Q2 2022 Zymeworks Inc Earnings Call

August 4, 2022

[music].

Thank you for standing by.

Yeah.

Thank you for standing by this is the conference operator, welcome to <unk> second quarter 2022 results conference call and webcast. As a reminder, all participants are in a listen only mode and the conference is being recorded after the presentation there will be an.

This is the conference operator.

You may disconnect your lines.

Welcome to Zymeworks second quarter 2022 results conference call and webcast.

Thank you for participating and have a pleasant day.

As a reminder, all participants are in a listen-only mode and the conference is being recorded. After the presentation, there will be an opportunity to ask questions.

The opportunity to ask questions to join the question queue Press Star then the number one one on your telephone keypad.

To join the question queue, press star, then the number 1, 1 on your telephone keypad.

I would now like to turn the conference over to Jack Spinks, Associate Director of Investor, Relations at Zymeworks.

Now I'd like to turn the conference over to Jack Spinks Associate director of Investor Relations at Fine works Jack. Please go ahead.

Jack, please go ahead.

Good afternoon and welcome everyone.

[inaudible] you can dial star 11 [inaudible] ご視聴ありがとうございました [music] Thank you for standing by.

Good afternoon and welcome everyone.

My name is Jack Spinks, Associate Director of Investor Relations here at Zymeworks.

This is the conference operator.

My name is Jack Spinks Associate director of Investor Relations here at <unk>.

Today, we will discuss our second quarter 2022 financial results as well as provide, an update to our ongoing business.

Welcome to Zymeworks second quarter 2022 results conference call and webcast.

Today, we will discuss our second quarter 2022 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, development of our product candidates, related clinical trials, anticipated data presentations, potential therapeutic effects of ZanaDataMap and our other product candidates, our proposed redomicile transactions and the anticipated timing and benefits, 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 impact of the ongoing COVID-19 pandemic and our anticipated response to the same, 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, impact of new hires, 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 in our stage of development.

As a reminder, all participants are in a listen-only mode and the conference is being recorded. After the presentation, there will be an opportunity to ask questions.

Before we begin I would like to remind you that we will be making a number of forward looking statements. During this call.

To join the question queue, press star, then the number 1-1 on your telephone keypad.

Including statements that relate to the implementation of our strategic priorities development of our product candidates related clinical trials anticipated data presentations.

I would now like to turn the conference over to Jack Spinks, Associate Director of Investor Relations at Zymeworks.

Jack, please go ahead.

<unk> therapeutic effects was added data Madden and our other product candidates.

Opposed we're domiciled transactions and the anticipated timing and benefits.

The 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 impact of the ongoing COVID-19 pandemic and our anticipated response to the same.

Good afternoon and welcome, everyone.

My name is Jack Spinks, Associate Director of Investor Relations here at Zymeworks.

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 impact of new hires our ability to execute new collaborations and partnerships and other information that is not historical information.

Today we will discuss our second quarter 2022 financial results, as well as provide an update to our ongoing business.

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 our stage in 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, development of our product candidates, related clinical trials, anticipated data presentations, potential therapeutic effects of ZanaDataMap and our other product candidates, our proposed redomicile transactions, and the anticipated timing and benefits. As a result of the COVID-19 pandemic, our 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 impact of the ongoing COVID-19 pandemic and our anticipated response to the same, 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, impact of new hires, 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 in our stage of development.

For discussion of these risks and uncertainties, we refer you to our latest SEC filings as, found on our website and as filed with the SEC.

For discussion of these risks and uncertainties, we refer you to our latest SEC filings as found on our website and as filed with the SEC.

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.

In addition, please note that today's earnings call does not constitute an offer to sell, or a solicitation of an offer to buy any securities or a solicitation of any vote or approval.

In addition, please note that today's earnings call does not constitute an offer to sell or a solicitation of an offer to buy any securities or a solicitation of any vote or approval.

In addition.

Please note that today's earnings call does not constitute an offer to sell or solicitation of an offer to buy any securities or a solicitation of any vote or approval.

In connection with the proposed redomicile transactions, Zymerx Delaware, Inc. is filed, with the SEC a registration statement on Form S-4 that includes a preliminary proxy statement slash prospectus.

In connection with the proposed redomicile transactions, Zymeworks Delaware Inc. is filed with the SEC a registration statement on Form S-4 that includes a preliminary proxy statement slash prospectus. The registration statement is not complete and will be further amended.

In connection with the proposed re domicile transactions with IMAX, Delaware, Inc. Has filed with the SEC a registration statement on form S. Four that includes a preliminary proxy statement slash prospectus.

The registration statement is not complete and will be further amended.

After the registration statement has been declared effective by the SEC, the final proxy, statement slash prospectus will be mailed to Zymerx security holders.

After the registration statement has been declared effective by the SEC, the final proxy statement slash prospectus will be mailed to Zymeworks security holders.

After the registration statement has been declared effective by the SEC. The final proxy statements filed prospectus, we mailed design work security holders.

You should carefully review the registration statement and other materials filed with the SEC by US enzyme works Delaware, Inc. As they will include important information about the proposed for domiciled transactions.

You should carefully review the registration statement and other materials filed with the, SEC by us and Zymerx Delaware, Inc. as they will include important information about the proposed redomicile transactions, including information about Zymerx and the directors and employees who may be deemed to be participants in the solicitation of proxies in favor of the proposed redomicile transactions.

You should carefully review the registration statement and other materials filed with the SEC by us and Zymeworks Delaware Inc. as they will include important information about the proposed redomicile transactions, including information about Zymeworks and the directors and employees who may be deemed to be participants in the solicitation of proxies in favor of the proposed redomicile transaction.

Including information about XI marks and the directors and employees, who may be deemed to be participants in the solicitation of proxies.

Favor of the proposed re domicile transaction.

These documents are available free of charge at the SEC's website at www.sec.gov.

These documents are available free of charge at the SEC website at Www Dot SEC Dot Gov.

Later in this call, Ken Galbraith, our Chair and Chief Executive Officer, will be discussing our financial results, including certain adjusted non-GAAP measures.

Later in this call Ken Galbraith, our chair and Chief Executive Officer will.

We'll be discussing our financial results, including certain adjusted non-GAAP measures.

A description of our adjusted 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.

A description of our adjusted 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.

As a reminder, the audio and slides from this call will be available on <unk> website later today.

Now, I will turn the call over to Ken, our Chair and CEO.

Now I will turn the call over to Ken <unk>.

<unk> and CEO .

Ken?

Ken.

Thanks, Jack and thank you everyone for joining us today for our second quarter earnings call.

As a reminder, I'd like to note that while I'll be presenting the prepared remarks today are members of our executive team will be available for questions and answers. Following this portion of the call.

Before I speak to our financial results I'd like to briefly announced the congratulate campus on his recent appointment as President. In addition to his current role as Chief operating Officer.

Neil has played an important role in the company reset over the past six months and this expansion of his leadership responsibilities as a natural step in the future growth and development of the company.

Also want to welcome Dr. Paul Mark <unk>, as our new Chief Scientific Officer, Paul starting with US on July 18th and has already begun to make valuable contributions to our early R&D efforts with this R&D colleagues.

Thanks, Jack, and thank you, everyone, for joining us today for our second quarter earnings call.

Thanks, Jack, and thank you everyone for joining us today for our second quarter earnings call.

With that I'd like to jump right into the overview of our financial results followed by an update on both our clinical and R&D programs as well as a noteworthy corporate update.

Followed by a few brief closing remarks before we open up the lines for question and answers.

As a reminder, I'd like to note that while I'll be presenting the prepared remarks today, members of our Executive Team will be available for questions and answers following this portion of the call.

As a reminder, I'd like to note that while I'll be presenting the prepared remarks today, members of our executive team will be available for questions and answers following this portion of the call.

This afternoon <unk> reported financial results for the quarter ended June 32022 as reported our revenue for the second quarter of 2022 was $5 4 million compared to $1 7 million in revenue for the same period of 2021.

Before I speak to our financial results, I'd like to briefly announce and congratulate Neal Klompas on his recent appointment as President, in addition to his current role as Chief Operating Officer. Neal has played an important role in the company reset over the past six months, and this expansion of his leadership responsibilities is a natural step in the future growth and development of the company.

Before I speak to our financial results, I'd like to briefly announce and congratulate Neil Kompas on his recent appointment as President, in addition to his current role as Chief Operating Officer. Neil has played an important role in the company reset over the past six months, and this expansion of his leadership responsibilities is a natural step in the future growth and development of the company.

Revenues for the most recent three month period, primarily related to a $5 million fee from the previously announced the trucker licensing agreement.

Research and development expense for the quarter ended June 32022 was $56 million compared to $50 7 million for the quarter ended in June 30 of 2021.

This increase from the prior year related primarily to higher clinical trial expenses presented data mab due to the continued ramp up of the horizon <unk> pivotal study and a corresponding increase in the associated drug manufacturing expenses, which were partially offset by the head count reduction from our previously announced restructuring.

While higher year over year due to the previously noted reasons, we recognize slightly lower research and development expenses quarter on quarter and we anticipate these expenses will continue to decline in the latter half of this year and into 2023 as we realize the benefit of our restructuring program completed earlier this year.

General and administrative expense for the quarter ended June 32022 were $15 2 million compared to $19 9 million for the quarter ended June 2021.

<unk> stock based compensation and restructuring expenses adjusted general and administrative expense increased by $1 3 million for the quarter ended June 32022, compared to the same period in 2021.

The increase year over year was primarily relate to an increase in professional fees and other expenses in 2022 and was partially offset by a reduction in general and administrative expenses from a reduction in head count as a result of our restructuring program.

<unk> net loss for the quarter ended June 32002 was $64 6 million compared to $67 5 million for the same period in 2021.

As I indicated earlier and worth repeating here, we anticipate our forecasted operating expenses will continue to decline in the second half of this year driven by a reduction in clinical expenses technical and manufacturing operation expenses and the impact of our restructuring program.

Our cash resources, consisting of cash cash equivalents and short term investments were $241 8 million as of June 32022.

Based on our current operating plan and in combination with proceeds from certain existing collaboration payments. We anticipate receiving we believe our cash resources will fund our planned operations into the second half of 2023 and potentially beyond this quarter, we announced our first step towards extending our runway as we recognized a $5 million fee from our licensing agreement with a truck and we look forward to building upon that progress.

And further extending our cash runway guidance for additional details 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 as available on our website at Www <unk> Dot com.

Before we go into our clinical update and as I mentioned earlier on this call our search for a new Chief Scientific Officer is complete as we brought Dr. Paul Moore on board to lead our early research and development group.

Paul brings with him a wealth of experience and knowledge in preclinical translational and early clinical development of novel Biologic based therapeutics with us.

Deep background developing by specific multi specifics and antibody drug conjugate.

Along with his background in farming and managing through partnerships and collaborations with pharmaceutical and biotech companies. We're very excited that Paul and the team and welcome his guidance and leadership.

I also want to welcome Dr. Paul Moore to Zymeworks as our new Chief Scientific Officer. Paul started with us on July 18th and has already begun to make valuable contributions to our early R&D efforts with his R&D colleagues.

I also want to welcome Dr. Paul Moore to Zymeworks as our new Chief Scientific Officer. Paul started with us on July 18th and has already begun to make valuable contributions, to our early R&D efforts with his R&D colleagues.

Given the announcement today of our early R&D day in October of this year yielded pivotal to the success of those programs and we look forward to sharing more about them in October .

With that I'd like to move on to a clinical update for our two lead programs.

With that, I'd like to jump right into the overview of our financial results, followed by an update on both our clinical and R&D programs, as well as a noteworthy corporate update, followed by a few brief closing remarks before we open up the lines for question and answers.

With that, I'd like to jump right into the overview of our financial results, followed, by an update on both our clinical and R&D programs, as well as a noteworthy corporate update, followed by a few brief closing remarks before we open up the lines for question and answers.

We made exciting progress this quarter for both our clinical candidates that are data mab or hurricane targeted bispecific antibody and that data maps overdose.

Or is <unk> 49, or her two targeting antibody drug conjugate.

This afternoon, Zymeworks reported financial results for the quarter ended June 30th, 2022. As reported, our revenue for the second quarter of 2022 was $5.4 million, compared to $1.7, million in revenue for the same period of 2021. Revenues for the most recent three-month period primarily related to a $5 million fee from, the previously announced ATTRECA licensing agreement.

Research and development expense for the quarter ended June 30th, 2022, was $56 million, compared, to $50.7 million for the quarter ended in June 30th, 2021. This increase in the prior year related primarily to higher clinical trial expenses for Xanadatamab, due to the continued ramp-up of the Horizon GEA-01 Pivotal Study, and a corresponding increase in the associated drug manufacturing expenses, which were partially offset by the headcount reduction from our previously announced restructuring.

I'd like to start by briefly highlighting clinical data was that a data map presented by our partner Beijing at the annual meeting of the American Society of clinical oncology or <unk> in June <unk>.

While higher year-over-year due to the previously noted reasons, we recognize slightly lower, research and development expenses quarter-on-quarter, and we anticipate these expenses will continue to decline in the latter half of this year and into 2023, as we realize the benefit of our restructuring program completed earlier this year. General and administrative expense for the quarter ended June 30th, 2022, was $15.2 million, compared to $19.9 million for the quarter ended June 2021.

Excluding stock-based compensation and restructuring expenses, adjusted general and administrative, expense increased by $1.3 million for the quarter ended June 30th, 2022, compared to the same period in 2021. The increase year-over-year was primarily related to an increase in professional fees, and other expenses in 2022, and was partially offset by a reduction in general and administrative expenses from a reduction in headcount as a result of our restructuring program.

Ximark's net loss for the quarter ended June 30th, 2022, was $64.6 million, compared to, $67.5 million for the same period in 2021.

As I indicated earlier, and worth repeating here, we anticipate our forecasted operating, expenses will continue to decline in the second half of this year, driven by a reduction in clinical expenses, technical and manufacturing operation expenses, and the impact of our restructuring program.

Our cash resources, consisting of cash, cash equivalents, and short-term investments, were, $241.8 million as of June 30th, 2022. Based on our current operating plan, and in combination with proceeds from certain existing, collaboration payments we anticipate receiving, we believe our cash resources will fund our planned operations into the second half of 2023, and potentially beyond. This quarter we announced our first step towards extending our runway as we recognize a $5, million fee from our licensing agreement with Atreca, and we look forward to building upon that progress, and further extending our cash runway guidance.

For additional details 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, as available on our website at www.ximarks.com.

Results from this phase <unk> study of that data map in the frontline setting of her two positive breast cancer and gastric cancer were presented in two separate poster sessions.

Finally, before we go into a clinical update, and as I mentioned earlier on this call, our, search for a new chief scientific officer is complete, as we brought Dr. Paul Moore on board to lead our early research and development. Paul brings with him a wealth of experience and knowledge in preclinical, translational, and early clinical development of novel biologic-based therapeutics. With his deep background developing bispecifics, multispecifics, and antibody drug conjugates, along with his background in forming and managing strategic partnerships and collaborations with pharmaceutical and biotech companies, we're very excited to have Paul on the team and welcome his guidance and leadership.

Both datasets demonstrated promising antitumor activity and a manageable safety profile for the treatment of advanced or metastatic disease within a data mab given in combination with standard of care chemotherapy.

The regimen given to the gastric cancer cohort also includes a PD one inhibitor Tesla the gastric cancer data presented provide support for the experimental regimens that are data map antigen and.

In combination with standard of care chemotherapy and the ongoing horizon <unk> pivotal study.

The maturing data from the fully enrolled breast cancer cohort will help to inform a potential development path presented data map and that indication.

Additionally, we anticipate presenting data at a major medical meeting before the end of the year from our ongoing study in later line. Her two positive hormone receptor positive breast cancer patients treated with that data map in combination with full restaurant and public Vickland Pfizer CDK four six inhibitor.

Dataset will also be important to informing our future development plans presented data mab in breast cancer.

We are continuing to make progress with our multicenter Global Phase two open label first line study of <unk> plus standard first line combination chemotherapy regimens in selected Gi cancers, including Gea, BTC and colorectal cancer.

The Gea cohort originally reported in September 2021 at Emo continues to follow the fully enrolled patient population and we hope to be able to present additional clinical data based on longer term follow up at a major medical meeting in the first half of 2023, including data related to duration of response progression free survival and overall survival.

<unk> as well as updated safety information.

We also continue to enroll patients in our cohort for first line BTC and first line colorectal cancers.

Furthermore, we also announced this quarter that we now expect topline data from our horizon BTC, one phase III pivotal clinical trial of <unk> monotherapy for the treatment of metastatic or advanced her to amplify biliary tract cancer to be available before the end of 2022.

Slightly earlier than previously announced with this timeline, we would expect to be able to present comprehensive clinical data from horizon <unk> one trial at a major medical meeting in the first half of 2023 now I'd like to share an update on our second clinical stage candidate <unk> or <unk> 49, a bypass topic her two targeting.

Drug conjugate.

We're very excited to announce that at the upcoming annual meeting of the European Society of medical oncology or <unk> in September in Paris, Dr. <unk> from the Memorial Sloan Kettering Cancer Center will be presenting preliminary results from our phase one study of a basket cohort of Hercules expressing solid cancers. Her many oral presentation will be the first.

Comprehensive disclosure of clinical data presented data about <unk>.

We look forward to sharing information about this program and Dr. <unk> presentation as well as our Investor Conference call and webcast on September 12.

Moving onto our preclinical product candidates earlier this year when we laid out our key strategic priorities, we announced our goal of having at least two investigational new drug application submitted by the end of 2024 I'm very pleased to announce we've made great strides in furthering that objective.

This afternoon, Zymeworks reported financial results for the quarter ended June 30th, 2022. As reported, our revenue for the second quarter of 2022 was $5.4 million, compared to $1.7 million in revenue for the same period of 2021. Revenues for the most recent three-month period primarily related to a $5 million fee from the previously announced Atreca licensing agreement.

