Good morning, everyone. Thank you so much for joining us for another session at the 41st J.P. Morgan Healthcare Conference. I'm Brian Cheng, I'm one of the senior biotech analysts here at the firm. Presenting next is Zymeworks. I'll turn over the stage to Zymeworks in a second, but the presentation will be followed by a Q&A session. The stage is yours.
Thank you very much. Good morning, everyone. Welcome to late Thursday morning on JP Morgan conference. Sincerely appreciate the opportunity to present to you here. I know all of you have sat through a whole host of presentations this week just to get to this one. Appreciate your patience in getting to this one. I'm gonna try and keep this light and flowing for you to the end and then leave a lot of time for questions, given the fact we've got a good informal situation here to answer questions. With that, I'll proceed. This is our legal disclaimer. Again, please refer you to our website and filings with SEC 'cause we will make forward-looking statements. I encourage you all to read these statements. Here's where we are a little bit.
I wanna tell you a little bit about where we're going forward as a company. This is what we do. At Zymeworks, I've been here for a year now. This is the focus of the company going forward. We're intentionally focusing on the most difficult to treat cancers where we have not seen meaningful improvement in long-term overall survival rates. I think that's the place for complex biologics like we design. We do it in two different ways. We not only design next generation antibody or conjugates to try and solve some of those complex problems, we also have in our history and still continue to design multispecific antibody therapeutics, which up till now have been bispecific antibodies, but we'll go in our next stage to trispecific. Out of those two platforms, we generate a whole host of products.
We're seriously targeted on first and second-line therapies where we can make a significant improvement in overall survival rates, something very meaningful, which is, I think, where we need to go with these biologics which we're able to engineer. We seek to use accelerated approval pathways wherever possible around the world, when we find something that makes a meaningful difference, we can get it to patients as broadly as we can, as quickly as we can. Not only do we practice what we think is world-leading science, but we do it with financial parameters in mind, that when we are successful with an R&D product, we're also successful financially for our business and also our shareholders, an important component of being a biotechnology company. This is our corporate value framework.
Worked really hard over the last year, as CEO of the company to accomplish a long list of things that were necessary to put us in the position to take advantage of the opportunities that are in front of us. First and foremost was to transform our financial position, which we did with a number of initiatives last year, but capped off with the collaboration we announced with Jazz Pharmaceuticals, which I'll talk about. I think in the current environment of current financial markets, it's really important to protect the R&D opportunities that you have to be able to fund great opportunities, and we've done that.
We have a cash runway through 2026, which allows us to take advantage of all the opportunities coming out of our R&D platforms and make sure we can develop those new therapies for patients who are desperately in need of something new and novel to make a meaningful difference in their lives. Last year, we also had the chance to deliver the first top-line data from our first pivotal study of our lead programs, zanidatamab, which I'll talk about. That data for us when we saw it and unblinded it was just astounding and unprecedented. I think we're very much looking forward to discussing that with regulatory agencies and discussing the path forward for patients who are in need of a HER2-targeted therapy for which there's no approved therapy now around the world.
We were extremely excited when we were able to turn over that data card. We also unveiled our earlier- safe platform opportunities in an extensive R&D day in October last year in New York. Talked a little bit about that. We were able to advance our second clinical stage asset, which is our ADC product format of our zanidatamab antibody, which I'll talk about. We also did a number of things which I thought were necessary to put us in a position to take advantage of the opportunities we have in front of us, re-domicile, move to Nasdaq. Also reset the organization around a very focused approach to how we're gonna build products and build a business in the future. Feel very happy about our progress last year.
We're very focused on execution of this plan this year and trying to do the same thing we did in 2022, which is set out a clear list of objectives, which I did last week. Ensure that we can meet or exceed expectations on every single one of those things that we outlined. That's the type of performance we need to have in this company. The way we look at our business now going forward is there's 5 very unique and different elements of enterprise value as we see it in the company. Our objective with 2023 is to progress every single one of those elements forward so that they're more valuable and more advanced by the end of 2023 compared to the beginning. That sets the stage.
I did set out these objectives last week, for both 2023 and 2024, just to give you a good forward-looking statement that's more than 1 year. We're very focused on in every single one of these priorities 'cause they're all important to build the type of business that we'd like to build.
