On August 23, 2021 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported its 2021 second quarter unaudited financial results (Press release, Legend Biotech, AUG 23, 2021, View Source [SID1234586817]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have made exciting progress in advancing our first investigational CAR-T therapy cilta-cel in the past few months, with key regulatory, data and manufacturing updates. This includes the acceptance of our applications for cilta-cel by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) and the presentation of additional efficacy and safety data from the CARTITUDE cilta-cel clinical development program at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) Annual meetings," said Ying Huang, PhD, CEO and CFO of Legend Biotech. "We look forward to a momentous second half of the year as we work towards bringing cilta-cel to patients living with multiple myeloma and providing their healthcare providers a new therapeutic option, in collaboration with Janssen."

Second Quarter 2021 Highlights

In May 2021, the rolling submission of the Biologics License Application (BLA) was accepted by the U.S. FDA for cilta-cel for the treatment of adults with relapsed or refractory multiple myeloma (RRMM), following the submission by Legend Biotech’s collaborator, Janssen Biotech, Inc. (Janssen). As part of the BLA acceptance, the FDA granted cilta-cel priority review and set the Prescription Drug User Fee Act (PDUFA) target action date for November 29, 2021.
In May 2021, the Marketing Authorisation Application (MAA) submitted by Janssen was accepted by the European Medicines Agency (EMA) for cilta-cel for the treatment of adults with RRMM.
In addition, a submission for cilta-cel was made to the Brazilian Health Regulatory Agency by Janssen in April 2021.
Longer term data from the CARTITUDE-1 trial of cilta-cel in 97 heavily pretreated patients with RRMM, which was presented at the 2021 ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) Annual meetings, showed 98 percent overall response rate, 80 percent stringent complete response rate (sCR), progression free survival rate of 66 percent and an overall survival (OS) rate of 81 percent at the 18-month follow-up. A full manuscript containing earlier data from the CARTITUDE-1 trial at 12.4-months of follow up was published in The Lancet in June 2021.
First results from Cohort A of the CARTITUDE-2 study of cilta-cel, which was featured at the 2021 ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) Annual meetings, showed early and deep responses in the cohort of 20 patients with progressive MM after 1-3 prior lines of therapy, and who were lenalidomide refractory, with a safety profile consistent with what has been observed in the CARTITUDE clinical development program.
On June 22, 2021, Legend Biotech announced the establishment of a state-of-the-art manufacturing facility in Belgium as part of a joint investment with Janssen, to expand global manufacturing capacity of innovative cellular therapies.
On May 21, 2021, Legend Biotech completed the sale of 20,809,805 ordinary shares in a private placement at a purchase price of $14.41625 per ordinary share (equivalent to $28.8325 per American Depositary Share, or ADS) and the issuance of a warrant exercisable for up to an aggregate of 10,000,000 ordinary shares, exercisable for a two-year period at an exercise price of $20.00 per ordinary share (equivalent to $40.00 per ADS), in each case, pursuant to a subscription agreement dated May 13, 2021, with an institutional investor.
In June 2021, the CARTITUDE clinical program expanded to include the initiation of the CARTITUDE-5 study (NCT04923893), a Phase 3 randomized study evaluating cilta-cel in patients with newly diagnosed MM (NDMM) for whom autologous stem cell transplant (ASCT) is not planned as initial therapy. The CARTITUDE-5 study will evaluate bortezomib, lenalidomide and dexamethasone, known as VRd, followed by cilta-cel versus VRd, followed by lenalidomide and dexamethasone, or Rd, maintenance therapy.
The ongoing Phase 2 CARTITUDE-2 study (NCT04133636) was expanded with the addition of two cohorts: Cohort E (high-risk NDMM, transplant not planned) and Cohort F (standard-risk NDMM).
In May 2021, Legend Biotech achieved a $15 million milestone payment related to a cilta-cel development milestone, according to the terms and conditions of an agreement with Janssen.
*In December 2017, Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. to develop and commercialize cilta-cel.

