On June 3, 2024, Royalty Pharma plc (the "Issuer") reported to have entered into an underwriting agreement (the "Underwriting Agreement"), by and among the Issuer, Royalty Pharma Holdings Ltd (the "Guarantor"), RP Management, LLC (the "Manager") and BofA Securities, Inc., Citigroup Global Markets Inc., J.P. Morgan Securities LLC, Morgan Stanley & Co. LLC and TD Securities (USA) LLC, as representatives of the several underwriters listed on Schedule I thereto (the "Underwriters"), pursuant to which the Issuer has agreed to issue and sell to the Underwriters $500 million aggregate principal amount of its 5.150% Senior Notes due 2029, $500 million aggregate principal amount of its 5.400% Senior Notes due 2034 and $500 million aggregate principal amount of its 5.900% Senior Notes due 2059 (collectively, the "Notes") in a registered public offering pursuant to an effective shelf registration statement on Form S-3 (Registration File No. 333-279905) (Filing, 8-K, Royalty Pharma , JUN 3, 2024, View Source [SID1234644140]). The Notes will be guaranteed on a senior unsecured basis by Royalty Pharma Holdings Ltd. The offering is expected to close on June 10, 2024, subject to the satisfaction of customary closing conditions. The description of the Underwriting Agreement contained herein is qualified in its entirety by reference to the Underwriting Agreement, a copy of which is included as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference.

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On June 3, 2024 BlueSphere Bio, a drug development company focused on the discovery of novel T-Cell receptor (TCR) based therapies, reported that the Food and Drug Administration (FDA) has cleared BlueSphere’s Investigational New Drug application (IND) for a Phase 1/2a trial (TCX-101) of its first-in-human (BSB-1001) product candidate for patients with relapsed or refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myeloid dysplastic syndrome (MDS), in conjunction with allogeneic hematopoietic stem cell transplantation (alloHSCT) (Press release, BlueSphere Bio, JUN 3, 2024, View Source [SID1234644080]). The Company anticipates enrolling the first patient in this multi-center, open-label study in 4Q2024. Notably, because of the unique product and trial design, the TCX-101 trial will enroll patients with active morphologic disease or cytogenetic features placing them at high risk of relapse. Additionally, patients will receive simultaneous administration of BSB-1001 with alloHSCT to optimally target residual leukemia, without the use of immunosuppressive drugs.

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BSB-1001 targets HA-1, a blood-restricted minor histocompatibility antigen (miHA) and is the first TCR-T cell therapy candidate generated using the Company’s TCXpress platform. TCXpress is an integrated, high-throughput TCR identification and screening platform that enables efficient TCR discovery with a competitive timeline. While BlueSphere is also developing assets for solid tumors and non-oncology indications, it has chosen to prioritize its high-risk leukemia programs in the clinic.

Simultaneously, BlueSphere also announced three additional blood-restricted miHA TCR product candidates that are ready for clinical development – all discovered utilizing the TCXpress platform. Together, these four TCR T-cell therapy candidates comprising the TCX-101 program positions the Company’s miHA portfolio with best-in-class HLA coverage in these hematologic indications.

"We are eager to begin treating patients in our TCX-101 trial," said Keir Loiacono, Esq., Chief Executive Officer of BlueSphere. "Our team is focused on accelerated identification, development and translation of novel products to the clinic. While alloHSCT provides a chance of a cure for patients, a large fraction of patients will still relapse or do not have it as an option because of active leukemia. Deploying a TCR-based approach to blood restricted antigens – like miHAs combined with alloHSCT – could provide new options for these patients. We believe that BlueSphere’s unique approach to product and trial design will, among other things, enable us to treat patients who previously were unable to receive alloHSCT because of the presence of active leukemia."

To further expand the reach of our TCR-based portfolio, BlueSphere has broadened its pipeline to address an additional subset of AML patients having mutated NPM1. Utilizing TCXpress, the Company identified and subsequently nominated a single lead TCR reactive against mutant NPM-1 for the TCX-102 program. As a testament to the power of our TCXpress platform and ability to accelerate translation to the clinic, the Company screened close to 700 million T cells and was able to select three (3) lead candidates in under six months, ultimately nominating a single TCR for clinical development. IND enabling work is underway with an IND filing anticipated in 2Q2025. The TCX-102 trial will be an autologous program and will not be given in combination with alloHSCT.

"The NPM1 mutation is a founder mutation present in approximately 30% of AML patients and is present throughout the duration of the disease, making it an ideal target for TCR-based therapy," said Erkut Bahceci, MD, Chief Medical Officer of BlueSphere. "The advancement of the TCX-102 program in patients with mutant NPM1 demonstrates our commitment to this disease space and underscores the power of our TCR discovery platform to discover rare and potent TCR candidates."

