On August 23, 2016 Medtronic plc (NYSE: MDT), the global leader in medical technology, reported that it has completed its acquisition of HeartWare International, Inc., a leading innovator of less-invasive, miniaturized, mechanical circulatory support technologies (MCS) for treating patients with advanced heart failure (Press release, Medtronic, AUG 23, 2016, View Source;p=RssLanding&cat=news&id=2196837 [SID:1234514704]). HeartWare will become part of the Heart Failure business within the Medtronic Cardiac Rhythm and Heart Failure division. Under the terms of the transaction, each outstanding share of HeartWare common stock has been converted into the right to receive $58.00 in cash, without interest, subject to any required withholding of taxes.

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HeartWare develops and manufactures miniaturized implantable heart pumps, or ventricular assist devices (VAD), to treat patients around the world suffering from advanced heart failure. Its flagship product, the HVAD System, features the world’s smallest full-support VAD and is indicated for refractory end-stage left-ventricular heart failure patients in the U.S. who are awaiting a heart transplant, as well as approved in Europe for long-term use in patients at risk of death from refractory, end-stage heart failure.
Medtronic estimates that the global VAD market is approximately $800 million currently, and worldwide is expected to grow in the mid-to-high single digits for calendar years 2016-17, and accelerate to high-single/low-double digits beyond calendar year 2017.
"Not only does the current HeartWare portfolio expand Medtronic leadership across the heart failure continuum, its product pipeline – when married with our expertise – can result in progressively less-invasive heart pumps that have the potential to benefit even more patients," said David Steinhaus, M.D., vice president and general manager of the Heart Failure business, and medical director for the Cardiac Rhythm and Heart Failure division at Medtronic. "Today, Medtronic offers the industry’s leading cardiac resynchronization therapy devices, including MR-conditional CRT-defibrillators; MCS therapy for advanced heart failure patients; heart failure diagnostics; and meaningful expert analysis through Medtronic Care Management Services, including the recently launched Beacon Heart Failure Management Service."

The acquisition of HeartWare broadens the Medtronic portfolio of therapies, diagnostic tools and services for patients suffering from heart failure, aligning with Medtronic’s Mission of alleviating pain, restoring health and extending life. The acquisition is part of the Company’s therapy innovation strategy to surround the physician with innovative products while focusing on patients and disease states.

"This is an exciting moment, as more than 600 HeartWare employees are now part of the broader Medtronic organization," said Doug Godshall, who served as president and chief executive of HeartWare for the past decade. "HeartWare has delivered incredible advancements for patients suffering from heart failure, through the commercialization of the HVAD system and pipeline development, and I am convinced that being part of Medtronic will allow us to accelerate meaningful innovations even more quickly."

Heart failure, also known as congestive heart failure, is a condition in which the heart isn’t pumping enough blood to meet the body’s needs. Heart failure usually develops slowly after an injury to the heart. Some injuries may include a progressive deterioration of the heart muscle, heart attack, untreated high blood pressure, or heart valve disease. Heart failure remains a leading cause of hospitalization and death in the United States, and its prevalence continues to increase, affecting more than 5 million people in the U.S. alone. The cost of heart failure is high. Healthcare expenditures in the U.S. on heart failure are estimated to be approximately $39 billion per year, making it one of the largest expenses to the healthcare system. With the aging of the population, Medtronic estimates that the number of patients with heart failure could exceed 8 million by 2030.

This transaction is expected to meet Medtronic’s long-term financial metrics for acquisitions. Medtronic does not intend to modify its fiscal year 2017 revenue outlook or earnings per share (EPS) guidance as a result of this transaction, although it is expected to provide increased confidence in the company’s ability to deliver on its FY17 revenue growth outlook. In addition, Medtronic expects minimal to no net EPS dilution from this transaction for the first two years as the company intends to offset the expected dilutive impact. The acquisition is expected to be earnings accretive in year three.

In collaboration with leading clinicians, researchers and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular disease and cardiac arrhythmias. The company strives to offer products and services of the highest quality that deliver clinical and economic value to healthcare consumers and providers around the world.

