, JUN 25, 2019, View Source [SID1234537261]). The study is known as TJ011133 (NCT Number: NCT03934814). TJC4 is a differentiated fully human CD47 monoclonal antibody internally developed for the treatment of advanced malignant tumors. The study is intended to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of TJC4 in patients with advanced solid tumors and lymphoma when administered as a single agent and in combination with other cancer treatment agent(s).

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"TJC4 is the second drug candidate from I-Mab’s proprietary innovative pipeline to enter clinical studies in the US. Compared to other clinical stage CD47 antibodies, TJC4 is designed to improve the hematologic safety profile while exerting strong anti-tumor activities. It has the potential to be a best-in-class drug," Dr. Joan Shen, Head of R&D at I-Mab noted. "We aim to rapidly advance the clinical development of TJC4 and validate its designed advantages in the treatment of solid tumors and hematological malignancies around the world."

Horizon Oncology Center dosed the first patient in the Phase 1 clinical trial of TJC4. Wael A. Harb, MD, Chief Medical Officer of Verdi Oncology & Director of Clinical Research of Horizon Oncology Center, commented, "I-Mab’s TJC4 is a promising and differentiated CD47 antibody, which is supported by data from I-Mab’s pre-clinical studies. We are excited to participate in this important clinical study."

About CD47 and TJC4

CD47 is a glycoprotein over-expressed in a wide variety of cancers and delivers a "don’t eat me" signal to tumor-engulfing macrophage through its ligand known as SIRPα. Blockade of CD47 by TJC4 enables macrophage to engulf cancer cells as a potential treatment option for cancers. TJC4 also known as TJ011133 is a differentiated CD47 monoclonal antibody and designed to minimize inherent binding to normal red blood cells by this class of monoclonal antibodies yet preserve its strong anti-tumor activities. TJC4 recognizes a unique epitope on CD47 and exhibits a minimal binding to red blood cells. The hematologic safety advantage of TJC4 has been demonstrated in a series of robust pre-clinical and toxicological studies including those in cynomolgus monkeys, while it maintains superb anti-tumor activities.

On June 25, 2019 AbbVie Inc. (NYSE: ABBV) and Allergan plc (NYSE: AGN) reported that the companies have entered into a definitive transaction agreement under which AbbVie will acquire Allergan in a cash and stock transaction for a transaction equity value of approximately $63 billion, based on the closing price of AbbVie’s common stock of $78.45 on June 24, 2019 (Press release, AbbVie, JUN 25, 2019, View Source [SID1234537262]).

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"This is a transformational transaction for both companies and achieves unique and complementary strategic objectives," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "The combination of AbbVie and Allergan increases our ability to continue to deliver on our mission to patients and shareholders. With our enhanced growth platform to fuel industry-leading growth, this strategy allows us to diversify AbbVie’s business while sustaining our focus on innovative science and the advancement of our industry-leading pipeline well into the future."

"This acquisition creates compelling value for Allergan’s stakeholders, including our customers, patients and shareholders. With 2019 annual combined revenue of approximately $48 billion, scale in more than 175 countries, an industry-leading R&D pipeline and robust cash flows, our combined company will have the opportunity to make even bigger contributions to global health than either can alone," said Brent Saunders, chairman and chief executive officer, Allergan. "Our fast-growing therapeutic areas, including our world class medical aesthetics, eye care, CNS and gastrointestinal businesses, will enhance AbbVie’s strong growth platform and create substantial value for shareholders of both companies."

Strategic Rationale

·New growth platforms and leadership positions to diversify and expand revenue base:

The combined company will consist of several attractive franchises with leadership positions across immunology, hematologic oncology, medical aesthetics, neuroscience, women’s health, eye care and virology. Allergan’s product portfolio will be enhanced by AbbVie’s commercial strength, expertise and international infrastructure.

Immediate scale and enhanced profitability for AbbVie’s growth platform: AbbVie’s enhanced growth platform, comprised of growing and durable franchises across highly-attractive therapeutic areas, is expected to grow at a high-single digit annual growth rate well into the next decade, from more than $30 billion in 2020.

·Financially attractive with immediate EPS accretion: This transaction is expected to be 10% accretive to adjusted earnings per share over the first full year following the close of the transaction, with peak accretion of greater than 20%.1 ROIC is expected to exceed AbbVie’s cost of capital within the first full year.

