On November 9, 2021 Kezar Life Sciences, Inc., (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing breakthrough treatments for immune-mediated and oncologic disorders, reported financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, Kezar Life Sciences, NOV 9, 2021, View Source [SID1234594952]).

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"Excellent progress continues across our programs, as we reached target enrollment in both of our Phase 2 trials with KZR-616 and announced our first patient dosed with KZR-261. Achieving full enrollment in our MISSION and PRESIDIO studies is an important milestone for KZR-616 as a potentially differentiated treatment option for patients suffering from lupus nephritis, dermatomyositis and polymyositis. We look forward to sharing interim results from MISSION at our upcoming event this month, with topline results from both studies expected in the second quarter of 2022," said John Fowler, Kezar’s Co-founder and Chief Executive Officer.

Clinical Highlights & Updates

KZR-616: Selective Immunoproteasome Inhibitor

MISSION – Phase 2 clinical trial in patients with lupus nephritis (LN) (NCT03393013)

Kezar’s upcoming Investor and Analyst Day, scheduled for Monday, November 15, 2021, at 4:30 p.m. ET/1:30 p.m. PT, will include a presentation featuring interim MISSION data, as well as a presentation from Samir V. Parikh, MD, Associate Professor of Medicine, Nephrology, The Ohio State University Wexner Medical Center.
The MISSION Phase 2 open-label trial in patients with active, proliferative LN has reached target enrollment of 20 subjects. The primary efficacy endpoint for the trial is the number of patients with a 50% reduction in urine protein/creatine ratio (UPCR) after 24 weeks of treatment when compared to baseline.
Kezar expects to report topline data in the second quarter of 2022.
PRESIDIO – Phase 2 clinical trial in patients with active dermatomyositis (DM) or polymyositis (PM) (NCT04033926)

The PRESIDIO Phase 2, placebo controlled, cross-over trial of KZR-616 in DM and PM has completed target enrollment of 24 subjects. The primary efficacy endpoint for the trial is the mean change from start to end of KZR-616 treatment in the Total Improvement Score (TIS), which ranges from 0 to 100.
Kezar expects to report topline data in the second quarter of 2022.
The PRESIDIO open-label extension study is available for patients completing the PRESIDIO trial, which evaluates KZR-616 for up to a maximum of 96 weeks (NCT04628936).
KZR-261: Protein Secretion Inhibitor

KZR-261-101 – Phase 1 clinical trial in patients with locally advanced or metastatic solid malignancies (NCT05047536)

In August, Kezar announced an IND submission for KZR-261 for the treatment of advanced solid malignant tumors, and in October, the first patient was dosed in its Phase 1 clinical trial.
KZR-261 is a novel, broad-spectrum, anti-tumor agent that acts through direct interaction and inhibition of the Sec61 translocon.
The Phase 1 clinical trial of KZR-261 will be conducted in two parts: dose escalation in subjects with locally advanced or metastatic solid malignancies for whom no therapeutics are available and dose expansion in subjects with selected tumor types. The trial will assess safety and tolerability, including determination of a recommended Phase 2 dose, evaluate pharmacokinetics and pharmacodynamics, and explore the preliminary anti-tumor activity.
Officer Appointment

In October, Gitanjali Jain was appointed as Kezar’s Vice President, Investor Relations and External Affairs, joining with nearly 15 years of healthcare industry and investor relations experience. As a member of the management team and executive committee, Ms. Jain will lead Kezar’s overall investor relations and public relations corporate efforts.

Credit Facility

On November 4, 2021, Kezar entered into a credit facility with Oxford Finance. Under the terms of the loan agreement, Oxford Finance will provide Kezar with borrowing capacity of up to $50 million across five potential tranches. The initial $10 million funded at closing, and an additional $10 million will be available at Kezar’s option in the second half of 2022. Additional tranches would become available upon achieving milestones related to the MISSION Phase 2 clinical trial, PRESIDIO Phase 2 clinical trial and/or KZR-261 Phase 1 clinical trial. There are no warrants or financial covenants associated with the credit facility. Capital Advisors Group, Inc acted as financial advisor to Kezar.