The Tender Offer and Merger
The tender offer for all of the outstanding shares of HeartWare common stock expired as scheduled immediately after 11:59 p.m. Eastern time on August 22, 2016. Computershare Trust Company, N.A., the depositary and paying agent for the tender offer, has advised Medtronic that 14,952,817 shares of HeartWare common stock were validly tendered and not properly withdrawn in the tender offer, representing approximately 85.15% of the outstanding shares. All of the conditions to the tender offer have been satisfied, and on August 23, 2016, Medtronic Acquisition Corp., a subsidiary of Medtronic, accepted for payment and will promptly pay for all shares validly tendered and not properly withdrawn in the tender offer.

Following acceptance of the tendered shares, Medtronic completed its acquisition of HeartWare through the merger of Medtronic Acquisition Corp. with and into HeartWare without a vote of HeartWare’s stockholders pursuant to Section 251(h) of the Delaware General Corporation Law. As a result of the merger, HeartWare became a wholly-owned subsidiary of Medtronic. In connection with the merger, all HeartWare shares not validly tendered into the tender offer (other than shares (i) owned by HeartWare as treasury stock or owned by Medtronic, Inc. or Medtronic Acquisition Corp., which shares were cancelled and retired and cease to exist or (ii) held by any person who was entitled to and has properly demanded statutory appraisal of his or her shares) have been cancelled and converted into the right to receive the same $58.00 per share in cash, without interest, subject to any required withholding of taxes, as will be paid for all shares that were validly tendered and not properly withdrawn in the tender offer. HeartWare common stock will cease to be traded on The NASDAQ Stock Market LLC.

On August 23, 2016 Immune Therapeutics, Inc. (OTCQB-IMUN) ("IMUN"), a clinical-stage biopharmaceutical company involved in the commercialization, manufacturing, distribution and marketing of its novel immunotherapies to combat chronic, life-threatening diseases through the activation and modulation of the body’s immune system reported that through its wholly owned subsidiary TNI Biotech International, Ltd. it has initiated a clinical trial in Malawi LDN for the prevention of cervical cancer (Filing, 8-K, TNI BioTech, AUG 23, 2016, View Source [SID:1234514706]).

IMUN, in conjunction with the College of Medicine Malawi, has initiated a clinical study with LDN for the prevention of cervical cancer. This is an open-label, multicenter study designed to determine the safety and acceptability of a single-visit approach to cervical cancer prevention in patients. Using a single-visit approach to prevent cervical cancer, women will be examined through visual inspection of the cervix with acetic acid wash (VIA) and, if tests results are positive, patients will be offered immediate cryotherapy of the precancerous lesion. The secondary objectives are to determine life extension, to improve the immune system of immune comprised patients by starting treatment with LDN.

The Brewer Foundation in partnership with IMUN arranged both the funding for the trial and the donation of the Wallach LL100 Cryosurgical system necessary to run the trial and treat patients.

"The joint goal of this ever-important initiative is to empower the people of Malawi and to provide affordable health solutions to those most vulnerable. With this trial, we, with IMUN and its subsidiaries, hope to combat cervical cancer and immediately start saving lives in our ongoing initiative to improve global health," stated His Excellency, Ambassador Jack Brewer, Founder and Executive Director of JBF Worldwide.

Noreen Griffin, Chief Executive Officer of IMUN, said "With the increase in the number of patients in Africa suffering from cancer, the need for affordable non-toxic therapies becomes more important every day. We, with our partners GB Pharma and The Jack Brewer Foundation, intend to be part of finding a solution."

Dr. Frank Taulo, the head of the OBGYN Department for Queen Elizabeth Central Hospital in Blantyre and Principal Investigator of the trial, explained, "Since the beginning of the cervical cancer prevention programme in Malawi, strides have been made regarding scaling up of the screening services and premalignant lesions treatment using cryotherapy. One of the biggest challenges has been the inadequate cryotherapy medical device. The timely donation of 10 cryotherapy guns has alleviated tremendously this anomaly. Now several centers are able to treat these lesions."

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On August 22, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported the addition of new clinical markers to its FoundationOne and FoundationOne Heme products, which are designed to enhance oncologists’ insight into potential response to immunotherapies (Press release, Foundation Medicine, AUG 22, 2016, View Source [SID:1234514660]). This ability to determine TMB and MSI from its assays is additional to the existing comprehensive profiling of genes provided by FoundationOne and FoundationOne Heme. Taken together, the molecular information provided by Foundation Medicine provides unique insights to physicians and enhances their ability to predict response to immunotherapies, identify targeted therapeutic options, and improve access to clinical trials all from a single assay.

