Zymeworks Inc. Progress on its 2019 Corporate Priorities Call
May 29, 2019 PM UTC
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ZYME.N - Zymeworks Inc
Zymeworks Inc. Progress on its 2019 Corporate Priorities Call
May 29, 2019 / 12:30PM GMT
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Corporate Participants
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* Ali Tehrani
Zymeworks Inc. - Co-Founder, President, CEO & Director
* Anthony J. Polverino
Zymeworks Inc. - Chief Scientific Officer & Executive VP of Early Development
* David Poon
Zymeworks Inc. - VP of Business Development and Alliance Management
* Diana F. Hausman
Zymeworks Inc. - Chief Medical Officer
* Ryan Dercho
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Conference Call Participants
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* David Novak
Raymond James Ltd., Research Division - MD & Healthcare Research Analyst
* Eunshuk Shim
Canaccord Genuity Limited, Research Division - Associate
* Wangzhi Li
Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology
* Xiaobin Gao
Barclays Bank PLC, Research Division - Research Analyst
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Presentation
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Operator [1]
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Welcome to the Zymeworks Media Report, Webcast and Conference Call. As a reminder, (Operator Instructions) the conference is being recorded. (Operator Instructions)
I would now like to turn the conference over to Zymeworks. Please go ahead.
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Ryan Dercho, [2]
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Thank you. Good morning and welcome, everyone. My name is Ryan Dercho, Senior Director of Corporate Affairs at Zymeworks. Today, we will provide an update on Zymeworks' key business drivers, including clinical trial activity and development plans for our lead assets as well as strategic summary of recently announced partnerships.
The call will be led by Dr. Ali Tehrani, Zymeworks' President and Chief Executive Officer, who will be joined by Dr. Diana Hausman, Zymeworks' Chief Medical Officer; and Dr. David Poon, Zymeworks' Vice President, Business Development and Alliance Management. The speakers will be available for Q&A after the prepared remarks.
Before we begin, I would like to remind you that we will be making forward-looking statements during this call. Forward-looking statements can be identified by words such as will, continue, aim, may, potential of, initiate, lead to, look forward to, expect, believe, plan, anticipate, enable and similar words. Forward-looking statements are based upon our current expectations and various assumptions and are subject to the usual risks and uncertainties associated with companies in our industry and at our stage of development. For a discussion of these risks and uncertainties, we refer you to 10-Q for the quarter ended March 31, 2019, as well as to our other filings with the SEC.
As a reminder, the audio of today's event will be available on Zymeworks' website later today.
I will now turn the call over to Ali.
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [3]
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Thank you, Ryan, and welcome, everyone. The first few months of 2019 have been another productive period for Zymeworks. Today's call ahead of ASCO serves as a midyear report on our 2019 performance and provides context for our priorities hitting into the second half of the year.
In January, we announced our 2019 corporate goals, which included initiating multiple Phase II studies for ZW25, expanding the global clinical development of ZW25 into Asia and Europe, reporting additional ZW25 clinical data for single agent and/or combination studies, reporting clinical data for the ZW49 open-label Phase I trial, establishing additional drug development collaborations with a focus on new platforms and supporting our partners as they continue to nominate new Azymetric-based bispecific antibody candidates for clinical development.
During the first half of the year, we made meaningful headway on each of these objectives. On this call, we will highlight our progress to date and provide an overview of how we expect the second half of the year to unfold.
Diana will start with a discussion of our lead clinical assets ZW25 and ZW49. Following Diana's remarks, David will discuss our business development initiatives and I will provide summary comments before opening up the call for Q&A.
Now I would like to turn the call over to Diana to discuss our clinical strategy.
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Diana F. Hausman, Zymeworks Inc. - Chief Medical Officer [4]
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Thanks, Ali. At Zymeworks, we've always taken a science-based approach to our clinical development strategy. We strongly believe that to address the spectrum of medical need in patients with HER2-expressing cancers, 2 complementary mechanisms of action are required. One for when HER2 is the driver of the cancer biology and the other for when HER2 is primarily an address that can be used to differentiate cancer cells from normal cells.
