Thank you for standing by. Welcome to Schrödinger's webcast to review the phase I data for SGR-1505. My name is Rob, and I'll be your operator for today's call. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press star one. Please be advised that this call is being recorded at the company's request. Now, I would like to introduce your host for today's conference, Ms. Jaren Madden, Chief Corporate Affairs Officer and Head of Investor Relations. Please go ahead.
Thank you, and good morning, everyone. Welcome to today's webcast, where we will review phase I data from the clinical study of SGR-1505 being presented at the European Hematology Association Annual Congress. Earlier today, we issued a press release summarizing this data, which is available on our website at schrodinger.com. During today's call, management will make statements that are forward-looking and made pursuant to the Safe Harbor Provisions of the Private Securities Litigation Reform Act of 1995, including without limitation, statements related to our strategy, business plans, objectives, the expected therapeutic and clinical benefits of our product candidates, including SGR-1505, initial results from phase I clinical study of SGR-1505, and the potential of our platform. Actual results may differ materially due to a number of important factors, including considerations described in the risk factor section and elsewhere in the filings we make with the SEC.
These forward-looking statements represent our views only as of today, and we caution you that, except as required by law, we may not update them in the future, whether as a result of new information, future events, or otherwise. Moving to our agenda, this morning, Ramy Farid, our CEO, will provide a brief overview of the company. Then, Karen Akinsanya, President, Head of Therapeutics R&D and Chief Strategy Officer Partnerships, will discuss the rationale for our program and summarize the discovery of SGR-1505. Margaret Dugan, our Chief Medical Officer, will then review the therapeutic landscape and phase I data. Karen will wrap up with the opportunity and next steps for 1505, and then we'll open the call for Q&A with our speakers, as well as Richie Jain, our Chief Financial Officer. Over to you, Ramy.
Thanks, Jaren, and thank you, everyone, for joining us today. It's a really exciting day for Schrödinger with the first presentation of clinical data from our proprietary pipeline at EHA. Before I hand things over to Karen and Margaret to walk through in detail our MALT1 program, I'd like to give you a quick overview of the company first. As you can see on this slide, we have three businesses that synergistically generate value from our computational platform. We license our software to pharmaceutical, biotech, and material science companies, and also academic institutions globally. As you can see here, we have about 1,800 customers, and our retention rate is extremely high. In fact, it's 100% in the cohort of customers spending over $100,000 per year. We also have a collaboration business where we earn upfront payments and milestones and are eligible for royalties on sales.
We've also co-founded a number of biotech companies in which we have equity stakes. Finally, in the third box there, you see we have our proprietary pipeline, including our three programs phase I, where we have the potential to generate value through partnerships or other collaborations. As I said earlier, these businesses are highly synergistic. We receive significant feedback from our customers, which is used, of course, to enhance our platform, which in turn benefits our collaborators and our proprietary programs. The extensive validation we've gotten from our collaborations and proprietary programs has really been instrumental in growing our software business. On the next slide here, I'd like to spend a moment describing our vision for the future of drug discovery that drives the development of our computational platform. I think everybody understands this very well, that drug discovery is incredibly challenging.
It's a multi-parameter optimization problem, and successful drugs precisely balance a number of key properties such as potency, selectivity, permeability, solubility, and you see there are a number of other properties there. What's particularly challenging is that these properties are anti-correlated. In other words, when one property's optimized, the others tend to get worse, which is why people often refer to drug discovery as a Whac-A-Mole problem. Our goal is to enumerate massive amounts of novel chemical space and then to develop methods to compute all the properties that we just talked about that are required for a molecule to be a drug.
We have demonstrated that by combining highly accurate physics-based methods, as accurate actually as doing experiment, combining that with machine learning to allow for scale-up, for massive scale, this vision that is described here for drug discovery is being realized, where high-quality molecules can be discovered more rapidly with a much higher probability of success. On the next slide, we are really proud of the extensive validation of our platform in the form of a number of collaborative programs that we have worked on that have entered the clinic, and even two that are on the market, as you can see here. We also have a number of collaborative programs that are progressing through discovery and preclinical development.
