Q4 2021 Zymeworks Inc Earnings Call

Operator: Thank you for standing by. This is the conference operator. Welcome to the Zymeworks fourth quarter and year-end results conference call-in 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. To join the question queue, press star then the number 1 on your telephone keypad.

Thank you for standing by this is the conference operator, welcome to the <unk> 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'll be an opportunity to ask questions to join the question queue Press Star one.

Press Star then the number one on your telephone keypad should you need assistance during the conference call you May signal, an operator by pressing star and then zero I would now like to turn the conference over to Jack Spinks manager of Investor Relations. That's Iwerks Jack. Please go ahead.

Operator: Should you need assistance during the conference call, you may signal an operator by pressing star and then 0. I would now like to turn the conference over to Jack Spinks, Manager of Investor Relations at Zymeworks. Jack, please go ahead.

Jack Spinks: Good afternoon and welcome, everyone. My name is Jack Spinks, Manager of Investor Relations here at Zymwerks. Today, we will discuss our fourth quarter and year-end 2021 financial results, as well as provide an update on 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 a Product Candidate and related clinical trials Anticipated clinical data present. Potential Therapeutic Effects of Standard Datamab and our other product candidates Respected, Financial Performance, and Future Financial Position.

Good afternoon, and welcome everyone. My name is Jack Spinks manager of Investor Relations here at <unk>.

Today, we will discuss our fourth quarter and year end 2021 financial results as well as provide an update to our ongoing business.

Jack Spinks: The Commercial Potential of Technology Platforms and Product Candidates, and the anticipated continued receipt of revenue from existing and future partners Our pre-clinical 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 on our current expectations and various assumptions and are subject to the usual risks and uncertainties associated with companies in our industry and at our stage of development.

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.

<unk> therapeutic effects of standard data Madden and our other product candidates.

Expected financial performance and future financial position the.

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 at our stage of development for.

Jack Spinks: 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.

For a discussion of these risks and uncertainties refer you to our latest SEC filings is 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.

Descriptions 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 Dot Zyme works Dot com under the Investor Relations tab.

Jack Spinks: 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.

As a reminder, the audio and slides from this call will be available on the <unk> website later today with that I will turn the call over to Neil Columbus, Our Chief operating officer.

Neil.

Neil Klompas: Thanks, Jack. And hello, everyone. Thank you for joining us today for our first earnings call of 2020. 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 conference. 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.

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 who will be available for Q&A. Following this portion of the call.

I'd also like to highlight the 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 <unk> shareholders and report on our progress as always we look forward to the opportunities for <unk>.

Public dialogue with our shareholders and those tuning in.

I would like to quickly touch on two items.

Neil Klompas: First, I want to highlight the larger corporate objectives that we as the management team are seeking to achieve. With our 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 cancer.

First I want to highlight the larger corporate objectives that we as a management team are seeking to achieve.

With our 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.

Neil Klompas: 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 Astley, Ph.

While we continue to make some internal adjustments as we work towards that goal Zimmer 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 earning announcement I would like to start the call by congratulating, Chris Astley Ph D, who has been promoted effective immediately to senior Vice President and Chief Financial Officer.

Neil Klompas: D., 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 have held since 2007, I will remain in my current position as Chief Operating Officer.

As I pass along the role of CFO , one that I've held since 2007 will remain in my current position as Chief operating officer.

Neil Klompas: Chris has been an important leader on 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's 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.

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 utilized Christmas 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.

Neil Klompas: This afternoon, Zymeworks reported financial results for the quarter and year ended December 31st, 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 Beijing for a development milestone, $8 million from Janssen for two development milestones, and $5 million from Iconic Therapeutics, received in conjunction with their licensing of XB002, formerly Icon2, which incorporates our ZymLink 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.

This afternoon <unk> reported financial results for the quarter and year ended December 31st 2021.

As reported our revenue for the year ended December 31st 2021 was 26.7 million compared to $39 million in revenue for the year ended December 31st 2020.

Revenue for 2021 included 8 million from Beijing for a development milestone.

<unk> 8 million from Janssen for two development milestones.

$5 million from iconic therapeutics received in conjunction with their licensing of Xb Zero-zero, two formerly icon, two which incorporates our zine linked to a b C technology as.

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 nonrecurring upfront fees expansion payments or milestone payments from collaboration and licensing arrangements.

Neil Klompas: Expansion Payments, or Milestone Payments from Collaboration and Licensing Arrangements. Research and development expense for the year ended December 31st, 2021, was $199.8 million, compared to $171.2 million for the year ended December 31st, 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 expenses for the year ended December 31st, 2021 were $42.6 million, compared to $55.2 million for the year ended December 31st, 2020.

Research and development expense for the year ended December 31st 2021 was $199 8 million compared to $171 2 million for the year ended December 31st 2020.

This increase is primarily due to higher salary and benefits expenses from additional head count 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 31st 2021 was $42 6 million compared to $55 2 billion for the year ended December 31st 2020.

Neil Klompas: 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 historical liability-classified, excluding stock-based compensation expense, general and administrative expense increased on a non-GAAP basis by 9.1 million, or 23% 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.

In 2021 general and administrative expense included a noncash 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 noncash Mark.

To market revaluation of certain historical 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 head count and professional fees.

Partially offset by U S state sales tax refund we recognized in 2021.

Neil Klompas: As of December 31st, 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 expenses.

As of December 31st <unk> 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 our research and development expenses and decrease in revenue and interest income, partially offset by lower general and administrative expense.

Neil Klompas: Our cash resources consisted of cash, cash equivalents, and short-term investments but excluding the proceeds from our recently completed public offering, which totaled $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. With that in mind, I'll move into some clinical highlights.

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 Dot Zheimer dotcom.

With that I'll move into some clinical highlights.

Neil Klompas: Let me start by providing an update on Xanadatamab, our lead product candidate, a novel HER2-targeting biparatopic antigen. This year will be crucial to the development and commercialization of ZanaDataMap as we will be working towards multiple key milestones and data readouts that will help determine its commercial path.

