Cullinan Therapeutics, Inc. (CGEM) Earnings Call Transcript & Summary

Good morning, and thank you, everyone, for joining us today. Today is the last day of JP Morgan's 40th Annual Healthcare Conference. My name is Tarun Soni, I'm a Vice President in JPMorgan's Healthcare Investment Banking Group. Before I introduce you to our presenter for the session, I want to call your attention to the blue button on your screen which says ask a question. You may submit your questions here, and I can address it during the Q&A session. With that, I'm very pleased to introduce you to Nadim Ahmed, CEO of Cullinan Oncology. I know he's very excited to tell you a little bit about the story. So over to you, Nadim.

Good morning, Tarun, and everyone watching. It's great to be with you today. And so let me start out by providing a little strategic background to Cullinan Oncology as a company. So starting with Slide 3. If I can move it. So we have a very broad and deep pipeline. So we now have 8 programs across multiple platforms and multiple indications across hematology and solid cancers. And we have assets that have the potential to either be best-in-class or first-in-class. Our lead program, CLN-081, for non-small cell lung cancer patients with EGFR exon 20 insertion mutations is currently ongoing in Phase I/IIa and we recently provided the clinical update, which further supports the differentiated clinical profile that we're seeing for 081. And of course, we are very pleased to receive breakthrough therapy designation from the FDA recently, which further underscores the differentiated profile that we're seeing with 081 in the clinic. In addition to 081, we now have another 2 programs that enter the clinic at the end of December. So that was CLN-619 and CLN-049. So CLN-049 is our FLT3 T cell engager, and CLN-619 is our MICA antibody. We're fortunate to have a robust cash on hand position at the company. So this really allows us to deploy capital to advance the pipeline very expeditiously, but continue to in-source innovation. And so as we look at our preclinical pipeline also, we have a broad pipeline there, too. We have 2 assets that are currently in IND-enabling studies, which should enter the clinic in the next 12 to 18 months. And also, we continue to replenish the pipeline. So we made announcement earlier this week. We're excited about collaboration that we have with Mount Sinai to work together on a novel HPK1 degrader program. So very excited about that possibility as well. And I think a couple of things I'd say that are unique about Cullinan Oncology that we take a very disciplined approach to either in-sourcing innovation or the way we actually advance our program. So 3 key criteria I'd point out here. So the assets have to have the potential at least to either be first-in-class or best-in-class. We're really focusing on those molecules that can activate the immune system or target key oncogenic drivers. And the molecule has to at least preclinically have the potential promise of single-agent activity. I'm fortunate to be surrounded by a very experienced senior leadership team, very strong scientific capabilities that really allows us to target the assets that we're bringing in as well as the agents we're advancing. As I mentioned earlier, we're very platform agnostic. So within the company, we have small molecules, biologics, T cell engagers, fusion proteins. And where we're really focusing on are areas of differentiation. So whether it's a differentiated platform or another mechanism of action. And across the broader Cullinan Oncology team, we have deep scientific expertise that really allows us to kind of push and accelerate our internal programs, but also allows us access to a network of collaborators, both in academia as well as company partners. And so you can see the pipeline here. As I mentioned, 8 programs. Obviously, 081 is a very important program for us and is our lead program. But you can also see beyond 081, we have a very deep pipeline across solid tumors and hematology indications and across multiple platforms also. So 8 programs across various stages of development with 3 already in the clinic, another 3 assets in IND-enabling studies and then 2 other programs at the candidate selection stage including the newly announced HPK1 degrader program. So let me dive into the pipeline a little bit and start out by talking about CLN-081, on Slide 7. So CLN-081 is a very interesting molecule. It's a novel oral EGFR inhibitor with a unique chemical structure which allows it to preferentially target mutant exon 20 versus the wild-type variant. And we think this contributes to the therapeutic profile that we're seeing in the clinic. So 081 is in an ongoing Phase I/IIa trial, as I mentioned earlier, testing a broad range of doses from 30 to 150 mg BID in non-small cell patients harboring again, the exon 20 insertion mutation. It's a heavily pretreated patient population with about 2/3 of patients having received 2 or more prior lines of therapy. And this table summarizes the response rates that we've seen today. So we see a confirmed response rate of 39% and which compares very favorably to other agents in this space. And in totality, we see a 97% excellent disease control rate of 35 or 36 patients. So following ASCO, we were very pleased with the response rate we now see in a larger group of patients. And when you look at the 150 mg BID dose, we see a confirmed objective response rate of 27%, which we believe is perhaps driven somewhat by the tolerability profile, which I'll go on to discuss. So moving to Slide 8. You can see here that CLN-081, especially at the 100 mg BID dose really has a differentiated and favorable safety profile, which is especially important in the context of the efficacy that we just discussed. So this table breaks down key treatment-related AEs, especially those that are wild type EGFR associated toxicities across the 100 mg dose, the 150 mg dose and across all dose levels. So at the 100 mg dose, you can see that no patients experienced Grade 3 or greater rash or diarrhea. And in fact, for rash and diarrhea when you look at Grade 1 and 2 toxicities, it's heavily skewed at a ratio of 3:1 for both ration diarrhea towards Grade 1, which we think is very encouraging. Also with the protocol, all of these events were manageable with conventional supportive care, and we didn't require systemic GI prophylaxis to manage the diarrhea that was observed. At the 100 mg dose, we did see 1 patient with Grade 3 pneumonitis which is known to be a toxicity with EGFR TKI inhibitors. However, you'll see in the footnote, this was a patient that had some confounding factors. At the 150 mg BID dose, we did expand enrollment since we presented the data at ASCO, now up to 11 patients. And what we found was Grade 3 diarrhea in 2 patients, Grade 3 rash in 1 patient. And we also saw 2 patients with transaminitis either Grade 3 or Grade 4. And also, we saw a patient with Grade 3 pneumonitis at the 150 mg dose. Again, some confounding factors. But I think the most important aspect of the 150 mg dose in addition to the step-up in toxicity, you can see on this slide that we see a significant increase in treatment-related dose reductions as well as