On the next slide, we also have an extensive track record of generating value from molecules that we've discovered, either in collaboration with biotech companies that we've co-founded, such as Nimbus and Morphic, and you see there are a number of other ones here, or from proprietary programs that we've partnered with pharma companies such as BMS, Lilly, and most recently, Novartis. I'll now turn it over to Karen to discuss the mechanistic rationale for MALT1 inhibition, and she'll also summarize our discovery of SGR-1505 before handing it over to Margaret.
Thank you, Ramy. Good morning, everyone. MALT1 is an emerging genetically validated target that drives proliferation of NF-kappa B-addicted lymphomas. It is located downstream of BTK in the NF-kappa B signaling pathway, making it an attractive target for potentially a broad range of B-cell malignancies. Our preclinical data indicates that MALT1 inhibition is retained even in BTK-resistant models. We have also generated preclinical data showing a potential role for MALT1 as a combination agent with BTK and BCL2 inhibitors. Here, we show the steps we took to discover SGR-1505, and you can see the impact our platform had on the discovery process. We scored many times more potential molecules for the optimal combination of drug-like properties while ultimately synthesizing many fewer molecules, all of which got us to our development candidate in just 10 months, a fraction of the time needed with traditional methods.
The characteristics of SGR-1505 in preclinical assays and in vivo indicated a strong profile for further development. We completed the discovery and early clinical development studies in the time it can typically take to generate a development candidate. We knew from previous disclosures that inhibiting MALT1 had promise, but it was unclear whether the toxicities observed in the clinic with a prior compound were related to the target or were molecule-based. Initial evidence that SGR-1505 was well tolerated became available in 2023 when we reported data from our 73-person healthy volunteer study. The data we are sharing today builds on our prior successes. I will now turn the presentation over to Margaret to provide an overview of the relapsed refractory B-cell malignancy therapeutic landscape and a review of phase I data.
Thank you, Karen, and good morning, everyone. As Karen described earlier, the Bruton's tyrosine kinase, or BTK for short, is a key signaling molecule in the B-cell receptor signaling pathway that plays an important role in the survival and spread of malignant B-cells. BTK inhibitors were first introduced into the armamentarium for the treatment of B-cell malignancies in November 2013, with the first approval of ibrutinib for mantle cell lymphoma in patients who have received at least one prior therapy. Further approvals then followed for ibrutinib, including the treatment of CLL, SLL, Waldenström's macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. Subsequently, additional BTK inhibitors, including acalabrutinib, zanubrutinib, and pirtobrutinib, received their first approvals, starting with relapsed refractory mantle cell lymphoma.
Given the higher overall response rates and prolonged duration of responses for this class of agents, all of these agents, except pirtobrutinib, went on to be approved for the treatment of frontline CLL, either as a single agent or in combination regimens. CLL has been classified by the International CLL IPI Working Group into four risk categories of low, intermediate, high, and very high, based on genetic, biochemical, and clinical parameters. These categories define the five-year survival rate as 63% and 23% for high and very high subgroups, respectively. Although BTK inhibitors have provided excellent overall clinical outcomes, there remains an unmet medical need for novel agents and combinations to treat these higher-risk subgroups of patients with CLL. The concept of minimal residual disease, or MRD, is being evaluated to monitor disease in CLL.
As suggested by the graph, patients with CR who remain MRD positive may benefit from further treatment, while patients who revert from MRD negative to MRD positive may also benefit from further treatment. This represents an opportunity to use agents with new mechanisms of action and favorable safety profiles in this setting of MRD. I will now review phase I clinical data being presented at this year's European Hematology Association meeting. I'm very excited to share the preliminary data from phase I study in patients with relapsed or refractory B-cell malignancies. SGR-1505 was observed to have a favorable safety profile and was well tolerated. Pharmacodynamic data confirms strong target engagement, and we have observed preliminary efficacy across a broad range of B-cell malignancies in a difficult-to-treat patient population.
Our data are more mature in patients with indolent lymphomas, and we are very pleased to see monotherapy activity in patients with CLL and Waldenström's macroglobulinemia. In the following slides, I will provide more detail on these results. As a reminder, the primary objective of phase I study is to evaluate the safety and tolerability of SGR-1505 as monotherapy and to identify the maximum tolerated dose or maximum administered dose and the recommended dose for further clinical development. The secondary objectives are to characterize the pharmacokinetic profile and identify preliminary anti-tumor activity. Evaluation of pharmacodynamics is an exploratory endpoint. The study enrolled patients with relapsed or refractory B-cell malignancies following at least two prior lines of therapy. The protocol was designed to evaluate up to six dose levels with dosing schedules of either once daily or every 12 hours.
