On November 21, 2022 TriSalus Life Sciences, Inc. ("TriSalus") (the "Company"), an oncology therapeutics company in the process of going public through a business combination transaction (the "Business Combination") with MedTech Acquisition Corporation (Nasdaq: MTAC) ("MedTech" or "MTAC"), reported a presentation for investors with additional information regarding its ongoing Pressure-Enabled Regional Immuno-Oncology ("PERIO 01") and ("PERIO 02") clinical studies for primary and metastatic liver tumors (Press release, TriSalus Life Sciences, NOV 21, 2022, View Source [SID1234624286]).

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"We are commercializing our TriNav Infusion System (TriNav) and developing SD-101 to potentially enable more patients with liver and pancreatic tumors to benefit from immunotherapeutics and the current standard of care," said Mary Szela, President and Chief Executive Officer of TriSalus. "Today we are providing recent clinical data from our SD-101 studies so investors can better understand the progress to date and the potential upside that our company can generate."

"The initial findings from these studies offer encouraging data supporting TriSalus’ proprietary Pressure-Enabled Drug Delivery ("PEDD") method," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus. "This promising clinical data demonstrate that SD-101 delivered via TriNav may support broad immune effects in liver tumors and eliminate myeloid-derived suppressor cells ("MDSC"). Importantly, the data further substantiates the potential of our therapeutic platform to significantly improve immunotherapy outcomes for patients with liver and pancreatic tumors."

Highlights of the presentation include:

Data is consistent with the hypothesis that TriNav can achieve high SD-101 levels in the liver with limited systemic exposure using the PEDD method.

SD-101 delivered via TriNav is associated with evidence of induction of immunostimulatory cytokines in the blood and has demonstrated reductions in liver tumor monocytic MDSC levels.

To date, 27 patients have been treated with 123 infusions of SD-101 in the PERIO trials, with no serious cytokine adverse events related to SD-101 or serious adverse events related to TriNav or PEDD.

The Company expects PERIO 01 and PERIO 02 Phase 1 response data in December 2022. The studies continue to enroll at higher SD-101 dose levels in combination with checkpoint inhibitors.

The full presentation has been filed with the Securities and Exchange Commission ("SEC") and is accessible on TriSalus’ investor relations page at View Source

About TriSalus and Its Proposed Business Combination with MedTech

TriSalus is an oncology therapeutics company integrating immunotherapy with disruptive delivery technology to transform the treatment paradigm for patients with liver and pancreatic tumors.

TriSalus’ proprietary platform approach addresses immune dysfunction in liver and pancreatic tumors by combining its highly effective drug delivery technology with immunotherapeutics. The TriSalus platform comprises the TriNav Infusion System and SD-101, a class C toll-like receptor 9 (TLR9) agonist. TriNav is an FDA-cleared device that is designed to administer established and emerging therapeutics. SD-101, the Company’s investigational TLR9 agonist, is being delivered via TriNav to selected sites, including tumors in the liver. TriNav is the latest TriSalus asset for the proprietary PEDD method of administration which has been shown to overcome intra-tumoral pressure through modulation of pressure and flow to increase delivery of therapeutic agents.

As previously announced on November 14, 2022, TriSalus has entered into a definitive merger agreement with MedTech (the "Merger Agreement"), a publicly traded special purpose acquisition company in connection with the proposed business combination and related transactions between the parties. Upon the closing of the transaction, which is expected to occur in the first quarter of 2023, the combined company will be a publicly traded company and its common stock is expected to be listed on the NASDAQ Stock Exchange under the ticker "TLSI". The transaction is subject to the satisfaction of the necessary regulatory approvals and customary closing conditions, including the approval of MedTech’s shareholders.

On November 21, 2022 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that Dr. Eliav Barr, senior vice president and head of Global Clinical Development, chief medical officer, Merck Research Laboratories, is scheduled to participate in a virtual fireside chat at the 5th Annual Evercore ISI HealthCONx Conference on Thursday, Dec. 1, 2022 at 9:40 a.m. ET (Press release, Merck & Co, NOV 21, 2022, View Source [SID1234624285]).

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Investors, analysts, members of the media and the general public are invited to watch a live video webcast of the presentation at this weblink.

On November 21, 2022 Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Imago BioSciences, Inc. ("Imago") (Nasdaq: IMGO) reported that the companies have entered into a definitive agreement under which Merck, through a subsidiary, will acquire Imago for $36.00 per share in cash for an approximate total equity value of $1.35 billion (Press release, Merck & Co, NOV 21, 2022, View Source [SID1234624284]).