As you may have read in the earnings release that went out earlier. This afternoon, we announced two key items that will help us accomplish this objective.

Research and development expense for the quarter ended June 30th, 2022 was $56 million, compared to $50.7 million for the quarter ended in June 30th, 2021. This increase in the prior year related primarily to higher clinical trial expenses for ZanaDataMab due to the continued ramp-up of the Horizon GEA-01 Pivotal Study, and a corresponding increase in the associated drug manufacturing expenses, which were partially offset by the headcount reduction from our previously announced restructuring.

While higher year-over-year due to the previously noted reasons, we recognize slightly lower research and development expenses quarter-on-quarter, and we anticipate these expenses will continue to decline in the latter half of this year and into 2023, as we realize the benefit of our restructuring program completed earlier this year. General and administrative expense for the quarter ended June 30th, 2022 was $15.2 million, compared to $19.9 million for the quarter ended June 2021.

Excluding stock-based compensation and restructuring expenses, adjusted general and administrative expense increased by $1.3 million for the quarter ended June 30th, 2022, compared to the same period in 2021. The increase year-over-year was primarily related to an increase in professional fees and other expenses in 2022, and was partially offset by a reduction in general and administrative expenses from a reduction in headcount as a result of our restructuring program.

Given the announcement today of our early R&D day in October of this year, he'll be, pivotal to the success of those programs, and we look forward to sharing more about them in October.

First we announced the date of our early R&D day, which will take place on October 20 of this year in New York City. This will be an important step in presenting data from our two lead preclinical platforms, our industry, leading multi specific antibody therapeutic platform and our next generation <unk> based ADC platform details of the meeting and the webcast will be available shortly on our.

With that, I'd like to move on to a clinical update for our two lead programs.

We've made exciting progress this quarter for both our clinical candidates, Xanadatamab, our HER2-targeted bispecific antibody, and Xanadatamab zovodotin, or ZW49, our HER2-targeted antibody drug conjugate.

I'd like to start by briefly highlighting clinical data with Xanadatamab presented by, our partner Beijing at the annual meeting of the American Society of Clinical Oncology, or ASCO, in June. Results from this phase 1b2 study of Xanadatamab in the frontline setting of HER2-positive, breast cancer and gastric cancer were presented in two separate poster sessions. Both datasets demonstrated promising anti-tumor activity and a manageable safety profile for, the treatment of advanced or metastatic disease with Xanadatamab given in combination with standard of care chemotherapy.

The regimen given to the gastric cancer cohort also included the PD-1 inhibitor, Tizla.

The gastric cancer data presented provides support for the experimental regimen of Xanadatamab, and Tizla in combination with standard of care chemotherapy in the ongoing Horizon GEA-01 pivotal study.

The maturing data from the fully enrolled breast cancer cohort will help to inform a, potential development path for Xanadatamab in that indication.

Our web site.

He'll be presenting data highlighting multiple preclinical product candidates.

So incredibly exciting to announce our two lead preclinical product candidates VW 191, and CW 171.

GW 171 is a novel and differentiated Bispecific T cell engaging antibody that was generated using our asymmetric bi specific platform. The same platform that helped generate that data map our lead product candidate.

GW 171 is designed to target the potential treatment of multiple solid tumor indications.

It's an important step in further diversification of our portfolio of antibody based therapeutics.

CW 191 is an antibody drug conjugate built using our recently announced <unk> based ADC platform and utilizes a cap of pizza and derive payload that we believe can be competitive in areas with high unmet clinical need such as ovarian cancer and other gynecological cancers.

CW 191 represents our second announced antibody drug conjugate the first things that a data map silver dotan and the first ADC built using our <unk> platform, while we're not disclosing the targets on this call I will note that importantly, both of these preclinical product candidates will represent our first step outside of that <unk> targeted therapy space, while we strongly believe both set of data.

And as I did about though it doesn't have the potential to address unmet needs in a range of cancer indications, we recognize the diversification beyond her too is an important next step one that it started with this announcement and advancement of these two candidates our overall mission and <unk> and the future R&D focus is clearly on novel multifunctional targeted therapies for difficult to treat.

Cancers.

Those with the lowest five year overall survival rates and where our advanced biologics may be able to make progress towards significantly improved outcomes for patients with cancers of the pancreas liver lung esophagus stomach colon ovary and certain hematological cancers, we look.

Look forward to expanding on both our two lead preclinical product counties additional preclinical product candidates our platforms and overall future scientific vision later this year in October at our R&D day, So stay tuned for further details.

The second key item, helping us achieve our objective of two IND applications by 2024 is the hiring of Dr. Palmer.

As you likely saw from our press release or the summer Paul brings with him a wealth of knowledge and biology preclinical development and translational research, but also the development of multiple FDA approved biologics for patients with difficult to treat cancers and autoimmune conditions.

Paul's hiring expertise will be key to the continued development and advancement of our preclinical product portfolio and in combination with our existing exceptional team of scientists and engineers will help further advance our portfolio of therapeutics.

Zymeworks net loss for the quarter ended June 30, 2022, with $64.6 million, compared to $67.5 million for the same period in 2021.

Given the exciting quarter, we've had on the clinical and R&D side of things. We also have an important update on the corporate side that's worth discussing here.

As I indicated earlier, and worth repeating here, we anticipate our forecasted operating expenses will continue to decline in the second half of this year, driven by a reduction in clinical expenses, technical and manufacturing operation expenses, and the impact of our restructuring program.

Our cash resources, consisting of cash, cash equivalents, and short-term investments, were $241.8 million as of June 30, 2022. Based on our current operating plan and in combination with proceeds from certain existing collaboration payments we anticipate receiving, we believe our cash resources will fund our planned operations into the second half of 2023 and potentially beyond.

In July of this year, we announced our plan to become a Delaware Corporation or.

While largely administrative in nature of this proposed re domicile is something that we believe provides important benefits to the business and our shareholders, both near term and long term.

While discussed previously on our July 15 conference call I will highlight again, a few key items.

We believe the proposed domicile from British Columbia to Delaware enhances alignment with our U S shareholder base and peer biotechnology companies and expands the potential institutional investor base in the United States.

So expands our eligible passive investment base in United States by enabling potential inclusion of <unk> and leading indices, such as select Russell and S&P indices.

<unk> reduces complexities and certain costs related to our future operations from a tax legal commercialization partnering and monetization standpoint.

While we believe there are many benefits important to highlight that as a result of this proposed re domicile simers will not change its name brand or ticker symbol and will not be moving employees out of Vancouver.

Given the tax efficient nature of the structure. We also don't believe the company or our U S shareholders will have an adverse taxable events and Canadian shows that elect to receive exchangeable shares can elect to defer all or part of any Canadian capital gains tax.

This process will require a special meeting of our security holders and approval of two thirds of the votes cast to approve the share exchange and re domicile to the U S as well as approval by the New York stock exchange and relevant Canadian courts of law.

Exactly when that spending will take place is largely dependent on the SEC review process for the S. Four filing however, we hope that it will occur within the next few months.

Completion of the re domicile is expected to occur in the fourth quarter of 2022, pending an affirmative shareholder vote and relevant court and regulatory approvals.

It's worth noting that the exchangeable share structure, we're proposing in the overall mechanism for affecting the re domicile of the Delaware is a well known and established administrative process that has been used successfully by other Canadian companies to re domicile to U S jurisdictions.

We also do not believe there'll be any impact to our patients operations business development efforts or other important corporate items as a result of this process.

To learn more about the structure process benefits or other items associated with the proposed re domicile, we would encourage everyone listening to consulting information. We previously filed with the SEC as well as the preliminary proxy statement prospectus filed on form S. Four with the SEC by <unk>, Delaware, Inc. Due to the regulated nature of communications relating to the proposed <unk>.

We're not planning to address questions regarding this matter during the Q&A session of this call and instead would refer you to the filings previously mentioned.

As we look ahead to the remainder of 2022 I will briefly highlight a few important key catalysts.

Additionally, we anticipate presenting data at a major medical meeting before the end, of the year from our ongoing study in later-line HER2-positive, hormone receptor-positive breast cancer patients treated with Xanadatamab in combination with Fulvestrant and Palvocyclin, Pfizer's CDK4-6 inhibitor.

I'll start with that data Mab were expected in the fourth quarter. This year. We're excited to present results from our late line her two positive hormone receptor positive metastatic breast.

Breast cancer study data.

<unk> in combination with the restaurant and publicly.

This dataset will also be important to informing our future development plans for Xanadatamab, in breast cancer.

We are continuing to make progress with our multicenter global phase 2 open-label first-line, study of Xanadatamab plus standard first-line combination chemotherapy regimens in selected, GI cancers, including GEA, BTC, and colorectal cancer.

We also now say an update to the timing of data from our pivotal trial horizon BTC, one where we now expect top line data to be announced late this year.

The GEA cohort, originally reported in September 2021 at ESMO, continues to follow the fully, enrolled patient population, and we hope to be able to present additional clinical data based on longer-term follow-up at a major medical meeting in the first half of 2023, including data related to duration of response, progression-free survival, and overall survival, as well as updated safety information.

Presenting <unk> adult and we're very excited to have announced in late July our acceptance to present at the European Society for medical Oncology Conference in Paris on September 12.

So it will be the first public release of data for our second product candidate and first antibody drug conjugate presented data.

Given the announcement today of our early R&D day in October of this year, he'll be pivotal to the success of those programs, and we look forward to sharing more about them in October.

Our preclinical product portfolio, we will be presenting data from both our lead preclinical product candidates VW, one anyone and CW 171, and our early R&D day in October of this year.

With other preclinical candidates that were excited to finally be able to share more information about with the public.

With that, I'd like to move on to a clinical update for our two lead programs.

Finally, I want to end with a short discussion about the potential impact of the continuing COVID-19 endemic on our workforce and operations.

We've been fortunate in 2022 to date to have minimal impact on our operations from the Covid endemic and government restrictions in response to regional outbreaks around the world.

We've made exciting progress this quarter for both our clinical candidates. Xanadatamab, our HER2-targeted bi-specific antibody, and Xanadatamab zovidotin, or ZW49, our HER2-targeted antibody drug conjugate.

I'd like to start by briefly highlighting clinical data with Xanadatamab presented by our partner Beijing at the annual meeting of the American Society of Clinical Oncology, or ASCO, in June. Results from this Phase 1b2 study of Xanadatamab and the frontline setting of HER2-positive breast cancer and gastric cancer were presented in two separate poster sessions. Both data sets demonstrated promising anti-tumor activity and a manageable safety profile for the treatment of advanced or metastatic disease with Xanadatamab given in combination with standard of care chemotherapy.

As we've seen recently, a new wave of infections from several sub brands is sweeping across the globe, but again, some cases to record infections and increase optimizations and fatalities in certain geographic regions.

Actively reviewing our current policies to protect the well being of our employees and their families.

In the event of any changes in government restrictions and to ensure the continuity of our operations.

Further as our activities are global in nature, we could be affected in the future in certain regions and the vintage changes in government restrictions on our ability to progress our business as we expect it to.

We will continue to evaluate any enhanced risks of the covenant damage to our global operations and take steps to mitigate any impact on our operations wherever possible.

We truly hope that a return to normalization in the face of the Covid epidemic continues but will ensure we are prepared for any new restrictions.

The regimen given to the gastric cancer cohort also included the PD-1 inhibitor Tizla.

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

The gastric cancer data presented provides support for the experimental regimen of Xanadatamab and Tizla in combination with standard of care chemotherapy in the ongoing HORIZON GEA-01 pivotal study.

The maturing data from the fully enrolled breast cancer cohort will help to inform a potential development path for Xanadatamab in that indication.

As a reminder to ask a question. Please press star one on your telephone keypad.

Additionally, we anticipate presenting data at a major medical meeting before the end of the year from our ongoing study in later-line HER2-positive, hormone-receptor-positive breast cancer patients treated with Xanadatamab in combination with fulvestrant and palvocyclin, Pfizer's CDK4-6 inhibitor.

If youre using a speakerphone please pick up your handset before pressing any case, we will pause for a moment as callers join the queue.

This dataset will also be important to informing our future development plans for Xenodatamab, in breast cancer.

We are continuing to make progress with our multicenter global phase 2 open-label first-line, study of Xenodatamab plus standard first-line combination chemotherapy regimens in selected, GI cancers, including GEA, BTC, and colorectal cancer.

We also continue to enroll patients in our cohorts for first-line BTC and first-line, colorectal cancers. Furthermore, we also announced this quarter that we now expect top-line data from our, Horizon BTC-01 phase 2 pivotal clinical trial of Xenodatamab monotherapy for the treatment of metastatic or advanced HER2-amplified biliary tract cancer to be available before the end of 2022, slightly earlier than previously announced. With this timeline, we would expect to be able to present comprehensive clinical data, from Horizon BTC-01 trial at a major medical meeting in the first half of 2023.

All right. Our first question comes from the line of Hugo <unk> with Citi. Your line is open.

Now I'd like to share an update on our second clinical stage candidate, Xenodatamab zobidotin, or ZW49, a biparatopic HER2-targeting antibody-drug conjugate.

We're very excited to announce that at the upcoming annual meeting of the European Society, of Medical Oncology, or ESMO, in September in Paris, Dr. Kumal Jhaveri from the Memorial Sloan Kettering Cancer Center will be presenting preliminary results from our phase 1 study, of a basket cohort of HER2-expressing solid cancers. Her mini-oral presentation will be the first comprehensive disclosure of clinical data, for Xenodatamab zobidotin.

Thanks for taking the questions Hi, Kennon team I just wanted to ask about your strategy in first line biliary given the data from Topaz. One earlier this year from Mckinsey questions, just given that data and obviously, depending on the results of the phase III any plus Genesis in first line biliary that youre running just wondering whether you'd consider.

We look forward to sharing information about this program at Dr. Jhaveri's presentation, as well as our investor conference call and webcast at ESMO on September 12th.

Adding to the list and that to the first liability regimen, which could build on the learnings from Topaz one because if you were to do the quad regimen of <unk> plus <unk> plus Gen. Six in your pivotal trial in biliary, perhaps this could be an interesting way to differentiate from Topaz one I'm curious your thoughts on that that strategy. Thank you.

Moving on to our preclinical product candidates, earlier this year when we laid out our key, strategic priorities, we announced our goal of having at least two investigational new drug applications submitted by the end of 2024.

Yes. Thanks for the question and again I think as you said, we're we're extremely optimistic in our current pivotal study using Danny as monotherapy in second line patient populations and that has the potential to be the the <unk>.

I'm very pleased to announce we've made great strides in furthering that objective. As you may have read in the earnings release that went out earlier this afternoon, we announced, two key items that will help us accomplish this objective.

First, we announced the date of our early R&D day, which will take place on October, 20th this year in New York City.

Her to targeted therapy for that patient population so.

We also continue to enroll patients in our cohorts for first-line BTC and first-line, colorectal cancers. Furthermore, we also announced this quarter that we now expect top-line data from our, Horizon BTC-01 phase 2 pivotal clinical trial of Xanadatamab monotherapy for the treatment of metastatic or advanced HER2-amplified biliary tract cancer to be available before the end of 2022, slightly earlier than previously announced. With this timeline, we would expect to be able to present comprehensive clinical data, from Horizon BTC-01 trial at a major medical meeting in the first half of 2023.

We're optimistic by the data we saw previously was that a data map, we're happy to be able to get to a top line dataset earlier than we had expected.

I think we're still.

Recruiting in our ongoing phase II study with first line biliary tract cancer patients.

So that is an interim data set for us I think at the time that we have our ability to attract.

Cancer data later this year will.

We will be prepared then to talk about the nature of regulatory filings and next steps in looking at whether we can expand the patient population beyond the the.

The current pivotal study into additional expandable.

Expanded label indications and obviously, we're following all the competitive datasets that might be available.

For this patient population of though we are the only ones really with a <unk> targeted therapy for the patients that.

That we're really looking to treat so I think well have more to say about that once we get to our pivotal data.

Uh huh.

The data release later this year if that's okay.

This will be an important step in presenting data from our two lead preclinical platforms, our industry-leading multi-specific antibody therapeutic platform, and our next generation, TOPO-based ADC platform. Details of the meeting and the webcast will be available shortly on our website.

Now I'd like to share an update on our second clinical stage candidate, Xanadatamab zilvidotin, or ZW49, a biparatopic HER2-targeting antibody drug conjugate.

While we're presenting data highlighting multiple preclinical product candidates, it's, also incredibly exciting to announce our two lead preclinical product candidates, ZW191 and ZW171. ZW171 is a novel and differentiated bispecific T-cell engaging antibody that was generated, using our asymmetric bispecific platform, the same platform that helped generate Vanadatamab, our lead product candidate. ZW171 is designed to target the potential treatment of multiple solid tumor indications, and is an important step in further diversification of our portfolio of antibody-based therapeutics.

CW191 is an antibody drug conjugate built using our recently announced TOPO-based ADC, platform and utilizes a kappa-thecin-derived payload that we believe can be competitive in areas with high unmet clinical need, such as ovarian cancer and other gynecological cancers.

CW191 represents our second announced antibody drug conjugate, the first being Xenodatamab, zovudotin, and the first ADC built using our TOPO platform.

While we're not disclosing the targets on this call, I will note that, importantly, both of these preclinical product candidates will represent our first step outside of the, HER2 targeted therapy space. While we strongly believe both Xenodatamab and Xenodatamab zovudotin have the potential, to address unmet needs in a range of cancer indications, we recognize that diversification beyond HER2 is an important next step, one that has started with this announcement and advancement of these two candidates.

Our overall mission at Ximarks and the future R&D focus is clearly on novel, multifunctional, targeted therapies for difficult-to-treat cancers, those with the lowest five-year overall survival rates, and where our advanced biologics may be able to make progress towards significantly improved outcomes for patients with cancers of the pancreas, liver, lung, esophagus, stomach, colon, ovary, and certain hematological cancers.