Key Upcoming Milestones

As part of the acceptance of the BLA for cilta-cel for the treatment of adults with RRMM, the FDA has set the PDUFA target action date for November 29, 2021.
In collaboration with Janssen, Legend Biotech intends to present updated data from the CARTITUDE-1 and the CARTITUDE-2 studies at major medical conferences in 2021.
Legend Biotech anticipates supporting investigators to submit a manuscript on the clinical data update from LEGEND-2 study in 2021.
Legend Biotech intends to use the data from the CARTIFAN-1 study in support of a regulatory submission to the China Center for Drug Evaluation (CDE) in the second half of 2021, seeking approval of cilta-cel for the treatment of adults with RRMM.
Legend Biotech’s collaboration partner, Janssen, anticipates submitting a New Drug Application (NDA) to the Japan Pharmaceuticals and Medical Devices Agency in the second half of 2021, seeking approval of cilta-cel for the treatment of adults with RRMM.
Legend Biotech expects to initiate its Phase 1 clinical trial of LB1901 in RR T-cell lymphoma (TCL) in the United States in 2021.
Financial Results for Three Months and Six Months Ended June 30, 2021

Cash and Cash Equivalents and Time Deposits

As of June 30, 2021, Legend Biotech had approximately $488.2 million of cash and cash equivalents and approximately $174.6 million in time deposits.

Revenue

Revenue for the three months ended June 30, 2021 was $20.2 million compared to $11.6 million for the three months ended June 30, 2020. The increase of $8.6 million was primarily due to two additional milestones achieved pursuant to Legend Biotech’s agreement with Janssen in the fourth quarter of 2020 and in the second quarter of 2021, respectively. Revenue for the six months ended June 30, 2021 was $33.9 million compared to $23.1 million for the six months ended June 30, 2020. The increase of $10.8 million was primarily due to the aforementioned two additional milestones achieved. Milestone payments are constrained as a result of the uncertainty of whether the milestone will be achieved, but included as customer consideration for revenue recognition when the associated milestone is achieved and the uncertainty relieved. In half year of 2021, this resulted in a larger amount of revenue recognized from the contract liabilities. Legend Biotech has not generated any revenue from product sales to date.

Research and Development Expenses

Research and development expenses for the three months ended June 30, 2021 were $83.5 million compared to $53.6 million for the three months ended June 30, 2020. This increase of $29.9 million was primarily due to a higher number of clinical trials with more patients enrolled and a higher number of research and development product candidates. Consistently, research and development expenses for the six months ended June 30, 2021 was $154.5 million compared to $101.6 million for the six months ended June 30, 2020 with an $52.9 million increase.

Administrative Expenses

Administrative expenses for the three months ended June 30, 2021 were $9.2 million compared to $4.5 million for the three months ended June 30, 2020. The increase of $4.7 million was primarily due to Legend Biotech’s expansion of supporting administrative functions to aid continued research and development activities. Due to the consistent business expansion, administrative expenses for the six months ended June 30, 2021 increased by $10.1 million, which was $18.0 million for the six months ended June 30, 2021 compared to $7.9 million for the six months ended June 30, 2020.

Selling and Distribution Expenses

Selling and distribution expenses for the three months ended June 30, 2021 were $16.8 million compared to $9.6 million for the three months ended June 30, 2020. This increase of $7.2 million was primarily due to increased costs associated with commercial preparation activities for cilta-cel. Driven by the same commercial preparation activities, selling and distribution expenses for the six months ended June 30, 2021 was $30.2 million compared to $16.1 million for the six months ended June 30, 2020.

Other Income and Gains

Other income and gains for the three months ended June 30, 2021 was $1.7 million compared to $1.3 million for the three months ended June 30, 2020. Other income and gains for the six months ended June 30, 2021 was $2.4 million compared to $3.8 million for the six months ended June 30, 2020. The decrease of $1.4 million was primarily due to larger government grant and interest income received in the first half of the year in 2020.

