On March 24, 2023 Integra LifeSciences Holdings Corporation (the "Company") reported that it has entered into an amended and restated credit agreement with a syndicate of lending banks, Bank of America, N.A., as Administrative Agent, Swing Line Lender and L/C Issuer, Citibank N.A., JPMorgan Chase Bank, N.A., Morgan Stanley MUFG Loan Partners, LLC, PNC Bank, N.A., Truist Securities, Inc. and Wells Fargo Bank, N.A., as Co-Syndication Agents, and The Bank of Nova Scotia, BMO Harris Bank N.A., BNP Paribas, Capital One, National Association, Citizens Bank, N.A., DNB Bank ASA, New York Branch, Santander Bank, N.A. and TD Bank, N.A., as Co-Documentation Agents (the "Amendment and Restatement") (Filing, 8-K, Integra LifeSciences, MAR 24, 2023, View Source [SID1234629312]).

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The Amendment and Restatement makes an aggregate principal amount of up to $2.075 billion available to the Company through the following facilities: (i) a $1.3 billion revolving credit facility, and (ii) a $775 million term loan facility, which includes a $60 million sublimit for the issuance of standby letters of credit and a $60 million sublimit for swingline loans. The Amendment and Restatement extends the credit facility’s maturity date from February 3, 2025 to March 24, 2028, subject to certain springing maturity conditions.

Borrowings under the Amendment and Restatement bear interest, at the Company’s option, at a rate equal to (i) term SOFR (as defined in the amendment and restatement) in effect from time to time plus 0.10% plus the applicable rate (ranging from 1.00% to 1.75%) or (ii) the highest of (x) the weighted average overnight Federal funds rate, as published by the Federal Reserve Bank of New York, plus one half of 1.0%, (y) the prime lending rate of Bank of America, N.A. or (z) the one-month Term SOFR plus 1.0%. The applicable rates are based on the Company’s consolidated total leverage ratio (defined as the ratio of (a) consolidated funded indebtedness as of such date to (b) consolidated EBITDA for the period of four consecutive fiscal quarters ending on such date) at the time of the applicable borrowing.

The Company will also pay an annual commitment fee of 0.15% to 0.30% on the daily amount by which the commitments under the revolving credit facility exceed the outstanding loans and letters of credit under the revolving credit facility.

A copy of the Amendment and Restatement is attached as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated by reference herein.

In addition, on March 24, 2023, the Company and the subsidiary guarantors of the Company entered into a ratification agreement to the Amendment and Restatement with Bank of America, N.A., as Administrative Agent (the "Ratification Agreement"). A copy of the Ratification Agreement is attached as Exhibit 10.2 to this Current Report on Form 8-K and is incorporated by reference herein.

ITEM 2.03 CREATION OF A DIRECT FINANCIAL OBLIGATION OR AN OBLIGATION UNDER AN OFF-BALANCE SHEET ARRANGEMENT OF A REGISTRANT

The information set forth in Item 1.01 above is incorporated by reference into this item.

ITEM 9.01 FINANCIAL STATEMENTS AND EXHIBITS

(d) Exhibits

10.1
Seventh Amended and Restated Credit Agreement, dated as of March 24, 2023, among Integra LifeSciences Holdings Corporation, the lenders party thereto, Bank of America, N.A., as Administrative Agent, Swing Line Lender and L/C Issuer, Citibank N.A., JPMorgan Chase Bank, N.A., Morgan Stanley MUFG Loan Partners, LLC, PNC Bank, N.A., Truist Securities, Inc. and Wells Fargo Bank, N.A., as Co-Syndication Agents, and The Bank of Nova Scotia, BMO Harris Bank N.A., BNP Paribas, Capital One, National Association, Citizens Bank, N.A., DNB Bank ASA, New York Branch, Santander Bank, N.A. and TD Bank, N.A., as Co-Documentation Agents.
10.2
Ratification Agreement, dated as of March 24, 2023, between Integra LifeSciences Holdings Corporation, the Subsidiary Guarantors of Integra LifeSciences Holdings Corporation and Bank of America, N.A., as Administrative Agent.

On March 24, 2023 Biocept, Inc. (Nasdaq: BIOC), a leading provider of molecular diagnostic assays, products and services, reported enrollment of the first patient in the FORESEE clinical trial with the Company’s proprietary cerebrospinal fluid assay CNSide (NCT05414123) (Press release, Biocept, MAR 24, 2023, View Source [SID1234629311]). This first patient was seen at the UT Southwestern Medical Center, one of the largest and most respected hospitals in the nation.

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The FORESEE trial is a multicenter, prospective clinical trial expected to enroll 40 patients with breast or non-small cell lung cancer (NSCLC) who have suspicious or confirmed leptomeningeal metastases (LM). The goal of the FORESEE trial is to evaluate the performance of CNSide in monitoring the LM’s response to treatment and to assess the impact of CNSide on treatment decisions made by physicians.

