On November 22, 2019 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported updated Phase 1 data for single agent ZW25 in heavily pretreated patients with HER2‑expressing solid tumors in a mini oral presentation by Dr. Do-Youn Oh, study investigator and Professor at Seoul National University, at the ESMO (Free ESMO Whitepaper) Asia 2019 Congress, taking place November 22 – 24 in Singapore (Press release, Zymeworks, NOV 22, 2019, View Source [SID1234551595]). Zymeworks and its collaborator BeiGene, Ltd. plan to advance ZW25 into potentially registration-enabling global studies in HER2-expressing biliary tract cancer (BTC) and gastroesophageal adenocarcinoma (GEA), based on these durable and consistent clinical data.

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"The promising ZW25 data at ESMO (Free ESMO Whitepaper) Asia further build momentum for the expanding footprint of our ZW25 clinical development program with BeiGene," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "Cancer is a global fight, and this strong collaboration helps us to rapidly execute on upcoming late-stage studies for people with HER2-expressing cancers worldwide."

"The encouraging clinical data on ZW25 supports further evaluation of this bispecific antibody in HER2-expressing solid tumors," said John V. Oyler, Co-Founder, CEO, and Chairman of BeiGene. "We’re enthusiastic about the meaningful progress of ZW25 since we established the collaboration with Zymeworks one year ago and look forward to leveraging our unique strengths and expertise to advance ZW25 clinical development globally."

The updated single agent results of the ongoing Phase 1 trial of ZW25 in patients with HER2‑expressing solid tumors include additional safety and anti-tumor activity data from those presented at the ESMO (Free ESMO Whitepaper) 2019 Congress.

ZW25 Clinical Results Presented Today

Safety, Anti-Tumor Activity, and Biomarker Results of the HER2-Targeted Bispecific Antibody ZW25 in HER2-Expressing Solid Tumors (Presentation# 61O, Mini Oral on Friday, November 22 at 3:30 pm SGT)

Data were reported from 69 patients diagnosed with HER2-expressing solid tumors other than breast cancer who received ZW25 at the recommended dose of either 10 mg/kg weekly or 20 mg/kg every other week. Overall, patients received a median of three prior systemic therapies. Those with BTC, GEA, and colorectal cancer (CRC) received a median of 4.5, 3, and 5.5 prior systemic therapies, respectively. Forty-one (59%) patients received prior HER2‑targeted therapies, including 93% of GEA patients. Eleven patients were diagnosed with BTC, 28 with GEA, 14 with CRC, and 16 with other HER2‑expressing cancers, including endometrial, ovarian, pancreatic, and salivary gland.

Fifty-seven of 69 patients were response evaluable at the time of data cut-off. Overall, the disease control rate (DCR) was 70%, comprising 25 (44%) partial responses and 15 (26%) with stable disease, and 18 (32%) patients experienced disease control for greater than six months. In the nine evaluable biliary tract cancer patients, the DCR was 78%, and the objective response rate (ORR) was 67%. In the 13 CRC and 23 GEA patients, ORRs were 46% and 39%, respectively. Notably, confirmed responses were seen across additional tumor types, including a 100% decrease in target lesions in a patient with pancreatic cancer. The overall median progression-free survival was 5.5 months and is still evolving.

Among all patients, ZW25 was well tolerated as an outpatient therapy. The most common treatment-related adverse events (TRAE) were diarrhea (43%), infusion-related reaction (26%), and nausea (13%). All TRAEs were Grade 1 or 2.

About the Phase 1 Clinical Trial

Zymeworks’ Phase 1 study has three parts. From part one of the study (the dose-escalation phase), the recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly. In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess ZW25’s single-agent tolerability and anti-tumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase) is underway and evaluating ZW25 in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels. More information about ZW25 clinical trials can be found at clinicaltrials.gov.

About ZW25

ZW25 is being evaluated in Phase 1 and Phase 2 clinical trials across North America and South Korea. It is a 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 anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. The FDA has granted Fast Track designation to ZW25 for first-line gastroesophageal adenocarcinoma in combination with standard of care chemotherapy and Orphan Drug designation to ZW25 for the treatment of both gastric and ovarian cancers.

