On December 13, 2019 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, and Mirati Therapeutics (NASDAQ:MRTX), a clinical-stage targeted oncology company, reported preliminary data from an ongoing Phase 1b trial of investigational anti-PD-1 antibody tislelizumab in combination with investigational tyrosine kinase inhibitor sitravatinib in patients with platinum-resistant ovarian cancer, which demonstrated antitumor activity and was generally well tolerated (Press release, BeiGene, DEC 13, 2019, View Source [SID1234552364]). Results from the Phase 1b clinical trial were presented at the 2019 European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress on December 13, 2019 in Geneva, Switzerland.

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"Tislelizumab and sitravatinib have both demonstrated antitumor activity as single agents, so we’re encouraged by the early evidence showing the potential for these two agents to work together to treat advanced solid tumors, including platinum-resistant ovarian cancer," said Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. "We continue to make progress in the collaboration with Mirati Therapeutics and we look forward to continued enrollment in the trial and further clinical data on the combination of tislelizumab and sitravatinib, a compound that has a unique tyrosine kinase inhibition profile."

"We were eager to enter into this collaboration with BeiGene because we believe sitravatinib, a spectrum-selective receptor tyrosine kinase inhibitor, may help increase the activity of anti-PD-1 antibodies such as tislelizumab in patients whose solid tumors exhibit resistance," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer, Mirati Therapeutics, Inc. "The initial results from this Phase 1b trial suggest further development of this combination for the treatment of advanced solid tumors, including platinum-resistant ovarian cancer, is warranted."

Summary of Preliminary Results from the Phase 1b Trial in Platinum-Resistant Ovarian Cancer

Abstract 94O

This open-label, multi-center Phase 1b trial (NCT03666143) of tislelizumab in combination with sitravatinib consists of nine disease-specific cohorts in patients with advanced solid tumors. The results presented at ESMO (Free ESMO Whitepaper) I-O were from cohort E in 20 patients with recurrent platinum-resistant ovarian cancer who did not have prior exposure to anti-PD-1/PD-L1 agents. Patients were treated with tislelizumab at 200 mg IV every three weeks and sitravatinib at 120mg orally once daily. At the data cutoff of July 17, 2019, 17 patients were evaluable and preliminary results included:

Seven patients achieved a partial response (PR), including four confirmed PRs; the overall response rate (ORR) was 23.5% (4/17, 95% CI: 6.8%, 49.9%); eight patients achieved stable disease (SD);

The median duration of response (DoR) was not reached (95% CI: 12.29 weeks, not reached);

The median progression-free response (PFS) was 18 weeks (95% CI: 12.29 weeks, not reached), and the PFS rate at 3 months and 6 months was 88.2% (95% CI: 60.6%, 96.9%) and 35.3% (95% CI: 9.0%, 63.8%), respectively;

All 20 patients in this cohort experienced treatment-emergent adverse events (TEAEs) of any grade;

Fifteen patients (75%) experienced at least one grade ≥ 3 TEAE, with the most common being hypertension (25%) and fatigue (10%);

Immune-related TEAEs were hypothyroidism (20%), diarrhea (15%), and rash (15%);

Six patients (30%) discontinued the study treatment due to TEAEs; and

Two patients experienced TEAEs leading to death, abdominal pain and respiratory failure, both of which were considered unrelated to treatment by the study investigator.
BeiGene and Mirati entered into an exclusive license agreement for the development, manufacturing and commercialization of Mirati’s sitravatinib in Asia (excluding Japan), Australia, and New Zealand in January 2018. Clinical trials for tislelizumab and sitravatinib are ongoing in patients with non-small cell lung cancer, renal cell carcinoma, melanoma, hepatocellular cancer and gastric cancer.

About Tislelizumab

Tislelizumab (BGB-A317) is an investigational humanized IgG4 anti–PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug candidate produced from BeiGene’s immuno-oncology biologics program and is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

Select ongoing clinical trials of tislelizumab include a Phase 3 clinical trial in patients with second-line or third-line non-small cell lung cancer (NSCLC); a Phase 3 clinical trial in first-line patients with hepatocellular carcinoma (HCC); a Phase 3 clinical trial in second-line patients with esophageal squamous carcinoma (ESCC); a Phase 3 clinical trial in first-line patients with gastric cancer (GC); a Phase 3 clinical trial in first-line patients with ESCC; and a Phase 2 clinical trial in second- or third-line patients with HCC. The aforementioned trials are enrolling patients in multiple countries, including the United States, Europe, and China.

