On July 10, 2019, Forty Seven reported that entered into an exclusive license and collaboration agreement with Ono Pharmaceutical Co., Ltd., or Ono (Filing, 8-K, Forty Seven, JUL 10, 2019, View Source [SID1234537499]). Under the agreement, we granted Ono an exclusive license to develop, manufacture and commercialize 5F9, our monoclonal antibody against CD47, as well as other anti-CD47 antibodies controlled by us in Japan, South Korea, Taiwan and the ASEAN countries, or the Ono Territory. We retain all rights to 5F9 and other licensed antibodies outside of the Ono Territory.

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Under the agreement, the parties will collaborate on the development, manufacturing and commercialization of 5F9 and other licensed antibodies. Each party will be responsible for conducting development and commercialization of licensed antibodies in its respective territory at its own cost. Further, each party will have the right to participate, at its cost, in global clinical studies of 5F9 and other licensed antibodies conducted by the other party. We will initially be responsible for supplying 5F9 and other licensed antibodies to Ono for development and commercialization within the Ono Territory at Ono’s cost. Ono has the right to elect that such manufacturing activities be transferred to Ono. During the term of the agreement, neither party may manufacture or commercialize any competing products in the Ono Territory.

We will receive a one-time upfront payment of approximately $15.8 million from Ono and will be eligible to receive up to an additional approximately $104 million at current exchange rates if specified future development and commercial milestones are achieved by Ono. We are also eligible to receive tiered percentage royalties spanning from the mid-teens to the low-twenties on future net sales of 5F9 and other licensed antibodies in the Ono Territory, subject to certain offsets. Ono’s obligation to pay royalties expires, on a product-by-product and country-by-country basis, on the later of (1) the expiration of the first regulatory exclusivity for such product in such country, (2) the expiration of the last to expire patent controlled by us that covers the composition of matter of a licensed antibody in such product in such country, or (3) the tenth anniversary of the first commercial sale of such product in such country.

The agreement will remain in effect until the expiration of all of Ono’s royalty obligations, after which Ono’s license shall be fully paid-up. Ono may terminate the agreement on a country-by-country basis for convenience upon 90 days’ prior written notice to us prior to the first commercial sale of the first licensed product in the Ono Territory, or 180 days’ prior written notice after such first sale. Either party may also terminate the agreement for the other party’s uncured material breach or insolvency, subject to specified notice and cure periods. In the event of any early termination, all rights in 5F9 and other licensed antibodies will revert to us, subject to certain royalties due to Ono in the case of Ono’s termination for our breach or insolvency.

This summary is qualified in its entirety by reference to the text of the exclusive license and collaboration agreement which we intend to file as an exhibit to our Quarterly Report on Form 10-Q for the quarter ending September 30, 2019.

On July 10, 2019 Medtronic plc (the "Company") (NYSE:MDT) reported the pricing terms of the previously announced cash tender offers by its wholly-owned indirect subsidiaries, Medtronic, Inc., Medtronic Global Holdings S.C.A. ("MGH") and Covidien International Finance S.A. ("CIFSA" and, together with Medtronic, Inc. and MGH, the "Offerors"), for any and all (the "Any and All Tender Offer") of the approximately $1.175 billion in aggregate principal amount of the outstanding Notes listed in Table 1 below (the "Any and All Notes") and up to $4.35 billion (the "Aggregate Maximum Purchase Price") combined aggregate purchase price (excluding accrued and unpaid interest to, but not including, the applicable settlement date and excluding fees and expenses related to the Tender Offers) (the "Maximum Tender Offer" and, together with the Any and All Tender Offer, the "Tender Offers") for the outstanding Notes listed in Table 2 below (the "Maximum Tender Offer Notes," and collectively with the Any and All Notes, the "Notes") (Press release, Medtronic, JUL 10, 2019, View Source;p=RssLanding&cat=news&id=2403406 [SID1234537472]).

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The terms of the Tender Offers are described in the Offer to Purchase, dated June 24, 2019 (the "Offer to Purchase"), and remain unchanged except by (i) the previously announced increase of the Aggregate Maximum Purchase Price and (ii) the increase of certain of the Series Tender Caps described in the Offer to Purchase (a) from $100 million to $150 million with respect to Medtronic, Inc.’s 4.625% Senior Notes due 2045 and (b) from $200 million to approximately $450 million with respect to Medtronic, Inc.’s 4.375% Senior Notes due 2035.