We look forward to expanding on both our two lead preclinical product candidates, additional, preclinical product candidates, our platforms, and overall future scientific vision later this year in October at our R&D day, so stay tuned for further details.

Second key item helping us achieve our objective of two I&D applications by 2024 is the hiring, of Dr. Paul Moore.

As you likely saw from a press release earlier this summer, Paul brings with him a wealth, of knowledge in biology, preclinical development, and translational research, but also the development of multiple FDA-approved biologics for patients with difficult-to-treat cancers and autoimmune conditions.

Exactly when this meeting will take place is largely dependent on the SEC review process for the S4 filing.

We're very excited to announce that at the upcoming annual meeting of the European Society, of Medical Oncology, or ESMO, in September in Paris, Dr. Kumal Jhaveri from the Memorial Sloan Kettering Cancer Center will be presenting preliminary results from our Phase I study, of a basket cohort of HER2-expressing solid cancers.

Paul's hiring and expertise will be key to the continued development and advancement, of our preclinical product portfolio, and in combination with our existing exceptional team of scientists and engineers, will help further advance our portfolio of therapeutics.

However, we hope that it will occur within the next few months.

Her mini-oral presentation will be the first comprehensive disclosure of clinical data, presented by Zilverdoten.

Given the exciting quarter we've had on the clinical and R&D side of things, we also had, an important update on the corporate side that's worth discussing here. In July of this year, we announced our plan to become a Delaware corporation. While largely administrative in nature, this proposed redomicile is something that we believe, provides important benefits to the business and our shareholders, both near-term and long-term.

Completion of the redomicile is expected to occur in the fourth quarter of 2022, pending an affirmative shareholder vote and relevant court and regulatory approvals. It's worth noting that the exchangeable share structure we're proposing and the overall mechanism for effecting the redomicile to Delaware is a well-known and established administrative process that has been used successfully by other Canadian companies to redomicile to U.S. jurisdictions.

While discussed previously on our July 15th conference call, I will highlight again a, few key items. We believe the proposed redomicile from British Columbia to Delaware enhances alignment with, our U.S. shareholder base and peer biotechnology companies and expands the potential institutional investor base in the United States. Also expands our eligible passive investment base in the United States by enabling potential, inclusion of Ximerx in leading indices, such as select Russell and S&P indices, and reduces complexities and certain costs related to our future operations from a tax, legal, commercialization, partnering, and monetization standpoint.

We also do not believe there will be any impact to our patients, operations, business development efforts, or other important corporate items as a result of this process.

While we believe there are many benefits, it's important to highlight that as a result, of this proposed redomicile, Ximerx will not change its name, brand, or ticker symbol, and will not be moving employees out of Vancouver.

To learn more about the structure, process, benefits, or other items associated with the proposed redomicile, we would encourage everyone listening to consult the information we've previously filed with the SEC, as well as the preliminary proxy statement prospectus filed in Form S4 with the SEC by Zymeworks Delaware, Inc.

Given the tax-efficient nature of the structure, we also don't believe the company or our U.S, shareholders will have an adverse tax to events, and Canadian shareholders that elect to receive exchangeable shares can elect to defer all or part of any Canadian capital gains.

Due to the regulated nature of communications relating to the proposed redomicile, we are not planning to address questions regarding this matter during the Q&A session of this call and instead would refer you to the filings previously mentioned.

This process will require a special meeting of our security holders and approval of two-thirds of the votes cast to approve the share exchange and redomicile to the U.S., as well as approvals by the New York Stock Exchange and relevant Canadian courts of law.

As we look ahead to the remainder of 2022, I will briefly highlight a few important key catalysts.

I'll start with ZanaDataMap.

We look forward to sharing information about this program at Dr. Jhaveri's presentation, as well as our investor conference call and webcast at ESMO on September 12th.

Moving on to our preclinical product candidates, earlier this year, when we laid out our key, strategic priorities, we announced our goal of having at least two investigational new drug applications submitted by the end of 2024.

Does that mean that that's going to include the her two positive breast in her two positive gastroesophageal two seismic per Kid Q3 weekly regimen or are we going to see.

First, we announced the date of our early R&D day, which will take place on October, 20th of this year in New York City. This will be an important step in presenting data from our two lead preclinical platforms, our industry-leading multi-specific antibody therapeutic platform, and our next-generation topo-based ADC platform. Details of the meeting and the webcast will be available shortly on our website.

While we're presenting data highlighting multiple preclinical product candidates, it's also, incredibly exciting to announce our two lead preclinical product candidates, ZW191 and, ZW171. ZW171 is a novel and differentiated bispecific T-cell-engaging antibody that was generated, using our azimetric bispecific platform, the same platform that helped generate Vanadatamab, our lead product candidate. ZW171 is designed to target the potential treatment of multiple solid tumor indications, and is an important step in further diversification of our portfolio of antibody-based therapeutics.

ZW191 is an antibody drug conjugate built using our recently announced topo-based ADC, platform and utilizes a capathetin-derived payload that we believe can be competitive in areas with high unmet clinical need, such as ovarian cancer and other gynecological cancers.

ZW191 represents our second announced antibody drug conjugate, the first being Vanadatamab, zovudotin, and the first ADC built using our topo platform.

While we're not disclosing the targets on this call, I will note that importantly, both, of these preclinical product candidates will represent our first step outside of the HER2 targeted therapy space. While we strongly believe both Vanadatamab and Vanadatamab zovudotin have the potential, to address unmet needs in a range of cancer indications, we recognize that diversification beyond HER2 is an important next step, one that has started with this announcement and advancement of these two candidates.

Our overall mission at Zymarks and the future R&D focus is clearly on novel, multifunctional, targeted therapies for difficult-to-treat cancers, those with the lowest five-year overall survival rates, and where our advanced biologics may be able to make progress towards significantly improved outcomes for patients with cancers of the pancreas, liver, lung, esophagus, stomach, colon, ovary, and certain hematological cancers.

I'll start with ZanaDataMap, where, expected in the fourth quarter this year, we're excited, to present results from our late-line HER2-positive, hormone-receptor-positive, metastatic, or breast cancer study of ZanaDataMap in combination with fulvestrant and paleobleciclin.

The second key item helping us achieve our objective of two IND applications by 2024, is the hiring of Dr. Paul Moore. As you likely saw from a press release earlier this summer, Paul brings with him a wealth, of knowledge in biology, preclinical development, and translational research, but also the development of multiple FDA-approved biologics for patients with difficult-to-treat cancers and autoimmune conditions. Paul's hiring and expertise will be key to the continued development and advancement, of our preclinical product portfolio, and in combination with our existing exceptional team of scientists and engineers, will help further advance our portfolio of therapeutics.

We also announced today an update to the timing of data from our pivotal trial, HORIZON-BTC-01, where we now expect top-line data to be announced late this year.

As Paul discussed previously on our July 15th conference call, I will highlight again, a few key items. We believe the proposed redomicile from British Columbia to Delaware enhances alignment with, our U.S. shareholder base and peer biotechnology companies and expands the potential institutional investor base in the United States.

Basket of her two positive cancers outside of breast and gea at ESMO just clarify thank you.

Also expands our eligible passive investment base in the United States by enabling potential, inclusion of XIME works in leading indices, such as select Russell and S&P indices, and reduces complexities and certain costs related to our future operations from a tax, legal, commercialization, partnering, and monetization standpoint.

While we believe there are many benefits, it's important to highlight that as a result, of this proposed redomicile, XIME works will not change its name, brand, or ticker symbol, and we will not be moving employees out of Vancouver.

Given the tax-efficient nature of the structure, we also don't believe the company or our U.S, shareholders will have an adverse taxable event, and Canadian shareholders that elect to receive exchangeable shares can elect to defer all or part of any Canadian capital gains tax.

This process will require a special meeting of our security holders and approval of two-thirds, of the votes cast to approve the share exchange and redomicile to the U.S., as well as approvals by the New York Stock Exchange and relevant Canadian courts of law.

Exactly when this meeting will take place is largely dependent on the SEC review process, for the S-IV filing, however, we hope that it will occur within the next few months. The acceptance of the redomicile is expected to occur in the fourth quarter of 2022, pending, an affirmative shareholder vote and relevant court and regulatory approvals.

For ZanaDataMap Zovudotin, we're very excited to have announced in late July our acceptance, to present at the European Society for Medical Oncology Conference in Paris on September, 12th. This will be the first public release of data for our second product candidate and first, antibody drug conjugate, ZanaDataMap Zovudotin.

It's worth noting that the exchangeable share structure we're proposing and the overall, mechanism for effecting the redomicile to Delaware is a well-known and established administrative process that has been used successfully by other Canadian companies to redomicile to, U.S. jurisdictions.

Regarding our preclinical product portfolio, we will be presenting data from both our lead, preclinical product candidates, ZW191 and ZW171, at our early R&D day in October of this year, along with other preclinical candidates that we're excited to finally be able to share more information about with the public.

We also do not believe there will be any impact to our patients, operations, development efforts, or other important corporate items as a result of this process.

Yes ill ask Dr. Neil Josephson to address the question of what patients were recruited in that study and what youre likely to see it ease mode with respect to that.

Finally, I want to end with a short discussion about the potential impacts of the continuing, COVID endemic on our workforce and operations. We've been fortunate in 2022 to date to have minimal impact on our operations from the, COVID endemic and government restrictions in response to regional outbreaks around the world. As we've seen recently, a new wave of infections from several sub-variants is sweeping across, the globe, leading in some cases to record infections and increased hospitalizations and fatalities in certain geographic regions.

To learn more about the structure, process, benefits, or other items associated with the, proposed redomicile, we would encourage everyone listening to consult the information we've previously filed with the SEC, as well as the preliminary proxy statement prospectus filed on Form S-IV with the SEC by Xymarks Delaware, Inc. Due to the regulated nature of communications relating to the proposed redomicile, we are, not planning to address questions regarding this matter during the Q&A session of this call and instead would refer you to the filings previously mentioned.

We are actively reviewing our current policies to protect the well-being of our employees, and their families in the event of any changes in government restrictions and to ensure the continuity of our operations.

As we look ahead to the remainder of 2022, I will briefly highlight a few important key, catalysts.

Further, as our activities are global in nature, we could be affected in the future in certain, regions in the event of changes in government restrictions on our ability to progress our business as we expected to.

We will continue to evaluate any enhanced risks of the COVID endemic to our global operations, and take steps to mitigate any impact on our operations wherever possible.

We truly hope that a return to normalization in the face of the COVID endemic continues, but we'll ensure we are prepared for any new restrictions.

Sure. Thanks.

Thanks, Ken This is Neil Josephson.

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

Yes, the patients that will be presented at ESMO will include breast cancer.

Her two positive breast cancer her two positive gastric cancer and then.

A mix of other her two positive tumors.

So youll see all of the patients had been enrolled on the CW 49 study and that does include breast and gastric cancer.

And should we expect that coming out of ESMO that we'll be able to learn the recommended phase two dose going forward for this program.

So we will have information about about dosing and about.

What doses, we will we will potentially take forward.

So I think that that you're referring to a phase II dose singular phenomenon and certainly.

There.

We will have a recommended dose that we will be taking forward.

But it is.

There could be more than one that we would that we would pursue depending on on all of the results of the phase one study.

And then just one last one I guess for Kevin just in terms of higher level strategy in the ADC World, obviously, given the destiny breast data early in the year from in her too.

Strategically are you going to be kind of pivoting away from her to breast and focusing more on her suggest or esophageal and other her two positive cancers for your ADC or do you believe that you still want to pursue her two breast aggressively. Thank you.

Yes, I think and I think I heard you targeted therapy, we feel very comfortable with that data in the pivotal studies, we have ongoing right now and ability to track cancer and the <unk> study, which is under recruitment.

As you know we have other data.

In breast cancer and beyond that that could be interesting for expansion beyond the initial markets in BTC and <unk> that we hope to serve pending positive data and successful approval.

So I think we're quite excited about it.

The potential impact on <unk>.

The her two population.

Including in combination with other agents, which of course was the basis for the <unk> plus <unk> plus four restaurants breast cancer study, which is recruiting nicely.

And.

<unk> submitted an abstract for presentation, you hope to be able to present that in the in the fourth quarter. So I think with respect to <unk> I think we feel comfortable with the positioning of that.

We're expected in the fourth quarter of this year, we're excited to present results from our late-line HER2-positive, hormone-receptor-positive, metastatic, or breast cancer study of ZanaDataMap in combination with fulvestrant and palmitocycline.

In the patient population and the benefit we could have for patients beyond what's currently available and also what's in development.

Developments I think with respect to either be 49.

We're working hard as you know to find a dosing regimen or more than one dosing regimen that we can take forward that would provide efficacy to justify future clinical development possibilities and also the tolerability around that efficacy.

And we look forward to sharing that information.

And in our Investor webcast I think we're giving a lot of thought to VW 49 in the clinical development strategy in light of as.

As you say other competitive products that have come to market and the developments.

And we think we think we have a strategy around clinical development is going to be 49 or <unk>.

That we think could be compelling and could provide a benefit to patients beyond what might be available from from other therapies either in the market or in development right. Now. So I think we're very committed to <unk> and the CW <unk> 49, as being two potential products that could help that patient population as.

As we talked about with our earlier stage program I think going beyond that.

Those two agents.

I think there is a host of other targets in other cancer indications that we laid out that we think we are advanced biologics would definitely benefit that.

Of that patient population and potentially provide benefits that can't be seen with other product formats, and so with our future product pipeline, we will be going beyond that.

Other her two targeted patient population.

And exploring other other potential indications with those agents.

Great. Thanks, Thanks, Ken I appreciate you're welcome. Thank you.

As a reminder, to ask a question, please press star 11 on your telephone keypad.

Please standby for our next question.

If you're using a speakerphone, please pick up your handset before pressing any keys.

All right. Our next question comes from the line of Gena Wang with Barclays. Your line is open.

We will pause for a moment as callers join the queue.

Thank you Kevin.

The question is Tom for Gina.

All right, our first question comes from the line of UGAL Nochemovitz with Citi.

We have two questions one for <unk> 49, so for the updated data at upcoming data in asthma.

Your line is open.

Patient and can we expect in total and especially from the.

Cohort ways.

<unk> three week dosing and what kind of runoff duration.

Thanks for taking the questions.

Would you expect in.

Hi, Ken and team.

And secondly for <unk> just wondering.

How is the enrollment.

Going forward the GAA pivotal trial given the first.

First Lang Triple combo in place.

Yes. Thank you for the questions it looks like the deal, but I'm afraid you'll have to wait until the abstract is available on September five and then obviously our presentation.

Which will be provided by our investigator on September 12.

To get the total details about patients.

Which have been disclosed at that time.

We also will have an investor webcast on September 12, after our many oral presentation to provide additional information.

I'm afraid for that one youre going to have to wait until the actual <unk> Mo conference.

On slide 25, I think we're we're quite encouraged by our patient recruitment so far on the Gea study.

As you are aware, we chose not to recruit patients in the United States.

Because of the accelerated.

Approval that occurred there was another competitive therapy. So we're recruiting an entirely outside the United States and I think we're quite happy with the recruitment.

That's ongoing with that study I think as we've seen with others in our <unk> studies. They tend to accelerate later in the clinical study time period and that happened with our pivotal study in BTC, which will read out before the end of this year.

We also announced today an update to the timing of data from our pivotal trial, Horizon BTC-01, where we now expect top-line data to be announced late this year.

For ZanaDataMap Zovudotin, we're very excited to have announced in late July our acceptance to present at the European Society for Medical Oncology Conference in Paris on September 12th. This will be the first public release of data for our second product candidate and first antibody drug conjugate, ZanaDataMap Zovudotin.

Regarding our preclinical product portfolio, we will be presenting data from both our lead preclinical product candidates, ZW191 and ZW171, at our early R&D day in October of this year, along with other preclinical candidates that we're excited to finally be able to share more information about with the public.

Finally, I want to end with a short discussion about the potential impacts of the continuing COVID endemic on our workforce and operations. We've been fortunate in 2022 to date to have minimal impact on our operations from the COVID endemic and government restrictions in response to regional outbreaks around the world. As we've seen recently, a new wave of infections from several sub-variants is sweeping across the globe, leading in some cases to record infections and increased hospitalizations and fatalities in certain geographic regions.

We are actively reviewing our current policies to protect the well-being of our employees and their families in the event of any changes in government restrictions and to ensure the continuity of our operations.

Further, as our activities are global in nature, we could be affected in the future in certain regions in the event of changes in government restrictions on our ability to progress our business as we expected to.

We will continue to evaluate any enhanced risks of the COVID endemic to our global operations and take steps to mitigate any impact on our operations wherever possible.

I think it's happened in our study was there any and Paolo unsold restaurants.

We truly hope that a return to normalization in the face of the COVID endemic continues, but we'll ensure we are prepared for any new restrictions.

Well I think as soon as investigators.

Got some experience to the agent we saw recruitment track up nicely.

In that regard and I think we're excited to see the same thing.

The data we put out at emo.

On the first one.

It had been a first line patients with Danny and then at <unk> and chemo.

We're very encouraging to investigators.

We've obviously continued to follow the patient population, which is now fully enroll the chemo.

Very encouraging to investigators.

We've obviously continued to follow the patient population, which is now fully enrolled and we hope to give an update of that.

In the first half of 2023, I think we're very encouraged by the longer term follow up without fully enrolled patient population and the benefits it seems to be being provided by any post chemo regimen.

And also given the fact that chemotherapy regimen as you know.

Has dropped out for a number of cycles.

Patients remain on <unk> alone.

So I think all of those things together I think will encourage further clinical study enrollment and we do expect it to accelerate as our other studies.

As we get.

Further through the clinical study itself.

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

Thank you.

As a reminder, to ask a question, please press star 11 on your telephone keypad.

If you're using a speakerphone, please pick up your handset before pressing any keys.

Yes.

Nick Abbott with Wells Fargo. Your line is open.

We will pause for a moment as callers join the queue.

I just wanted to ask about your strategy in first-line biliary given the data from Topaz, One earlier this year from Nifinzi plus Gemsys.

