Thank you for standing by. This is the conference operator. Welcome to the Zymeworks Fourth Quarter and Year-End Results Conference Call and Webcast. As a reminder, all participants are in listen-only mode, and the conference is being recorded. After the presentation, there will be an opportunity to ask questions. Operator instructions. I would now like to turn the conference over to Jack Spinks, Manager of Investor Relations at Zymeworks. Jack, please go ahead.

Good afternoon, and welcome everyone. My name is Jack Spinks, Manager of Investor Relations here at Zymeworks. Today, we will discuss our fourth quarter and year-end 2021 financial results as well as provide an update to our ongoing business. Before we begin, I would like to remind you that we will be making a number of forward-looking statements during this call, including statements that relate to the implementation of our strategic priorities; clinical development of our product candidates, related clinical trials, anticipated clinical data presentations, potential therapeutic effects of zanidatamab, and other product candidates; expected financial performance and future financial position; the commercial potential of technology platforms and product candidates; anticipated continued receipt of revenue from existing and future partners; our preclinical pipeline; anticipated sufficiency of cash resources and other potential sources of cash to fund our planned operations into the second half of 2023 and potentially beyond; the anticipated completion of, scope of and potential cost savings from our announced targeted reduction in workforce; our ability to execute new collaborations and partnerships; and other information that is not historical information. Forward-looking statements are based upon our current expectations and various assumptions, and are subject to the usual risks and uncertainties associated with companies in our industry and in our stage of development. For a discussion of these risks and uncertainties, refer you to our latest SEC filings as found on our website and as filed with the SEC. Later in this call, Neil will be discussing our financial results, including certain non-GAAP measures. A description of our non-GAAP measures and a reconciliation to the most directly comparable financial results as determined in accordance with GAAP are described in detail in our press release, which is available on our website at www.zymeworks.com under the Investor Relations tab. As a reminder, the audio and slides from this call will be available on the Zymeworks website later today. With that, I will turn the call over to Neil Klompas, our Chief Operating Officer. Neil?

