Mersana Therapeutics, Inc. (0M40.F) Earnings Call Transcript & Summary

Good morning, and welcome to Mersana Therapeutics Immunosynthen STING-Agonist ADC Platform Webinar. [Operator Instructions] I would now like to turn the call over to Sarah Carmody, Executive Director, Investor Relations and Corporate Communications. Please proceed.

Good morning. Welcome to Mersana's webinar highlighting our Immunosynthen STING-Agonist ADC platform and pipeline. A replay of today's webinar will be available on the Investors & Media section of our website. After our prepared remarks, we will open the call for Q&A. Before we begin, I'd like to mention that our call will contain forward-looking statements within the meaning of federal securities laws. These are not statements of historical facts and are based on management's beliefs and assumptions and on information currently available. They are subject to risks and uncertainties that could cause the actual results and the implementation of company's plans to vary materially, including: the risks that our early, encouraging preclinical results for our clinical and pipeline development candidates are not necessarily predictive of the results of our future discovery programs or clinical studies; that the identification of the company's development and product candidates and new platforms involve decisions to prioritize certain candidates over others; that the development of such candidates will take longer and/or cost more than planned; and that our ability to submit an investigational new drug application within our expected time line will not be met, if at all. These risks are discussed in the company's SEC filings, including, without limitation, the company's annual report on Form 10-K filed on February 28, 2020, the company's quarterly report on Form 10-Q for the quarterly period ended March 31, 2020, filed on May 8, 2020, and subsequent filings. In addition, while we expect the COVID-19 pandemic might adversely affect the company's preclinical and clinical development efforts, business operations and financial results, the extent of the impact on the company's operations and the value of the market for the company's common stock will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantine, physical distancing and business closure requirements in the U.S. and in other countries and the effectiveness of actions taken globally to contain and treat the disease. Except as required by law, the company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future. With that, I'll turn the call over to Anna Protopapas, Mersana's President and Chief Executive Officer.

Thank you, Sarah. Good morning, everyone, and thank you for joining us today to learn more about our innovative Immunosynthen STING-Agonist ADC platform and pipeline. Joining me today with prepared remarks are Tim Lowinger, our Chief Science and Technology Officer; and Marc Damelin, our Executive Director and Head of Biology. As you all know, Tim has been with Mersana since almost the beginning and has been the architect of our innovative and highly differentiated platforms. Marc joined Mersana several years ago, with extensive experience in ADCs and ADC biology and has been instrumental in spearheading our Immunosynthen effort. Combining our unique expertise in ADC design and optimization with foundational understanding of cancer biology, we have been able in a short period of time and with limited resources, not only to develop Immunosynthen STING-Agonist platform, an exciting way to stimulate the innate immune system, but also develop a promising pipeline of preclinical molecules. We are ready to move our first Immunosynthen ADC into IND-enabling studies and expect to be able to move into the clinic in Q1 of 2022. Tim and Marc have a rich agenda to cover today. Tim will focus on the therapeutic and mechanistic rationale for the Immunosynthen STING-Agonist ADC platform as well as the development and optimization of the platform, while Marc will focus on the preclinical data supporting the potential of the platform as well as the selection of our first Immunosynthen ADC. With that short introduction, I will now hand it off to Tim.

