On December 30, 2019 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics targeting infectious diseases and cancers based on its proprietary arenavirus platform, reported that the first patient has been dosed in a Phase 1/2 clinical trial (NCT04180215) of HB-201, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers. This trial is HOOKIPA’s first clinical trial in immuno-oncology (Press release, Hookipa Pharma, DEC 30, 2019, View Source [SID1234553433]).

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HB-201 is a TheraT platform-based vector (replication attenuated) from the arenavirus family expressing a non-oncogenic but highly antigenic E6/E7 fusion protein from HPV16. In preclinical studies, HB-201 was observed to be highly immunogenic, resulting in a robust CD8+ T cell response as compared to the levels induced by other approaches including adoptive cell therapies. In addition to strong immunogenicity, HOOKIPA observed robust anti-tumor activity in mouse models. HOOKIPA believes that HB-201 has the potential to provide therapeutic benefit to patients across the HPV16+ cancer setting.

Joern Aldag, Chief Executive Officer at HOOKIPA, commented: "We are excited to begin first-in-human testing with HB-201, our first clinical trial in immuno-oncology. Translating our promising preclinical data to cancer patients is an important milestone. We believe HOOKIPA’s approach can supercharge the natural defence mechanisms by inducing strong T cell responses to the benefit of patients affected by cancer and infectious diseases."

About the HB-201 Clinical Trial

The HB-201 Phase 1/2 trial is an open-label dose-escalation and dose-expansion trial in 100 patients with treatment-refractory HPV16+ cancers. It is designed to evaluate the safety and tolerability and preliminary efficacy of HB-201 as monotherapy and in combination with an immune checkpoint inhibitor.

For Phase 1 dose escalation, the patient population will be divided into two groups of 20 patients, each: the first group will include patients with progressing HPV16+ tumors who will receive monthly intravenous (IV) administration of HB-201; the second group will include patients with progressing HPV16+ tumors and an accessible tumor site who will receive one intratumoral (IT) administration of HB-201 followed by monthly IV administration of HB-201.

The primary endpoint of the Phase 1 portion of this trial will be to evaluate safety and tolerability to determine the recommended dose for the Phase 2 portion. Secondary endpoints will evaluate anti-tumor activity, as defined by RECIST (Response Evaluation Criteria In Solid Tumors) 1.1, and immunogenicity. The Phase 2 portion of the trial will also investigate the efficacy of HB-201 alone and in combination with a PD-1 inhibitor. HOOKIPA expects to provide interim safety, dose escalation, and efficacy data from HB-201 in late 2020 or early 2021. These data will be supplemented by a series of translational data sets designed to demonstrate the mechanism of action.

About Human Papillomavirus

Human Papillomavirus (HPV) is estimated to cause about 5% of the worldwide burden of cancer including approximately 99% of cervical cancers, 25% to 60% of head and neck cancers, 70% of vaginal cancers and 88% of anal cancers1. The majority of these cancers are caused by the HPV serotype 16. Most infections with HPV are cleared from the body with no lasting consequences. However, in some cases, HPV DNA becomes integrated into chromosomal DNA. When host cells take up this DNA, they express the HPV E6 and E7 proteins. This can potentially lead to cancer since expression of these proteins leads to alterations in cell cycle control, which in turn predisposes these cells to becoming cancerous.

On December 30, 2019 Varian (NYSE: VAR) reported that Dow Wilson, chief executive officer, and Chris Toth, president of Oncology Systems, will present at the J.P. Morgan Healthcare Conference in San Francisco, scheduled for 10:30 a.m. Pacific Time on Monday, January 13, 2020 (Press release, Varian Medical Systems, DEC 30, 2019, View Source [SID1234552627]).

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On December 30, 2019, Bausch Health Companies Inc. (the "Company") reported that it has completed its previously announced offering of $1,250,000,000 aggregate principal amount of its 5.000% Senior Notes due 2028 (the "2028 Notes") and $1,250,000,000 aggregate principal amount of its 5.250% Senior Notes due 2030 (the "2030 Notes," together with the 2028 Notes, the "Notes") (Filing, 8-K, Bausch Health, DEC 30, 2019, View Source [SID1234552628]).

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The Notes were offered in the United States and sold to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act"), and outside the United States to non-U.S. persons pursuant to Regulation S under the Securities Act. The Notes have not been and will not be registered under the Securities Act or any state securities law and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements.

