Kymera Therapeutics, Inc. (NASDAQ:KYMR) Q3 2023 Earnings Call Transcript

Kymera Therapeutics, Inc. (NASDAQ:KYMR) Q3 2023 Earnings Call Transcript November 4, 2023

Operator: Good day, and welcome to the Kymera Therapeutics Third Quarter 2023 Results Call. [Operator Instructions]. Please note that this event is being recorded. I’d like to turn the conference over to Ms. Justine Koenigsberg, Vice President of Investor Relations. Please go ahead.

Justine Koenigsberg: Good morning, and welcome to Kymera’s Quarterly Update. Joining me on this morning’s call are Nello Mainolfi, Founder, President, and CEO; Jared Gollob, our Chief Medical Officer; and Bruce Jacobs, Chief Financial Officer. Following our remarks and presentation, we will open the call to questions. During the Q&A portion of the call, please limit your question to one and a related follow-up so that we will have enough time to address everyone’s questions. Please note that we will be referencing slides in our corporate presentation during Jared’s remarks. The slides can be accessed in the Investors section of our website, under Events and Presentations, and will be shown during the call for those on the webcast.

Before we begin, today’s discussion will include forward-looking statements about our future expectations, plans, and prospects. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected. A description of these risks can be found in our most recent 10-Q filed with the SEC. Any forward-looking statements speak only as of today’s date, and we assume no obligation to update any forward-looking statements made on today’s call. With that, I would now like to turn the call over to Nello.

Nello Mainolfi: Thank you, Justine, and thanks, everybody, for joining us today. We’re excited to review our recent progress and several critical milestones that the company has achieved. As we are near the end of 2023, I’m extremely proud of the strong execution by our team that has led to continued progress in our clinical studies across multiple programs along with innovative pipeline advancements to support our future growth. Before we detail that progress, I want to share a few thoughts on where Kymera is in our mission to building a best-in-class, fully integrated, global degrader medicine company. In doing so, I hope to provide you with an important lens through which you can view our achievements and our strategic decisions regarding the portfolio.

Our unique approach to developing a new generation of medicines using TPD has resulted in a robust pipeline, both in the clinic and underway to the clinic, highlighted by multiple programs that are guided by and consistent with our goal of creating groundbreaking medicines. I hope there is broad appreciation for all that Kymera’s accomplished since our founding only seven years ago. We have taken four programs in the clinic, demonstrating fidelity of translation of PK/PD and safety across each of those programs. We have shown early clinical proof of concept for three of them as you will hear soon. Our unique strategy has allowed us to achieve multiple TPD firsts, including conducting the first I&I study in healthy volunteers and patients with KT-474, targeting IRAK4.

In addition, we’ve been the first degrade, and elusive transcription factor like, STAT3. More strategically, for KT-474, we formed a critical collaboration with Sanofi, one of the leaders in the I&I space. And that program is now advancing in Phase II development, with the first patient in the first trial just recently dosed. We have built industry-leading knowledge and capabilities that we’re leveraging each and every day. And we have developed a best-in-class pipeline of innovative and highly valuable programs, some of which we would be excited to share with you over the coming months. An important cornerstone of Kymera’s success has been our unique approach to target selection, which has several key tenets that guide our strategy and, of course, our research and development efforts.

Our focus is and has always been on genetically validated targets that are either undrugged or inadequately drug within pathways with clear validation and where TPD is the best or only solution. Importantly, we target large market opportunities where the unmet needs are significant and where we believe that there is a greater probability and opportunity for significant commercial success. With regards to therapeutic areas, our programs have progressed over the last several years. And as you can see from the pipeline slide on our website and in our corporate presentation, Slide 6, our portfolio is increasingly leaned towards immunology. This is a purposeful strategy orientation guided by several factors that have influenced our strategic and investment decisions.

You will hear a more complete overview of this focus at our R&D Day on January 4. But today, I’d like to highlight a few. First, it is clear that I&I is an area where the understanding of the underlying biology has increased dramatically. Second, the large commercial opportunities within I&I are mostly dominated by biologics that have helped validate key pathways and targets, but also create an opportunity for other more convenient modalities. And at last but least for today, to that point, we believe that TPD can provide a unique solution with strong efficacy and biologics-like specificity, but with the flexibility of all our small molecules. Importantly, we hope you all appreciate that we have demonstrated early but convincing evidence of our potential in I&I with KT-474.