Thanks, Anna. Good morning, everyone, and thanks for joining us this morning. Marc and I are excited to share with you some of the science behind our Immunosynthen ADC platform and the pipeline we are building with it. Over the course of the discussion, we hope to give you a better understanding of why we believe an Immunosynthen ADC approach has the potential to more safely and effectively activate the innate immune system and how we feel our approach is differentiated from other approaches as well as give you a sense of the pipeline we are building and when the first Immunosynthen ADC is expected to reach the clinic. Of course, we all recognize that immunotherapy has been a revolution in the treatment of cancer, and this has been especially driven by the success with checkpoint inhibitors and their ability to reactivate adaptive immunity or, as some people describe it, release the brakes on the adaptive immune system. Following the success of modulating the adaptive immune system, many scientists and clinicians believe that activating the innate immune system or stepping on the gas represents the next opportunity to deliver new breakthroughs in IO. There are different ways in which one can approach activating the innate immune system and, at the outset, we considered many of them. Ultimately, we made the deliberate choice to pursue STING-agonism over other approaches for several reasons, which will hopefully be clearer by the end of this presentation. STING agonism has been studied extensively, both preclinically and clinically, with the clinical data reported to-date based on intratumoral injections. Although the clinical results with this approach have not yet achieved the vision of activating the innate immune system, they have demonstrated that STING activation can lead to biological activity, including reduction of injected tumor lesions as well as various biological markers of intratumoral inflammation. We believe that an ADC approach is ideally suited to fully exploit the potential of STING-based activation of the innate immune system and to overcome the hurdles that have limited progress to-date. The initial clinical approach is to harness the potential of STING used intratumoral injection, as shown in the left panel in this slide, in an effort to elicit a localized effect and avoid the potential toxicities of systemic exposure to an immune activator. However, intratumoral injection is limited to accessible tumors, and it's impossible to reach every lesion, including metastatic sites. Recently, some companies are pursuing systemic administration of small molecule STING-agonist as shown in the middle panel. This can result in greater biodistribution, including the metastatic lesions, but risk systemic inflammation and activation of immune cells outside of tumor. Not only could this cause toxicity concerns but it has also been reported that STING activation of T-cells, for example, can be counterproductive and can lead to the death of cells that you want to contribute to efficacy. That's why we believe the ADC approach, as depicted in the right most panel, is ideal. It offers the potential to combine the convenience of systemic administration with localized targeted delivery of the STING-agonist to all tumor lesions. In addition, it allows for active uptake by both tumor cells and tumor resident immune cells, while avoiding delivery to immune cells outside of tumor and also can greatly enhance the pharmacokinetics of the STING-agonist. At SITC last week, we presented what we consider to be important differentiators of our Immunosynthen STING ADC platform relative to other approaches to innate immune activation, and I'd like to touch on a few highlights from that presentation. First, we presented preclinical evidence that we believe overturns a widely held misconception that, although the STING pathway is expressed in both tumor cells and immune cells, the STING pathway is silent in tumor cells and therefore can't contribute to innate immune activation. What we have demonstrated through multiple experiments, both in vitro and in vivo, is that the STING pathway in tumor cells is indeed intact and if effectively activated can meaningfully contribute to an antitumor response. This is in contrast to TLRs, for example, which are not expressed in tumor cells. We also showed that Immunosynthen ADCs delivered to both tumor cells and tumor-resident immune cells in a target dependent manner, activating both cell types and delivering what I call a one-two punch, resulting in potent and robust antitumor responses with excellent tolerability. Over the next few slides, I'll share some of the data that support these findings, but let me first explain what I mean about a one-two punch. The goal with an Immunosynthen ADC is to selectively deliver the STING-agonist to tumor cells and tumor-resident immune cells while avoiding delivery to healthy tissues. So how do we achieve this? As shown here, the antibody binds to a target antigen on tumor cells localizing delivery to the tumor and providing a mechanism for active internalization into the tumor cell. As the ADC collects and organizes in the tumor environment, it can also interact with myeloid cells resident in the tumor, resulting in binding of the Fc portion of the antibody to Fc gamma receptors on the myeloid cells. As shown here, Fc gamma-mediated internalization into the myeloid cell results in STING activation of that immune cell, providing punch number one. Similarly, antigen-mediated internalization into the tumor cell results in activation of the STING pathway in the tumor cell, providing punch number two. Because T-cells and B-cells do not express Fc gamma receptors, the Immunosynthen ADC does not deliver to those cell types, even if they are present in tumor. In addition, because the Fc gamma-mediated uptake is also antigen dependent, only myeloid cells in the tumor microenvironment, as opposed to myeloid cells elsewhere in the body, are activated. So what evidence do we have to support this? Well, let's first turn to data supporting this one-two punch, this dual delivery of targeted innate immune activation. In this experiment, we used 3 different variants of Immunosynthen ADCs to demonstrate this. In blue is our Immunosynthen ADC, which recognizes our target antigen and is capable of Fc gamma receptor binding to the myeloid cell. As a control, in gray, we have an Immunosynthen ADC on a