The proceeds of the Notes offerings, along with cash on hand, will be used to finance amounts owed under the Company’s recently announced $1.21 billion settlement agreement relating to the U.S. putative securities class litigation filed in the U.S. District Court for the District of New Jersey (which is subject to court approval) and redeem $1.24 billion aggregate principal amount of the Company’s outstanding 5.875% Senior Notes due 2023, as well as to pay related fees and expenses.

The Notes Indenture

The Notes were issued pursuant to the indenture, dated as of December 30, 2019 (the "Indenture"), among the Company, the guarantors named therein and The Bank of New York Mellon, as trustee.

Interest and Maturity

Pursuant to the Indenture, the 2028 Notes will mature on January 30, 2028 and the 2030 Notes will mature on January 30, 2030. Interest on the Notes will be payable semi-annually in arrears on each January 30 and July 30, beginning on July 30, 2020.

Guarantees

The Notes will initially be jointly and severally guaranteed on a senior unsecured basis by each of the Company’s subsidiaries that is a guarantor under the Company’s existing credit agreement (the "Credit Agreement"), the Company’s existing senior secured notes (the "Existing Senior Secured Notes") and the Company’s existing senior unsecured notes (together, the "Note Guarantors").

Ranking

The Notes and the guarantees related thereto will be:

• senior unsecured obligations of the Company and the Note Guarantors, as applicable;
• pari passu in right of payment with all existing and future unsubordinated indebtedness of the Company or the applicable Note Guarantor;
• senior in right of payment to all existing and future indebtedness of the Company or the applicable Note Guarantor that expressly provides for its subordination to the Notes or the applicable guarantee;
• structurally subordinated to all existing and future indebtedness and other liabilities of the Company’s subsidiaries that do not guarantee the Notes to the extent of the value of such subsidiaries’ assets; and
• effectively subordinated to all existing and future secured indebtedness of the Company or the applicable Note Guarantor, including the Credit Agreement and the Existing Senior Secured Notes, to the extent of the value of the assets securing such indebtedness.
Redemption

The 2028 Notes will be redeemable at the option of the Company, in whole or in part, at any time on or after January 30, 2023, at the redemption prices as set forth in the Indenture.

The 2030 Notes will be redeemable at the option of the Company, in whole or in part, at any time on or after January 30, 2025, at the redemption prices as set forth in the Indenture.

In addition, the Company may redeem some or all of the 2028 Notes prior to January 30, 2023 at a price equal to 100% of the principal amount thereof plus a "make-whole" premium. Prior to January 30, 2023, the Company may redeem up to 40% of the aggregate principal amount of the 2028 Notes using the net cash proceeds of certain equity offerings at the redemption price set forth in the Indenture.

In addition, the Company may redeem some or all of the 2030 Notes prior to January 30, 2025 at a price equal to 100% of the principal amount thereof plus a "make-whole" premium. Prior to January 30, 2023, the Company may redeem up to 40% of the aggregate principal amount of the 2030 Notes using the net cash proceeds of certain equity offerings at the redemption price set forth in the Indenture.

Upon the occurrence of a change of control (as defined in the Indenture), unless the Company has exercised its right to redeem all of the Notes of a series, as described above, holders of the Notes of such series may require the Company to repurchase such holder’s Notes, in whole or in part, at a purchase price equal to 101% of the principal amount of such Notes plus accrued and unpaid interest to, but excluding, the purchase date applicable to such Notes.

Certain Covenants

The Indenture contains covenants that limit the ability of the Company and any of its restricted subsidiaries (as such term is defined in the Indenture), to, among other things:

• incur or guarantee additional indebtedness;
• make certain investments and other restricted payments;
• create liens;
• enter into transactions with affiliates;
• engage in mergers, consolidations or amalgamations; and
• transfer and sell assets.

On December 30, 2019 XBiotech Inc. (NASDAQ: XBIT) reported that closing of the sale of the Company’s True Human antibody Bermekimab to Janssen Biotech, Inc. (Janssen), a Janssen Pharmaceutical Company of Johnson & Johnson (Press release, XBiotech, DEC 30, 2019, View Source [SID1234552629]). Upon closing, Janssen paid XBiotech $750 million, with $75 million held in escrow for 18 months. Should Janssen pursue bermekimab indications outside of dermatology, XBiotech could also receive up to $600 million in additional payments upon completion of certain commercialization authorizations. In addition to the bermekimab acquisition, Janssen and XBiotech entered into manufacturing supply and clinical services agreements. Revenue from these agreements are expected to generate positive cash flow for XBiotech over the next two years.