In fact, we believe strongly that the success we’ve had with our IRAK4 program will help shape how we approach these new opportunities. We have countless learnings from that program, starting with the development of the molecule itself, including our extensive preclinical work, and the key insight we’ve gained from running what we believe is the largest healthy volunteers subsequent patient study in the TPD space. And now, KT-474 is undergoing Phase II studies with our partner, Sanofi. This wealth of experience and knowledge gives us a high degree of confidence in our ability to execute on many new opportunities, some of which we will be sharing with all of you in the coming months. We’ve also made important progress in the clinic with KT-333, which targets STAT3, and KT-253, our MDM2 degrader.

Jared will provide updates on both programs later during the call. At a high level, we’re very excited that KT-333 will appear in an ASH abstract later this morning and would be featured in a poster presentation, with updated clinical data at the ASH meeting in December. It’s important to note that we’re seeing early signs of clinical activity, even at those levels that were not predicted to be clinically active, but where we are, nonetheless, seeing robust STAT3 degradation. Jared will share a few highlights on this call. And we will be able to say more once the accepted abstract is publicly released, which should be shortly after our call concludes this morning. We’re also excited about early days emerging from KT-253 Phase I dose escalation study.

We’ve demonstrated both proof of mechanism and early signs of clinical activity in initial dose levels, even earlier than we expected. The early clinical activity, lack of thrombocytopenia neutropenia in the presence of antitumor activity makes us optimistic about the translation of anti-grade rationale of increased therapeutic index and full realization of p53 pathway potential. With regards to KT-413, a degrader, we have decided to discontinue the program. Let me first say that this decision is not driven by any clinical data or safety concerns that we have with the program. We are degrading the targets in blood as we had expected, and we have not experienced those limiting toxicities. Rather, our decision to discontinue KT-413 reflects our commitment to the program that more closely fit the previously mentioned strategic focus of the company.

More specifically, when we evaluate the evolving healthcare landscape, especially in oncology and the market opportunity and the competitive landscape in the diffuse large B-cell lymphoma and juxtapose that with the enormous opportunities we have in our emerging pipeline, we have decided the right strategic decision is to focus our resources on those high-value programs. It should also be noted that we did not take this decision lightly nor did we make it without thinking about the potential impact on patients. But as many of you already know, the DLBCL market is well served today with numerous active agents. And we believe promising therapies will continue to emerge in the relapsed/refractory and frontline settings. Ultimately, we believe that Kymera can have the greatest impact by focusing on areas of significant unmet patient need where TPD can have the greatest impact.

We’ve built a team with leading expertise in drug discovery and development capabilities, which we believe provides Kymera with a strong competitive advantage. And perhaps, most importantly, as I’ve already highlighted, we have shown our ability to execute with the development of KT-474, which has achieved another significant milestone with the dosing of the first patient in the Phase II study. At our immunology R&D Day in January, we would provide an even clearer picture of the strategic focus that we’re outlining today, highlighted by what we believe are both important and exciting pipeline disclosures. We’re confident then, when we share the details around our next program and our strategies for building Kymera into an industry-leading, fully integrated biotech company, you will appreciate our enthusiasm for the enormous opportunities those programs represent.

I can tell, and I would likely repeat these when we gather in January, I’ve never been more encouraged and excited by the pipeline opportunities on which Kymera is poised to capitalize. Finally, Kymera remains very well capitalized, which puts us in a strong position to execute on the opportunities our pipeline presents. As we noted in today’s press release, we have extended our runway into the first half of 2026. This takes us well beyond several key catalysts and data readouts that we expect to be important derisking events for our clinical and preclinical pipeline, including Phase II data on KT-474, further POC readouts for our oncology programs, and important updates on our pipeline. More details about which will be shared at an upcoming Immunology R&D Day.

Let me pause here and turn the discussion to Jared.