Let me start by providing an update on zama data map, our lead product candidate a novel her two targeting by per topic antibody.

This year will be crucial to the development and commercialization of Santa data Mab as we will be working towards multiple key milestones and data readouts that will help determinants commercial path.

Neil Klompas: The first upcoming milestone for Xanadatomab in 2022 will be completing enrollment in our first pivotal trial, Horizon BTC01, evaluating Xanadatomab as a monotherapy in previously treated advanced or metastatic HER2 amplified biliary tract cancer, or BTC. We expect to complete enrollment in 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 invaluable patient population of at least 75 subjects, with two-thirds of patients being recruited in countries outside China.

The first upcoming milestone for Zander data map in 2022 we'll be completing enrollment for our first pivotal trial horizon B T. C zero, one evaluating zanna data mab as a mono therapy in previously treated advanced or metastatic hurt you 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.

Neil Klompas: As a reminder, Xanadatamab 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-4, in combination with standard of care chemotherapy. Xanadatamab 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.

As a reminder, zander data Mab has been granted breakthrough therapy designation by the FDA for patients with previously treated her two gene amplified BTC as well as to fast track designations one for previously treated or recurrent her two positive B T C and another for first line gastro.

Soften Gilles Edina carcinoma, or gea for short in combination with standard of care chemotherapy.

Zander data map has also received orphan drug designation for the treatment of BTC and G. A in the United States and for gastric cancer and B T C in the European Union.

Neil Klompas: In addition, we are continuing enrollment for Xanadatamab's second pivotal study, HORIZON GEA-01, which is a randomized global pivotal study evaluating Xanadatamab in combination with chemotherapy and with or without Beijing's anti-PD-1 antibody Tizolizumab for first-line patients with locally advanced or metastatic HER2-positive GEA. This study is supported by promising results with Xanadamab in combination with chemotherapy and Firstline-GEA that we presented in October of last year at the European Society for Medical Oncology Annual Conference.

In addition, we are continuing enrollment presented data <unk> second pivotal study horizon G. A zero, one which is a randomized global pivotal study evaluating zander data map in combination with chemotherapy and with or without Beijing's anti PD, one tuzla lithium.

Mab for first line patients with locally advanced or metastatic her two positive gea.

This study is supported by promising results with Zander data Mab in combination with chemotherapy in first line G. E that we presented in October of last year at the European Society for medical Oncology annual Congress.

Neil Klompas: As we spoke about in detail in November's Horizon 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. Xanadatomab plus standard of care chemotherapy or Xanadatomab plus Tizolizumab plus standard of care chemotherapy.

As we spoke to in detail in November's Horizon G E zero, one 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 G. A trastuzumab plus chemotherapy versus one of two experimental arms Xanadu.

Data Mab plus standard of care chemotherapy.

Sure Zander data Mab, plus Tesla lithium mab plus standard of care chemotherapy.

Neil Klompas: 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. We expect enrollment, which is currently continuing as anticipated, to be completed by the end of 2025. 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 believed that issues unrelated to Xanadatamab raised by the Oncologic Drugs Advisory Committee, or ODAC, have little bearing on the Horizon GEA-01 study.

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 2020 three.

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 believed.

Debt issues unrelated to Zander data mab raised by the Oncologic drugs Advisory committee or <unk> have little bearing on the horizon G E Zero one study.

Neil Klompas: In addition to continued progress on the two ongoing pivotal studies for xanadatumab, we, in conjunction with our Asia-Pacific partner, Beijing, have generated important data for HER2-positive GEA and breast cancer that will be presented at the upcoming annual ASCO 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 Zanadamab and the significance of the data reported at that meeting.

In addition to continued progress on the two ongoing pivotal studies for Zander data Mab, we in conjunction with our Asia Pacific partner Beijing have generated important data in her two positive gea and breast cancer that has been submitted for presentation at the upcoming annual <unk> 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 Zanna, Dan map and the significance of the data reported at that meeting.

Neil Klompas: I would also like to highlight that while we are aware of potential impacts to certain supply chains following Wuji being placed on the non-verified list by the U.S. Department of Commerce, we do not anticipate any impacts on Zymeworks' supply chain or product portfolio. Specifically, the constraints placed upon WUJI 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.

I would also like to highlight the wall, we are aware of potential impacts to certain supply chains. Following wuxi being placed on the non verified left by the U S Department of Commerce, we do not anticipate any impacts design work supply chain or product portfolio.

Specifically the constraints placed upon wuxi pertained 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 are you.

Neil Klompas: Finally, I'd like to provide a brief update on ZW49, our clinical stage biparatopic antibody drug concept. We have an ongoing study evaluating ZW49 as monotherapy in an open-label phase one clinical trial in patients with HER2-expressing solitude. We have completed enrollment of 30 patients in the every three weeks expansion cohort, which we initiated in 2021. And, in parallel, we continue to evaluate a weekly dosing record. Currently, as we continue to work towards establishing a recommended phase 2 dose, no maximum tolerable dose has been reached, and we have not observed any dose-limiting toxicities today.

Finally, I'd like to provide a brief update on Z to be 49 are clinical stage by per topic antibody drug conjugate.

We have an ongoing study evaluating Z to be 49 as monotherapy in an open label phase one clinical trial in patients with her two 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 two dose no maximum tolerable dose has been reached and we have not observed any dose limiting toxicities to date.

Neil Klompas: As we have previously indicated, 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 platform. 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.

As we have previously guided we continue to expect the VW forty-nine 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 <unk> to be 49, 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 I N DS or their foreign equivalents for at least two novel Therapeutics by the end of 'twenty 'twenty four.

Neil Klompas: 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 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.

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 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 noncore programs.

Neil Klompas: 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 outlicensing, partnership, and funding opportunities In tandem, we will also continue to pursue partnership opportunities for Xanadatamab, particularly as we look to expand Xanadatamab into additional indications, like colorectal, breast, and lung cancers, and into earlier lines of therapy, where Xanadatamab's combinability and toxicity profile make it appealing to patients and physicians.