nonbinding antibody, which doesn't recognize a target antigen, but is still capable of Fc gamma binding to the myeloid cell. And finally, in green, we have an Immunosynthen ADC, which binds the target antigen, but has been mutated to eliminate binding to the Fc gamma receptor on the myeloid cell. We then tested all of these variants in an assay, as described in the center of this slide, where we coated the target antigen on a plate and then added immune cells engineered to light up if the STING pathway is activated. As you can see in the graph, the free STING payload, shown in bright pink, results in STING activation. However, the fully competent Immunosynthen ADC, shown in blue, activates the myeloid cell effectively at 40x lower STING-agonist concentrations demonstrating the benefit of active delivery by the ADC into the myeloid cell. In contrast, the nonantigen binding control ADC in gray is much worse than the free payloaded activating STING, and the Fc mutant shown in green is completely inactive. So antigen-dependent Fc mediated delivery by the ADC is how we deliver punch number one to the immune cell in a targeted manner. So what about punch number two? Well, to evaluate that, we use the same variance of the ADC, but we now test them in a coculture of antigen expressing tumor cells and peripheral blood mononuclear cells, or PBMCs, which are immune cells. In this assay, we have labeled the tumor cells so we can carefully monitor their growth or death over time with bars above the line representing tumor cell growth and bars below the line representing tumor cell death. As you can see, the nonbinding controlled Immunosynthen ADC, represented by the gray bars, has no effect and the tumor cells continue to grow. In contrast, the targeted Immunosynthen ADC in blue results in potent cell killing at both concentrations. However, what initially surprised us was that the Fc mutant ADC, which combined and internalized into the tumor cell, but not the immune cell, also shows clear activity in tumor cell death. Because this green ADC doesn't internalize into the myeloid cell, we hypothesized that this effect must be the result of tumor cell intrinsic STING activation. To confirm this, the same experiment was performed again, but with one important change, using CRISPR, we knocked out the STING pathway in the tumor cells. And as you see here, when we repeated this experiment with these tumor cells, the Fc mutant ADC in green is now also clearly inactive. Supporting the punch number two is a result of tumor cell intrinsic STING activation. The one-two punch isn't only limited to in vitro experiments. Here, you see a very similarly designed experiment conducted in vivo. As you can see, in 2 different tumor models targeting 2 different antigens with 2 different antibodies, the results are very consistent. In both cases, the nonbinding control Immunosynthen ADC, shown in gray, is completely inactive demonstrating the need for antigen targeting for the effect. In blue, the targeted Fc competent Immunosynthen ADC delivers a one-two punch, resulting in deep and durable regressions after a single low dose of about 3 milligrams per kilogram. And again, the Fc mutant Immunosynthen ADC, which combined and internalized into the tumor cell, but not the myeloid cell, is active, demonstrating the benefit of tumor cell intrinsic STING activation or punch number two alone. So at a high level, that is the data that we presented at SITC last week and why we are excited about the potential of Immunosynthen ADCs to fully exploit innate immune activation. Immunosynthen ADCs provide us the opportunity for an innate immune one-two punch in both tumor cells and tumor-resident immune cells, unlike TLRs, the expression of which is restricted only to the immune cells. For more details on the characterization of our Immunosynthen ADCs and their biological effects in vitro and in vivo, I would refer you to our SITC 2020 poster, which is available on our website. Next, I'd like to turn our attention to how we develop the Immunosynthen platform and pipeline. We took a holistic approach to build the optimal STING-Agonist ADC platform. We didn't simply swap out a cytotoxic payload for a STING-Agonist and call that a STING ADC platform. We built it from the ground up using our expertise in ADCs and our understanding of the rules of ADC design. First, we developed our own novel STING-Agonist payload by specifically selecting and optimizing what we determined to be the best variant for an ADC approach selected from hundreds of candidates. With the optimal payload in hand, we then specifically developed a linker and scaffold for the novel agonist precisely matched to provide optimal pharmacokinetics and drug-like properties. In parallel, we evaluated and validated multiple targets we thought were appropriate for Immunosynthen ADC, and we selected an optimal antibody for each target based on our assessment of each antibody's affinity, epitope and developability. Armed with our choices for the optimal Immunosynthen platform and optimal antibodies for multiple targets, we combined the work streams to create a pipeline of potential Immunosynthen ADC development candidate. This slide represents some of the iterations and how we leveraged our expertise in ADCs to drive platform refinement. We believe we understand the rules to create optimal ADCs, and we have the experience and the tools to do so efficiently. As shown here, using the same antibody and STING-Agonist payload, we iterated and optimized the scaffold, modifying and incorporating different modules that can influence the drug-like properties of the ADC. Rather than being satisfied with a suboptimal variant such as those represented by the orange or purple curves, we pushed the optimization until we achieved what we believe is the optimal Immunosynthen platform, one that provides us with potent and durable responses after a single low dose, as shown by the green line at the left in this in vivo study, matched with excellent stability in pharmacokinetics, as shown on the right. As we set out to build a pipeline of Immunosynthen ADCs, we generated a list of what we wanted to demonstrate preclinically to convince us of the value of the platform and the value of potential pipeline candidates. On the subsequent slides, we will show you that we achieved all of these objectives. And with that, I'll turn it over to Marc to tell you more.