Thanks, Jack, and hello everyone. Thank you for joining us today for our first earnings call of 2022. Before we dive in, I'd like to note that while I'll be presenting the prepared remarks today, our entire executive team will be available for Q&A following this portion of the call. I'd also like to highlight that going forward, in addition to periodic conference calls where we'll discuss and highlight significant matters, we anticipate holding quarterly earnings calls as we look to increase the regular cadence of engagement with Zymeworks shareholders and report on our progress. As always, we look forward to the opportunities for public dialogue with our shareholders and those tuning in. I would like to quickly touch on two items. First, I want to highlight the larger corporate objectives that we as a management team are seeking to achieve. With a corporate restructuring already well underway, we are continuing to align and increase our focus across the organization with the overarching goal of building a leading biopharmaceutical company with an exciting and expanding pipeline of product candidates from early discovery research through late-stage clinical development that we hope will make a significant difference for patients around the world with hard to treat cancers. While we continue to make some internal adjustments as we work towards that goal, Zymeworks has a clinically relevant drug, next generation technology platforms that can build truly novel therapeutics and a focused team that can execute and deliver upon our stated objectives. This is key as we look to make significant progress towards achieving our corporate objectives through a more value-focused, cost-efficient and effective organization. Second, as you may have seen in today's earnings announcement, I would like to start the call by congratulating Chris Astle, PhD who has been promoted effective immediately to Senior Vice President and Chief Financial Officer. As I pass along the role of CFO, one that I've held since 2007, I will remain in my current position as Chief Operating Officer. Chris has been an important leader in the finance team, and I look forward to continuing to work with him in his new capacity. Given the importance of financial discipline to every clinical-stage biotech company, we will no doubt utilize Chris' deep finance and accounting background to its fullest, and I welcome Chris into this new role. With that, I would like to jump right into an overview of our financial results, followed by a discussion of our clinical programs and upcoming catalysts. And lastly, a general corporate update on some of our previously announced strategic priorities. This afternoon, Zymeworks reported financial results for the quarter and year ended December 31, 2021. As reported, our revenue for the year ended December 31, 2021 was $26.7 million compared to $39 million in revenue for the year ended December 31, 2020. Revenue for 2021 included $8 million from BeiGene for a development milestone, $8 million from Janssen for two development milestones, $5 million from Iconic Therapeutics received in conjunction with their licensing of XB002, formerly ICON-2, which incorporates our ZymeLink ADC technology, as well as $5.7 million from our partners for research and development support under various cost sharing arrangements. This decrease in revenue year-over-year was primarily related to the timing of revenue received from non-recurring upfront fees, expansion payments, or milestone payments from collaboration and licensing arrangements. Research and development expense for the year ended December 31, 2021 was $199.8 million compared to $171.2 million for the year ended December 31, 2020. This increase is primarily due to higher salary and benefits expenses from additional headcount and increases in expenses related to clinical trials and research and development, which were partially offset by a decrease in drug manufacturing activities. General and administrative expense for the year ended December 31, 2021 was $42.6 million compared to $55.2 million for the year ended December 31, 2020. In 2021, general and administrative expense included a non-cash stock-based compensation recovery of $5.6 million compared to an $18.2 million expense from equity-classified awards, offset by a $23.8 million recovery from the non-cash mark-to-market revaluation of certain historically liability-classified awards. Excluding stock-based compensation expense, general and administrative expense increased on a non-GAAP basis by $9.1 million or 23% in 2021 compared to 2020. The increase was primarily due to higher salary and benefits expenses from additional headcount and professional fees, partially offset by a U.S. state sales tax refund we recognized in 2021. As of December 31, Zymeworks' net loss for the year was $211.8 million in 2021 compared to $180.6 million in 2020. The increase in net loss was primarily due to increases in research and development expenses and a decrease in revenue and interest income, partially offset by lower general and administrative expense. Our cash resources consisting of cash, cash equivalents and short-term investments, but excluding the proceeds from our recently completed public offering, was $252.6 million at the end of the reporting period. For additional color on our quarterly results and for a description of our non-GAAP financial measures and a reconciliation of GAAP to non-GAAP financials, I encourage you to review our earnings release and other SEC filings available on our website at www.zymeworks.com. With that, I'll move into some clinical highlights. Let me start by providing an update on zanidatamab, our lead product candidate, a novel HER2-targeting biparatopic antibody. This year will be crucial to the development and commercialization of zanidatamab as we will be working towards multiple key milestones and data readouts that will help determine its commercial path. The first upcoming milestone for zanidatamab in 2022 will be completing enrollment for our first pivotal trial, HERIZON-BTC-01 evaluating zanidatamab as a monotherapy in previously treated advanced or metastatic HER2-amplified biliary tract cancer, or BTC. We expect to complete enrollment for this pivotal study by the middle of this year. This study is based on a primary endpoint of objective response rate as determined by independent central review in an evaluable patient population of at least 75 subjects with two-thirds of patients being recruited in countries outside China. As a reminder, zanidatamab has been granted Breakthrough Therapy designation by the FDA for patients with previously treated HER2 gene-amplified BTC as well as two Fast Track designations, one for previously treated or recurrent HER2-positive BTC and another for first-line gastroesophageal adenocarcinoma, or GEA for short, in combination with standard of care chemotherapy. Zanidatamab has also received Orphan Drug designation for the treatment of BTC and GEA in the United States, and for gastric cancer and BTC in the European Union. In addition, we are continuing enrollment for zanidatamab's second pivotal study, HERIZON-GEA-01, which is a randomized, global pivotal study evaluating zanidatamab in combination with chemotherapy and with or without BeiGene's anti-PD-1 tislelizumab for first-line patients with locally advanced or metastatic HER2-positive GEA. This study is supported by promising results with zanidatamab in combination with chemotherapy in first-line GEA that we presented in October of last year at the European Society for Medical Oncology Annual Congress. As we spoke to in detail in November's HERIZON-GEA-01 launch webcast and conference call, this pivotal trial is an open-label, global three-arm trial that will compare the current standard of care in first-line GEA, trastuzumab plus chemotherapy versus one of two experimental arms, zanidatamab plus standard