Thank you for standing by. This is the conference operator. Welcome to Zymeworks' 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 opportunity to ask questions. To join the question queue, press star then the number one one on your telephone keypad. I would now like to turn the conference over to Jack Spinks, Associate Director of Investor Relations at Zymeworks. Jack, please go ahead.
Good afternoon and welcome, everyone. My name is Jack Spinks, Associate Director of Investor Relations here at Zymeworks. 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'll 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 zanidatamab 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 pre-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.
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 of development. For a 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. 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 connection with the proposed redomicile transactions, Zymeworks Delaware Inc. has filed with the SEC a registration statement on Form S-4 that includes a preliminary proxy statement/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/prospectus will be mailed to Zymeworks security holders. 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. These documents are available free of charge at the SEC's website at www.sec.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.
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. Now, I will turn the call over to Ken, our Chair and CEO. 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, 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 announce and congratulate Neil Klompas 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. I also want to welcome Dr. Paul Moore to Zymeworks as our new chief scientific officer.
Paul started with us on July 18 and has already begun to make valuable contributions to our early R&D efforts with his R&D colleagues. 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. This afternoon, Zymeworks reported financial results for the quarter ended June 30, 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 Altreca 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 June 30th, 2021. This increase in the prior year related primarily to higher clinical trial expenses for zanidatamab 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 recognized slightly lower research and development expenses quarter-over-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 30th, 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. Zymeworks' 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 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 recognized a $5 million fee from our licensing agreement with Altreca, 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.zymeworks.com.
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 group. 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. 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.
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, zanidatamab, our HER2-targeted bispecific antibody, and zanidatamab zovodotin, or ZW49, our HER2-targeted antibody drug conjugate. I'd like to start by briefly highlighting clinical data with zanidatamab presented by our partner BeiGene at the annual meeting of the American Society of Clinical Oncology, or ASCO, in June. Results from this phase Ib/II study of zanidatamab in the frontline setting of HER2-positive breast cancer and gastric cancer were presented in two separate poster sessions. Both data sets demonstrated promising antitumor activity and a manageable safety profile for the treatment of advanced or metastatic disease with zanidatamab given in combination with standard of care chemotherapy. The regimen given to the gastric cancer cohort also included the PD-1 inhibitor tislelizumab.
The gastric cancer data presented provides support for the experimental regimen of zanidatamab and tislelizumab 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 zanidatamab in 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 HER2-positive, hormone receptor-positive breast cancer patients treated with zanidatamab in combination with fulvestrant and palbociclib, Pfizer's CDK4/6 inhibitor. This data set will also be important to informing our future development plans for zanidatamab in breast cancer. We are continuing to make progress with our multicenter global phase II open label first line study of zanidatamab 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 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. 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 HERIZON-BTC-01 phase II pivotal clinical trial of zanidatamab 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 HERIZON-BTC-01 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, zanidatamab zovodotin, 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 for Medical Oncology, or ESMO, in September in Paris, Dr. Komal 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. Her mini oral presentation will be the first comprehensive disclosure of clinical data for zanidatamab zovodotin. 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. I am 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 20, 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 for the meeting and the webcast will be available shortly on our website. While we'll be 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 zanidatamab, 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 camptothecin-derived payload that we believe can be competitive in areas with high unmet clinical need, such as ovarian cancer and other gynecological cancers.
ZW-191 represents our second announced antibody-drug conjugate, the first being zanidatamab zovodotin, 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 zanidatamab and zanidatamab zovodotin 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 Zymeworks 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. Stay tuned for further details. 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 our press release earlier this summer, Paul brings with him a wealth of knowledge in 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'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. 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. 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 Zymeworks 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, Zymeworks 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 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-4 filing.
However, we hope that it will occur within the next few months. 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 affecting 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. 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 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-4 with the SEC by Zymeworks 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 look ahead to the remainder of 2022. I will briefly highlight a few important key catalysts. I'll start with zanidatamab, where expected in the fourth quarter this year, we're excited to present results from our late-line HER2-positive hormone receptor-positive metastatic breast cancer study of zanidatamab in combination with fulvestrant and palbociclib.
We also announced today an update to the timing of data from our pivotal trial, HERIZON-BTC-01, where we now expect top- line data to be announced late this year. For zanidatamab zovodotin, 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, zanidatamab zovodotin. 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 data program 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 subvariants 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. We truly hope that a return to normalization in the face of the COVID endemic continues, but will ensure we are prepared for any new restrictions. With that, I will turn the call over to the operator to begin the question and answer session.