I truly believe after 2022 and having been here for a year, there's something really special about this company's products, our experience and what we've done so far in applying that to develop a whole range of products in a portfolio from both our ADC platform and our multispecific platform, especially around trispecifics, to really generate a fantastic oncology portfolio that I think if we focus it on the most difficult to treat cancers, first- and second-line approaches and meaningful differences can really build a portfolio that we'll be proud of in this company and ensure that we're financially successful for the business and our shareholders. Beyond that, we're mission-driven, as I talked about. The key for us is to have focus. We have a very innovative approach to how we use our ADC and multispecific platform together in an integrated fashion.
I'll talk a little bit about that as we go along. I believe we have the opportunity to truly improve patient outcomes for these difficult to treat cancers, as I talked about. For us, that's the focus of where we should spend our time. It is the most difficult. It is scientifically the most challenging, but I think it's the most rewarding for us if we're able to solve problems that have not been able to be solved before. I think some of the structure and things that we're creating inside will be able to do it. Right now, I have all the capital, talent, and opportunities I need to be successful. That's a very unique and special position to be in, and we're gonna ensure that we do not squander that opportunity.
Hopefully, in 2023, you'll see that we're making the most of that opportunity for patients and for ourselves and for our shareholders as we move forward. We have a number of technology platforms, four are shown here. These are novel and unique platforms that we've developed over our time in the company. We've applied these specifically for our partners products through our history. Most of it is based upon the original Azymetric platform, which is kind of a validated, unique multispecific antibody platform that allows us to create both bi- and tri-specific antibodies with IgG1-like biophysical properties. We did most of this early in our life as a company for other people's products, and we still have a range of those in development.
Our intention and focus going forward is to apply this for our own portfolio more so than for other partners. This is the same platform that's been key to the generation of our two lead programs, both zanidatamab, which is our biparatopic bispecific HER2 antibody, and zanidatamab zovodotin, which is our ADC product format of the same antibody. As mentioned earlier, our other area of focus is on the ADC platform, where we have worked very hard over the past period of time to select a novel, brand-new, proprietary TOPO1i payload for ourselves, still using our unique linker thoughts and also designing what we hope are best-in-class antibodies to provide those linkers and payloads the ability to do what we would really like them to do.
We also have the ability to utilize immune modulation or tumor-specific co-stimulation in order to better address the targets and indications we're working on. I think what's key here is our approach is slightly different than maybe companies who are focused solely on ADCs or solely on bispecifics or multispecifics. We start with target indication and then apply which of our platforms we think might get us the highest probability of a meaningful difference in outcomes. We have the ability to design multiple structures and approaches around a target or indication of interest as opposed to just apply the platform that exists within the company. I think that will hopefully truly be an advantage in creating extremely novel and valuable products in the future.
While not on the stage, 'cause he's hiding in the front row, our Chief Scientific Officer, Paul Moore, has been very helpful to define the strategy you see here. He was brought on mid last year, hosted our early R&D day, and I think we're already starting to see in our R&D portfolio his contribution. Again, as you'll notice in the slide, we're gonna utilize both of these key focus areas, multispecifics and antibody drug conjugates, hopefully in a very equal way. Our portfolio over the next few years will be balanced between products generated by both of those platforms, and they will be significantly differentiated in clinically validated therapeutics as we're building them.
I think we're gonna try and use these platforms to develop five new INDs in 5 years, of which I hope all 5 of those are very exciting, differentiated, and useful and meaningful therapeutics. We will continue to utilize some additional candidates for partnerships beyond those 5, which we would like to keep unencumbered and full rights to over the next few years. Those additional partnerships which we look to form starting this year will help to fund the development and progression of the programs beyond our own capabilities of the five new ones over 5 years. We have a growing list of potential best-in-class therapeutics, which will grow. Our first product candidate you're seeing here is zanidatamab, which was the...
which was the global licensing agreement that we have with Jazz Pharmaceuticals announced this year to complement our partnership with BeiGene. Also announced the first of two ongoing pivotal studies in top-line data, that was announced in December. We're gonna look to continue to grow the value of the brand, complete the additional clinical study which is ongoing in first-line GEA, seek our first ability to make a regulatory filing with the BTC data in markets where we can. We will continue to look to grow the brand with our partner Jazz in BeiGene beyond the initial pivotal studies in BTC and GEA.