As previously announced in our strategy update in January we believe we have multiple potential opportunities to monetize noncore early stage R&D programs, including intellectual property and product candidates targeting IL 12.

C D forty-seven and met as well as a novel Ace two decoy program targeting Sars Cov two.

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 Zander data map, particularly as we look to expanding zanna data map into additional indications like colorectal breast and lung cancers and into earlier lines of therapy, whereas Ana datum, Abbs combinability and toxicity profile make it appealing.

To patients and physicians.

Neil Klompas: 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 year. As previously mentioned on January 19th, we completed an immediate reduction in 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. However, the reduction in overall employee headcount is well under.

Moving on and 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 19th we completed an immediate reduction of the senior leadership team followed by a streamlining of our workforce targeting a head count reduction of at least 25% by the end of the year.

The reduction in overall employee head count is well underway.

Neil Klompas: While we expect to exceed the targeted headcount reduction of 25% by March 1st, we anticipate that the majority of the cost savings related to a reduction in the workforce will be reflected in our 2023 financial year. 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, changing global biotech sentiments, and a background of global macroeconomic events, we were very pleased with the support shown from both current and new investors who participated in this financing.

While we expect to exceed the targeted head count reduction of 25% by March 1st we anticipate that the majority of the cost savings related to a reduction in workforce will be reflected in our 'twenty 'twenty three 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 shifts.

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.

Neil Klompas: 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 GNA and R&D spend, including our headcount reductions, will provide us with an extension of our 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 strategy, 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.

Looking at our runway with our reported cash balance at December 31st 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 head count reductions will provide us an extension of current cash.

Cash runway into the second half of 'twenty 'twenty three.

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.

Neil Klompas: 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 for our two pivotal clinical studies for Xanadatumab, Horizon BTC01 and Horizon GEA01. Additionally, identifying and executing upon strategies for the future clinical development path of ZanaDataMap.

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 presented data Mab Horizon B T C zero, one and horizon G E zero one.

Identifying and executing upon strategies for the future clinical development path Rosanna data man.

Neil Klompas: 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.

Presenting data at a major medical meeting and finalizing a clear clinical development path for Z W 49.

Selecting and advancing at least two novel Therapeutics by the end of 'twenty 'twenty four.

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 noncore 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.

Neil Klompas: 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 shown 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.

As we continue to reset and focus the company on maximizing both shareholder value and patient outcomes Zyme works 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.

Neil Klompas: 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.

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 XI works.

With that I will turn the call over to the operator to begin the question and answer session.

With me today to answer questions as our chair and Chief Executive Officer Kenneth Galbraith.

Our Chief Medical Officer, Dr. Neil Josephson, and our newly promoted Chief Financial Officer, Chris Astley.

Operator: Thank you. We will now begin the question and answer session. To join the question queue, you may press star then one on your telephone keypad.

Thank you we will now begin the question and answer session to join the question queue. You May Press Star then one on your telephone keypad, you'll hear atone acknowledging your request. If you are using a speakerphone. Please pick up your handset before pressing any keys to withdraw your question.

<unk> Press Star then two we will pause for a moment as callers join the queue.

Operator: You will hear a tone acknowledging your request. If you are using a speakerphone, please pick up your handset before pressing any. To withdraw your question, please press star, then two. We will pause for a moment as callers join the queue. Our first question comes from Stephen Willey of Stiefel. Please go ahead. Hi, guys. Can you hear me?

Our first question comes from Stephen Willey of Stifel. Please go ahead.

Unknown Attendee: Yeah, so we can hear you. Okay, cool. Hi guys, this is Juliane for Steve. Thank you for taking my questions. If you guys don't mind, can you please just comment on the status of your confirmatory Phase 3 BPC trial, whether you guys are still viewing this trial as a first-line trial, and maybe if you could provide maybe timing on this trial, that would be great. And then I will have a follow-up question. No, good.

Hi, guys can you hear me.

Yes, we can hear you.

Oh, Okay Cool hi, guys. This is calling on.

Steve. Thank you for taking my question. If you like the mine can you why are you get the car.

Got.

Got a south yard confirmatory.

E B to keep trial, where did he go Bakersfield hearing this time as a first line trial.

If you could provide that.

Alright.

Timing on that would be great and then I'll I won't have a follow up question.

Thank you.

Neil Josephson: Thanks for the question. Again, as you know, we're currently enrolling the second line BTC study with NANI, and we expect that to be fully enrolled by mid this year, and then, as you know, the primary endpoint is response rates. 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 studies.

No. Thanks for the question again, we're as you know we are currently enrolling.

The second one because the study was Danny.

We expect that to be fully enrolled by mid this year.

And then as you know the primary endpoint is response rates. So after we have that data would be R. R.

Expectation to review that data with regulatory agency in the U S.

And that's when we have discussions about the nature of the confirmatory studies. So I don't think we'll prejudge those.

Neil Josephson: I don't think we'll prejudge those future regulatory interactions, and once we have an update on that after we have our data and have that regular interaction, then I think we'll be clear to make a disclosure about the nature of the confirmatory study around that indication. Great. That's helpful.

It's a regulatory interactions and once we have an update about that after we have our data and have that regular interaction that I think we'll be able to make a disclosure about the nature of the confirmatory study around around.

We're on that indication.

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

Great. That's helpful and my next question is actually related Tuesday that with your 49.

I'm just wondering if you I have been enrolling Amy hartzell.

After that we're expecting patients into the <unk>.

That's your 49 development program.

Whether you think actually there is an opportunity for you or not.

Does that at all.

Her skills that we're expensing patients. Thank you.

Yeah.

Neil Josephson: Yeah, we've not yet enrolled patients with low-expression tumors in the ZW49 study. Obviously, we're aware of the opportunity. We're aware of the announcement that AV and HMA haven't seen the data yet. Obviously, that's an opportunity for us to consider in the future. But we're not currently enrolling those patients in our phase one study. Great. Thank you so much.

Yes, we have not yet.

<unk>.

Based on the low present in tumors and the CW 49 study.