As a reminder, to ask a question, please press star one one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing any keys. We will pause for a moment as callers join the queue. All right, our first question comes from the line of Yigal Nochomovitz . Your line is open.
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-1 earlier this year from durvalumab plus gemcitabine. Given that data and obviously depending on the results of the phase II zanidatamab plus gemcitabine in first-line biliary that you're running, just wondering whether you'd consider adding tislelizumab to the first-line biliary regimen, which could build on the learnings from TOPAZ-1. Because if you were to do the quad regimen of zanidatamab plus tislelizumab plus gemcitabine in your pivotal trial in biliary, perhaps this could be an interesting way to differentiate from TOPAZ-1. I'm curious your thoughts on that strategy. Thank you.
Yeah, thanks for the question. Again, I think, as you said, we're, you know, we're extremely optimistic in our current pivotal study, using zani as monotherapy in second line patient populations, and that has the potential to be the, you know, the first, HER2 targeted therapy for that patient population. You know, we're optimistic about the data we saw previously with zanidatamab. We're happy to be able to get to a top line data set earlier than we had expected. I think we're, you know, still, you know, recruiting in our ongoing phase II study with first line biliary tract cancer patients. 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 pivotal study into additional expanded label indications. 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. 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.
Okay, got it. Specifically on ESMO and the mini oral presentation for ZW49 that's coming up, I think you mentioned that it's gonna feature a basket cohort of HER2-positive cancers. I just wanted to check, does that mean that that's gonna include the HER2-positive breast and HER2-positive gastroesophageal at the 2.5 mg per kg Q3 weekly regimen? Or are we gonna see a basket of HER2-positive cancers outside of breast and GEA at ESMO? Just clarify. Thank you.
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.
Sure. Thanks, Ken. This is Neil Josephson. 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. You'll see all of the patients that have been enrolled on the ZW49 study, and that does include breast and gastric cancer.
Should we expect that coming out of ESMO, that we'll be able to learn the recommended phase II dose going forward for this program?
We will have information about dosing and what doses we will potentially take forward. I think that you're referring to a phase II dose singular phenomenon, and certainly we will have a recommended dose that we will be taking forward. It could be more than one that we would pursue depending on all of the results of the phase I study.
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 breast data earlier in the year from Enhertu, you know, strategically, are you gonna 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 wanna pursue HER2 breast aggressively? Thank you.
I think in HER2 targeted therapy, you know, we feel very comfortable with zanidatamab in the pivotal studies we have ongoing right now in biliary tract cancer and the GEA study, which is under recruitment. As you know, we have other data in breast cancer and beyond that could be interesting for expansion beyond the initial markets in BTC and GEA that we hope to serve pending positive data and successful approvals. I think we're quite excited about zanidatamab in its potential impact on the HER2 population including in combination with the other agents, which, of course, was the basis for the zanidatamab plus palbociclib plus fulvestrant breast cancer study, which you know is recruiting nicely. We've submitted an abstract for presentation.
We hope to be able to present that in the fourth quarter. I think with respect to zanidatamab, 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, 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. 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 into development. We think we have a strategy around clinical development of ZW49 or zanidatamab zovodotin 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. I think we're very committed to zanidatamab 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. 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, Ken. Appreciate it.
Oh, you're welcome.
Yeah, thank you.
Please stand by for our next question. All right, our next question comes from the line of Gena Wang with Barclays. Your line is open.
Thank you, Ken and team, for taking the question. This is Tom for Gena. We have two questions, one for ZW49. For the updated upcoming data in ESMO, 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? Secondly, for ZW25, just wondering, how is the enrollment going for the GEA pivotal trial given the first line triple combo in place?
Yeah, thank you for the questions. With respect to ZW49, I'm afraid you'll have to wait until the abstract is available on September 5, 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. We also will have an investor webcast on September 12, after our mini oral presentation to provide additional information. I'm afraid for that one you're gonna have to wait until the actual ESMO conference. With ZW25, I think we're quite encouraged by our patient recruitment so far in the GEA study. 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.
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 other zanidatamab 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. I think it's happened in our study with zanidatamab and palbociclib and fulvestrant, where I think as soon as investigators got some experience with the agent, we saw recruitment pick up nicely in that regard. 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 zanidatamab and tislelizumab and chemo were very encouraging to investigators. We've obviously continued to follow those 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 zanidatamab post the chemo regimen. Given the fact that chemotherapy regimen, as you know, is dropped after a number of cycles, and patients remain on tislelizumab alone.