On June 3, 2024 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer reported that the first patient has been enrolled in the Phase II part of the randomized Phase I/II clinical trial of the individualized therapeutic cancer vaccine, TG4050, in the adjuvant treatment of head and neck cancer (Press release, Transgene, JUN 3, 2024, View Source [SID1234644069]). Patient screening and enrollment are active, with the aim of enrolling 80 patients internationally in the overall Phase I/II trial.

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TG4050 is based on Transgene’s myvac viral vector platform and NEC’s cutting-edge AI capabilities for the identification and prediction of the most immunogenic neoantigens for each patient. The therapeutic vaccine, TG4050, is being jointly developed by Transgene and NEC in head and neck cancer.

TG4050 advancing to Phase II part based on Phase I data showing immunogenicity and first signs of clinical benefit.

The promising TG4050 Phase I data presented at AACR (Free AACR Whitepaper) 2024 (see press release distributed on April 9, 2024, here) showed strong immunogenicity, persistent cellular immune response as well as signs of clinical benefit for patients. At the time of the analysis, only patients in the control arm had relapsed, while all patients who received TG4050 were disease-free. Based on these promising data, Transgene and its partner NEC have decided to move forward with an extension of the randomized trial consisting of a Phase II part. This Phase II part will continue investigating single-agent TG4050 in patients with newly diagnosed, locoregionally advanced, HPV-negative, squamous cell carcinoma of the head and neck (SCCHN) in the adjuvant setting following completion of surgery and chemoradiotherapy.

Although some advancements in the treatment of SCCHN have been made, there remains a significant medical need for these patients, including in the adjuvant setting. With the current standard of care, 30% to 40% of patients are expected to relapse within 24 months following surgery and adjuvant therapy. Despite completed Phase III trials, immune checkpoint inhibitors have yet to demonstrate significant benefits for these patients.

TG4050 is the only individualized neoantigen cancer vaccine currently being developed in a randomized trial in the adjuvant treatment of head and neck cancer.

Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene commented, "The inclusion of the first patient in the Phase II part of our Phase I/II trial marks a further milestone for Transgene. In the ongoing trial, TG4050 is targeting patients with head and neck cancer at high-risk of relapse, with the aim of extending disease-free survival. The Phase I data we have generated indicate that TG4050 enables the induction of specific cellular immune responses that persist up to 7 months post treatment initiation, with all treated patients remaining disease-free after a median follow-up of 18.6 months. We are encouraged by these promising clinical outcomes and look forward to generating data from the Phase II part of the trial. Personalized cancer vaccines are an extremely exciting development and, if successful, could also be utilized to treat other forms of cancer to improve and extend the lives of patients."

This international, multicenter, open label, two-arm trial is currently screening patients in France at IUCT-Oncopole (Toulouse) and Institut Curie (Paris). Additional sites in France, Europe and the US will be added in the coming months. Overall, the Phase I/II trial will randomize approximately 80 patients. The inclusion of the last patient in the Phase II part of the study is expected in Q4 2025.

TG4050 is designed based on each patient’s tumor

TG4050 is an individualized immunotherapy derived from Transgene’s myvac platform, combining Transgene’s biotechnology known-how and expertise with NEC’s artificial intelligence (AI) capabilities. Cancer vaccines of this type are individually designed to stimulate and educate the patient’s immune system to fight against their own cancer. This viral-based immunotherapy integrates about thirty tumor neoantigen, identified and selected from tumor sequencing to generate the most effective immune response.

On June 3, 2024 Diakonos Oncology Corp., a clinical-stage immuno-oncology company, reported that Chief Financial Officer and Head Of Business Development Anthony Baldor will give a company presentation at the 2024 BIO International Convention June 3 – 6, 2024 in San Diego (Press release, Diakonos Oncology, JUN 3, 2024, View Source;6-2024 [SID1234644068]). The corporate update will be June 4 at 3 pm PT in Company Presentation Theater 2 at the San Diego Convention Center.

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Mr. Baldor’s presentation will include a review of Diakonos’ highly differentiated double-loaded autologous dendritic cell vaccines for cancer, and an operational update on the company’s plans for growth, including clinical development outlook and expansion of its leadership team.

Diakonos recently completed a Phase 1 trial of DOC1021, its lead vaccine for glioblastoma multiforme (GBM), and is planning a Phase 2 study. The US Food and Drug Administration has granted Fast Track and Orphan Drug status for DOC1021. Two other clinical trials are under way with dendritic cell vaccines targeting pancreatic cancer and angiosarcoma.

"We are very excited about the results of our Phase 1 trial for GBM," Mr. Baldor said. "Data observed to date give us great confidence in our dendritic cell vaccines and their potential to treat a broad range of solid tumor cancers, including the most deadly. Twelve month survival is currently at 90% for evaluable patients, and the therapy is well tolerated."