Given that data and obviously depending on the results of the phase two Zany plus Gemsys, in first-line biliary that you're running, just wondering whether you'd consider adding Tizolizumab to the first-line biliary regimen, which could build on the learnings from Topaz, One.

Yes.

If you were to do the quad regimen of Zany plus Tizolizumab plus Gemsys in your pivotal, trial in biliary, perhaps this could be an interesting way to differentiate from Topaz, One.

Thanks, Paul was almost dropping off to sleep.

So maybe the clinical community the press release.

All right, our first question comes from the line of Yigal Nochomovitz with Citi.

I'm curious your thoughts on that strategy.

Progress towards previously and alcohol delivery upon new partnerships collaborations.

There is an opportunity.

And in your prepared comments.

Can you provide us with some.

Clarity on what this progress is and maybe what.

Patients should be.

Your line is open.

Thank you.

Yes. Thanks for the question Nik and I'll do my Best I think as we talked about earlier in the year.

Thanks for taking the questions.

First one we're making very nice progress this year without the benefits of resources of new partners.

Hi, Ken and team.

I just wanted to ask about your strategy in first-line biliary, given the data from TOPAS-1 earlier this year from Infinzi plus GEM-SYS.

Given that data, and obviously depending on the results of the phase 2 Zany plus GEM-SYS in first-line biliary that you're running, just wondering whether you'd consider adding Tizolizumab to the first-line biliary regimen, which could build on the learnings from TOPAS-1.

Because if you were to do the quad regimen of Zany plus Tizolizumab plus GEM-SYS in your pivotal trial in biliary, perhaps this could be an interesting way to differentiate from TOPAS-1.

And I think we're working real nicely with Beijing.

I'm curious your thoughts on that strategy.

And our areas of cooperation.

So I think what I'm really excited at the progress that we're making without the benefit of additional resources.

Thank you.

Yeah, thanks for the question.

We've got active and very wide ranging discussions underway throughout the portfolio that I think will allow us to do what we talked about in January as the importance of this company.

Yeah, thanks for the question, and again, I think, as you said, we're, you know, we're, extremely optimistic in our current PIVL study using ZANI as model therapy in second-line patient populations, and that has the potential to be the, you know, the first HER2-targeted therapy for that patient population, so, you know, we're optimistic by the data we saw previously with ZANIDATA-MAB.

We're happy to be able to get to a top-line data set earlier than we had expected.

Using a more wholesome and integrated partnership model. So I think we'll be able to monetize the value that we've generated to date I think we can find ways to accelerate and broaden our business plans that will make us more competitive.

In light of an enhanced competition in the her two space and.

And I think most importantly leave open the possibility for a broader transaction, including an outright acquisition in the future.

From an existing partner or a brand new third party and we've heard that is very important for our shareholders.

We've listened to that and we will make sure that we don't eliminate that possible in the future from the partnerships and collaborations that we're going to form. So we've got active in wide ranging discussions underway, but having done. This a long time, we won't provide any specific guidance about timeframe or a structure or a parkey of nature.

I think we're, you know, still, you know, recruiting in our ongoing Phase 2 study with first-line biliary tract cancer patients, and so that is an interesting, data set for us.

I think at the time that we have our biliary tract cancer data later this year, we'll be prepared then to talk about the nature of regulatory filings and next steps in looking at whether we can expand the patient population beyond the current PIVL study into additional expanded label indications, and obviously, we're following, all the competitive data sets that might be available for this patient population, although, you know, we're the only ones really with a HER2-targeted therapy for the patients that we're really looking to treat, so I think we'll have more to say about that once we get to our PIVL data release later this year, if that's okay.

We'll get these deals done and announced them and explain the rationale and the impact on the company.

As I said earlier in general I think working in a more fulsome integrated partnership model throughout the portfolio is very important to <unk> and that will be doing from from now until the future. So we fully expect to be able to complete a number of partnerships and collaborations in 2022, and 2023, which will allow us to operate are busy.

A little bit differently than we did before January of this year. So we're working hard on it we wont give any specific guidance.

So things are complete them all be happy to explain the rationale for per transactions once they're complete.

Okay, got it, and then specifically on ESMO and the mini-oral presentation for ZW49 that's, coming up, I think you mentioned that it's going to feature a basket cohort of HER2-positive cancers.

I just wanted to check, does that mean that that's going to include the HER2-positive breast and HER2-positive gastroesophageal at the 2.5 mg per kg Q3 weekly regimen, or are we going to see a basket of HER2-positive cancers outside of breast and GEA at ESMO?

Okay.

And then just moving on to <unk>.

Please go ahead Ed.

Just clarify, thank you.

Once we've seen the data.

Well, we have clarity around.

Uh huh.

Please go ahead is active in patients who use <unk>.

<unk> and <unk>.

Hello Hello.

It's a low quarter as Neil mentioned, we're seeing more and more of these patients coming in.

Presumably a lot of the data we're going to see it is always going to be on patients.

Enrolled cohort two or the use of it Jason.

Just wondering.

As opposed to market option, allowing them to failure.

Local blue book.

Future development options are you considering.

Please go ahead.

Yeah, I'll ask Dr. Neil Josephson to address the question of what patients were recruited in that study and what you're likely to see at ESMO with respect to that.

Yes, really good question that can again.

Fortunately youre going to have to wait until.

Until he's mode.

See our presentation and in the Investor webcast will be as fulsome as we can.

About.

About all of those questions, which you just asked obviously as I think we mentioned earlier we're seeing.

And more on her two failures in all of our studies.

We didn't exclude in her two failures in does need to be 49 studies.

So.

It could be patients in there what we can make of the data and how long those patients been studied is something you'll have to wait till you get to two emo I think our goal at <unk> is the company's never reported clinical data on <unk> to be 49 since the start of its R&D a number of years ago and I think we want to provide the fulsome data set that we can about what.

We see with this agent from an efficacy and Tolerability standpoint the.

The rationale for our regimen or more than one regimen, which might be available to go forward.

And also our clinical development plan next steps for our clinical belt and plan that we think makes sense.

Because we think we have an agent that could be.

Extremely competitive and we'd like to to invest further in the clinical development of that molecule.

In light of what we see in competition in light of what we see is unmet needs in specific indications.

In the her two space.

Whether that includes strategies around.

Looking at future patient populations, who progress.

After her too.

It's obviously something that we and others are considering an understanding how you would.

Address that patient population with local development plan and what the economic value would be to that sort of clinical development plan. So we will have as much to say as we can on September 12th, but unfortunately until we get to that point, you'll have to wait to have that.

Sure, thanks, Ken.

This is Neil Josephson.

Question addressed.

Okay. Okay, and then just last one maybe on the clarification I think.

Danny <unk> co investor that you've submitted an abstract that was clarified that the good quarter and.

Presumably this is.

Yes.

Yes, the patients that will be presented at ESMO will, include breast cancer, HER2-positive breast cancer, HER2-positive gastric cancer, and then a mix of other HER2-positive tumors, so you'll see all of the patients that have been enrolled on the CW49 study, and that does include breast and gastric cancer.

Yes.

Yes, we didn't we didn't specify the conferences, we've obviously given guidance about it being met.

Medical meeting to be held in the Q4 that will be focused in this indication, but we wouldnt be specific about that until we had our abstract submitted I think we're as we said before we're quite excited about this potential combination in this patient population.

And again, I think, as you said, we're extremely optimistic in our current pivotal study, using Zany as monotherapy in second-line patient populations. And that has the potential to be the first HER2-targeted therapy for that patient population. So we're optimistic by the data we saw previously with Zanidatumab.

And should we expect that coming out of ESMO that we'll be able to learn the recommended, phase 2 dose going forward for this program? So, we will have information about dosing and about what doses we will potentially take forward.

The studies recruited very nicely and again accelerated over time, which is always a good sign where the clinical study.

We're happy to be able to get to a top-line data set earlier than we had expected.

So, I think that you're referring to a phase 2 dose singular phenomenon, and certainly, we will have a recommended dose that we will be taking forward, but there could be more than one that we would pursue, depending on all of the results of the phase 1 study.

And we're excited to present, our current finding.

In this study and so we've moved as quickly as we can to get.

To get that so we did submit an abstract to a medical meeting that occurs in the fourth quarter I can confirm that.

And as soon as we're able to say that we had an abstract accepted will provide those details.

And look forward to being able to present that before the end of this year.

Okay terrific.

Thanks.

Please standby for our next question.

Our next question comes from the line of Charles Zhou with Guggenheim Securities. Your line is open.

I think we're still recruiting in our ongoing Phase 2 study with first-line biliary tract cancer patients.

And then just one last one, I guess, for Ken, just in terms of higher-level strategy in, the ADC world, obviously, given the Destiny breast data earlier in the year from in HER2, you know, strategically, are you going to be kind of pivoting away from HER2 breast and focusing more on HER2 gastroesophageal and other HER2-positive cancers for your ADC, or do you believe that you still want to pursue HER2 breast aggressively?

Hello, everyone and thanks for taking my questions and congrats on all the progress. My first question is regarding Gws 49, and I understand you're not commenting on the whatever you may or may not present at ESMO I had us related question and not specific to ESMO, but I'll just look.

And so that is an interesting data set for us.

Thank you.

Yeah, I think in, you know, I think in HER2-targeted therapy, we, you know, we feel very comfortable, within a data map in the pivotal studies we have ongoing right now on ability to track cancer and the GEA study, which is under recruitment.

As you know, we have other data in breast cancer and beyond that, that could be interesting, for expansion beyond the initial markets in BTC and GEA that we hope to serve, pending positive data and successful approval.

And obviously, we're following all the competitive data sets that might be available for this patient population.

Although we're the only ones really with a HER2-targeted therapy for the patients that we're really looking to treat.

So I think we'll have more to say about that once we get to our pivotal data release later this year, if that's okay.

At your updated slides it looks like you may have cleared two five milligrams per kg at the Q3 weekly dose and also looks like you've already cleared wanted to hash weekly and are evaluating one seven slide weekly that doesn't exactly <unk> take a rocket scientist to see that your exposures are effectively nearly doubled I'm just kind of.

Wondering like all of them.

How we should be thinking about.

Things like the impact of CMS total area under the curve and exposure as far as efficacy and toxicity signals may be concerned with antibody drug conjugates.

Okay, got it.

No. Thanks for the thanks for the question Charles and again I think we're.

And then specifically on ESMO and the mini-oral presentation for ZW49 that's coming up, I think you mentioned that it's going to feature a basket cohort of HER2-positive cancers. I just wanted to check, does that mean that that's going to include the HER2-positive breast and HER2-positive gastroesophageal at the 2.5 mg per kg Q3 weekly regimen?

So I think we're quite excited about ZENI-DataMap and its potential impact on the HER2 population, including in combination with other agents, which, of course, was the basis for the ZENI-DataMap plus PALBO plus Fulvestrance Breast Cancer Study, which, you know, is recruited nicely.

We will try and get ahead of the IMO meeting I mean, obviously the company has spent some time studying every three week dosing with <unk> 49, and we should be able present, a pretty fulsome picture there of.

Or are we going to see a basket of HER2-positive cancers outside of breast and GEA at ESMO?

Just clarify.

Thank you.

What efficacy, we think we see and what the side effect profile is of that agent.

In picking a recommended phase II dose and obviously, we've we've gone up in that dose escalation dose expansion as you've mentioned.

Yeah, I'll ask Dr. Neal Josephson, to address the question of what patients were recruited in that study and what you're likely to see at ESMO with respect to that.

As you know the company started a weekly dosing regimen.

To try and understand what.

Sure.

What happened to efficacy and Tolerability and we've been working through that process in the dose escalation and dose expansion and we look forward to present everything that we have.

Thanks, Ken.

This is Neal Josephson.

And you know, we've submitted an abstract for presentation, we hope to be able to present, that in the fourth quarter.

At emo in what the future direction might.

So I think with respect to ZENI-DataMap, I think we feel comfortable with the positioning, of that in the patient population and the benefit we could have for patients beyond what's currently available and also what's in development.

Yes, the patients that will be presented at ESMO, will include breast cancer, HER2-positive breast cancer, HER2-positive gastric cancer, and then a mix of other HER2-positive tumors.

<unk> B and.

So you'll see all of the patients, that have been enrolled on the CW49 study, and that does include breast and gastric cancer.

And again I think not to get ahead of IMO, but I wouldn't.

Be unreasonable to expect that there may be more than one dosing regimen, which might be suitable for patient populations.

The study in the future.

And again as you know some agents I think including trials.

Have more than one dosing regimens might be applicable.

But we'll look forward to presenting.

Everything we've done to date, because we've never presented clinical data on <unk> would be 49 since the <unk> will present all of the phase one data we have will provide some feedback on the next steps that we think will have a belt and plan.

I think with respect to ZW49, you know, we've been working hard, as you know, to find a, dosing regimen or more than one dosing regimen that we can take forward that would provide efficacy to justify future clinical development possibilities and also the tolerability around that efficacy.

And should we expect that coming out of ESMO, that we'll be able to learn the recommended phase two dose going forward for this program? So we will have information about dosing, and about what doses we will potentially take forward.

Including what recommended dose we would study in that development plan as.

As well as additional studies that we might have ongoing with CW 49 at the time of use most so I think you'll get a full sense of those questions in and trying to address.

The specific things you mentioned about <unk>, and AUC and how that might relate to tolerability and the relationship between the efficacy if you generate and the tolerability of that you have to accept.

Generate that efficacy I think we're really encouraged by the phase one program. We've done its very fulsome I think we've done some really good work around the strategic strategically how we can continue to develop CW 49 in light of a different competitive environment than when we started and we still think there is a.

So I think that you're referring, to a phase two dose singular phenomenon, and certainly we will have a recommended dose that we will be taking forward.

But there could be more than one that we would pursue, depending on all of the results of the phase one study.

And then just one last one, I guess, for Ken, just in terms of higher level strategy in the ADC world, obviously given the Destiny breast data earlier in the year from in HER2, strategically, are you gonna be kind of pivoting away from HER2 breast and focusing more on HER2 gastric cancer or focusing more on HER2 gastroesophageal and other HER2 positive cancers for your ADC?

Or do you believe that you still wanna pursue, HER2 breast aggressively?

Thank you.

Yeah, I think in HER2 targeted therapy, we feel very comfortable with Xanadata MAD in the pivotal studies we have ongoing right now on biliary tract cancer and the GEA study, which is under recruitment.

As you know, we have other data in breast cancer, and beyond that, that could be interesting for expansion beyond the initial markets in BTC and GEA that we hope to serve pending positive data and successful approval.

So I think we're quite excited about Xanadata MAD, and its potential impact on the HER2 population, including in combination with the other agents, which of course was the basis for the Xanadata MAD plus PALBO plus Fulvestrance Breast Cancer Study, which is recruited nicely.

A really good place there's going to be 49 based on its unique mechanism of action associated with the ADC that we constructed.

To take forward in the clinic, and we look forward to giving a fulsome discussion at ESMO during the poster presentation in our investor webcast to be held after that and explaining the rationale on answering all those questions would you just poised now on September 12, so unfortunate.

And we've submitted an abstract for presentation.

And we look forward to sharing that information at ESMO and in our investor webcast.

We hope to be able to present that in the fourth quarter.

I think we've been giving a lot of thought to ZW49 and the clinical development strategy, in light of, as you say, other competitive products that have come to market in the development.

And we think we have a strategy around clinical development of ZW49 or ZENI-DataBeds over, DOTAN that we think could be compelling and could provide a benefit to patients beyond what might be available from other therapies either in the market or in development right now.

So I think we're very committed to ZENI-DataBed and to ZW49 as being two potential products, that could help that patient population.

As we talked about with our earlier stage program, I think going beyond those two agents, I think there's a host of other targets in other cancer indications that we laid out that we think we, you know, our advanced biologics could definitely benefit that patient population and potentially provide benefits that can't be seen with other product formats.

And so with our future product pipeline, we'll be going beyond the HER2-targeted patient, population and exploring other potential indications with those agents.

Great.

Thanks.

Wait for those.

Got it yet fully understand and maybe just one more regarding biliary tract cancer and the Readouts that you have now coming at year end of 'twenty two.

So I think with respect to Xanadata MAD, I think we feel comfortable with the positioning of that in the patient population and the benefit we could have for patients beyond what's currently available and also what's in development.

I think with respect to ZW49, we've been working hard, as you know, to find a dosing regimen or more than one dosing regimen that we can take forward that would provide efficacy to justify future clinical development possibilities and also the tolerability around that efficacy.

And we look forward to sharing that information, at ESMO and in our investor webcast.

I think we've been giving a lot of thought to ZW49, and the clinical development strategy in light of, as you say, other competitive products that have come to market in the developments. And we think we have a strategy, around clinical development of ZW49 or Xanadata Bezoba-Dotan that we think could be compelling and could provide a benefit to patients beyond what might be available from other therapies, either in the market or in development right now.

So I think we're very committed to Xanadata Bev, and to ZW49 as being two potential products that could help that patient population.

I understand we're probably split splitting hairs with this question, but I guess, what exactly drove that change in guidance.

Early 'twenty three to year end 'twenty, two and your patients only need to be independently assessed on the primary endpoint or is there also a minimum follow up that needs to be met as well. Thanks.

Yes no.

The updated guidance is is just the fact that operationally, we're performing I think better than we than we did in prior years and it was one of the things I think I laid out in mid January is that the company would try and focus on fewer priorities and by focusing on for your priorities, we would try to improve operational performance and get things done.

More quickly in a higher quality way or allow us to things more broadly and I think this is one instance, where I think our our folks in clinical operations and clinical research and biometrics and regulatory have done an extremely good job of.

Working with this dataset and now we feel comfortable that we'll be able to.

<unk> top line data to be announced before the end of this year as opposed into early 2023, and then also obviously gives us an earlier opportunity to present the full dataset.