On November 21, 2019, AbbVie Inc. ("AbbVie") reported that sale of $30 billion aggregate principal amount of its senior unsecured notes, consisting of (i) $750,000,000 aggregate principal amount of senior floating rate notes due May 2021 (the "May 2021 Floating Rate Notes"), (ii) $750,000,000 aggregate principal amount of senior floating rate notes due November 2021 (the "November 2021 Floating Rate Notes"), (iii) $750,000,000 aggregate principal amount of senior floating rate notes due 2022 (the "2022 Floating Rate Notes"), (iv) $1,750,000,000 aggregate principal amount of 2.150% senior notes due 2021 (the "2021 Notes"), (v) $3,000,000,000 aggregate principal amount of 2.300% senior notes due 2022 (the "2022 Notes"), (vi) $3,750,000,000 aggregate principal amount of 2.600% senior notes due 2024 (the "2024 Notes"), (vii) $4,000,000,000 aggregate principal amount of 2.950% senior notes due 2026 (the "2026 Notes"), (viii) $5,500,000,000 aggregate principal amount of 3.200% senior notes due 2029 (the "2029 Notes"), (ix) $4,000,000,000 aggregate principal amount of 4.050% senior notes due 2039 (the "2039 Notes") and (x) $5,750,000,000 aggregate principal amount of 4.250% senior notes due 2049 (the "2049 Notes" and, together with the May 2021 Floating Rate Notes, the November 2021 Floating Rate Notes, the 2022 Floating Rate Notes, the 2021 Notes, the 2022 Notes, the 2024 Notes, the 2026 Notes, the 2029 Notes and the 2039 Notes, the "Notes").

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The offering of the Notes (the "Offering") was made pursuant to a confidential offering memorandum, dated November 12, 2019.

The Notes are governed by an indenture, dated November 8, 2012 (the "Base Indenture"), by and between AbbVie and U.S. Bank National Association, as trustee (the "Trustee"), as supplemented by Supplemental Indenture No. 7, dated November 21, 2019 (the "Supplemental Indenture"), by and between AbbVie and the Trustee. The Notes are unsecured, senior obligations of AbbVie and will rank equally in right of payment with all of AbbVie’s existing and future unsecured, senior indebtedness, liabilities and other obligations.

The May 2021 Floating Rate Notes will bear interest at a floating rate, reset quarterly, equal to the Benchmark (as defined in the Supplemental Indenture), which will initially be three-month London Inter-Bank Offered Rate ("LIBOR") plus 0.350% per annum, and will mature on May 21, 2021. The November 2021 Floating Rate Notes will bear interest at a floating rate, reset quarterly, equal to the Benchmark, which will initially be three-month LIBOR plus 0.460% per annum, and will mature on November 19, 2021. The 2022 Floating Rate Notes will bear interest at a floating rate, reset quarterly, equal to the Benchmark, which will initially be three-month LIBOR plus 0.650% per annum, and will mature on November 21, 2022. The 2021 Notes will bear interest at a rate of 2.150% per annum and will mature on November 19, 2021. The 2022 Notes will bear interest at a rate of 2.300% per annum and will mature on November 21, 2022. The 2024 Notes will bear interest at a rate of 2.600% per annum and will mature on November 21, 2024. The 2026 Notes will bear interest at a rate of 2.950% per annum and will mature on November 21, 2026. The 2029 Notes will bear interest at a rate of 3.200% per annum and will mature on November 21, 2029. The 2039 Notes will bear interest at a rate of 4.050% per annum and will mature on November 21, 2039. The 2049 Notes will bear interest at a rate of 4.250% per annum and will mature on November 21, 2049.

The Offering was conducted in connection with AbbVie’s previously announced acquisition (the "Acquisition") of Allergan plc ("Allergan"). AbbVie expects to use the net proceeds from the Offering to fund a portion of the aggregate cash consideration due to Allergan shareholders in connection with the Acquisition and to pay related fees and expenses, with any remaining net proceeds being used for general corporate purposes. If (i) the Acquisition has not been consummated on or prior to January 30, 2021 or (ii) prior to such date, AbbVie notifies the Trustee that it will not pursue the consummation of the Acquisition, then AbbVie will be required to redeem all of the Notes then outstanding at a special mandatory redemption price equal to 101% of the aggregate principal amount of the Notes, plus accrued and unpaid interest, if any, to, but not including, the applicable special mandatory redemption date.

Following the closing of the Offering, the commitments under the bridge credit facility entered into by AbbVie, as borrower, on June 25, 2019 were reduced to $2,200,360,000 as a result of AbbVie receiving net cash proceeds from the issuance of the Notes.

The foregoing summary of the Notes does not purport to be complete and is qualified in its entirety by reference to the full text of (i) the Base Indenture attached as Exhibit 4.1 hereto; (ii) the Supplemental Indenture attached as Exhibit 4.2 hereto; and (iii) the forms of the Notes attached as Exhibits 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 4.10, 4.11 and 4.12 hereto, the terms of which are in each case incorporated herein by reference.