Third Quarter 2021 Financial Results

Cash, cash equivalents and marketable securities totaled $120.8 million as of September 30, 2021, compared to $140.4 million as of December 31, 2020. The decrease in cash, cash equivalents and marketable securities was primarily attributable to cash used by the company in operations to advance its clinical-stage programs, offset by $11.7 million of net proceeds from the issuance of common stock through September 30, 2021, under the company’s "at-the-market" sales program. In October, Kezar received an additional $4.4 million of net proceeds from the issuance of additional common stock under the ATM program.
Research and development expenses for the third quarter of 2021 increased by $2.2 million to $10.5 million compared to $8.3 million in the third quarter of 2020. This increase was primarily related to advancing the KZR-616 clinical program in multiple indications and the KZR-261 clinical program.
General and administrative expenses for the third quarter of 2021 increased by $0.7 million to $4.0 million compared to $3.3 million in the third quarter of 2020. The increase was primarily due to an increase in stock-based compensation and personnel and recruiting expenses as a result of an increase in headcount and salaries.
Net loss for the third quarter of 2021 was $14.5 million, or $0.28 per basic and diluted common share, compared to a net loss of $11.3 million, or $0.23 per basic and diluted common share, for the third quarter of 2020.
Total shares of common stock outstanding were 48.6 million shares as of September 30, 2021. Additionally, there were outstanding pre-funded warrants to purchase 3.8 million shares of common stock at an exercise price of $0.001 per share and outstanding options to purchase 6.9 million shares of common stock at a weighted-average exercise price of $5.85 per share, each as of September 30, 2021.
About KZR-616

KZR-616 is a novel, first-in-class, selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Preclinical research demonstrates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Data generated from Phase 1a and 1b clinical trials provide evidence that KZR-616 exhibits a favorable safety and tolerability profile for development in severe, chronic autoimmune diseases. Phase 2 trials are underway in multiple severe autoimmune diseases.

About KZR-261

KZR-261, a novel, first-in-class protein secretion inhibitor, is the first clinical candidate to be nominated from Kezar’s research and discovery efforts targeting the protein secretion pathway. KZR-261 is a broad-spectrum anti-tumor agent that acts through direct interaction and inhibition of Sec61 activity. The compound was discovered by Kezar through a robust medicinal chemistry campaign in which several scaffolds were progressed through the company’s proprietary platform evaluating Sec61 modulation. KZR-261 has demonstrated several encouraging properties that lead to its potential to be an anti-cancer agent, and a Phase 1 trial is underway for the treatment of solid tumor malignancies.

About Lupus Nephritis

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). LN is a disease comprising a spectrum of vascular, glomerular and tubulointerstitial lesions and develops in approximately 50% of SLE patients within 10 years of their initial diagnosis. LN is associated with considerable morbidity, including an increased risk of end-stage renal disease requiring dialysis or renal transplantation and an increased risk of death. There are limited approved therapies for the treatment of LN. Management typically consists of induction therapy to achieve remission and long-term maintenance therapy to prevent relapse.

About Dermatomyositis and Polymyositis

Dermatomyositis (DM) and Polymyositis (PM) are two of the five types of autoimmune myositis diseases. Both are chronic, debilitating, inflammatory autoimmune myopathies that are distinguished by inflammation of the muscles as well as the skin (in DM). Approximately 30,000 to 120,000 people in the United States are living with these severe and progressive inflammatory myopathies that are characterized by marked morbidity and associated mortality. While debilitating muscle weakness is the hallmark of these myopathies, including compromised muscles of respiration, other internal organ system dysfunctions can be equally disabling. The aim of treatment for these diseases is to suppress inflammation, increase muscle strength and prevent long-term damage to muscles and extramuscular organs; however, treatment options are limited for DM, and there are currently no approved treatments for PM.