Standard-of-care methods to diagnose or assess the treatment response of LM (i.e., clinical evaluation, MRI and cytology) have limited sensitivity and specificity. This creates challenges for physicians to manage LM or determine the best course of treatment. CNSide is a Laboratory Developed Test (LDT) that is used commercially at the physician’s discretion, with samples processed in Biocept’s CLIA-certified, CAP-accredited laboratory.

"The enrollment of the first patient in the FORESEE clinical study is a major milestone for the management of patients with leptomeningeal disease," said Michael Youssef, MD, Assistant Professor in the Department of Neurology and the Department of Hematology and Oncology at UT Southwestern Medical Center. "We are excited to be at the forefront of this innovation, which will greatly benefit patients."

Priya Kumthekar, MD, Associate Professor of Neurology and Medicine (hematology and oncology) at the Feinberg School of Medicine at Northwestern University and Principal Investigator of the FORESEE trial, said, "I am impressed by the ease of use and the versatility of the CNSide technology, and how it can facilitate disease diagnosis and management for our leptomeningeal patients who are truly in need of improved diagnostics and therapeutics."

"The FORESEE trial evaluates the medical and clinical utility, when compared to standard of care, of the CNSide laboratory test, a revolutionary technology designed to detect cells in the cerebral spinal fluid of central nervous system brain metastasis patients," said Sam Riccitelli, Chairman and interim President and CEO of Biocept. "The test can be used to detect the presence of tumor, as well as guide and monitor therapy, an area of critical need for these terminally ill patients."

Dr. Kumthekar is a consultant to Biocept and Dr. Youssef has no financial interest in Biocept.

About CNSide

Using our proprietary CNSide assay to analyze and interrogate CSF-TCs and cfDNA for certain biomarkers, physicians can be better informed about the actionable molecular information associated with a patient’s metastatic cancer and develop a personalized cancer treatment plan. Through CNSide, Biocept’s test menu focuses on cancer biomarkers that are clinically actionable based on clinical treatment guidelines listed by the National Comprehensive Cancer Network (NCCN). For more information, please visit https://biocept.com/technology/.

On March 24, 2023 MAIA Biotechnology, Inc., (NYSE: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported financial results for the full year ended December 31, 2022, and provided a corporate update (Press release, MAIA Biotechnology, MAR 24, 2023, View Source [SID1234629310]).

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"We are very pleased with the progress MAIA has made in recent months, including but not limited to, expanding the THIO-101 trial to Europe and outlining the plan to initiate the Company’s second go-to-market trial for THIO-102," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "As we head into 2023, we remain excited to share the safety data from Part A of the THIO-101 trial, advance patient enrollment at sites in Europe, and seek to receive IND clearance in the U.S."

Corporate Highlights

Dosed first two patients in Europe in ongoing Phase 2 trial (THIO-101): Dosing has commenced in Europe in MAIA’s Phase 2 clinical trial, THIO-101, evaluating THIO in patients with advanced Non-Small Cell Lung Cancer (NSCLC).

Outlined plan to initiate second Phase 2 go-to-market trial (THIO-102): MAIA is planning to conduct a second Phase 2 trial to evaluate THIO in sequential combination with the immunotherapies pembrolizumab or atezolizumab, which are the most used checkpoint inhibitors in oncology. The Company has demonstrated encouraging preclinical results in colorectal, liver, and small cell lung cancer models.

Presented preclinical data validating efficacy of THIO in hepatocellular carcinoma (HCC) at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 37th Annual Meeting: Conducted an oral presentation, which indicated that THIO, a first-in-class telomere-targeted agent, may enhance the overall therapeutic efficacy of current immune checkpoint inhibitor-based treatments for HCC.

Expanded Phase 2 THIO-101 trial to Europe: Regulatory authorities in three European countries, Hungary, Poland, and Bulgaria, approved the implementation of THIO-101.

Held Pre-IND meeting with FDA for planned U.S. expansion of THIO-101 Phase 2 Trial for NSCLC: MAIA received positive initial feedback from the FDA regarding its manufacturing, preclinical, and clinical development plan. MAIA also obtained guidance from the FDA on the assessment of its safety and efficacy in THIO-101, which will be incorporated in the U.S. IND application.

Advanced new telomere-targeting molecule program: MAIA is designing and evaluating multiple telomere-targeting compounds designed to modify the telomeric structure through the cancer cell – intrinsic telomerase activity, and thus cause the death of these cells. The studies, conducted in vitro in multiple cancer cell lines and in vivo in several pre-clinical cancer models, demonstrated the intended mechanism of action and high-level anti-cancer activity for these new molecules.

Full Year 2022 Financial Results

Cash Position: The Company had cash totaling approximately $10.9 million as of December 31, 2022, compared to $10.6 million in cash as of December 31, 2021.

Research and Development (R&D) Expenses: R&D expenses were approximately $8.9 million for the year ended December 31, 2022, compared to approximately $3.5 million for year ended December 31, 2021. The increase for the year was primarily due to the increase in clinical expenses related to clinical preparation and the startup of the THIO trials of approximately $3.1 million, an increase in payroll and bonus expenses of approximately $2.2 million, an increase in other expenses related to research and development of approximately $0.1 million and an increase of approximately $0.02 million in professional fees offset by a decrease in stock-based compensation of approximately $0.05 million. R&D expenses included approximately $0.9 million and $0.9 million of non-cash stock compensation expense in the year 2022 and 2021, respectively.

