On August 18, 2022, Amgen Inc. (the "Company") reported that issued and sold $1,250,000,000 aggregate principal amount of the Company’s 4.050% Senior Notes due 2029 (the "2029 Notes"), $750,000,000 aggregate principal amount of the Company’s 4.200% Senior Notes due 2033 (the "2033 Notes"), and $1,000,000,000 aggregate principal amount of the Company’s 4.875% Senior Notes due 2053 (the "2053 Notes" and, together with the 2029 Notes and the 2033 Notes, the "Notes") (Filing, 8-K, Amgen, AUG 18, 2022, View Source [SID1234618477]). The Notes are registered under an effective Registration Statement on Form S-3 (Registration No. 333-236351) (the "Registration Statement"), filed on February 10, 2020, 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 August 18, 2022 (the "Officer’s Certificate"), setting forth the terms of the Notes. Net proceeds to the Company from the offering were approximately $2,976,217,500, 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 2029 Notes will pay interest at the rate of 4.050% per annum, the 2033 Notes will pay interest at the rate of 4.200% per annum and the 2053 Notes will pay interest at the rate of 4.875% per annum, which, in the case of the 2029 Notes, shall be payable in cash semi-annually in arrears on February 18 and August 18 of each year, beginning on February 18, 2023 and, in the case of the 2033 Notes and 2053 Notes, shall be payable in cash semi-annually in arrears on March 1 and September 1 of each year, beginning March 1, 2023. The 2029 Notes will mature on August 18, 2029, the 2033 Notes will mature on March 1, 2033 and the 2053 Notes will mature on March 1, 2053.

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.

On August 18, 2022 AIM ImmunoTech Inc. (NYSE: American AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders, and viral diseases – including COVID-19, the disease caused by the SARS-CoV-2 virus – reported the commencement of its Phase 2 study of Ampligen as a therapy for locally advanced pancreatic cancer ("LAPC") (AMP-270) following receipt of Institutional Review Board ("IRB") approval for the trial protocol (Press release, AIM ImmunoTech, AUG 18, 2022, View Source [SID1234618476]).

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AIM Chief Executive Officer Thomas K. Equels commented, "We are pleased to reach this important step in the development of Ampligen. Receiving IRB approval for our Phase 2 study of Ampligen for the treatment of LAPC is the pivotal precursor to the recruitment, enrollment and treatment of patients with locally advanced pancreatic cancer. We look forward to providing further updates on the development of this important therapy."

The Company’s Phase 2 study Investigational New Drug ("IND") application was previously cleared by the U.S. Food and Drug Administration ("FDA"). An IRB is a group that operates under FDA regulations and ensures, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research.

The AMP-270 clinical trial is a randomized, open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen versus a no treatment control group following FOLFIRINOX for subjects with locally advanced pancreatic adenocarcinoma. Secondary objectives include comparing safety and tolerability. AMP-270 is expected to enroll approximately 90 subjects in up to 30 centers across the United States and Europe. The Buffett Cancer Center at the University of Nebraska Medical Center and Erasmus MC in the Netherlands are expected to be the primary study sites.

"We expect study sites to be open and recruiting patients in late Q3/early Q4 of 2022, with every hope of first dose in the first patient by the end of Q4 2022," commented Kazem Kazempour, Ph.D., President and CEO of Amarex Clinical Research, LLC, AIM’s Contract Research Organization for AMP-270.

For more information about the AMP-270 please visit ClinicalTrials.gov and reference identifier NCT05494697.

The Company recently reported new, positive data following evaluation of the initial data reported from the single-center, named patient program at Erasmus for both metastatic and LAPC patient populations, analyzing the subset of patients with LAPC. While the predominance of the data collected by Erasmus is in metastatic cancer and those data show high statistical significance, a small cohort of five (5) LAPC patients also exhibited marked improvement with the Ampligen maintenance therapy following FOLFIRINOX. The overall survival from the start of FOLFIRINOX therapy of two (2) of the patients was 34 and 43 months and one patient was still surviving at the last reported checkup in April 2022 at 54 months See: AIM Press Release July 20, 2022.