treatment-related dose discontinuations. So when we look at the totality of the efficacy and safety dose -- data, it really supports moving forward with the 100 mg BID dose. Moving to Slide 9 now. I did mention the response rates earlier on. So obviously, quantity of response is important, but quality of response is equally important. And so we were pleased to see for the first time, we were able to assess durability data from this study in the 13 patients in the Phase I cohort. And using Kaplan-Meier estimates, we saw a median duration of response of greater than 15 months and a progression-free survival or median progression-free survival of 12 months and a disease control rate of 92%. So again, these durability data compare very favorably with other agents in the same class. And so of course, we continue to follow up for the Phase IIa patients, and we'll have durability data to report on those patients in the future, but we are very encouraged by the quality of response we've now seen in this study. I mentioned earlier, we're very excited about the breakthrough therapy designation we recently received from the FDA. And so that really underscores the differentiated profile that we see with 081, but at the same time, it also encourages us regarding the regulatory pathway and the fact that accelerated approval is still open for us. So that's the summary of CLN-081. Based on the updated data, we see a very favorable profile in terms of efficacy, both quality and quantity of responses, and we also are encouraged by the favorable safety profile we have seen so far in a heavily pretreated group of patients with a significant unmet need. So let me now turn to the other clinical stage programs. So Slide 11. This is CLN-049, which is a novel T cell engager targeting FLT3 in a Phase I study for relapsed/refractory AML patients. FLT3 is a very well-validated target in AML, and it's actually expressed in a substantial majority of AML patients. And fortunately, very low expression on normal myeloid cells. So the unique approach we have with 049 is that it targets the extracellular domain of FLT3. So that allows it to target both mutant and wild-type FLT3. So it expands the addressable patient population to 80% plus versus the mutant FLT3 kinase population of around 25%, that's addressed by currently approved agents. The fact that we see low FLT3 expression on normal myeloid cells is good relative to other targets like CD33, CD123. And also the construct of the antibody is in line with other T cell engagers that we've seen in the lymphoma space that have encouraging high levels of activity and low levels of CRS. We also have a silent Fc backbone in this molecule. So that will prolong the half-life and allow potentially for less frequent dosing and no need for continuous infusion, for example. And as I mentioned, 049 is in the clinic now in relapsed/refractory AML patients, a study just opened for accrual in December. So we look forward to sharing those data with you in the future. And on Slide 12, you can see some of the proof points we've seen preclinically with 049. So we're seeing promising preclinical activity. In the upper left chart, you can see the activity of 049 in both wild type and mutant FLT3, and the complete inbreeradication of AML cells in these FLT3 lines. So very encouraging data that shows that the agent targets both mutant and wild-type FLT3. On the top right graph, you can see compared to controlled CD3 antibodies, you don't see activation of T cells of 049 in the absence of target FLT3 cells, which potentially portends for a favorable safety profile. In the bottom left, in the xenograft model, you can see a nice dose-dependent survival curve showing improved survival with increasing doses, and this is at very low doses. We also -- in the bottom right graph, we also transplanted human AML blast directly into mice. And as you can see from this graph, we see a complete eradication of AML cells from the bone marrow. So very encouraging preclinical data, of course, now we're in the clinic. So let's now turn to our third clinical program, which is CLN-619 on Slide 14. CLN-619 is a first-in-class molecule targeting MICA and MICB. MICA and MICB are ligands for NKG2D, which really activate receptors in the immune system, but especially mainly on NK cells. MICA, MICB is broadly expressed on tumor cells. They actually send a kill-me signal to the immune system, especially NK cells. However, what happens in the tumor microenvironment is that tumor cells are very clever and they send proteases that cause cleavage on the cell surface, which sheds MICA and MICB, essentially evading the immune system and masking these cells. And these cells essentially become invisible to the immune system. And so that's a way that these tumors evade and escape the immune system. Now MICA and MICB is broadly expressed across solid and liquid tumors. And soluble MICA and MICB is actually shown to be a prognostic marker and I'll show you that in the subsequent slide. So we believe we're set to online. We have a first-in-class potential here with the first monoclonal antibody targeting this agent now in the clinic. And essentially, what 619 does is it keeps MICA and MICB on the cell surface, which allows elimination by the immune system through various mechanisms, including invoking both the innate and adaptive immune system through multiple mechanisms, including ADCC. So those tumor cells that escape the immune system when MICA and MICB is shared are no longer able to escape the immune system because 619 keeps MICA and MICB on the cell surface. We also have very broad alia coverage of MICA and MICB of over 95%. And as I mentioned, 619 is now in the clinic, and we're doing a parallel evaluation of this novel agent as both monotherapy and combination therapy across a range of solid tumors. In the next slide, Slide 15, you can see both a biological rationale for the target MICA and MICB as well as the interesting preclinical data that we've generated to date. So in the top-right graph, you can see a heat map, which shows a range of NKG2D ligands across a range of tumors. And the red and the pink denote the very high expression levels we see of MICA and MICB, again, portending for pan canter activity with this novel agent. In the top left, I mentioned that shed MICA is a negative prognostic indicator. So you can see in the study in patients a retrospective study that patients that had shed MICA shown by soluble MICA in the plasma did much worse in terms of survival when patients had high levels of shed MICA versus those that had low levels. Turning to the bottom half of this graph, we can look at the preclinical activity now. So in the left graph, you see complete tumor eradication in a xenograft module at all doses of CLN-619. And at the same time, pharmacodynamically in the right graph, you see that at all doses of CLN-619, you see complete prevention of shedding of MICA and MICB. So again, the preclinical package is very strong here. And of course, we'll see the data from the clinical study in the subsequent months. Now I'll also talk about 2 assets in our preclinical pipeline, given the time constraints of the presentation. So we're very excited about CLN-617, which is a