10-Q – Quarterly report [Sections 13 or 15(d)]

Epizyme has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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AnPac Bio Announces Pricing of Approximately $2.9 Million Underwritten Public Offering of American Depositary Shares

On November 9, 2021 AnPac Bio-Medical Science Co., Ltd. (NASDAQ: ANPC, the "Company"), a biotechnology company with operations in China and the United States focusing on early cancer screening and detection, reported the pricing of an underwritten public offering of 1,301,928 of its American Depositary Shares ("ADSs") at a public offering price of $2.22 per share, for gross proceeds to the Company of approximately $2.9 million, before deducting the underwriting discount and other offering expenses payable by the Company (Press release, Anpac Bio, NOV 9, 2021, View Source [SID1234595377]). This includes the full exercise of the underwriter’s over-allotment option.

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EF Hutton, division of Benchmark Investments, LLC is acting as the sole book-running manager for the offering. The offering is expected to close on or about November 12, 2021, subject to customary closing conditions.

The shares of ADSs described above are being offered by AnPac Bio-Medical Science Co., Ltd. pursuant to a "shelf" registration statement on Form F-3 (File No. 333-256630) that became effective with the Securities and Exchange Commission (SEC) on June 7, 2021, the base prospectus contained therein and the accompanying prospectus supplement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

IASO Biotheraputics Completes Enrollment of First Patient in CT120’s Phase I/II Registrational Clinical Trial

On November 9, 2021 IASO Biotherapeutics (IASO Bio), a clinical-stage biopharmaceutical company engaged in discovering, developing, and manufacturing innovative medicines, reported that the company’s in-house-developed fully human CD19/CD22 dual-targeted chimeric antigen receptor (CAR)-T cell therapy (CT120) has completed enrollment of the first patient in the phase I/II registrational clinical trial for the treatment of CD19/CD22-positive relapsed/refractory B-cell non-Hodgkin’s lymphoma (r/r B-NHL) (Press release, IASO Biotherapeutics, NOV 9, 2021, View Source [SID1234595332]). CT120 is the first fully human dual-targeted CAR-T cell therapy approved to enter the clinical stage. The clinical trial of CT120 in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) will also start soon.

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The study is a phase I/II, multi-center clinical trial (registration number: CTR20212328). The phase I trial aims to evaluate the safety and tolerability of CT120 in patients with r/r B-NHL and to determine the maximum tolerated dose (MTD) of CT120 treatment and/or the recommended phase 2 dose (RP2D). The phase II trial aims to evaluate the efficacy of CT120 in the treatment of patients with B-NHL.

"This clinical trial greatly reduces the economic burden on patients, and makes it possible for them to benefit early from this innovative drug," said Professor Jianfeng Zhou at Tongji Hospital of Tongji Medical School of Huazhong University of Science and Technology, the principal investigator of the trial. "CT120 is the first dual-targeted CAR-T cell therapy to enter the clinical stage. Compared with available single-targeted CAR-T cell therapy, CT120 is expected to further reduce the risk of tumor recurrence clinically and prolong patient survival. In the exploratory clinical trial, CT120 has shown well-tolerated safety and good efficacy. Our hospital will take an ethics- and science-based approach to work with all partners to advance the trial so as to benefit more patients."

Dr. Wen (Maxwell) Wang, CEO of IASO Bio said, "On October 13th we received approval from the Human Genetic Resources Administration of China, on the 14th we signed a research agreement with Tongji Hospital, and on the 15th we held the project kick-off meeting. After screening, the first patient was enrolled at the end of October. We’d like to sincerely thank Professor Zhou for working closely with our team throughout the process."

"CT120 is the first fully human dual-targeted CAR-T candidate, and a highly innovative product independently developed by IASO Bio. The IIT study showed that CT120 can benefit not only CAR-T-naïve patients with relapsed/refractory B-NHL or B-ALL, but also patients whose disease progressed during or after treatment with the murine single-targeted CD19 CAR-T cell therapy. The company still has a pipeline of competitive products that are expected to achieve IND milestones. We look forward to leveraging our world-leading platform IMARS to develop more innovative fully human products and deliver on our mission of ‘making innovative treatment the backbone therapy to cure patients’," Dr. Wang noted.