In addition to a pivotal Phase 2 clinical trial in patients with relapsed or refractory (R/R) classical Hodgkin’s lymphoma (cHL) and a pivotal Phase 2 clinical trial in patients with locally advanced or metastatic urothelial cancer, BeiGene is conducting a Phase 3 clinical trial in first-line patients with non-squamous NSCLC; a Phase 3 clinical trial in first-line patients with squamous NSCLC; a Phase 3 clinical trial in patients with first-line nasopharyngeal cancer (NPC); a Phase 3 clinical trial in first-line patients with urothelial carcinoma (UC); a Phase 3 clinical trial in patients with localized ESCC; and a Phase 2 trial in patients with MSI-H or dMMR solid tumors. These studies have been enrolling patients primarily in China.

New drug applications (NDA) for tislelizumab in patients with R/R cHL and in patients with previously treated locally advanced or metastatic UC have been accepted and granted priority review by the China National Medical Products Administration (NMPA, formerly known as CFDA). BeiGene has full development and commercial rights to tislelizumab worldwide.

About Sitravatinib

Sitravatinib is an investigational spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combinations of anti-PD-1 checkpoint inhibitors, in patients whose cancers have progressed despite treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including the ongoing potentially registration-enabling Phase 3 trial of sitravatinib in combination with a checkpoint inhibitor in non-small cell lung cancer (NSCLC). In addition, sitravatinib combinations with checkpoint inhibitors are being evaluated in selected checkpoint inhibitor naïve patients.

Sitravatinib is also being evaluated as a single-agent in a Phase 1b expansion clinical trial emphasizing enrollment of patients whose tumors harbor specific mutations in the CBL protein. When CBL is inactivated by mutation, multiple RTKs, including TAM, VEGFR2 and KIT, are dysregulated and may act as oncogenic tumor drivers in NSCLC and melanoma.

On December 13, 2019 OncoSec Medical Incorporated ("OncoSec") (Nasdaq:ONCS), a company developing late-stage intratumoral cancer immunotherapies, reported interim results from KEYNOTE-890, an ongoing Phase 2 study of TAVO (intratumoral IL-12) in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 checkpoint inhibitor, in patients with metastatic, chemotherapy-refractory triple negative breast cancer (mTNBC) (Press release, OncoSec Medical, DEC 13, 2019, View Source [SID1234552363]).

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Patients who previously had progressed after an average of three prior lines of chemotherapy were enrolled in the KEYNOTE-890 study to evaluate if the addition of TAVO could provide meaningful clinical activity when combined with KEYTRUDA. The interim analysis, presented on December 12, 2019, at the San Antonio Breast Cancer Symposium, included more than half of the patients (14 out of 25) enrolled in the KEYNOTE-890 study evaluating tumor responses, related immunological responses and safety.

Four of the 14 patients showed a rapid tumor reduction and had a confirmed partial response by RECIST v1.1 (ORR 28.5%), including a deep partial response in a patient with multiple liver, bone, skin and nodal metastases and a short disease-free interval following neoadjuvant chemotherapy. All responses are ongoing (range: 6 to 9 months) and a median duration of response (DOR) has not yet been reached. Three of the four patients with a partial response experienced deepening tumor shrinkage over six months.

These interim findings compare favorably to the response rate (range of 6-10%) observed with KEYTRUDA as a monotherapy in mTNBC patients 1,2.

Stable disease was observed in three patients (21.4%), with two stable disease patients reporting 20% or greater tumor shrinkage. Of the seven patients who progressed following treatment, two received only one cycle of combination treatment prior to rapid clinical deterioration. Regression of both TAVO treated and untreated lesions were observed. Regression of distal visceral lesions were also observed. Additionally, 3 of the 4 responding patients’ lesions were PD-L1 negative by IHC analysis before treatment (1 patient was undetermined).

"Metastatic TNBC is a heterogeneous disease with a poor prognosis where very few pre-treated patients achieve an objective response to PD-1/PD-L1 checkpoint inhibitor therapy," said Melinda L. Telli, MD, Stanford University School of Medicine. "These preliminary data suggest that TAVO may enhance sensitivity to pembrolizumab in mTNBC patients with a 28.5% ORR reported. I’m encouraged by the tumor responses observed in PD-L1 negative patients and the overall safety profile."

Importantly, TAVO and pembrolizumab were well tolerated, with only 3 of 16 patients experiencing grade 3 treatment-related adverse events with combination treatment.

