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 Zymeworks Inc. ("Zymeworks"), a clinical-stage biopharmaceutical company 
 dedicated to the discovery, development and commercialization of 
 next-generation multifunctional biotherapeutics, today announced results 
 from the dose escalation portion of the first-in-human study of ZW25, a 
 novel Azymetric™ bispecific antibody targeting two distinct domains of 
 the HER2 receptor.
 
 
 ZW25 was well-tolerated at all dose levels evaluated with single agent 
 anti-tumor activity in patients with advanced HER2-expressing cancers 
 that had progressed after multiple lines of therapy, including 
 HER2-targeted agents. These results provide the framework for further 
 advancement of ZW25 across multiple cancer indications.
 
 
 A total of 16 patients were enrolled in the study, including 8 with 
 breast cancer, 6 with gastric, gastroesophageal junction, or esophageal 
 (GE) cancer, and 2 with other HER2-expressing cancers. All patients were 
 heavily pretreated having received a median of 4 prior systemic regimens 
 for metastatic disease, which included trastuzumab. Breast cancer 
 patients were also treated with T-DM1 (n=8); pertuzumab (n=6), and 
 lapatinib (n=6) and had a median of 6 prior HER2-targeted regimens for 
 metastatic disease.
 
 
 "Despite the benefits provided by currently-available HER2-targeted 
 therapies, significant medical need remains," said Dr. Diana Hausman, 
 Chief Medical Officer of Zymeworks. "We are very encouraged by the 
 safety profile and single agent anti-tumor activity of ZW25 in patients 
 with advanced breast or GE cancer that has progressed after prior 
 HER2-targeted therapies. These results will guide further development in 
 the expansion cohort portion of this study."
 
 
 Patients were treated with weekly ZW25 at 5 mg/kg (n=3), 10 mg/kg (n=6), 
 or 15 mg/kg (n=7) in cycles of 4 weeks each. ZW25 was well-tolerated at 
 all dose levels, with no dose-limiting toxicities. The majority of 
 adverse events (AEs) were Grade 1 or 2, with no treatment-related 
 serious AEs and no changes in cardiac function. The most common AEs were 
 diarrhea and infusion reactions, reported in 7/16 patients each. 
 Treatment-related Grade 3 AEs occurred in a single patient and included 
 hypophosphatemia, fatigue, and arthralgia. Eight patients had anti-drug 
 antibodies (ADA) prior to initiating treatment with ZW25; there was no 
 evidence of increases from baseline levels and no patients developed new 
 ADA.
 
 
 Durable single-agent anti-tumor activity was seen with patients having 
 received up to 8 cycles of treatment at the time of data cut-off. In 14 
 response-evaluable patients (defined as undergoing at least one tumor 
 restaging), best overall response (BOR) was 2 partial response (PR), 4 
 stable disease (SD), and 8 progressive disease (PD). The majority of 
 patients with measurable disease had a decrease in the size of target 
 lesions. BOR in 8 breast cancer patients was 2 PR, 3 SD (&gt; 6 months in 
 one patient), and 3 PD, for an overall disease control rate (CR, PR, or 
 SD) of 63%. Three of the breast cancer patients developed PD due to 
 brain metastases but maintained systemic disease control at the time of 
 progression. BOR in 4 response-evaluable patients with GE cancers 
 included SD &gt; 4 cycles in 1 patient, and 3 PD. Four patients remain 
 active on study.
 
 
 "We will continue to rapidly advance development across multiple cancer 
 indications, with the goal of establishing ZW25 as the HER2-targeted 
 therapy of choice for physicians and their patients," said Dr. Ali 
 Tehrani, President and CEO of Zymeworks. "These results also highlight 
 the value of Zymeworks' Azymetric bispecific platform and support the 
 accelerated development of additional multifunctional therapeutics in 
 our candidate pipeline."
 
 
 ZW25 Phase 1 Clinical Trial Details
 
 
 The dose escalation portion of the study enrolled patients with 
 HER2-expressing cancers (either HER2 IHC 1+, 2+ or 3+, or FISH-positive) 
 whose cancer had progressed after treatment with all therapies known to 
 confer clinical benefit. HER2 status was assessed in archived or fresh 
 biopsies locally and at a central laboratory. Patients with HER2-high 
 breast cancer (HER2 IHC 3+ or IHC2+ and FISH-positive) had to have 
 received previous treatment with trastuzumab, pertuzumab, and T-DM1. 
 Patients with HER2-high gastric or gastroesophageal cancers had to have 
 been previously treated with trastuzumab. Patients could have measurable 
 or non-measurable tumor lesions per RECIST 1.1. Patients with known 
 active brain metastases were excluded from the study. Patients were 
 assessed during treatment for safety, including changes in cardiac 
 function, tumor response per RECIST 1.1 every 8 weeks, ZW25 drug levels, 
 and potential development of anti-drug antibodies.
 
