Entry into a Material Definitive Agreement

On March 2, 2023 Amgen Inc. (the "Company") reported that it has issued and sold $2,000,000,000 aggregate principal amount of the Company’s 5.250% Senior Notes due 2025 (the "2025 Notes"), $1,500,000,000 aggregate principal amount of the Company’s 5.507% Senior Notes due 2026 (the "2026 Notes"), $3,750,000,000 aggregate principal amount of the Company’s 5.150% Senior Notes due 2028 (the "2028 Notes"), $2,750,000,000 aggregate principal amount of the Company’s 5.250% Senior Notes due 2030 (the "2030 Notes"), $4,250,000,000 aggregate principal amount of the Company’s 5.250% Senior Notes due 2033 (the "2033 Notes"), $2,750,000,000 aggregate principal amount of the Company’s 5.600% Senior Notes due 2043 (the "2043 Notes"), $4,250,000,000 aggregate principal amount of the Company’s 5.650% Senior Notes due 2053 (the "2053 Notes") and $2,750,000,000 aggregate principal amount of the Company’s 5.750% Senior Notes due 2063 (the "2063 Notes" and, together with the 2025 Notes, the 2026 Notes, the 2028 Notes, the 2030 Notes, the 2033 Notes, the 2043 Notes and the 2053 Notes, the "Notes"). The Notes are registered under an effective Registration Statement on Form S-3 (Registration No. 333-269670) (the "Registration Statement"), filed on February 9, 2023, and were issued pursuant to an indenture, dated as of May 22, 2014 (the "Indenture"), between the Company and The Bank of New York Mellon Trust Company, N.A., as trustee, and an officer’s certificate, dated as of March 2, 2023 (the "Officer’s Certificate"), setting forth the terms of the Notes (Filing, 8-K, Amgen, MAR 2, 2023, View Source [SID1234628048]). Net proceeds to the Company from the offering were approximately $23,766,627,500 ("Net Cash Proceeds"), after deducting underwriters’ discounts and estimated offering expenses payable by the Company.

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The relevant terms of the Notes are set forth in the Indenture, included as Exhibit 4.1 of the Company’s Current Report on Form 8-K, filed on May 22, 2014, and incorporated herein by reference, and the Officer’s Certificate (including the forms of the Notes) attached hereto as Exhibit 4.2 and incorporated herein by reference.

The 2025 Notes will pay interest at the rate of 5.250% per annum, the 2026 Notes will pay interest at the rate of 5.507% per annum, the 2028 Notes will pay interest at the rate of 5.150% per annum, the 2030 Notes will pay interest at the rate of 5.250% per annum, the 2033 Notes will pay interest at the rate of 5.250% per annum, the 2043 Notes will pay interest at the rate of 5.600% per annum, the 2053 Notes will pay interest at the rate of 5.650% per annum and the 2063 Notes will pay interest at the rate of 5.750% per annum, which shall be payable in cash semi-annually in arrears on March 2 and September 2 of each year, beginning on September 2, 2023. The 2025 Notes will mature on March 2, 2025, the 2026 Notes will mature on March 2, 2026, the 2028 Notes will mature on March 2, 2028, the 2030 Notes will mature on March 2, 2030, the 2033 Notes will mature on March 2, 2033, the 2043 Notes will mature on March 2, 2043, the 2053 Notes will mature on March 2, 2053 and the 2063 Notes will mature on March 2, 2063.

The Company plans to use the Net Cash Proceeds to fund its acquisition of Horizon Therapeutics plc (the "Acquisition") pursuant to the transaction agreement entered into on December 11, 2022 (the "Transaction Agreement"). The offering is not conditioned upon the consummation of the Acquisition; however, if (i) the consummation of the Acquisition does not occur on or before the later of (x) January 31, 2024 or (y) such later date to which the Transaction Agreement as in effect on March 2, 2023 may be extended in accordance with its terms (the "Special Mandatory Redemption End Date"), (ii) prior to the Special Mandatory Redemption End Date, the Transaction Agreement is terminated or (iii) the Company otherwise notifies the trustee of the Notes that it will not pursue the consummation of the Acquisition, the Company will be required to redeem the Notes of each series then outstanding, other than the 2063 Notes, at a special mandatory redemption price equal to 101% of the principal amount of the Notes to be redeemed plus accrued and unpaid interest to, but excluding, the special mandatory redemption date, as further described in the final prospectus supplement, dated February 15, 2023, filed in connection with the offering of the Notes.

In the event of a change in control triggering event, as defined in the Officer’s Certificate, the holders of the Notes may require the Company to purchase for cash all or a portion of their Notes at a purchase price equal to 101% of the principal amount of Notes, plus accrued and unpaid interest, if any. The descriptions of the Indenture, the Officer’s Certificate and the Notes in this report are summaries and are qualified in their entirety by the terms of the Indenture, the Officer’s Certificate and the Notes, respectively.