We began the study by enrolling patients with indolent malignancies. Once we reached 300 milligrams once daily and 100 milligrams every 12 hours, the protocol enabled us to enroll patients with aggressive B-cell malignancies into the study. Currently, we have defined the maximum administered dose as 300 milligrams once daily and 150 milligrams every 12 hours. At the time of our mid-May data cutoff, 49 patients were enrolled and evaluable for safety, including 18 patients with CLL or SLL, 9 patients with DLBCL, 6 with Waldenström's macroglobulinemia, and 5 with marginal zone lymphoma. This is a highly refractory patient population with a median of four prior lines of therapy. 55% of patients had previous BTK inhibitor exposure, while 18% had been treated with a BCL2 inhibitor, and 18% were double-exposed to both BTK and BCL2 inhibitors.
As shown on this slide, SGR-1505 was observed to have a favorable safety profile and was well tolerated. 43% of patients experienced a treatment-related adverse event, with the observed frequency of the more common adverse events not exceeding 12%. There were no dose-limiting toxicities observed and no deaths due to adverse events. All adverse events characterized as blood bilirubin increases were asymptomatic, were seen in patients with known UGT1A polymorphisms, and none were grade 4. There were no cases of Hy's law observed. Additionally, no cardiorenal toxicities were observed, a key point of differentiation versus previously reported MALT1 safety data, and an important aspect of our targeted product profile. We also wanted to understand the relationship between dose and inhibition of MALT1, which we assessed using IL-2 as a biomarker.
Preliminary data indicated that SGR-1505 inhibited T-cell-derived IL-2 upon ex vivo stimulation, achieving the PD target of approximately 90% inhibition at steady state in the majority of PD-available patients treated at doses of 150 milligrams or greater once daily and at all every 12-hour doses. Dosing every 12 hours provided more sustained IL-2 inhibition compared to once-daily dosing. Approximately 90% inhibition of IL-2 was observed as early as day eight. Turning to our preliminary efficacy data, 45 patients were evaluable for efficacy, and we were very pleased to see monotherapy clinical activity across a broad range of relapsed or refractory B-cell malignancies. This waterfall chart shows the best change in tumor size for all efficacy-available patients by dose levels. For Waldenström's macroglobulinemia, this is represented by best change in serum IgM levels.
The bar-shaded blue represent the once-daily dosing cohorts, while the bar-shaded green represent the every 12-hour dosing cohorts. As seen in the legend, we have indicated other key information, including whether a patient was still on treatment and whether patients had previously been treated with a BTK inhibitor or double-exposed to a BTK and BCL2 inhibitor. In this heavily pretreated patient population, the majority of patients have had some evidence of tumor shrinkage. Looking from left to right and beginning with patients with indolent disease, three out of 17 CLL patients responded. These responses were independently reviewed and confirmed, one PR and two PR with lymphocytosis. Two of these three CLL patients with partial responses were double-exposed to BTK and BCL2 inhibitors.
We also reported a partial metabolic response in one patient with a marginal zone lymphoma, and responses were seen in all five patients with Waldenström's macroglobulinemia, all of whom were last treated with a BTK inhibitor prior to starting SGR-1505. As I noted earlier, we recently began enrolling patients with aggressive lymphomas into the 300 milligram daily and 100 milligram every 12-hour dosing cohorts. A PR was also reported in one of the four ABC DLBCL patients. Taken together, 10 out of 45 patients across multiple dose levels responded for an overall response rate of 22%. We are also reporting initial data showing duration of treatment for 33 patients with indolent lymphomas, as these were the first patients to come on study.
While it is too early to report a median duration of response, we are encouraged that 13 of these patients remained on study at the time of the data cutoff, and a patient with Waldenström's macroglobulinemia has been on treatment for nearly two years. More than half of the evaluable CLL or SLL patients have been previously exposed to a BTK inhibitor. 35% of evaluable CLL or SLL patients were double-exposed to both BTK and BCL2 inhibitors. Of these patients, encouraging preliminary efficacy signals have been seen in two of six patients. Overall, these preliminary data are very encouraging. SGR-1505 was observed to be well tolerated with a favorable safety profile. Pharmacodynamic data confirmed inhibition of MALT1, and we have demonstrated monotherapy activity in a range of B-cell malignancies, including CLL or SLL and Waldenström's macroglobulinemia, in a highly refractory patient population.