At a peer reviewed conference in the first half of 2023, So I don't think its down to anything related to the patient results of the patient population. We're studying I think it's down to two just great operational performance by our team and I think I hope that the focus we've had on doing fewer things and doing them better and that this is an example of it and I think.

You will hopefully continue to see that.

Throughout the portfolio and throughout all of our operations that were we're much more nimble and much more focused as an organization and this will allow us to get things done a better way, which ultimately to.

Enhanced competitive ability.

With both <unk> and <unk> to be 49, and GW 171, and <unk> 91, and other things that come out of our preclinical portfolio.

Great. Thanks for taking the questions and look forward to your upcoming datasets. Thanks.

Thanks, Ken.

Thanks Charles.

Appreciate it.

Please standby for our next question.

Oh, you're welcome.

Our next question comes from the line of.

Stephen Wiley with Stifel. Your line is open.

Yeah.

Thank you.

Yes, good afternoon, thanks for taking the questions.

Spare you the GW. According nine question.

As we talked about with our earlier stage program, I think going beyond those two agents.

Maybe one on the earlier stage pipeline and I guess I'm not looking to steal any of your R&D day event funder, but.

I think there's a host of other targets in other cancer indications that we laid out that, we think we, you know, our advanced biologics would definitely benefit that patient population and potentially provide benefits that can't be seen with other product formats.

I know that T cell redirected bi specifics have been.

Pretty hard.

I think they've proven to be even more difficult than the solid tumor space.

A lot of those challenges obviously.

Non safety Tolerability so.

Just wondering if you can speak a little bit to how you think you can overcome some of these.

Challenges and whether or not that's going to occur through.

Through target selection is it going to be.

Playing around with CD, three affinities and variance is it going to be balanced.

I'm just curious as to how you're thinking you can improve upon specifically in the solid tumor space.

And so with our future product pipeline, we'll be going beyond the HER2-targeted patient, population and exploring other potential indications with those agents.

No. Thanks for the question and again, presumably 49, we're very excited to talk to folks about.

The progress we've made and I just don't want to get ahead of the emo pre.

Presentation.

So sorry for not being able to address any of those things in advance, but it's <unk>.

Five weeks away hopefully.

I think in the early stage portfolio, we have a number of programs ongoing I think the two we identified now where we're excited about and we think that can help us meet our goal of getting <unk>.

IND filings.

2024.

For these two programs I think on 191, the ADC program with a new triple payload, we're quite excited about.

Using our new payload and are different.

Platform.

In this way so we're excited to talk about that I think on the multi specific antibody therapeutic program I think we have some very specific thoughts around some of the things that you mentioned and I think the specific targets that we're looking at going after and some of the other things that you mentioned are things that we think are.

Competitively positive for us and our ability to do this and I think we can differentiate ourselves by addressing some of the issues and setbacks that I think <unk> seen previously with this.

So we've done a really extensive assessment of different bispecific formats. I mean, this is where the company started with design a whole range of bi specifics for our partners and ourselves I think we have a good reputation for being.

Great.

Thanks, Ken.

Bright and smarts.

Engine protein engineers, and we've used that specifically with 171.

So I think through the assessment and the work that we've done previously we've used that to come up what we think is a really interesting product candidate that we look forward to taking forward in the clinic.

<unk>, 20th we're happy to lay out as.

As much detail as we can about both of these candidates other programs.

We're working on as well as the strategy of moving forward and explain the rationale.

Or how we hope to turn these two agents into and the successful clinical candidates from an efficacy and Tolerability standpoint, and we'll be happy to address all of that on October 20th at our early R&D day.

Oh, you're welcome.

Alright, thanks for taking question.

Yeah.

Yeah, thank you.

All right.

Our next question.

Comes from the line of.

Cash Tiwari with Jefferies. Your line is open.

Please stand by for our next question.

Hi, This is Amy <unk>, thanks, and thanks for taking our question just wanted to get the company current spot on the acceptable rate with Ipass capable for.

All right.

Our next question comes from the line of Gina Wong with Barclays.

Our dose luncheon I talk with more off target.

Well it seems like occupancy is generally more related to the NIM is the relationship between propane applicable linear based on I guess with the current.

Current PK data that youre looking at or is there a sweet spot that you kind of hope there.

Engagement that you're evaluating.

Your line is open.

Thank you, Ken and Amy, for taking the question.

Thank you, Ken and team, for taking the question.

Thanks for the question I mean again I don't think we will talk about too much detail before he's no, but I'll just pause and ask if Dr. Neil Josephson wants to say.

This is Tone for Gina.

Anything about your question of whether we'll just wait until September 12 and answer them.

We have two questions, one for ZW49.

Yeah.

I would reiterate what you said, Ken which is that that data.

Data that we have at the conference.

We.

Said that that we were evaluating different yes.

Regimens to try to look at C, Max and and exposure.

I'm not sure that we ever made specific.

Comments about.

What was more related to two which which PK parameter, but we'll we'll lay out all of the data that we have.

At the Ash conference.

Great. Thanks, So much and then I guess I know you guys aren't talking so much about.

But when we see data from your potential go forward Joe.

I guess just from a high level standpoint, where the beef deflation and africom canvas.

Or is it still too early.

Do you want to take that one Neil yes sure.

Yeah, I I E.

You know.

Again to what we said, which was whereas I think youll have to wait until ESMO to to actually see the data.

In terms of.

Of dosing, we will have information about about dosing.

You know as as we've.

And multiple times.

There may be more than one dose that we would take forward.

And.

And then in terms of.

To your question about.

Two I think that that.

You know it.

You have a different molecule than two it has.

Different.

Payload it has a different market action.

Okay.

It has.

Profile from from an adverse event standpoint so.

I don't think that that we.

We are looking at this as as.

Our direct to her to at all I think that.

And with that development path for this molecule that.

Our unique from what in her two can develop and so.

Well as we lay out information we will also try to.

<unk> start to give information about how we're going to take a molecule forward.

Great. Thank you so much.

And Amy just a follow up for a decision that we make like a recommended phase II dose we will provide all the data to support the rationale for decisions that we're making with its clinical development programs should exceed you should be expect to be able to see the supporting data and rationale and then make your own determination about about our interpretation.

An analysis of conclusions about that data.

That's super helpful. Thank you so much.

Yeah.

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

That's great. Thank you operator, and thank you for your attendance today and for all of your questions. We had a really exciting quarter.

Quarter on all fronts, and we really look forward to the next opportunity to to <unk>.

<unk> additional data, we're looking forward to emo on both our parts of the presentation a webcast.

We also have four different investment conference attendance.

Which allows us to present and have meetings on the same week as these now and so we look forward to be able to explain further the data that we're presenting the future decisions, where we have going forward.

Data supports of those decisions and rationale so we look forward to that and please look forward to.

So save the date notices for October 20th in our early R&D day, we're really looking forward to two showing the next agents to come out of the engine.

And Jen and technology platforms that we have a time works and I think you'll find them very interesting for the future of the company beyond <unk> and CW 49. So please.

Keep an eye out for that October 20th David They are in your calendar and we look forward to seeing you. Some of you at emo and I'm talking about our presentation. Our next investor webcast on September 12. So thank you very much for your time and look forward to seeing you soon.

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

Sure.

As Johan during Q&A, you can dial star one one.

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So for the updated upcoming data in asthma, how many patients can we expect in total and especially from the cohort with one three-week dosing?

And what kind of follow-up duration would you expect?

This is Tung for Gina.

To ask questions to join the question queue Press Star then the number one.

We have two questions, one for ZW49.

One on your telephone keypad I would now like to turn the conference over to Jack Spinks Associate director of Investor Relations at <unk>. Jack. Please go ahead.

And secondly, for ZW25, just wondering how is the enrollment going for the GA pivotal trial, given the first line triple combo in place?

So for the updated upcoming data in asthma, how many patients can we expect in total, and especially from the cohort with one three-week dosing?

Good afternoon and welcome everyone.

Yeah, thank you for the questions.

And what kind of follow-up duration would you expect?

My name is Jack Spinks Associate director of Investor Relations here at <unk> today, we will discuss our second quarter 2022 financial results as well as provide an update to our ongoing business.

With respect to ZW49, I'm afraid you'll have to wait until the abstract is available on September 5th.

And then obviously our presentation, which will be provided by our investigator on September 12th, to get the total details about patients which are being disclosed at that time.

And secondly, for ZW25, just wondering, how is the enrollment going for the GA pivotal, trial given the first-line triple combo in place?

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 development of our product candidates related clinical trials anticipated data presentations.

Therapeutic effects as Ana data Madden and our other product candidates.

Bose, we're domiciled transactions and the anticipated timing and benefits.

The expected financial performance and future financial position.

The commercial potential of technology platforms and product candidates.

As I stated continued receipt of revenue from existing and future partners.

Clinical pipeline anticipated impact of the ongoing COVID-19, pandemic and our anticipated response to the same.

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.

Impact of new hires our ability to execute new collaborations and partnerships and other information that is not historical information.

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.

In addition.

Please note that today's earnings call does not constitute an offer to sell or a solicitation of an offer to buy any securities or a solicitation of any vote or approval.

The registration statement is not complete and will be further amended.

After the registration statement has been declared effective by the SEC. The final proxy statement prospectus, we mail design with security holders.

Including information about XI marks and the directors and employees, who may be deemed to be participants in the solicitation of proxies.

<unk> of the proposed we're domiciled transaction.

These documents are available free of charge at the SEC website at Www Dot SEC Gov.

Later in this call Ken Galbraith, our chair and Chief Executive Officer will.

We'll be discussing our financial results, including certain adjusted non-GAAP measures.

As a reminder, the audio and slides from this call will be available on the <unk> website later today.

Now I will turn the call over to Ken.

<unk> and CEO .

We also will have an investor webcast on September 12th after our mini oral presentation to provide additional information.

Yeah, thank you for the questions.

Ken.

Thanks, Jack and thank you everyone for joining us today for our second quarter earnings call.

So I'm afraid for that one, you're going to have to wait until the actual EASMO conference.

With respect to ZW49, I'm afraid you'll have to wait until the abstract is available on, September 5th, and then obviously our presentation, which will be provided by our investigator on September 12th, to get the total details about patients which are being disclosed at that time.

Before I speak to our financial results I'd like to briefly announced and congratulate clump as on his recent appointment as President. In addition to his current role as Chief operating Officer.

Also want to welcome Dr. Paul <unk> as our new Chief Scientific Officer, Paul started with US on July 18th and has already begun to make valuable contributions to our early R&D efforts with this R&D colleagues.

With ZW25, I think we're quite encouraged by our patient recruitment so far in the GEA study.

We also will have an investor webcast on September 12th after our mini-oral presentation to provide, additional information.

With that I'd like to jump right into the overview of our financial results followed by an update on both our clinical and R&D programs as well as a noteworthy corporate update.

Followed by a few brief closing remarks before we open up the lines for question and answers.

As you're aware, we chose not to recruit patients in the United States because of the accelerated approval that occurred there with another competitive therapy.

So I'm afraid for that one, you're going to have to wait until the actual ECMO conference.

So we're recruiting it entirely outside the United States.

And I think we're quite happy with the recruitment that's ongoing with that study.

I think as we've seen with others in our data map studies, they tend to accelerate later in the clinical study time period.

With ZW25, I think we're quite encouraged by our patient recruitment so far in the GEA, study.

We were aware we chose not to recruit patients in the United States because of the accelerated, approval that occurred there with another competitive therapy.

And that happened with our pivotal study in BTC, which we'll read out before the end of this year.

And I think it's happened in our study with Danny and Palbo and Sylvester, where I think as soon as investigators got some experience with the agent, we saw recruitment track up nicely in that regard.

Revenues for the most recent three month period, primarily related to a $5 million fee from the previously announced the trucker licensing agreement.

Research and development expense for the quarter ended June 32022% to <unk> $56 million compared to $50 7 million for the quarter ended in June 30 of 2021. This increase from the prior year related primarily to higher clinical trial expenses presented data mab due to the continued ramp up of horizon Gea O. One pivotal study and a corresponding increase in the associated drug manufacturing.

Expenses, which were partially offset by the head count reduction from our previously announced restructuring.

Higher year over year due to the previously noted reasons, we recognized slightly lower research and development expenses quarter on quarter and we anticipate these expenses will continue to decline in the latter half of this year and into 2023 as we realize the benefit of our restructuring program completed earlier this year.

General and administrative expense for the quarter ended June 32022 were $15 2 million compared to $19 9 million for the quarter ended June 2021, excluding.

Excluding stock based compensation and restructuring expenses adjusted general and administrative expense increased by $1 3 million for the quarter ended June 32022, compared to the same period in 2021.

<unk> net loss for the quarter ended June 32002 was $64 6 million compared to $67 5 million for the same period in 2021.

And I think we're excited to see the same thing.

As I indicated earlier and worth repeating here, we anticipate our forecasted operating expenses will continue to decline in the second half of this year driven by a reduction in clinical expenses tactical or manufacturing operation expenses and the impact of our restructuring program or.

Our cash resources, consisting of cash cash equivalents and short term investments were $241 8 million as of June 32022 based.

Based on our current operating plan and in combination with proceeds from certain existing collaboration payments. We anticipate receiving we believe our cash resources will fund our planned operations into the second half of 2023 and potentially beyond this quarter, we announced our first step towards extending our runway as we recognized a $5 million fee from our licensing agreement with <unk> and we look forward to building upon that progress.

Before we go into our clinical update and as I mentioned earlier on this call our search for a new Chief banking officer is complete as he brought Dr. Paul more onboard to lead our early research and development group.

Paul brings with him a wealth of experience and knowledge in preclinical translational and early clinical development of novel Biologic based therapeutics with.

With his deep background, developing bispecific multi specifics and antibody drug conjugate.

Along with his background, informing and managing seeking partnerships and collaborations with pharmaceutical and biotech companies. We're very excited that Paul and the team and welcome his guidance and leadership.

The announcement today of our early R&D day in October of this year, he will be pivotal to the success of those programs and we look forward to sharing more about them in October .

So we're recruiting it entirely outside the United States, and I think we're quite happy, with the recruitment that's ongoing with that study.

With that I'd like to move on to a clinical update for our two lead programs.

I think as we've seen with others in our data map studies, they tend to accelerate later, in the clinical study time period, and that happened with our pivotal study in BTC, which we'll read out before the end of this year.

We made exciting progress this quarter for both our clinical candidate data map, our hurricane targeted bispecific antibody and that data maps, zorba dotan or CW, <unk> 49, or her two targeting antibody drug conjugate.

And I think it's happened in our study with Zannie and Palbo and Silvestrant, where I, think as soon as investigators got some experience with the agent, we saw recruitment track up nicely in that regard.

And I think we're excited to see the same thing.

I think the data we put out at ESMO on the first-line treatment of first-line patients, with Zannie and Benadryl-Mavank chemo were very encouraging to investigators.

I'd like to start by briefly highlighting critical data was that a data map presented by our partner Beijing at the annual meeting of the American Society of clinical oncology or <unk> in June <unk>.

We've obviously continued to follow the patient population, which is now fully enrolled in, chemo.

We're very encouraging to investigators.

We've obviously continued to follow the patient population, which is now fully enrolled, and, we hope to give an update of that in the first half of 2023. I think we're very encouraged by the longer-term follow-up of that fully enrolled patient population, and the benefit that seems to be being provided by Zannie plus the chemo regimen, and also given the fact that chemotherapy regimen, as you know, is dropped after a number of cycles and patients remain on Zanadate and Mabalone.

So I think all those things together, I think, will encourage further clinical study enrollment, and we do expect it to accelerate, as our other studies have, as we get further through the clinical study itself.

Results from that Phase <unk> study of that data <unk> in the frontline setting of her two positive breast cancer and gastric cancer were presented in two separate poster sessions.

Thank you.

Nick Abbott with Wells Fargo, your line is open.

Thanks.

I was almost dropping off to sleep there.

Datasets demonstrated promising antitumor activity and a manageable safety profile for the treatment of advanced or metastatic disease within a data mab given in combination.

Asian with standard of care chemotherapy.

The regimen given to the gastric cancer cohort also included the PD one inhibitor Tesla the gastric cancer data presented provides support for the experimental regimen is that a data map antigen.

In combination with standard of care chemotherapy, and the ongoing horizon Gea <unk> pivotal study.

The maturing data from the fully enrolled breast cancer cohort will help to inform a potential development path for that data map and that indication.

Additionally, we anticipate presenting data at a major medical meeting before the end of the year from our ongoing study in later line. Her two positive hormone receptor positive breast cancer patients treated with that data map in combination will for restaurant and public Vickland Pfizer CDK four six inhibitor <unk>.

This dataset will also be important to informing our future development plans for example data mab in breast cancer.

I think the data we put out at EASMO on the first-line treatment of first-line patients with Zanny and Benedetta Medvan chemo were very encouraging to investigators.

We are continuing to make progress with our multicenter Global Phase III Open label first line study of <unk> plus standard first line combination chemotherapy regimens in selected Gi cancers, including Gea, PTC and colorectal cancer.

We've obviously continued to follow the patient population, which is now fully enrolled in chemo.

Cohort originally reported in September 2021 at Emo continues to follow the fully enrolled patient population and we hope to be able to present additional clinical data based on longer term follow up at a major medical meeting in the first half of 2023, including data related to duration of response progression free survival and overall survival.

We're very encouraging to investigators.

We've obviously continued to follow the patient population, which is now fully enrolled.

And we hope to give an update of that in the first half of 2023. I think we're very encouraged by the longer-term follow-up of that fully enrolled patient population and the benefit that seems to be provided by Zanny plus the chemo regimen.

As well as updated safety information.

We also continue to enroll patients in our cohort for first line BTC and first line colorectal cancers.

And also given the fact that chemotherapy regimen, as you know, is dropped after a number of cycles and patients remain on the data map alone.

Furthermore, we also announced this quarter that we now expect top line data from our horizon <unk>, one phase III pivotal clinical trial data Mab mono therapy for the treatment of metastatic or advanced her two amplified biliary tract cancer to be available before the end of 2022 slightly earlier than previously announced with this timeline we would.