The applicable Total Consideration for each series of Notes is based on the applicable reference yield plus a fixed spread, in each case as set forth in the tables below, and is payable to holders of the Notes who validly tendered and did not validly withdraw their Notes on or before 5:00 p.m., New York City time, on July 9, 2019 (the "Early Tender Deadline") and whose Notes are accepted for purchase by the applicable Offeror. The Reference Yields listed in the tables were determined at 11:00 a.m., New York City time, on July 10, 2019 by the lead dealer managers (identified below). The applicable Total Consideration for each series of Notes includes an early tender premium of $30 per $1,000 principal amount of Notes validly tendered and not validly withdrawn by such holders and accepted for purchase by the applicable Offerors (the "Early Tender Premium").

Per $1,000 principal amount of Notes that are tendered and accepted for purchase.
The applicable Total Consideration includes the early tender premium of $30 per $1,000 principal amount of Notes.
The offers with respect to the Maximum Tender Offer Notes are subject to the Aggregate Maximum Purchase Price of $4.35 billion and the Series Tender Caps. All references to the aggregate purchase price for the Maximum Tender Offer Notes include the applicable Total Consideration or Tender Offer Consideration (as defined below) and exclude applicable accrued interest and fees and expenses related to the Maximum Tender Offer. The Offerors will purchase an aggregate principal amount of Maximum Tender Offer Notes having an aggregate purchase price up to the Aggregate Maximum Purchase Price, subject to the Acceptance Priority Level and the Series Tender Caps as set forth in the table above.
The Offerors expect to pay the purchase price for the Notes accepted for purchase with the net proceeds of the previously announced public offering of senior notes by MGH, which was completed on July 2, 2019. Subject to the satisfaction or waiver of all remaining conditions to the Tender Offers described in the Offer to Purchase having been either satisfied or waived by the applicable Offeror, the Offerors intend to accept for purchase validly tendered Notes in the principal amounts indicated in the table above.

Notes not accepted for purchase will be promptly credited to the account of the registered holder of such Notes with The Depository Trust Company or otherwise returned in accordance with the Offer to Purchase.

All payments for Notes purchased in connection with the Early Tender Deadline will also include accrued and unpaid interest on the principal amount of Notes tendered up to, but not including, the early settlement date, which is currently expected to be July 12, 2019. In accordance with the terms of the Tender Offers, the withdrawal deadline was 5:00 p.m., New York City time, on July 9, 2019. As a result, tendered Notes may no longer be withdrawn, except in certain limited circumstances where additional withdrawal rights are required by law (as determined by the applicable Offeror).

Although the Tender Offers are scheduled to expire at 12:00 midnight, New York City time, on July 24, 2019 (one minute after 11:59 p.m., New York City time, on July 24, 2019), or any other date and time to which the applicable Offeror extends such Tender Offer, because holders of Maximum Tender Offer Notes subject to the Tender Offers validly tendered and did not validly withdraw Maximum Tender Offer Notes on or prior to the Early Tender Deadline for which the aggregate consideration payable exceeds the Aggregate Maximum Purchase Price, the Offerors do not expect to accept for purchase any tenders of Maximum Tender Offer Notes after the Early Tender Deadline. Holders of Any and All Notes who validly tender such notes following the Early Tender Deadline and at or prior to the applicable expiration date will only receive the applicable Tender Offer Consideration (the "Tender Offer Consideration") for Notes accepted for purchase, which is equal to the applicable Total Consideration minus the applicable Early Tender Premium.

Information Relating to the Tender Offers

Barclays Capital Inc., BofA Merrill Lynch and Goldman Sachs & Co. LLC are acting as the dealer managers (the "Dealer Managers") for the Tender Offers. The information agent and tender agent is Global Bondholder Services Corporation ("Global Bondholder"). Copies of the Offer to Purchase and related offering materials are available by contacting Global Bondholder at +1-866-470-4200 (U.S. toll-free) or +1-212-430-3774 (banks and brokers). Questions regarding the Tender Offers should be directed to Barclays Capital Inc., Liability Management Group at +1-212-528-7581 (collect) or +1-800-438-3242 (toll free), BofA Merrill Lynch, Liability Management Group, at +1-980-387-3907 (collect) or +1-888-292-0070 (toll-free) or Goldman Sachs & Co. LLC at +1-212-357-0215 or +1-800-828-3182 (toll free).

None of the Offerors, the Company or their affiliates, their respective boards of directors or managing members, the Dealer Managers, Global Bondholder or the trustee with respect to any series of Notes is making any recommendation as to whether holders of Notes should tender any Notes in response to any of the Tender Offers, and neither the Offerors nor any such other person has authorized any person to make any such recommendation. Holders must make their own decision as to whether to tender any of their Notes, and, if so, the principal amount of Notes to tender.