Dose escalation is complete, and we plan to discuss the next steps for this program with the FDA later this year. I want to thank the investigators, patients, and their families who have been involved with this clinical study. We are very appreciative of your support. I will now turn the call back to Karen.
Thank you, Margaret. With these results in hand, we are very enthusiastic about the potential for MALT1. As we can see, the treatment landscape for B-cell malignancies has continued to evolve. Most notably, BTK inhibitors such as ibrutinib and next generation covalent and non-covalent inhibitors have been the mainstay of therapy for several decades. While these agents have brought significant improvements to the lives of patients, resistance mutations such as C481S and L528W have emerged and are associated with treatment failure. This dynamic creates an opportunity to explore additional emerging targets such as MALT1. The development of acquired resistance remains an ongoing challenge that is yet to be fully resolved. Mechanisms underlying treatment resistance include secondary mutations within the drug target and activation of bypass pathways. MALT1 has been shown to be an escape mechanism in B-cell malignancies.
Potential strategies to prevent and overcome resistance include targeting bypass mechanisms and combining therapies. We have evaluated the potential for SGR-1505 to be used as part of a combination regimen. Deeper anti-tumor activity was observed when SGR-1505 was combined with BTK and BCL2 inhibitors in preclinical studies. Exploring combinations in the clinical setting is a key next step for the SGR-1505 development program. Approved targeted therapies like BTK inhibitors have demonstrated clinical success and widespread use. However, for patients with resistance to BTK agents, new approaches are needed. Drugs like SGR-1505 that are well tolerated and target a distinct cellular pathway via inhibition of MALT1 have potential as future therapeutic options. Based on the genetic evidence, as well as available preclinical and now clinical data, we believe MALT1 inhibition has potential in multiple indications.
We are particularly excited that all evaluable Waldenström's macroglobulinemia patients responded, despite having prior BTK therapy. We are also encouraged by the responses observed in double-exposed CLL patients. The efficiency with which we identified SGR-1505 is another compelling example of the power of using computation at scale in drug discovery. We believe the data we have shown today, while preliminary, suggest SGR-1505 could be a best-in-class MALT1 inhibitor and that this target has a potentially important role in the treatment of B-cell lymphomas. Finally, SGR-1505 is an advanced example of the larger portfolio, which includes wholly owned and collaboration molecules. We look forward to sharing initial data from our other two proprietary assets, our CDC7 inhibitor, SGR-2921, and our Wee1/Myt1 dual inhibitor, SGR-3515, in the second half of this year. We will now take your questions.
Thank you. We will now begin the question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again. We ask that you please limit yourself to one question and one follow-up. Your first question comes from the line of Michael Yee from Jefferies. Your line is open.
Hey, guys. Thanks for taking our questions. This is Kyle Yang from Michael Yee. Could you please briefly talk about your strategy in more aggressive lymphomas, particularly in DLBCL, given we only saw one response there? Could you please elaborate your development strategy there to maximize your efficacy and benefits in these patients? Are you going to do a dose expansion study with 300 mcg dose? If that's the case, when should we expect the data? Thanks so much.
Thanks for the question. I'll start, and then maybe Margaret can add to this. One of the things that Margaret shared in terms of the design of the study is that we had dose-escalated in indolent patients as per the protocol. The aggressive patients were really only recently brought on study. That one response that you saw was a result of the most recent patients on study. With respect to the next steps and how we think about the study, obviously, we're still completing the phase one. Margaret, would you like to add?
Yes. We believe we have a comprehensive package for pharmacokinetics, safety, pharmacodynamics, and efficacy that we will be discussing with the FDA, which is the next step to learn about the recommended phase II dose with them. We are continuing to enroll more patients in terms of aggressive lymphomas as the protocol dictated that they could not be enrolled till we were at the higher doses on both schedules. As we accumulate more data, we'll be able to design further studies in aggressive lymphomas as well.
Just a quick follow-up, guys. Prior to your discussions with the FDA, what kind of data do you have to show to support the development of combination strategy in phase II, for example? Thanks.