first-in-class cytokine therapy combining IL-12 and IL-2. So IL-12 and IL-2 very well described in the literature having potent activity. The problem with these cytokines is the systemic toxicity that we're seeing with these agents. And so we believe we have a unique molecule here that combines both IL-12 and IL-2, but we also include a collagen binding protein in the construct, which allows the tumor to actually retain the cytokine so you don't get leakage. So with 617, you see a co-delivery of both IL-12 and IL-2, which means we get synergistic activity. This is an intratumoral approach. And as I mentioned, we have a unique retention strategy here because of the collagen binding domains. The other interesting aspect of this molecule is that we have potential for memory T cell response and abscopal effects, which is important because just having activity at the site of the tumor injection is, obviously, not as important as having a systemic effect. The other thing is that we have in the construct, native IL-12 and IL-2, so it reduces the risk of immunogenicity. And also, just importantly, unlike other intratumoral approaches, 617 doesn't rely on viral or nucleic acid delivery. So it really allows us to control the dose that's being delivered. So with 617, we have a pan cancer opportunity as monotherapy and also in combination with checkpoint inhibitors. On Slide 18, you can see some of the data that we've generated already that we're very excited about. In the top left, in a very refractory primary tumor xenograft model, you see 100% complete response rate. Essentially, these mice are cured when injected with 917 (sic) [ 617 ] and you see a minimal effect with a checkpoint inhibitor in this setting because of how tough this refractory model is. Now when you look on the right-hand side, which is even more interesting, we -- you see that we induce a very strong systemic T cell memory response. So we take the mice that have been cured, in the top-right corner, reinject tumor into those patients with no treatment, and you see that in 9 out of 10 cases, the tumor is completely rejected. And even in the tenth case, you see a significant delay in progression of that tumor. So inducing a strong memory T cell response, which is very encouraging. And then in the bottom panel, you see a systemic immune response with both monotherapy and combination therapy in a similar model. So we take mice, and draft 2 tumors. So one tumor is injected with both anti-PD-1 and the combination of 617 as well as monotherapy and you see a nice effect for both monotherapy and 617 combined with checkpoint inhibitor, where you see complete tumor aggression. And even more encouragingly, in the untreated tumor, you see an abscopal effect here where monotherapy, you see a significant eradication of the tumor and you see synergistic activity with complete eradication of the tumor with the combination therapy approach. So we're very excited by the very robust preclinical package we've generated for 617. And the last molecule I'll talk about is CLN-978, which we believe has best-in-class potential for hematologic malignancies. It's a CD19 CD3 T cell engager. Now of course, CD19 is very well validated now clinically and commercially with agents that have been approved and T cell engagers as a modality have also been very well validated. So we believe we have a best-in-class potential here with this construct. You see we have an engineered molecule here that has very high affinity for CD19 and a long half-life. So from a differentiation perspective, this means that this agent has the potential to really target low-expressing CD19 cells. So for example, this may be a mechanism resistant for CD19 CAR-T and other T cell engagers. So in that post-CAR-T setting, you can imagine the potential to salvage patients with this high -- with this T cell engager that is activated by low levels of CD19. And at the same time in other settings, you can imagine having this off-the-shelf therapy can make this agent very accessible to a broad range of patients relative to, for example, autologous approaches. And also, the fact that this target is very low-level expression CD19 is potentially favorable relative to, for example, CD19 targeted ADCs where you need a relatively high level of targeted expression so that you can deliver the payload in a safe environment. And you can see in the bottom right here in this antitumor study in an in vivo model. We compared 978 directly with an approved CD19 agent, and you see superior antitumor activity. So we're very excited about CD19, CD3 978 entering into the clinic in 12 to 18 months. So hopefully, I've given you a flavor of all the work that the company has been doing in the past 12 months. We've had a very busy year of achievement in 2021. So I'd really like to thank the team for that. And we also have a significant number of milestones coming up in the next 12 to 18 months. So reflecting on the year, as I mentioned, we made significant advancements, especially with CLN-081, where we were able to update the Phase IIa data, and we also now have breakthrough therapy designation, which is really important. We also took 2 additional molecules into the clinic. So the pipeline continues to advance with 049 and 619 entering the clinic. And then over the next 12 to 18 months, we're very excited about the key value creation milestones ahead of us. So for example, regulatory activities with CLN-081, which will allow us to initiate a pivotal second-line study, of course, but at the same time, also initiate a frontline study, which will allow potentially even more patients to benefit from 081. With 049, our FLT3 T cell engager and 619 MICA, MICB antibody, hopefully, we'll plan to present clinical data updates over the next 12 to 18 months. And our fusion protein IL-2, IL-12 will enter into the clinic in the next 12 to 18 months as well as our next-generation best-in-class CD19 T-cell engagers. So lots of activity ahead, a promising future. And so in conclusion, I'd say, again, we have a very broad and deep pipeline of 8 programs that are either best-in-class and/or first-in-class potential. We're, of course, very encouraged by the CLN-081 data that we've seen to date, including the breakthrough therapy designation. But beyond CLN-081, which is, of course, a very important program for us. You can see a range of best-in-class, first-in-class molecules across hematology and solid tumor indications. So we have a very deep and rich pipeline beyond 081. And in the next 12 to 18 months, we'll have 5 highly differentiated assets entering into the clinic, which really reflects our evolution into a later-stage oncology company. And then I would say the progression of our pipeline will really drive significant value for our investors, but more importantly, allow us to deliver innovative medicines for cancer patients. So in closing, I'd really like to thank my colleagues at Cullinan Oncology for their relentless dedication, especially during this global pandemic as well as our colleagues at JPMorgan that provided the opportunity today for us to provide the exciting story of Cullinan Oncology. So with that, thanks for your attention. And Tarun, I'll turn it over to you for the Q&A session.