of care chemotherapy or zanidatamab plus tislelizumab plus standard of care chemotherapy. The global diverse patient population will be randomized one to one to one, with a total of 714 patients enrolled from approximately 300 sites in 38 countries. And we expect enrollment, which is currently continuing as anticipated, to be completed by the end of 2023. It is important to note that due to the global nature of this trial, and through extensive consultation with the FDA prior to its launch, we strongly believe that issues unrelated to zanidatamab raised by the Oncologic Drugs Advisory Committee, or ODAC, have little bearing on the HERIZON-GEA-01. In addition to continued progress on the two ongoing pivotal studies for zanidatamab, we in conjunction with our Asia Pacific partner, BeiGene, have generated important data in HER2-positive GEA and breast cancer that has been submitted for presentation at the upcoming annual American Society of Clinical Oncology meeting in June of this year. Subject to the acceptance of our abstracts, we will look forward to reporting these important data and holding an investor event to discuss the status of our development program for zanidatamab and the significance of the data reported at that meeting. I would also like to highlight that while we are aware of potential impacts to certain supply chains following WuXi being placed on the non-verified list by the U.S. Department of Commerce, we do not anticipate any impacts to Zymeworks' supply chain or product portfolio. Specifically, the constraints placed upon WuXi pertain to capital equipment purchases that do not impact any of our manufacturing operations and do not limit product import or export to other jurisdictions, including the U.S. or EU. Finally, I'd like to provide a brief update on ZW49, our clinical-stage biparatopic antibody-drug conjugate. We have an ongoing study evaluating ZW49 as monotherapy in an open-label Phase 1 clinical trial in patients with HER2-expressing solid tumors. We have completed enrollment of 30 patients in the every-three-week expansion cohort, which we initiated in 2021. And in parallel, we continue to evaluate a weekly dosing regimen. Currently, as we continue to work towards establishing a recommended Phase 2 dose, no maximum tolerated dose has been reached, and we have not observed any dose-limiting toxicities to date. As we have previously guided, we continue to expect the ZW49 data to be presented at a major medical meeting in the second half of this year. The data presented will inform our clinical development path for ZW49, and we look forward to providing further updates at that time. In addition to our clinical-stage assets, our R&D teams are continuing to focus on generating product candidates utilizing our therapeutic platforms. Our goal, as previously highlighted, is to have filed INDs or their foreign equivalents for at least two novel therapeutics by the end of 2024. We hope to be able to provide an update on our R&D program and current preclinical work in the fourth quarter of this year and at an event hosted by our R&D team. On the partnership and collaboration front, we remain acutely focused on value creation as we aggressively pursue partnerships and collaborations for our clinical and R&D assets and monetization of our non-core programs. As previously announced in our strategy update in January, we believe we have multiple potential opportunities to monetize non-core early stage R&D programs, including intellectual property and product candidates targeting IL-12, CD47 and MET, as well as a novel ACE2 decoy program targeting SARS-CoV-2. We look forward to providing updates in the future as we make progress towards these and other potential out-licensing, partnership and funding opportunities. In tandem, we will also continue to pursue partnership opportunities for zanidatamab, particularly as we look to expand zanidatamab into additional indications like colorectal, breast and lung cancers and into earlier lines of therapy where zanidatamab's combined ability and toxicity profile make it appealing to patients and physicians. Moving on, I now want to touch on recent progress we have made towards one of our key objectives, improving our financial position, including cash burn and cash runway for the coming years. As previously mentioned, on January 19, we completed an immediate reduction of the senior leadership team, followed by a streamlining of our workforce targeting a headcount reduction of at least 25% by the end of the year. The reduction in overall employee headcount is well underway. While we expect to exceed the targeted headcount reduction of 25% by March 1, we anticipate that the majority of the cost savings related to our reduction in workforce will be reflected in our 2023 financials. In addition, we recently closed an underwritten public offering where we received gross proceeds of $115 million. Despite headwinds from a rapidly changing rate environment, shifting global biotech sentiments and the background of global macroeconomic events, we were very pleased with the support shown from both current and new investors who participated in this financing. Looking at our runway. With our reported cash balance at December 31, 2021 of $252.6 million, we anticipate that the proceeds from this financing, combined with the reduction in G&A and R&D spend, including our headcount reductions, will provide us an extension of current cash runway into the second half of 2023. Additionally, we believe that as a result of successfully executing on our previously mentioned partnership and monetization strategies, as well as by identifying and realizing further operating efficiencies gained through our restructuring, we will be able to update our runway guidance through the end of 2023 and potentially beyond in future updates. I would now like to take a moment to reiterate the importance of our key strategic priorities we recently provided in January. To remind those listening in, these key strategic priorities include the full recruitment of our two pivotal clinical studies for zanidatamab, HERIZON-BTC-01 and HERIZON-GEA-01, identifying and executing upon strategies for the future clinical development path of zanidatamab, presenting data at a major medical meeting and finalizing a clear clinical development path for ZW49. Selecting and advancing at least two novel therapeutics by the end of 2024, aggressively pursuing and executing new partnerships and collaborations in order to support the development and commercialization of our clinical and early stage R&D pipeline, continuing to support and advance our core technology platforms and collaborations, and continuing to improve on our financial position through partnerships, collaborations, non-core asset monetization and other sources of non-dilutive funding. Each of these is a core component in rebuilding and enhancing value and moreover, in the overall success of our company. As we continue to reset and focus the company on maximizing both shareholder value and patient outcomes, Zymeworks remains incredibly well positioned to execute on our ambitious plan. We have a pivotal stage therapeutic that has exhibited clinically meaningful data and is well tolerated. We have multiple upcoming data catalysts and ongoing clinical trials and indications where we are clearly competitive. And we have a world-class R&D team and platforms capable of creating truly novel drug candidates. I look forward to providing updates as we progress towards completing these key priorities. And now more than ever, I remain excited for the future of Zymeworks. With that, I will turn the call over to the operator to begin the question-and-answer session. With me today to answer questions is our Chair and Chief Executive Officer, Kenneth Galbraith; our Chief Medical Officer, Dr. Neil Josephson; and our newly promoted Chief Financial Officer, Chris Astle.