Thanks, Tim. Tim described how we built the platform from the ground up, optimizing every component and how they fit together. In parallel, we invested a lot of effort to better understand the most effective ways to target the ADC. We explored Immunosynthen ADCs against immune cell antigens, tumor cell antigens and tumor associated antigens. As Tim showed you, we can activate STING in the immune cells, even when we target tumor and tumor associated antigens. You don't need an immune cell target to reach the immune cells. We have focused on tumor and tumor-associated antigens because this is where we saw the most promising activity, likely due to the one-two punch. Our Immunosynthen ADCs consistently show robust antitumor activity and frequently sustained tumor regressions after a single low dose. In this example, for a tumor-targeted ADC, we see sustained tumor regressions, while, in contrast, the control nonbinding ADC and the unconjugated antibody have no activity. These results demonstrate the target dependent activity of the Immunosynthen ADC. Furthermore, the benchmark Sting-Agonist and IV agonist published as noted showed minimal activity in preclinical studies, even though it was administered at a 50-fold higher payload dose than the Immunosynthen ADC, a dose of the IV agonist that is very close to its maximum tolerated dose. We observed immune cell infiltration into the tumor within 72 hours of administering the Immunosynthen ADC, and that's exactly what we'd expect as a result of STING pathway activation in the tumor. Specifically, the brown staining in the middle panel shows substantial immune cell infiltration as well as tumor necrosis at 72 hours. Again, this effect is target dependent since it isn't seen with the control ADC. We specifically interrogated the induction of mouse cytokines in the tumor microenvironment in a mouse bearing a human tumor xenograft. And in that way, we demonstrated the activation of the STING pathway in mouse cells by an Immunosynthen ADC that recognizes only the human tumor cells. These results are consistent with the data Tim showed demonstrating the Fc receptor mediated internalization of the ADC into immune cells in a tumor target dependent manner. In other words, this is another way to see the first punch that activates STING in immune cells. We also observed the induction of human STING pathway cytokine in vivo by measuring the expression level specifically of human genes using Nanostring technology. We saw the robust activation of STING pathway genes in a target dependent manner. These results are also consistent with the studies that Tim showed with the Fc mutant ADC and the STING knockout tumor cells. Tumor cells typically don't activate STING when they're cultured under standard conditions in the lab. But what we discovered is that within the tumor microenvironment, Immunosynthen ADCs activate STING in the tumor cells, which directly contributes to the antitumor activity, in other words, the second punch. Also very important data is the induction of tumor-specific immunological memory by the Immunosynthen ADC. Specifically, immune competent mice that had been cured of their tumors by the ADC were reimplanted with the original targeted tumor as well as with a new tumor they hadn't seen before. The targeted tumor didn't grow back in any of the animals, while the new tumor grew back in all the animal. This demonstrated the induction of tumor-specific immunological memory by the Immunosynthen ADC, a one-two punch that puts the tumor down for the count. Our Immunosynthen ADCs have greatly improved tolerability over the IV benchmark. In this study in mice, systemic cytokines were only modestly elevated by the Immunosynthen ADCs administered at a dose that induced sustained tumor regressions. On the other hand, the IV benchmark induced high elevations of the cytokines at a dose that didn't even have much antitumor activity. Remember, this is one of the design advantages of an ADC approach over a systemically administered free agonist. More importantly, we have demonstrated excellent tolerability in nonhuman primates, the most relevant species for toxicology evaluation. The results were consistent with 4 different targets with fully cross-reactive antibodies. We observed modest cytokine elevations consistent with the observations in mice. There have been no adverse findings in clinical pathology or histopathology. Furthermore, our Immunosynthen ADCs exhibit excellent stability and extended exposure in repeat dose studies. As I mentioned, we've validated multiple tumor and tumor-associated antigens with the Immunosynthen platform. Here are representative in vivo studies for 4 tumor cell targets. In all cases, we saw significant antitumor activity after a single low dose of less than 1 to 3 mg per kg by antibody, which is substantially below the well tolerated doses of at least 9 mg per kg in nonhuman primates. Significant antitumor activity after a single low dose is in contrast to preclinical data reported with other approaches to innate immune stimulation. And here are representative studies for 2 tumor-associated antigens, where we also saw target dependent activity after a single low dose. The consistently robust results with Immunosynthen ADCs across targets, tumor models and mouse strains are striking, especially in the IO space and demonstrate the broad applicability of the Immunosynthen platform. The robust efficacy data, together with the excellent tolerability in nonhuman primates for the 4 targets we've tested so far, highlight the opportunity to rapidly build a pipeline on the Immunosynthen platform. We have a discovery stage pipeline of Immunosynthen ADCs, representing a suite of targets across multiple clinical indications in areas of high unmet medical need. Now I'd like to share a snapshot of data from our first Immunosynthen development candidate, XMT-2056. We're rapidly advancing this candidate toward the clinic, but we aren't disclosing the target at this time to maintain our competitive advantage. The left panel shows the potent activation in immune cells via Fc receptor internalization. The middle panel shows the potent induction of CXCL10 in a coculture of tumor cells and immune cells. You can see that the Immunosynthen ADC is about 1,000-fold more potent than the free payload. The right panel shows an in vivo study with sustained tumor regression after a single low dose of 1 mg per kg. And the bottom panel describes the key observations from the nonhuman primate toxicology studies with XMT-2056. We conducted single dose and repeat dose studies at 9 mg per kg and did not have any mortality or clinical signs. XMT-2056 exhibited an excellent pharmacokinetic profile in nonhuman primates. The ADC is highly stable, meaning the payload doesn't fall off as demonstrated by the parallel curves for total antibody and conjugated drug. Importantly, the PK profiles after the first and second dose are comparable, which is consistent with the absence of anti-drug antibody or ADA, that if present could clear the ADC quickly after the second dose. The right panel demonstrates the therapeutic index for XMT-2056. The exposure in monkey at the well tolerated dose is approximately 10x higher than the exposure in mouse that induces sustained tumor regression. We are excited about XMT-2056 and are initiating IND-enabling studies with the objective of an IND in Q1 of 2022. I'll now pass it back to Tim for concluding remarks.