 
 About ZW25
 
 
 ZW25 is Zymeworks' lead product candidate currently being evaluated in a 
 Phase 1 clinical trial in the United States, based on Zymeworks' 
 Azymetric™ platform. It is a bispecific antibody that can simultaneously 
 bind two non-overlapping epitopes of HER2, known as biparatopic binding, 
 resulting in dual HER2 signal blockade, increased binding and removal of 
 HER2 protein from the cell surface, and potent effector function. These 
 combined mechanisms of action have led to significant anti-tumor 
 activity in preclinical models of HER2-expressing cancer. Zymeworks is 
 developing ZW25 as a best-in-class HER2-targeting antibody intended as a 
 treatment option for patients with any solid tumor that expresses HER2.
 
 
 About Zymeworks Inc.
 
 
 Zymeworks is a clinical-stage biopharmaceutical company dedicated to the 
 discovery, development and commercialization of next-generation 
 multifunctional biotherapeutics, initially focused on the treatment of 
 cancer. Zymeworks' suite of complementary therapeutic platforms and its 
 fully-integrated drug development engine provide the flexibility and 
 compatibility to precisely engineer and develop highly-differentiated 
 product candidates. Zymeworks' lead product candidate, ZW25, is a novel 
 bispecific antibody currently being evaluated in a Phase 1 clinical 
 trial. Zymeworks is also advancing a deep pipeline of preclinical 
 product candidates and discovery-stage programs in immuno-oncology and 
 other therapeutic areas. In addition to Zymeworks' wholly-owned 
 pipeline, its therapeutic platforms have been further leveraged through 
 multiple strategic partnerships with global biopharmaceutical companies.
 
 
 Forward Looking Statements
 
 
 This press release includes &#34;forward-looking statements&#34; within the 
 meaning of the U.S. Private Securities Litigation Reform Act of 1995 and 
 &#34;forward-looking information&#34; within the meaning of Canadian securities 
 laws, or collectively, forward-looking statements. Forward-looking 
 statements include statements that relate to Zymeworks' Phase 1 clinical 
 trial, ASCO presentation and other information that is not historical 
 information. In addition, any statements or information that refer to 
 expectations, beliefs, plans, projections, objectives, performance or 
 other characterizations of future events or circumstances, including any 
 underlying assumptions, are forward-looking. All forward-looking 
 statements are based upon our current expectations and various 
 assumptions. We believe there is a reasonable basis for our expectations 
 and beliefs, but they are inherently uncertain. We may not realize our 
 expectations, and our beliefs may not prove correct. Actual results 
 could differ materially from those described or implied by such 
 forward-looking statements as a result of various factors, including, 
 without limitation, market conditions and the factors described under 
 "Risk Factors" in our registration statement on Form F-1 and in our 
 supplemented PREP prospectus dated April 27, 2017 filed in connection 
 with our initial public offering on May 3, 2017 (copies of which filings 
 may be obtained at <a xmlns="http://www.w3.org/1999/xhtml" href="http://cts.businesswire.com/ct/CT?id=smartlink&amp;url=http%3A%2F%2Fwww.sec.gov&amp;esheet=51569389&amp;newsitemid=20170604005034&amp;lan=en-US&amp;anchor=www.sec.gov&amp;index=1&amp;md5=9ee8486fbb2882befca4f1176842b18d" rel="nofollow" rel="nofollow">www.sec.gov</a> 
 and <a xmlns="http://www.w3.org/1999/xhtml" href="http://cts.businesswire.com/ct/CT?id=smartlink&amp;url=http%3A%2F%2Fwww.sedar.com&amp;esheet=51569389&amp;newsitemid=20170604005034&amp;lan=en-US&amp;anchor=www.sedar.com&amp;index=2&amp;md5=61f513c77f0d4c7700ec3052f0013a30" rel="nofollow" rel="nofollow">www.sedar.com</a>). 
 Consequently, forward-looking statements should be regarded solely as 
 our current plans, estimates and beliefs. You should not place undue 
 reliance on forward-looking statements. We cannot guarantee future 
 results, events, levels of activity, performance or achievements. We do 
 not undertake and specifically decline any obligation to update, 
 republish or revise any forward-looking statements to reflect new 
 information, future events or circumstances or to reflect the 
 occurrences of unanticipated events, except as may be required by law.
 
 
 
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