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"We continue to invest in our pipeline with a focus on applying our unique capabilities to unlock the value of breakthrough science for the patients we serve," said Robert M. Davis, president and chief executive officer, Merck. "This acquisition of Imago augments our pipeline and strengthens our presence in the growing field of hematology."

Imago is a clinical stage biopharmaceutical company developing new medicines for the treatment of myeloproliferative neoplasms (MPNs) and other bone marrow diseases. Imago’s lead candidate bomedemstat (IMG-7289), an investigational orally available lysine-specific demethylase 1 (LSD1) inhibitor, is currently being evaluated in multiple Phase 2 clinical trials for the treatment of essential thrombocythemia (ET), myelofibrosis (MF), and polycythemia vera (PV), in addition to other indications.

"This milestone is a testament to more than a decade of pioneering research by Imago scientists and the entire Imago team’s unwavering dedication to improving the lives of patients," said Dr. Hugh Y. Rienhoff, Jr., Founder and Chief Executive Officer, Imago BioSciences. "This agreement leverages Merck’s industry-leading clinical development expertise to maximize the therapeutic potential of bomedemstat while providing important value for shareholders. I would also like to acknowledge with gratitude the early investors – Blackstone Life Sciences, Frazier Healthcare, Omega Funds, Amgen Ventures, and MRL Ventures Fund who placed their faith in Imago beginning in 2014, as well as the outstanding study investigators and their patients who have made the clinical development of bomedemstat possible."

"Evidence indicates that LSD1 plays an important role in the maturation of blood cells in the bone marrow," said Dr. Dean Y. Li, president, Merck Research Laboratories. "We look forward to working with the Imago team to further investigate the potential of bomedemstat for patients with myeloproliferative neoplasms."

Under the terms of the acquisition agreement, Merck, through a subsidiary, will initiate a tender offer to acquire all outstanding shares of Imago. The closing of the tender offer will be subject to certain conditions, including the tender of shares representing at least a majority of the total number of Imago’s outstanding shares, the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions. Upon the successful completion of the tender offer, Merck’s acquisition subsidiary will be merged into Imago, and any remaining shares of common stock of Imago will be canceled and converted into the right to receive the same $36 per share price payable in the tender offer. The transaction is expected to close in the first quarter of 2023.

Myeloproliferative neoplasms
Myeloproliferative neoplasms are a group of diseases of the bone marrow characterized by excessive production of red blood cells, platelets, or certain white blood cells. Myeloproliferative neoplasms progress over time as the number of extra cells build up in the blood and/or bone marrow. This may lead to bleeding problems, anemia, infection, fatigue, thrombosis or other signs and symptoms. Certain myeloproliferative neoplasms may become acute myeloid leukemia (AML). Myeloproliferative neoplasms include chronic myelogenous leukemia (CML), polycythemia vera, primary myelofibrosis, essential thrombocythemia, chronic neutrophilic leukemia, and chronic eosinophilic leukemia.

About lysine-specific demethylase 1 (LSD1)
LSD1, also called KDM1A, discovered in 2004, is a member of a group of epigenetic proteins that regulate gene expression through chemical modifications of proteins, RNA and DNA. LSD1 regulates the maturation of bone marrow stem cells and is essential for the differentiation of progenitor cells into mature megakaryocytes and granulocytes and production of blood cells. Given the role that LSD1 plays in the function of malignant blood cells, targeting LSD1 for the treatment of blood cancers offers a new mechanism for the treatment of diseases associated with high morbidity and mortality.

Important Information About the Tender Offer
The tender offer described in this press release has not yet commenced. This press release is for informational purposes only and is neither an offer to purchase nor a solicitation of an offer to sell any shares of the common stock of Imago or any other securities, nor is it a substitute for the tender offer materials described herein. At the time the planned tender offer is commenced, a tender offer statement on Schedule (TO), including an offer to purchase, a letter of transmittal and related documents, will be filed by Merck Sharp & Dohme LLC ("Merck") and M-Inspire Merger Sub, Inc., a wholly-owned subsidiary of Merck, with the Securities and Exchange Commission (the "SEC"), and a solicitation/recommendation statement on Schedule 14D-9 will be filed by Imago with the SEC. The offer to purchase shares of common stock of Imago will only be made pursuant to the offer to purchase, the letter of transmittal and related documents filed as a part of the Schedule TO.