We are aware of the opportunity, where we're aware of the announcement.

We haven't seen the data yet.

Obviously, that's an opportunity for us to consider in the future, but we're not currently enrolling.

Those patients are obviously there'll be 49 phase one.

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

Thank you for your question.

Unknown Attendee: That's all for me. Thank you for your questions. Our next question comes from Gina Wang of Barclays, please go ahead. Thanks, guys. Thanks for taking... Conqueror Jeanne, I have two questions, one regarding Danny and the other one... And I, starting with Danny. As you now, Abstract Submission to ASCII. Give it a little bit more color.

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

Hey, guys.

Thanks for taking our questions. This is Tom for Gina.

I have two questions one regarding to Danny and the other one regarding VW 49, starting with Danny.

As you announced.

Abstract submission to ask though.

Can you just give a little bit more color.

Unknown Attendee: What exactly the study..., be is that the Zanikimo P-to-1 combo in the first line and the phase two ZANI plus those attacks that are in the first line of. Thank you. Thank you.

What exactly the study.

Would be is that does any chemo PD one combo in the first line G.

<unk>.

And the phase twos any plus docetaxel in the first line of Oh, my past with breast cancer.

And if so can you help us to set the expectation on how many patients and the follow up duration at the readout.

Unknown Attendee: Patience, Alan. Markham and Patience, and the follow-up of your... No, thank you for 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 as well, too, and then also as they are presented at the conference. So 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 going to be presented on the posters at that meeting or in the presentations at that meeting. Okay, that's fair. So for this AW49, I'm just wondering what your bar is, or what you would recommend.

Thank you for the first part of your question again, we just wanted to clarify that we have made.

Uh huh.

Abstract submissions for Ampco, obviously, we need to wait until those are accepted.

All this online and then we'll be glad to talk about them.

At that time, I would love to and then also.

As they are presented at the conference I don't think we'll add any more color to that.

The out of stocks and so we know that there it's up to them.

We understand what we've presented in the poster.

Our reputation for that.

Okay, that's fair.

So far the CW 49, just wondering what would you what would be your bar or what kind of profile. What you look for to format go no go into fishing.

Neil Josephson: What profile would you look for to form a go-no-go decision? Is that comparable to, like, in HER2? I just want to hear your comments.

Is that comparable to <unk>.

Just wanted.

To hear your color on that.

Neil Josephson: Yeah, I think from our standpoint, this is early clinical development. So we're trying to find a dosing regimen that we think will allow us to optimize efficacy in 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 the decision will be 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.

Yes, I think from our standpoint. This is early clinical development. So we're trying to find the dosing regimen.

That will allow us to optimize the efficacy and patient populations in the phase II.

Honestly, where we're working on.

More frequent regimen of dosing for <unk> 49 on a once weekly basis, which we hope will give us the therapeutic window that we need to move forward into phase III.

Thank you.

Based more on the totality of the data that we've seen.

Neil Josephson: And I think after we finish this last cohort group 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's an exciting compound.

In phase one has been a pretty extensive phase one program for <unk>.

<unk> 49, and I think after we finish.

The last cohort group this year.

Then we will be able to make a decision based on the totality of the data rather than a specific benchmark because it is early clinical development.

Neil Josephson: 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 on the Phase 1 study in a peer-reviewed publication in the second half, which will provide the rationale for how we're moving that forward into Phase 2. Just a quick follow-up on the ADC technology platform. What kind of improvement in chemistry or technology? Should we expect any in the next one? He's very, like, has multiple eyes.

We're aware of the opportunity or presumably 49, we think it's exciting.

We just need to find a regimen that we think is appropriate to move forward into phase III and we'll be able to provide all of that data on the phase one study in a peer reviewed publication in the second half and provide the rationale for how we're moving that forward.

Okay.

Okay, maybe just a quick follow up on the ADC technology platform.

Like what kind of.

<unk> chemistry or technology.

Should we expect.

Next generation of your ADC platform and with <unk>.

Considering like multiple ind's will be will be up and running.

Neil Josephson: Yop, and Running. Yeah, so as you're aware, DW49 was moved into 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 don't think we haven't talked much about it yet.

In the next years.

Yes. So as you are aware is going to be 49 was moved into the clinical studies.

Number of years ago.

Current and next generation ADC platform that we're working on with our preclinical candidates.

Lately difference.

ADC platform that we think is very competitive.

World Class.

Neil Josephson: 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, including NR2, and what our strategy is of bringing forward on that, what So I think once we have that forum later this year, we'll be able to talk more fulsomely about that. Thank you for your questions. Our next question comes from Yigal Nochomovitz of Citigroup. Please go ahead.

And I think were havent talked much about it yet.

We're hoping to have an R&D forum in the fourth quarter of this year.

Fully explain the new platform that we have why we think it's next generation why we think its world class what targets were specifically trying to pursue with that technology.

I would like to think it has some benefits over and above.

What we're seeing today with adcs and putting in her to and what our strategy is bringing forward on that what the team is what the partnership strategy is so I think once we have that form later this year, we'll be able to talk more fulsomely.

About that.

Thank you.

Thank you for your question.

Our next question comes from Egalet <unk> of Citigroup. Please go ahead.

Unknown Attendee: Hi, Kenneth and Gene, thanks for taking the question. So obviously, you're aware of the TOPAS-1 data, the phase 3 trial that AstraZeneca did in first-line biliary, which... Triple Condole, Gunnick Tindy, James Fitz.

Hi management, Thanks for taking the question.

So you are aware of the Topaz one data the phase III trial with Astrazeneca. The first time in the area, which.

Congo.

This showed a median.

Unknown Attendee: [inaudible] Showed a median life of about 13 months, and PFS of 7 months. So given that, I just wanted to get your thoughts in terms of competitive positioning versus that data. Are you going to move ahead with the pivotal for Xanax plus chemo and first find abilities? And what would be the factors that give you confidence that you can improve upon what AstraZeneca has shown in TOPAZ 1 with Zerva plus chemo? Yeah, that's a really good question.

13 months PFS of seven months.