This press release shall not constitute an offer to sell, a solicitation to buy or an offer to purchase or sell any securities. The Tender Offers are being made only pursuant to the Offer to Purchase and only in such jurisdictions as is permitted under applicable law.

The full details of the Tender Offers, including complete instruction on how to tender Notes, are included in the Offer to Purchase. The Offer to Purchase contains important information that should be read by holders of Notes before making a decision to tender any Notes. The Offer to Purchase may be downloaded from Global Bondholder’s website at View Source or obtained from Global Bondholder, free of charge, by calling toll-free at +1-866-470-4200 (bankers and brokers can call collect at +1-212-430-3774).

On July 10, 2019 Geneos Therapeutics, a clinical-stage biotech company, a spin-out of Inovio Pharmaceuticals (NASDAQ: INO), reported that the first cancer patient was dosed using the company’s GT-EPIC Neoantigen-Targeting Personalized Vaccine Technology (Press release, Geneos Therapeutics, JUL 10, 2019, View Source [SID1234537471]). In this first-in-human treatment – part of a clinical collaboration between Geneos and Washington University School of Medicine in St. Louis – a patient with Anaplastic Astrocytoma, a form of advanced brain cancer, is being treated on a Compassionate Use basis with the patient’s own tumor-derived neoantigen vaccine. The target neoantigens were identified using Washington University’s proprietary neoantigen prediction algorithm – pVAC-Seq. The vaccine, which targets 30 antigens including all 27 tumor specific neoantigens and 3 tumor antigens identified from the patient’s tumor, was designed and administered based on the GT-EPIC Platform.

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Dr. Niranjan Y. Sardesai, Geneos’ Chief Executive Officer, said "This first-in-human treatment is an important milestone for Geneos as it demonstrates the company’s rapid biopsy-to-treatment implementation of its GT-EPIC technology platform to target cancer neoantigens on a personalized basis. Geneos is pleased to collaborate with Washington University, a pioneer in developing neoantigen-targeting therapies, in this first-in-human treatment. This collaboration highlights some of the key advantages of the GT-EPIC platform such as the ability to move rapidly into the clinic to treat cancers and to target upwards of all (30+) targetable antigens in the patient in a single administration."

The patient’s treatment is led by neurosurgeon Dr. Gavin Dunn and medical oncologist Dr. Tanner Johanns, who treat patients at Siteman Cancer Center at Washington University and Barnes-Jewish Hospital. "We partnered with Geneos to use its technology in building a personalized cancer vaccine tailored to the mutated proteins found in this patient’s tumor. We were drawn to the speed and versatility of the Geneos platform, along with its safety record and clinical immunogenicity data from previous human studies in both cancer and infectious diseases. Therefore, we approached Geneos about supporting our effort to make the experimental treatment available to this patient who otherwise has limited treatment options. We look forward to expanding this collaboration and evaluating the same technology to generate personalized neoantigen vaccines for the treatment of additional tumor types," Johanns said.

Cancer neoantigens – the mutations and genomic changes that accumulate as tumors develop – have been recognized as important targets in the development of immune mediated treatments for cancer. These neoantigens are recognized by the immune system as being foreign and generate immune responses directed at the cancer. The GT-EPIC Platform is based on a DNA vaccine platform which Geneos exclusively licensed from Inovio Pharmaceuticals (NASDAQ:INO), and allows the company to develop exquisitely personalized therapies tailored to each patient’s unique tumor mutations. Geneos, along with its collaborators at The Wistar Institute, recently published preclinical, proof-of-concept animal model data in the prestigious journal, Cancer Immunology Research, demonstrating the functional advantages of the Geneos Platform.

For more information on the company, visit www.geneostx.com.

About Geneos Therapeutics’ GT-EPIC Neoantigen-Targeting Platform
Geneos Therapeutics’ GT-EPIC Neoantigen-Targeting Platform is based on a clinically-validated DNA vaccine platform exclusively licensed from Inovio Pharmaceuticals, Inc. (NASDAQ: INO) for use in developing personalized, neoantigen-targeting immunotherapies. The platform has been used extensively and safely by Inovio Pharmaceuticals in the clinical treatment of patients with over 2,000 patients treated and over 6,000 administrations. The GT-EPIC platform allows Geneos to develop exquisitely personalized DNA-based therapies tailored to each patient’s unique tumor mutations. The GT-EPIC platform is poised to deliver the following key advantages: ability to drive potent and broad T cell immune responses, capability to target an unprecedented number of neoantigens in a single formulation, and a rapid manufacturing turnaround time. Geneos believes that these are the three key differentiators that will drive the company, and the oncology space, into the next generation of immunotherapies.