With that in mind, while ZW25 and ZW49 both leverage the HER2 receptor to impart their therapeutic effect, they do so in fundamentally different ways. The unique biparatopic binding of ZW25 to HER2 results in multiple mechanisms of action that shutdown HER2-mediated signaling. This makes it particularly well suited for patients whose tumor growth is primarily driven by HER2 as is more often seen in earlier stages of disease and lines of treatment.
We've seen encouraging safety and antitumor activity with single-agent ZW25 as well as in combination with chemotherapy in heavily pretreated patients. This observed tolerability coupled with the potential for increased efficacy make ZW25 well suited for use in earlier lines of treatment, including in combination with standard of care therapy such as those used in neoadjuvant and adjuvant settings.
In contrast, ZW49 uses the HER2 receptor as an address to bind to and deliver its payload, which is designed to kill the cancer cell irrespective of whether the growth of that HER2-expressing cell is driven by HER2 signaling.
In addition, the enhanced payload delivery of ZW49 due to its bispecific backbone and unique biparatopic binding has demonstrated preclinical efficacies in models with low to high levels of HER2 expression, including models that are resistant to treatment with trastuzumab or T-DM1.
For these reasons, ZW49 may initially be better suited for later lines of therapy for HER2 high expressing patients where resistance to other HER2-targeted agents has developed as well as in patients whose tumors have lower expression of the HER2 receptor.
We continue to be excited about the potential for both ZW25 and ZW49 and have made significant progress in their clinical development since our last update, some of which I'd like to share with you today.
Focusing first on ZW25, we continue to enroll patients into our multi-cohort Phase I study. We've expanded our experience with over 100 patients treated to date in the United States, Canada and South Korea with ZW25 either as a single agent or in combination with chemotherapy. This broad and robust dataset includes patients with breast or gastroesophageal cancers that have progressed after prior HER2-targeted treatment as well as patients with other HER2-overexpressing cancers, including colorectal cancer, ovarian and endometrial cancers and cancers of the biliary tract like gallbladder cancer and cholangiocarcinoma. Again, these are all patients whose cancers have progressed after standard of care therapies nor otherwise without approved treatment options.
As our data has expanded and matured, we continue to be very encouraged by the consistent safety, tolerability and antitumor activity we see with ZW25 and plan on presenting an update to the data we presented last year at the EORTC-NCI-AACR Symposium with larger patient numbers and longer follow-ups at an upcoming medical meeting this fall.
We've also been evaluating ZW25 in combination with paclitaxel or capecitabine in patients with advanced breast and gastroesophageal cancers with low to high levels of HER2 expression. Again, we are quite encouraged by the data that we've seen to date and believe that the additional -- that the addition of chemotherapy to ZW25 adds meaningful value, further expanding its therapeutic potential.
Based on this growing experience, we continue to have confidence in the potential of ZW25 to address unmet need across a wide range of HER2-overexpressing cancers, including breast cancer, gastroesophageal and other gastrointestinal malignancies such as biliary tract and colorectal cancer and other cancer types as well.
Our initial development strategy focuses on opportunities designed to get ZW25 to patients as soon as possible. This includes orphan or niche indications where HER2 therapies are not currently approved, where patients have progressive disease after receiving standard of care treatment and where there is a potential for accelerated regulatory approval based on response rate and duration of response. These patients often have no approved treatment options available to them and are also unable to tolerate additional chemotherapy or other potentially toxic treatments.
Examples of such potential indications include biliary tract cancer, where HER2 can be overexpressed in approximately 12% of tumors. Treatment options are limited for patients with unresectable or metastatic biliary tract cancer with no approved targeted agents and median survival is less than 6 months for patients who've progressed after first line of chemotherapy.