Patients demonstrated encouraging immunological responses in tumor and blood consistent with an IL-12-associated mechanism of action, including significantly increased on-treatment proliferating T cell subsets in the periphery and increased gene expression signatures associated with productive immunological responses in the tumor. Biomarker analysis of patient tumor and blood samples are ongoing.

"These data show a strong signal for clinical benefit with TAVO enhancing sensitivity to pembrolizumab in treating metastatic TNBC patients who were previously unresponsive to multiple prior rounds of therapy," said Kellie Malloy, Chief Clinical Development Officer at OncoSec. "They also confirm the consistent safety profile of TAVO as a well-tolerated cancer immunotherapy. We look forward to continuing development and plan to expand this clinical program and the KEYNOTE-890 trial."

To date, the KEYNOTE-890 study has enrolled 24 of the planned 25 patients. OncoSec expects to report the full data results in 2020.

About Triple Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. As a result, TNBC does not respond to therapies targeting these markers, making it more difficult to treat. Approximately 10-20% of patients with breast cancer are diagnosed with TNBC.

About KEYNOTE-890

KEYNOTE-890 is designed as a multicenter Phase 2 open-label trial focusing on patients with a histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC and at least 1 prior line of approved systemic chemotherapy or immunotherapy. 25 patients are expected to be enrolled. Each patient will undergo 3-week treatment cycles with pembrolizumab administered as a 30-minute IV infusion day 1 of every cycle (flat dose of 200 mg) and treated with TAVO on days 1, 5 and 8 every six weeks.

On December 13, 2019 Omeros Corporation (Nasdaq: OMER) ("Omeros"), a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, complement-mediated diseases, disorders of the central nervous system and immune-related diseases, including cancers, reported the full exercise and closing of the sale of 572,518 shares of common stock to the underwriter of its previously announced public offering pursuant to the underwriter’s option under the underwriting agreement to purchase additional shares of common stock (Press release, Omeros, DEC 13, 2019, View Source [SID1234552362]). When combined with shares sold in the closing that occurred on December 9, 2019, Omeros sold an aggregate of 4,389,311 shares of common stock in the offering at $13.10 per share and the total gross proceeds to Omeros, before deduction of underwriting discounts and other estimated offering expenses, were approximately $57.5 million.

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Cantor Fitzgerald & Co. acted as the sole book-running manager for the offering.

Omeros intends to use the net proceeds from the offering for general corporate purposes, including funding clinical trials, pre-clinical studies, manufacturing, build out of commercial infrastructure and other costs associated with advancing its development programs and product candidates toward regulatory submissions and potential commercialization. Omeros may also use the net proceeds for working capital, the repayment of debt obligations, acquisitions or investments in businesses, products or technologies that are complementary to its own, and other required capital expenditures.

The securities described above were offered by Omeros pursuant to a shelf registration statement on Form S-3 (File No. 333- 235349) that was filed with the Securities and Exchange Commission (the "SEC") on December 4, 2019, which became automatically effective upon filing. A final prospectus supplement relating to and describing the terms of the offering was filed with the SEC on December 6, 2019 and is available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained by contacting Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Ave., 6th Floor, New York, New York 10022, or by email at [email protected].

On December 13, 2019 West Pharmaceutical Services, Inc. (NYSE: WST), a global leader in innovative solutions for injectable drug administration, reported that the Company’s Board of Directors has approved a first-quarter 2020 dividend of $0.16 per share (Press release, West Pharmaceutical Services, DEC 13, 2019, View Source [SID1234552361]). The dividend will be paid on February 5, 2020, to shareholders of record as of January 22, 2020.

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On December 10, 2019, the Company’s Board of Directors authorized a share repurchase program for calendar-year 2020 authorizing the repurchase of up to 848,000 shares of the Company’s common stock from time to time on the open market or in privately-negotiated transactions, as permitted under Exchange Act Rule 10b-18. The number of shares to be repurchased and the timing of such transactions will depend on a variety of factors, including market conditions. The share repurchase program is expected to be completed by December 31, 2020. The Company’s previously-authorized share repurchase program will expire on December 31, 2019.

The Company also announced that management will be presenting an overview of the business at the J.P. Morgan Healthcare Conference in San Francisco, California, at 4:30 p.m. PST on Wednesday, January 15, 2020.

A live audio webcast of the presentations and a copy of the presentation materials will be accessible from the Company’s website at www.westpharma.com/en/investors.