Thank you, Nadim, for the great presentation. I just want to call out again, if you want to ask any questions, please use the feature on our conference portal. It says ask a question, and I can ask your question to Nadim. I don't see any questions, Nadim for the moment, but I would begin with one of the key question, which is that in your new role as the CEO at Cullinan, how are you thinking about the strategic direction of the company changing, if at all? And with that, the second part of the question is that you recently had a deal with Mount Sinai for your HPK1 degrader. So shall we expect more such deals? And how are you thinking about it?

Sure. Thanks, Tarun. So I would say, in general, the overall strategic direction of the company is not changing. We have a continued focus, as I mentioned, on first-in-class, best-in-class assets. And so that remains in place, and we'll continue to both in-source innovation that meet our criteria and also advance assets that meet our criteria as well, both internally and externally. The one thing I would add, though, with the Board bringing me in with my experience, especially in late-stage development and commercialization is, we now have an additional option to actually take molecules all the way through to late-stage development and ultimately commercialization, which is based on my experience. So yes, ultimately, we do have an ambition to become an end-to-end fully integrated biotech company. And so for the right molecules and the right circumstances, we'll take them all the way through to commercialization. But at the same time, we'll also continue to partner and in-source innovation. And so to the second part of your question, look, in this business, while we would like everything to succeed in R&D, everything doesn't succeed. So for me, it's really important to continue to replenish our pipeline. And as I mentioned, we do have a robust cash-on-hand position, which does allow us to continue to do both the deals like Mount Sinai as well as advance all of our programs that we have today, either preclinical or clinically or into the clinic or late-stage development as well. So I'm very excited about the future. No overall big change to the strategic direction of the company, but we now have the added option of going all the way through to commercialization.