Jared Gollob : Thanks, Nello. The focus of my comments today will be primarily on KT-333 and KT-253 and new clinical data we are announcing this morning. As Nello mentioned, we’re very happy that our clinical abstract relating to KT-333, our first-in-class small molecule degrader of STAT3 was accepted for a poster presentation at ASH. The full abstract will be available online shortly, but I will share a few highlights shown on Slide 29. And we, of course, will be available for follow-up once the full abstract is released. For context, July 10 was our abstract data cutoff date. As of that date, 21 patients have been treated across five dose levels, of which 12 were evaluable for disease response. The patients included a variety of liquid and solid tumors.

All our comments today are based on that July 10 cutoff date. The data in the abstract show continued evidence in blood of robust STAT3 protein degradation in humans, with associated STAT3 pathway inhibition with dose levels three and beyond expected to be clinically active, along with potential early signs of antitumor activity. As mentioned, there were 12 evaluable patients in dose levels one through four, of which just two were liquid tumors at dose level two. Of those two liquid tumor patients treated at dose level two, we saw one partial response after two cycles in a patient with CTCL, a T-cell lymphoma, where we saw substantial activity with the STAT3 degrader in a preclinical STAT3-dependent mouse model. Among the 10 solid tumor patients available for disease assessment, which is a group where we do not expect to see monotherapy clinical activity based on our preclinical studies, we saw a stable disease in three patients after two cycles at dose levels three and four.

Importantly, from a safety perspective, no DLTs were observed, and no drug-related SAEs were reported. Safety and PD were consistent with previous updates. These early findings are encouraging and support the potential of heterobifunctional degraders for targeting previously undruggable transcription factors implicated in diseases. Accrual is ongoing, and therefore, we expect to present additional data in patients with hematological malignancies, including T-cell lymphomas and leukemias, and solid tumors beyond what is in the abstract. We look forward to providing more details, both after the publication of the abstract today, as well as next month at the ASH meeting at the time of the poster presentation. Additionally, in September, we announced that the FDA granted Fast Track designation for KT-333 for the treatment of relapsed/refractory cutaneous T-cell lymphoma and relapsed/refractory peripheral T-cell cell lymphoma.

We’re happy that FDA gave this designation to the program as it further highlights the promise of degrading STAT3, a protein that has historically been undruggable for the treatment of patients with CTCL and PTCL. Turning now to KT-253, our MDM2 degrader. We are disclosing clinical data from Arm A of the ongoing Phase Ia trial for the first time this morning. We are pleased to report that we have demonstrated KT-253 clinical proof of mechanism and initial signs of clinical activity in just the first two dose levels in patients. We have slides that highlight some of our results in the corporate presentation posted in the IR section of our website, but I will briefly summarize and we can take questions in Q&A. As shown on Slide 32, KT-253 degrades MDM2, the crucial regulator of the most common tumor suppressor p53.

p53 remains intact and close to 50% of cancers, meaning that it retains its ability to modulate cancer cell growth. While small molecule inhibitors have been developed to stabilize and upregulate p53 expression. They have been found to induce a feedback loop that increases MDM2 protein levels, which can repress p53, and therefore limit their efficacy. In preclinical studies, KT-253 has shown the ability to overcome the MDM2 feedback loop, and thereby robustly activate the p53 pathway even with brief exposures. As shown on Slide 33, KT-253 is greater than 200-fold more potent than MDM2 small molecule inhibitors in upregulating p53, and killing p53 wild-type cancer cells. Slide 34 shows that KT-253 more effectively upregulates and activates p53 in tumors in vivo, compared to small molecule MDM2 inhibitors.

And this translates into antitumor responses in AML and ALL models with just single doses of KT-253. These results support an intermittent dosing strategy for KT-253 that enables maximum p53 pathway activation for a limited period of time in tumor cells, leading to rapid apoptosis, while mitigating the impact of target engagement in normal cells in order to improve the therapeutic index relative to MDM2 small molecule inhibitors. As shown on Slide 35, the KT-253 Phase Ia trial is an open-label dose escalation study, where adult patients with relapsed or refractory high-grade myeloid malignancies, ALL, lymphomas and solid tumors receive IV doses of KT-253 once every three weeks. The study is intended to evaluate safety, tolerability, PK/PD, and initial clinical activity, and allow us to identify the recommended Phase II dose.

