Delcath Systems Achieves Medical Device Regulation Certification for CHEMOSAT® in Europe

On March 2, 2022 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that on February 28 its CHEMOSAT Hepatic Delivery System received Medical Device Regulation (MDR) certification under the new European Medical Devices Regulation [2017/745/EU]. Since April 2012, Chemosat had been certified under a previous regulation, the Medical Device Directive [2007/47/EC] (MDD), which is being replaced by MDR (Press release, Delcath Systems, MAR 2, 2022, View Source [SID1234609371]).

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Achieving MDR certification entails a detailed evaluation from a designated EU Notified Body, including an audit of quality systems and a review of documentation supporting safety and performance claims for the device. MDR greatly expands upon existing MDD requirements including the level of clinical evidence supporting claims, post-marketing surveillance, database traceability, unique device identification (UDI) and increased supply chain oversight. Under MDR, CHEMOSAT’s designation has changed from a Class IIb to a Class lll medical device.

AMGEN ANNOUNCES 2022 SECOND QUARTER DIVIDEND

On March 2, 2022 Amgen (NASDAQ:AMGN) reported that its Board of Directors declared a $1.94 per share dividend for the second quarter of 2022 (Press release, Amgen, MAR 2, 2022, View Source [SID1234609370]). The dividend will be paid on June 8, 2022, to all stockholders of record as of the close of business on May 17, 2022.

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Prokarium Exercises Option for an Exclusive Worldwide License for the Use of Salmonella Immunotherapy in the Treatment of Bladder Cancer

On March 2, 2022 Prokarium, a biopharmaceutical company pioneering the oncology field of microbial immunotherapy, reported it exercised its option with Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois — CHUV) for an exclusive, worldwide license for the use of Salmonella immunotherapy in the treatment of bladder cancer (Press release, Prokarium, MAR 2, 2022, View Source [SID1234609369]).

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"This intellectual property is an important milestone for our lead oncology program as it enters clinical development in 2023 and also lays the groundwork for expanding Salmonella immunotherapy into other solid tumors," said Livija Deban, PhD, Chief Scientific Officer of Prokarium. "Microbial immunotherapy is the gold standard-of-care in the treatment of bladder cancer. However, high recurrence rates and limited treatment options are currently available for patients. Prokarium is introducing a differentiated, efficacious microbial immunotherapy to a market that has seen little disruption in over 30 years."

In exchange for the exclusive license, Prokarium will make an upfront payment, as well as additional payments upon achievement of development and commercialization milestones, and, if any product is approved, will pay royalties on net sales.

"Since initiating our collaboration with Prokarium in 2019, our team at the Department of Urology at CHUV has generated a robust preclinical data package demonstrating that Prokarium’s proprietary Salmonella bacteria generates quantitatively and qualitatively superior immune responses with different kinetics compared to the standard-of-care," said Dr Denise Nardelli-Haefliger, Head of the Urology Research Unit. "Together with Prof Patrice Jichlinski, Prof Beat Roth, Dr Ilaria Lucca and Dr Sonia Domingos-Pereira, we are thrilled to see that the results of our collaboration have the potential to expand the disease-free interval and improve quality of life in patients with non-muscle invasive bladder cancer (NMIBC)."

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer represents 5% of all new cancer cases in the US and accounts for 550,000 new cases yearly worldwide. The clinical staging is determined by the depth of invasion into the bladder wall. More than 70% of cases are diagnosed at an early stage, also known as non-muscle invasive bladder Cancer (NMIBC). Despite early diagnosis, the only approved therapies are Bacillus Calmette-Guérin (BCG), which often faces shortages, and chemotherapy, both delivered intravesically. Because of its high incidence and the limited number of treatment options, a huge unmet medical need remains in NMIBC.