I mean, I think the conversation with the FDA will be about the recommended phase II dose as monotherapy. I think the data that we would have to show for combination is really around safety. As you're aware, for combinations, one will have to study the safety of that combination as an initial step. I don't know that there's any additional data we have to show the FDA other than the package that we've accumulated, which is that the drug is safe and well tolerated, that we've hit the target, and that we think that there is an opportunity now to go ahead and study this in combination with BTK inhibitors.
Okay. Thanks so much, guys.
Thank you. Your next question comes from a line of Evan Segerman from BMO Capital Markets. Your line is open.
Hi there. This is Conor McKay on for Evan. Thanks for taking our question and congrats on all the data. I guess maybe with these data in hand, can you maybe share a little bit how you're thinking about the development path from here? Would you look to partner the combination studies with other companies who may have approved BTK agents, or would you look to run those studies internally? Thank you.
Yeah. As we've discussed in the past, and you had us again reiterate today, we do believe that MALT1 is a drug that will be effective in combinations based on our preclinical package. We believe that the access to those drugs is going to be best acquired in the setting of a partnership because the standard of care agents are in the hands of large pharma at this point. Yes, we do believe that the combination studies, as we've said, are the future of this mechanism and that that is probably best done in the context of a partnership. As you're aware, there's many types of partnerships that one can pursue.
Thank you.
Your next question comes from a line of Mani Foroohar from Leerink Partners. Your line is open.
Hey, guys. Thanks for taking our question. You have Ryan on for Manny. Just hoping you could elaborate a little more on what you hope to see in a phase II trial design in terms of indication selection, as well as I know you, Karen, you briefly talked about partnerships, and just wondering your perspective on what you think an ideal partner looks like and what they'd be able to bring to the table. Thanks.
Maybe, Margaret, you can take the first question about the phase II design and preliminary thoughts. Obviously, we haven't concluded that at this point, given that we are still looking towards the FDA interaction. Maybe, Margaret, you can share your thoughts.
Thank you, Karen. As we continue to enroll patients again, we're accumulating more data in the indications of CLL and Waldenström, where we are excited about the level of activity we're seeing there, especially in terms of enrolling more patients with double-exposed CLL exposed to both BTK and BCL2 inhibitors because that's where the field is leading in the treatment of CLL. We are accumulating more data in terms of the aggressive lymphomas. We showed the one responder in ABC DLBCL. Again, we were restricted until the later phases of this study in enrolling the variety of aggressive lymphomas. As the data emerges and depending upon the level of activity in a specific B-cell malignancy subtype, that will dictate the design of the phase II studies.
From a partnership perspective, I think you asked about the type of partner. I mean, I think as you saw in our review of the landscape, the standard of care agents, that space is evolving. Obviously, you've got first-generation BTK inhibitors, you've got the covalents, then you've got the non-covalents, and then you have additional types of BTK inhibitors that are emerging. That is still to be determined. Obviously, MALT1, we believe, will be part of the future landscape in treatment of B-cell malignancies. That is going to require some additional thought about the best potential combination for that situation.
Your next question comes from a line of Vikram Porochit from Morgan Stanley. Your line is open.
Hi, good morning, everyone. Thanks for taking our questions. We have two. First, you mentioned that it took around 10 months for you all to identify 1505. We were wondering, was there anything specific about your work on this target or this program that helped you collapse timelines, or do you think that there are kind of read-throughs here to how quickly you're able to develop other programs in your proprietary pipeline? Is that 10 months scalable across the pipeline, or is that something specific to the 1505 that you were able to work with?
For CLL and SLL, just kind of based on the activity levels you're seeing currently, I guess, where would you see 1505 fitting kind of into the commercial kind of treatment paradigm based on what's already available and then also some of the other competitive agents in development for the indication? Thank you.
Yeah. With regard to your question about whether this is transferable to other programs, absolutely. There are certain requirements. For example, as we've said many times, the availability of an initial structure of the target and understanding of the binding site. We really think when you have that, and then the methods are quite accurate, it's possible to then, as we said in the presentation, numerate huge amounts of chemical space and identify high-quality molecules. Absolutely transferable, and not just by us, but of course by our customers who happen to have access to the technology, the scale that's required to be able to explore this amount of chemical space.