Other potential indications include colorectal cancer, where HER2 is overexpressed in up to 5% of tumors as well as gynecological malignancies, including subsets of endometrial cancer, where HER2 can be expressed in up to 33% of tumors. We believe that the single-agent antitumor activity we've observed to date as well as the overall safety profile will allow ZW25 to address the unmet need faced by many of these patients who've progressed after standard of care treatment. We are continuing to expand our experience in such settings and have been engaging with the FDA to discuss possible next steps.
We are also focusing on indications where HER2-targeted therapies are currently available, but where there remains a large unmet need including in HER2-positive gastric and gastroesophageal junction cancer. As we presented at the EORTC meeting in Dublin last November, we've seen responses in over 40% of patients with HER2-expressing gastroesophageal cancers that have progressed after multiple lines of prior therapy, including trastuzumab.
Based on these results from heavily pretreated patients as well as the experience we've been accruing in chemotherapy combinations in our ongoing Phase I study, we recently opened a Phase IIa study evaluating ZW25 in combination with standard of care chemotherapy regimen as first-line treatment for HER2-overexpressing gastroesophageal cancer. This study is currently open at sites in North America, and we plan to have sites open and recruiting in South Korea this fall. The primary purpose of this study is to confirm the safety and antitumor activity of ZW25 with first-line gastric cancer chemotherapy regimen. Based on initial safety and response data from this study, we are planning to start a registrational study in 2020 in coordination with our partner BeiGene pending input from regulatory authorities.
In lieu of precedent set by other HER2 agents for greater activity in earlier lines of treatment as well as in combination with cytotoxic agents, we are excited to be moving this program forward as we believe ZW25 will provide greater and meaningful improvements in clinical outcomes from patients as measured by response rate, progression-free survival and overall survival compared to the currently approved first-line treatment regimen of trastuzumab and chemotherapy.
We are also continuing to evaluate ZW25 and HER2-positive breast cancer, where we are focusing on moving into earlier lines of treatment as well as on enabling chemotherapy in cytotoxin-free approaches.
We are planning to evaluate ZW25 with and without chemotherapy in a neoadjuvant setting. We believe ZW25 may have an even greater impact on tumor biology in this earlier line of treatment because unlike late-line metastatic breast cancer, these tumors have not been previously exposed to HER2-targeted therapy.
We anticipate that the single-agent neoadjuvant study will begin later this year. The goal for this study is to demonstrate good tolerability and improvement in the pathologic complete response rate compared to historical data, supporting further development in combination with chemotherapy.
Success in the neoadjuvant setting would support further development in early lines of treatment for HER2-positive breast cancer, including in the adjuvant setting as well as first-line treatment for metastatic disease.
In addition to the approaches we've outlined above, we're also looking at other areas in breast cancer where ZW25 can help address unmet need. One area that has been highlighted is the need to develop highly effective chemotherapy-free treatment. As part of these efforts, we're excited to announce that we plan to move forward with the new Phase II clinical trial in breast cancer, evaluating ZW25 in combination with a CDK4/6 inhibitor in hormonal therapy as a strategy to improve outcomes for patients with metastatic HER2-expressing, HR-positive breast cancer.
As a bit of background, CDK4/6 works as a critical driver of cell proliferation and plays an important role in the growth and progression of hormone receptor-positive breast cancer, which make up the majority of all breast cancers. CDK4/6 inhibitors such as palbociclib, abemaciclib and ribociclib have been approved as single agents and in combination with hormonal therapy, where they provide significant clinical benefit for patients with HER2-negative, ER-positive tumors.
The CDK4 pathway has also been shown to mediate resistance to HER2-targeting therapies and treating resistant tumor cells with CDK4/6 inhibitors can resensitize them to anti-HER2 agents.
Furthermore, signaling through the HER2 pathway has been proposed as a potential resistance mechanism to hormonal therapy even in patients whose tumors do not overexpress HER2. Based on this, we're excited to move forward with this study, which will initially evaluate patients with HER2-positive, HR-positive breast cancer that has progressed after trastuzumab, pertuzumab and T-DM1. Based upon the initial results, there is the potential to evaluate ZW25 and CDK4/6 inhibition in earlier lines of therapy as well as in patients without HER2 gene amplification.