About Ampligen

Ampligen is AIM’s dsRNA product candidate being developed for globally important cancers, viral diseases and disorders of the immune system. Ampligen has demonstrated in the clinic the potential for standalone efficacy in a number of solid tumors. Additionally, Ampligen has shown success in increasing survival rates and efficacy in the treatment of animal tumors when used in combination with checkpoint blockade therapies.

Ampligen is currently being evaluated as a combinational therapy for the treatment of a variety of solid tumor types in multiple clinical trials – both underway and planned – at major cancer research centers around the country. Ampligen is being used to treat pancreatic cancer patients in an Early Access Program approved by the Inspectorate of Healthcare in the Netherlands at Erasmus Medical Center. Additionally, Ampligen is also approved in Argentina for the treatment of severe chronic fatigue syndrome and is currently being evaluated in SARS-CoV-2/COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Post COVID Conditions.

On August 18, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on the TakeAim Lymphoma Phase 1/2 study of emavusertib after reviewing the comprehensive data package submitted by Curis (Press release, Curis, AUG 18, 2022, View Source [SID1234618474]).

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"We are excited to announce that FDA has completed its review of the TakeAim Lymphoma study and has lifted the partial clinical hold. We are working with our clinical sites to quickly resume enrollment of new patients in this study in the third quarter," said James Dentzer, President and Chief Executive Officer of Curis.

Previously, Curis announced that the FDA had placed separate partial clinical holds on the TakeAim Leukemia and TakeAim Lymphoma studies on April 4 and April 11, 2022, respectively. The partial hold on the TakeAim Leukemia study was issued by the FDA Division of Hematologic Malignancies 1 (DHM1), which regulates clinical studies in leukemia. The partial hold on the TakeAim Lymphoma study, and the lifting of that hold, was issued by the FDA Division of Hematologic Malignancies 2 (DHM2), which regulates clinical studies in lymphoma. The partial clinical hold was lifted following agreement with the FDA on Curis’s strategy for rhabdomyolysis identification and management, as well as on the enrollment of at least nine additional patients at the 200 mg dose level of emavusertib in combination with ibrutinib.

With the partial clinical hold lifted on the TakeAim Lymphoma study, the Company is updating its timeline for clinical data release to reflect the availability of updated preliminary data from this study in 2023. In addition, Curis is proactively discussing the clinical plans for emavusertib, including alignment on optimal dose and development path, with DHM2 for the TakeAim Lymphoma study.

About Emavusertib (CA-4948)

Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-kB protein complex. Additionally, third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutations such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, emavusertib was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS.

About TakeAim Leukemia

The TakeAim Leukemia study (NCT04278768) is a Phase 1/2 open-label dose escalation, dose expansion clinical trial investigating emavusertib as a monotherapy and in combination with azacitidine or venetoclax in patients with relapsed or refractory (R/R) AML or high risk MDS. After dose escalation in both monotherapy and combination therapy to determine the recommended Phase 2 dose (RP2D), we plan to expand five cohorts: monotherapy in AML patients with spliceosome and FLT3 mutations, monotherapy in patients with MDS and spliceosome mutations and combination therapy with azacitidine or venetoclax in patients without spliceosome or FLT3 mutations. The goals of the study are to determine several parameters including safety, maximum tolerated dose (MTD), RP2D and signals of activity.

About TakeAim Lymphoma

The TakeAim Lymphoma study (NCT03328078) is a Phase 1/2 open-label, dose escalation, dose expansion clinical trial investigating emavusertib as monotherapy and in combination with ibrutinib in patients with R/R hematologic malignancies, such as non-Hodgkin’s lymphoma and other B cell malignancies. After dose escalation in both monotherapy and combination therapy to determine the RP2D, we plan to expand four cohorts for combination treatment: marginal zone lymphoma, activated b-cell diffuse large b-cell lymphoma, primary CNS lymphoma, and patients developing adaptive resistance to ibrutinib monotherapy. The goals of the study are to determine several parameters including safety, MTD, RP2D and signals of activity.