The second question with respect to CLL, SLL, Margaret shared with you that there are very different risk categories in CLL. I think one of the things that we're going to be discussing with KOLs and with future partners is really the question of which subset one should go after. It's very clear that people who are double-exposed to BTK and BCL2 inhibitors who are failing therapy have very limited remaining options. We think that's particularly interesting with respect to a novel mechanism like MALT1, but there's a lot more to discuss. Margaret, do you want to add anything to that?
No, I think as we've shown in the, as I alluded to in terms of the armamentarium in CLL, I think there's many of these related to BTK inhibitors and BCL2 inhibitors. The MALT1 inhibitors offer a huge opportunity in order to enhance those activities across all stages of the CLL.
Got it. Thank you for the context.
Your next question comes from a line of David Lebowitz from Citi. Your line is open.
Hi, good morning. Thank you for taking our questions. This is Ike Lee on for David Lebowitz. Could you remind us about the development pathway that Ibrutinib took when it first got discovered and went through its long regulatory process of indications and label expansions? How does that inform your thinking previously discussed about picking the next indication forward? Thanks.
Yeah. The landscape has changed quite significantly since Ibrutinib was developed. As Margaret alluded to, and perhaps, Margaret, I can turn this over to you. You actually explained during the presentation the history of Ibrutinib approval. Maybe you can comment on how you think that might impact the next steps.
Yes, thank you, Karen. Imbruvica began its first approval in Waldenström's macroglobulinemia as well as they had other studies ongoing in the other indications in B-cell lymphoma. That was quickly followed with approvals in the relapsed refractory setting. Traditional in oncology is to go where there is the most unmet medical need. Imbruvica, as well as the other companies, then moved these compounds forward into earlier lines, frontline CLL, frontline other of these B-cell malignancies, and then started to work in terms of improving upon those activity levels with combination of agents in the frontline setting mostly. We see where we are now that we have the similar encouraging data in Waldenström's macroglobulinemia in the unmet medical need situation, which is standard phase I development.
We are highly encouraged that the five out of five who are immediately failing a BTK inhibitor have responded to the MALT1 inhibitor 1505. We will look forward to further developing that initially in those who have failed BTK inhibitor, as that would be the traditional development path. In terms of CLL, there are opportunities that exist now, having failed a BTK and a BCL2 inhibitor, which is why we are continuing to enroll those CLL patients who have what we call double-exposed. We will follow that pattern as that is dictated by the early development in the phase one program. In addition, we will look to the combination approach, as we said, the preclinical data as well as the need to have another pathway besides the BTK pathway that will help improve upon the existing activity seen with BTK and BCL2 inhibitors.
Just a quick follow-up here. When you talk about the indications like WM and maybe CLL, SLL, have you done the market research yet as to how large the market opportunity is, especially in some of these later lines, the fact that you have to wait until they fail BTK inhibitors and such? Is it a little bit too early to be doing that research?
Yeah. Obviously, we're excited about these results. We believe that that's work that's ahead of us. We have not done a deep dive into very specific numbers, but obviously, that's an interesting next step in collaboration with partners, potential partners, and also with KOLs.
Thanks. Congrats on the process.
Thank you.
Thank you. Again, if you'd like to ask a question, press star 1 on your telephone keypad. Your next question comes from a line of Matt Hewitt from Craig-Hallum. Your line is open.
Good morning, and thanks for taking the questions. Maybe first up, how important is it to have a partnership in place before you kick off a phase II study? I'm just curious, is that something that is necessary, especially as you're talking to the FDA about structure of the trial and targets and whatnot, or is that something that you could do on your own and hopefully the potential partner agrees with the trial setup?
Thanks, Matt. One thing I will just reiterate, and Ramy covered this actually on his slide when he talked about how we've been sort of progressing our pipeline, is that we are constantly in conversation with partners to understand and align on what we believe the opportunities are for the targets that we're working on. While we're not talking about specific partnerships today, we have been discussing the opportunity for a MALT1 inhibitor, for how one might pursue this with both partners, potential partners, with KOLs, and really getting a sort of picture of how the industry and the community in the B-cell malignancy space would receive a MALT1 inhibitor and what kind of sequencing of indications and opportunities there are. I don't believe that we necessarily need a partner to be able to do those studies, but that discussion has been ongoing.