Bristol Myers Squibb Announces Accepted Amounts and Pricing Terms of its Tender Offers

On March 2, 2022 Bristol-Myers Squibb Company (NYSE:BMY) ("Bristol Myers Squibb"), with its wholly-owned subsidiary Celgene Corporation ("Celgene") (collectively, the "Offerors"), reported the accepted amounts and pricing terms of their previously announced 22 separate offers to purchase for cash notes issued by the Offerors listed in the tables listed herein (Press release, Bristol-Myers Squibb, MAR 2, 2022, View Source [SID1234609368]).

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The outstanding debt securities listed in (i) the first table below labeled "2025 Pool" are referred to collectively as the "2025 Pool Notes," (ii) the second table below labeled "2026 Pool" are referred to collectively as the "2026 Pool Notes," (iii) the third table below labeled "2027 Pool" are referred to collectively as the "2027 Pool Notes," (iv) the fourth table below labeled "2029 Pool" are referred to collectively as the "2029 Pool Notes," and (v) the fifth table below labeled "High Coupon Pool" are referred to collectively as the "High Coupon Pool Notes." The High Coupon Pool Notes, the 2025 Pool Notes, the 2026 Pool Notes, the 2027 Pool Notes and the 2029 Pool Notes are referred to collectively as the "Notes," and each series of Notes is referred to as a "series." We refer to each offer to purchase a series of Notes for cash as an "Offer," the offers to purchase the 2025 Pool Notes collectively as the "2025 Pool Offers," the offers to purchase the 2026 Pool Notes collectively as the "2026 Pool Offers," the offers to purchase the 2027 Pool Notes collectively as the "2027 Pool Offers," the offers to purchase the 2029 Pool Notes collectively as the "2029 Pool Offers," the offers to purchase the High Coupon Pool Notes collectively as the "High Coupon Pool Offers," and all the offers to purchase Notes are referred to collectively as the "Offers."

The table below indicates, among other things, the aggregate principal amount of Notes tendered as of 5:00 p.m. (New York City time) on March 1, 2022 (the "Early Tender Deadline") and accepted in each Offer, the Offer Yield (each as defined below), the proration factor, if any, and the total consideration for each $1,000 principal amount of each series of Notes validly tendered at or prior to the Early Tender Deadline and accepted for purchase (the "Total Consideration"), as calculated at 9:00 a.m. (New York City time) today, March 2, 2022 in accordance with the terms of the Offer to Purchase dated February 15, 2022 (as it may be amended or supplemented from time to time, the "Offer to Purchase"), as amended by Bristol Myers Squibb’s press release dated March 1, 2022:

(1)


The "Offer Yield" is equal to the applicable Reference Yield (as defined in the Offer to Purchase), which is based on the bid-side price of the applicable Reference U.S. Treasury Security (as specified in the Offer to Purchase)) plus the applicable Fixed Spread (as specified in the Offer to Purchase).

(2)


Includes the Early Tender Premium (as defined in the Offer to Purchase). Payable per each $1,000 principal amount of each specified series of Notes validly tendered at or prior to the Early Tender Deadline and accepted for purchase.

*


Denotes a series of Notes for which the Total Consideration, the Tender Consideration (as defined in the Offer to Purchase), and the Offer Yield were determined taking into account the par call date, instead of the maturity date, of the Notes of such series in accordance with standard market practice.

The Offerors’ obligations to accept Notes tendered in the Offers are subject to the terms and conditions described in the Offer to Purchase, as amended by Bristol Myers Squibb’s press release dated March 1, 2022, which sets forth a detailed description of the Offers, including: (a) the Acceptance Priority Procedures (as defined in the Offer to Purchase), and (b) the following Amended Maximum Acceptance Amounts (as defined in the Offer to Purchase):

all of the 2025 Pool Notes tendered as of the Early Tender Deadline (the "2025 Pool Maximum");
$500 million maximum aggregate principal amount of the 2026 Pool Notes (the "2026 Pool Maximum");
all of the 2027 Pool Notes tendered as of the Early Tender Deadline (the "2027 Pool Maximum");
$1.6 billion maximum aggregate principal amount of the 2029 Pool Notes (the "2029 Pool Maximum"); and
$1.5 billion maximum aggregate principal amount of the High Coupon Pool Notes (the "High Coupon Pool Maximum").
The withdrawal rights for the Offers expired at 5:00 p.m. (New York City time) on March 1, 2022. The Offers will each expire at 11:59 p.m. (New York City time) on March 15, 2022, unless extended or earlier terminated by the Offerors (such date and time with respect to an Offer, as the same may be extended with respect to such Offer, the "Expiration Date").

