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.

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, 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 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 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ: MOR) reported that it has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for tafasitamab, an anti-CD19 antibody, for the treatment of relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) (Press release, MorphoSys, DEC 30, 2019, View Source [SID1234552626]). The BLA submission is based on the primary analysis data from the L-MIND trial of tafasitamab in combination with lenalidomide in patients with r/r DLBCL and the retrospective observational matched control cohort Re-MIND evaluating efficacy outcomes of r/r DLBCL patients who received lenalidomide monotherapy.

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"The BLA submission marks a significant milestone in MorphoSys’ history and demonstrates our dedication to address the high medical need in relapsed or refractory DLBCL," said Dr. Malte Peters, Chief Development Officer of MorphoSys. "If approved, tafasitamab and lenalidomide could become an alternative treatment option for patients with this serious disease."

The FDA has a 60-day filing review period to determine whether the BLA is complete and acceptable for filing. MorphoSys will communicate the agency’s decision.

About L-MIND
L-MIND is a single arm, open-label phase 2 study, investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) after up to two prior lines of therapy, including an anti-CD20 targeting therapy (e.g. rituximab), who are not eligible for high-dose chemotherapy and subsequent autologous stem cell transplantation. The study’s primary endpoint is objective response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS). In May 2019, the study reached its primary completion. Primary analysis data with a cut-off date of November 30, 2018 included 80 patients enrolled into the trial who had received tafasitamab and lenalidomide and had been followed-up as per protocol for at least one year. Efficacy results in this update were based on response rates assessed by an independent review committee for all 80 patients. Based on earlier reported interim data from L-MIND, in October 2017 the U.S. FDA granted Breakthrough Therapy Designation for tafasitamab plus lenalidomide in this patient population.

About Re-MIND
Re-MIND, an observational retrospective study, was designed to isolate the contribution of tafasitamab in the combination with lenalidomide and to prove the combinatorial effect. The study compares real-world response data of patients with relapsed or refractory DLBCL who received lenalidomide monotherapy with the efficacy outcomes of the tafasitamab-lenalidomide combination, as investigated in MorphoSys’s L-MIND trial. Re-MIND collected the efficacy data from 490 r/r DLBCL patients in the U.S. and EU. Qualification criteria for matching patients of both studies were pre-specified. As a result, 76 eligible Re-MIND patients were identified and matched 1:1 to 76 of 80 L-MIND patients based on important baseline characteristics. Objective response rates (ORR) were validated based on this subset of 76 patients in Re-MIND and L-MIND, respectively. The primary endpoint of Re-MIND has been met and shows a statistically significant superior best ORR of the tafasitamab/lenalidomide combination compared to lenalidomide monotherapy.

About tafasitamab (MOR208)
Tafasitamab (MOR208) is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. Fc-modification of tafasitamab is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. Tafasitamab has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be involved in B cell receptor (BCR) signaling.
MorphoSys is clinically investigating tafasitamab as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) is investigating the safety and efficacy of tafasitamab in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the U.S. FDA granted Breakthrough Therapy Designation for tafasitamab plus lenalidomide in this patient population. Re-MIND, the real-world data lenalidomide alone matched control cohort met its primary endpoint in October 2019, demonstrating clinical superiority of the tafasitamab/lenalidomide combination compared to lenalidomide alone. The ongoing phase 3 study B-MIND assesses the combination of tafasitamab and bendamustine versus rituximab and bendamustine in r/r DLBCL. In addition, tafasitamab is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.