Entry into a Material Definitive Agreement

On December 19, 2022 (the "Closing Date"), Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company") entered into a credit agreement (the "Credit Agreement") by and among the Company, as a borrower and guarantor; certain direct subsidiaries of the Company, as the initial subsidiary borrowers; the lenders and issuing banks from time to time party thereto; and JPMorgan Chase Bank, N.A., as administrative agent, swingline lender, and an issuing bank (Filing, 8-K, Regeneron, DEC 19, 2022, View Source [SID1234625449]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Credit Agreement provides for a $750 million senior unsecured five-year revolving credit facility (with a $25 million sublimit for swingline borrowings and a $50 million sublimit for letters of credit) (the "Credit Facility") and replaces the Company’s previously existing $750 million revolving credit facility, which was contemporaneously terminated as described in Item 1.02 below. The loans under the Credit Facility have a variable interest rate based on either the Secured Overnight Financing Rate-based rate or the alternate base rate (or other applicable rate with respect to non-dollar borrowings), plus an applicable margin that varies with the Company’s debt rating and total leverage ratio. The Credit Agreement includes an option for the Company to elect to increase the commitments under the Credit Facility and/or to enter into one or more tranches of term loans in the aggregate principal amount of up to $500 million, subject to the consent of the lenders providing the additional commitments or term loans, as applicable, and certain other conditions.

As set forth in the Credit Agreement, the Company has the option to amend the Credit Agreement to establish environmental, social, and governance targets which will be used to adjust pricing under the Credit Facility, subject to parameters to be provided in the amended Credit Agreement.

The proceeds of the loans under the Credit Facility may be used to finance the working capital needs, and for general corporate or other lawful purposes, of Regeneron and its subsidiaries. The Company has guaranteed all obligations under the Credit Facility.

The Credit Agreement contains operating covenants and a maximum total leverage ratio financial covenant. Operating covenants include, among other things, limitations on (i) the incurrence of indebtedness by the Company’s subsidiaries, (ii) liens on assets of the Company and its subsidiaries, and (iii) certain fundamental changes and the disposition of assets by the Company and its subsidiaries. The Credit Agreement contains other customary covenants, representations and warranties, and events of default.

The Credit Facility matures, and all amounts outstanding thereunder will become due and payable in full, on December 19, 2027. The Credit Agreement includes an option for the Company to elect to extend the maturity date of the Credit Facility, subject to the consent of the extending lenders and certain other conditions. Amounts borrowed under the Credit Facility may be prepaid, and the commitments under the Credit Facility may be terminated, at any time without premium or penalty. As of the date of this report, no borrowings were outstanding under the Credit Facility.

The foregoing summary of the Credit Agreement is qualified in its entirety by the full text of the Credit Agreement, which is attached as Exhibit 10.1 hereto and is incorporated herein by reference.

Nuvation Bio Doses First Patient in Phase 1b Combination Study of NUV-868

On December 19, 2022 Nuvation Bio Inc. (NYSE: NUVB), a biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, reported that it has dosed the first patient in a Phase 1b study of its BD2-selective BET inhibitor, NUV-868, in combination with olaparib (Press release, Nuvation Bio, DEC 19, 2022, View Source [SID1234625428]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 1b study will be conducted under two separate dosing regimens. Patients in the first regimen will be dosed with NUV-868 in combination with olaparib for the treatment of ovarian cancer, pancreatic cancer, metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer and other solid tumors. Patients in the second regimen will be dosed with NUV-868 in combination with enzalutamide for the treatment of mCRPC.

"We are excited to build upon the progress of our Phase 1 monotherapy study of NUV-868 with the initiation of dosing in this Phase 1b combination study. We expect this study to provide a deeper understanding of the potential benefit that NUV-868 can offer a wide range of patients with advanced solid tumors," said David Hung, M.D., Founder, President and Chief Executive Officer of Nuvation Bio. "This milestone underscores the continued clinical momentum of our pipeline as we work to tackle some of the greatest unmet needs in oncology."

As part of the Phase 1b study, NUV-868 will be administered at escalating dose levels in combination with olaparib until the recommended Phase 2 combination dose is determined.

Oxford BioDynamics in San Francisco for the 41st Annual J.P. Morgan Healthcare Conference

On December 19, 2022 Oxford BioDynamics Plc (AIM: OBD, the Company), a biotechnology company developing precision medicine tests for immune health based on the EpiSwitch 3D genomics platform, reported that its senior leadership will be in San Francisco during the 41st Annual J.P. Morgan Healthcare Conference, Jan 9-12 2023 (Press release, Oxford Biodynamics, DEC 19, 2022, View Source [SID1234625427]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

OBD concluded a successful year in 2022, with its flagship EpiSwitch Checkpoint Inhibitor Response Test (CiRT) made available and in commercial use both in the UK and the US, where it also received a unique reimbursement code by the American Medical Association’s CPT (Current Procedural Terminology) Editorial Board. The year has also seen compelling data and clinical utility described by renowned oncologists with pharma collaborators at leading global conferences, such as ASCO (Free ASCO Whitepaper) 2022 and ESMO (Free ESMO Whitepaper) 2022.