The Notes will rank equal in right of payment to all of the Company’s other existing and future senior unsecured indebtedness, senior in right of payment to all of the Company’s existing and future subordinated indebtedness, effectively subordinated in right of payment to all of the Company’s subsidiaries’ obligations (including secured and unsecured obligations) and subordinated in right of payment to the Company’s secured obligations, to the extent of the assets securing such obligations.

Permanent Reduction of Bridge Credit Facility

On December 12, 2022, the Company, Citibank, N.A. ("Citibank"), as administrative agent, Bank of America, N.A. ("Bank of America"), as syndication agent, and Citibank and Bank of America as lead arrangers and book runners entered into a bridge credit facility (the "Bridge Credit Facility") (as filed in our Current Report on Form 8-K on December 12, 2022) providing for borrowings of up to $28.5 billion to finance the Acquisition. The commitments under the Bridge Credit Facility were automatically reduced on December 22, 2022 by the amount of our term loan credit facility (as filed in our Current Report on Form 8-K on December 22, 2022) entered into by the Company, Citibank, as administrative agent, Bank of America, as syndication agent, Citibank, Bank of America, Goldman Sachs Bank USA and Mizuho Bank, Ltd., as lead arrangers and bookrunners, and Goldman Sachs Bank USA and Mizuho Bank, Ltd. as documentation agents providing for (1) a $2,000,000,000 18-month term loan tranche and (2) a $2,000,000,000 3-year term loan tranche.

Following the issuance and sale of the Notes described above, the commitments under the Bridge Credit Facility have been further reduced by the amount corresponding to the Net Cash Proceeds to the Company from the Notes offering.

Allogene Therapeutics Announces Participation in Two Upcoming Investor Conferences

On March 2, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported that it will participate in two upcoming investor conferences (Press release, Allogene, MAR 2, 2023, View Source [SID1234628047]).

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Cowen 43rd Annual Health Care Conference
Monday, March 6, 2023
8:10AM PT/11:10AM ET

Oppenheimer 33rd Annual Healthcare Conference
Tuesday, March 14, 2023
9:00AM PT/12:00PM ET

Any available webcasts will be posted to the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following a live webcast, a replay will be available on the Company’s website for approximately 30 days.

Entry into a Material Definitive Agreement

On March 2, 2023 Keryx Biopharmaceuticals, Inc., a wholly-owned subsidiary of Akebia Therapeutics, Inc. (the "Company"), and Siegfried Evionnaz SA ("Siegfried") reported that it has entered into Amendment No. 5 to Master Manufacturing Services and Supply Agreement (the "Amendment"), which further amends the Master Manufacturing Services and Supply Agreement dated December 20, 2017 (as amended, the "Supply Agreement") (Filing, 8-K, Akebia, MAR 2, 2023, View Source [SID1234628046]).

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Pursuant to the Amendment, the Company agreed to purchase a minimum quantity of drug substance for Auryxia at a predetermined price. As a result of the Amendment, the term of the Supply Agreement expires on December 31, 2024, subject to the Company’s option to extend through December 31, 2026 by providing 12 months’ prior written notice to Siegfried.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by reference to the Amendment, a copy of which the Company expects to file as an exhibit to its Quarterly Report on Form 10-Q for the three months ending March 31, 2023.

Agios to Participate in March Investor Conferences

On March 2, 2023 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported that the company is scheduled to present at the following March investor conferences (Press release, Agios Pharmaceuticals, MAR 2, 2023, View Source [SID1234628045]).

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Cowen 43rd Annual Health Care Conference on Monday, March 6, 2023 at 1:30 p.m. ET; and
Oppenheimer 33rd Annual Healthcare Conference on Monday, March 13, 2023 at 12:00 p.m. ET.
Live webcasts of the presentations can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. Replays of the webcasts will be archived on the Agios website for at least two weeks following each presentation.

Aeglea BioTherapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Program Updates

On March 2, 2023 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported financial results for the fourth quarter and full year 2022, and provided program updates (Press release, Aeglea BioTherapeutics, MAR 2, 2023, View Source [SID1234628044]).

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"Since joining the company, I have been impressed by the programs and the potential impact that they may have on patient lives. In 2023, we are highly focused on execution, specifically the generation of data from our pegtarviliase Phase 1/2 clinical trial in Classical Homocystinuria and, assuming success with those data, preparations to advance into a potential pivotal trial," said Jeffrey Goldberg, president and chief executive officer of Aeglea. "We are also continuing to work with our partner Immedica Pharma AB to support the EMA [European Medicines Agency] review process for the Marketing Authorization Application for pegzilarginase for the treatment of Arginase 1 Deficiency. A decision by the EMA regarding the approval of the pegzilarginase Marketing Authorization Application is expected in late 2023. By delivering on these objectives, I believe we will be in a strong position to bring forward solutions that can positively impact the lives of our patient communities."

Program and Corporate Updates

Pegtarviliase in Homocystinuria


Received Fast Track Designation from the U.S. Food and Drug Administration (FDA). Fast Track Designation is designed to expedite the FDA’s review of innovative, new drugs that demonstrate the potential to address unmet medical need.