About Inhibition of Protein Secretion

In mammalian cells, the secretion of proteins such as cytokines and growth factors and the expression of cell surface transmembrane proteins such as receptor tyrosine kinases and immune checkpoint molecules involve a process called cotranslational translocation. For most proteins, this process occurs via the Sec61 translocon, a highly conserved multi-subunit protein complex found in the membrane of the endoplasmic reticulum of all cells. Kezar scientists have been researching the protein secretion pathway and ways to drug this important cellular pathway for more than five years and developed novel and robust assays to discover and develop small molecule inhibitors of Sec61. As a result, Kezar has established a broad library of protein secretion inhibitors for potential development across a wide range of diseases.

On November 9, 2021 vTv Therapeutics Inc. (Nasdaq:VTVT) reported financial results for the third quarter ended September 30, 2021, and provided an update on the progress of its clinical programs (Press release, vTv Therapeutics, NOV 9, 2021, View Source [SID1234594988]).

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"We plan to refocus vTv’s strategy on TTP399. TTP399 is unique and the most important product in our portfolio with strong equity value potential to our shareholders", said Deepa Prasad, president and CEO, vTv Therapeutics. "Biotech is about innovation and meeting the unmet medical needs for patients. TTP399 does exactly this in seeking to solve the unmet need for type 1 diabetic patients experiencing hypoglycemic episodes. We are excited the FDA supports our effort by granting us Breakthrough Therapy Designation. Hypoglycemia is the most common acute complication for type 1 diabetes with onset occurring quickly and often without warning. We believe TTP399 can address this critical unmet need for type 1 diabetic patients worldwide."

Recent Achievements and Outlook

Corporate

Leadership. On October 19, 2021, Deepa Prasad was appointed to the role of President and CEO, and joined the board of directors. Deepa is a recognized healthcare leader with more than 20 years of experience across startup funding, operations, investment banking, and healthcare policy. Most recently, Deepa led investments in innovative life science companies as a managing director at West River Group.

Strategic Focus. We plan to implement a strategy to focus our efforts on the continued development of TTP399 as a potential treatment for patients with type 1 diabetes ("T1D") and TTP273 as a potential treatment for patients with cystic fibrosis related diabetes, as well as continuing to support our currently partnered programs. Given the strategic focus on these programs, we plan to pause our development activities in the United States on HPP737 while we evaluate strategic options for it. As part of this planned strategic focus, we are also evaluating cost reductions which may include reductions in our workforce.

Balance Sheet. The Company strengthened its balance sheet during the quarter through utilization of the at-the-market equity program with Cantor Fitzgerald, ending the quarter with $19.6 million of cash, cash equivalents and marketable securities.
Type 1 Diabetes

Mechanistic Study of Ketoacidosis with TTP399. In October 2021, the Company announced positive results from the mechanistic study of TTP399 in people with type 1 diabetes. Patients with type 1 diabetes taking TTP399 experienced no increase in ketone levels relative to placebo during a period of acute insulin withdrawal, indicating that treatment with TTP399 presents no increased risk of ketoacidosis. In addition, patients taking TTP399 had improved fasting plasma glucose levels and experienced fewer hypoglycemic events relative to those taking placebo, consistent and supportive of the previously announced phase 2 SimpliciT1 Study results.

Pivotal Study Planning. The Company is planning two pivotal, placebo-controlled clinical trials of TTP399 in subjects with type 1 diabetes and is engaged with the FDA on the optimal clinical trial designs for these studies. The Company expects to begin these pivotal studies in the first half of 2022.
Third Quarter 2021 Financial Results

Cash Position: The Company’s cash position as of September 30, 2021, was $19.6 million compared to $10.8 million as of June 30, 2021.

Revenue: Revenue for the third quarter of 2021 was $3.0 million, attributable to the satisfaction of milestones under the license agreements with Newsoara Biopharma Co., Ltd. and Reneo Pharmaceuticals, Inc. Revenue for the second quarter of 2021 was an insignificant amount.

R&D Expenses: Research and development expenses were $2.4 million in each of the three months ended September 30, 2021 and June 30, 2021, respectively.

G&A Expenses: General and administrative expenses were consistent between periods at $2.2 million for each of the three months ended September 30, 2021 and June 30, 2021.