It is comprised of two Arms, with ascending doses of KT-253 in each arm. Arm A is in patients with advanced solid tumors and lymphomas and Arm B is in patients with relapsed/refractory high-grade myeloid malignancies including AML and ALL. We dosed our first patient in Arm A, and have fully enrolled the first two dose levels in Arm A, with enrollment to dose level 3 ongoing. Enrollment on to Arm B has also been recently initiated following demonstration of on-target pharmacology and the first two dose levels of Arm A. As of the October 20 data cutoff date, a total of nine patients with solid tumors have been enrolled on to dose levels one through three of Arm A, and have received a mean of 2.3 cycles with a range of one to six cycles. As shown in Slide 36, proof of mechanism has already been demonstrated in the first two dose levels, with exposure-dependent upregulation of plasma GDF15 levels.

GDF15 is a transcriptional target of p53, and as such, it serves as a downstream biomarker of p53 upregulation following MDM2 degradation. In addition to the dose proportional increase in plasma KT-253 levels between dose levels one and dose levels two in cycle one, the GDF15 maximum fold increase over baseline during cycle one was 10 in dose level one, and 30 in dose level two. The kinetics of GDF15 change following the cycle one dose is shown on Slide 36, for a subject on dose level one, where brisk upregulation over the first 24 hours after dosing was followed by a recovery towards baseline over the subsequent six days. This was consistent with the pattern of p53 activation in preclinical models associated with KT-253 antitumor activity.

Clinical response results for all patients within a dose cohort were available for dose level one, and are shown on Slide 37. Even though based on exposures, we did not expect this dose level to be clinically active, we were encouraged to see that among the three solid tumor patients treated on dose level one, there was one confirmed partial response after four cycles with treatment continuing after six cycles, one confirmed stable disease after four cycles with the patient subsequently discontinued from the study after six cycles for lack of response, and one patient with disease progression after cycle one. The patient with a partial response had Merkel cell carcinoma, metastatic to abdominal lymph nodes and skin who had previously been treated with chemotherapy as well as multiple different immune checkpoint inhibitors.

As shown on Slide 37, the lymph node metastases were responding after the first two cycles of treatment as was the skin metastasis. And after four cycles, there was an approximately 60% reduction in nodal tumor burden and resolution of the skin metastasis. There were no dose-limiting toxicities. As shown on Slide 38, the most common drug-related AEs occurring in two or more patients included grade 1, 2 nausea, and grade 1 diarrhea. one patient at dose level one had an SAE of grade 3 hypotension during cycle four that was due to diminished oral intake deemed related to study drug. Treatment included IV fluids in the patient remains on study without dose reduction or recurrence of hypotension. There were no neutropenia or thrombocytopenia AEs even in patients who had received up to six cycles of therapy.

In summary, on Slide 39, these promising interim clinical data showing evidence of target engagement and p53 pathway activation, along with initial signs of antitumor activity without DLTs, including typical hematological toxicity, are supportive of our therapeutic hypothesis for MDM2 degraders, and the potential to improve the therapeutic index compared to MDM2 small molecule inhibitors. As we continue to explore the safety and clinical activity of KT-253 in both solid and liquid tumors in Phase Ia, we are also putting together a comprehensive preclinical and clinical data set examining the factors impacting in vivo response to intermittent dosing with KT-253 across multiple different solid and liquid tumor types in order to derive patient selection biomarkers for the next stage of development after Phase Ia. Disclosure of additional clinical data as well as preclinical data, informing a biomarker-based patient selection strategy is planned for 2024.

Finally, a quick update on KT-474, our IRAK4 degrader, which is now in Phase II development under the direction of our partner, Sanofi. As we recently disclosed, the first patient in the HS trial has been dosed, and we are excited about the significant milestone for Kymera. In addition, the AD trial recently commenced, and we will report news of the first patient dosed in that trial after it occurs. The details around the study designs for both trials are available on clinicaltrials.gov, and we have a summary on Slide 20. At a high level, the trials are powered to show a treatment effect relative to placebo and will also provide a comprehensive assessment of safety and on-target PD. Dose escalation was informed by the safety, PD, and clinical efficacy data from the patient cohort in our Phase I study, and both trials will evaluate KT-474 versus placebo for 16 weeks.