In addition to all that I just described as part of our efforts to address the totality of HER2 biology, we'll continue to look at other opportunities for development, including investigator-sponsored trials where we can evaluate potential biomarkers to identify patients who may obtain the greatest benefit from ZW25 as well as other potential indications where ZW25 may be of value.
Overall, as we have treated more patients with different types of cancers for longer periods of time, our conclusions and plans for ZW25 remain consistent. ZW25 is an active agent that is well tolerated and has the potential to address unmet need in a range of clinical settings.
Turning to ZW49. We are currently conducting our first-in-human Phase I dose escalation and cohort expansion study, and we're pleased with the progress and results so far. Multiple sites across North America are now open and recruiting, including the recent additions of Memorial Sloan Kettering Cancer Center and Sarah Cannon Research Institute to complement our first site NEXT Oncology in San Antonio with more sites to come in the near future. I'm happy to report that enrollment is going well and there is great interest at our sites.
With respect to study design, based on the IND-enabling data we shared with the FDA, we were able to start our dose escalation at 1 milligram per kilogram. And as such, we believe we should be at the biologically optimum dose in our first 1 to 4 cohorts, allowing us to open up multiple expansion cohorts in early 2020.
While we may see antitumor activity at lower doses, we plan to continue dose escalation to identify the maximum tolerated dose of ZW49 as this information may prove useful for the development of future Zymelink ADCs. To date, the study is going well, and we hope to provide updated safety and initial antitumor activity at a major medical meeting this fall.
So as you can see, a tremendous amount of exciting work is underway or beginning, keeping our hands very full. As I mentioned previously, in order to take full advantage of the differences between ZW25 and ZW49, we are prioritizing studies based on the best pairing of patient need and mechanism of action.
In the case of ZW25, we have our multi-cohort Phase I study ongoing to collect additional data across a range of tumor types. We also have an ongoing Phase IIa study in first-line gastric cancer patients, and pending data and input from the FDA and other regulatory agencies. A potential registration-enabling trial is slated to begin in 2020.
For breast cancer, we're looking forward to gaining experience in the neoadjuvant setting as well as the new combination trial with CDK4/6 inhibitor. As more data is generated, we will refine our tumor target, line of therapy and approach, single agent versus combination therapy.
All of us know people whose lives have been affected by cancer. As a physician and oncologist, my whole career has been focused on helping patients. Along with the entire team at Zymeworks, we're dedicated to getting powerful new medicines to patients as quickly as possible, giving them and their physicians new options for safe and highly effective treatment.
With that, I'd like to turn the call over to David to give a business development update.
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David Poon, Zymeworks Inc. - VP of Business Development and Alliance Management [5]
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Thanks, Diana, and good morning, everyone. Our business development strategy was designed with 3 critical elements. First, provide validation of our platform technologies. Second, provide nondilutive funding to offset our cash consumption as we further develop our technologies and advance our pipeline. And third, provide an additional future revenue stream.
With 9 partners, across 3 technology platforms, we have executed very well on our strategy. Today, I will speak to the 3 elements supporting our strategies, including development of new partnerships, expansion of existing partnerships and facilitating our partners' progress.
So far in 2019, we have announced the addition of Iconic Therapeutics as a new partner, the expanded partnership with GSK and the achievement of multiple development milestones by our partners.
Starting with Iconic Therapeutics. They joined a roster of existing partners including Merck, Lilly, GSK, Celgene, Daiichi Sankyo, J&J, LEO Pharma and BeiGene. In total, our list of collaborators include a diverse mix of companies at different stages of development, underscoring our multipronged approach to creating value for patients, for our partners and for our investors.
This new partnership with Iconic is the first licensing deal we have put into place for our Zymelink antibody-drug conjugate or ADC platform technology. This deal validates the potential of Zymelink to expand the therapeutic window for ADCs and build on a strong preclinical data demonstrated with ZW49.
Iconic gained access to Zymelink and its user technology in combination with their tissue factor antibody to create a novel tissue factor-targeted ADC called ICON-2. ICON-2 is currently in late-stage preclinical development and is expected to enter clinical trials next year.