·Significant cash flow generation: The success and scale of the combined commercial business ensures funding capacity and flexibility for simultaneous robust pipeline investment, debt reduction and capital return to shareholders. The combined companies generated $19 billion in operating cash flow in 2018.

Structure and Governance

Upon completion of the transaction, AbbVie will continue to be incorporated in Delaware as AbbVie Inc. and have its principal executive offices in North Chicago, Ill. AbbVie will continue to be led by Richard A. Gonzalez as chairman and chief executive officer. Two members of Allergan’s Board, including chairman and chief executive officer, Brent Saunders, will join AbbVie’s Board upon completion of the transaction.

Transaction Details

Under the terms of the Transaction Agreement, Allergan Shareholders will receive 0.8660 AbbVie Shares and $120.30 in cash for each Allergan Share that they hold, for a total consideration of $188.24 per Allergan Share.2 The transaction represents a 45% premium to the closing price of Allergan’s Shares on June 24, 2019.

AbbVie anticipates that the Acquisition will provide annual pre-tax synergies and other cost reductions of at least $2 billion in year three while leaving investments in key growth franchises untouched. The synergies and other cost reductions will be a result of optimizing the research and early stage portfolio, and reducing overlapping R&D resources (~50%), driving efficiencies in SG&A, including sales and marketing and central support function costs (~40%), and eliminating redundancies in manufacturing and supply chain, and leveraging procurement spend (~10%). The synergies estimate excludes any potential revenue synergies.3

AbbVie is expected to generate significant annual operating cash flow, which will support a debt reduction target of $15 to $18 billion before the end of 2021, while also enabling a continued commitment to Baa2/BBB or better credit rating and continued dividend growth.

It is expected that, immediately after the closing of the Acquisition, AbbVie Shareholders will own approximately 83% of AbbVie on a fully diluted basis and the Allergan Shareholders will own approximately 17% of AbbVie on a fully diluted basis.

1 The statement that this transaction is earnings accretive should not be interpreted to mean that the earnings per share in the current or any future financial period will necessarily match or be greater than those for the relevant preceding financial period.

2 Subject to adjustment in accordance with the Exchange Ratio Modification Number.

3 There are various material assumptions underlying the synergies and other cost reductions which may result in the synergies and other cost reductions being materially greater or less than estimated. The estimates should therefore be read in conjunction with the bases and assumptions for these synergy numbers which are set out in Appendix I of this announcement. The synergies and other cost reductions have been reported on in accordance with Rule 19.3(b) of the Irish Takeover Rules by (i) PricewaterhouseCoopers LLP and (ii) Morgan Stanley & Co. International plc. Copies of their respective reports are included in Appendix IV and Appendix V to this announcement. Each of PricewaterhouseCoopers LLP and Morgan Stanley & Co. International plc has given and not withdrawn its consent to the issue of this announcement with the inclusion of its report and context in which it is included. The synergy and earnings enhancement statements in this section should not be construed as a profit forecast or interpreted to mean that the earnings of AbbVie and/or Allergan in 2019, or in any subsequent period, would necessarily match or be greater than or be less than those of AbbVie and/or Allergan for the relevant financial period or any other period. The synergies estimate excludes any potential revenue synergies.

The transaction is subject to the Conditions set out in Appendix III of the Rule 2.5 Announcement, including certain regulatory approvals and approval by Allergan’s Shareholders.

Conference Call and Other Materials

AbbVie will host an investor conference call today at 7:30 a.m. Central to discuss this transaction. The call will be webcast through AbbVie’s Investor Relations website at investors.abbvie.com. An archived edition of the call will be available after 11 a.m. Central. Presentation materials for the investor conference call are available here.

Conference call details:

Date:

Tuesday, June 25, 2019

Call start time:

7:30 a.m. Central time

Dial-in numbers:

877-934-8565 (toll free) or 210-795-9161 (international)

Passcode:

ABBVIE

Please place your call by 7:15 a.m. Central time in order to be cleared for the start of the call at 7:30 a.m. Central time.

Call replay:

800-846-1910 (toll free) or 402-280-9953 (international)

Replay code:

62519

In addition, an infographic highlighting the key attributes of this transaction is available here.