Other Income/(Expense): Other expense for the three months ended September 30, 2021 was $0.2 million and was attributable to the gains related to a reduction in fair value of the warrants to purchase shares of our own stock issued to a related party (the "Related Party Warrants") offset by losses driven by the decrease in the fair value of our investment in Reneo Pharmaceuticals, Inc. (the "Reneo Investment"). Other income for the three months ended June 30, 2021 of $3.8 million was driven by changes in value of the Reneo Investment and gains related to the reduction in fair value of the Related Party Warrants.

Net Loss Before Non-Controlling Interest: Net loss before non-controlling interest was $1.5 million for the third quarter of 2021 compared to net loss before non-controlling interest of $0.8 million for the second quarter of 2021.

Net Loss Per Share: Diluted net loss per share was ($0.02) for the three months ended September 30, 2021 compared to diluted net loss per share of ($0.01) for the three months ended June 30, 2021, based on weighted-average diluted shares of 61.1 million and 58.6 million for the three-month periods ended September 30, 2021 and June 30, 2021, respectively.

On November 9, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, Mersana Therapeutics, NOV 9, 2021, View Source [SID1234595039]).

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"We have made significant progress towards our vision of building UpRi into a foundational medicine in ovarian cancer and advancing a diverse pipeline addressing areas of high unmet medical need. Over the course of next year, we expect UPLIFT to be fully enrolled, UP-NEXT to be initiated and enrolling, UPGRADE to be charting the path in combinations and to have multiple assets in the clinic addressing a diverse set of targets," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "Our promising pipeline assets are generated by our innovative platforms Dolaflexin, Dolasynthen and Immunosynthen, which act as efficient product engines creating value now and into the future."

Recent Highlights and Anticipated Milestones

Upifitamab Rilsodotin (UpRi), first-in-class Dolaflexin ADC targeting NaPi2b:

Reported updated interim data in almost 100 patients from the UpRi ovarian cancer expansion cohort. Data continued to demonstrate a clinically meaningful and consistent profile for UpRi with a confirmed objective response rate (ORR) of 34% in the two-thirds of patients with NaPi2b high ovarian cancer. Data continued to show a differentiated tolerability profile for UpRi without the severe neutropenia, neuropathy and ocular toxicities seen with other ADC platforms. These data support the potential for UpRi to demonstrate a clinically meaningful benefit in the ongoing registration-enabling UPLIFT study in platinum-resistant ovarian cancer, a setting in which the single-agent chemotherapy standard of care has an ORR of no more than 12% and carries substantial toxicities.

Introduced UP-NEXT, a Phase 3 study of UpRi monotherapy maintenance, informed by FDA feedback. UP-NEXT is designed to establish UpRi as a maintenance agent following treatment with platinum doublets in platinum-sensitive ovarian cancer. Watch-and-wait remains the standard of care for patients who have previously received or are poorly served by existing maintenance agents, as well as patients who achieve only stable disease to platinum doublets. UP-NEXT is designed to provide data to address these unmet needs. The Company plans to provide more details on the final design of UP-NEXT and expects to initiate the study in 2022.

UPLIFT, a single-arm registration study in platinum-resistant ovarian cancer, continues to enroll. UPLIFT is enrolling a broader population of patients with platinum-resistant ovarian cancer than other studies in this indication through more flexible inclusion criteria with respect to lines of therapy and underlying comorbidities, the use of a robust diagnostic assay capturing two-thirds of the patients as NaPi2b high for the primary endpoint, as well as a secondary endpoint in the overall population. The Company plans to enroll approximately 100 patients with high NaPi2b expression and up to 180 patients overall and expects the study to be substantially enrolled during the summer of 2022.

Enrollment continues in UPGRADE, the Company’s Phase 1 combination umbrella study. UPGRADE is a Phase 1 dose-escalation study evaluating the combination of carboplatin with UpRi followed by UpRi continued until progression. The dose escalation portion of the study is intended to determine the recommended Phase 2 dose in combination with carboplatin. The expansion portion of the study is intended to provide proof of concept for a potential new standard of care for platinum-sensitive ovarian cancer earlier in the disease by demonstrating that the combination of platinum and UpRi followed by UpRi continuation could result in improved efficacy and tolerability with the ultimate goal of improved clinical benefit for patients. The study will inform further development of UpRi in this broader and earlier line patient population.