Got it. That's great. Just a quick check on that. Would you say your partnership is essentially going to be with academia or you are planning to do it like with big pharma or someone like other players? How are you thinking about it?

Yes. Look, I mean, we're open for business and we're willing to talk to anyone that has interesting assets that meet our criteria. We continue to have discussions with large pharma partners as well as smaller biotech companies. And we also continue our academic collaborations, which I think we have a very strong network based on the people at Cullinan Oncology that have these relationships. So for us, it's actually more about the profile of the asset as opposed to where it comes from.

Got it. That makes sense. So just moving on to your lead asset, probably CLN-081, for exon 20 EGFR and CLC patients. The market is becoming a little bit competitive, I guess, and there are some approved agents in combination therapies, which are already there. So how are you thinking about positioning or differentiating your asset compared to these agents and similar other products in the market as well?

Sure. Look, the first thing I would say is, I think, we have good molecules that are approved in this setting, and we need more therapies for these patients because there's clearly an unmet need. So let me say that first. And then secondly, I would say, look, based on the emerging data that we have seen now with 081, I think, we see a favorable safety profile, certainly based on our mechanism of action, which I think provides differentiation. I spoke earlier about the quantity of response, but now for the first time, we're seeing the quality of response. So I'm very encouraged by the durability we're seeing both in terms of median duration of response and progression-free survival. So although I'm a very competitive commercial guy, I always like to be first in class and best in class. But if I can't have first-in-class, I think, the potential to be best-in-class is exciting for us. So we do feel we have a potentially strong competitive position with the profile of CLN-081.