On December 13, 2019, Sarepta Therapeutics, Inc. (the "Company") reported that it entered into a loan agreement (the "Credit Agreement") with BioPharma Credit PLC, a public limited liability company incorporated under the laws of England and Wales, as the collateral agent and a lender ("BioPharma"), and BioPharma Credit Investments V (Master) LP, a Cayman Islands exempted limited partnership, as a lender (together with BioPharma in its capacity as a lender, and each of their respective successors and assigns at any time party to the Credit Agreement, the "Lenders" and each a "Lender") that provides for a senior secured term loan facility of up to $500.0 million to be funded in two tranches: (i) a Tranche A Loan in an aggregate principal amount of $250.0 million (the "Tranche A Loan") to be funded on or about December 20, 2019 (the "Tranche A Funding Date"), subject to entering into a security agreement (the "Security Agreement") and delivery of other customary deliverables; and (ii) a Tranche B Loan in an aggregate principal amount of up to $250.0 million (the "Tranche B Loan", and together with the Tranche A Loan, the "Term Loans"), to be funded at the option of the Company, and at the Company’s option, in increments of $50.0 million and no later than December 31, 2020, and in any event upon no less than 75 days’ notice (unless the Lenders agree to a shorter notice period) (Filing, 8-K, Sarepta Therapeutics, DEC 13, 2019, View Source [SID1234552360]).

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The Term Loans mature on the 48th-month anniversary of the Tranche A Funding Date (the "Maturity Date"). Borrowings under the Credit Agreement bear interest at a fixed rate equal to 8.50% per annum payable quarterly in arrears. 50.0% of the interest on the Tranche A Loan payable during the first twelve (12) months following the Tranche A Funding Date may be paid-in-kind at the election of the Company. All unpaid principal (including accrued and capitalized paid-in-kind interest) with respect to the Term Loans is due and payable on the Maturity Date.

The Company will pay to each Lender a funding fee equal to 1.75% on the funded amount of the Term Loans, payable when each Term Loan is funded. At the time of prepayment or repayment of any amount of the Term Loans, the Company will pay to each Lender a fee equal to 2.00% of the Term Loans held by such Lender being prepaid or repaid. In addition, in the event a tranche is prepaid in whole or in part prior to the Maturity Date, it will be subject to a prepayment fee. On or prior to the third anniversary of the applicable funding date, the prepayment fee is 2.00% of the principal amount prepaid, thereafter and prior to the Maturity Date, the prepayment fee is 1.00% of the principal amount prepaid. In addition to the prepayment fees, in connection with a full or partial prepayment of a tranche prior to the second anniversary of the applicable funding, a "make-whole" amount will be payable equal to the foregone interest from the date of prepayment through the second anniversary.

All obligations under the Credit Agreement as of the Tranche A Funding Date will be secured, subject to certain exceptions, by security interests in (collectively, the "Collateral"): (1) U.S. intellectual property owned by, and rights to U.S. intellectual property licensed to, the Company relating to any pharmaceutical composition in which eteplirsen or golodirsen is indicated to be administered for use in the treatment of Duchenne muscular dystrophy ("DMD") in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 or 53 skipping, respectively, or for any other use approved by the FDA (the "Products"), (2) 100% of the equity interests directly held by the Company in certain wholly owned domestic subsidiaries and 65% of the equity interests in certain other wholly owned domestic subsidiary, and (3) all of the Company’s personal property, including, without limitation, cash held in all deposit accounts of the Company. Any non-U.S. intellectual property related to the Products and intellectual property unrelated in any way to the Products anywhere are not part of the Collateral.

The Credit Agreement contains negative covenants that, among other things and subject to certain exceptions, restrict the Company’s ability to:

sell or dispose of assets, including certain intellectual property;

amend, modify or waive certain material agreements or organizational documents;

consolidate or merge;

incur additional indebtedness;

incur additional liens on the Collateral;

pay dividends or make any distribution or payment on or redeem, retire or purchase any equity interests; and

make payments of certain subordinated indebtedness.

The Credit Agreement requires the Company to have consolidated liquidity of at least $100,000,000 as of the last day of each month. Additionally, the Credit Agreement contains certain customary representations and warranties, affirmative covenants and provisions relating to events of default, including nonpayment of principal, interest and other amounts; failure to comply with covenants; the occurrence of a material adverse change in (i) the ability of the Company to fulfill the payment or performance obligations under the Credit Agreement and related documents or (ii) the binding nature of the Credit Agreement and related documents; the rendering of judgments or orders or the acceleration or payment default by the Company in respect of other indebtedness in excess of $10 million; and certain insolvency and ERISA events. A change of control of the Company triggers a mandatory prepayment of the Term Loans.