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.

On June 25, 2019 Taiwan Liposome Company, Ltd. ("TLC") (Nasdaq: TLC, TWO: 4152), a clinical-stage specialty pharmaceutical company dedicated to the development and commercialization of novel nanomedicines designed to target areas of unmet medical need in osteoarthritis, pain management, ophthalmology and oncology, reported the signing of a development and license agreement with Birdie Biopharmaceuticals Inc. ("Birdie"), a wholly owned subsidiary of Seven and Eight Biopharmaceuticals Corp (Press release, Taiwan Liposome Company, JUN 25, 2019, View Source [SID1234537247]). Birdie and Seven and Eight Biopharmaceuticals are clinical stage biotech companies focused on the development of immunotherapy to treat cancer.

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Under the agreement, Birdie will engage TLC in the development and manufacturing of a liposomal formulated dual agonist product against toll-like receptors 7 and 8 (TLR7/8) utilizing TLC’s NanoX technology. Birdie will be responsible for the product’s preclinical and clinical development, regulatory filing and commercialization. TLC will be responsible for the formulation development and manufacturing. TLC will receive an upfront payment and is eligible to receive up to US$49 million in potential milestone payments. In addition, TLC is also eligible to royalties based on the net sales.

"This agreement leverages our expertise and gives further validation to our technology platform’s capability to expand into other areas such as immunotherapy for the treatment of cancer," commented TLC President George Yeh. "Our NanoX liposome technology has distinct advantages of achieving desirable pharmacokinetic profiles and preferential distribution to tumor tissues. We are delighted to partner with Birdie and working together on this collaboration to bring a potential new innovative therapy to cancer patients."

"TLR7/8 are amongst the most promising targets for immuno-oncology and our dual agonists have demonstrated the ability to stimulate specific types of innate immune response, generating enhanced anti-tumor immunity," said, Walter Lau, Ph.D., Chief Executive Officer of Birdie and Seven and Eight Biopharmaceuticals. "Following our recent announced collaboration with a major pharma partner on combination trials with established checkpoint inhibitors, we are excited to be working with TLC to develop a potential best-in-class next generation product. We believe that the robust, scalable and replicable manufacturing process of TLC’s NanoX technology formulates a sustainable competitive advantage and the potential to commercialize worldwide."

On June 25, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug application (IND) for ARV-471, an oral estrogen receptor (ER) PROTAC protein degrader, designed to selectively target ER for the treatment of patients with locally advanced or metastatic ER positive / HER2 negative breast cancer (Press release, Arvinas, JUN 25, 2019, View Source [SID1234537248]). Arvinas expects to initiate a Phase 1 clinical trial for ARV-471 in the third quarter of 2019.

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"ARV-471 is our second program in six months to receive IND clearance, and we are pleased to be advancing it into the clinic and progressing Arvinas’ portfolio of PROTAC protein degraders for the treatment of patients with cancer and other life-threatening diseases," said John Houston, Ph.D., President and CEO of Arvinas. "We hope the activity ARV-471 demonstrated preclinically will translate into a new, beneficial treatment for patients with locally advanced or metastatic ER positive/HER2 negative breast cancer."

In the United States, breast cancer is the second most common cancer and the second leading cause of cancer death in women. The American Cancer Society estimates that in 2019, there will be approximately 268,000 women diagnosed with invasive breast cancer in the United States. Metastatic breast cancer accounts for approximately 6% of newly diagnosed cases. Approximately 80% of newly diagnosed breast cancers are ER positive, with many patients developing resistance to current treatment options over time.

ARV-471 is a PROTAC protein degrader specifically designed to target and degrade ER. The Phase 1 trial will assess the safety, tolerability, and pharmacokinetics of ARV-471, and will also include measures of anti-tumor activity and pharmacodynamic readouts as secondary endpoints.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity as a single agent and in combination with a CDK4/6 inhibitor when compared to a standard of care agent, fulvestrant, dosed as single agent or in combination with a CDK4/6 inhibitor. Arvinas believes the differentiated pharmacology of ARV-471, including its iterative degradation activity, has the potential to translate into meaningful clinical benefit for patients.