General and Administrative (G&A) Expenses: G&A expenses were approximately $6.1 million for the year ended December 31, 2022, compared to approximately $4.3 million for the year ended December 31, 2021. The increase for the year was primarily due to approximate increases in payroll and bonus expenses of $0.9 million, an increase of approximately $0.9 million of other expenses related to the costs of operating as a public company, an increase in professional fees of approximately $0.3 million offset by a decrease in stock-based compensation of approximately $0.3 million. G&A expenses included approximately $1.4 million and $1.8 million of non-cash stock compensation expense in the years ended December 31, 2022, and 2021, respectively. In addition, ratchet share expense was approximately $1.1 million for the year ended December 31, 2022, compared to no expense for the year ended December 31, 2021.

Other Income (Expense): Other income was approximately $0.4 million for the year ended December 31, 2022, and other expense for the year ended December 31, 2021 was approximately $4.8 million. Other income in the year ended December 31, 2022, consisted primarily of approximately $0.3 million in Australian research and development incentives and approximately $0.1 million of the change in the fair values of warrant liability. Other expense for the year ended December 31, 2021 primarily consisted of interest expense for convertible notes of approximately $0.8 million, expense for the change in the fair values of the warrant liability of approximately $1.5 million, expense for the change in the fair value of the bifurcated embedded features of approximately $0.2 million, and the loss on extinguishment of convertible notes of approximately $2.3 million.

Net Income (Loss): Net loss was approximately $15.7 million for the year ended December 31, 2022, as compared to net loss of approximately $12.6 million for the year ended December 31, 2021.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is an investigational telomere-targeting agent currently in clinical development to evaluate its activity in non-small cell lung cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

On March 24, 2023 ProfoundBio, a clinical stage biotechnology company focused on the development of novel antibody-based therapeutics with curative potential, reported its two posters from its lead program, PRO1184, a folate receptor alpha (FRα)-directed exatecan-based antibody-drug conjugate (ADC) with a novel hydrophilic linker, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 14 – 19, 2023 (Press release, ProfoundBio, MAR 24, 2023, View Source [SID1234629309]). The presentations will highlight PRO1184 preclinical data demonstrating the potential of ProfoundBio’s novel, proprietary technology platform to improve the activity and safety of ADCs, and the study design of the first-in-human clinical trial (NCT05579366).

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"PRO1184 demonstrates strong efficacy across diverse tumor types, histologies and target expression levels with a well-tolerated profile in preclinical models. PRO1184 is a promising development candidate for the treatment of FRα-expressing solid tumors." Said Zhu Chen, PhD, Chief Scientific Officer.

"The first clinical trial for PRO1184 is actively enrolling at sites in the US and soon in China. We are gratified by the interest we have received in this clinical trial from experienced investigators. We believe it is a potential best-in-class ADC candidate that could benefit patients with not only high but also low FRa expressing cancer." said Baiteng Zhao, PhD, Chief Executive Officer. "Our presentations further demonstrate the potential of our proprietary ADC technology and provide more confidence to expect positive clinical results from PRO1184 and our other programs. I look forward to bringing better therapeutic solutions forward to help patients with cancer."

Details of ProfoundBio presentations at the AACR (Free AACR Whitepaper) annual meeting:

A poster entitled "Novel folate receptor alpha-directed antibody-drug conjugate PRO1184 demonstrates broad antitumor activity with a promising safety profile in preclinical models" will be presented on April 17, 2023 1:30 – 5:00 pm.

A poster entitled "Phase 1/2 study of PRO1184, a novel folate receptor alpha-directed antibody-drug conjugate, in patients with locally advanced and/or metastatic solid tumors" will be presented on April 18, 2023 1:30 – 5:00 pm.

About PRO1184

PRO1184 is a folate receptor alpha (FRα)-directed ADC with a novel proprietary hydrophilic linker and the exatecan payload. PRO1184 is currently being evaluated in a Phase 1 clinical trial for patients with advanced solid tumors (NCT05579366).

On March 24, 2023 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported that it plans to host a conference call on Thursday, March 30, 2023, at 8:30 a.m. ET to discuss its financial results for the fourth quarter and full-year ended December 31, 2022 and provide a corporate update (Press release, Theriva Biologics, MAR 24, 2023, View Source [SID1234629308]). The call was originally scheduled for Monday, March 27, 2023, at 8:30 a.m. ET.

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Individuals may participate in the live call via telephone by dialing 1-877-451-6152 (domestic) or 1-201-389-0879 (international) and using the conference ID: 13736047. Participants are asked to dial in 15 minutes before the start of the call to register. Investors and the public can access the live and archived webcast of this call via the "News & Media" section of the company’s website, View Source, under "Events" or by clicking here, up to 90 days after the call.