Got it. And just related to it, the data, I guess, what you presented is in previously heavily treated patients, I believe. So what's your view in terms of are you exploring this agent in the frontline setting as well? Because probably Tagrisso or some of the other TKIs, maybe the first line of defense for these metastatic patients. So how are you thinking about taking this product in the earlier lines of setting, if at all, and moving maybe, I don't know if it has any value in the actant setting as well? So any color on that?

Yes. So look, I think with CLN-081, based on the profile, we're seeing our clinical development team is really looking at how can the maximum number of patients benefit from this therapy. So I think the fact that we're seeing such robust efficacy and safety data in the heavily pretreated setting. Of course, the natural next step is to bring this into the first-line trial setting. And so that's part of the milestones that I mentioned over the next 12 to 18 months. We would want to start to initiate a frontline trial so that even more patients can benefit. Of course, we'll have to discuss study design, et cetera, with the FDA, but that's certainly in our plans because we want to make sure that as many patients as possible can benefit from CLN-081 in the future.

Got it. And so first of all, congratulations on getting the breakthrough tariff designation for this asset. So how does it expedite any process for you in terms of your discussions with the FDA? Or what are the next steps for it?

Sure. So first, let me say, we are still planning to provide a regulatory update in first Q of the -- first quarter of this year, which we've said previously. And I think for us, the BTD designation was somewhat of a derisking event. So one, I think, it further validates the differentiated profile of 081. Now we have external validation of that, which we're pleased with. But at the same time, it also clearly indicates that the accelerated approval pathway is still open to us. And so I think on both those fronts, it was quite a derisking event for us. And of course, we'll continue to engage with the agency. And then the third aspect of breakthrough therapy designation, of course, is that it gives you the opportunity to have enhanced discussions with the FDA because they want to help you expedite your program. That's why they give that sort of designation because of the unmet need. So we'll look to avail ourselves of the opportunity to continue to have even more enhanced discussions with the FDA, and then we'll provide a regulatory update in Q1 of this year.

Got it. So that's a nice segue. What shall we expect in this regulatory update?

Sure. So the things that obviously we're interested in is if you assume that the accelerated approval pathway is still open, part of the discussion will be the study design, for example, for our pivotal study and what that looks like. And so clearly, we'd want to have agreement with the FDA on that. That will give us an idea of time lines also of initiating study and when study will be complete. And so there -- I think, there are a few things that we really want to get engagement with the FDA on in terms of moving forward from a regulatory perspective and ultimately, approval.

Got it. So just maybe a last question on this asset itself. How are you thinking of bringing this asset into the market? First, from a clinical perspective, do you think a combination with some of the EGFR TKIs would make sense if you are moving in the frontline setting that can enhance the value? Or -- and the second part of the question is, are you going to partner with some other agent for this agent?

Sure. So our near-term immediate focus, of course, is the pivotal study that will ultimately get us to approve in the second-line plus setting, which is a monotherapy approach. So heavy focus on that for now. And so we need to continue to drive the momentum there. And then you had asked a question about the frontline setting. So I can use that as an example. There, of course, there are a range of study designs that the clinical development team is looking at. So without revealing our cards too much, I think, they can range from different types of combination approaches.

Got it. Any particular combination that you feel based on your knowledge? I don't want to reveal all your cards, but anything that you can share with us that looks [indiscernible] to you.

I think there are a range of options on the table, Tarun.

Okay. Got it. So then probably, I would move to some of the other agents, which is for the CLN-049 for AML. This space is kind of evolving a lot. And so what can you tell us more about the specific bispecific landscape? And how does your molecular gain differentiate compared to the rest of other molecules in development?

Sure. I think, first, I would say we have some very good agents that target FLT3 that are already approved on the Marketplace and obviously serving an important unmet need. With CLN-049, as I mentioned earlier, I think, the fact that we bind to the extracellular domain of FLT3, allows us to target both mutant and wild-type FLT3, which actually opens up a much bigger pool of addressable patients of 80% plus compared to the 25% or so patient population targeting mutant FLT3. So that's obviously an advantage. Two, we are the first in clinic antibody that's targeting FLT3 in this way. And so we're excited about that first-in-class potential. And look, AML is a very, very tough disease. I know personally, I've launched 2 drugs in that space and one more recently. And so I do think the potency of this molecule will be important for this type of disease, where we still see very dismal prognosis. So I think if you have a potent agent, that targets a large addressable patient population, you have the opportunity to significantly impact this disease. And of course, we've just started the clinical study. So we hope to see the preclinical data translate into the clinical setting moving forward. But this is one of those agents that has the potential to be both first-in-class and/or best-in-class as well.