Completed enrollment and evaluation of UpRi in the NSCLC adenocarcinoma expansion cohort. The Company observed modest single-agent activity that did not meet its internal threshold for advancement and has decided to deprioritize further clinical evaluation of UpRi in this indication. The safety profile of UpRi in lung adenocarcinoma was generally consistent with the favorable profile observed with UpRi at the 36 mg/m2 dose level selected for further advancement in ovarian cancer.
XMT-1592, first Dolasynthen ADC targeting NaPi2b:

Phase 1 dose escalation study of XMT-1592 is ongoing. The Company continues dose exploration in order to determine the recommended Phase 2 dose and expects this to continue into 2022. The Company plans to provide further details of the XMT-1592 development plan alongside its 2022 milestones and goals early next year.
XMT-1660, first-in-class Dolasynthen ADC targeting B7-H4:

Investigational New Drug (IND)-enabling studies of XMT-1660 ongoing with Phase 1 studies expected to start in early 2022. B7-H4 is expressed in high unmet need tumors such as breast, endometrial and ovarian. B7-H4 is expressed on both tumor cells and immunosuppressive tumor-associated macrophages (TAMs). This provides the potential for both a direct, cytotoxic antitumor effect as well as for additional payload delivery to the tumor microenvironment that could further contribute to immunogenic cell death, dendritic cell activation, and stimulation of an immune response consistent with the features of the Company’s unique DolaLock payload.
XMT-2056, first-in-class HER2-targeted Immunosynthen STING-agonist ADC:

Presented new preclinical data for XMT-2056 at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Triple Meeting) in October 2021. In vitro and in vivo studies demonstrate that Immunosynthen STING-agonist ADCs activate the STING pathway in both tumor-resident immune cells and tumor cells, offering the potential for an increased therapeutic index and an advantage over other innate immune activating pathways. The Company developed XMT-2056 based on a differentiated anti-HER2 antibody that binds a novel epitope, providing the opportunity for combinations with well-established anti-HER2 therapies. In preclinical models, XMT-2056 showed efficacy in combination with trastuzumab. In both high and low HER2 models, XMT-2056 demonstrated increased efficacy in comparison to benchmark agents such as a trastuzumab-TLR7/8 agonist ADC as well as a small molecule systemically-administered STING agonist. XMT-2056 was generally well-tolerated in non-human primate studies with no clinical signs and no adverse findings in clinical pathology or histopathology after single and repeat IV doses. The Company plans to initiate a Phase 1 study of XMT-2056 in early 2022.
Corporate:

Increased financial flexibility with additional access to capital. The Company entered into a new credit facility at favorable terms for up to $100 million with Oxford and Silicon Valley Bank of which $60 million is available immediately, with remaining balance primarily available upon achievement of certain pipeline and UpRi related milestones. In connection with this new facility, the Company retired the prior debt financing agreement with Silicon Valley Bank.
Strengthened leadership team with key appointments. In August 2021, the Company announced the appointment of Tushar Misra, Ph.D., as Chief Manufacturing Officer. Dr. Misra was most recently EVP, Head of Technical Development & Manufacturing at Laronde and has held senior leadership positions at Wave Life Sciences, Takeda Pharmaceuticals and Sunovion Pharmaceuticals. In October, the Company appointed Mohan Bala, Ph.D., as SVP, Strategic Product Planning & Program Leadership. Dr. Bala was most recently Chief Operating Officer at Constellation Pharmaceuticals and has over 20 years of clinical development and commercialization experience.
Upcoming Events

Mersana plans to present a poster entitled, "STING-agonist ADCs targeting tumor-associated antigens coordinate immune-mediated killing of antigen-negative cancer cells," at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) during the live poster display session available from November 12 – 13, 2021.
Mersana plans to give a corporate presentation at the 2021 Stifel Virtual Healthcare Conference scheduled for November 17, 2021.
Mersana plans to participate in a fireside chat at the Evercore ISI 4th Annual HealthconX scheduled for December 1, 2021.
Third Quarter 2021 Financial Results

Cash and cash equivalents as of September 30, 2021, were $191.7 million, compared to $255.1 million in cash and cash equivalents as of December 31, 2020. Net cash used in operating activities in the third quarter of 2021 was $36.1 million.