Other Expenses

Other expenses for the three months ended June 30, 2021 was $2.3 million compared to $0.04 million for the three months ended June 30, 2020. The increase of $2.26 million was primarily due to higher foreign currency exchange loss, loss from disposal of assets and other expenses in the second quarter of 2021. Consistently, other expenses for the six months ended June 30, 2021 was $4.4 million compared to $0.08 million for the six months ended June 30, 2020, with an increase of $4.32 million.

Finance Costs

Finance costs for the six months ended June 30, 2021 was $0.09 million compared to $4.1 million for the six months ended June 30, 2020. The decrease was primarily due to finance costs related to the issuance of convertible redeemable preferred shares in 2020, which were fully converted into ordinary shares upon the completion of Legend Biotech’s initial public offering in June 2020.

Fair Value Loss of Warrant Liability

Fair value loss of warrant liability for the six months ended June 30, 2021 was $1.6 million caused by changes of fair value of a warrant, which was issued to an institutional investor through a private placement in May 2021. Concurrently, 20,809,805 ordinary shares were offered and sold to the institutional investor. The warrant was assessed as a financial liability with a fair value of $83.3 million as of June 30, 2021 and a fair value loss of $1.6 million was recorded for the six months ended June 30, 2021.

Fair Value Loss of Convertible Redeemable Preferred Shares

For the six months ended June 30, 2020, Legend Biotech reported a one-time non-cash charge of $80.0 million caused by changes of fair value of Series A convertible redeemable preferred shares (Series A Preferred Shares). Upon listing on the Nasdaq Global Market, all outstanding Series A Preferred Shares were converted into ordinary shares of Legend Biotech and all accrued but unpaid dividends were settled in the form of ordinary shares of Legend Biotech.

Loss for the Period

For the three months ended June 30, 2021, net loss was $91.6 million, or $0.33 per share, compared to a net loss of $134.9 million, or $0.63 per share, for the three months ended June 30, 2020. Net loss was $172.5 million, or $0.63 per share, for the six months ended June 30, 2021 compared to $179.1 million, or $0.86 per share, for the six months ended June 30, 2020.

On August 23, 2021 Samyang Biopharm USA, Inc. (View Source) a global biotech subsidiary of the Samyang Holdings Pharmaceuticals Corp. (View Source), reported that the company has entered into a three-year research collaboration with Dr. Hyun-Sung Lee, Assistant Professor of Surgery and Director of the Systems Onco-Immunology Laboratory (SOIL) at Baylor College of Medicine (Press release, Samyang Biopharmaceuticals, AUG 23, 2021, View Source [SID1234586816]). Samyang has awarded Dr. Lee a sponsored research grant which will utilize the capabilities of his laboratory to investigate the potential role of SYB-010, Samyang’s lead Immuno-Oncology asset, in sensitizing the tumor-immune microenvironment to immune checkpoint inhibitors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This alliance leverages Dr. Lee’s proven approach to immuno-oncology drug discovery and provides Samyang with the ideal research partner for this program," stated Barbara Natke, Ph.D., MBA, Head of Translational Sciences and Acting Vice President of Business Development, Samyang Biopharm USA. "Samyang is constantly looking for novel drug discovery platforms with the potential to transform drug development to address the unmet needs of patients. This strategic collaboration is a significant step in meeting that goal."

The primary goal of this study is to determine the predictive role of soluble MHC Class 1 Chain-Related Protein (sMIC) in identifying non-responders to immune checkpoint therapy and to determine the role of SYB-010, an anti-MIC therapy, in overcoming such resistance.

"Improving outcomes for cancer patients is only possible through a clear understanding of the potential of investigational drugs like SYB-010" said, Dr. Hyun-Sung Lee. "This partnership and financial support will leverage our established expertise in studying cancer-immune system networks through state-of-the-art single-cell platforms to answer questions around resistance to checkpoint immunotherapy, which is a significant hurdle in realizing the full potential of such therapies."