Thank you. We will now begin the question-and-answer session. Operator instructions. Our first question comes from Stephen Willey of Stifel. Please go ahead.

Hi, guys. Can you hear me?

Yes, we can hear you.

Okay, cool. Hi, guys. This is Julie on for Steve. Thank you for taking my questions. If you don't mind, can you basically just comment on the status of your confirmatory Phase 3 BTC trial, whether you are still viewing this time as a first-line trial? And maybe if you could provide timing on this trial, that would be great. And then I will have follow-up questions afterwards. Thank you.

Thanks for the question. Again, as you know, we're currently enrolling the second-line BTC study with zanidatamab and we expect that to be fully enrolled by mid this year. And then, as you know, the primary endpoint is the response rate. So after we have that data, it would be our expectation to review that data with the regulatory agency in the U.S., and at that time have discussions about the nature of the confirmatory study. So I don't think we'll prejudge those future regulatory interactions. And once we have an update about that after we have our data and have that regulatory interaction, I think it will be clear to make a disclosure about the nature of the confirmatory study around that indication.

Great, that's helpful. And my next question is actually related to ZW49. So I'm just wondering if you have been enrolling any HER2-expressing patients into the ZW49 development program and whether you think there is an opportunity for these assets in HER2-expressing patients. Thank you.

