Medtronic announces pricing of €3.5 billion of senior notes

On September 15, 2022 Medtronic plc (the "Company") ( NYSE:MDT) reported that its wholly-owned subsidiary, Medtronic Global Holdings S.C.A. ("Medtronic Luxco"), has priced an offering (the "Offering") of €500,000,000 principal amount of 2.625% senior notes due 2025, €1,000,000,000 principal amount of 3.000% senior notes due 2028, €1,000,000,000 principal amount of 3.125% senior notes due 2031 and €1,000,000,000 principal amount of 3.375% senior notes due 2034 (collectively, the "Notes") (Press release, Medtronic, SEP 15, 2022, View Source [SID1234619601]). All of Medtronic Luxco’s obligations under the Notes will be fully and unconditionally guaranteed by the Company and Medtronic, Inc., a wholly-owned indirect subsidiary of Medtronic Luxco, on a senior unsecured basis.

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The net proceeds of the Offering are expected to be used to repay at maturity Medtronic Luxco’s outstanding 0.00% Senior Notes due 2022, 0.375% Senior Notes due 2023 and 0.00% Senior Notes due 2023 and for general corporate purposes. While Medtronic Luxco may elect at a later date to repay, redeem or repurchase such notes prior to maturity, it currently has no intention to repay, redeem or repurchase such notes prior to maturity. The Offering is expected to close on September 21, 2022, subject to customary closing conditions. The joint book-running managers for the Offering are Barclays Bank PLC, BofA Securities Europe SA, Citigroup Global Markets Limited and HSBC Continental Europe.

The Offering is being made only by means of a prospectus dated February 28, 2020 and prospectus supplement (together, the "Prospectus"). You may get these documents for free by visiting EDGAR on the Securities and Exchange Commission website at www.sec.gov. Alternatively, copies of the Prospectus for the Offering may be obtained by contacting Barclays Bank PLC, toll-free at +1-888-603-5847, BofA Securities Europe SA, at +33(0) 1 8770 0000, Citigroup Global Markets Limited, toll-free at +1-800-831-9146 and HSBC Continental Europe, at +1-866-811-8049.

J INTS BIO’s Novel Oral 4th Generation EGFR-TKI ‘JIN-A02’ effective against both cis and trans isomers of C797S mutations – ESMO 2022

On September 15, 2022 J INTS BIO reported the poster presentation of its novel, orally administered 4th generation EGFR-TKI ‘JIN-A02’ at the ESMO (Free ESMO Whitepaper) 2022, that showed high potency of JIN-A02 against both cis and trans isomers of C797S mutation (Press release, J INTS BIO, SEP 15, 2022, View Source;esmo-2022-301625927.html [SID1234619600]). This year’s edition of the European Society for Medical Oncology Congress (ESMO 2022) was held in Paris, France from 9th to 13th September.

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Professor Cho, Byoung Chul, poster presentation of further preclinical data of its Novel Oral 4th Generation EGFR-TKI ‘JIN-A02’ at the 2022 European Society for Medical Oncology Congress in Paris, France (ESMO 2022)
Professor Cho, Byoung Chul, poster presentation of further preclinical data of its Novel Oral 4th Generation EGFR-TKI ‘JIN-A02’ at the 2022 European Society for Medical Oncology Congress in Paris, France (ESMO 2022)
Even though EGFR-TKI have improved treatment outcomes of patients with EGFR mutant NSCLC, resistance inevitably emerges with disease progression and often with CNS metastasis. C797S mutation is one of the most common on-target resistance mutation after the use of 3rd generation TKIs such as Osimertinib. ‘JIN-A02’ is a novel 4th generation EGFR-TKI, which is highly selective and potent against C797S double and triple mutations, with high BBB penetrance and intracranial efficacy.

The allelic context in which this C797S mutation is acquired, cis or trans isomers, have significant implications for treatment outcomes. This is especially so when C797S positive tumor are in cis form together with T790M mutation. In such situations, there are no available treatments.