I think all those things together, I think, will encourage further clinical study enrollment. We do expect it to accelerate as our other studies have, as we get further through the clinical study itself.
Thank you.
Mm-hmm.
Nick Abbott with Wells Fargo, your line is open.
Thanks. I was almost dropping off to sleep there. 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. You didn't address that in your prepared comments. Can you provide us with some, you know, 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 making very nice progress this year without the benefits and resources of new partners. I think we're working well, you know, nicely with BeiGene in our areas of cooperation. I think, you know, I'm really excited about the progress that 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. 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. 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. We've heard that's very important to our shareholders, and we've listened to that, and we will make sure that we don't eliminate that possibility in the future from the partnerships and collaborations that we're going to form. We've got active and wide-ranging discussions underway, but having done this a long time, we won't provide any specific guidance about timeframe or structure or party or 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 January, I think, working in a more fulsome integrated partnership model throughout the portfolio is very important to Zymeworks, and that's what we'll be doing from now until the future. 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. 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. No problem. Great, Ken. Just moving on to the ZW49 ESMO. You know, once we've seen this data, will we have clarity around whether the ZW49 is active in patients who've failed Enhertu? I know last quarter, you know, 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 at ESMO is going to be on patients that were, you know, enrolled prior to broader use of Enhertu. I'm just wondering whether, you know, there's a faster market option following HER2 failure and, you know, more broadly, what future development options are you considering for ZW49?
Yeah. Really good question, Nick. Again, you know, unfortunately, you're gonna have to wait till ESMO 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. Obviously, as I think we mentioned earlier, we're, you know, we're seeing more and more on HER2 failures in all of our studies. We didn't exclude HER2 failures in the ZW49 studies. So, you know, 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 till you get to ESMO. I think, you know, our goal at ESMO is, you know, the company's never reported clinical data on ZW49 since the start of its IND a number of years ago.
I think we wanna provide the, you know, 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 with a clinical development plan and what the economic value would be to that sort of clinical development plan. 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, just also maybe one clarification. I think you said the zanidatamab zovodotin that you've submitted an abstract. Just clarifying that you did say that. I'm presuming this is to San Antonio.
Yeah, we didn't specify the conference. You know, 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. I think we're, as I said before, quite excited about this potential combination in this patient population. The study is recruited very nicely and again, accelerated over time, which is always a good sign with a clinical study. We're excited to present our current findings in this study. We've moved as quickly as we can to get that. We did submit an abstract to a medical meeting that occurs in the fourth quarter, let me confirm that.
As soon as we're able to say that we had an abstract accepted, we'll provide those details and look forward to be able to present that before the end of this year.
Okay. Terrific. Thanks, then.
Yeah, thanks.
Please stand by for our next question. All right, our next question comes from the line of Charles Zhu 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 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. It looks like you may have cleared 2.5 mg per kg at the Q3 weekly dose. It 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 kinda wondering, you know, like, 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, specifically those may be concerned with antibody-drug conjugates. Thanks.
Thanks for the question, Charles. Again, I think we're, you know, we won't try and get ahead of the ESMO meeting. I mean, obviously the company has spent some time studying every two-week dosing with ZW49 and, you know, we should be able to present a pretty fulsome picture there of what efficacy we think we see and what the side effect profile is of that agent in picking a recommended phase II dose. Obviously we've gone up in the dose escalation, 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.
We've been working through that process in the dose escalation and dose expansion. We look forward to present everything that we have at ESMO and what the future direction might be. 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. I think as you know, some agents, I think including traz, have more than one dosing regimen which might be applicable. We'll look forward to presenting, you know, everything we've done to date 'cause we've never presented any clinical data on ZW49 since the IND. Present all the phase I data we have.
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. I think you'll get a full sense of those questions and try and address the specific things you mentioned about Cmax and AUC and how that might relate to tolerability and the relationship between the efficacy you could generate and the tolerability that you have to accept to generate that efficacy. I think we're really encouraged by the phase I 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 for ZW49 based on its unique mechanism of action associated with the ADC that we constructed to take forward in the clinic. We look forward to, you know, 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 posed now, on September 12. Unfortunately, you have to wait for those.
Got it. Yep, fully understand. Maybe just one more regarding biliary tract cancer and the readout that you have now coming at the year-end of 2022. I understand we're probably splitting hairs with this question, but I guess what exactly drove the change in guidance from early 2023 to year-end 2022? 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? Thanks.