The Company expects that its available funds will be sufficient to support its operating plan commitments into the first half of 2023.

Research and development expenses for the third quarter of 2021 were $35.3 million, compared to $16.5 million for the same period in 2020. The difference was primarily due to an increase in manufacturing, clinical and regulatory expenses, an increase in headcount and advancement of diagnostic development efforts for the NaPi2b biomarker. Non-cash stock-based compensation expense included in these research and development expenses increased by $1.7 million.

General and administrative expenses for the third quarter of 2021 were $10.1 million, compared to $5.9 million during the same period in 2020 primarily due to an increase in headcount and consulting and professional fees. Non-cash stock-based compensation expense included in these general and administrative expenses increased by $1.4 million.
Net loss for the third quarter of 2021 was $45.5 million, or $0.63 per share, compared to net loss of $22.5 million, or $0.33 per share, for the same period in 2020. Weighted average common shares outstanding for the quarters ended September 30, 2021 and September 30, 2020 were 71,753,004 and 68,419,192, respectively.
Conference Call Details
Mersana Therapeutics will host a conference call today at 8:00 a.m. ET to report financial results for the third quarter 2021 and provide certain business updates. To access the call, please dial 877-303-9226 (domestic) or 409-981-0870 (international) and provide the Conference ID 2116349. A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com.

On November 9, 2021, (i) Teva Pharmaceutical Finance Netherlands II B.V. ("Teva Finance II"), a wholly owned subsidiary of Teva Pharmaceutical Industries Limited (the "Company"), reported that issued €1,100,000,000 aggregate principal amount of 3.750% Sustainability-Linked Senior Notes due 2027 (the "2027 Euro Notes") and €1,500,000,000 aggregate principal amount of 4.375% Sustainability-Linked Senior Notes due 2030 (the "2030 Euro Notes" and, together with the 2027 Euro Notes, the "Euro Notes"); and (ii) Teva Pharmaceutical Finance Netherlands III B.V (Filing, 8-K, Teva, NOV 9, 2021, View Source [SID1234595238]). ("Teva Finance III" and, together with Teva Finance II, the "Issuers"), a wholly owned subsidiary of the Company, issued $1,000,000,000 aggregate principal amount of 4.750% Sustainability-Linked Senior Notes due 2027 (the "2027 USD Notes") and $1,000,000,000 aggregate principal amount of 5.125% Sustainability-Linked Senior Notes due 2029 (the "2029 USD Notes" and, together with 2027 USD Notes, the "USD Notes" and together with the Euro Notes, the "Notes").

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Teva intends to use the net proceeds from the Notes to (i) fund the announced tender offer for a maximum combined aggregate purchase price (exclusive of accrued and unpaid interest) of up to $4,000,000,000 (equivalent) (upsized from a previously announced cap of $3,500,000,000), (ii) pay fees and expenses in connection therewith, (iii) to fund the repayment of outstanding debt upon maturity, tender offer or earlier redemption and (iv) the extent of any remaining proceeds, for general corporate purposes.

The Euro Notes were issued pursuant to a Senior Indenture, dated as of March 14, 2018 (the "Euro Notes Base Indenture"), by and among Teva Finance II, the Company, as guarantor, and The Bank of New York Mellon, as trustee, as supplemented by the Third Supplemental Indenture, dated as of November 9, 2021 (the "Euro Notes Supplemental Indenture" and, together with the Euro Notes Base Indenture, the "Euro Notes Indenture"), by and among Teva Finance II, the Company, as guarantor, The Bank of New York Mellon, as trustee, and The Bank of New York Mellon, London Branch, as paying agent. The USD Notes were issued pursuant to a Senior Indenture, dated as of March 14, 2018 (the "USD Notes Base Indenture"), as supplemented by the Third Supplemental Indenture, dated as of November 9, 2021 (the "USD Notes Supplemental Indenture" and, together with the USD Notes Base Indenture, the "USD Notes Indenture" and, together with the Euro Notes Indenture, the "Indentures"), in each case, by and among Teva Finance III, the Company, as guarantor, and The Bank of New York Mellon, as trustee.