Announced in late November 2022 the completion of dosing of two patients in the third cohort of the Phase 1/2 clinical trial. Patients in the third cohort receive 1.35 mg/kg of pegtarviliase administered subcutaneously once weekly.

Pegzilarginase in Arginase 1 Deficiency


Transitioning patients who participated in the PEACE Phase 3 long-term extension (LTE) and Phase 1/2 open-label extension (OLE) studies into one simplified open-label trial. The PEACE LTE and Phase 1/2 OLE studies were closed in the first quarter of 2023.

Continuing to progress the review of the Marketing Authorization Application submission with the EMA for the potential approval of pegzilarginase. EMA approval can facilitate possible patient access and regulatory approval in many other geographies, including Latin America and the Middle East.

Corporate


Appointed Jeffrey Goldberg, a highly experienced executive with strong operational and rare disease background, as president and chief executive officer.

Strengthened senior management team with the promotions of Linda Neuman, MD, MBA, to chief medical officer and Cortney Caudill, MBA, to the newly created role of chief product officer. Ms. Caudill will serve as a strategic leader and team supervisor of Aeglea’s clinical programs.


Implemented changes to corporate structure to increase operational efficiency. Additionally, the company halted preclinical work on Cystinuria and other unnamed pipeline programs. The company will evaluate potential strategic options for these programs in order to maximize their value.

Upcoming Events


ACMG Annual Clinical Genetics Meeting, Salt Lake City, Utah
o
Long-Term Efficacy and Safety of Pegzilarginase for Arginase 1 Deficiency: 2 Years of Experience in the Phase 2 Extension Study
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Featured platform presentation on March 16, 2023 at 8:45-9:00 am MST

Fourth Quarter 2022 Financial Results

Aeglea recognized development fee revenues of $0.2 million in the fourth quarter of 2022, as a result of its license and supply agreement with Immedica Pharma AB for the commercial rights to pegzilarginase in Europe and several countries in the Middle East (License and Supply Agreement). The revenues recorded in the fourth quarter of 2022 are related to manufacturing services. Aeglea recognized $3.6 million for the fourth quarter of 2021 in development fee revenues.

Research and development expenses totaled $14.3 million for the fourth quarter of 2022 and $16.8 million for the fourth quarter of 2021. The decrease was primarily related to a decrease in Biologics License Application (BLA) activities for pegzilarginase and reductions in headcount and recruiting activities.

General and administrative expenses totaled $5.0 million for the fourth quarter of 2022 and $7.3 million for the fourth quarter of 2021. This decrease was primarily due to a reduction in commercialization activities for pegzilarginase and a reduction in headcount and related expenses.

Net loss totaled $18.8 million and $20.4 million for the fourth quarter of 2022 and 2021, respectively, which includes non-cash stock compensation expense of $1.4 million and $2.1 million for the fourth quarter of 2022 and 2021, respectively.

Full Year 2022 Financial Results

As of December 31, 2022, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $57.3 million. The company expects its cash, cash equivalents and marketable securities will enable it to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2023.

Aeglea recognized development fee revenues of $2.3 million in the year ended December 31, 2022, as a result of its License and Supply Agreement. The revenues recorded in the year ended December 31, 2022 are primarily related to the PEACE Phase 3 clinical trial and the submission of the BLA. Aeglea recognized $18.7 million in license and development fee revenues for the year ended December 31, 2021.

Research and development expenses totaled $58.6 million for the year ended December 31, 2022 and $57.1 million for the year ended December 31, 2021. The increase was primarily associated with activities involved in closing the PEACE Phase 3 trial and initiation activities for the new open-label study for the treatment of patients with Arginase 1 Deficiency and Investigational New Drug-enabling activities conducted for AGLE-325 in the first half of the year. These increases were partially offset by decreases due to the completion of non-clinical toxicology studies for pegtarviliase and a reduction in preclinical lab activities.

General and administrative expenses totaled $28.5 million for the year ended December 31, 2022 and $27.3 million for the year ended December 31, 2021. This increase was primarily due to an increase in commercial capabilities and infrastructure expenses in the first half of the year.

Net loss totaled $83.8 million and $65.8 million for the years ended December 31, 2022 and 2021, respectively, which includes non-cash stock compensation expense of $7.1 million and $8.0 million for the years ended December 31, 2022 and 2021, respectively

About Pegtarviliase in Homocystinuria

Pegtarviliase is a novel recombinant human enzyme, which is engineered to reduce elevated levels of total homocysteine circulating in the plasma by degrading the amino acid homocysteine and its dimer. Pegtarviliase is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of total homocysteine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including lens dislocation, skeletal abnormalities, vascular complications and neurologic effects, as well as the potential for sudden and early death. In preclinical studies, pegtarviliase improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. Pegtarviliase has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease and Fast Track Designations.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality. The PEACE Phase 3 clinical trial met its primary endpoint with a 76.7% reduction in mean plasma arginine compared to placebo. Additionally, 90.5% of pegzilarginase treated patients achieved normal plasma arginine levels.