OBD’s EpiSwitch platform was developed to diagnose patients and determine how individuals might respond to disease or treatment, leveraging the Company’s deep understanding of how the 3D configuration of the genome plays a crucial role in gene regulation. The Company’s flagship product, the EpiSwitch CiRT, is a first-of-its-kind precision medicine blood test that predicts a cancer patient’s likely response to Immune Checkpoint Inhibitors (ICIs), including widely used anti-PD-L1 and anti-PD-1 therapies. Despite their potential benefit, it is estimated that 70%+ of patients treated with an ICI will not have a clinical response.

OBD’s CEO Dr Jon Burrows and CSO Dr Alexandre Akoulitchev will be attending meetings to discuss details of the unique EpiSwitch platform, as well as future plans for its use. If you would like to meet the team, please contact [email protected]

Zymeworks Announces Positive Topline Data in the Pivotal HERIZON-BTC-01 Trial of Zanidatamab

On December 19, 2022 Zymeworks Inc. (NASDAQ: ZYME), a clinical-stage biotechnology company developing multifunctional biotherapeutics, reported positive topline results from the pivotal Phase 2b HERIZON-BTC-01 open-label, single-arm clinical trial investigating zanidatamab, a HER2-targeted bispecific antibody, as monotherapy in patients with previously treated HER2-amplified and expressing BTC (Press release, Zymeworks, DEC 19, 2022, View Source [SID1234625426]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The positive topline results showed that 41.3% (95% CI: 30.4, 52.8) of enrolled patients with HER2-amplified and expressing (IHC2+ and 3+) disease achieved an objective response as assessed by independent central review. The median duration of response was 12.9 months (95% CI: 5.95 to not reached). The safety profile of zanidatamab in this trial was consistent with that observed in previously reported monotherapy studies, with no new safety signals identified. Full results from the pivotal trial are expected to be presented at a medical meeting in 2023.

Biliary tract cancers, including gallbladder cancer and cholangiocarcinoma, are diagnosed in more than 210,000 people every year1, with most patients presenting with inoperable disease2. Disease control with front-line therapy is modest and patients need treatment options after progression3,4. The human epidermal growth factor receptor 2 (HER2) is a promising target in approximately 5%-10% of cholangiocarcinomas and up to 20% of gallbladder cancers5. Currently no HER2-targeted therapy has been approved for the treatment of BTC.

"Through our work with the BTC patient community, we see first-hand the challenge these patients face in not only getting a diagnosis, but in the limited treatment options available," said Stacie Lindsey, Founder & CEO of the Cholangiocarcinoma Foundation. "Each investigative trial begins to close the gap on this high unmet medical need by helping to bring more treatment options to BTC patients and we’re looking forward to watching zanidatamab’s progression through the global regulatory review process."

"We are thrilled to report these positive topline data from the HERIZON-BTC-01 clinical trial, which further support the potential of zanidatamab as a new chemotherapy-free therapeutic option for HER2-amplified and expressing BTC. These data demonstrate that zanidatamab, as a single agent, improves on the current standard of care for patients in a difficult-to-treat disease who currently have a poor prognosis based on the limited treatment options currently available," said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. "I want to thank all of the patients, their families and the investigators who participated in this important study."

Conference Call for Investors and Analysts

Zymeworks management will host a conference call and webcast for investors and analysts on December 19, 2022 at 8:00 am ET. The event will be webcast live with dial-in details and webcast replays available on Zymeworks’ website at View Source

About HERIZON-BTC-01

HERIZON-BTC-01 is a global, multicenter, open-label, single-arm study (NCT04466891) with a primary endpoint of confirmed objective response rate (cORR) by independent central review (ICR) per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints include duration of response (DOR), proportion of subjects with a DOR ≥16 weeks, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. HER2 amplification, as determined centrally by in situ hybridization (ISH) in tumor tissue, was an inclusion criterion for all subjects enrolled into the two study cohorts: Cohort 1, the primary efficacy cohort, with tumor tissue showing HER2 immunohistochemistry (IHC) 2+ or 3+ staining, and Cohort 2 with tumor tissue showing HER2 IHC 0 or 1+ staining. The study was initiated in July 2020 and has active sites in North America, Asia Pacific, Europe, and South America, and shares sites with the pivotal Phase 3 trial, HERIZON-GEA-01 (NCT05152147), in first-line gastroesophageal adenocarcinoma (GEA) patients.

About Zanidatamab

Zanidatamab is an investigational, bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks continues to enroll subjects in the Phase 3 randomized clinical trial, HERIZON-GEA-01, evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab for HER2-expressing GEA. Zymeworks has entered into separate agreements with each of BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercialize zanidatamab throughout various countries around the world.

Zymeworks has an ongoing Expanded Access Program (EAP) for use of zanidatamab in patients with HER2-positive advanced solid tumors who are not eligible for zanidatamab clinical trials, meet the criteria for EAP, and who in the opinion of the treating oncologist, would potentially benefit from treatment with zanidatamab. Additional information is available on our website at View Source

Illumina To Webcast Upcoming Investor Conference

On December 19, 2022 Illumina, Inc. (NASDAQ: ILMN) reported that its executives will be speaking at the following investor conference (Press release, Illumina, DEC 19, 2022, View Source [SID1234625424]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

41st Annual J.P. Morgan Healthcare Conference on January 9, 2023
Presentation at 3:45pm Pacific Time (6:45pm Eastern Time) immediately followed by a Q&A Session to begin at approximately 4:05pm Pacific Time (7:05pm Eastern Time)

The webcast can be accessed through the Investor Info section of Illumina’s website at investor.illumina.com. A replay will be posted on Illumina’s website after the event and will be available for at least 30 days following.