Got it. So then it's a kind of a nice segue as you are saying that you are moving from preclinical to clinical. What is like you have mentioned in your presentation some of the time lines for the clinical data? And what is the benchmark that you think which is there that you are targeting or hoping to achieve in your data set?

Yes. So I would say at the moment, because we're only just started studies for both 049 and 619 in December, it's a bit early to give guidance other than saying we would plan to have a clinical update in the next 12 to 18 months, but we've really got to accrue more patients and dose more patients. And then as it pertains to benchmarks in AML specifically, I think, when you kind of look at some of the approved agents in the relapsed/refractory space, and as I mentioned, some of those I've launched myself, it's clear that there's a need for a higher complete response rate. So I think we'd be looking at the complete response rates that we induce in relapsed/refractory AML patients, for example.

Got it. And I want to touch about the other assets that you have in your pipeline, and that looks pretty exciting because there's a lot of other your colleague or peers, I would call it, which are also developing, which is CLN-619 for solid tumors. So Fate Therapeutics has announced allogeneic CAR NK cell therapy that has the MICA/B targeting. How do you see, again, your product differentiated with your competitor's product? And what would you call it, it's kind of really appealing in this domain?

Sure. So let me start out by saying I know Scott, Ed and the team at Fate. They're good friends and former colleagues of mine and that they have a really strong scientific team there. So let me start out by saying that first. I think, look, a couple of things I would say is having an antibody that is completely off the shelf is something that oncologists are used to doing from a modality perspective. So presumably, there's obviously a convenience factor there as well. We also invoked both the innate and the adaptive immune system. So I think there's a potential advantage there as well. We won't need to have conditioning chemotherapy with each cycle of treatment. So I think there are some effects of CLN-619 that are different. But at the same time, I think, Fate is doing great science and especially pushing the boundaries of what we can do with NK cells and allogeneic approaches.

Got it. Just in the interest of time, I just want to call attention that if any of our viewers have any questions, please feel free to use the feature on our portal of ask a question. We are just going to wrap up this session in a couple of minutes. So I really want to -- there are no questions, Nadim, from the portal at this moment of time. But I would love to hear your thoughts on your CLN-978, which is a CD19 by CD3 targeted approach that you have. And there are a lot of CD20 and CD3 approaches by different players, which are there in the market. How do you see your approach kind of differentiated with that? Or maybe if there are any read-throughs that we can draw or parallels from the CD20, CD3 from other agents.

Sure. So look, I would say, I'm somebody who's been very close to the CD19 market involved in the development and approval of at least one CD19 CAR-T, which I'm very proud about actually. So I would say the fact that this antibody construct has been engineered to really target low levels of CD19. So for example, CD19 loss has been implicated in certain patient subtypes. For example, with CAR-T, where we do see relapses in patients. So you can envisage a setting where in the post-CAR-T setting, you could have activity with an agent that targets very low levels of CD19 expression, for example. In addition to the broader group of patients, this is an alternative approach, again, an off-the-shelf approach that could be applied and accessible to a broader group of patients. And then, for example, relative to CD19 ADCs where you need a relative high expression level of CD19s, you could see a CD19 that targets low expression levels could have utility there also. And I think as we think about the future, it's really good that we're seeing so many treatments in lymphoma. You may see a future where you see CD19 and CD20 approaches combined to push efficacy even further. So I do think all of this research is actually great news for patients as we kind of create more modalities and look at combination approaches moving forward.

Got it. Thanks a lot, Nadim, for sharing all your views, and it has been great speaking with you. This -- we are almost there for the time for our session. So I want to thank all of our viewers and thanks a lot to you, Nadim, as well for sharing your views with us. I hope everyone enjoyed our conference and today is the last day of our conference. So wish you best of luck and have a great rest of the conference. Thank you.

Thanks, Tarun.

Thank you.