The withdrawal rights for the Offers expired at 5:00 p.m. (New York City time) on March 1, 2022. As previously announced, all conditions of the Offers were deemed satisfied or waived by the Offerors by the Early Tender Deadline. As previously announced, the Offerors have elected to exercise their Early Settlement Right (as defined in the Offer to Purchase). The Early Settlement Date (as defined in the Offer to Purchase) will occur on March 4, 2022.

Since the aggregate principal amount of the 2025 Pool Notes, 2026 Pool Notes, 2027 Pool Notes, 2029 Pool Notes, and High Coupon Pool Notes validly tendered and not validly withdrawn at or prior to the Early Tender Deadline meets or exceeds the 2025 Pool Maximum, 2026 Pool Maximum, 2027 Pool Maximum, 2029 Pool Maximum, or High Coupon Pool Maximum, as applicable, the Offerors will accept such Notes for purchase according to the Acceptance Priority Procedures and proration steps as described in the Offer to Purchase. Holders of Notes (each, a "Holder" and collectively, "Holders") validly tendered at or prior to the Early Tender Deadline that are accepted for purchase by the Offerors will receive the applicable Total Consideration, in cash. Because the aggregate principal amount of Notes validly tendered and not validly withdrawn at or prior to the Early Tender Deadline exceeded the Amended Maximum Acceptance Amounts, there will be no Final Settlement Date (as defined in the Offer to Purchase) and no additional tenders of Notes will be accepted for purchase by the Offerors after the Early Tender Deadline. As described in the Offer to Purchase, Notes tendered and not accepted for purchase will be promptly returned to the tendering Holder’s account.

The Total Consideration that will be paid on the Early Tender Deadline for each series of notes accepted for purchase does not include a cash payment equal to accrued and unpaid interest (the "Accrued Coupon Payment") on such Notes to, but not including, the Early Settlement Date. For the avoidance of doubt, interest will cease to accrue on the Early Settlement Date for all Notes accepted in the Offers. Under no circumstances will any interest be payable to Holders because of any delay on the part of Global Bondholder Services Corporation, as the tender agent and information agent, The Depository Trust Company or any other party in the transmission of funds to Holders. See the Offer to Purchase for additional information.

All Notes accepted in the Offers will be cancelled and retired and will no longer remain outstanding obligations of the relevant Offeror. Following the Price Determination Date (as defined in the Offer to Purchase), the Offerors may elect to redeem all or a portion of Bristol Myers Squibb’s 3.875% Notes due 2025 or 3.200% Notes due 2026 or Celgene’s 3.875% Notes due 2025 that are not tendered and accepted in the Offers in accordance with the terms of the optional redemption provisions in the indentures governing such Notes.

The Offerors have retained Deutsche Bank Securities Inc., BofA Securities, Inc. and Goldman Sachs & Co. LLC as dealer managers for the Offers. Questions regarding terms and conditions of the Offers should be directed to Deutsche Bank Securities Inc. at (866) 627-0391 (toll-free) or (212) 250-2955 (collect) or BofA Securities, Inc. at (888) 292-0070 (toll-free) or (980) 683-3215 (collect) or Goldman Sachs & Co. LLC at (800) 828-3182 (toll-free) or (212) 902-5962 (collect). Global Bondholder Services Corporation is acting as the tender agent and the information agent for the Offers (the "Tender and Information Agent").