Not mentioned here, I just wanna highlight that zanidatamab was recently selected for inclusion in the I-SPY platform trial with patients with HER2-expressing tumors in the neoadjuvant setting of localized advanced breast cancer. Jazz mentioned this on Monday in their presentation. It's a really exciting development and I think an opportunity where I think zanidatamab has the potential to be beneficial, and we're really excited that Jazz has seen fit to put that forward into that platform, and we're really excited to look at what the results might be from that. I just wanna talk beyond zanidatamab about some of our exciting R&D efforts. Again, we have a unique ability to develop antibody-based therapeutics in two different modalities.
As I said, when we look to generate a candidate, we first look to the areas of highest unmet need, as I said. We look to see how our technology platforms can be utilized around that target indication of interest. We have two different platforms, but we also have different tools in our toolbox that we can apply in specific situations where we think we can generate additional efficacy and a meaningful difference from standard of care. It's all done on a fit for purpose basis. We design specifically using those tools around each target or indication. It's not a plug-and-play situation or platform.
Fortunately, we have the internal capabilities and experience to be able to do that in a meaningful way, both in antibody-drug conjugates and in the multispecific side of our business, which for a small emerging biotech is very unusual and unique, and we wanna take advantage of that for ourselves and also potentially for partners. Next slide. This is just again the circle of how we look at opportunities. Things that are in this circle are the areas of the highest unmet need we saw where we've not made a meaningful difference. When we look to apply our technology, this is the patient population that we're seeking out. It is the most difficult.
These are the problems that have been the longest unsolved from our sector to date, but this is where we believe these unique and complex biologics that we can generate should be applied to try and solve these problems. Those are the areas that you'll see future clinical candidates come from in those indications. First area of focus, just wanna talk a little bit more about our MSAT program. Again, we have multiple avenues and ways to use this, as you can see here. As noted, our lead multi-specific candidate is ZW171, which you'll hear more about as it makes its way towards IND. We believe that moving beyond biparatopic antibodies towards tri-specifics, which target multiple tumor-associated antigens in the same antibody is kinda the next step.
We truly believe the next bispecific will be something that is a tri-specific, and that's where we wanna move to next with our experience and our technology. We're working to develop the next generation of tri-specific candidates to potentially address and maybe get mechanisms that have not been seen before, which might generate efficacy and breakthroughs in those difficult-to-treat cancers, as I mentioned. We have the ability to utilize these platforms to build different types of trivalent antibodies. We can utilize co-stimulation where we think that might be beneficial, or checkpoint inhibition with PD-1 to help address the problems of earlier T-cell engaging antibodies. This is our first one. ZW171 is a 2+ 1 format of a bispecific T-cell engaging antibody. Mesothelin has always been an interesting target.
It's validated, also by folks who weren't successful in being able to work in this target, but it's a high area of unmet need, when you look at all the indications that mesothelin might be an interesting target for. Our antibody utilizes a very unique geometry, that drives high-avidity binding and a unique CD3 receptor that redirects our body's T-cells towards cancer cells and will potentially address previous issues seen with cytokine release syndrome. There are several aspects of what we're designing in the ZW171, which would be unique and differentiated to us.
We've extensively assessed the different formats and geometries for numerous antibodies using our Azymetric platform, and the result is something that we believe will provide the optimal activity level and safety profile to address mesothelin as a target, and we're rapidly approaching an IND in 2024 to then prove that in the clinic. Next slide. As mentioned, we have the ability to utilize our ADC strategy for indications that we think is an appropriate approach. We think it's very unique to us. It does involve right now our novel Topo1 proprietary payload. As we move forward, we do have the ability, as we have before, to look at other novel targets, novel linkers and novel payloads, and we'll continue to build and regenerate the platforms as we move products forward from those platforms.
On the ADC side, our lead preclinical product candidate, ZW191, is a folate receptor alpha targeting ADC that utilizes our novel Topo1 payload. Folate receptor, as you saw this week, is a clinically validated target with the potential to address a range of tumors, both gynecological, lung, triple-negative breast, and other solid tumors. Where we think we're able to differentiate is with a novel antibody, which improves internalization, payload delivery, and tumor penetration. We think the antibody is one of the keys to this ADC, which we're developing now. We think it will potentially address lower levels of folate receptor alpha expression in tumors in order to be able to reach all the patients which might possibly benefit from something that targets folate receptor alpha.