Yes, we have not yet enrolled patients with low HER2 expression tumors in the ZW49 study. Obviously, we're aware of the opportunity and we're aware of the announcement that a competitor had made. We haven't seen the data yet, but obviously that's an opportunity for us to consider in the future. But we're not currently enrolling those patients in our ZW49 Phase 1.

Great. Thank you so much. That's all for me.

Thank you for your questions.

Our next question comes from Gena Wang of Barclays. Please go ahead.

Hi, guys. Thanks for taking our questions. This is Tom for Gena. I have two questions, one regarding zanidatamab and the other regarding ZW49. Starting with zanidatamab, as you announced the abstract submission to ASCO, can you give a little bit more color on what exactly the study will be? Is that the zanidatamab plus chemotherapy plus PD-1 combo in first-line GEA and the Phase 2 zanidatamab plus docetaxel in first-line metastatic breast cancer? And if so, can you help us set the expectation on how many patients and the follow-up duration at the readout?

I'll take it from the first part of your question. Again, we just wanted to clarify that we had made abstract submissions for ASCO. Obviously, we need to wait until those are accepted and published online. And then we'll be glad to talk about them at that time, including as they're presented at the conference. I don't think we'll add any more color to those abstracts until we know that they're accepted and we understand what's presented in the posters or presentations at that meeting.

Okay, that's fair. So for ZW49, what would be your bar or what kind of profile would you look for to make a go/no-go decision? Is that comparable to like in HER2? Just want to hear your color on that.

Yes, I think from our standpoint, it is early clinical development. So we're trying to find a dosing regimen that we think will allow us to optimize the efficacy and patient populations in Phase 2. And obviously we're working on a more frequent regimen of dosing for ZW49 on a once-weekly basis, which we hope will give us the therapeutic window that we need to move forward into Phase 2. So I think this is typically based more on the totality of the data that we've seen in Phase 1. It's been a pretty extensive Phase 1 program for ZW49. And I think after we finish this last cohort this year, then we'll be able to make a decision based on the totality of the data rather than a specific benchmark, because it is early clinical development. We're aware of the opportunity for ZW49. We think it is an exciting compound. We just need to find a regimen that we think is appropriate to move forward into Phase 2. And we'll be able to provide all that data from the Phase 1 study in a publication in the second half, which will provide the rationale for how we're moving that forward.

Maybe just a quick follow up on the ADC technology platform. What kind of improvement in chemistry or technology should we expect in the next generation of your ADC platform, considering multiple INDs will be up and running in the next years?

So as you're aware, ZW49 was moved into the clinical studies a number of years ago. Our current next-generation ADC platform that we're working on with our preclinical candidates is a completely different ADC platform that we think is very competitive and world class. And I think we haven't talked too much about it yet. We're hoping to have an R&D forum in the fourth quarter of this year to fully explain the new platform that we have, why we think it's next generation, why we think it's world class, what targets we're specifically trying to pursue with that technology, why we might think it has some benefits over and above what we're seeing today with ADCs in HER2, and what our strategy is looking forward and what the partnership strategy is. So I think once we have that forum later this year, we'll be able to talk more fully about that.

Thank you.

Our next question comes from Yigal Nochomovitz of Citigroup. Please go ahead.

Hi, Kenneth and team. Thanks for taking the question. So obviously you're aware of the TOPAZ-1 data, the Phase III trial, where AstraZeneca did in first-line biliary the triple combo of durvalumab and GemCis which showed median OS of about 13 months, PFS of seven months. Given that, I wanted to get your thoughts in terms of competitive positioning versus that data. Are you going to move ahead with the pivotal for zanidatamab plus chemo in first-line biliary? And what would be the factors that give you confidence that you can improve upon what AstraZeneca has shown in TOPAZ-1 with durvalumab plus chemo? Thanks.

That's a really good question. I'm going to pass to Neil Josephson to talk a little bit about the TOPAZ data and how zanidatamab can be effective in biliary tract cancer.