AbbVie’s lead financial advisor is Morgan Stanley & Co. LLC who has delivered a fairness opinion and has provided the committed financing for the transaction, and its legal advisors are Kirkland & Ellis LLP and McCann FitzGerald. PJT Partners LP is also serving as a financial advisor to AbbVie. Allergan’s exclusive financial advisor is J.P. Morgan Securities LLC and its legal advisors are Wachtell, Lipton, Rosen & Katz and Arthur Cox.

Key Questions and Answers

1. What are the strategic and financial benefits of this transaction?

This transaction achieves unique and complementary strategic objectives for both organizations. Combining Allergan’s diversified on-market product portfolio with AbbVie’s growth platform and deep expertise in R&D, commercial strength and international footprint will create a leading biopharmaceutical company with approximately $48 billion in combined 2019 revenue. This combination also enhances AbbVie’s ability for robust investment in its industry-leading pipeline of innovative therapies throughout the next decade and enables AbbVie to deliver on its mission to better serve patients.

The financial benefits include immediate 10% earnings-per-share accretion over the first full year of the combination, with peak accretion of greater than 20%. The transaction will generate annual pre-tax synergies and other cost reductions of at least $2 billion in year three, with a return on invested capital to exceed AbbVie’s cost of capital within the first full year.

2. When do you anticipate this transaction to close and what is the leadership structure for the new combined company?

We anticipate closing of the transaction by early 2020, subject to regulatory and Allergan’s shareholder approvals. The combined company will continue to be incorporated in Delaware and have its principal executive offices in North Chicago, Ill. Richard A. Gonzalez will serve as the chairman and chief executive officer through the Humira loss of exclusivity in 2023. AbbVie’s Board will include two Allergan board members, including Allergan’s chairman and chief executive officer, Brent Saunders.

3. Does this transaction represent a change in your fundamental strategy for AbbVie?

This transaction enhances our ability to continue to advance our mission to develop a consistent stream of innovative medicines to create a remarkable impact on people’s lives. AbbVie will now have a more diversified product portfolio with several leadership positions in high value therapeutic areas and an industry-leading pipeline of next-generation therapies with ensured capacity for continued investment across our innovative pipeline.

4. What is the benefit of doing a transaction of this size versus smaller bolt-on acquisitions?

This transaction is designed to meet a different strategic imperative than smaller bolt-on acquisitions. Its ability to deliver immediate scale to the AbbVie growth platform with Allergan’s on-market diversified product portfolio meets our strategic goal to reduce reliance on Humira and allows us to continue expanding our focus on high-innovation science throughout the next decade.

Smaller bolt-on acquisitions provide opportunities for future growth, but also require significant R&D investment amid scientific and clinical uncertainty. This transaction offers immediate compelling financial and strategic value to our shareholders with a much lower risk profile.

5. What is your level of confidence in your ability to operate the combined company given that it represents somewhat of a change in the mix of businesses from what AbbVie has been?

We are highly confident in our ability to enhance the value of Allergan’s existing commercial franchises and capitalize on next-generation pipeline programs. AbbVie has a proven track record of industry leading financial performance and commercial expertise in building market-leading franchises in immunology, hematologic oncology, and other areas, and our geographic scale will enable us to unlock additional value in Allergan’s franchises. Our senior leadership team is experienced in leading diverse businesses and we are confident in our future success.

6. What are your plans for capital allocation for the combined company? How do you intend to address the debt levels of the combined company?

The combined company will produce robust cash flow which will support continued growth of our dividend, further investment in our pipeline, and reduction of debt. We intend to reduce debt levels by $15-$18 billion by the end of 2021, with further deleveraging through 2023.

7. What do you view as the largest risks associated with the transaction?

Any transaction of this magnitude involves a series of regulatory approvals and integration complexities. Both companies have organizations that are highly experienced at integrating businesses and we expect that process to be efficient and thorough.

About AbbVie and Acquirer Sub

AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.

Acquirer Sub, a wholly-owned subsidiary of AbbVie, is a limited liability company organized in Delaware solely for the purpose of effecting the Acquisition. To date, Acquirer Sub has not conducted any activities other than those incidental to its formation and the execution of the Transaction Agreement.