"Dr. Lee’s expertise and deep understanding of cancer research; particularly in the areas of systems biology and immunology, will provide valuable insights into the potential of SYB-010, which in pre-clinical models has shown a clear immunomodulatory effect along with a reduction in tumor growth," said Helen Hyun Jung Lee, President & CEO, Samyang Biopharm USA, Inc. "Samyang is delighted at the opportunity to partner with a scientist of Dr. Lee’s stature and we look forward to this collaboration as it will provide a foundation for the advancement of our compound into 2022 clinical trials and the opportunity to treat patients."

About SYB-010
SYB-010 (formerly CuraB-10), is a first-in-class therapeutic acquired by Samyang Biopharm USA from CanCure, LLC, in 2019. In cancer model systems, SYB-010 potently activates both the T lymphocyte and NK (natural killer) cell arms of the anti-tumor immune response. In animal models that are not responsive to inhibitors of PD-1, PD-L1 or CTLA-4, SYB-010 has the potential to work synergistically when combined with to those therapies to broaden the potential for an immune attack on cancer alone. The compound is currently in Investigational New Drug (IND)-enabling studies.

On August 23, 2021 Veracyte, Inc. (Nasdaq: VCYT), a global diagnostics company, reported that it has been awarded a Top Workplaces honor by the Bay Area News Group for the eighth consecutive year (Press release, Veracyte, AUG 23, 2021, View Source [SID1234586815]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The annual award is based solely on employee feedback gathered through an anonymous, third-party survey administered by Energage, LLC, a leading provider of technology-based engagement tools. The survey measures 15 culture drivers that are critical to organizational success, including alignment, execution and engagement.

Veracyte employees participating in the 2021 Top Workplaces survey ranked the company most highly for doing things efficiently and well, having senior managers who understand what is happening at the company, holding meetings that make good use of employee time, having strong interdepartmental coordination, going in the right direction, and operating by strong values.

"The results of this survey suggest that Veracyte employees at all levels feel confident in the quality of our work, leadership and processes, and that they believe in our strategy," said Marc Stapley, Veracyte’s chief executive officer. "As we continue our global expansion, we are committed to ensuring that Veracyte remains a top workplace for every one of our employees worldwide. This has been a core Veracyte value since the company’s 2008 founding, and will be essential to achieving our vision of improving outcomes for patients all over the world at every step of their journey."

The Bay Area News Group published the complete list of 2021 Top Workplaces winners on Sunday, August 22. The list is available at the Bay Area News Group website.

On August 23, 2021 TransCode Therapeutics, Inc. (Nasdaq: RNAZ), an emerging RNA oncology company, created on the belief that cancer can be defeated through the intelligent design and effective delivery of RNA therapeutics, reported recent business progress and second quarter 2021 financial results (Press release, TransCode Therapeutics, AUG 23, 2021, View Source [SID1234586814]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"2021 has so far been foundational for TransCode, highlighted by our recent initial public offering and listing on Nasdaq. With resources from the IPO and additional support from the NIH, we are driving progress across our organization, including key staff additions who bring valued expertise to our team and advancement of our preclinical work," said Michael Dudley, co-founder, president and CEO of TransCode Therapeutics. "Looking forward, we are positioning to move our pipeline into clinical development, as we seek to demonstrate the power and versatility of our TTX platform in solving the challenges of RNA delivery in oncology. We remain on track to submit an exploratory Investigational New Drug Application (eIND) in the first quarter of 2022 to test our lead therapeutic candidate, TTX-MC138, in a Phase 0 study in metastatic solid tumors. We believe this study has the potential to establish proof-of-mechanism for our platform, upon which we hope to build a broad and diverse pipeline of therapeutics and diagnostics with the potential to reach previously undruggable genetic targets."