On August 18, 2022 The European Medicines Agency (EMA) reported that it had adopted a positive opinion regarding the application for conditional approval of Kinpeygo for the treatment of IgA nephropathy, and on July 15th the European Commission issued the market authorization for Kinpeygo in the European Economic Area (EEA) (Press release, Calliditas Therapeutics, AUG 18, 2022, View Source [SID1234618473]).

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This is the first time that any drug has achieved approval for this rare disease in Europe and we are delighted that we can contribute a piece of the puzzle in the broader effort to improve care for patients with orphan diseases. We have now initiated the transfer of our market authorization to our partner, STADA, and look forward to seeing Kinpeygo being launched in Europe. Having now received approval in both the US and

Europe we are looking forward to the regulatory process in China, where our partner, Everest Medicines, plans to file for approval with the NMPA in the second half of this year.

In the US we continue to have significant success in our early commercial efforts. Net revenues from TARPEYO grew by over 250% when compared to Q1, resulting in net revenues of SEK 63.6 million ($6.6m) from TARPEYO for Q2. This reflects the continued strong interest from nephrologists, with unique prescribers growing from 111 in Q1 to 314 prescribers during Q2 with enrolments growing significantly from 134 in Q1 to 315 in Q2. This is a testament both to the unmet medical need perceived by nephrologists for this patient group as well as significant interest from prescribers generated due to the strong proteinuria and eGFR data associated with our product.

We are thrilled to be another step closer to bringing the first approved medication in IgAN to patients around the world, and look forward to continuing to expand access for patients with an unmet medical need for the rest of the year and beyond."

CEO Renée Aguiar-Lucander

Summary of Q2 2022
April 1 – June 30
Net sales amounted to SEK 64.0 million, whereof TARPEYO net sales amounted to SEK 63.6 million, for the three months ended June 30, 2022. No net sales were recognized for the three months ended June 30, 2021.
Operating loss amounted to SEK 209.8 million and SEK 159.4 million for the three months ended June 30, 2022 and 2021, respectively.
Loss per share before and after dilution amounted to SEK 3.62 and SEK 3.22 for the three months ended June 30, 2022 and 2021, respectively.
Cash amounted to SEK 846.8 million and 709.3 million as of June 30, 2022 and 2021 respectively.
Significant events during Q2 2022, in summary
In May 2022, Calliditas announced that the first patient had been randomized in the Group’s proof-of-concept Phase 2 study in patients with squamous cell carcinoma of the head and neck (SCCHN) with the NOX 1 and 4 inhibitor, setanaxib.
In May 2022, Calliditas announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the granting of a conditional marketing authorisation for Kinpeygo for the treatment of IgA nephropathy.
In May 2022, the Annual General Meeting of Calliditas was held and, among other things, the meeting decided on the election of Henrik Stenqvist and Elisabeth Björk to the Board of Directors and the establishment of a U.S. At-the-Market framework, pursuant to which Calliditas may, at its option, sell American Depositary Shares ("ADSs") in the United States.
Significant events after the reporting period
In July 2022, Calliditas announced that the European Commission (EC) granted conditional marketing authorization for Kinpeygo for the treatment of IgA nephropathy (IgAN) in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/gram. Kinpeygo is an orphan medicinal product and became the first and only approved treatment for IgAN in Europe. Kinpeygo will be marketed in the European Economic Area (EEA) exclusively by STADA Arzneimittel AG.
Investor Presentation August 18, 2022 14:30 CET
Audio cast with teleconference, Q2 2022

The information in the press release is information that Calliditas is obliged to make public pursuant to the EU Market Abuse Regulation. The information was sent for publication, through the agency of the contact persons set out above, on August 18, 2022 at 07:00 a.m. CET.

On August 18, 2022 Vivesto reported that it will publish its Q2 report for 2022 on August 25, 2022, at 08.00 am CEST (Press release, Vivesto, AUG 18, 2022, View Source [SID1234618472]). The company will hold a conference call and an online presentation on the same day at 10.00 am CEST. The call will be hosted by Acting CEO Christer Nordstedt and Acting CFO Robert Maiorana. The presentation will be in English and followed by a question-and-answer session.

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