On November 21, 2019 Biogen Inc. (Nasdaq: BIIB) reported that it will present at the Evercore ISI 2nd Annual HealthCONx Conference (Press release, Biogen, NOV 21, 2019, http://investors.biogen.com/news-releases/news-release-details/biogen-present-evercore-isi-2nd-annual-healthconx-conference [SID1234551616]). The webcast will be live on Tuesday, December 3, at 11:45a.m. ET, with Anirvan Ghosh, Ph.D., Senior Vice President and Head of Research and Early Development at Biogen. To access the live webcast, please visit Biogen’s Investors section at www.investors.biogen.com. An archived version of the webcast will be available following the presentation.

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On November 21, 2019 iOmx Therapeutics AG (iOmx), a biopharmaceutical company developing cancer therapeutics based on novel immune checkpoint targets, reported that its Vice President, Antibody Development, Stefanie Urlinger, PhD, delivered a podium presentation highlighting the discovery of IGSF11, a novel immune checkpoint molecule on tumor cells, using its iOTarg discovery platform at the 11th PEGS Europe Protein & Antibody Engineering Summit (PEGS Europe 2019) in Lisbon, 12-18 November, 2019 (Press release, iOmx Therapeutics, NOV 21, 2019, View Source [SID1234551604]).

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The podium presentation, titled, "A Comprehensive Screening Platform to Identify the Next Generation of Cancer Immunotherapy Targets," reports the identification of IGSF11, a postulated VISTA interaction partner, as an important immune checkpoint molecule on tumor cells using iOTarg, the company’s proprietary, high-throughput target discovery platform. In an MC38 murine colon adenocarcinoma mouse model, CRISPR knockout of IGSF11 resulted in a >70% reduction in tumor growth, independently validating the target. Interestingly, patients refractory to anti-PD1 or anti-CTLA4 therapies overexpress IGSF11 and exhibit poor progression-free survival.

Based on these findings, iOmx is developing a novel anti-IGSF11 antibody as monotherapy in patients with solid tumor indications that are resistant to PD-1/PD-L1 therapies. The company presented data showcasing their IGSF11-specific antibodies which block the interaction to VISTA and exhibit strong immune lysis of tumor cells in vitro. Additionally, beyond IGSF11, iOTarg resulted in the identification of other novel immune checkpoint targets and unique immune evasion biologies against which iOmx is pursuing first-in-class drug development projects – all in the pre-clinical stage.

"Current limitation of the approved immune checkpoint inhibitors to induce response in majority of cancer patients requires us to identify and drug additional key vulnerabilities in refractory tumors," said Nisit Khandelwal, Ph.D., co-founder and Senior Vice President of iOmx Therapeutics. "PEGS Europe 2019 Summit is an ideal event to showcase the ability of iOmx’ iOTarg genetic screening platform to systematically identify novel and druggable immune checkpoint targets, such as IGSF11, that are expressed by PD-L1 non-responsive tumors. Based on our findings, we have initiated pre-clinical development of a first-in-class IGSF11-targeting antibody that eliminates tumor induced immune suppression, especially in anti-PD-1 refractory tumors. Furthermore, we continue to investigate new immuno-oncology targets with our unique iOTarg discovery engine."

On November 21, 2019 Tikcro Technologies Ltd. (OTCQB: TIKRF), a pre-clinical stage developer of antibodies for cancer immune-therapy, reported its financial results for the third quarter ended September 30, 2019 (Press release, Tikcro, NOV 21, 2019, View Source [SID1234551603]).

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"We have concluded the pre-clinical development stage of our anti-CTLA-4 antibody, which shows strong comparative results in cancer treatment assays," said Aviv Boim, CEO of Tikcro. "At this stage, we plan to reduce operating expenses. We expect to close our lab facilities and cease pre-clinical development efforts, which incurred $546,000 of R&D expenses in the previous twelve-month period. Due to the significant costs associated with production and clinical trials as well as the evolution of the immune therapy antibody market, we will continue to explore strategic opportunities for this antibody program and other alternatives."

Financial Results for the Third Quarter Ended September 30, 2019
Net loss for the third quarter of 2019 was $237,000, or $0.02 per diluted share, compared to a net loss of $266,000, or $0.03 per diluted share, for the same period last year.

As of September 30, 2019, the company reported $4.45 million in cash, cash equivalents and short-term bank deposits.