About CT120

CT120 is an autologous dual-target CAR-T therapy. Its extracellular domain contains two fully human single-chain fragment variable (scFv) sequences that can specifically bind to CD19 and CD22, identifying tumor cells with CD19 and CD22 expressions, thereby reducing the tumor escape caused by the loss of target antigen. Adopting a fully human design, CT120 has low immunogenicity, reduces the ADA effect, and improves CAR-T cells’ viability.

Compared to the intracellular costimulatory signal CD28, CT120’s intracellular costimulatory signal 4-1BB and CD3ζ have lower neurotoxicity and improved viability of CAR-T cells, thus more durable efficacy. Upon binding with CD19/CD22 antigens on the tumor cells, CT120 eliminates targeted tumor cells through the release of granzyme and perforin while simultaneously releases cytokine to promote the proliferation of CAR-T cells, thus achieves its durable antitumor activity.

About Non-Hodgkin Lymphoma (NHL)

Lymphoma arises from immune cells. It may cause various organ damage and is commonly associated with a complicated pathological process. Lymphoma has two subtypes: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). NHL accounts for around 90% of all lymphoma cases, and 85% of NHL cases are B-NHL, which has numerous subtypes, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and small lymphocytic lymphoma (CLL). According to a Frost & Sullivan report, there were approximately 92,800 new incidences of NHL in China in 2020 with a total patient population of 514,200 and is expected to reach 632,300 in 2025. NHL has a high mortality rate, with a five-year survival rate of just 37% in China. The National Cancer Institute reports that the rate of new cases of non-Hodgkin lymphoma was 19.6 per 100,000 men and women per year. The death rate was 5.4 per 100,000 men and women per year. Non-Hodgkin lymphoma represents 4.3% of all new cancer cases in the U.S.

Novartis Walks Away from $2.6 Billion Xencor Collaboration

On November 9, 2021 Xencor reported Novartis terminated its rights to develop vibecotamab, a CD123 x CD3 blood cancer bispecific, which was part of a 2016 collaboration valued at $2.6 billion (Press release, Xencor, NOV 9, 2021, View Source [SID1234595329]).

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Since the collaboration was first forged, Novartis has slowly stepped away from the partnership. In 2019, the Swiss pharma giant backed away from developing XmAb13676, a CD20 x CD3 bispecific antibody, following a strategic pipeline reprioritization. Now, Novartis is terminating rights to the vibecotamab program, effective February 2022.

In 2019, shortly after Novartis dumped development rights to XmAb13676, the other asset was hit with a partial clinical hold by the U.S. Food and Drug Administration. The CD123 x CD3 blood cancer bispecific was assessed in a Phase I study for acute myeloid leukemia. Two patients in the trial died.

CD123 is a tumor-associated antigen overexpressed on the surface of some tumor cells. The CD3 complex is a group of proteins on the surface of T-cells. Multiple companies have taken this approach against leukemia, but results have been less than encouraging.

In 2016, Janssen and Genmab saw a hold placed on their CD123 x CD3 candidate for acute myeloid leukemia. Cellectis also caught a clinical hold on two Phase I trials of its CD123 asset, UCART123.

Xencor announced Novartis’ decision in its third quarter financial report. The company stated that it would continue the ongoing study of vibecotamab, but it no longer intends further internal development of the drug once it is complete.

There is still hope that something from the partnership with Novartis could be salvaged through the development of another asset. Earlier this year, the larger company selected a candidate to develop. The outcome for that study is still off in the future.

Although the partnership with Novartis has taken a significant blow, Xencor could see fruit from a collaboration with Janssen. In October, the two companies entered into a partnership to advance the development of plamotamab and XmAb CD28 bispecific antibody combinations to treat patients with B-cell malignancies. Under terms of that deal, Janssen secured exclusive worldwide development and commercial rights to plamotamab, an investigational tumor-targeted XmAb bispecific antibody, currently in Phase I clinical development as a potential treatment for patients with CD20-expressing hematologic malignancies.

Xencor is paying 20% of costs, including those for a subcutaneous formulation study that is expected to enter clinical studies in 2022. In the meantime, Xencor will continue, at its own expense, the combination study of plamotamab, tafasitamab and lenalidomide.

Xencor is also partnered with Bristol Myers Squibb on the development of potential antibody treatment for COVID-19. The two companies will advance the development of Xencor’s Xtend Fc technology.

Entry into a Material Definitive Agreement.

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.