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While Janssen acquired all rights to bermekimab, XBiotech remains free to use its True Human Antibody discovery program to develop new antibody therapeutics targeting IL-1⍺ (the same target as bermekimab) and to commercialize these therapeutics for all non-dermatological diseases. XBiotech plans to re-enter clinical development expeditiously with next generation anti-IL-1⍺ therapeutics.

The Company plans to use proceeds from the sale and the services agreements to fund discovery and development of its next generation True Human anti-IL-1⍺ antibody program and to advance other antibody therapeutics in the Company’s pipeline, including its infectious disease program. The Company will also have sufficient cash to support a significant capital transaction, such as a stock repurchase, subject to final board review and approval.

John Simard, XBiotech’s President & CEO, commented, "We are pleased to have Janssen acquire bermekimab and look forward to seeing superior efficacy and safety of this True Human Antibody in ongoing dermatological clinical trials and beyond. The transaction is an important validation of our True Human platform and the cutting-edge science behind targeting IL-1⍺ and enables us to continue to exploit the vast potential for next generation True Human anti-IL-1⍺ therapeutics outside of dermatology. With the close of the transaction, we are in a stronger position to create extraordinary value for shareholders."

On December 30, 2019 Eli Lilly and Company (NYSE: LLY) reported the opening of the LIBRETTO-531 clinical trial [NCT04211337] for selpercatinib, also known as LOXO-292, for treatment-naïve RET-mutant medullary thyroid cancer (MTC) patients (Press release, Eli Lilly, DEC 30, 2019, View Source [SID1234552630]). This is the second Phase 3 trial to open for selpercatinib, a highly selective and potent, oral investigational new medicine in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. Enrolled trial participants will be randomized to receive either selpercatinib or physician’s choice of cabozantinib or vandetanib as initial treatment of their advanced or metastatic RET-mutant MTC.

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"Approximately 60 percent of people with medullary thyroid cancer have an activating RET point mutation, yet the current therapeutic options are not ideal for many patients," said Lori Wirth, MD, medical director of the Center for Head and Neck Cancer, Massachusetts General Hospital Cancer Center. "This Phase 3 trial of selpercatinib in patients with advanced or metastatic RET-mutant MTC seeks to confirm a new standard of care that we hope will provide a more effective treatment option for this patient population."

"While medullary thyroid cancer is rare, the occurrence of RET mutations in MTC is high," said Gary Bloom, executive director for ThyCa: Thyroid Cancer Survivors’ Association, Inc. "For that reason, we are very excited about the opening of this Phase 3 trial because it shows promise for patients with advanced and metastatic RET-mutant MTC. Due to new treatment options, it is imperative that MTC patients discuss with their medical doctors if and when they should undergo genomic testing of their tumors. This will ensure that people with RET tissue mutations have access to potential treatments and clinical trials such as this one for selpercatinib."

Trial Background
LIBRETTO-531 is a randomized Phase 3 clinical trial of patients with treatment-naïve RET-mutant MTC. The trial will enroll 400 patients with advanced or metastatic RET-mutant MTC who have received no prior systemic therapy for metastatic disease. Enrolled trial participants will be randomized 2:1 to receive either selpercatinib or physician’s choice of cabozantinib or vandetanib as initial treatment of their advanced or metastatic RET-mutant MTC. RET mutations may be identified using local testing. This trial’s efficacy endpoints are progression-free survival (PFS), treatment failure-free survival (TFFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). For patients randomized to the control arm, crossover is allowed at progression.

About Selpercatinib (LOXO-292)
Selpercatinib, also known as LOXO-292, is a highly selective and potent, oral investigational new medicine in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types with varying frequency. Selpercatinib was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms.

Selpercatinib has received breakthrough designations in RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancers.

About RET-Altered Cancers
Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2 percent of non-small cell lung cancer, 10-20 percent of papillary and other thyroid cancers and a subset of other cancers. Activating RET point mutations account for approximately 60 percent of MTC. RET fusion cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET.

About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly’s commitment to people with cancer, please visit www.LillyOncology.com.