Interest will be payable on the Notes semi-annually in arrears on May 9 and November 9 of each year, beginning on May 9, 2021, until their maturity dates of May 9, 2027 for the 2027 Euro Notes and the 2027 USD Notes, May 9, 2029 for the 2029 USD Notes and May 9, 2030 for the 2030 Euro Notes. The Euro Notes and the USD Notes are senior unsecured obligations of Teva Finance II and Teva Finance III, respectively, and the Notes are guaranteed on a senior unsecured basis by the Company.

From and including May 9, 2026 (the "Step-up Date"), the interest rate payable on the 2030 Euro Notes and the 2029 USD Notes shall increase by:

(a) 0.125% per annum unless Teva has achieved the Regulatory Submissions Target as of the Testing Date (each as defined in the Euro Notes Supplemental Indenture and the USD Notes Supplemental Indenture);

(b) 0.125% per annum unless Teva has achieved the Product Volume Target as of the Testing Date (each as defined in the Euro Notes Supplemental Indenture and the USD Notes Supplemental Indenture); and

(c) 0.125% per annum unless Teva has achieved the Emission Reduction Target as of the Testing Date(each as defined in the Euro Notes Supplemental Indenture and the USD Notes Supplemental Indenture);

At maturity or upon earlier redemption of the 2027 Euro Notes and/or the 2027 USD Notes (but only if such redemption is on or after the Step-up Date), the following premiums shall be payable on the 2027 Euro Notes and/or the 2027 USD Notes:

(a) 0.150% of the principal amount repaid unless Teva has achieved the Regulatory Submissions Target as of the Testing Date;

(b) 0.150% of the principal amount repaid unless Teva has achieved the Product Volume Target as of the Testing Date; and

(c) 0.150% of the principal amount repaid unless Teva has achieved the Emission Reduction Target as of the Testing Date.

Teva Finance II may redeem the Euro Notes of any series, in whole or in part, at any time or from time to time, upon at least 10 days’, but not more than 60 days’, prior notice delivered to the registered address of each holder of the Euro Notes to be redeemed with a copy of such notice delivered to the trustee and the paying agent. Subject to any adjustments in accordance with the premium payment for the 2027 Euro Notes, the Euro Notes will be redeemable at a redemption price equal to the greater of (1) 100% of the principal amount of the Euro Notes of such series to be redeemed or (2) the sum of the present values of the Remaining Scheduled Payments (as defined in the Euro Notes Indenture) of the Euro Notes of such series being redeemed discounted, on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months), at the applicable Reinvestment Rate (as defined in the Euro Notes Indenture), plus accrued and unpaid interest thereon, if any to, but not including, the redemption date; provided that if Teva Finance II elects to redeem the 2027 Euro Notes at any time on or after February 9, 2027 (three months prior to the maturity date of the 2027 Euro Notes) or to redeem the 2030 Euro Notes at any time on or after February 9, 2030 (three months prior to the maturity date of the 2030 Euro Notes), Teva Finance II may redeem the such Euro Notes, in whole or in part, at a redemption price equal to 100% of the principal amount of such series of Euro Notes then outstanding to be redeemed, plus accrued and unpaid interest thereon, if any, to, but not including, the redemption date.