It's very important that we're all aligned on the opportunity for MALT1 and how best to pursue it.
I guess maybe a follow-up to that would be in a situation, and I don't know that this is necessarily it, but in a situation where you are talking to potential partners, but they have divergent pathways that they would want to explore, how do you choose or select which path to take knowing that it may limit your potential for a partner?
If I'm following your question, I'm going to start with a scientific answer, which is that the decision around which pathway or fungal pathway to choose, let's say, to combine with a MALT1 is really based on existing data. We showed you today BCL2 inhibitors and BTK inhibitors in our hands in preclinical studies combined very well with a MALT1 inhibitor and enhanced the response. The discussion around whether one would choose a first-generation, a next-generation, a BTK or BCL2 inhibitor, I think is ahead of us. I think that every company is going to have their own view on that, but I think we'll be able to settle on the right decision for patients and for the asset as a next step.
All right. That's helpful. Thank you.
Your next question comes from a line of Brendan Smith from TD Cowen. Your line is open.
Hi, this is Jackie on for Brendan. Thanks for taking the questions. Do you have any color onto when we could potentially see any type of follow-on efficacy data? How do you expect that kind of package would be structured in terms of expected timelines and cohort size?
Margaret, do you want to take that question?
Yes, thank you. We've completed the dose escalation, and we're continuing to enroll patients with a focus on where we've seen activity to date, CLL, Waldenström's, and the aggressive lymphomas. We will be discussing this with the FDA. Further data that we'll be able to provide, we'll see the ASH deadline is in August. We've given you the data up until May, towards mid-end of May. We'll see how much more substantive information that we have that we could put into a presentation at that time.
That's super helpful. Maybe one brief one. Is there any specific result or finding in particular you would say, you would highlight that differentiates 1505 most within this competitive landscape?
I think what we've seen and demonstrated is that the compound has a reserved safety profile that is very safe and well tolerated. I think that distinguishes this compound from the ability in order to move forward as a single agent, but more importantly, to combine it with the other agents that are being used in the B-cell malignancies, of which we know they do have substantial toxicities. It's obvious that you can't move forward without having efficacy, and we do have efficacy as well across multiple B-cell malignancies. For us, the most important aspect here is that we are safe.
Great. Thank you so much.
Your next question comes from a line of Michael Yee from Jefferies. Your line is open.
Hey, guys. Thank you for the follow-up. Following along the important idea of safety, can you clarify the interpretation of blood bilirubin elevations versus the numbers that we're seeing for laboratory bilirubin elevations and how that would compare to the competitor, for example, J&J, which had numbers that were concerning for them? How does this fit into the idea of your combination, which of course is really the focus with EMOs or other agents? You expect that 300 milligrams will be the dose that will be safe and should be okay. Thank you.
Thanks, Mike. Maybe I can start, and Margaret can give you some more detail on the findings. Mike, you're reiterating, I think, the observation in the prior clinical disclosure for MALT1 inhibitor that there were adverse events of hyperbilirubinemia and safety concerns around dose-limiting toxicity, cardiorenal in nature, which we believe would limit the potential for combinations. What Margaret shared with you today is that we have blood lab changes, and maybe Margaret can fill you in there on the difference between the AEs that were seen with the prime molecule and what we're seeing here in terms of blood bilirubin changes and who we're seeing them in. Margaret?
Yes, thank you, Karen. What we've reported in terms of bilirubin blood increases as an adverse event, those were dictated by the protocol where ever a lab abnormality is elevated and causes either study discontinuation or high level, it's reported as an adverse event. However, these were not with associated toxicities that you would ordinarily see with an elevated bilirubin. There was no jaundice, no itching. They were pretty much asymptomatic. They were low grade, and only one was it associated with some transaminase elevations, which were intermittent and not suggestive of having hepatic toxicity. When you look at the overall incidence of lab abnormalities of having bilirubin elevations, they also are predominantly low grade, and they did not translate into a high level of adverse events.
I think one more observation is that we're seeing this in individuals who have what are called UGT1A1 polymorphisms. This is where people have a mutation in that particular enzyme. They're the ones where one is seeing more of these blood increases in bilirubin. As we've discussed, there are drugs that are on the market that have this kind of characteristic, including the HIV inhibitors.
I am showing no further questions at this time. That concludes today's call. You may now disconnect.