So I think all those things together, I think, will encourage further clinical study enrollment.

And we do expect it to accelerate as our other studies have as we get further through the clinical study, itself.

To be able to present comprehensive clinical data from horizon <unk>, one trial at a major medical meeting in the first half of 2023 now I'd like to share an update on our second clinical stage candidate set of data map overdose or VW 49, a bypass topic Hershey targeting antibody drug conjugate.

Thank you.

Nick Abbott with Wells Fargo, your line is open.

Thanks.

I was almost dropping off to sleep there.

We're very excited to announce that at the upcoming annual meeting of the European Society of medical oncology or <unk> in September in Paris, Dr. <unk> Youre very from the Memorial Sloan Kettering Cancer Center will be presenting preliminary results from our phase one study of a basket cohort of Hercules expressing solid cancers or many oral presentation will be the first call.

Prehensile disclosure of clinical data presented data about zelle it out and we look forward to sharing information about this program at Dr. <unk> presentation, as well as our Investor Conference call and webcast <unk> on September 12.

So, Ken, maybe the first one for me is the press release states your progress towards previously announced goals of delivering upon new partnerships, collaborations, monetization opportunities.

Moving onto our preclinical product candidates earlier this year when we laid out our key strategic priorities, we announced our goal of having at least two investigational new drug application submitted by the end of 2024 I'm very pleased to announce that we've made great strides in furthering that objective.

We didn't address that in your prepared comments.

So, Ken, maybe the first one for me, is the press release states your progress towards previously announced goal of delivering upon new partnerships, collaborations, monetization opportunities.

So can you provide us with some clarity on what this progress is and maybe what expectations should be?

As you May have read the earnings release that went out earlier. This afternoon, we announced two key items that will help us accomplish this objective.

You didn't address that in your prepared comments.

Yeah, thanks for the question, Nick, and I'll do my best.

So, can you provide us with some clarity on what this progress is and maybe what expectations should be?

Yeah, thanks for the question, Nick, and I'll do my best.

I think as we talked about, earlier in the year, we're first, we're making very nice progress this year without the benefits and resources of new partners.

Web site.

And I think we're working well, you know, nicely with Beijing in our areas of cooperation.

We'll be presenting data highlighting multiple preclinical product candidates.

So, I think, you know, I'm really excited about, the progress we're making without the benefit of additional resources.

It's also incredibly exciting to announce our two lead preclinical product candidate GW 191, GW 171.

I think, you know, we've got active and very wide ranging discussions underway throughout the portfolio that I think will allow us to do what we talked about in January is the importance of this company using a more fulsome and integrated partnership model.

So, I think we'll be able to monetize the value that we've generated to date.

I think we can find ways to accelerate and broaden our business plans that will make us more competitive in light of an enhanced competition in the HER2 space.

And I think most importantly, you know, leave open the possibility for, you know, a broader transaction, including an outright acquisition in the future from an existing partner or a brand new third party.

GW 171 is designed to target the potential treatment of multiple solid tumor indications and is an important step in further diversification of our portfolio of antibody based therapeutics.

<unk> cancer and other gynecological cancers.

191 represents our second announced antibody drug conjugate the first things that a data mab silver dotan and the first ADC built using our <unk> platform.

While we are not disclosing the targets on this call I will note that importantly, both of these preclinical product candidates will represent our first step outside of that <unk> targeted therapy space. While we strongly believe both ventilator map and has added about though it doesn't have the potential to address unmet needs in a range of cancer indications, we recognize the diversification beyond her too is an important next step.

One that it started with this announcement and advancement of these two candidates our overall mission of <unk> in the future R&D focus is clearly on novel multifunctional targeted therapies for difficult to treat cancers.

Those are the lowest five year overall survival rates and where our advanced biologics may be able to make progress towards significantly improved outcomes for patients with cancers of the pancreas liver lung esophagus stomach colon ovary and certain hematological cancers.

Look forward to expanding on both our two lead preclinical product candidate additional preclinical product candidates our platforms and overall future scientific vision later this year in October at our R&D day. So stay tuned for further details secondly, Adam helping us achieve our objective of two IND applications by 2024 is the hiring of Dr. Palmer as you.

We saw from our press release or the summer Paul brings with him a wealth of knowledge and biology preclinical development and translational research, but also in the development of multiple FDA approved biologics for patients with difficult to treat cancers and autoimmune conditions Paul.

And we've heard that's very important for our shareholders.

I think as we talked about earlier in the year, you know, we're first we're making very nice progress this year without the benefits and resources of new partners.

Given the exciting quarter, we've had on the clinical and R&D side of things. We also have an important update on the corporate side that's worth discussing here.

And I think we're working well, you know, nicely with Beijing in our areas of cooperation.

And we've listened to that.

In July of this year, we announced our plan to become a Delaware Corporation or.

While largely administrative in nature of this proposed re domicile is something that we believe provides important benefits to the business and our shareholders, both near term and long term.

So I think, you know, I'm really excited about the progress we're making without the benefit of additional resources.

I think, you know, we've got active and very wide ranging discussions underway throughout the portfolio that I think will allow us to do what we talked, about in January is the importance of this company using a more fulsome and integrated partnership model.

While discussed previously on our July 15 conference call I will highlight again, a few key items.

So I think we'll be able to monetize the value that we've generated to date.

And we will make sure that we don't eliminate that possible in the future from the partnerships and collaborations that we're going to form.

We believe the proposed domicile from British Columbia to Delaware enhances alignment with our U S shareholder base and peer biotechnology companies and expansive potential institutional investor base in the United States.

So, we've got active and wide ranging discussions underway.

Also expands our eligible passive investment base in United States by enabling potential inclusion of <unk> and leading indices, such as select Russell and S&P indices.

And reduces complexities and certain costs related to our future operations from a tax legal commercialization partnering and monetization standpoint.

But having done this a long time, we won't provide any specific guidance about timeframe or structure or party of nature.

While we believe there are many benefits important to highlight that as a result of this proposed re domicile dimers will not change its name brand or ticker symbol and will not be moving employees out of Vancouver.

We'll get these deals done and announce them and explain the rationale and the impact on, the company.

As I said earlier in January, I think working in a more fulsome integrated partnership mantle throughout the portfolio is very important to Zymerks and that's what we'll be doing from now until the future.

So, we fully expect to be able to complete a number of partnerships and collaborations in 2022 and 2023, which will allow us to operate our business a little bit differently than we did before January of this year. So, we're working hard on it.

We won't give any specific guidance until things are, complete and then we'll be happy to explain the rationale for transactions once they're complete.

Yes, that's all good.

Thank you.

Exactly when that spending will take place is largely dependent on the SEC review process for the S. Four filing however, we hope that it will occur within the next few months.

Completion of the re domicile is expected to occur in the fourth quarter of 2022, pending an affirmative shareholder vote and relevant court and regulatory approvals.

Worth, noting that the exchangeable share structure, we're proposing in the overall mechanism for affecting the re domicile of the Delaware is a <unk>.

Well known and established administrative process that has been used successfully by other Canadian companies to re domicile to the U S jurisdictions.

We also do not believe there'll be any impact to our patients operations.

Development efforts or other important corporate items as a result of this process.

And then just moving on to the Z-squared EDMO.

Now, we're not planning to address questions regarding this matter during the Q&A session of this call and instead would refer you to the filings previously mentioned.

You know, once we've seen this data, will we have clarity around whether V-squared is active in patients who have failed NR2?

I know last, on the last quarter, Neal mentioned we're seeing more and more of these patients coming in, but presumably a lot of the data we're going to see is most going to be on patients that were enrolled prior to broader use of NR2.

As we look ahead to the remainder of 2022 I will briefly highlight a few important key catalysts.

So I'm just wondering whether there's a faster market option following NR2 failure, and more broadly, what future development options are you considering for V-squared?

We'll find ways to accelerate and broaden our business plans that will make us more competitive in light of an enhanced competition in the HER2 space.

I'll start with that of data Mab were expected in the fourth quarter. This year. We're excited to present results from our late line her two positive hormone receptor positive metastatic breast.

Yeah, really good question, Nick.

And I think most importantly, you know, leave open the possibility for a broader transaction, including an outright acquisition in the future from an existing partner or a brand new third party.

Breast cancer study of that.

<unk> in combination with both restaurants and publicly.

And again, I, you know, unfortunately, you're going to have to wait until EASMODE to, you know, see our presentation, and in the investor webcast, we'll be as fulsome as we can about all those questions, which you just asked.

And we've heard that's very important for our shareholders.

We also now say an update to the timing of data from our pivotal trial horizon BTC, one where we now expect top line data to be announced late this year.

And we've listened to that and we will make sure that we don't eliminate that possible in the future from the partnerships and collaborations that we're going to form.

Obviously, as I think we mentioned earlier, we're seeing more and more NR2 failures in all of our studies. We didn't exclude NR2 failures in the ZW49 studies.

So we've got active and wide ranging discussions underway.

So, you know, there could be patients in there.

But having done this a long time, we won't provide any specific guidance about timeframe or structure or party of nature.

And also a clinical development plan, next steps for a clinical development plan that we think makes sense because we think we have an agent that could be extremely competitive and we'd like to invest further in the clinical development of that molecule in light of what we see in competition, in light of what we see as unmet needs and specific indications in the HER2 space.

Presenting <unk> adult and we're very excited to have announced in late July our acceptance to present at the European Society for medical Oncology Conference in Paris on September 12.

Whether that includes strategies around looking at future patient populations who progress after an HER2 is obviously something that we and others are considering and understanding how you would address that patient population in the clinical development plan and what the economic value would be to that sort of clinical development plan.

So, we'll have as much to say as we can on September 12th, but unfortunately, until we get to that point, you'll have to wait to have that question addressed.

Okay, and then just want to make a clarification.

I think you said that the vanipalbo colvestrum that you submitted is an abstract.

So it will be the first public release of data for our second product candidate and first antibody drug conjugate presented data.

Could you just clarify that you did say that and presume that this is to the San Antonio?

Regarding our preclinical product portfolio, we will be presenting data from both our lead preclinical product candidates VW, one anyone and CW 171 at our early R&D day in October of this year.

Yeah, we didn't specify the conference.

We've obviously given guidance about it being a medical meeting to be held in the Q4 that would be focused on this indication, but we wouldn't be specific about that until we had our abstract submitted.

Along with other preclinical candidates that were excited to finally be able to share more information about with the public.

We'll get these deals done and announce them and explain the rationale and the impact on the company.

As I said earlier in January, I think working in a more fulsome integrated partnership mantle throughout the portfolio is very important to Zymerx.

Finally, I want to end with a short discussion about the potential impacts of the continuing COVID-19 endemic on our workforce and operations.

And that's what we'll be doing from now until the future.

We've been fortunate in 'twenty two to date to have minimal impact on our operations from the Covid endemic and government restrictions in response to regional outbreaks around the world.

So we fully expect to be able to complete a number of partnerships and collaborations in 2022 and 2023, which will allow us to operate our business a little bit differently than we did before January of this year. So we're working hard on it.

We won't give any specific guidance until things are complete and then we'll be happy to explain the rationale for transactions once they're complete.

And then just moving on to the Z-squared to Edmo, once we've seen this data, will we have clarity around whether the Z-squared is active in patients who have failed NFR2?

I know on the last quarter, Neil mentioned we're seeing more and more of these patients coming in, but presumably a lot of the data we're going to see Edmo is going to be on patients that were enrolled prior to broader use of NFR2.

What future development options are you considering for B2?

Actively reviewing our current policies to protect the well being of our employees and their families.

In the event of any changes in government restrictions and to ensure the continuity of our operations.

Further as our activities are global in nature, we could be affected in the future in certain regions in the event the changes in government restrictions on our ability to progress our business as we expect it to we.

We will continue to evaluate any enhanced risks of the covenant damage to our global operations and take steps to mitigate any impact on our operations wherever possible.

We truly hope that a return to normalization in the face of the Covid epidemic continues but will ensure we are prepared for any new restrictions.

Really good question, Nick.

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

And again, unfortunately, you're going to have to wait until ESMO to see our presentation, and an investor webcast will be as fulsome as we can about all those questions which you just asked.

As a reminder to ask a question. Please press star one on your telephone keypad.

If youre using a speakerphone please pick up your handset before pressing any case, we will pause for a moment as callers join the queue.

Obviously, as I think we mentioned earlier, we're seeing more and more on HER2 failures, in all of our studies.

All right. Our first question comes from the line of Hugo <unk> with Citi. Your line is open.

We didn't exclude in HER2 failures in the ZW49 studies.

So there could be patients in there.

What we can make of the data and how long those patients have been studied is something, you'll have to wait to get to ESMO.

Thanks for taking the questions Hi, Ken and team I just wanted to ask about your strategy in first line biliary given the data from Topaz. One earlier this year from Mckinsey plus Genesis given that data and obviously, depending on the results of the phase III <unk> plus <unk> in first line biliary that Youre running just wondering whether you would consider.

Adding to the <unk> to the first liability regimen, which could build on our learnings from Topaz one because if you were to do the quad regimen of <unk> plus <unk> plus gen assists in your pivotal trial in biliary, perhaps this could be an interesting way to differentiate from Topaz one I'm curious your thoughts on that that strategy. Thank you.

I think we're, as you said before, we're quite excited about this potential combination in this patient population.

I think our goal at ESMO is the company's never reported clinical data on ZW49 since, the start of its IND a number of years ago, and I think we want to provide the fulsome data set that we can about what we see with this agent from an efficacy and tolerability standpoint, the rationale for a regimen or more than one regimen which might be available to go forward, and also a clinical development plan, next steps for a clinical development plan that we think makes sense because we think we have an agent that could be extremely competitive and we'd like to invest further in the clinical development of that molecule in light of what we see in competition, in light of what we see as unmet needs and specific indications in the HER2 space.

Whether that includes strategies around looking at future patient populations who progress, after an HER2 is obviously something that we and others are considering and understanding how you would address that patient population in the clinical development plan and what the economic value would be to that sort of clinical development plan.

Her to targeted therapy for that patient population so.

We're optimistic by the data we saw previously with ventilator Mab were happy to be able to get to a top line dataset earlier than we had expected.

The study is recruited very nicely and again accelerated over time, which is always a good sign with a clinical study.

I think we're still.

Recruiting in our ongoing phase III study with first line biliary tract cancer patients.

And we're excited to present our current findings in this study.

And so we've moved as quickly as we can to get that.

And so that is an answering dataset for us I think at the time that we have our ability to attract.

So, we did submit an abstract to a medical meeting that occurs in the fourth quarter and we confirm that.

Cancer data later this year, we will be prepared then to talk about the nature of regulatory filings and next steps in looking at whether we can expand the patient population beyond the current pivotal study into additional.

Expanded label indications and obviously, we're following all the competitive datasets that might be available.

For this patient population of though we are the only ones really with a <unk> targeted therapy for the patients that.

So we'll have as much to say as we can on September 12th, but unfortunately, until we, get to that point, you'll have to wait to have that question addressed.

That we're really looking to treat so I think I'll have more to say about that once we get to two are our pivotal data.

Okay.

Uh huh.

The data release later this year if that's okay.

Okay got it and then specifically on ESMO and the many oral presentation, presumably 49, that's coming up I think you mentioned that it is going to feature a basket of a basket cohort of her two positive cancers I just wanted to check. This does that mean that that's going to include the her two positive breast in her two positive gastroesophageal.

The $2 five Meg per kg Q3 weekly regimen or are we going to see.

Our basket of her two positive cancers outside of breast <unk> at ESMO.

Clarify thank you.

Yes, I'll ask Dr. Neil Josephson to address the question of what patients were recruited in that study and what youre likely to see at ESMO with respect to that.

Sure.

Ken This is Neil Joseph.

Yes.

<unk> that will be presented at ESMO will include breast cancer.

Her two positive breast cancer <unk> positive gastric cancer.

And then.

A mix of other her two positive tumors.

So youll see all of the patients had been enrolled on the CW 49 study and that does include breast and gastric cancer.

And should we expect that coming out of ESMO that we'll be able to learn the recommended phase two dose going forward for this program.

So we will have information about about dosing and about.

Uh huh.

What doses, we will we will potentially take forward.

So I think that that you're referring to a phase II dose singular phenomenon and certainly.

There.

We will have a recommended dose that we will be taking forward.

But there.

There could be more than one that we would that we would pursue depending on on all of the results of.

And then just also a little clarification, I think you said that the vanipalbo colvesterol, that you've submitted in abstract, so just clarify that you did say that and presumably this is to San Antonio?

The phase one study.

And then just one last one I guess for Ken just in terms of higher level strategy in the ADC World, obviously, given the destiny breast data early in the year from in her too.

Strategically are you going to be kind of pivoting away from her to breast and focusing more on her two gastroesophageal and other her two positive cancers for your ADC or do you believe that you still want to pursue her two breast aggressively. Thank you.

Yes, I think and I think in here if you targeted therapy, we feel very comfortable with that data in.

Pivotal studies, we have ongoing right now and ability to track cancer.

And the <unk> study, which is under recruitment.

No we have other data.

In breast cancer and beyond that that could be interesting for expansion beyond the initial market then BTC NGA that we hope to serve pending positive data and successful approval.

So I think we're quite excited about that.

Its potential impact on <unk>.

On the <unk> population.

Including in combination with other agents, which of course was the basis for the <unk> plus <unk> plus four restaurants breast cancer study, which is recruiting nicely.

And as soon as we're able to say that we had an abstract accepted, we'll provide those details and look forward to being able to present that before the end of this year.

And we've submitted an abstract for presentation, we hope to be able to present that in the fourth quarter. So I think with respect to <unk> I think we feel comfortable with the positioning of that.

In the patient population and the benefit we could have for patients beyond what's currently available and also within <unk>.

Developments I think with respect to VW 49.

We are working hard as you know to find a dosing regimen or more than one dosing regimen that we can take forward.