Second Quarter 2021 and Recent Highlights

Completed an initial public offering of 7,187,500 shares of common stock, including full exercise of the underwriters’ option to purchase additional shares, resulting in aggregate gross proceeds of $28.8 million, before deducting underwriting discounts and commissions and other offering expenses.
Awarded a Fast-Track Small Business Innovation Research (SBIR) grant from National Institutes of Health (NIH), totaling $2.3 million expected over three years to support the clinical evaluation of TTX-MC138. The Company expects to use these funds for translational experiments to identify and optimize a method for measuring miR-10b expression in breast cancer clinical samples, as well as IND-enabling activities and measurement of delivery and target engagement of TTX-MC138.
Strengthened the Company’s leadership team with several key appointments, including:
Judy Carmody, Ph.D., as SVP of Operations, Susan Duggan as VP of Clinical Operations, Dustan Bonnin as VP of Corporate Strategy and Subrata Ghosh, Ph.D., as Principal Scientist; and
Dejan Juric, M.D., appointed to its Scientific Advisory Board. Dr. Juric, a renowned expert in personalized cancer medicine and breast cancer specialist, is currently serving as director of the Henri and Belinda Termeer Center for Targeted Therapies and Investigational Cancer Therapeutics Program at Massachusetts General Hospital.
Advanced preclinical work for TTX-MC138, the Company’s lead program, targeting miR-10b for treatment of metastatic solid tumors. The Company has completed development of a diagnostic assay validating a method for measuring miR-10b expression in patient blood and tissue samples. This new assay should support future TTX-MC138 clinical trials including the initial Phase 0 study.
Initiated IND-enabling activities to support its planned eIND filing for TTX-MC138.
Planned Upcoming Milestones

TransCode continues to advance its portfolio and has set the following goals:

TTX-MC138
Submission to FDA of an eIND application in the first quarter of 2022.
Initiation of Phase 0 clinical study evaluating TTX-MC138 for treatment of metastatic solid tumors later in 2022.
Concurrent completion of IND-enabling studies to support second half of 2022 filing an IND application for a Phase I clinical trial of TTX-MC138.
Publication of preclinical results supporting its TTX delivery platform in the second half of 2021.
Second Quarter Financial Highlights

Cash and Cash Equivalents: As of June 30, 2021, cash and cash equivalents totaled approximately $80 thousand, excluding approximately $25.4 million in net proceeds from the Company’s July IPO.
R&D Expenses: Research and development expenses were approximately $212 thousand in the second quarter of 2021, compared to approximately $75 thousand in the second quarter of 2020. The increase was primarily due to purchases of materials, license fees, lab facility expenses, costs related to development of intellectual property, and share-based compensation expenses.
G&A Expenses: General and administrative expenses were approximately $144 thousand in the second quarter of 2021, compared to approximately $177 thousand in the second quarter of 2020. The increase was primarily due to increased legal, accounting, insurance, and investor relations costs associated with the Company’s IPO and to share-based compensation expenses.
Operating Income (Loss): Operating loss was approximately $356 thousand in the second quarter of 2021, compared to approximately $92 thousand in the second quarter of 2020. Net income was approximately $2.8 million, or $0.60 per basic share and $0.51 per diluted share, for the second quarter of 2021, compared to a net loss of approximately $127 thousand, or $0.03 per basic and diluted share, for the second quarter of 2020. The results in the second quarter of 2021 primarily reflect a change in fair value of derivative liabilities related to convertible promissory notes. The convertible promissory notes automatically converted into common stock upon completion of the IPO. In the foreseeable future, the Company expects that operating losses will increase substantially and does not expect net profits.
Financial Guidance

TransCode expects that its cash and cash equivalents as of June 30, 2021, together with net proceeds from its initial public offering and the SBIR award, are sufficient to fund planned operations through year-end 2022.