Under the terms of our agreement with Iconic, in addition to development and commercial milestones and with single-digit royalties and product sales, Zymeworks will maintain co-promotion rights if the ADC drug candidate is commercialized by Iconic. Alternatively, if Iconic self-license rights to this agent, Zymeworks will receive a share of any revenue generated. Both companies believe that Iconic's unique antibody combined with Zymeworks' novel ADC platform will enable a wide therapeutic window maybe superior to other agents in development.
As you may recall shortly after the Iconic-Zymeworks partnership was established, Exelixis announced that it entered into an exclusive option and license agreement with Iconic for the ICON-2 program. As I just described, if Exelixis executes its option, Zymeworks will receive a percentage of all revenue received by Iconic as well as tiered mid-single-digit royalties on any product sales.
Importantly, the data generated by the ICON-2 Zymelink Tissue Factor ADC has now been examined during 2 separate diligent processes, first by Iconic and subsequently by Exelixis. In addition, we believe that the ICON-2 program is in good hands at Exelixis with its clinical development capabilities and robust commercial oncology infrastructure.
In addition to the licensing of a new ADC platform, we also recently expanded our relationship with GSK, further establishing ourselves as the partner of choice in the development of bispecifics. Many large pharma companies are currently investigating bispecific antibodies as an essential part of the drug discovery and development platforms. In addition to the general interest in engaging the synergistic targets and biological pathways, these companies are looking for distinctive attributes, including developability and adaptability that differentiates new bispecific technologies for different applications.
One such element that resonated with GSK is ease with which our Azymetric platform allows existing antibodies to be quickly reengineered into a bispecific format by robustly and specifically directing the correct pairing of different anybody light chains to their heavy chain partners. This key piece of technology not previously licensed by GSK was what drove the expansion.
It is also worth noting that this expanded agreement allows GSK to apply the Azymetric platform to treat infectious diseases, which broadens the utility of our platform beyond oncology in autoimmune and inflammatory disorders. We believe this agreement serves as validation both for our technology and its potential breadth of applications.
As a result of this new deal, our third with GSK, Zymeworks will now be eligible for increased milestone payments up to potential value of USD 1.1 billion and royalties.
Our other partners are also making progress in the development of their Azymetric-based bispecific programs. As a recap, recall that earlier this year, we announced that Eli Lilly announced their second bispecific program into the clinic, triggering a USD 8 million milestone payment.
In addition, Daiichi Sankyo achieved a research milestone in our 2016 partnership by selecting an immune-engager candidate for late-stage preclinical development, with Zymeworks receiving a USD 3.5 million milestone payment.
Today, we're happy to announce that one of our long-standing partners, Merck, achieved also a late-stage preclinical milestone for their Azymetric bispecific therapeutic candidate. As a result, Zymeworks will receive a milestone payment of USD 2 million. This novel bispecific was developed by Merck in collaboration with Zymeworks using our proprietary Azymetric and EFECT therapeutic platforms. This program has now completed late-stage preclinical studies and is one step closer to clinical development.
Overall, we continue to be impressed with the progress of our existing partners and the fact that they're making use of our therapeutic platform in building differentiated therapeutics. We're looking forward to providing more updates later this year on these as well as potentially new partnerships.
With that, I'd like to turn the call back over to Ali.
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [6]
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Thanks, David. I want to conclude our update by summarizing what we heard and the key takeaways. We are well on our way to deliver on our communicated 2019 priorities, including several clinical inflection points as highlighted in our development time line on Slide 20 and likely on your screen. We've initiated dialogue with the FDA and plan to benefit from their input advise as we proceed with our plans. To this effect, we have been working with the FDA to leverage programs such as the Fast Track designation to potentially further accelerate development.
With the Fast Track designation, we would be eligible for frequent communications with the FDA, accelerate approval and priority review and rolling submission of the marketing application. This designation would support our objective of getting important new therapies to patients as quickly as possible.