Further, we do wanna utilize our bystander activity with our Topo1 payload and our protease-cleavable linker to derive potent efficacy, and we're very much looking forward to getting this in the clinic in 2024 as well. As I mentioned before, our goal is shown here. We're moving quite rapidly from being more of a platform company to more of a product-specific company. Over the next 5 years, we hope to move five great innovative molecules into clinical studies. Speak about our commercial collaborations, one of which is new. Again, there are rounds out of zanidatamab, which is our lead clinical biparatopic antibody in the HER2 space. In December of this year, hopefully some of you noticed, we did sign a great licensing agreement with Jazz, who's a fantastic partner, for zanidatamab.
I think the financial terms of the arrangement for us were fantastic, but I think they were relative to the value that both Jazz and we see in zanidatamab, and that's what this deal reflects. Not only do we get a substantial upfront payment to transform our financial position, but as of October nineteenth last year, all of the ongoing costs related to development of zanidatamab are being taken care of by Jazz, which obviously provides us additional ability to use our cash runway on the rest of the pipeline and not zanidatamab itself.
We're still continuing to manage all the ongoing clinical studies, Jazz will take responsibility for anything new in developing zanidatamab for here, but we're so excited to have Jazz as a partner, we're working really hard right now with the data which we got in December and working hard on seeing how we can find a path forward to market with that. In 2018, we had our first zanidatamab relationship formed with BeiGene for Asia Pacific territories, not including Japan, but also including Australia and New Zealand. BeiGene has been a fantastic partner for us in co-developing zanidatamab, we're looking forward to utilizing their commercial expertise with Jazz to commercialize zanidatamab as we seek approvals. As I said, we have two pivotal studies ongoing. One we reported top line data in December.
We'll report out the full data set in a peer-reviewed forum in the first half of 2023. Our GEA pivotal study continues to go on, and our expectation is that we will have data from that study available in 2024 on a full approval pathway, not accelerated approval pathway. Next week in San Francisco, if you're sticking around, we will have the ASCO GI Symposium, and we'll have a really encouraging update from our phase II study of zanidatamab plus chemo in a first-line GEA patient population. We look forward to reporting those results with Jazz next week here in San Francisco again. Zanidatamab zovodotin is our HER2 ADC product format of the same antibody. We retain rights to that.
It's not included in the Jazz licensing agreement, so we're looking to push this forward from our phase I data into a number of different cohorts to study this HER2 ADC uniquely in combination with standards of care, not as a monotherapy, where we would generally look to position ADCs. We think there are a number of interesting indications in the HER2 space that we can test as a basket of indications, as well as continuing to explore interest in the HER2 low population, and also looking at a positioning of what happens for patients who fail T-DXd, which is now becoming commonly prescribed for many cancers, but also breast cancer primarily.
We look forward to generating additional clinical data over this year and next year, and our goal will be to use that data to hopefully attract a partner who'd be willing to work with us starting in 2025 to work in a registration pathway outside the U.S. while we retain U.S. rights and move forward in hopefully more than one of these indications towards approval. Seen that one. We also still have a number of license platform license agreements out of our legacy platform concept there where the company started. This does provide capital to us. It provides insight to us as to how others use our platform.
These still all exist in the company, and I think will provide some cash flow for us in 2023 and 2024, and we look forward to these partners advancing these programs in the clinic or from preclinical to clinical studies. To wrap up, we have a very strong position financially. I think it's really important in the current biotech equity markets. At the end of last year, we had $490 million in cash, plus not counting an additional $30 million in reimbursement from Jazz we expect for Q4 R&D costs with zanidatamab. We gave guidance last week that we expect to provide an operating cash burn of around $90 million-$120 million of that cash burn, and it provides with a cash runway out through at least 2026, if not beyond.
I think, as I said, we put ourselves in a position where we are financially strong enough to take advantage of all the opportunities that come out of our R&D engine. And that's might be a unique position in today's environment and where everyone would like to go. I think it's very important to find a way to finance the good opportunities that come out of it and not have to shelve them or delay them. Key expected milestones are shown here for 2023 and 2024. I think we had a very full agenda last year of some great milestones.
I think 2023 is gonna be as fulsome and active in driving every aspect of our business forward and advancing it. We look forward to explaining the first of those key milestones next week with our data at the ASCO GI Symposium here in San Francisco. This is the last investment highlights. As I said, I'm in a very unique position as a CEO of an emerging biotech right now in that I have all the capital I need to drive R&D programs forward and drive value into our business. I've got all the talent inside the company I need right now to be successful in that. It's a very experienced group who are the group which brought zanidatamab and zanidatamab zovodotin into the clinic and towards approval. I feel comfortable with that.