And that would provide efficacy to justify future clinical development possibilities and also the tolerability around that efficacy.

Okay.

And we look forward to sharing that information.

And in our Investor webcast I think we're giving a lot of thought to VW 49 in the clinical development strategy in light of that.

Terrific.

As you say other competitive products that have come to market and the developments.

Thank you.

And we think we think we have a strategy around clinical development is going to be 49 or <unk>.

Yeah.

Thanks.

As we talked about with our earlier stage program I think going beyond that.

Those two agents.

I think there is a host of other targets in other cancer indications that we laid out that we think we are advanced biologics would definitely benefit.

Of that patient population and potentially provide benefits that can't be seen with other product formats, and so with our future product pipeline, we will be going beyond that.

Her two targeted patient population.

And exploring other other potential indications with those agents.

Great. Thanks, Thanks, Ken how Youre welcome. Thank you.

Yeah.

We've obviously given guidance about it being a medical meeting to be held in the Q4 that, would be focused on this indication, but we wouldn't be specific about that until we had our abstract submitted.

We didn't specify the conference.

Please standby for our next question.

Please stand by for our next question.

All right.

Our next question comes from the line of Charles Zhu with Guggenheim Securities.

I think we're, as we said before, we're quite excited about this potential combination in, this patient population.

Your line is open.

The study is recruited very nicely and again, accelerated over time, which is always a good, sign with a clinical study.

All right. Our next question comes from the line of Gena Wang with Barclays. Your line is open.

Hello, everyone, and thanks for taking my questions, and congrats on all the progress.

And we're excited to present our current findings in this study.

And so we've moved as quickly as we can to get that.

Thank you Ken and team.

The question is Tom for Gina.

My first question is regarding ZW49, and I understand you're not commenting on, you, know, whatever you may or may not present at ESMO.

We have two questions one for <unk> 49, so for the updated data at upcoming data in asthma.

I had a related question, not specific to ESMO, but I'm just looking at your updated, slides.

So we did submit an abstract to a medical meeting that occurs in the fourth quarter, and we confirmed that.

It looks like you may have cleared 2.5 milligrams per kg at the Q3 weekly dose, and also looks, like you've already cleared 1.5 weekly and are evaluating 1.75 weekly.

And as soon as we're able to say that we had an abstract accepted, we'll provide those, details and look forward to being able to present that before the end of this year.

It doesn't exactly take a rocket scientist to see that your exposures have effectively, nearly doubled.

I'm just kind of wondering, you know, like, you know, how we should be thinking about, you know, things like the impact of CMAX total area under the curve and exposure as far as efficacy and toxicity signals may be concerned with antibody drug conjugates.

Patient and can we expect in total and especially from the.

The cohort ways.

<unk> three week dosing and what kind of half duration.

Would you expect.

And secondly for <unk> just wondering.

How is the enrollment.

Going forward the GAA pivotal trial given the.

First Lang Triple combo in place.

Thanks.

Okay.

Yes. Thank you for the questions with respect to the Abi Fortinet I'm afraid you'll have to wait until the abstract is available on September five and then obviously our presentation.

Terrific.

Thanks.

Which will be provided by our investigator on September 12.

Please stand by for our next question.

To get the total details about patients.

Which are being disclosed at that time.

So we'll have an investor webcast in September calls after our many oral presentation to provide additional information.

So I'm afraid for that one youre going to have to wait until the actual emo conference.

And CW 25, I think we're we're quite encouraged by our patient recruitment so far on the Gea study.

As you are aware, we chose not to recruit patients in the United States.

Because of the accelerated approval that occurred there was another competitive therapy. So we're recruiting an entirely outside the United States and I think we're quite happy with the recruitment.

That's ongoing with that study I think as we've seen with others in a data map studies. They tend to accelerate later in the clinical study time period and that happened with our pivotal study in BTC, which will read out before the end of this year.

And I think it's happened in our study was Danny and Paolo unsold restaurants.

I think as soon as investigators.

Got some experience to the agent we saw recruitment track up nicely.

That regard and I think we're excited to see the same thing I think the data we put out an emo.

On the first one.

Should have been a first line patients with Danny and then at <unk> and chemo.

Very encouraging to investigators.

We've obviously continued to follow the patient population, which is now fully enrolled the chemo were.

Very encouraging to investigators we've obviously continued to follow the patient population, which is now fully enrolled.

And we hope to give an update of that in the first half of 2023 I think we're very encouraged by the longer term follow up without fully enrolled patient population and the benefits it seems to be being provided by any post chemo regimen.

And also given the fact that chemotherapy regimen as you know.

It has dropped out for a number of cycles.

And patients remain on than it did in <unk> alone. So I think all of those things together I think will encourage further clinical study enrollment and we do expect it to accelerate as our other studies.

As we get.

Further through the clinical study itself.

All right.

Thank you.

Yeah.

No, thanks for the question, Charles.

Our next question comes from the line of Charles Zhu with Guggenheim Securities.

Yes.

Nick Abbott with Wells Fargo. Your line is open.

Your line is open.

Yes.

Thanks, Paul was almost dropping off to sleep.

So maybe the first one for me the press release.

Progress towards previously.

Liberty upon new partnerships collaborations.

Hello, everyone, and thanks for taking my questions, and congrats on all the progress.

Any additional opportunities you could address that in your prepared comments. So can you provide us with some.

Clarity on what the progress is and maybe.

Patients should be.

And, again, I think we're, you know, we won't try and get ahead of the ESMO meeting.

Yes, Thanks for the question Nik and I'll do my best.

We talked about earlier in the year.

First one we're making very nice progress this year without the benefits of resources of new partners.

And I think we're working real nicely with aging.

And our areas of cooperation.

So I think I'm really excited with the progress that we're making without the benefit of additional resources.

We've got active and very wide ranging discussions underway throughout the portfolio that I think will allow us to do what we talked about in January as the importance of this company.

Using a more fulsome an integrated partnership models I think we'll be able to monetize the value that we've generated to date I think we can find ways to accelerate and broaden our business plans that will make us more competitive.

In light of an enhanced competition in the her two space and.

And I think most importantly leave open the possibility for a broader transaction, including an outright acquisition in the future.

From an existing partner or a brand new third party and we've heard that is very important for our shareholders.

And we've listened to that and we will make sure that we don't eliminate that possible in the future from the partnerships and collaborations that we're going to form. So we've got active in wide ranging discussions underway, but having done. This a long time, we won't provide any specific guidance about timeframe or a structure or a parkey of nature.

We'll get these deals done and announce them and explain the rationale and the impact on the company.

As I said earlier in general I think working in a more fulsome integrated partnership mantle throughout the portfolio is very important design works and Thats will be doing from from now until the future. So we fully expect to be able to complete a number of partnerships and collaborations in 2022, and 2023, which will allow us to operate our.

A little bit differently than we did before January of this year. So we're working hard on it we wont give any specific guidance until things are complete and will be happy to explain the rationale for per transactions once they're complete.

Yes.

Okay.

And then just moving on to <unk>.

Please go ahead.

Okay.

Once we've seen that data.

We have clarity around when.

Please go ahead is active in patients who use <unk>.

<unk>.

Hello.

It's our lowest quarter as Neil mentioned, we're seeing more and more of these patients coming in.

Can you give me a lot of the data we're going to see it as most notably on patients.

Enrolled priority for the use of it Jason.

I'm just wondering.

As opposed to market option following in <unk>.

Locally work well.

Future development options, you're considering so please go ahead.

Yes, really good question, Nick and again.

Fortunately youre going to have to wait until.

Until he's mode to see our presentation and in the Investor webcast will be as fulsome as we can.

About.

About all of those questions, which you just asked obviously as I think we mentioned earlier we're seeing.

More and more on her two failures in all of our studies.

We didn't exclude in her two failures in does need to be 49 studies.

So.

There could be patients in there what we can make of the data and how long those patients been studied is something you'll have to wait till you get to two even though I think our goal at <unk> is the company's never reported clinical data on <unk> to be 49 since the start of its R&D a number of years ago, and I think we want to provide.

I mean, obviously, you know, the company has spent some time studying, you know, every, three-week dosing with ZW49, and, you know, we should be able to present a pretty fulsome picture there of, you know, what efficacy we think we see and what the side effect profile is of that agent in picking a recommended phase 2 dose.

Fulsome data set that we can about what we see with this agent from an efficacy and Tolerability standpoint.

The rationale for our regimen or more than one regimen, which might be available to go forward and also our clinical development plan next steps for clinical belt and plan that we think makes sense.

Because we think we have an agent that could be.

Extremely competitive and we'd like to to invest further in the clinical development of that molecule.

In light of what we see in competition in light of what we see is unmet needs in specific indications.

And the her two space.

Whether that includes strategies around.

Looking at future patient populations, who progress.

After her too.

Is obviously something that we and others are considering an understanding how you would.

Address that patient population with the current development plan and what the economic value would be to that sort of clinical development plan. So we will have as much to say as we can on September 12th, but unfortunately until we get to that point, you'll have to wait to have that question addressed.

Okay.

And then just last one maybe on the clarification I think.

Danny <unk> co investor submitted an abstract.

Clarify that as a good quarter and presumably this is telephone Antonio.

Yes, we didn't we didn't specify the conferences, we've obviously given guidance about it being a.

Medical meeting to be held in the Q4 that will be focused in this indication, but we wouldnt be specific about that until we had our abstract submitted I think were.

We said before we're quite excited about this potential combination in this patient population.

The studies recruited very nicely and again accelerated over time, which is always a good sign with a clinical study.

And we're excited to present, our current findings.

In this study and so we've moved as quickly as we can to get.

To get that so we did submit an abstract to a medical meeting that occurs in the fourth quarter I can confirm that.

And as soon as we're able to say that we had an abstract accepted will provide those details.

And look forward to being able to present that before the end of this year.

Okay terrific.

Thanks.

Please standby for our next question.

Our next question comes from the line of Charles Zhou with Guggenheim Securities. Your line is open.

Hello, everyone and thanks for taking my questions and congrats on all the progress. My first question is regarding GW 49, and I understand you're not commenting on the whatever you may or may not present at ESMO I had us related question not specific to ESMO, but I'm just.

My first question is regarding ZW49, and I understand you're not commenting on, you know, whatever you may or may not present at ESMO.

I had a related question, not specific to ESMO, but I'm just looking at your updated, slides.

At your updated slides it looks like you may have cleared two five milligrams per kg at the Q3 weekly dose and also looks like you've already cleared wanted to hash weekly and are evaluating <unk> seven slide weekly it doesn't exactly take a rocket scientist to see that your exposure to effectively nearly doubled I'm just kind of.

It looks like you may have cleared 2.5 milligrams per kg at the Q3 weekly dose, and also looks, like you've already cleared 1.5 weekly and are evaluating 1.75 weekly.

It doesn't exactly take a rocket scientist to see that your exposures have effectively, nearly doubled.

I'm just kind of wondering, you know, like, you know, how we should be thinking about, you know, things like the impact of CMAX, total area under the curve, and exposure as far as efficacy and toxicity, so that those may be concerned with antibody drug conjugates.

Wondering like all of them.

How we should be thinking about.

Things like the impact of C. Max total area under the curve and exposure as far as efficacy and toxicity signals may be concerned with antibody drug conjugates.

No, thanks for the question, Charles, and again, I think we're, you know, we won't try, and get ahead of the ESMO meeting.

No. Thanks for the thanks for the question Charles and again I think we're well.

We won't try and get ahead of the IMO meeting I mean, obviously the company has spent some time studying every three week dosing with the <unk> 49, and we should build present, a pretty fulsome picture there of.

I mean, obviously, the, you know, the company has spent some time studying, you know, every, 3-week dosing with ZW49, and, you know, we should be able to present a pretty fulsome picture there of, you know, what efficacy we think we see and what the side effect profile is of that agent in picking a recommended phase 2 dose, and obviously, we've gone up in the dose escalation and dose expansion, as you've mentioned.

What efficacy, we think we see and what the side effect profile is of that agent.

In picking a recommended phase II dose and obviously, we've we've gone up in the dose escalation dose expansion as you've mentioned.

And, obviously, we've gone up in the dose escalation and dose expansion, as you've mentioned.

As you know, the company started a weekly dosing regimen to try and understand what, would happen to efficacy and tolerability.

As you know, the company started a weekly dosing regimen to try and understand what, would happen to efficacy and tolerability, and we've been working through that process in the dose escalation and dose expansion, and we look forward to present everything that we have at ESMO and what the future direction might be, and again, I think, not to get ahead of ESMO, but I think, you know, there wouldn't be any reason to expect that there may be, you know, more than one dosing regimen, which might be suitable for patient populations to study in the future, and again, as you know, some agents, I think, including TRAS, have more than one dosing regimen, which might be applicable, but we'll look forward, to presenting, you know, everything we've done to date, because we've never presented any clinical data on ZW49 since the IND, so we'll present all the phase 1 data we have.

As you know the company started a weekly dosing regimen.

To try and understand what would happen to efficacy and Tolerability and we've been working through that process in the dose escalation and dose expansion.

And we've been working through that process in the dose escalation and dose expansion.

And we look forward to present everything that we have at ESMO and what the future direction, might be.

And we look forward to present everything that we have at.

<unk> and what the future direction might.

It might be.

And again I think not to get ahead of IMO, but I think.

And, again, I think not to get ahead of ESMO, but I think, you know, it wouldn't be unreasonable, to expect that there may be, you know, more than one dosing regimen which might be suitable for patient populations to study in the future. And, again, as you know, some agents, I think including TREADS, have more than one dosing, regimen which might be applicable.

Be unreasonable to expect that there may be more than one dosing regimen, which might be suitable for patient populations.

The study in the future.

Have more than one dosing regimens might be applicable.

But we'll look forward to presenting, you know, everything we've done to date because, we've never presented any clinical data on ZW49 since the IND. So we'll present all the phase one data we have.

Everything we've done to date, because we've never presented clinical data on <unk> would be 49 since the <unk> and all of the phase one data. We have we will provide some feedback on the next steps that we think will development plan.

We'll provide some feedback on the next steps that we see in the clinical development plan, including what recommended dose we would study in that development plan, as well as additional studies that we might have ongoing with ZW49 at the time of ESMO.

We'll provide some feedback on the next steps that we see in clinical development plan, including what recommended dose we would study in that development plan, as well as additional studies that we might have ongoing with ZW49 at the time of ESMO, so I think you'll get a full sense of those questions and try and address the specific things you mentioned about PMAX and AUC and how that might relate to tolerability, and the relationship between the efficacy you can generate and the tolerability that you have to accept to generate that efficacy.

As well as additional studies that we might have ongoing with CW 49 at the time of use most so I think you'll get a full sense of those questions in and trying to address.

So I think you'll get a full sense of those questions and try and address the specific, things you mentioned about PMAX and AUC and how that might relate to tolerability and the relationship between the efficacy you can generate and the tolerability that you have to accept to generate that efficacy.

This specific things you mentioned about <unk>, and AUC and how that might relate to tolerability and the relationship between the efficacy you can generate on the tolerability that you have to accept.

Generate that efficacy I think we're really encouraged by the phase one program. We've done its very fulsome I think we've done some really good work around the strategic strategically how we can continue to develop CW <unk> 49 in light of a different competitive environment than when we started and we still think there is a.

I think we're really encouraged by the phase one program we've done.

I think we're really encouraged by the phase 1 program we've done.

It's very fulsome.

I think we've done some really good work around the strategic, strategically how we, can continue to develop ZW49 in light of a different competitive environment than when we started. And we still think there's a really good place with ZW49 based on its unique mechanism, of action associated with the ADC that we constructed to take forward in the clinic.

I think we've done some really good work around the strategic, strategically how we can continue, to develop ZW49 in light of a different competitive environment than when we started, and we still think there's a really good place for ZW49 based on its unique mechanism of action associated with the ADC that we constructed to take forward in the clinic, and we look forward to giving a fulsome discussion at ESMO during the poster presentation and our investor webcast to be held after that and explaining the rationale and answering all those questions which you just poised now on September 12th, so unfortunately, you'll have to wait for those.

A really good place is going to be 49 based on its unique mechanism of action.

To take forward in the clinic, and we look forward to giving a fulsome discussion at ESMO during the poster presentation in our investor webcast to be held after that and explaining the rationale in answering all those questions would you just poised now on September 12, so unfortunate.

And we look forward to giving a fulsome discussion at ESMO during the poster presentation and, our investor webcast to be held after that and explaining the rationale and answering all those questions which you just poised now on September 12th.

So unfortunately, we have to wait for those.

Got it, yep, fully understand.

Got it.

Wait for those.

Yep.

Fully understand.

And maybe just one more regarding biliary tract cancer and the readout that you have, now coming at the year end of 2022.

Got it yet fully understand and maybe just one more regarding biliary tract cancer and the Readouts that you have now coming at year end of 'twenty two.

I understand we're probably splitting hairs with this question, but I guess what exactly, drove the change in guidance from early 23 to year end 22, and do your patients only need to be independently assessed on the primary endpoint, or is there also a minimum follow-up that needs to be met as well?

I understand we're probably split splitting hairs with this question, but I guess, what exactly drove that change in guidance.

Thanks.

Early 'twenty three to year end, 'twenty, two MW or patients only need to be independently assessed on the primary endpoint or is there also a minimum follow up that needs to be met as well. Thanks.

Yeah.

Yeah, no, I think the updating guidance is just the fact that operationally we're performing, I think better than we did in prior years, and it was one of the things I think I laid out in mid-January is that the company would try and focus on fewer priorities, and by focusing on fewer priorities, we would try to improve operational performance and get things done more quickly in a higher quality way or allow us to do things more broadly.

No, I think the updating guidance is just the fact that operationally we're performing, I think, better than we did in prior years.

Yes.

And it was one of the things I think I laid out in mid-January is that the company would, try and focus on fewer priorities, and by focusing on fewer priorities, we would try to improve operational performance and get things done more quickly in a higher quality way or allow us to do things more broadly.