INVESTORS AND SECURITY HOLDERS ARE URGED TO READ BOTH THE TENDER OFFER MATERIALS CAREFULLY (INCLUDING AN OFFER TO PURCHASE, A RELATED LETTER OF TRANSMITTAL AND CERTAIN OTHER TENDER OFFER DOCUMENTS) AND THE SOLICITATION/RECOMMENDATION STATEMENT ON SCHEDULE 14D-9 REGARDING THE OFFER, AS THEY MAY BE AMENDED FROM TIME TO TIME, WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION THAT INVESTORS AND SECURITY HOLDERS SHOULD CONSIDER BEFORE MAKING ANY DECISION REGARDING TENDERING THEIR SECURITIES.

Investors and security holders may obtain a free copy of the offer to purchase, the related letter of transmittal, certain other tender offer documents and the solicitation/recommendation Statement (when available) and other documents filed with the SEC at the website maintained by the SEC at www.sec.gov or by directing such requests to the Information Agent for the tender offer, which will be named in the tender offer statement. In addition, Merck and Imago will file annual, quarterly and current reports and other information with the SEC, which are available to the public from commercial document-retrieval services and at the SEC’s website at www.sec.gov. Copies of the documents filed with the SEC by Merck may be obtained at no charge on Merck’s internet website at www.merck.com or by contacting Merck at 126 East Lincoln Avenue P.O. Box 2000 Rahway, NJ 07065 USA, or (908) 740-4000. Copies of the documents filed with the SEC by Imago may be obtained at no charge on Imago’s internet website at www.imagobio.com or by contacting Imago at 303 Twin Dolphin Drive 6th Floor, Redwood City, CA 94065 or (415) 529 5055.

Advisors
Morgan Stanley & Co. LLC acted as financial advisor to Merck in this transaction and Gibson Dunn & Crutcher LLP as its legal advisors. Centerview Partners LLC acted as financial advisor to Imago and Latham and Watkins LLP as its legal advisors.

On November 21, 2022 Umoja Biopharma, Inc., an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells to treat patients with solid and hematologic malignancies and IASO Biotherapeutics ("IASO Bio"), a clinical-stage biopharmaceutical company engaged in discovering, developing, and manufacturing innovative medicines, reported that they have entered into a research agreement to evaluate Umoja’s iCIL platform with IASO’s best-in-class CARs (Press release, Umoja Biopharma, NOV 21, 2022, View Source [SID1234624283]). The collaboration will focus on bringing off-the-shelf therapies to patients with hematological malignancies, initially acute myeloid leukemia (AML), with a goal of increasing patient accessibility.

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"We believe that developing off-the-shelf therapies using our iCIL platform and IASO’s CARs will pave the way to broader patient access to top-line therapies in hematological malignancies," said Andy Scharenberg, M.D., co-founder and Chief Executive Officer of Umoja. "As medicine and science have progressed, so have patient outcomes in cancer, but we still have a way to go. Collaborations like this between Umoja and IASO seek to push the next phase of cancer treatment forward."

Umoja’s iPSC-based allogeneic cell therapy platform uses its synthetic receptor enabled differentiation (ShRED) manufacturing process to direct differentiation and expansion of iCILs, a novel class of innate lymphocyte, with potent anti-tumor activity. ShRED generated-iCILs retain functionality in feeder-free culture after 100 days and, as ShRED does not require feeder-cells to induce effector cell expansion, these cells retain their proliferative capacity without the need for multiple complex raw materials.

"We are very pleased to enter a collaboration with Umoja," said Wen (Maxwell) Wang, M.D., Ph.D., Chief Executive Officer of IASO Bio. "The benefit of our fully-human CAR constructs to treat patients with hematologic malignancies have been validated in clinical trials of our broad set of targets and indications. We are excited to develop next generation novel cell therapies by combining our CAR constructs with Umoja’s novel ShRED technologies with potentially lower cost."

IASO’s strong capability in screening potentially best-in-class CARs utilizing its proprietary fully-human antibody discovery platform (IMARS), a high-throughput CAR screening platform, and executing clinical trials rapidly, as well as its fully in-house GMP facility for plasmid, virus vector, and CAR-T cell manufacturing with over 90% success rate aims to bring its innovative therapies to a broader population globally.