J INTS BIO believes that JIN-A02 will be pivotal in the treatment of patients with EGFR mutant NSCLC harboring C797S double or triple mutations, regardless of allelic context. And the company is expecting the Phase I/IIa clinical study for JIN-A02 to start recruitment before the end of this year.

Caravan Biologix, Inc. Collaborates with MDimune on Cell-Derived NanoVesicles for Cancer

On September 15, 2022 Caravan Biologix, Inc., a developer of novel cell-derived vesicle (CDV) therapeutics targeting specific cancers and gene therapy-related diseases, reported that it has entered into an agreement with Seoul-based MDimune Inc. to apply their nanovesicle technology to enhance the effects of chimeric antigen receptor-expressing natural killer (CAR-NK) cells on various solid tumor cancers. Research findings should provide important insights as Caravan continues to advance the development of its proprietary Mini-CAR platform for stand-alone therapeutics and whole-cell CAR co-therapies (Press release, Caravan Biologix, SEP 15, 2022, View Source [SID1234619599]).

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"We are pleased to establish this collaboration with MDimune, a developer of bio-extrusion and delivery," stated Tom Malcolm, Ph.D., CSO and Founder of Caravan Biologix. "Findings from this collaboration will support our mini-CAR-NK CDV program, which focuses on treating primary liver carcinomas and other human diseases."

Seung Wook Oh, Ph.D., Chief Scientific Officer of MDimune added, "We are thrilled to launch this collaboration with Caravan Biologix. By joining the advanced mini-CAR-NK technology of Caravan and the enormous therapeutic potential of our vesicle technology, we hope to be able to demonstrate that our BioDrone platform can significantly escalate the therapeutic promise of current CAR-T/NK-based therapies."

"The signing of this agreement with Caravan Biologix is another important corporate milestone for MDimune. I am very pleased that our highly innovative and detail-oriented analytical approach to produce the highest quality of cell-derived vesicles at low cost has convinced Caravan Biologix to work with us on such an important endeavor to effectively treat patients with solid tumor cancers. It is clear that new solutions are needed to properly address the complexities associated with traditional whole cell CAR therapeutics," stated Dr. Oh.

TIBSOVO® (ivosidenib) Now Available from Onco360 for the Treatment of Adult Patients with IDH1-mutant Acute Myeloid Leukemia or Previously Treated, IDH1-mutant Metastatic Cholangiocarcinoma

On September 15, 2022 Onco360, the nation’s leading independent Specialty Pharmacy, reported that it has been selected by Servier Pharmaceuticals to be a specialty pharmacy partner for TIBSOVO (ivosidenib), which is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with newly diagnosed acute myeloid leukemia (AML) in combination with azacitidine or as monotherapy in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, relapsed or refractory AML, or locally advanced or metastatic cholangiocarcinoma that has been previously treated (Press release, Onco360, SEP 15, 2022, View Source [SID1234619597]).

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"Onco360 is honored to partner with Servier Pharmaceuticals and become a specialty pharmacy provider for TIBSOVO patients," said Benito Fernandez, Chief Commercial Officer, Onco360. "We are dedicated to supporting the highly specialized needs of patients battling IDH1-mutant AML or cholangiocarcinoma across the United States."

According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, it is estimated that 20,050 new cases of AML will be diagnosed in 2022 in the United States with a corresponding 11,540 deaths in 2022. Approximately 6-9% of AML cases are found to have IDH1 mutations. The median age at the time of initial AML diagnosis is 68 years. The five-year overall survival for AML patients is only 30.5%.1,2

According to the American Cancer Society, approximately 8,000 patients are diagnosed with cholangiocarcinoma, a bile duct cancer, on an annual basis in the United States. Approximately 13% of cholangiocarcinoma cases are found to have IDH1 mutations. The average age at the time of initial cholangiocarcinoma diagnosis is 70-72 years old dependent upon tumor location. The five-year overall survival for cholangiocarcinoma patients, regardless of cancer stage, is only 9-10% dependent upon tumor location.3,4

TIBSOVO is commercialized by Servier Pharmaceuticals. Please see the full prescribing information for TIBSOVO at Tibsovopro.com.