I think more importantly, we have a wealth of opportunities in our platforms right now of targets of interest, indications of interest, and additional partners who'd like to work with us around the core. I feel very comfortable that we'll be able to show some advancement and success in 2023 in a way that hopefully exceeds expectations that exist now for the company. I look forward to reporting that progress to you during the course of the year and happy to answer any questions right now.
Great. We'll switch over to the Q&A session. I'm joined by Paul Moore, their Chief Scientific Officer. We also have mic runners on stage for those of you who are in the live audience. For those of you who are joining on the conference site, please feel free to submit your questions through the question portal. maybe just to kickstart.
Sure.
discussion today, maybe, you've got a strong balance sheet now, from your Jazz deal. You're turning a new page on your R&D portfolio. Maybe just talk about. It'll be great to talk about just how you think about the next step for. What are the, some of the key learnings that you've got from developing zanidatamab to passing on to Jazz, and how do you use that learnings and apply it to the R&D portfolio as you're moving forward to the INDs filings in 2024?
Yeah, great question. I think there's a lot of learnings from the experience that we have as an organization from developing ZANI and ZW49, which we did from concept stage right through to advanced clinical studies and eventually through to hopefully approval with zanidatamab. I think there's things we learn along the way that are unexpected. I think one of the things that we've noticed now, having seen clinical data from a pivotal study with zanidatamab, is there's something unique about the mechanism in that product that we think is related to the biparatopic binding, which is more than predicted. I think when the company started out with that concept, it was, you know, repeating the mechanism you might see in HERCEPTIN and PERJETA in a single antibody.
There's something about the biparatopic binding aspect of that that creates a unique mechanism that's driving what we think are these unexpected and unprecedented results, starting with what we saw in BTC, and I think people will see it again next week when they look at our GEA data. There's something going on that wasn't what we expected we would get, fortunately it's better than we thought. That makes us want to explore that more. What is that mechanism? What's happening? We do have a publication, on this coming out, I think in the next month, to describe the mechanism that we've seen with zanidatamab. Now that we're seeing clinical data, it's not really a thesis. We think that's driving the consistent deep responses we see with zanidatamab in every patient population that we treat.
That consistency and depth turns into durable benefit, which we hope turns into, you know, much more improved overall survival of the patient populations in our studies. We'll get an indication of that next week as the direction of the overall survival we're seeing in our smaller phase II program, which is a, you know, a mimic of what we're doing in our pivotal study right now. We take learnings like that, so that makes us want to understand where that biparatopic binding on an antibody or on an ADC might be beneficial. There's not that much clinical experience of people in our industry on pharma or biotech with understanding these bispecific or biparatopic binding mechanisms on antibodies or ADCs. When we think about zanidatamab zovodotin, which is our HER2 ADC format, it's the same biparatopic binding.
We're interested to see what do we get out of the mechanism that can be translated into a preferential clinical benefit from that. We take those learnings and apply them to how we think about building the next molecules going forward.
Great. Maybe a couple questions on Zani. You reported data, positive data, HERIZON-BTC-01, just a couple weeks ago. Jazz opted in, and you got the second tranche. You report data also in GEA next week at ASCO GI. How do you think about the opportunities beyond BTC and GEA? Any expectations on, you know, how much Zani can do, you know, assuming that it could be approved in the near term? Any expectations on Zani?
Yeah. I think obviously, you know, BTC, our top line data clearly indicates we're providing a meaningful clinical benefit for our patient population, where there's no HER2 approved targeted therapy. That's a really unique and special opportunity for us, and we're looking to see how we can get that available to patients as quickly as possible. The first-line GEA study that's in pivotal studies is, you know, a substantial opportunity for us globally. I think next week we'll get some other indication data about how competitive and meaningful is our regimen with Zani and chemo going to be. That'll be a good question for after next week when you look at that.
I think if you look at the phase I study that we did with zanidatamab years ago, there was a range of single-agent activity responses we saw in a whole host of HER2 expressing and amplified tumors. We brought BeiGene on as a partner, which allowed us to do a little bit more in Asia-Pacific. One of the benefits of having this Jazz partnership is not just to confirm the commercialization arrangements for Zani, with BeiGene, but also to provide the additional capital and resources to fully explore all the areas where zanidatamab has the potential to get a meaningful benefit.
