On July 11, 2019 Castle Biosciences, Inc., a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of a study that establishes an evidence-based population to guide appropriate use of the DecisionDx-Melanoma test in patients with thinner tumors (Press release, Castle Biosciences, JUL 11, 2019, View Source [SID1234537475]). The study was published in the peer-reviewed journal SKIN: The Journal of Cutaneous Medicine.

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Current best practice for the use of DecisionDx-Melanoma includes informing two key treatment plan decisions following a melanoma diagnosis. First, for most patients with cutaneous melanoma who are eligible for a sentinel lymph node biopsy (SLNB), DecisionDx-Melanoma can identify patients at low risk of positivity and inform the decision to undergo this surgical procedure. This can include patients with tumor thickness less than or equal to 2.0 mm with no minimum thickness criteria.

The second use for DecisionDx-Melanoma is designed to predict an individual’s risk of recurrence to help physicians determine an appropriate level of follow-up, imaging and referrals. Previously published validation studies have reported that the test can accurately determine risk of recurrence in patients with Stage I-III melanoma, including tumors with a thickness less than 1.0 mm. The purpose of this study was to determine whether an evidence-based thickness threshold can be established for this second use to further guide appropriate clinical use of the test in patients with thinner (1.0 mm or less) melanoma tumors.

Key Study Findings:

An analysis of a large, multicenter dataset (n=1,479) that calculated event rates by tumor thickness and DecisionDx-Melanoma class result found a separation of recurrence rates between Class 1A (lowest risk) and Class 2B (highest risk) at a threshold of 0.3 mm.
In a separate analysis of tumors ≤1.0 mm thick tested clinically (n=8,944) and at a large dermatopathology practice (n=437), tumors with a thickness between 0.3 mm and 1.0 mm showed a 10.8% and 15.7% non-Class 1A result, respectively, suggesting that there is a benefit of risk assessment for this portion of the thin tumor population.
In two multicenter studies (n=403) that included 160 patients with tumors ≤1.0 mm, most patient management changes made following DecisionDx-Melanoma testing were recommended for those with a tumor thickness ≥0.3 mm.
These results suggest a minimum Breslow thickness of 0.3 mm as an appropriate population to use DecisionDx-Melanoma to guide decisions on follow-up for cutaneous melanoma patients. Based on a previously published validation study, the test can also be used to inform decisions on SLNB in most eligible patients with tumor thickness less than or equal to 2.0 mm (no minimum tumor thickness).

"Accurate risk assessment is especially important in patients with thinner melanomas because a substantial proportion of melanoma-specific deaths occur in patients initially diagnosed with thin melanomas," commented study co-author Clay J. Cockerell, M.D., Cockerell Dermatopathology, Dallas, Texas. "These results establish an evidence-based population of patients with thin tumors who are appropriate for DecisionDx-Melanoma testing to inform follow-up decisions in the context of current melanoma management strategies."

The full published study results can be accessed at the journal’s website.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 3,100 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and five prospective risk of recurrence studies including more than 780 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter study cohorts that included more than 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

More information about the test and disease can be found at www.SkinMelanoma.com.

On July 11, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported its presence at the Health Physics Society ("HPS") 64th Annual Meeting that is being held July 7th – 11th in Orlando, Florida (Press release, Actinium Pharmaceuticals, JUL 11, 2019, View Source [SID1234537474]). During HPS, Actinium presented the findings of two studies that support the safety of healthcare professionals who provide care to patients treated with Iomab-B, Actinium’s lead product candidate, which is being studied in the pivotal Phase 3 SIERRA trial. The studies evaluated radiation exposure to healthcare professionals who cared for patients treated with Iomab-B and the exposure from handling blood samples from patients following Iomab-B infusion. Both studies reported minimal radiation exposure to the respective healthcare professionals. One study of 105 healthcare professionals from 5 SIERRA sites that provided care to patients receiving Iomab-B observed a mean cumulative radiation exposure of 0.09 mSv or millisieverts, which is significantly less than the 50 mSv annual occupational dose limit for staff. Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the CD45 targeting antibody, apamistamab, and the radioisotope iodine-131 that is intended to be a re-induction and conditioning agent prior to a BMT or Bone Marrow Transplant. The SIERRA trial is a multicenter, 150 patient study for patients with active, relapsed or refractory AML or Acute Myeloid Leukemia that is the only randomized Phase 3 trial to offer a potentially curative BMT to this patient population for which there is no standard of care.