On July 10, 2019 TARIS Bio reported the dosing of the first patient in a Phase 1b clinical trial evaluating the investigational product TAR-200 in combination with Opdivo (nivolumab), a programmed death-1 (PD-1) immune checkpoint inhibitor from Bristol-Myers Squibb (Press release, TARIS Biomedical, JUL 10, 2019, View Source [SID1234537470]). The combination will be assessed for safety, tolerability and preliminary efficacy in patients with muscle-invasive bladder cancer (MIBC). This trial is being conducted as part of a clinical collaboration between the companies; Bristol-Myers Squibb is also an equity investor in TARIS.

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Bladder cancer affects more than 2.7 million patients worldwide and is among one of the most expensive types of cancers to treat on a per-patient lifetime basis. MIBC is an aggressive and often lethal form of the disease, with the potential for rapid progression and metastasis. The preferred standard of care for MIBC is radical cystectomy (surgical removal of the bladder) with a neoadjuvant course of platinum-based chemotherapy. This neoadjuvant therapy has been shown to confer a survival benefit to patients versus cystectomy alone. Unfortunately, this therapy is utilized in less than 15% of patients scheduled for cystectomy, due primarily to concerns around patient frailty and potential delays to surgery. [i] A neoadjuvant regimen such as the combination of TAR-200 plus Opdivo, which has the potential to be used in the large majority of patients not receiving platinum-based therapy, would address a substantial unmet need.

"This clinical trial will be the first to evaluate the combination of the locally-administered TAR-200 system with a systemic PD-1 checkpoint inhibitor, approved for previously treated adults with advanced bladder cancer," said Christopher J. Cutie, M.D., Chief Medical Officer of TARIS. "We are eager to evaluate the potential antitumor and immunologic synergy of this product combination administered prior to surgery."

"We are excited to be working with BMS, an industry leader in oncology, on this clinical study," said Tony Kingsley, President and Chief Executive Officer of TARIS. "It illustrates TARIS’ commitment to advancing new therapies for this serious disease, and the potential of TAR-200 to improve outcomes for patients. In parallel, TARIS continues to study TAR-200 as a single agent for the treatment of MIBC patients not receiving surgery."

The open-label, multi-center, single group assignment Phase 1b clinical study will enroll up to 25 patients with MIBC who are scheduled for radical cystectomy. TAR-200 and Opdivo will each be administered on day one of four consecutive 21-day dosing cycles, for a total dosing period of 84 days prior to radical cystectomy. Information about the trial is available on ClinicalTrials.gov, identifier #NCT03518320.

About TAR-200
TARIS’ lead investigational product, TAR-200, is designed to release the chemotherapeutic agent gemcitabine continuously in the bladder for multiple weeks. TARIS believes that TAR-200 has the potential to harness gemcitabine’s both direct antitumor and immuno-oncologic activity without meaningful systemic drug exposure, yielding a powerful therapy and mitigating systemic side-effects. TAR-200 has been granted Fast Track status by the U.S. Food and Drug Administration for the potential treatment of MIBC patients unfit for curative-intent therapy.

On July 10, 2019 Biomarck Pharmaceuticals, Ltd reported that statistical significance (p=0.02) was achieved in improvement of Overall Response Rate (ORR) in the BIO-11006/SOC group compared to standard of care alone at 3 months in the Phase 2 study in NSCLC (Press release, BioMarck Pharmaceuticals, JUL 10, 2019, View Source [SID1234537469]). This study compares standard of care alone, (pemetrexed/carboplatin; SOC) to SOC plus BIO-11006 in 60 patients with stage 4, NSCLC.

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BIO-11006/SOC also showed less Disease Progression (DP) than SOC alone (7% to 17% respectively) and more Partial Response (PR) than SOC (40% to 30%).

BIO-11006 was well tolerated with cough, dyspnea and headache being most commonly (5%) related adverse events. This compares favorably to the myelosuppression, liver and renal toxicity of other commonly used agents.

In Vivo studies have shown BIO-11006 can inhibit NSCLC metastases and reduce tumor size in several animal species. Those treated with BIO-11006 also did not lose weight over the treatment period. This study is intended to give confirmation of these findings in a clinical setting.

About the Phase 2 study
This is a SOC controlled randomized, parallel group, clinical study evaluating BIO-11006 in addition to SOC in patients who have end stage NSCLC. The primary endpoint is progression free survival (PFS) at three months with secondary endpoints of response rate (RR), overall survival (OS) at 3 and 12 months. Body weight is also a clinical endpoint. For more information please visit View Source ID number NCT 03472053