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"Cancer immunotherapies are at the forefront of cancer treatment, and new, quantitative approaches are needed to predict clinical responses to this important, but also expensive, class of therapies," said Vincent Miller, M.D., chief medical officer of Foundation Medicine. "Prior to our ability to measure TMB and MSI with FoundationOne, these biomarkers could only be detected separately, either through tests such as immunohistochemistry, polymerase chain reaction (PCR) or whole exome sequencing. Importantly, high-quality, predictive TMB scoring can only be accurately performed with sophisticated algorithms developed to work with broad, hybrid capture-based platforms that can analyze all relevant alterations simultaneously. Integrating this capability to measure TMB and MSI with one tissue sample, and reported in one test, represents an important advance in clinical care."

A growing body of evidence, most recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting this year, validates the ability of a new independent marker, TMB, to predict the likelihood of response to cancer immunotherapies. TMB is reported as the total number of DNA mutations per megabase in a tumor sequence. This phenomenon has been validated across a wide range of tumor types, including advanced bladder cancer, lung cancer, breast cancer, colorectal cancer, advanced head and neck cancer and melanoma. Some tumors develop high TMB as a result of defective mismatch repair of DNA, a condition in which the length of certain DNA areas becomes more widely varied than normal. This condition, which is referred to as MSI-high and MSI-high tumors, almost always has a high TMB.

"The ability to accurately measure multiple biomarkers simultaneously, including TMB and MSI, is an important advance for the field of cancer immunotherapy, and one that is unique to Foundation Medicine," said Thomas George, M.D., GI oncology program director, University of Florida. "Foundation Medicine’s combination of advanced sequencing platforms and highly-specific algorithms gives me access to all relevant genomic biomarkers for my patients at once, helping to save both time and tissue."

"We were encouraged by the findings presented at ASCO (Free ASCO Whitepaper), including the possibility of identifying patients more likely to benefit from checkpoint inhibitor immunotherapy," said Dr. Miller. "Our goal is to empower doctors and patients with a full range of relevant, actionable genomic information, and we’re excited to offer our distinctive solution to estimate TMB and MSI simultaneously and with exceptional accuracy, supported by sophisticated algorithms and rooted in contextual insights from our knowledgebase FoundationCORE. This is something no other next-generation sequencing platform offers."

Independent of the FoundationOne and FoundationOne Heme assays, Foundation Medicine also offers testing for PD-1 and PD-L1 protein expression, providing, in combination with the FoundationOne assays, a full suite of cancer immunotherapy assays for oncologists.

On August 22, 2016 Pfizer Inc. (NYSE:PFE) and Medivation, Inc. (NASDAQ:MDVN) reported that they have entered into a definitive merger agreement under which Pfizer will acquire Medivation, a biopharmaceutical company focused on developing and commercializing small molecules for oncology, for $81.50 a share in cash for a total enterprise value of approximately $14 billion (Press release, Medivation, AUG 22, 2016, View Source [SID:1234514661]). The Boards of Directors of both companies have unanimously approved the merger, which is expected to be immediately accretive to Pfizer’s Adjusted Diluted EPS upon closing, approximately $0.05 accretive in the first full year after close with additional accretion and growth anticipated thereafter. Pfizer does not expect the transaction to impact its current 2016 financial guidance.

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"The proposed acquisition of Medivation is expected to immediately accelerate revenue growth and drive overall earnings growth potential for Pfizer," said Ian Read, chairman and chief executive officer, Pfizer. "The addition of Medivation will strengthen Pfizer’s Innovative Health business and accelerate its pathway to a leadership position in oncology, one of our key focus areas, which we believe will drive greater growth and scale of that business over the long-term. This transaction is another example of how we are effectively deploying our capital to generate attractive returns and create shareholder value."

Medivation’s portfolio includes XTANDI (enzalutamide), an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. XTANDI is the leading novel hormone therapy in the United States today and generated approximately $2.2 billion in worldwide net sales over the past four quarters, as recorded by Astellas Pharma Inc., with whom Medivation entered an agreement in 2009 to develop XTANDI globally and commercialize jointly in the U.S. Since its approval for advanced metastatic prostate cancer by the U.S. Food and Drug Administration in 2012, XTANDI has treated 64,000 men to date in the U.S. alone. Medivation and Astellas have built a robust development program for XTANDI, including two Phase 3 studies in non-metastatic prostate cancer and another Phase 3 study in hormone-sensitive prostate cancer. It is also being further developed in Phase 2 studies for the potential treatment of advanced breast cancer and hepatocellular carcinoma.