Thank you. TOPAZ-1 is an important study. It's an important advance for patients with biliary tract cancer. It's something that we have to look at in terms of if we are going to go into first-line biliary tract cancer as a potential and likely standard of care therapy. In terms of where zanidatamab is going to focus, zanidatamab is going to focus on patients that have HER2 amplification and expression. And we know from our experience in later-line biliary tract cancer that we have a very active agent. And so we feel confident that for patients with HER2-amplified and overexpressing biliary tract cancer that zanidatamab in any line of therapy can improve outcomes. So I don't want to take anything away from the advances which are significant, but we're looking to improve outcomes in a specific population and we have a drug that targets an oncogenic driver in that population and believe that it can add to whatever benefit is given more generally to biliary tract cancer patients.

Okay, great. That's very helpful. Also related to TOPAZ-1, it's interesting since it shows checkpoint modulation can work in biliary and become part of standard of care. Have you thought about exploring zanidatamab plus tislelizumab plus chemo in first-line biliary, or maybe even a chemo-free approach of zanidatamab plus tislelizumab in first-line biliary to compete against AstraZeneca's regimen?

Yes, we are definitely interested in the combination of zanidatamab with a PD-1 inhibitor. As you know, we're pursuing that in gastric indications. But as you point out, there's now evidence that PD-1 inhibitors have a place in biliary tract cancer, so it would be something we would be interested in looking at. In terms of a specific study, we don't have anything planned or designed at this point.

Okay. And then just switching over to ZW49, you saw the competitive DESTINY-Breast04 data for HER2 where they reported positive PFS and OS results. How is that impacting your strategic thinking about developing ZW49 in the HER2-low population?

Again, to echo Ken's comments, we are interested in HER2-low. It's not something that we've specifically enrolled in the Phase 1 study now, but it is something we believe ZW49 can play a role in. Also, while both are ADCs, they have different mechanisms and characteristics, so it's not as if one and the other can't have roles in the same disease. HER2-targeted ADCs are active, and we believe that if we develop ZW49 for HER2-low it could have a place and role as well.

Our next question comes from Akash Tewari of Jefferies. Please go ahead.

Hi, guys. So previously the team had talked about aggressively finding partners for ZW25 to get value for the asset. But that has created a situation where investors have a difficult time understanding the market opportunity. If we assume ZW25 does not get partnered, which programs would Zymeworks be able to run by itself? What would be the approximate cost of those studies? And in a situation where ZW25 doesn't get partnered, what would be your base case expectation? And then, on ZW49, is there any concern that the eye toxicity seen with that ADC might be related to ZymeLink technology and therefore be a broader platform-related issue? What can you comment on that theoretical concern? Thanks.

Thanks for the questions. On your first question, today we've started and expect to complete two pivotal trials for zanidatamab with our regional partner, BeiGene, who has rights in China, Korea and some other Asia Pacific markets. So we can undertake robust clinical development of that agent. Our second study in first-line GEA is a 714-patient study across 38 countries, so we're capable of conducting large global trials. From a commercial strategy, we've said consistently that in the HER2-expressing tumor marketplace we need partners who can help us compete and broaden zanidatamab's potential. That's what we're looking for. We think there's interest in the marketplace. We're seeing recent data that may redefine how patients are classified and potentially open treatment to more patients. We believe zanidatamab is a good agent with differentiated mechanism and we think it has a place in treating HER2-expressing tumors beyond BTC and GEA. We expect partnerships will help us commercialize results globally and pursue additional pivotal studies in areas where zanidatamab can be competitive. That is our base case: we will seek partnerships to allow broader competition, funding, and commercialization globally. That is true for zanidatamab, ZW49 and our early research programs. We have an active partnering program and believe there's interest in our platforms that produced zanidatamab and ZW49 and our next-gen platforms. I'll let Neil address the question about eye toxicity on ZW49.