So given that I just wanted to get your thoughts in terms of competitive positioning versus that data.

Are you going to move ahead with a pivotal presenting plus chemo in first line.

What would be the factors that give you confidence that you can improve upon what astrazeneca has shown and topaz, one with <unk> plus chemo.

Yes.

Neil Josephson: Again, I think I'm going to pass over to Neal Josephin, our CMO, to just talk a little bit about the TOPAZ data and how our use of Xani can be effective in patient populations with biliary tract cancer. Yeah, thank you. So, you know, TOPAZ 1 is an important study. It's an important advance for patients with biliary tract cancer and 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.

Really good question.

Again, I think I was going to pass over to Neil Josephson.

Just talk a little bit about that.

And how our use of Danny.

Can be effective in patient populations ability breakthroughs yeah. Thank you. So topaz one is an important study.

In advance for patients with biliary tract cancer is something that you have to look at it.

In terms of if we are going to go into first line on biliary tract cancer as as a potential unlikely on standard of care therapy.

Neil Josephson: In terms of where Xani is going to focus, Xani is going to focus on patients that have HER2 amplification and expression. And we know from our experience in later-stage biliary tract cancer that we have a very active agent. And so, you know, we feel confident that for patients with HER2-amplified and overexpressing biliary tract cancer, Xanadatamab in any line of therapy can improve outcomes. So, you know, I don't, you know, I don't want to take away anything from this advance.

In terms of Where's Danny is going to focus that he's going to focus on patients that have heard two amplification and expression and we know from them from our experience in later line biliary tract cancer, and we have a very active agent and so.

We feel confident that.

Uh huh.

For patients with her two amplified and over expressing biliary tract cancer and Jana data man in any line of therapy and improve the outcomes on that so.

I don't.

I don't want to take away anything from an advanced the advances is significant.

Neil Josephson: The advance is significant, but we're looking to improve on a specific population, and we have a drug that targets an oncogenic driver in that population, believe that it can add to whatever benefit is given in general to biliary tract cancer patients. Okay, great, that's very helpful. And then, just also related to TILPAS-1, obviously, it's very interesting research since it's showing that immune modulation can work in biliary tract infections on top of standard of care.

We're looking to improve on this specific population and we have a drug that targets.

An oncogenic driver in that population leave that David can add to whenever benefit.

Is given and in general people are track cancer patients.

Okay great.

That's very helpful. And then just also related to Topaz. One obviously, it's a very interesting study showing with immune modulation can work and build area on top of standard of care I'm. Just wondering if you've thought about exploring zanni plus as Elizabeth <unk> plus chemo in first line bill rate or maybe even the chemo free approach.

Neil Josephson: I'm just wondering if you've thought about exploring Xani plus tizolizumab plus chemo in first-line biliary, or maybe even the chemo-free approach of Xani plus tizolizumab in first-line biliary, which could give you potentially more options to compete against AstraZeneca.

Coach Danny.

And first line biliary, which could get you essentially.

More options to compete against Astrazeneca is regimen.

Neil Josephson: Yeah, we definitely are interested in the combination of xanadatamab with PD-1 inhibitors. I mean, as you know, we're pursuing that in gastric indications. But as you point out, there's now evidence that it's active in biliary tract cancer, or PD-1s have a role in biliary tract cancer. So yes, it would be something that we would be interested in looking at in terms of a specific study. We don't have anything planned or designed at this point.

Yes, we definitely are interested in in.

Combination of.

Xander, Adam that with PD one inhibitor.

As you know we're pursuing.

That in the gastric.

Indications.

But as you pointed out.

There is now evidence that it's that it's.

Active in biliary tract cancer or PD ones have a placement in biliary tract cancer. So yes, it would be something that we would be we would be interested in looking at in terms of a.

A specific study we don't have anything planned are designed at this point.

Neil Josephson: Okay, and then just switching over to ZW49, obviously you saw the other competitive trial, DESTINY-BREX-04 for an HER2, which showed that they hit on PFS and OS, although they didn't disclose the details yet. Just wondering how that's impacting your strategic course and thinking with respect to developing ZW49 in the HER2 low population.

Okay, and then just switching over to <unk> 49.

Obviously the other.

Kind of a trial destiny, Brian zero for her and her too.

So.

Hit on PFS and OS.

Although they didn't disclose the details yet just wondering how thats impacting your strategic course in thinking with respect to developing TWD 49 in the Hertz.

Low population. Thank you.

Neil Josephson: So, again, to sort of echo some of Ken's comments, I think that, you know, we are interested in, you know, heart 2 low. It's not something that we've specifically been looking at in the phase 1 study now, but it is definitely something that we believe Xanadatum, sorry, ZW49, can play a role in. You know, in addition, I would say that HER2 and ZW49, while they are both ADCs, they have different mechanisms for action, so it's not as if one and the other can't have roles in the same disease.

Yeah. So so again just sort of.

Echo some of Ken's comments I think that that.

We are interested in in.

Far too low.

Something that we specifically.

Looking at in the Phase one study now, but it is definitely something that we believe.

As an addendum I'm sorry 49.

Play a role in.

In addition, I would say that that in her too.

<unk>.

GW 49, while they are both adcs they have.

Different mechanisms of action, so it's not us.

Yes.

Yes.

And the other half.

Have roles on the same disease so.

Neil Josephson: So, you know, it's definitely true that HER2 is a very, very active drug. We believe that ZW49, if we develop it, can have, you know, in HER2 low, an indication and a place and a role as well. Thank you very much.

It's definitely true that <unk> is a very very active drugs.

We believe that that GW 49.

If you develop it can have.

In hard to LOE was have a indication of placed in a role as well.

Thank you very much.

Unknown Attendee: Our next question comes from Akash Tiwari of Jeffreys. Please go ahead. Hey guys.

Our next question comes from a cash <unk> of Jefferies. Please go ahead.

Unknown Attendee: So previously, the Zyme team had talked about aggressively finding partners for ZW25 to get full value of the asset. But it's also kind of created a situation where investors have a difficult time understanding the market opportunity. If we assume ZW25 does not get a partner, which programs would Zyme be able to run by itself? And what would be the approximate cost of those studies?