In addition, Medivation has a promising, wholly-owned, late-stage oncology pipeline, which includes two development-stage oncology assets, talazoparib and pidilizumab. Talazoparib, currently in a Phase 3 study for the treatment of BRCA-mutated breast cancer, has the potential to be a highly potent PARP inhibitor and could be efficacious across several additional tumors. Pidilizumab is an immuno-oncology (IO) asset being developed for diffuse large B-cell lymphoma and other hematologic malignancies and has the potential to be combined with IO therapies in Pfizer’s portfolio.

"We believe the combination with Pfizer is the right next step in our growth trajectory and is a testament to the passion and dedication by which the Medivation team has delivered on our mission to profoundly transform patients’ lives through medically innovative therapies," said David Hung, M.D., founder, president and CEO of Medivation. "This compelling transaction will deliver significant and immediate value to our stockholders and provides new opportunities for our employees as part of a larger company. We believe that Pfizer is the ideal partner to extend the reach of our blockbuster XTANDI franchise and take our promising, late-stage assets – talazoparib and pidiluzimab – to their next stages of development so that they can be made available to patients as quickly as possible."

"The proposed acquisition of Medivation will build upon Pfizer’s success with our IBRANCE (palbociclib) launch in HR+/HER2- metastatic breast cancer and with our strong immuno-oncology portfolio, and will transform Pfizer into a leading oncology company," said Albert Bourla, group president, Pfizer Innovative Health. "IBRANCE and XTANDI are anchor brands in breast and prostate cancer respectively, giving Pfizer leadership in two hormone-driven cancers. Similar to IBRANCE in the breast cancer setting, XTANDI is being explored for its potential to move from metastatic prostate cancer to treat earlier stages of non-metastatic prostate cancer. In addition, Medivation’s portfolio within prostate cancer and across diverse tumors will complement Pfizer’s broad IO portfolio. Finally, Medivation adds commercial scale to better compete with other top tier oncology companies in advance of the potential emergence of Pfizer’s IO pipeline expected in the next few years. Together, we believe Pfizer and Medivation can bring the full force of our combined research and resources to combat two of the most common cancers, as well as speed cures and make accessible breakthrough medicines to patients, redefining life with cancer."

Cancer remains the second leading cause of death in the U.S. and a "Top 10" killer worldwide. According to the American Cancer Society, breast cancer and prostate cancer are among the top three cancers by annual incidence in the U.S. There are several parallels between breast and prostate cancer, including the incidence of prostate cancer in the U.S., which is similar to that of breast cancer with approximately 280,000 cases per year.

Pfizer expects to finance the transaction with existing cash.

Under the terms of the merger agreement, a subsidiary of Pfizer will commence a cash tender offer to purchase all of the outstanding shares of Medivation common stock for $81.50 per share, net to the seller in cash, without interest, subject to any required withholding of taxes. The closing of the tender offer is subject to customary closing conditions, including U.S. antitrust clearance and the tender of a majority of the outstanding shares of Medivation common stock. The merger agreement contemplates that Pfizer will acquire any shares of Medivation that are not tendered into the offer through a second-step merger, which will be completed promptly following the closing of the tender offer. Pfizer expects to complete the acquisition in the Third- or Fourth-Quarter 2016.

Pfizer’s financial advisors for the transaction were Guggenheim Securities and Centerview Partners, with Ropes & Gray LLP acting as its legal advisor. J.P. Morgan Securities and Evercore served as Medivation’s financial advisors, while Cooley LLP and Wachtell, Lipton, Rosen & Katz served as its legal advisors.

On August 22, 2016 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) reported financial results for the second quarter of 2016 (Press release, ImmunoCellular Therapeutics, AUG 22, 2016, View Source [SID:1234514665]).