On November 21, 2022, Thermo Fisher Scientific Inc. (the "Company") reported that issued €500,000,000 aggregate principal amount of 3.200% Senior Notes due 2026 (the "2026 Notes") and €750,000,000 aggregate principal amount of 3.650% Senior Notes due 2034 (the "2034 Notes", and, together with the 2026 Notes, the "Euro Notes") in a public offering (the "Euro Offering") pursuant to a registration statement on Form S-3 (File No. 333-263034) and a preliminary prospectus supplement and prospectus supplement related to the offering of the Euro Notes, each as previously filed with the Securities and Exchange Commission (the "SEC") (Filing, 8-K, Thermo Fisher Scientific, NOV 21, 2022, View Source [SID1234624282]).

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The Euro Notes were issued under an indenture, dated as of November 20, 2009 (the "Base Indenture"), and the Twenty-Fifth Supplemental Indenture, dated as of November 21, 2022 (the "Euro Supplemental Indenture" and, together with the Base Indenture, the "Euro Indenture"), between the Company, as issuer, and The Bank of New York Mellon Trust Company, N.A., as trustee (the "Trustee").

The 2026 Notes will mature on January 21, 2026 and the 2034 Notes will mature on November 21, 2034. Interest on the 2026 Notes will be paid annually in arrears on January 21 of each year, commencing on January 21, 2023, and interest on the 2034 Notes will be paid annually in arrears on November 21 of each year, commencing on November 21, 2023.

Prior to December 21, 2025, in the case of the 2026 Notes, and August 21, 2034, in the case of the 2034 Notes (each such date, a "Euro Par Call Date"), the Company may redeem either series of Euro Notes, in whole at any time or in part from time to time, at a redemption price equal to the greater of (1) 100% of the principal amount of the Euro Notes to be redeemed and (2) the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Euro Notes being redeemed (not including any portion of the payments of interest accrued but unpaid as of the date of redemption and assuming that such notes to be redeemed matured on their applicable Euro Par Call Date), discounted to the date of redemption on an annual basis (ACTUAL/ACTUAL (ICMA)), using a discount rate equal to the Comparable Bond Rate (as defined in the Euro Indenture) plus 20 basis points, in the case of the 2026 Notes, and 25 basis points, in the case of the 2034 Notes, plus, in each case, accrued and unpaid interest on the Euro Notes being redeemed, if any, to, but excluding, the date of redemption.

In addition, on and after the applicable Euro Par Call Date, the Company may redeem some or all of the Euro Notes at a redemption price equal to 100% of the principal amount of the Euro Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding the date of redemption.

Upon the occurrence of a change of control (as defined in the Euro Indenture) of the Company and a contemporaneous downgrade of the Euro Notes below an investment grade rating by at least two of Moody’s Investors Service, Inc., S&P Global Ratings, a division of S&P Global, Inc., and Fitch Ratings, Limited, the Company will, in certain circumstances, be required to make an offer to purchase the Euro Notes at a price equal to 101% of the principal amount of the Euro Notes, plus any accrued and unpaid interest to, but excluding, the date of repurchase.

The Euro Notes are general unsecured obligations of the Company. The Euro Notes rank equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of the Company and rank senior in right of payment to any existing and future indebtedness of the Company that is subordinated to the Euro Notes. The Euro Notes are also effectively subordinated to any existing and future secured indebtedness of the Company to the extent of the assets securing such indebtedness, and are structurally subordinated to all existing and any future indebtedness and any other liabilities of its subsidiaries.
The Euro Indenture contains limited affirmative and negative covenants. The negative covenants restrict the ability of the Company and its subsidiaries to incur debt secured by liens on Principal Properties (as defined in the Euro Indenture) or on shares of stock of the Company’s Principal Subsidiaries (as defined in the Euro Indenture) and engage in sale and lease-back transactions with respect to any Principal Property. The Euro Indenture also limits the ability of the Company to merge or consolidate or sell all or substantially all of its assets.

Upon the occurrence of an event of default under the Euro Indenture, which includes payment defaults, defaults in the performance of affirmative and negative covenants, bankruptcy and insolvency related defaults and failure to pay certain indebtedness, the obligations of the Company under the Euro Notes may be accelerated, in which case the entire principal amount of the Euro Notes would be immediately due and payable.

Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Company, has issued an opinion to the Company, dated November 21, 2022, regarding the Euro Notes. A copy of this opinion is filed as Exhibit 5.1 hereto.