Thanks, Marc. The data presented here today provides strong validation for the potential differentiation of the Immunosynthen platform from other approaches and its applicability across multiple targets. Disclosed here for the first time is the depth of our Immunosynthen ADC pipeline. With our Immunosynthen ADC platform, we have the ability to deliver STING-agonism and its one-two punch against a very wide range of targets. We stand poised to advance the first of these programs into IND-enabling studies. In summary, we believe Immunosynthen ADCs have the potential to specifically address the limitations of current approaches to activate innate immunity and STING. Immunosynthen ADCs deliver a one-two knockout punch from STING activation in cancer cells and tumor resident immune cells as we showed at SITC 2020. We have optimized the platform using our ADC expertise, and we are building a deep pipeline of Immunosynthen ADCs with a broad range of clinical indications and potential for value-creating partnerships. Finally, we are excited that XMT-2056 has been selected as the first Immunosynthen ADC with initiation of Phase I dose escalation expected in the first quarter of 2022. And with that, I will turn the call over to the operator for Q&A.

[Operator Instructions] Our first question comes from Tom Shrader of BTIG.

Wow, 3 questions, I don't think I've ever asked 3 questions. I think the most obvious question is, have you tried Fc enhanced antibodies, given your mechanism? And then the second question, your memory response, is it significantly different than the memory response generated by any other sort of deep antitumor response? So is it more than just a good response to a PD-1 antibody would provide? Is there really something different here? So that's what I got.