Yeah, no. I think the update in guidance is just the fact that operationally we're performing, I think, better than we did in prior years. 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. By focusing on fewer priorities, we would try to improve our operational performance and get things done more quickly in a higher quality way or allow us to do things more broadly. 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.
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. 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. 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. I think I hope that you know the focus we've had on doing fewer things and doing them better and that this is an example of it.
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. This will allow us to get things done in a better way, which will ultimately lead to, you know, enhanced competitive ability with both zanidatamab ZW49 and ZW171 and ZW191 and other things that come out of our preclinical portfolio.
Great. Thanks for taking the questions and look forward to your upcoming data sets.
Thanks, Charles.
Please stand by for our next question. Our next question comes from the line of Stephen Willey with Stifel. Your line is open.
Yeah, good afternoon. Thanks for taking the question, and I'll spare you the ZW49 question. Maybe one on the earlier stage pipeline, and I guess I'm not looking to steal any of your R&D Day event thunder. You know, I know that T-cell redirected bispecifics 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. 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 gonna occur through target selection. Is it gonna be playing around with CD3 affinities and variants? Is it gonna be valency? Just curious as to how you're thinking you can improve upon this, specifically in the solid tumor space.
Thanks.
No, thanks for the question. Again, you know, for ZW49, we're very excited to talk to folks about the progress we've made, and I just don't wanna 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. You know, I think in the early stage portfolio, you know, we have a number of programs ongoing. 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 topo payload, we're quite excited about, you know, using our new payload and our different platform in this way.
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. I think the specific targets that we're looking to go 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. I think we can differentiate ourselves by addressing some of the issues and setbacks that I think you've seen previously with this. We've done a really extensive assessment of different bispecific formats. I mean, this is where the company started.
We designed a whole range of bispecifics for 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 ZW171. 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. 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 explain the rationale for how we hope to turn these two agents into successful clinical candidates from an efficacy and tolerability standpoint.
We'll be happy to address all that on October 20th, at our early R&D Day.
All right. Thanks for taking the question.
Mm-hmm.
Our next question comes from the line of Akash Tewari with Jefferies. Your line is open.
Hi, this is Amy Young for Akash. Thanks so much for taking our question. Just wanted to get the company's current stance on the acceptable rates of iTox with the move forward dose. You mentioned iTox is more off-target and related to Cmax. While it seems like efficacy is generally more related to Cmin. 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 dosing regimens that you're evaluating?
Thanks for the question, Amy. Again, I don't think we'll talk about too much detail before ESMO, but I'll just pause and ask if Dr. Neil Josephson wants to say anything about your question or whether we'll just wait until September twelfth and answer it then.
Yeah. I would reiterate what you said Ken, which is that you know, we'll like the data that we have at the ESMO conference. I think that we said that we were evaluating different dosing regimens to try to look at Cmax 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 ESMO conference.
Great. Thanks so much. I guess, I know you guys aren't talking too much about ESMO, but, will we see data from your potential go forward dose? I guess just from a high level standpoint, would it be sufficient enough to compare versus Enhertu, or is it still too early?
You wanna take that one, Neil?
Yeah, sure. You know, again, to what we said, which was I think you'll have to wait until ESMO to actually see the data. You know, in terms of dosing, we will have information about dosing. You know, as we've reiterated multiple times, there may be more than one dose that we would take forward. In terms of your question about too, I think that you know, it have a different molecule than Enhertu. It has a different payload. It has a different mechanism of action. You know, it has a different profile from an adverse event standpoint.
I don't think that we are looking at this as a direct to Enhertu at all. I think that the development paths for this molecule that are unique from what Enhertu can develop. You know, we'll you know, as we you know, lay out information, we'll also try to start to give information about how we're gonna take the molecule forward.
Great. Thank you so much.
Yeah. Amy, just to follow up. For you know for 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 this clinical development program. 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, that's super helpful. Thank you so much.
Mm-hmm.
There appears to be no further questions. I'd like to turn the conference back over to Zymeworks for closing remarks.
That's great. Thank you, operator. Thank you for your attendance today and for all of your questions. We've had a really exciting quarter on all fronts, and we really look forward to the next opportunity to present some additional data. We're looking forward to ESMO on both our poster presentation and webcast. We also have four different investment conference attendance, which allows us to present and have meetings on the same week of, as ESMO. 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 look forward to that. 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 Zymeworks, and I think you'll find them very interesting for the future of the company beyond zanidatamab and ZW49. Please keep an eye out for that October 20th date and save it in your calendar. We'll look forward to seeing you, some of you at ESMO and talking about our presentation, our next investor webcast on September 20th. 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.