The foregoing description is qualified in its entirety by reference to the full text of the Base Indenture and the Euro Supplemental Indenture, which are filed with this report as Exhibits 4.1 and 4.2 hereto, respectively. Each of the foregoing documents is incorporated herein by reference.

USD Offering

On November 21, 2022, the Company issued $600,000,000 aggregate principal amount of 4.800% Senior Notes due 2027 (the "2027 Notes") and $600,000,000 aggregate principal amount of 4.950% Senior Notes due 2032 (the "2032 Notes" and, together with the 2027 Notes, the "USD Notes") in a public offering (the "USD Offering") pursuant to a registration statement on Form S-3 (File No. 333-263034) and a preliminary prospectus supplement and prospectus supplement related to the offering of the USD Notes, each as previously filed with the SEC.

The USD Notes were issued under the Base Indenture and the Twenty-Sixth Supplemental Indenture, dated as of November 21, 2022 (the "USD Supplemental Indenture" and, together with the Base Indenture, the "USD Indenture"), between the Company and the Trustee.

The 2027 Notes will mature on November 21, 2027, and the 2032 Notes will mature on November 21, 2032. Interest on the USD Notes will be paid semi-annually in arrears on May 21 and November 21 of each year, commencing on May 21, 2023.

Prior to October 21, 2027, in the case of the 2027 Notes, and August 21, 2032, in the case of the 2032 Notes (each, a "USD Par Call Date"), the Company may redeem either series of USD Notes, in whole at any time or in part from time to time, at a redemption price equal to the greater of (1) 100% of the principal amount of the USD Notes of such series to be redeemed and (2) the sum of the present values of the remaining scheduled payments of principal and interest in respect of the USD Notes of such series being redeemed (not including any portion of the payments of interest accrued but unpaid as of the date of redemption and assuming that such USD Notes to be redeemed matured on their applicable USD Par Call Date), discounted to the date of redemption on a semi-annual basis (assuming a 360-day year of twelve 30-day months), at the Treasury Rate (as defined in the USD Indenture) plus 15 basis points, in the case of the 2027 Notes, and 20 basis points, in the case of the 2032 Notes, plus, in each case, accrued and unpaid interest on the USD Notes of such series being redeemed, if any, to, but excluding, the date of redemption.
In addition, on and after the applicable USD Par Call Date, the Company may redeem some or all of the USD Notes at a redemption price equal to 100% of the principal amount of the USD Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding the date of redemption.

Upon the occurrence of a change of control (as defined in the USD Indenture) of the Company and a contemporaneous downgrade of the USD Notes below an investment grade rating by at least two of Moody’s Investors Service, Inc., S&P Global Ratings, a division of S&P Global, Inc., and Fitch Ratings, Limited, the Company will, in certain circumstances, be required to make an offer to purchase the USD Notes at a price equal to 101% of the principal amount of the USD Notes, plus any accrued and unpaid interest to, but excluding, the date of repurchase.

The USD Notes are general unsecured obligations of the Company. The USD Notes rank equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of the Company and rank senior in right of payment to any existing and future indebtedness of the Company that is subordinated to the USD Notes. The USD Notes are also effectively subordinated to any existing and future secured indebtedness of the Company to the extent of the assets securing such indebtedness, and are structurally subordinated to all existing and any future indebtedness and any other liabilities of its subsidiaries.

The USD Indenture contains limited affirmative and negative covenants. The negative covenants restrict the ability of the Company and its subsidiaries to incur debt secured by liens on Principal Properties (as defined in the USD Indenture) or on shares of stock of the Company’s Principal Subsidiaries (as defined in the USD Indenture) and engage in sale and lease-back transactions with respect to any Principal Property. The USD Indenture also limits the ability of the Company to merge or consolidate or sell all or substantially all of its assets.

Upon the occurrence of an event of default under the USD Indenture, which includes payment defaults, defaults in the performance of affirmative and negative covenants, bankruptcy and insolvency related defaults and failure to pay certain indebtedness, the obligations of the Company under the USD Notes may be accelerated, in which case the entire principal amount of the USD Notes would be immediately due and payable.

Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Company, has issued an opinion to the Company, dated November 21, 2022, regarding the USD Notes. A copy of this opinion is filed as Exhibit 5.2 hereto.

The foregoing description is qualified in its entirety by reference to the full text of the Base Indenture and the USD Supplemental Indenture, which are filed with this report as Exhibits 4.1 and 4.3 hereto, respectively. Each of the foregoing documents is incorporated herein by reference.