Obviously, those decisions are Jazz's to make, and they're starting to make them, such as including zanidatamab in the I-SPY study, which puts Zani in a neoadjuvant setting, which is, you know, might be really interesting to see how that happens. I, you know, I think there are a number of other opportunities that they could decide to look at for further clinical development for zanidatamab, and I'll wait for them to give guidance on how and when they're going to do that. It's, it's definitely one of the things that's really interesting about zanidatamab, is the ability for it to be broadly applicable across a diverse number of therapeutic indications in oncology in the HER2-targeted space. I fully expect that Jazz will grab all of those opportunities as they move forward.
Great. Maybe switch gear to some of your preclinical assets. ZW191 targeting folate receptor alpha. Maybe Paul can opine on this a little bit. How do you design this molecule? You know, especially the mechanism is already validated, but there are some differentiation that Ken talked about earlier today.
Right.
What are some of the key thinking behind the ZW191 program? What are the key components that you manipulate-?
Sure.
To make it work?
Sure. First of all, it's an antibody-drug conjugate, it's got an antibody and a drug conjugate. We think both about the drug conjugate and the antibody. When we looked at the drug conjugate, the payload, that's our topoisomerase, that's kind of been more validated more recently in the clinic, and we have our own proprietary TOPO1i payload. We've attached that to a folate receptor alpha antibody that we selected and benchmarked the antibody itself for its properties to deliver an ADC. We combined that, and then we've kind of characterized the profile of that, compared it to clinical benchmarks and are very comfortable both with the efficacy profile against a deeper number of folate receptor expressing models.
Also on the safety profile, we're very encouraged by the safety profile that we think can differentiate it from, you know, both on the efficacy and in the safety based on, you know, on the other molecules that are, you know, in the clinic.
As you move into INDs in 2024, what are some of the key gating factors for you to start the studies? Can you talk about the work that the preparation behind the scene for each of the programs, the ZW191 and the ZW171?
Yeah. I mean, it's just, it's just time and day-to-day work of, you know, taking a biologic into the clinic. I don't think there's anything special about that. It's just the time for manufacturing, the time for GLP talks, preparing clinical sites, deciding where we do that. I think the approach we decided to take with ZW171, ZW191's a little bit different in terms of clinical development in the early stages, where we're gonna take a global approach. I think the one thing we learned is you wanna go fast in clinical development, and we need to go fast. You need to be able to access patients early in clinical studies anywhere in the world. I think you'll see us do something that's not as US-centric as maybe we've done previously.
You'll see early clinical sites in phase I on a global basis, so you can access patients where you're trying to, you know, pull out someone with a specific no mutation and a specific characteristic. You'll see us expand, and we talked about this last week in our announcement rapidly into Europe and Asia Pacific to complement the U.S. much earlier in the clinical stage than maybe was done before in our company or has done. I think that's necessary now in the current environment where clinical trial speed is really important. Clinical studies in the U.S. are slowing down dramatically, and I think the time and cost related to that, you need to take a bit of a global approach. That's something different.
We have specific internal targets now about how to go much more quickly from target selection to first regulatory filing. We're working on every aspect of that. Speed is extremely important to our ability to compete, and you'll see us move nimbly and much more quickly than maybe we've done previously in the company.
That's an interesting point. When we look at the ZW191, the ZW171 indication, there's one that overlaps. How do you think about which one to prioritize, you know, in terms of the INDs cadence? You know, when we look into assuming maybe we will have data in 2024, 2025, how should we think about just the cadence of potential data from your early studies?
I think you'll see us define the clinical indication of interest before we get into the clinic. I think that's really important. Sometimes the structure differentiates your molecule, allows you to differentiate your clinical strategy. I think in designing our folate receptor program, our thoughts are, you know, if we're able to find antibody which works well in mid expression or low expression, different range of expression, that will open up not only a broader group of ovarian cancer patients to applicable treatment, but it might also allow us to really seriously consider triple-negative breast cancer, lung cancer, other indications. I think we will try to select those before even getting clinical data. The other thing we'll do is we'll work on a basket of indications all at the same time.
You've seen that with the ZW49 guidance we gave last week. Working on a basket of indications, I think is gonna be necessary to adapt to new rules in the U.S. around the Inflation Reduction Act, which I think is gonna truncate sales eventually earlier than you might have expected in the U.S. It also tells you you need to explore ex-U.S. markets in a much more significant way to make up that delta you're gonna lose as a commercial opportunity later on. Basket of opportunities, global execution from the very first phase I set. The indications of interest might reflect a differentiation from where others have gone forward. You can't assume that just 'cause it's a folate receptor alpha antibody program, that our lead indication is gonna be ovarian cancer.