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Andrew Gengos, ImmunoCellular Chief Executive Officer, commented: "We are pleased with the progress we made in the first half of this year, and believe that 2016 will be a year of accomplishment for our company. The first patient in the ICT-107 phase 3 trial was treated in June – a major achievement for our company. Today, more than 140 patients have been screened and clinical site activation is accelerating. We currently have activated 60 clinical sites in the US, two in Canada, and one in the UK, with more expected to come in the third quarter. With ICT-107, ImmunoCellular is one of a small number of companies in the cancer immunotherapy arena that we believe to be in the final stage of clinical development. In light of these achievements, our confidence remains high for the value and quality of our phase 3 program, and the therapeutic and commercial potential of ICT-107. The phase 1 open-label trial of ICT-121 in patients with recurrent glioblastoma has completed enrollment, reaching the target of 20 patients. The trial is being conducted at six sites in the US and preliminary results are expected in about 9 months. We are grateful for the continued support of the medical and scientific cancer community, and the confidence placed in our company by our collaborators."

Upcoming Goals and Milestones:

ICT-107:
Continue to bring US, Canadian and European clinical sites online, with the goal of having all sites in all 10 countries activated by the end of 2016.
Anticipate randomization of all patients by the end of 2017, and an additional 2-3 years from then to achieve the at least 274 required events.
Plan to conduct a futility interim analysis at 30% of events, or at about the 2-year mark, and an efficacy interim analysis at 67% of events, or at about the 2½ -year mark.
Present updated immune monitoring data from the ICT-107 phase 2 trial and updated long-term survival data from the phase 1 trial at the Society for NeuroOncology annual scientific meeting in November 2016 in two oral presentations.
ICT-121:
Continuing to monitor patients, with data expected in about 9 months.
Research:
Anticipate having one or more T cell receptors identified for a Stem-to-T-cell clinical candidate or candidates by year-end 2016.
Initial attempt to package a T cell receptor DNA sequence in the lentivirus/gene therapy construct by year-end 2016.
Continued progress in collaboration with University of Maryland on projects that have application to existing dendritic cell immunotherapy and Stem-to-T-cell technology platforms.
Second Quarter 2016 Financial Results

For the quarter ended June 30, 2016, ImmunoCellular incurred a net loss of $5.3 million, or $0.06 per basic and diluted share, compared to a net loss of $3.2 million, or $0.03 per basic and diluted share, for the quarter ended June 30, 2015.

During the second quarter 2016, ImmunoCellular incurred $4.4 million of research and development expenses compared to $2.3 million in the prior year quarter while general and administrative expenses remained relatively constant between periods. The $2.1 million increase in research and development expenses primarily reflects the additional expenses associated with the phase 3 trial of ICT-107.

For the six months ended June 30, 2016, ImmunoCellular incurred a net loss of $11.0 million, or $0.12 per basic and diluted share, compared to a net loss of $4.6 million, or $0.05 per basic and diluted share, During the six months ended June 30, 2016, ImmunoCellular incurred $9.2 million in research and development expenses compared to $4.4 million in the prior year.

ImmunoCellular also reported that cash used in operations during the six months ended June 30, 2016 was $11.2 million compared to $6.9 million in the prior year. The increase primarily reflects that additional research and development expenditures in the current year. As of June 30, 2016, ImmunoCellular had $11.9 million in cash.

Subsequent to June 30, 2016, ImmunoCellular entered into an underwriting agreement with Maxim Group LLC, pursuant to which it sold 34,550,000 shares of common stock, pre-funded warrants to purchase 12,450,000 shares of ImmunoCellular’s common stock and base warrants to purchase 35,250,000 shares of its common stock. The common stock and base warrants were sold at a combined public offering price of $0.16, and the base warrants were approved for listing on the NYSE MKT under the symbol "IMUC.WS." The pre-funded warrants were sold to certain investors in lieu of common stock less the $0.01 per share exercise price for each pre-funded warrant. The base warrants have an exercise price of $0.1921 per share. Additionally, ImmunoCellular granted the underwriters a 45 day option to purchase up to an additional 7,050,000 shares of common stock and/or base warrants to purchase 5,287,000 shares of its common stock. On August 12, 2016, the underwriters exercised the option to purchase 4,478,625 of additional base warrants at a price of $0.01266 per base warrant. The gross proceeds from the offering are approximately $7.5 million.

Additionally, the terms of the California Institute of Regenerative Medicine (CIRM) award were modified such that ImmunoCellular received an additional $1.5 million in July 2016 as part of the initial award received from CIRM. The total amount of the award and other award conditions remain unchanged.