You asked specifically about eye toxicity as possibly being a component of the underlying ADC technology. Eye toxicity has been observed across a variety of ADCs, so it's a class-related issue to some extent. There can be off-target ocular toxicity with ADCs and sometimes on-target effects depending on the antigen expression in ocular tissues. The goal is to find a dosing regimen and indication with the best therapeutic index. I don't see the keratitis and ocular findings with ZW49 as different in kind from those seen with other ADCs. Our focus is to develop it in a way that maximizes benefit and minimizes adverse events, and that's where we're headed.

Our next question comes from Jessica Fye of JPMorgan. Please go ahead.

Hi. Good afternoon. This is JL on for Jess. Thank you for taking our questions. We have a couple of clarifying questions. On zanidatamab, can you confirm what dataset you plan to submit to ASCO? And if the BeiGene dataset is positive in first-line breast cancer, what's your development plan there? Do you plan to run a new Phase 2 in the U.S. by yourself, or do you plan to look for a new partner? On ZW49, your press release says there were no dose-limiting toxicities observed with the weekly dosing. But just curious, what about the every-three-week dosing regimen that you are also evaluating? Have you seen any outstanding safety signals there? Lastly, you mentioned ODAC earlier — could you clarify the key issues raised by ODAC and whether they relate to your trial in combination with PD-1 inhibitor?

Thanks. On the first question, all we can confirm is that we've made a number of abstract submissions to ASCO. We need to wait until those are accepted and publicly available, and then we'll discuss the accepted content and present it at the conference, including an investor event. We won't add more color until they're accepted. Regarding future development beyond BTC and GEA, we've done work in breast cancer, colorectal cancer and lung cancer, so we'll look at potential opportunities beyond BTC and GEA and disclose decisions when made. On ODAC, after the recent events at the FDA and ODAC for another program, we've had a few investor questions and we wanted to clarify our situation is not similar with respect to our global GEA study. Our HERIZON-GEA-01 is global with about 300 sites in 38 countries and was discussed with the FDA prior to launch. We believe it will be sufficient to support filings in major markets. So we're not concerned that ODAC events for other drugs bear on our global study for zanidatamab.

On dose-limiting toxicities, the statement that no dose-limiting toxicities were observed applies to both the weekly and the every-three-week evaluations to date. We've evaluated 30 patients in the every-three-week expansion cohort and are continuing to evaluate the weekly regimen to find an appropriate dose. We'll release more detailed data in the second half of the year, which will include dosing and safety across cohorts.

Our next question comes from Charles Zhu of Guggenheim Securities. Please go ahead.

Hi. This is Edward on for Charles. A question on ZW49. In the preclinical data, you showed that on a mass-equivalent basis, you had better efficacy than trastuzumab-based ADCs. But clinically, trastuzumab-derived ADCs dose every three weeks at 5 to 6 mg/kg depending on the indication, and you're exploring 2.5 mg/kg weekly for ZW49. How do you think about exposure levels you'll be able to get with this different dosing regimen and how competitive you think you could be? Do you think that will translate into efficacy?

We will release data later this year where you'll be able to see what doses we've gone to in the weekly and every-three-week regimens and the exposures achieved. As a reminder, while both are ADCs, they have different mechanisms of action and potential clinical niches. Our challenge is to find dosing and indications where ZW49 can meet unmet needs, including potentially in HER2-low disease.

There appear to be no further questions. I'd like to turn the conference back over to Zymeworks for closing remarks.

Thank you, operator. I just wanted to close and say we really appreciate your time on the call. I know there have been world events today that everyone's been paying attention to, which are much more important than a biotech company's earnings call. We certainly appreciate your time and attention. Our thoughts are completely with those in Ukraine and their families who may be worried both inside and outside of Ukraine, and we're thinking about them as part of this call. We really appreciate your attention today. We look forward to reporting more progress on what I hope is a really exciting year for Zymeworks in 2022. We look forward to reporting progress in the weeks and months ahead, and answering your questions as we can about that. So thank you for your attention and time. We look forward to talking to you again.

This concludes today's conference call. You may disconnect your lines. Thank you for participating, and have a pleasant day.