Sure. Tom, maybe, Marc, would you like to answer that?

Sure. Regarding the Fc enhanced antibodies, we have not done experiments with that. And I think the reasoning is we would be worried about increased activation of STING in the periphery because, if we enhance the interaction with immune cells without the tumor-dependent binding, we might get extra peripheral activation. So the IgG that we use is the perfect balance to enable the tumor target-dependent activation of the tumor-resident immune cells. Regarding the memory, I can't answer your question because we haven't done all of the studies to fully characterize the immunological memory that you saw, but we have seen the induction of memory in a tumor-specific manner with multiple targets.

And our next question comes from Jonathan Chang of SVB Leerink.

First question, how is your STING-Agonist ADC platform differentiated from other similar early-stage programs in development in the competitive landscape?

Sure. Jonathan, well, I think as we pointed out, our preclinical data demonstrates that we're very effective after a single low IV dose across multiple targets and antibodies, that we deliver a one-two punch, so that our Immunosynthen ADCs activate the innate immune system in both tumor-resident immune cells, but also in the tumor cells. And we've demonstrated that tumor cell activation can also meaningfully contribute to that antitumor effect, unlike, I think, many other innate immune stimulating approaches. And finally, I also want to underscore the tolerability in pharmacokinetics that we've seen in nonhuman primates, where, as Marc showed you, after multiple IV doses, at exposures that are significantly higher than the exposures in mouse required for deep and durable responses, it is very well tolerated with no signs of anti-drug antibodies, et cetera, or immunogenicity. So taken together, we think that our preclinical package compares very favorably with what we've seen from other approaches. And we're very excited to move this forward to the clinic.

Got it. Second question, how are you thinking about potential business development opportunities for the STING-Agonist ADC platform, given the potentially broad applicability of this platform?

Sure. Anna, maybe that's a question you'd like to address?

Yes, I'll be happy to address it. Thanks for the question, Jonathan. We have received -- there was a fair amount of interest from potential partners. Given the strength of the data that Tim and Marc just walked you through, I think, as always, we will look at what are the benefits of that partnership and does it meet our strategic criteria. We partner with capabilities and resources that would help us accelerate the program while allowing us, Mersana, to [ attain ] sufficient long term upside, I think would be something that we would consider. So we're open to it, but it has to be the right partnership that meet the strategic criteria.

Got it. And just one last question for me. Are you willing to provide any high-level color on how you're thinking about which targets to pursue in the clinic at this time?

We selected our first ADC based on a few different criteria, the speed to IND, the understanding of the antigen and its role on the tumor, and the breadth of indications representing areas of high unmet need. I think at this point, we will not give more color on the target. As we get closer to IND, I think we'll be more open to disclosing the target, but not at this point. We want to retain our competitive advantage.

And our next question comes from Boris Peaker of Cowen.

I guess I wanted to just ask kind of a broader question. If we look at immuno-oncology agents in general, there's clearly been more success in developing antagonists compared to agonists. I'm curious -- and there's many reasons people believe in it from sensitivity to dosing to various feedback mechanisms. Curious what we could learn from other agonists to incorporate here to maximize the positive outcome?

Sure. I think, Boris, the -- our approach has been that, focusing especially on STING, we've seen clinically that that's been limited to intratumoral injection. And we really think that that's one of the hurdles that has really resulted in STING not realizing its full potential. As we showed with the IV approach with an Immunosynthen STING ADC not only can we deliver to all lesions, not only the injectable lesions, but we also demonstrated that we can get much better uptake into the cell and much better potency, where, in that head-to-head comparison, the small molecule was 40 to 100x less potent than it was when it was part of the ADC because we get active delivery into that cell. So we think that an ADC approach is ideally suited to fully realize the potential of STING-agonism, not only from the delivery aspect, the efficacy aspect, but as we also showed from the tolerability aspect, because why did other companies focus on intratumoral STING injections? Because they were concerned about systemic tolerability. And as we've shown in the nonhuman primate studies after multiple IV doses at much higher exposures than what's required for the efficacy, we see that it is very well tolerated. So we think that this approach really has the potential to maximize STING-agonism in a safe and effective way.