The HS study will enroll up to approximately 100 patients, and the AD study up to 115 patients. Both studies include standard endpoints measuring skin lesion burden and symptoms. In the HS study, these include AN count, HiSCR, IHS4, and pain measures. While in the AD trial, these include EASI score, along with vIGA-AD and Pruritus measures. Both HS and AD represent important indications with significant unmet patient needs, and we’re excited to see our partner, Sanofi, advance the program into Phase II. As noted in the clinicaltrials.gov posting, both trials have primary completion dates in Q1 2025, anticipating completion of enrollment in 2024, and top line data in the first half of 2025. I’ll pause here and turn the discussion to Bruce to review the financials.

Bruce Jacobs : Thanks, Jared. As I review our Q3 financial highlights, please reference the financial tables found in today’s press release. For the quarter, we recognized $4.7 million of collaboration revenue, all of which was related to our Sanofi collaboration. At the end of the quarter, our deferred revenue total on the balance sheet was approximately $43.8 million that reflects Sanofi partnership revenue that we expect to recognize over the next several years, excluding the receipt of any potential future milestones. As announced last week, Kymera will receive a $40 million milestone payment, triggered by the first patient dosed in the KT-474 HS trial. We include this milestone and the next milestone we expect for the first patient dosed in the AD study in our cash runway guidance, although it is not reflected in the cash balances at the end of the quarter.

Given that both of these payments are anticipated to occur in the fourth quarter of ’23, we expect both to initially be recorded as deferred revenue and to begin being recognized as revenue in the fourth quarter of 2023. With respect to operating expenses, R&D for the quarter was $48.1 million. Of that, approximately $5.8 million represented noncash stock-based compensation, making the adjusted cash R&D spend $42.3 million, which excludes that stock-based comp and reflects a 5% increase from the comparable amount in the prior quarter. On the G&A side, our spending for the quarter was $14.1 million, of which $5.9 million represented noncash stock-based comp, the adjusted cash G&A spend of $8.2 million, again, excluding stock-based compensation, reflects a 5% decrease from the comparable amount in the prior quarter.

We ended the third quarter of 2023 with $435 million in cash and equivalents under our current operating plan, which again includes the aforementioned portfolio actions. We expect our cash and cash equivalents to fund the company into the first half of 2026. This concludes our prepared remarks, and we’d be happy to now address any questions. Operator?

Operator: [Operator Instructions]. First question will be from Brad Canino of Stifel. Please go ahead.

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Q&A Session

Brad Canino: Now, as I read the explanation for the strategic shift away from the IRAK med, I couldn’t help but think the same logic could be applied to STAT3 on the cancer side, at least as we think about the monotherapy potential in T-cell lymphomas. So, while I get that these STAT3 studies are also very useful as a proof of concept for your immunology developments, should we still think of STAT3 as having legs for you in oncology? And if so, what form? Thank you.

Nello Mainolfi : That’s a great question. So first, I just want to reiterate that the 413 was a clear strategic decision based on how we prioritize our pipeline. And again, the landscape in diffuse large B-cell lymphoma. As you know, STAT3 is a broad development program that spans both liquid tumors, solid tumors, as well as areas outside of oncology. So — I mean, as you know, we have a really high bar on how we make decisions on investing in the next phase of development. So, we’ll always have a point in the phase of development where we assess the opportunities ahead of us. Right now, the way that we look at STAT3 is that it is a multipronged development plan, which includes activities in liquid tumors, which we know are limited.

But I think we are working both in the clinic and preclinically to flesh out the opportunities in solid tumors. As you know, we’ve shown preclinically the activity that we’ve seen with other agents, including PD-1. We are — during our Phase I studies, collecting tumor biopsies to look at the signature in the tumor microenvironment with respect to how we modulate that. And we’re doing other studies that we haven’t disclosed yet preclinically to look at combination with this agent in solid tumors. So, I think, I wouldn’t say that the STAT3 program is in the — we’re looking at the STAT3 program the same way that we have evaluated the 413 program. I think there is a broad opportunity that we’re evaluating, again, in oncology, and as we said in the past, outside of oncology.