Offer and Distribution Restrictions

This announcement is for informational purposes only. This announcement is not an offer to sell or purchase, a solicitation of an offer to sell or purchase, or the solicitation of tenders with respect to any of Notes described herein. The Offers are being made solely pursuant to the Offer to Purchase. The Offers are not being made to Holders of Notes in any jurisdiction in which the making or acceptance thereof would not be in compliance with the securities, blue sky or other laws of such jurisdiction. In any jurisdiction in which the securities laws or blue sky laws require the Offers to be made by a licensed broker or dealer, the Offers will be deemed to be made on behalf of the Offerors by the dealer managers or one or more registered brokers or dealers that are licensed under the laws of such jurisdiction.

United Kingdom

The Offer to Purchase is only addressed to Holders where they would (if they were clients of the Offerors) be per se professional clients or per se eligible counterparties of the Offerors within the meaning of the rules of the Financial Conduct Authority (" FCA "). Neither the Offer to Purchase nor any other related documents or materials are addressed to or directed at any persons who would be retail clients within the meaning of the FCA rules and any such persons should not act or rely on them. Recipients of the Offer to Purchase and any other documents or materials relating to the Offer should note that the Offerors is acting on its own account in relation to the Tender Offer and will not be responsible to any other person for providing the protections which would be afforded to clients of the Offerors or for providing advice in relation to the Offer.

This announcement, the Offer to Purchase and any other documents or materials relating to the Tender Offer are not being made and such documents have not been approved by an authorized person for the purposes of section 21 of the Financial Services and Markets Act 2000. Accordingly, such documents and/or materials are not being distributed to, and must not be passed on to, the general public in the United Kingdom. The communication of such documents and/or materials as a financial promotion is only being made to persons outside the United Kingdom and to those persons in the United Kingdom falling within the definition of investment professionals (as defined by Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (" Financial Promotion Order ")) or persons who are within Article 43 of the Financial Promotion Order or any other persons to whom they may otherwise lawfully be communicated under the Financial Promotion Order and should not be relied on or acted on in the United Kingdom by any other persons.

EEA

In the EEA, this announcement and the Tender Offer will not, directly or indirectly, be made to, or for the account of, any person other than to qualified investors within the meaning of Article 2(e) of the Prospectus Regulation. Neither this announcement nor the Offer to Purchase, nor any other documentation or material relating to the Tender Offer, has been or will be submitted to a competent authority in the EEA for approval. Therefore, neither the Offer to Purchase nor any other documentation or material relating to the Tender Offer qualifies as an approved prospectus as meant in Article 6 of the Prospectus Regulation.

Accordingly, in the EEA, the Tender Offer may not be made by way of an "offer of securities to the public" within the meaning of Article 2(d) of the Prospectus Regulation and the Offer may not be promoted and is not being made to, any person in the EEA (with the exception of "qualified investors" within the meaning of Article 2(e) in conjunction with Article 1(4)(a) of the Prospectus Regulation). This announcement, the Offer to Purchase and any other documentation or materials relating to the Tender Offer (including memoranda, information circulars, brochures or similar documents) have not been forwarded or made available to, and are not being forwarded or made available to, directly or indirectly, any such person.

With regard to the EEA, this announcement and the Offer to Purchase have been transmitted only for personal use by the aforementioned qualified investors and only for the purpose of the Tender Offer. Accordingly, the information contained in this announcement and the Offer to Purchase may not be used for any other purpose or be transmitted to any other person in the EEA.

Memory Cytokine-Enhanced Natural Killer Cells Show Promising Results in Leukemia Patients; Data Support ImmunityBio’s Scaled m-ceNK Clinical Program

On March 2, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported study results that further demonstrate the potential for use of memory-like cytokine-enriched natural killer (m-ceNK) cells for the treatment of cancer (Press release, ImmunityBio, MAR 2, 2022, View Source [SID1234609367]). ImmunityBio has successfully scaled the process of generating over 20 billion m-ceNK cells from a single extraction of white blood cells from a donor or patient, and reports promising clinical data supporting the ongoing development of memory NK cells for the treatment of both liquid and solid tumors of all types.