We have a much more mature clinical dataset with ZW25 as single agent and in combination with different chemotherapies that support our long-standing conclusion that we have an active agent that is well tolerated across several different HER2-expressing tumor types. The totality of ZW25 clinical data gave us the conviction to start the Phase II trial of ZW25 plus chemotherapy in first-line gastric cancer and to plan to start the subsequent registrational study versus standard of care in 2020.
We're also on track to initiate the second registrational study for ZW25 as monotherapy in an orphan or niche indication, where targeted HER2 therapies are not currently approved and there's potential for accelerated regulatory approval. Interest in ZW25 from clinicians and investigators will likely lead to new studies, which could further shed light on the potential of this asset for meeting unmet need in different areas.
ZW49 dose escalation study is underway with multiple patients enrolled. Our aim is to start a broad dose expansion study in 2020. And clinical data from ZW49 study will likely pave the path to the development of other Zymelink-based ADCs by Zymeworks and its partners.
In addition, this has been a very productive time for us as business development remains an important component of our overall business strategy. We will continue to strengthen existing collaborations and foster new ones that showcase other Zymeworks platforms for the development of multifunctional protein therapeutics.
Taken together with the clinical plans that Diana described, the first half of this year has been extremely productive, setting up an important and data-rich second half of 2019. To support the demands of advancing our pipeline, we recently added 3 new executives, adding senior level capabilities in manufacturing operations, regulatory affairs as well as expanded clinical research competencies.
At Zymeworks, we're committed to developing protein-based medicines that can make a real impact for patients. Our vision is to create best-in-class medicines by applying our insights and technologies to address the biological processes that drive diseases. Already, we have begun to see the promise of our platform in the clinic. We look forward to showing its full potential in the future.
Operator, we're now happy to take some questions.
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Questions and Answers
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Operator [1]
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(Operator Instructions) Our first question comes from David Novak with Raymond James.
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David Novak, Raymond James Ltd., Research Division - MD & Healthcare Research Analyst [2]
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Just 2 quick questions from me to start. On the CDK4/6 inhibitor combination, will you guys be looking to choose 1 specific 4/6 inhibitor or will you be experimenting with all 3?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [3]
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David, thank you. this is Ali Tehrani. Currently, we have one in mind. And at a later point as the study gets underway, we will provide information on that. We have considered all 3 and believe that there could be opportunity to use all 3, but we do have a lead one in mind that at a later point as the study starts to get underway, we will certainly make available especially through clinicaltrials.gov.
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David Novak, Raymond James Ltd., Research Division - MD & Healthcare Research Analyst [4]
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Okay. Great. And just continuing on that line of thought, how are you guys thinking about patient selection in this trial? Will you be looking to selectively enrich for luminal ER-positive patients, for example or weeding out patients with mutations in ESR1? Some context around how you're thinking about patient selection would be great.
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [5]
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Sure. Diana, I would like you to take this one.
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Diana F. Hausman, Zymeworks Inc. - Chief Medical Officer [6]
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Sure. Thanks. So initially, we will be taking a little bit broader all-comer approach for patients who are HER2-positive and ER-positive. Our initial -- the initial part of the study will likely be just to confirm the tolerability of the combination and then we will probably start to narrow down and do some more exploratory work looking at specific biomarkers for patient selection.
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Operator [7]
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Our next question is from Wangzhi Li with Ladenburg.
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Wangzhi Li, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology [8]
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Maybe if you -- starting with ZW49. You mentioned that the starting dose at 1 milligram per kilogram. Maybe to better understand that, based on your preclinic studies, what is the dose you expect to be or what is the minimum dose you expect to be biologically active or clinically active in human?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [9]
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Tony, would you mind taking this one?
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Anthony J. Polverino, Zymeworks Inc. - Chief Scientific Officer & Executive VP of Early Development [10]
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Not at all. Thank you very much for the question. So as indicated, the starting dose is 1 milligram per kilogram and that was based on some pretty extensive preclinical work we did to establish efficacy and safety of our molecules. And based on the totality of all of the data, we are actually very confident that we will be able to see biological activity within the first few dose cohorts. And just as a reminder, we are not anticipating an extensive number of dose escalations in our Phase I trial.