Teva Finance III may redeem the USD Notes, of any series, in whole or in part, at any time or from time to time, upon at least 10 days’, but not more than 60 days’, prior notice. Subject to any adjustments in accordance the premium payment for the 2027 USD Notes, the USD Notes will be redeemable at a redemption price equal to the greater of (1) 100% of the principal amount of the USD Notes to be redeemed or (2) the sum of the present values of the Remaining Scheduled Payments (as defined in the USD Notes Indenture) of the USD Notes of such series being redeemed discounted, on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months), using a discount rate equal to the sum of the Treasury Rate (as defined in the USD Notes Indenture) plus 50 basis points, in the case of the 2027 USD Notes, and 50 basis points, in the case of the 2029 USD Notes, plus in each case accrued and unpaid interest thereon, if any, to, but not including, the redemption date; provided that if Teva Finance III elects to redeem the 2027 USD Notes at any time on or after February 9, 2027 (three months prior to the maturity date of the 2027 USD Notes) or to redeem the 2029 USD Notes at any time on or after February 9, 2029 (three months prior to the maturity date of the USD Notes), Teva Finance III may redeem the USD Notes, in whole or in part, at a redemption price equal to 100% of the principal amount of such series of USD Notes then outstanding to be redeemed, plus accrued and unpaid interest thereon, if any, to, but not including, the redemption date.

The terms of the Indentures, among other things and subject to specified exceptions, limit the ability of (a) the Company and its subsidiaries to (i) create liens upon certain of their property and (ii) enter into sale-leaseback transactions; and (b) the applicable Issuer and the Company to merge, consolidate or sell, lease or convey all or substantially all of their assets. The Indentures provide for customary events of default, which include (subject in certain cases to customary grace and cure periods), among others, nonpayment of principal or interest; breach of other covenants or agreements in the Indentures; acceleration of certain other indebtedness; failure of the Company’s guarantee to be enforceable; and certain events of bankruptcy or insolvency. The offering of the Notes was registered under the Securities Act of 1933, as amended (the "Securities Act"), and is being made pursuant to the Company’s Registration Statement on Form S-3ASR (File No. 333-260519) and the prospectus included therein (the "Registration Statement"), filed by the Company with the Commission on October 27, 2021, the preliminary prospectus supplement relating thereto, dated October 27, 2021, and filed with the Commission on October 27, 2021 pursuant to Rule 424(b)(3) promulgated under the Securities Act and the free writing prospectus related thereto, dated November 2, 2021, and filed with the Commission on November 2, 2021 pursuant to Rule 433 under the Securities Act.

The foregoing summary descriptions of the Euro Notes Base Indenture, Euro Notes Supplemental Indenture, USD Notes Base Indenture, USD Notes Supplemental Indenture and each series of Notes are not complete and are qualified in their entirety by reference to the Euro Notes Base Indenture, the Euro Notes Supplemental Indenture, the form of 2027 Euro Notes, the form of 2030 Euro Notes the USD Notes Base Indenture, the USD Notes Supplemental Indenture, the form of 2027 USD Notes and the form of 2029 USD Notes, which are filed as Exhibits 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7 and 4.8, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.

On November 9, 2021 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported its updated corporate presentation and recent webcasts (Press release, Greenwich LifeSciences, NOV 9, 2021, View Source [SID1234594841]).

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A webcast of the Company’s updated corporate presentation with comments by CEO Snehal Patel is available in the investor section of the Company’s website here.

Mr. Patel commented, "We are very excited to be presenting the combined analysis of our 5 year Phase IIb data from our recently published posters on one timeline, and we expect more upcoming publications. Integrated analysis of efficacy, immune response, and safety data has attracted the interest of large institutions, including large pharma, regional pharma, and biotech institutional investors, whom we are presenting to at investor and international partnering conferences. We have been discussing possible licensing of GP2, new investment banking partners, collaboration in our Phase III clinical trial, commercial manufacturing, expansion of our pipeline, expansion of our clinical trials in Europe, and initiation of additional GP2 Phase II/III trials."

Additional webcasts of Mr. Patel’s participation on a Benzinga cancer panel and a TD Ameritrade interview can be viewed at the links below:

On September 30, 2021, Mr. Patel participated in a live panel discussion at the Benzinga Healthcare Small-Cap Conference entitled: Immuno-Oncology – Harnessing the Human Body’s Power to Battle Cancer. A webcast of the entire panel discussion can be seen here with Mr. Patel speaking at the time points available at these links: 2:15, 18:03, and 34:00.

On July 20, 2021, Mr. Patel appeared as a featured guest in a live interview on TD Ameritrade Network’s The Watch List with host Nicole Petallides. A webcast of the interview can be seen here.

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.