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In a Phase 2 study sponsored by Washington University School of Medicine (NCT02782546), white blood cells retrieved from HCT donors to treat acute myeloid leukemia (AML) patients, were stimulated with cytokines (IL-12, -15, and -18) to form memory-like NK cells, and were re-infused to the patients, who also received ImmunityBio’s IL-15 superagonist Anktiva (N-803). The cytokine-stimulated NK cells safely augmented a leading treatment for AML-—HLA-haploidentical hematopoietic cell transplantation. The data showed that the cytokine-stimulated NK cells were persistent, showed increased production of interferon-gamma and functionality, and led to a complete response in 87% of patients after Day 28. The results were recently published in a peer-reviewed article ("Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia") in Science Translational Medicine.

NK cells are innate immune cells that are under investigation as a cell therapy for multiple types of cancer. A challenge of NK cell-based therapies, however, is ensuring that the cells persist and remain functional long-term. This study showed that memory-like NK cells derived from the same donor as the hematopoietic cell transplantation (HCT) persisted for at least two months after transplantation and were highly functional ex vivo. Together, these findings support the use of memory NK cells as a component of HCT for leukemia.

"This important study adds to the growing body of data that shows the cancer-fighting ability of NK cells can be enhanced by stimulating expansion and persistence of these cells," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "The study also showed that stimulated memory NK cells are effective with only a single infusion when given along with Anktiva support. To facilitate this approach, ImmunityBio has successfully scaled cytokine enrichment and expansion of m-ceNK cells, so cancer patients can receive multiple infusions of these potent and persistent m-ceNK cells generated from a single donation of white blood cells."

About Memory Cytokine-Enhanced NK Cells (m-ceNK):

ImmunityBio has successfully enriched and expanded NK cells obtained from peripheral blood of donors using a technique called apheresis to generate NK cells with a memory-like phenotype, which exhibit both high cytotoxicity and increased interferon-gamma production. These m-ceNK cells can be generated from an individual donor for autologous cell therapy, but have also been generated as an allogeneic product from cord blood. In addition to the high potential for enhanced efficacy, m-ceNK cells can be infused easily in an outpatient setting.

ImmunityBio has developed a novel method of m-ceNK cells production that yields multiple clinical-dose forms from a single apheresis (white blood cell collection) using the company’s proprietary NANT 001 Bioreactor (GMP-in-a-Box), thereby alleviating pressures on supply of starting material. An optimized cryopreservation protocol for maximum shelf-life and potency upon recovery was also established, a necessity for any off-the-shelf product. ImmunityBio is leveraging their ability to generate m-ceNK cells with potent cytotoxicity, increased IFN-gamma production, proliferative capacity, activation surface markers and memory response to establish a propriety method for generation, expansion, and cryopreservation of these cells for autologous use.

The QUILT 3.076 Study of Cryopreserved M-ceNK cells

Cryopreserved m-ceNK cells in combination with AnktivaÔ (N-803) will be tested in a 2-part Phase 1 study (NCT04898543) designed to evaluate safety in subjects with locally advanced or metastatic solid tumors; solid tumors comprise approximately 90% of adult cancers and 40% of all cancers in children, according to the American Cancer Society. The study will compare the quantity and characteristics of m-ceNK cells collected and cytokine-enriched from newly diagnosed patients who have not received prior treatment to m-ceNK cells generated from patients who have received at least two prior treatments for their cancer.

The study consists of two cohorts and there will be 10 participants in each cohort. Cohort 1 includes participants with newly-diagnosed, high-risk solid tumors who have not received prior treatment; and cohort 2 includes participants with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies. Participants will be enrolled in the two cohorts simultaneously.

Participants in Cohort 1 will participate in apheresis collection of lymphocytes (part A) and will not receive any investigational therapy in this study.
Participants in Cohort 2 will undergo an apheresis collection of lymphocytes (part A) prior to receiving 4 infusions of M-ceNK on days 1, 8, 15 and 22 along with N-803 on days 1 and 15.