On August 23, 2021 Thermo Fisher Scientific Inc. (the "Company") reported that it issued $700,000,000 aggregate principal amount of 1.750% Senior Notes due 2028 (the "2028 Notes"), $1,200,000,000 aggregate principal amount of 2.000% Senior Notes due 2031 (the "2031 Notes") and $1,200,000,000 aggregate principal amount of 2.800% Senior Notes due 2041 (the "2041 Notes" and, together with the 2028 Notes and the 2031 Notes, the "Notes") in a public offering (the "Offering") pursuant to a registration statement on Form S-3 (File No. 333-229951) and a preliminary prospectus supplement and prospectus supplement related to the offering of the Notes, each as previously filed with the Securities and Exchange Commission (the "SEC") (Filing, 8-K, Thermo Fisher Scientific, AUG 23, 2021, View Source [SID1234586813]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Notes were issued under an indenture, dated as of November 20, 2009 (the "Base Indenture"), and the Twenty-Second Supplemental Indenture, dated as of August 23, 2021 (the "Supplemental Indenture" and, together with the Base Indenture, the "Indenture"), between the Company, as issuer, and The Bank of New York Mellon Trust Company, N.A., as trustee.

The 2028 Notes will mature on October 15, 2028, the 2031 Notes will mature on October 15, 2031, and the 2041 Notes will mature on October 15, 2041. Interest on the Notes will be paid semi-annually in arrears on April 15 and October 15 of each year, commencing on April 15, 2022.

Prior to August 15, 2028 in the case of the 2028 Notes (two months prior to their maturity), July 15, 2031 in the case of the 2031 Notes (three months prior to their maturity) and April 15, 2041 in the case of the 2041 Notes (six months prior to their maturity) (each, a "Par Call Date"), the Company may redeem each series of 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 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 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 Notes to be redeemed matured on the 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 Indenture) plus 10 basis points, in the case of the 2028 Notes, 15 basis points, in the case of the 2031 Notes, and 15 basis points, in the case of the 2041 Notes, plus, in each case, accrued and unpaid interest on the Notes of such series being redeemed, if any, to, but excluding, the date of redemption.

In addition, on and after the applicable Par Call Date, the Company may redeem some or all of the Notes at a redemption price equal to 100% of the principal amount of the 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 Indenture) of the Company and a contemporaneous downgrade of the 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 Notes at a price equal to 101% of the principal amount of the Notes, plus any accrued and unpaid interest to, but excluding, the date of repurchase.

The Notes are general unsecured obligations of the Company. The 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 Notes. The 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 Indenture contains limited affirmative and negative covenants of the Company. 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 Indenture) or on shares of stock of the Company’s Principal Subsidiaries (as defined in the Indenture) and engage in sale and lease-back transactions with respect to any Principal Property. The 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 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 Notes may be accelerated, in which case the entire principal amount of the 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 August 23, 2021, regarding the 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 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.

The sale of the Notes was made pursuant to the terms of an Underwriting Agreement, which the Company entered into on August 9, 2021 (the "Underwriting Agreement"), with Barclays Capital Inc., Morgan Stanley & Co. LLC, BofA Securities, Inc. and Citigroup Global Markets Inc., as representatives of the several underwriters named in Schedule A to the Underwriting Agreement.

The Company expects that the net proceeds from the sale of the Notes will be approximately $3.05 billion, after deducting underwriting discounts and estimated offering expenses. The Company intends to use the net proceeds of the Offering to pay a portion of the cash consideration payable for the previously announced acquisition of PPD, Inc (the "PPD Acquisition"). The PPD Acquisition is subject to the satisfaction of customary closing conditions, including the receipt of applicable regulatory approvals. Pending completion of the PPD Acquisition, the Company may also determine to use a portion of the net proceeds of the Offering for general corporate purposes, which may include the acquisition of companies or businesses, repayment and refinancing of debt, working capital and capital expenditures or the repurchase of its outstanding equity securities or the Company may temporarily invest the net proceeds in short-term, liquid investments until they are used for their ultimate purpose.

The foregoing description is qualified in its entirety by reference to the full text of the Underwriting Agreement, which is filed with this report as Exhibit 1.1 hereto and is incorporated herein by reference.