Quickly in a higher quality way or allow us to things more broadly and I think this is one instance, where I think our our folks in clinical operations and clinical research and biometrics and regulatory have done an extremely good job of.

And I think this is one instance where I think our folks in clinical operations and, clinical research and biometrics and regulatory have done an extremely good job of working with this data set, and now we feel comfortable that we'll be able to have top-line data to be announced before the end of this year as opposed to early 2023.

Working with this dataset and now we feel comfortable that we'll be able to.

Top line data to be announced before the end of this year as opposed into early 2023, and then also obviously gives us an earlier opportunity to present the full dataset.

And that also obviously gives us an earlier opportunity to present the full data set at, a peer-reviewed conference in the first half of 2023.

So I don't think it's down to anything related to the patient results or the patient population, we're studying.

I think it's down to just great operational performance by our team, and I hope that the, focus we've had on doing fewer things and doing them better and that this is an example of it.

I think it's down to just great operational performance by our team.

And I think – I hope that the focus we've had on doing fewer things and doing them better, and that this is an example of it.

And I think you'll hopefully continue to see that throughout the portfolio and throughout, all of our operations that we're much more nimble and much more focused as an organization, and this will allow us to get things done in a better way, which will ultimately lead to enhanced competitive ability with both data maps, DW-49 and DW-171 and 191 and other things that come out of our preclinical portfolio.

And I think you'll hopefully continue to see that throughout the portfolio and throughout, all of our operations that we're much more nimble and much more focused as an organization. And this will allow us to get things done in a better way, which will ultimately lead, to enhanced competitive ability with both DataMap ZW49 and ZW171 and ZW191 and other things that come out of our preclinical portfolio.

You will hopefully continue to see that.

Great.

With both <unk> to be 49, and GW 171, and 191 and other things that come out of our preclinical portfolio.

Thanks for taking the questions and look forward to your upcoming data sets.

Great. Thanks for taking the questions and look forward to your upcoming datasets. Thanks.

Thanks, Charles.

Please stand by for our next question.

Our next question comes from the line of Steven Wiley with Stiefel.

Our next question comes from the line of Stephen Wiley with T-Cell.

Our next question comes from the line of.

Stephen Wiley with Stifel. Your line is open.

Your line is open.

Yeah.

Good afternoon.

Thanks for taking the question, and I'll spare you the DW-49 question.

Thanks for taking the questions.

Yes, good afternoon, thanks for taking the questions.

And I'll spare you the ZW49 question.

Spare you the GW. According nine question.

Maybe one on the earlier stage pipeline, and I guess I'm not looking to steal any of your, R&D data, Thunder, but I know that T-cell redirected by specifics have been pretty hard.

Maybe one on the earlier stage pipeline, and I guess I'm not looking to steal any of your, R&D data from the funder.

Maybe one on the earlier stage pipeline and I guess I'm not looking to steal any of your R&D day event Thunder, but.

But, you know, I know that T-Cell redirected by specifics have been pretty hard.

I know that T cell redirected bi specifics have been.

Pretty hard.

I think they've proven to be even more difficult in the solid tumor space and a lot of those, challenges, obviously, on safety tolerability.

I think they've proven to be even more difficult in the solid tumor space and a lot of those, challenges obviously on safety tolerability.

I think they've proven to be even more difficult than the solid tumor space.

A lot of those challenges obviously.

So just wondering if you can speak a little bit to how you think you can best overcome, some of these challenges and whether or not that's going to occur through target selection.

So just wondering, you know, if you can speak a little bit to how you think you can best, overcome some of these challenges and whether or not that's going to occur through target selection.

Non safety Tolerability so.

Just wondering if you can speak a little bit to how you think you can best overcome some of these.

Challenges and whether or not that's going to occur through.

Target selection is it going to be.

Is it going to be playing around with CD3 affinities and variants?

Playing around with CD, three <unk>, Barry and so is it going to be balanced.

Is it going to be valency?

Just curious as to how you're thinking you can improve upon this specifically in the, solid tumor space.

Just curious as to how you're thinking you can improve upon this specifically in the solid tumor space.

Thank you.

Thanks.

No, thanks for the question.

Thanks.

And again, you know, for ZB49, we're very excited to talk to folks about the progress, we've made.

No. Thanks for the question and again, presumably 49, we're very excited to talk to folks about.

The progress we've made and I just don't want to get ahead of the emo.

No.

I just don't want to get ahead of the ESMO presentation.

Thanks for the question.

So sorry for not being able to address any of those things in advance, but it's five, weeks away, hopefully.

<unk>.

So sorry for not being able to address any of those things in advance, but it's five.

And, again, you know, for ZB49, we're very excited to talk to folks about the progress, we've made.

You know, I think in the early stage portfolio, you know, we have a number of programs ongoing.

Five weeks away hopefully.

I think in the early stage portfolio, we have a number of programs ongoing I think the two we identified now where we're excited about and we think that can help us meet our goal of getting it.

I think the two we identified now we're excited about, and we think they can help us meet, our goal of getting IND filings by 2024 for these two programs.

IND filings.

2024.

I think on 191, the ADC program with the new TOEFL payload, we're quite excited about, you know, using our new payload and our different platform in this way. So we're excited to talk about that.

For these two programs I think on 191, the ADC program with a new triple payload, we're quite excited about.

Using our new payload and are different.

Platform.

In this way so excited to talk about that I think on the multi specific antibody therapeutic program I think we have some very specific thoughts around some of the things that you mentioned and I think the specific targets that we're looking at going after and some of the things that you mentioned are things that we think are.

I think on the multi-specific antibody therapeutic program, I think we have some very specific, thoughts around some of the things that you mentioned.

And I think the specific target that we're looking, going after, and some of the things, that you mentioned are things that we think are competitively positive for us in our ability to do this.

Competitively positive for us and our ability to do this and I think we can differentiate ourselves by addressing some of the issues and step back because I think you've seen previously with this.

And I think we can differentiate ourselves by addressing some of the issues and setbacks, that I think you've seen previously with this.

So we've done a really extensive assessment of different bi-specific formats.

So we've done a really extensive assessment of different bispecific formats. I mean, this is where the company started with design a whole range of Bispecific for partners and ourselves and I think we have a good reputation for being.

I mean, this is where the company started.

We designed a whole range of bi-specifics for partners and ourselves, and I think we, have a good reputation for being bright and smart protein engineers.

Bright and smart.

Engine protein engineers, and we've used that specifically with 171.

And we've used that specifically with 171. So I think through the assessment and the work that we've done previously, we've used, that to come up with what we think is a really interesting product candidate that we look forward to taking forward in the clinic.

And on October 20th, we're happy to lay out as much detail as we can about both of these, candidates, other programs that we're working on, as well as the strategy moving forward and explaining the rationale for how we hope to turn these two agents into successful clinical candidates from an efficacy and tolerability standpoint.

<unk>, 20th we're happy to lay out as.

As much detail as we can about both of these candidates other programs.

That we're working on as well as the strategy of moving forward and explain the rationale.

And we'll be happy to address all of that on October 20th at our early R&D day.

All right.

Thanks for taking the question.

Alright, thanks for taking the question.

Okay.

Our next question comes from the line of Akash Tiwari with Jeffries.

Our next question.

Comes from the line of.

Our cash Tiwari with Jefferies. Your line is open.

Your line is open.

Hi.

This is Amy Young for Akash.

Thanks so much for taking our question.

Hi, This is Amy anchor cause thanks, so much for taking our question just.

Just wanted to get the company's current stance on the acceptable rates of ITOX with the new, forward dose.

Just wanted to get the company current spot on the acceptable rates with Ipass capable for dose luncheon I talk with more off target.

You mentioned ITOX is more off-target and related to CNOX, but it seems like efficacy, is generally more related to CNIN.

Well it seems like occupancy is generally more related to the NIM is the relationship between coking applicable linear based on the current.

Is the relationship between safety and efficacy linear based on, I guess, the current PK data, that you're looking at, or is there a sweet spot that you're trying to hit with the dosage regimens that you're evaluating?

Current PK data that youre looking at or is there a sweet spot that you calibrate dosing regimens that youre evaluating.

Thanks for the question, Amy.

I just don't want to get ahead of the ESMO presentation, so sorry for not being able, to address any of those things in advance, but it's, you know, five weeks away, hopefully.

Again, I don't think we'll talk about too much detail before easement, but I'll just, pause and ask if Dr. Neal-Josephson wants to say anything about your question or whether we'll just wait until September 12th and answer it then.

Thanks for the question I mean again I don't think we will talk about too much detail before he's no, but I'll just pause and ask if Dr. Neil Josephson wants to say.

Anything about your question of whether we'll just wait until September 12 and answer them.

Yeah, I would reiterate what you said, Ken, which is that we'll look at the data that, we have at the ITO conference.

Yeah.

I would reiterate what you said, Ken which is that that will last.

Data that we have at the so.

Conference.

You know, I think in the early stage portfolio, you know, we have a number of programs ongoing.

I think that...

We said that we were evaluating different regimens to try to look at CMAX and exposure.

I think the two we identified now we're excited about, and we think they can help us meet, our goal of getting IND filings by 2024 for these two programs.

I think on 191, the ADC program with the new TOEFL payload, we're quite excited about, you know, using our new payload and our different platform in this way, so we're excited to talk about that.

We are.

I think on the multi-specific antibody therapeutic program, I think we have some very specific, some of the things that you mentioned, and I think the specific targets that we're looking going after and some of the things that you mentioned are things that we think are competitively positive for us in our ability to do this, and I think we can differentiate ourselves by addressing some of the issues and setbacks that I think you've seen previously with this.

<unk> said that that we were evaluating different yes.

Regimens to try to look at C Max and <unk>.

And exposure.

I'm not sure that we ever made specific comments about what was more related to which PK parameter, but we'll lay out all the data that we have at the conference.

Not sure that we ever made specific.

Comments about.

What was more related to two which which PK parameter, but we'll we'll lay out all the data that we have.

At the Ash conference.

Great.

Thanks so much.

Great. Thanks, So much and then I guess I know you guys aren't talking too much about.

And then I guess I know you guys aren't talking too much about ESMO, but will we see data, from your potential go-forward dose?

But well see.

Data from your potential go forward Joe.

And then I guess just from a high-level standpoint, would it be sufficient enough to compare versus, inferred to, or is it still too early?

And then I guess just from a high level standpoint, where the beef deflation and Africom canvas hurt you or is it still too early.

Do you want to take that one, Neil? Yeah, sure.

Do you want to take that one Neil.

Sure.

Yeah, again, to what we said, which was I think you'll have to wait until ESMO to actually, see the data.

Yeah.

Hi.

Again to what we said, which was whereas I think youll have to wait until ESMO to to actually see the data.

In terms of dosing, we will have information about dosing.

In terms of.

Of dosing, we will have information about about dosing.

<unk>.

As we've said multiple times, there may be more than one dose that we would take forward.

As as we can.

Multiple times.

There may be more than one dose that we would take forward.

And then in terms of your question about, I think that, you know, it has a different, molecule than two.

And then in terms of your question about.

Two I think that deck.

You have a different molecule than two it has.

It has a different payload.

Different.

It has a different mechanism of action.

<unk> it has a different action.

Okay.

It has a completely different profile from an adverse event standpoint.

It has.

Profile from from an adverse event standpoint, so I I don't think that that.

So I don't think that we are looking at this as a direct comparison to InHERtU at all.

We are looking at this as as.

Our direct to her to at all I think that.

I think that there are development paths for this molecule that are unique from what InHERtU, can develop.

Things that are development path for this molecule that.

Our unique from what in her two can develop and so.

So, you know, as we, you know, lay out information, we'll also try to start to give information, about how we're going to take the molecule forward.

As we lay out formation will also try to.

Start to give information about how we're going to take the molecule forward.

Great.

Thank you so much.

Great. Thank you so much.

Yeah.

And Amy, just to follow up, for, you know, for decisions we make, like a recommended, phase two dose, we will provide all the data to support the rationale for decisions that we're making with this clinical development program.

And Amy just a follow up for poor decisions, we make like a recommended phase II dose, we will provide all the data to support the rationale for decisions that we're making with its clinical development programs, who should exceed you should be expect to be able to see the supporting data and rationale and then make your own determination about.

So you should be, expect to be able to see the supporting data and rationale and then, make your own determination about, you know, our interpretation, analysis and conclusions about that data.

Our interpretation of analysis and conclusions about that data.

That's super helpful.

Thank you so much.

That's super helpful. Thank you so much.

There appears to be no further questions.

I'd like to turn the conference back over to Zymwerks for closing remarks.

That's great.

Yeah.

Thank you, Operator.

And thank you for your attendance today and for all of your questions.

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

So we've done a really extensive assessment of different bi-specific formats.

We've had a really exciting time, quarter on all fronts, and we really look forward to the next opportunity to, to present some additional data.

I mean, this is where the company started.

We designed a whole range of bi-specifics for our partners and ourselves, and I think, we have a good reputation for being bright and smart protein engineers, and we've used that specifically with 171.

That's great. Thank you operator, and thank you for your attendance today and for all of your questions. We had a really exciting quarter.

Quarter on all fronts, and we really look forward to the next opportunity to to.

To present, some additional data we're looking forward to emo on both our parts of the presentation. A webcast. We also have four different investment conference attendance, which allows us to present and have meeting on the same week as these moe and so we look forward to be able to explain further the data that we're presenting the future decisions.

We're looking forward to ESMO on both our reports and presentation of webcasts. We also have four different investment conference attendance, which allows us to present and, have meetings on the same week as ESMO.

And so we look forward to be able to explain further the data that we're presenting, the, future decisions we have going forward and what data supports those decisions and rationale.

We have going forward.

The data supports of those decisions and rationale so we look forward to that and please look forward.

So I think through the assessment and the work that we've done previously, we've used, that to come up with what we think is a really interesting product candidate that we look forward to taking forward in the clinic, and on October 20th, we're happy to lay out as much detail as we can about both of these candidates, other programs that we're working on, as well as the strategy moving forward and explaining the rationale for how we hope to turn these two agents into successful clinical candidates from an efficacy and tolerability standpoint, and we'll be happy to address all that on October 20th at our early R&D day.

So we look forward to that and please look forward to save the date notices for October, 20th and our early R&D day.

So save the date notices for October 20th in our early R&D day, we're really looking forward to two showing the next agents to come out of the App.

All right.

Thanks for taking the question.

We're really looking forward to, to showing the next agents to come out of the engine, and technology platforms that we have at Zymwerks.

Mm-hmm.

Our next question comes from the line of Akash Tiwari with Jeffries.

And Jen and technology platforms that we have assigned works and I think you will find them very interesting for the future of the company beyond <unk> and CW 49. So please.

Your line is open.

And I think you'll find them very interesting for the future of the company beyond Xanadata, MEV and ZW49.

Hi.

This is Amy Young for Akash.

Thanks so much for taking our question.

So please keep an eye out for that October 20th date and save it in your calendar.

Just wanted to get the company's current stance on the acceptable rates of ITOX with the new, forward dose.

You mentioned ITOX is more off-target and related to Xenax, but it seems like efficacy, is generally more related to Cmin.

Keep an eye out for that October 2008, as they are in your calendar and we look forward to seeing you. Some of you at emo and I'm talking about our presentation. Our next investor webcast on September 12. So thank you very much for your time and look forward to see you soon.

Thanks for the question, Amy.

And we'll look forward to, to seeing you, some of you at ESMO and, and talking about, our presentation, our next investor webcast on September 12th.

Again, I don't think we'll talk about too much detail before ease mode, but I'll just, pause and ask if Dr. Neal Josephson wants to say anything about your question or whether we'll just wait until September 12th and answer it then.

Yeah.

I would reiterate what you said, Ken, which is that we'll like the data that we have at, the ITO conference.

We said that we were evaluating different regimens to try to look at CMAX and exposure.

And we'll look forward to seeing some of you at ESMO and talking about our presentation, on our next investor webcast on September 12th.

I'm not sure that we ever made specific comments about what was more related to which PK parameter, but we'll lay out all the data that we have at the conference.

Great.

Thanks so much.

So thank you very much for your time and look forward to seeing you soon.

And then I guess, I know you guys aren't talking too much about ESMO, but will we see data, from your potential go-forward dose?

And then I guess just from a high-level standpoint, would it be sufficient enough to compare versus, inferred to, or is it still too early?

This concludes today's conference call.

Do you want to take that one, Neil? Yeah, sure.

Yeah, again, to what we said, which was, I think you'll have to wait until ESMO to actually, see the data.

In terms of dosing, we will have information about dosing.

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

As we've said multiple times, there may be more than one dose that we would take forward.

And then in terms of your question about, I think that, you know, it may have a different, molecule than the other two.

It has a different payload.

It has a different mechanism of action.

It has a completely different profile from an adverse event standpoint.

So I don't think that we are looking at this as a direct comparison to InHER-2 at all.

I think that there are things that are development paths for this molecule that are unique from, what InHER-2 can develop.

And so, you know, as we, you know, lay out information, we'll also try to start to give, information about how we're going to take the molecule forward.

Great.

Thank you so much.

Yeah.

So you should expect to be able to see the supporting data and rationale, and then make, your own determination about, you know, our interpretation, analysis, and conclusions about that data.

That's super helpful.

Thank you so much.

There appears to be no further questions.

I'd like to turn the conference back over to Zymwerx for closing remarks.

That's great.

Thank you, Operator.

And thank you for your attendance today and for all of your questions.

We've had a really exciting time.

We also have four different investment conference attendance, which allows us to present and, have meetings on the same week as ESMO.

And so we look forward to be able to explain further the data that we're presenting, the, future decisions we have going forward, and what data supports those decisions and rationale.

So we look forward to that.

And please look forward to save the date notices for October 20th and our early R&D day.

We're really looking forward to showing the next agents to come out of the engine and, technology platforms that we have at Zymwerx.

And I think you'll find them very interesting for the future of the company beyond Xanadata, MEV and ZW49.

So please keep an eye out for that October 20th date and save it in your calendar.

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