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Details of the HPS presentations on Iomab-B are as follows:

Title: Occupational Radiation Exposures to Clinical Staff Working With 131I – Iomab-B

Summary: Data from 105 healthcare professionals from five SIERRA sites was analyzed. Staff monitored when only providing care to Iomab-B treated patients had a mean cumulative exposure of 0.07 mSv despite high levels of radiation being administered with targeted Iomab-B while staff who provided care for multiple patients, including those receiving other forms or radiation therapy, had a mean cumulative exposure of 0.11 mSv. Radiation exposure levels to all staff were found to be minimal, with mean cumulative exposure of 0.09 mSv, contributing minimal exposure to the 50 mSv annual occupational limit. The study sited training, education, customized physical shielding and more advanced safety procedures as leading to minimal additional radiation exposure.

Title: Iomab-B Study Blood Sample Handling and Occupational Radiation Extremity Exposure

Summary: Radiation exposure levels were minimal and not a safety concern to clinical staff involved in blood specimen collecting and handling.

Dr. Qing Liang, Actinium’s Vice President, Head of Radiation Sciences, said, "The safety of patients and site staff is our number one concern, so I am excited that the data from these studies demonstrated minimal radiation exposure to staff caring for patients in the Iomab-B SIERRA trial. I am confident that our collective efforts, together with the supportive data presented here at the Health Physics Society Meeting, will have a positive impact on the SIERRA trial, Iomab-B and our other ARC therapeutic candidates."

"Staff at clinical sites are often surprised to learn that they can be exposed to higher amounts of radiation when flying on an airplane than compared to providing care to patients treated with Iomab-B. These study data solidly support this fact with the 0.09 mSv mean exposure to staff significantly lower than the 50 mSv annual occupational limit and even lower than the annual radiation 3 mSv, we all receive from natural background. Since joining Actinium, I have focused on building relationships with the radiation safety and nuclear medicine caregivers at existing and prospective sites for our SIERRA trial, educating site staff and working with my clinical colleagues to further optimize the SIERRA trial for patients and site staff. I believe that such efforts bode well not only for the SIERRA trail but also for Iomab-B in a commercial setting, assuming its approval," Concluded Dr. Liang."

The Health Physics Society has nearly 4,000 members including scientists, safety professionals, physicists, engineers and other professionals from academia, industry, the federal government and national laboratories.

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "The SIERRA trial is a complex study involving multiple stakeholders at sites, including transplant physicians, radiation safety officers, nuclear medicine physicians and the nursing staff who provide care that is critical for these patients. Our team has worked intensely to address the needs of each of these stakeholders and I am proud that our efforts have taken Iomab-B from the single center where it was originally studied at to 19 clinical trials sites in the SIERRA trial thus far. The two studies presented at HPS which demonstrated that staff can safely provide care to patients with minimal radiation exposure are important and augment the promising interim feasibility and safety data that we have presented from the SIERRA trial. We are focused on continuing to generate positive data from the SIERRA trial for Iomab-B as we see a tremendous opportunity to improve outcomes for a significant number of patients with our ARC’s focused on targeted conditioning for BMT and cell therapies."

On July 11, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that it will announce its second-quarter 2019 financial results on Friday, July 26 before the market opens (Press release, AbbVie, JUL 11, 2019, View Source [SID1234537473]). AbbVie will host a live webcast of the earnings conference call at 8 a.m. Central time (9 a.m. Eastern). It will be accessible through AbbVie’s Investor Relations website investors.abbvie.com. An archived edition of the session will be available later that day.

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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).