Hey, guys.

Previously the design team had talked about aggressively finding partners for <unk> 25 to get full value of the asset, but it's also kind of create a situation where investors have a difficult time understanding the market opportunity. If we assume 25 does not get partner, which programs would be able to run by itself and what would be the approximate cost of those studies and <unk>.

Kenneth Galbraith: And should a situation where 25 doesn't doesn't get partnered be our base case expectation? And then maybe just on ZW49, are there any concerns that the eye toxicity we've seen with that ADC might be related to the Zyme link technology and therefore be a broader platform related issue? What can you kind of comment on that theoretical concern? Thanks. No, thanks for the two questions. I'll take the first one; I'll ask Neil Jay to take the second one.

Situation, where 25 does it doesn't get partner would be our base case expectation and then maybe just on CW <unk> 49.

Is there any concerns that the eye toxicity, we've seen with that ADC might be related to the zyme linked technology and therefore be a broader platform related issue. What can you kind of comment on that theoretical concern.

Kenneth Galbraith: But, you know, just on your first question, so, you know, today, we've obviously been able to start and, you know, expect to complete two pivotal trials for ZANI in conjunction with our regional partner, Beijing, who, as you know, has rights in China, Korea, and some other markets in Asia Pacific. So we can certainly undertake some good clinical development of that agent. And again, our second study in First Line G8 had over 700,000 patients studied in 38 countries. So we're perfectly capable of doing that.

No. Thanks for the two questions I'll take the first one Neil David take the second one but.

Just on your first question so to date, we've obviously been able to to start.

<unk>.

To complete pivotal trials for Danny.

So with our regional partner Peking, who as you know has.

Price in China, Korea, and some other markets in Asia Pacific. So we can certainly undertake some some good clinical development of that agent and again, our second study.

<unk> has over 700 patients on in 48 countries.

Kenneth Galbraith: I think from a commercial strategy, we've said this pretty consistently from the day I started. I think, in this sort of expressing market, the expressing tumor marketplace right now, we need to be partnering and collaborating with someone who can help us compete and broaden out the potential of ZANI and DW49. And so that's what we're looking for. From our standpoint, we think there's interest in this marketplace. I think we're seeing, you know, potentially with the recent AZ data to redefine how these patients are classified and potentially open up treatment to a whole other range of patients that previously would not have been considered for therapy with HER2-targeted agents. So we're quite comfortable that we have a good agent in Danny.

Capable of doing that I think from a commercial strategy. We've said this pretty.

With me today I started I think.

In this way to expressing market expressing tumor marketplace right now we need to be partnering and collaborating with someone who can help us compete and broaden out the potential of Danny and TWD 49.

And so that's what we're looking for I think from our standpoint, we think there is any.

First in this marketplace.

I think we're seeing.

The potential even with a reasonably easy data to redefine how these patients are classified and potentially open up treatments or all other range of patients that previously would not have been considered for therapy with her two targeting so we're quite comfortable with that.

We have a good agent was aeneas active pivotal stages.

Kenneth Galbraith: In fact, we're in the pivotal stages with a very differentiated antibody mechanism. And we think Danny has a place in the treatment of patients with expressing tumors even beyond BTC and GA. And we're quite comfortable that there is interest in folks who would like to join us and Beijing to find a way to commercialize the results of those studies around the world and also embark upon additional studies in areas where we think Danny can be extremely competitive and provide a clinical benefit that patients may not be getting from other therapies.

With a very differentiated antibody mechanism and we think it has a place.

In the treatment of patients with <unk> expressing tumors even beyond <unk>.

And we're quite comfortable there is interest in folks who would like to join us in Beijing. The final way to commercialize the results of most of those studies around the world and also embarked upon additional pivotal studies in areas, where we think it can.

Can be extremely competitive and provide a clinical benefit that patients may not be getting from from other therapies. So.

Kenneth Galbraith: So for us, our base case is that we need partnership to be able to compete for good sources of funding. It's a good way for us to make, to optimize the value of the brand that we currently have.

For us our base cases that we mean partnering to compete.

It's a good source of funding is a good way for us to make to optimize the value of the brand that we currently have and that's true not just with any but also throughout the entire portfolio.

Kenneth Galbraith: And that's true, not just with Danny, but also throughout the entire portfolio with ZW49 and the early research team. So we have a pretty broad and active partnering program throughout the portfolio, and I think we're finding lots of interest in the technology platforms that we have that produce Danny and ZW49 and also the new platforms we have around the next-gen ABC and multi-specific platform format.

It will be 49, and the early research team. So we have a pretty broad.

Active Permian program throughout the portfolio and I think we're finding lots of interest in the technology platforms that we have produced and it'll be a 49 and also the new platforms, we have around Nextgen in D C and multi so.

Kenneth Galbraith: So that is our base case, that we will have partnerships in place to allow us to compete in a broader way than we currently have now, and it'll allow us to fund, obviously, a much broader clinical program going forward and support commercialization around the world. And I'll let Neil answer the ZW49 question for you.

Format. So that is our base case is that we will we will.

I'll have partnerships in place to allow us to compete in a broader way than we currently have known it allow us to fund obviously much broader clinical program going forward and support commercialization.

The World and I'll, let Neil answer there is there'll be 49 question for you.

Neil Josephson: So she asked specifically about eye toxicity as being potentially a component of the underlying ADC technology. And I guess it's, I would say that eye toxicity is something that is seen across a variety of ADCs, and so it's something that is inherent to, you know, how ADCs work. There's some off, you know, off-target toxicity in the eye with ADCs. And there are some indications there may be some on-target toxicities as well. I think that the goal is to try to come up with a dosing regimen and an indication where you have the best therapeutic index. And so I don't see that the keratitis or eye toxicity that we've said exists with CW49 is any different than with a toxicity that's eye toxicity or other toxicities that have been seen with other ADCs.

Yes, So you asked specifically about toxicity as being potentially.

Hum.