Diakonos’ dendritic cell vaccines activate robust cytotoxic TH1 cell signaling pathways that better harness a patient’s immune system to target and eliminate cancer cells by initiating a natural immune response. This is achieved without any genetic modification of the patient’s immune cells, which greatly simplifies the manufacturing process and significantly reduces costs when compared to leading cell therapy approaches.

On June 3, 2024 TriSalus Life Sciences, Inc. (Nasdaq: TLSI), an oncology company integrating its novel Pressure Enabled Drug Delivery (PEDD) technology with immunotherapy to transform treatment for patients with liver and pancreatic tumors, reported that data from its Phase 1b PERIO-02 clinical trial was presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting, taking place May 31-June 4, 2024, in Chicago, Illinois (Press release, TriSalus Life Sciences, JUN 3, 2024, View Source [SID1234644067]).

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The PEDD approach is a proprietary delivery mechanism developed by TriSalus that aims to overcome challenges of the tumor microenvironment (TME) by modulating pressure and flow to enhance local drug concentrations in tumors by improving intravascular therapeutic delivery. The PERIO-02 clinical trial is the hepatic arterial infusion (HAI) of nelitolimod with the PEDD method to enhance tumor response in combination with intravenous checkpoint inhibition in adults with Hepatocellular Carcinoma (HCC) or Intrahepatic Cholangiocarcinoma (ICC).

"The PEDD approach represents a promising new delivery method that addresses the limitations of intravenous infusions or needle injections to deliver therapeutics such as nelitolimod to immune cells throughout and surrounding the tumor microenvironment," said Mary Szela, Chief Executive Officer and President of TriSalus. "The findings from the PERIO-02 clinical trial demonstrate the potential of the PEDD method to treat patients with HCC and ICC and provide initial clinical validation that HAI of nelitolimod is well tolerated with encouraging immunologic activity. We look forward to presenting these data and engaging with the medical community at ASCO (Free ASCO Whitepaper)."

Key Findings from the Phase 1b PERIO-02 Clinical Trial

At the 4 mg dose in cohort C, three of three patients had disease control as best on-treatment response, with one complete response (CR) in the liver (5L ICC), one partial response (PR) (-31%), and one stable disease (SD). For patient 101-017, investigators noted decreases in the target liver lesion (31.3 to 17.5 mm), non-target liver lesion, and extra-hepatic lymph nodes on days 53 and 84 with CR of target liver lesions and stability of extra-hepatic nodal lesions reported on day 154.
Median progression-free survival (PFS) in the Cohort C 4 mg dose level is > 120 days. Median overall survival (OS) for this group has not been reached (range 120-170 days).
Immune effects of nelitolimod included increases in liver tumor CD4 and CD8 T cells and an increase in the CD8 T cell:MDSC ratio.
Gene expression changes revealed increased Th1 programming as well as increased expression of granzyme A, IFNγ, and CXCL10 in both liver tumor and surrounding normal liver.
Changes among plasma marker levels included increased IL-2R and CXCL10 expression, with decreased IL-17A, IDO, and NT5E (CD73).
"The PERIO-02 data presented by Dr. Sunyoung Lee from the University of Texas MD Anderson Cancer Center illustrate that SD-101 is well tolerated when given by the PEDD method in patients who often have underlying liver disease, in association with encouraging biologic activity. The effects noted in PERIO-02 patients, including liver myeloid derived suppressor cell depletion and broad tumor microenvironment immune stimulation, are consistent with previously reported data in metastatic liver tumors (PERIO-01) and locally advanced pancreatic adenocarcinoma (PERIO-03)," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus.

PERIO-02 is an open-label phase 1 trial of nelitolimod given by the PEDD method in HCC and ICC. The study consists of dose-escalation cohorts of nelitolimod alone (Cohort A), with IV pembrolizumab (Cohort B), or IV nivolumab + ipilimumab (Cohort C). Nelitolimod is delivered over two cycles, with three weekly doses per cycle. Blood, liver tumor, and normal liver biopsies are collected for correlative studies.

Details about the presentation can be found below and on the ASCO (Free ASCO Whitepaper) website. Additionally, a copy of the poster will be available on the publications page of the TriSalus website.

Title: PERIO-02: Phase 1b Pressure Enabled Regional Immuno-oncology Trial of nelitolimod (SD-101), a Class C TLR9 agonist, delivered via hepatic artery infusion +/- checkpoint inhibition in intrahepatic cholangiocarcinoma and hepatocellular carcinoma
Presenter: Dr. Sunyoung Lee, associate professor of Gastrointestinal (GI) Medical Oncology at the University of Texas MD Anderson Cancer Center
Date: Saturday, June 1, 2024
Session Time: 9:00-12:00 p.m. CT/10:00-1:00 p.m. ET
Poster Session: Developmental Therapeutics—Immunotherapy
Abstract: 2622