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Wangzhi Li, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology [11]
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Within the first few doses, okay. So maybe how many doses are going to be tasked in the dose escalation phase?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [12]
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We have not...
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Anthony J. Polverino, Zymeworks Inc. - Chief Scientific Officer & Executive VP of Early Development [13]
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Go ahead.
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [14]
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So here as Tony stated and it was in our script, at this point we're planning somewhere between 1 to 4 cohorts. And again, as in our prepared remarks, we do not necessarily see that those -- all of the cohorts being necessary to get the biologically relevant doses and activity. Nevertheless, our objective is to also get a better understanding -- clinical understanding of the Zymelink platform because we do want to develop other ADCs. So again, at this point, we're planning between 1 to 4 cohorts and do expect to see activity relatively quickly.
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Wangzhi Li, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology [15]
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Okay. Great. In terms of the safety, if I remember correctly, the monkey study, you showed I think the (inaudible) at or see even the lab-weighted trial per milligram per kilogram. So If we convert that to human dose, what kind of, I guess, the safety level or minimal safety level you expect to be?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [16]
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Tony?
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Anthony J. Polverino, Zymeworks Inc. - Chief Scientific Officer & Executive VP of Early Development [17]
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Absolutely. Thank you. So just a slight correction in our monkey studies. We have gone up to 18 milligrams per kilogram and we've established that at that dose that is our HNSTD. So we can go up to at least that dose and potentially even higher pending additional studies that we would confirm. If you did that in that conversion to the clinical scenario, as Ali and I have indicated previously, that would enable us to reach that activity within those first -- biologically active activity within those first few cohorts. And of course, having not established an MTD in those safety studies, we would need to establish that in the clinical setting.
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Wangzhi Li, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology [18]
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Okay. Got it. That's helpful. Maybe 2 more quicker clarification questions. One is for the ZW25 plus chemo combo in the Phase I. Are you also going to report data this fall along with ZW25 monotherapy data at a conference?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [19]
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Yes. We will provide data for both monotherapy and potentially chemo combo in several major fall conferences.
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Wangzhi Li, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology [20]
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Okay. Great. And lastly on the new trial, the ZW25 plus CDK4/6 inhibitor, just follow the prior question in the patient, looks like you brought you said all-comers initially. But I just wanted to clarify is -- like the patient when first diagnosed or first treated with CDK4/6 inhibitor -- sorry, they already -- like from the beginning they're already HER2-positive and ER-positive? Or you are targeting more for patient initially HER2-positive, but ER-negative and then develop ER-positive. Is this the mechanism or just maybe more clarity on that?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [21]
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Sure. Diana?
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Diana F. Hausman, Zymeworks Inc. - Chief Medical Officer [22]
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Sure. So the patient population will be patients who are HER2-positive, ER-positive at the time of screening. So whether they've acquired ER positivity, I can't say. We'll collect that data. But for the majority of patients, they don't acquire ER positivity or remove it. Some do but I expect that the majority of patients will have consistently been HER2-positive, ER-positive.
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Operator [23]
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(Operator Instructions) Our next question comes from Gena Wang with Barclays.
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Xiaobin Gao, Barclays Bank PLC, Research Division - Research Analyst [24]
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This is actually Xiaobin Gao on for Gena. Maybe 1 for ZW25. You mentioned that the initiation of Phase II for gastric cancer in combination with chemo was supported by both monotherapy and chemotherapy in your Phase I trial. Can you give more color about how much more like response or duration for response you saw for ZW25 in combination with chemo in your Phase I experience?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [25]
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Yes. Thank you for that. So again, as we mentioned in our prepared remarks, we were very satisfied with the totality of the data that we had on hand to be able to initiate this Phase II study, which of course will be a larger sample size of patients and will give us more clarity on how to proceed into the next step, which is the registrational study. So all of these studies are linked. All of these studies give us further insight and pave the path. At this point in time, we are not presenting specific information and that specific information, the data will come out at a major clinical conference later this year.