Uh huh.

Component of the of the underlying ADC technology, and I guess, it's I would say that I toxicity as is.

Something that that is seen across a variety of.

Adcs.

And so it's something that is that is inherent to two.

How adcs work.

There are some off.

Hum.

Off target toxicity.

In the eye with <unk> Adcs, there in some indications.

Some indications there may be some on target toxicities as well.

I think that the.

The goal is to try to come up with a dosing regimen and a.

An indication where you have the best.

Our therapeutic index and so.

Don't see that the tightest solar or <unk> Sydney.

Yes.

<unk> said is.

Yes.

Yes.

CW 49 is any different than.

<unk>.

Toxicity Thats I talking to your other toxicities that have been seen with other adcs.

Neil Josephson: The, you know, the issue for us is to try to develop it in a way where we can maximize the benefit of the drug and minimize the adverse events, and that's where we're headed. Our next question comes from Jessica Psi of J.P. Morgan. Please go ahead. Hey, good afternoon. This is JR On for JET.

The.

The issue for us is to try to develop it in a way where we can maximize the benefit of the drug and minimize the adverse events.

That's where we're headed.

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

Unknown Attendee: Thank you for taking our questions. So we have a couple of clarifying questions. On ZANI, can you confirm with us what data sets you plan to submit to ASCO? And if the Beijing data is positive in first-line breast cancer, what's your development plan over there? Do you plan to run a new study in phase two in the U.S. by yourself, or do you plan to look for a new partner? And on ZW49, I know that today's press release says that there was no dose-limiting toxicity observed with weekly dosing. I'm just curious.

Hey, Good afternoon. This is Jay on board.

Jeff. Thank you for taking our questions. So we have put a couple of clarifying questions.

Danny can you come from with US what data sets do you plan to submit to ethical and.

If the baked.

Patient data is positive in personal in breast cancer.

What's your developmental plan over there do you plan to run a new study in phase III Bayou.

In the U S by yourself or do you plan to to look for a new partner.

And on Tw 49.

Today's press release.

Yes that does no dose limiting toxicity observed with the dosing.

Just curious.

Unknown Attendee: What about the every-three-week dosing regimen that you are still evaluating currently? Have you seen any outstanding safety signals right there? And lastly, I think you mentioned something about ODEX, and I know that you just said we shouldn't be worried about that, but just would love to clarify: what are the key issues?

What about with the every three week dosing regimen to you. All soon graduating currently have you assumed any outstanding safety signals right there.

Lastly, I think you mentioned something about.

Oh deck and I know that you just said, we shouldnt be worried about that but just just would love to clarify what are the key issues.

Raised by all day.

Ah you try a prudent combination.

Based on that.

Kenneth Galbraith: Sure, thank you. Thanks for the questions. I'll answer the first and third, and I'll let Dr. Joseph answer the second one.

Sure. Thanks, Thanks for the question I'll answer the first and third and I'll, let Dr. Joseph answer the second one so on.

Kenneth Galbraith: So on the first question, all we've confirmed is that we've made a number of abstract submissions to ASCO, and I think we'll wait until those are accepted and publicly available to then be able to talk about what's in those data abstracts. And also, we'll obviously have the appropriate disclosure and investor event at ASCO around the actual presentations of those submissions. So we'll talk more about those things until we get to that point.

The first question you always get affirmative we've made a number of.

Abstract submissions to ask though and I think we'll wait until those are accepted and publicly available to them.

Be able to talk about what's in the abstract.

And also we'll obviously have.

The appropriate.

Disclosure and Investor event at <unk> around the actual presentations of those although submission so.

I'll talk more about those until we get to that yes at that point.

Kenneth Galbraith: Also, we have discussed publicly before that we're, you know, excited about the pivotal sites for BTC and GEA going forward with Beijing for ZANI. We think there's additional clinical development opportunities there for ZANI to find a place to treat patients effectively with tertiary stressing tumors that, you know, may not be may not be dealt with with other competitive agents. Which ones we go to next, though, we have not yet decided.

We have discussed previously publicly that we're we're excited to look a little closer because in gea going going forward with.

With aging or as any.

Think there's additional clinical development opportunities there.

Or is any of the plan in place.

Two to treat patients effectively with richer expressing tumors that may not be it may not be dealt with with other other competitive agents.

Once we go into next though we have not we have not decided obviously we've done a bunch of work in breast cancer. Both early and later stage, we've done work in colorectal cancer and we've actually done working in lung cancer as well. So we'll be looking at all the potential alternatives to go forward.

Kenneth Galbraith: Obviously, we've done a bunch of work on breast cancer, both early and later stage. We've done work on colorectal cancer, and we've actually done work on lung cancer as well. So we'll be looking at all the potential alternatives to go forward beyond BTC and GEA in the coming time period.

Beyond BTC and GE.

In the coming time period, and once we have made a decision about some will certainly make that disclosure, but as of today, we won't we won't be able to make that.

Kenneth Galbraith: And once we've made a decision about that, then we'll certainly make that disclosure. But as of today, we won't be able to make that disclosure as more data comes in is available to us. And as we make that publicly available, which we'll do at ASCO, I think it'll provide the rationale for the study we've already started. It'll provide the rationale for the next stage of clinical development for ZANI. So we won't we won't get ahead of that data in talking about it.

That disclosure as more data comes in and is available to us and as we make that publicly available, which we'll do it at <unk> I think the rationale or.

For the study we have already started and the rationale for the next stage of clinical development for presenting so we wont get ahead of that data.

And talking about it I think the third point again, we had a few questions about.

Kenneth Galbraith: I think the third point, again, we had a few questions about our ZANI study after the events of an event at Lilly at FDA at ODAC. And we were just trying to clarify that our situation is not similar with respect to our global study for ZANI. So in GEA, we're doing, you know, 300 sites in 38 different countries.

Are there any study after the events of intervention fully at FDA at <unk> and we were just trying to clarify that our situations not similar with respect to our global study presented at <unk>, we are doing.

300 sites in 38 different countries with a very global.