There may be several indications that might be one, but if we can differentiate the structure, we can differentiate our ability to access patients, which maybe not have been able to be reached with other agents around the same target. That's the same in mesothelin as with folate receptor. It's another level of differentiation beyond the structure.
Maybe just, last question, just wanna touch on your resource allocation in the next couple years. How should we think about your cash burn in, you know, in 2023, 2024? Well, you guided it for this year, but just near term, 'cause you talk about your cash runway. Is that inclusive of the IND start and also, you know, the next steps? Let's say, you know, the data looks positive for ZW191 and ZW171. Is that inclusive as of the positive data that could come out from those studies?
Yes. I think one of the things about the Jazz collaboration that goes along with the BeiGene collaboration is not just our current financial position, but, you know, as zanidatamab moves closer to approval and into market, those agreements that we have with BeiGene and Jazz provide additional financial foundation for us to continue to build and develop our portfolio. We can think about developing a portfolio of 5 INDs over the next 5 years, because we know that not only with current cash, but expected cash to come in, that we can continue to support those as they grow and develop in clinical studies. Never start something that you don't have the capability to know that you can get and keep going. We think we have that ability.
The majority of our spend in 2023 and 2024 is in Paul's budget. He's the one. There is some money around ZW49 in the clinic, but most of it's based around the two lead programs, but also moving other products in those platforms closer to IND, picking the next candidates. We're trying to accelerate all the products that might come out of the platform as far as we can. Again, starting things now because we have a solid foundation now, but we should, as zanidatamab successful commercially in the marketplace, out of our arrangements with BeiGene and Jazz, continue to benefit financially. Those proceeds can get put back in to continue to fund a pretty broad and extensive portfolio of oncology agents.
There was a question back there.
Oh, yeah, go ahead.
Thank you very much. Your bi-paratope product looks fantastic. My question relate to R&D approaches. You mentioned earlier that when you select a target, you were looking at what to do with it, right? Whether it's going to be bispecific, going to be ADC, going to be monoclonal antibody, what else? Maybe you can give us a little bit, in a sense of how do you go about it? How do you select, you know, can be doing a bispecific versus ADC versus other modalities?
It's a good.
Yeah. Yeah. I mean, it's a good... It's a great question. You know, at least, you know, maybe an example of the folate receptor. I mean, there, you know, we're talking about an antibody. We did consider a bi-paratope there as well, so we have that luxury of trying both. In that case, we found that the bi-paratope didn't give us a great advantage over a straight antibody. A lot of it's empirical. You just build the molecules and test them and see what the activity looks like. We're, you know, each target is, has to be treated differently there.
There are going to be other targets, maybe based on the level of expression, based on the level of normal versus tumor tissue, that you might feel may be more appropriate for an ADC or a redirected T-cell killing approach.
Yeah. I think strategically, the way we look at it is we're, you know, we're agnostic as to the approach somewhat. I think one of the things about being diverse around technology platforms is, you know, we don't look at a target and say, "I need to apply an ADC approach to that 'cause I'm an ADC company." We look at a target, look at indication of interest and look at how to solve it, and we can think about whether an ADC approach is the right way, is a biparatopic ADC approach is the right way. Eventually maybe a bispecific approach. We can look on the multispecific side and decide if we think a really great bispecific antibody in combination with something else might be interesting. Can we design a trispecific platform or construct and build in the co-stimulation PD-1 there itself?
I think we're really agnostic as to solution because of a range of things that we can apply to our technology platform. What you hope or the hope of that is that you're for a target or indication of interest, you're picking the best platform to address that issue, not just the platform you currently have in the company that you have to use. That is the theory. We have to prove that out by picking those things, applying the right platform, and hoping the clinical benefit justifies the thesis we had in picking one versus another. As, as Paul said, for the, for the folate receptor alpha antibody, our folks designed an amazing antibody that doesn't need anything else to be effective. We don't need to think about biparatopic or anything else. In an ADC construct, it's great.
Again, that's how I think the agnostic part of our platform and being so diverse in the platforms we have, hopefully allows us to design better products that really meet the needs of those patients against that target. If that makes sense, I hope.
Great. Thank you, Ken. Thank you, Paul. This concludes the end of our Q&A session. Thank you so much for joining us.
Thanks.
Thank you very much.