Syros and Tyme Technologies Announce Stockholder Approval of Merger

On September 15, 2022 Syros Pharmaceuticals, Inc. (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, and Tyme Technologies, Inc. (NASDAQ:TYME) reported the results of the special meetings of the stockholders of Syros and TYME, respectively, each held on September 15, 2022 (Press release, Syros Pharmaceuticals, SEP 15, 2022, View Source [SID1234619596]). At TYME’s special meeting, TYME’s stockholders voted in favor of all proposals, including the proposal to adopt the agreement and plan of merger, dated July 3, 2022 (the "Merger Agreement"), pursuant to which a direct, wholly owned subsidiary of Syros will merge with and into TYME, with TYME surviving as a wholly owned subsidiary of Syros (the "Merger"). At Syros’ special meeting, Syros’ stockholders also voted in favor of all proposals, including the proposal to approve the issuance of shares of Syros’ common stock to holders of TYME’s common stock in connection with the Merger and to certain of Syros’ investors in connection with a concurrent private investment in public equity ("PIPE") financing.

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The closings of the Merger and the PIPE financing are anticipated to take place on or around Friday, September 16, 2022. Following the closing of the Merger, the combined company will trade on The Nasdaq Global Select Market under the ticker symbol "SYRS," and will be led by Syros’ existing management team, including Nancy Simonian, M.D., Chief Executive Officer of Syros, and will remain focused on advancing Syros’ pipeline of small molecule medicines for the treatment of cancer.

In addition, Syros reported that it will effect a 1-for-10 reverse stock split of its common stock that will be effective on Friday, September 16, 2022, prior to the closings of the Merger and the PIPE financing. Syros’ common stock will begin trading on Nasdaq on a split-adjusted basis when the market opens on Monday, September 19, 2022. The new CUSIP number for Syros’ common stock following the reverse stock split is 87184Q206.

On September 15, 2022, the holders of a majority of Syros’ outstanding shares of common stock also approved the reverse stock split and gave Syros’ board of directors discretionary authority to select a ratio for the split ranging from 1-for-5 to 1-for-15. Syros’ board of directors approved the reverse stock split at a ratio of 1-for-10 on September 15, 2022.

The reverse stock split affects all issued and outstanding shares of Syros common stock, as well as the number of authorized shares of Syros common stock and the number of shares of common stock available for issuance under Syros’ equity incentive plans. The reverse stock split will reduce the number of shares of the Syros issued and outstanding common stock from approximately 63 million to approximately 6.3 million (which numbers do not give effect to the shares of Syros common stock to be issued in connection with the Merger and the PIPE financing). In addition, the reverse stock split will effect a reduction in the number of shares of common stock issuable upon the exercise of stock options and warrants and upon the vesting of restricted stock units outstanding immediately prior to the reverse stock split, with a proportional increase in the respective exercise prices. The reverse stock split will proportionately reduce the number of authorized shares of Syros’ common stock from 700 million shares (which is the number of authorized shares that will be outstanding immediately prior to the reverse stock split, in connection with Syros’ receipt of the approval of its stockholders to increase the number of authorized shares from 200 million to 700 million) to 70 million shares. The reverse stock split will not change the par value of the common stock or the authorized number of shares of preferred stock of Syros.

The reverse stock split will affect all holders of common stock uniformly and (before giving effect to the shares of Syros common stock to be issued in connection with the Merger and the PIPE financing) will not alter any stockholder’s percentage ownership interest in Syros, except to the extent that the reverse stock split would result in a stockholder owning a fractional share. No fractional shares of common stock will be issued in connection with the reverse stock split; stockholders who otherwise would be entitled to a fractional share of common stock will be entitled to receive a proportional cash payment.

Syros’ transfer agent, Computershare, is acting as the exchange agent for the reverse stock split. For those stockholders holding physical stock certificates, Computershare will send instructions for exchanging those certificates for shares held in book-entry form representing the post-split number of shares. Stockholders holding their shares in book-entry form or in brokerage accounts need not take any action in connection with the reverse stock split. Beneficial holders are encouraged to contact their bank, broker or custodian with any procedural questions.