Kenneth Galbraith: It's a very global, broad patient population that we're recruiting in that study, and we believe that it will be sufficient enough to be fallible in all major markets around the world. And that was the purpose of that study. We did have regulatory interaction with FDA before that study. So it's not a similar situation. We just wanted to preactively talk about that because we've had a few investor questions about that event that happened in Lilly. And It's not a similar situation.

Broad patient population that we're recruiting that study and we believe that will be sufficient enough to.

To.

The volatile in all major markets around the world.

The purpose of that study, we did have Brian regulatory Nash with FDA before that study. So it's not a similar situation. We just wanted to proactively.

Talk about that because we've got a few investor questions about about that event that happened.

And this is not a similar situation. So we're not concerned about that at all and I'll, let Dr. Joseph answer your CW 49 question about dose.

Kenneth Galbraith: So we're not concerned about that at all. I'll let Dr. Joseph answer your CW49 question about dose-limiting toxicity. Yeah, so the issue with dose-limiting toxicity or the announcement that that is true of both the Q week and the Q3 week. And I think what we're saying is that we've evaluated 30 patients at the Q3 week. And we're still trying to figure out what dose we'd like to get to or what we can get to and expand on in the Q week. And as noted, you know, we're going to release data on the second half of this year. And a lot of that information will be available at that time.

Dose limiting toxicities.

So the issue with dose limiting toxicity.

Now since that that.

Is true of both the two week and the Q3 week and I think what we're saying is that is that we have.

Evaluated 30 patients at the Q3 week and we're still trying to figure out what what dose we'd like to get to or what we what we can get to them and expand on into Q week.

And as noted we're going to release data on the second half of this year.

A lot of that information will be available at that time so.

Neil Josephson: So, you know, we'll have information about the dosing of multiple patients at the Q week and the expansion cohort at the Q3 week later this year. Once again, if you have a question, please press star, then 1. Our next question comes from Charles Zhu of Guggenheim Securities. Please go ahead. Hi, this is Edward on behalf of Charles Zhu. Just a question on DW-49.

Yes.

We'll have information about about dosing.

Multiple patients at the two week and the expansion cohort at the Q3 week later this year.

Okay.

Okay.

Okay.

Once again, if you have a question. Please press star then one or.

Unknown Attendee: In the preclinical data, you showed that on a mass equivalent basis, you have better efficacy actually than in HER2. But we know that you and that HER2 is dosed every three weeks at five to six mixes per tick, depending on the indication. And that for DW-49, you're going at 2.5 doses per tick every week. How do you think about the exposure levels that you'll be able to get with this different dosing regimen and how competitive do you think you could be? Do you think that would sort of translate into efficacy there?

Our next question comes from Charles <unk> of Guggenheim Securities. Please go ahead.

Hi, This is Edward on for Charles.

Just a question on <unk> 49, and the preclinical data you showed that aren't on the mass equivalent basis, you have better efficacy actually hurt you, but we know that <unk> and <unk> dose that.

Every three weeks at 5% to six makes for kicked depending on the indication and that <unk> 2049, youre going at $2 five an extra kick every week, how do you think about the exposure levels that you'll be able to get with this different dosing regimen and how competitive do you think you could be do you think that would sort of translate until that the.

The efficacy there.

Neil Josephson: So, you know, again, I can tell you that we're going to release data later this year, and at that point, you'll have a chance to see what dose we went to in the Q week, and then also in the Q3 week, we'll be talking about the exposures that we can achieve in the two different dosing regimens. And then, again, just to point out that HER2 and ZW49 are both ADCs, but they have very different mechanisms of action, and, you know, where their place is in the clinic could be very different. And for us, the challenge is to find out how we can meet the unmet needs of patients, and there still are unmet needs of patients that have HER2 positive disease, or even HER2 low disease, that we believe that Z There appear to be no further questions. I'd like to turn the conference back over to Zymeworks for closing remarks. Well, that's great.

So.

Again, I can I can tell you that we're going to release data later this year.

At that point, you'll have a chance to see what dose we've gone to on the on the two week and then also on the Q3 week, we'll be talking about the exposures that we that we can achieve in the two different dosing regimens and then again just to point out that in her too.

<unk>.

<unk> 49 are both adcs, but they have a much different mechanisms of action and.

Tom.

Where there are places in the clinic.

It could be very different and.

Alright.

For us the challenge is to find out how we can meet the unmet needs of patients and there still are unmet needs of patients.

Her two positive disease that or even hard to low disease that we believe that as EW 49 can help.

Amit.

Okay.

Kenneth Galbraith: Thank you, operator. And again, I just wanted to close by saying I really appreciate, we really appreciate everyone's time on the call today. I know there have been world events today that everyone's been paying attention to, which are, you know, much more important than a biotech company earnings call. But we certainly appreciate your time and attention. And again, our thoughts today at Zymeworks are completely with those in Ukraine and their families who may be worried outside of Ukraine. And we're just thinking about thinking about them as part of this call.

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

Well that's great. Thank you operator, and again I just wanted to close the thing I really appreciate it we really appreciate <unk> time to end the call I know there has been a world events today that everyone's been paying attention to which are much more important than a biotech company earnings call.

We certainly appreciate your time and attention and again, our thoughts today as iron works are completely with.

With those in the Ukraine and their families who may be worried outside of Ukraine and were.

Thinking about.

Kenneth Galbraith: So I really appreciate your attention today, and we look forward to reporting more progress on what I hope is a really exciting year for Zymeworks in 2022. And we look forward to reporting progress in the weeks and months ahead and then answering your questions as we can about that. So, thank you for your attention and time. I 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. [music] [inaudible] The Ultimate Parody Site! The End, www.mytrendyphone.co.uk [inaudible] The Ultimate Parody Site! [music] [inaudible]

Thinking about them.

Part of this call. So really appreciate your attention today and we look forward to reporting more progress on that I hope is a really exciting year for <unk> during 2022, and we look forward to reporting our progress in the weeks and months ahead of the in answering your questions.

As we can about that so thank you for your attention and I 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.

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