Got you. And my second question, what are your thoughts on optimizing the drug-to-antibody ratio. How do you anticipate it to compare to some of your other drugs in development?

Yes. So as you know, we've said for some time, we don't believe that ADCs are one size fits all. And I think we're one of the few companies that really has the ability to change drug-to-antibody ratio in meaningful ways. And as we showed with our DolaLock platform, we could do that from a of DAR of 2 to a DAR of 24, anywhere in between. So with STING, that is definitely a feature that we take into account as well. And we're very much about holistically designing an optimal ADC taking into account what is the target, what is the payload, what are the right drug-like properties. So that is a factor that we have taken into account with Immunosynthen ADCs as well.

[Operator Instructions] And our next question comes from Mike Ulz of Baird.

Just curious, given the potency that you're seeing preclinically, do you anticipate potentially seeing some single-agent activity in the clinic? Or are you more thinking combinations will be required?

Mike, no, based on the preclinical data and the mechanism, we feel that there is clearly an opportunity for single-agent activity with this approach. However, it's also an approach that lends itself easily for thinking about combinations. And that's something that we have also given thought to and are generating preclinical data to support. So especially when one looks at the tolerability profile that we're seeing preclinically, one can imagine a number of different combinations that might also make clinical sense, but single-agent activity is something we would also anticipate.

Got it. That's helpful. And then just in terms of the development strategy here. You mentioned very broad applicability across different targets and tumor types, et cetera. So just curious if the plan here is to get to some clinical proof-of-concept with 2056 first and then sort of advance some other opportunities or might you be advancing some of those other opportunities in parallel?

Sure. Well, I do think, as Anna mentioned, one of the factors in -- taken into account as we collected 2056 was speed to the clinic. And we're very excited about the preclinical data package. But getting into the clinic right now planned for first quarter 2022 allows us to gain clinical experience and factor that in for follow-on molecules or additional candidates. That doesn't mean that we would wait until that time. But Anna, maybe you want to comment overall on our strategy.

Yes. Mike, thanks for the question. I think the fact that we just shared with you a robust pipeline, I think, is a reflection of the productivity of the scientific group that Tim and Marc lead, and also the power to leverage a validated platform to efficiently generate a future pipeline. We will take the first molecule forward. We'll continue to work on the rest of the pipeline. But we will be disciplined as we have been in the past with investment choices for our portfolio. Ultimately, we want to maximize the benefit to patients. So we're going to look at all the options along the way as we learn more about the lead candidate and as we learn more about the rest of the pipeline, as we continue to study preclinically.

And our next question comes from David Nierengarten of Wedbush Securities.

First off, how -- I guess, in your preclinical studies, how generalizable has it been? Is it every tumor type has a response or are there some tumors that don't respond in your studies? And then for your initial plans or strategically, are you planning basically to go where IO can't at the moment? Or to try to compete against other IO strategies in tumors where you're more confident that the immune system is competent to react to the tumor?

Sure. Thanks for the question, David. So I think in our preclinical work, we've been very pleased to see that the platform works across multiple targets, multiple antibodies, as we showed you. And so we do believe we understand the rules for creating Immunosynthen ADCs and which targets are more appropriate and which ones might not be. In fact, we've demonstrated activity in a variety of models and a variety of mouse strains, including syngeneic models. So overall, we found it to be quite robust. And then the second question was with regards to clinical development, as we said in the beginning, I think, we see innate immune activation as a way to deliver potential breakthroughs in immuno-oncology. So of course, one takes into account what's been learned already with the checkpoint inhibitors with warm tumors versus colder tumors, et cetera. But the ultimate goal, at least for innate immune activator, would be to really expand the patient population that can really benefit from immuno-oncology approaches. And so I think that, that is very much what we hope to do.

And ladies and gentlemen, this does conclude our question-and-answer session. I would now like to turn the call back over to Anna Protopapas for any closing remarks.

Thank you for joining today. We've shared with you promising preclinical data supporting the potential of our Immunosynthen ADCs to stimulate the immune -- the innate immune system. We're moving our first molecule forward, and we look forward to continue to update you as we advance both our lead Immunosynthen ADC as well as the rest of our pipeline. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.