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Xiaobin Gao, Barclays Bank PLC, Research Division - Research Analyst [26]
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Got it. Maybe another quick follow-up on the ZW25 in combo with CDK4/6. Can you maybe help us understand if -- like previously, the HER2 therapy had been tried in combination with CDK4/6? And what was the outcome?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [27]
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Yes. Diana?
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Diana F. Hausman, Zymeworks Inc. - Chief Medical Officer [28]
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Sure. So there is the preclinical data. I believe there is actually a neoadjuvant study that showed an improvement in pathologic complete response rate. I believe it's from an Italian group like with the GUONE. There's also -- I think it's the PATRICIA study that's looked at trastuzumab and I believe palbociclib. That's not a randomized study but did see encouraging antitumor activity. We have some preclinical data in vitro looking at combinations of ZW25 and CDK4/6 inhibitors as well as hormonal therapy . So taking all of that data together, we're very excited to see what ZW25 can do in combination with CDK4/6 inhibition.
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Operator [29]
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Our next question is from Arlinda Lee with Canaccord Genuity.
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Eunshuk Shim, Canaccord Genuity Limited, Research Division - Associate [30]
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This is Ben Shim on for Arlinda. Many of my questions have been answered. I guess I just have a few general ones. There is a lot of value tied up in your partnerships and that's getting real hard to keep track of them. Can you tell us like from a management perspective, what are the indications of partnership activity? How frequent do you get an update from your partners as to how active each of these collaborations are? That's my first one.
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [31]
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Thank you. David?
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David Poon, Zymeworks Inc. - VP of Business Development and Alliance Management [32]
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Thank you for the question. And I think you probably appreciate with pharma partners, the level of updates with them, it really varies by collaboration and by partnerships. For some of our more active ongoing ones where, for example, with LEO Pharma, where we are actually doing some of the antibody research. Obviously, we're very plugged into those programs. And for other ones, for example, like with Lilly, where they're in the clinic, you would -- we would expect that those updates won't be as regular as you would for an actual active research program.
So it really spans the gamut. But for all the collaborations, we have very structured and timely touch points throughout the year, usually on a quarterly basis. And we do get updates. We do get -- we provide comments and thoughts on some of their work as well. So we are quite aware of what they're all up to and where all of the progress are happening. And with some of our prepared remarks earlier, we anticipate and hopeful that some time in the fall and winter as well, we will provide more updates at some of their progress from some of our other partners.
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Eunshuk Shim, Canaccord Genuity Limited, Research Division - Associate [33]
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Okay. Looking forward to it. I guess my last question is, it looks like Zymelink is going to be an asset that's going to get utilized quite a bit more. Is it fair to say that you're going to see some more deals in that platform in the near future?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [34]
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Yes. It is absolutely fair to say that, that is the case.
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Operator [35]
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Our next question is from David Novak with Raymond James.
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David Novak, Raymond James Ltd., Research Division - MD & Healthcare Research Analyst [36]
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I just wanted to get a bit more clarity around the Phase II chemo combo gastric/GEJ trial and how we should think about this trial once you ramp-up the pivotal trial in 2020? Will the Phase IIa remain open, so that we continue to gain further insight into PFS while you begin dosing in the pivotal?
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [37]
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Thank you, David. That's a very well way of putting it. Yes, the Phase II will remain open and we will continue to generate data. And as appropriate, we can share that with the community, but you captured that really well. It is as you put it.
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Operator [38]
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There appear to be no further questions. I'd like to turn the conference back over to Zymeworks for any closing remarks.
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Ali Tehrani, Zymeworks Inc. - Co-Founder, President, CEO & Director [39]
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Thank you to everyone that joined us early this morning, and we look forward to providing you with additional updates as the year progresses. We're very excited here at Zymeworks and it is time to get back to work. Thank you very much. Have a good day.
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Operator [40]
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This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.
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