Having said that, we will always be continuing to evaluate at every stage of development, whether our thesis is playing out the way that we planned versus not. And so, for now, we have full confidence in what this program can do. And the data that we’re sharing today and data that we haven’t shared yet continue to support our thesis.

Brad Canino: Okay. That’s helpful. And maybe to Jared, a follow-up on MDM2. It’s nice to see no trigger heme events. But could you discuss a bit more about the kinetics of the platelet changes you’re seeing? Because for DL1, at least you’ve gotten up to six cycles. So, are you seeing a return to baseline for those accounts by the start of the subsequent dose? I’m just trying to get a sense for the potential of any compound impact over cycles on counts as you move to those more potent dose levels. Thank you.

Jared Gollob: Yes, Brad. I mean so far, within these first two dose levels, we have not seen any thrombocytopenia or neutropenia. So, we have not seen any reduction in platelets or neutrophils.

Brad Canino: Thanks, so much.

Operator: [Operator Instructions]. Next question would be from Vikram Purohit of Morgan Stanley. Please go ahead.

Gospel M. Enyindah-Asonye : Good morning, everyone. This is Gospel on for Vikram. So, we have one question. So, given the release mentions a focus for the company on immunology moving forward, do you plan to keep developing the STAT3 and MDM2 programs beyond the initial clinical data sets? Or could those programs be halted or partnered up? Thank you.

Nello Mainolfi : Okay. Great question. So just to be clear, I think we’re seeing two important things today. One is that, as we have continued to say over the years, we want to make sure that we deploy our platform against clear unmet needs, and doing so by going after targets that have not been drugged or drugged well. We also said today, and we’ve said it over the years, that our focus is on large problems. So, problems that have not been solved by other technologies, and more importantly, in patient population that we believe are sizable. So, when we talk about immunology, we believe that, that is an area that is prime for this technology. We believe, as you’ll hear much more in January, that oral degrader medicines in immunology could offer really amazing opportunities for lots of diseases that now are either underserved or served only by injectable biologics.

Having said that, there are areas of oncology that still fulfill the investment thesis that I just outlined, meaning we believe that we have programs that can unlock larger opportunities by going after targets that have not been drugged or drugged well by other technologies. So, I think the main theme is going after, in this evolving landscape, sizable opportunities, and really deploying the technology where it’s best deployable. It is fair that we believe that the opportunities in immunology are probably both broader. And actually, I would say also, with less competition than I think we see in a very, very competitive oncology space. And we will continue to evaluate whether the case continues to be as we continue to evolve this program. So, I think at this point, that’s where we are.

As we go into January, I think the pipeline choices and the prioritization will be even clearer.

Operator: The next question will be from Marc Frahm of TD Cowen. Please go ahead.

Justine Koenigsberg : Marc, are you there?

Operator: We’ll come back to Marc. Next up, we have Geoff Meacham, Bank of America. Please go ahead.

Unidentified Analyst: This is John Joy on for Geoff Meacham. I guess kind of looking at KT-474, what are your clinical benchmarks in atopic dermatitis? Like is the bar to beat still [indiscernible]?

Nello Mainolfi : Great question. So, what we’re looking with our IRAK4 degrader, which is really a first-in-class medicine that is trying to — just to go back a second. The goal there is to block the path to the IL-1R/TLR pathway with a single oral molecule. And in doing so, being able to elicit the biological and hopefully clinical impact that upstream biologics are not able to do, and basically demonstrate the clinical activity of potentially all the upstream biologics in a single molecule. Obviously, the IL-1R/TLR pathway is not the IRAK4/STAT3 pathway. So, we look at IRAK4 as a broad anti-inflammatory agent that can be both effective, well tolerated, and oral, and so convenient for a broad patient population. So, our bar right now, in the absence of conclusive Phase III data that will allow us to position the drug commercially in a credible manner, I think at this stage, what we said in the past and continue to say is the target product profile for 474 is to be an oral active drug with a good safety profile.

And I would argue that, that is not present right now in either the HS or the AD market, and that’s really the goal of that development program.

Unidentified Analyst: Okay. Awesome. And then one quick follow-up. So, is there any read-through or material impact to Kymera from Sanofi’s increased R&D spend announcement?

Nello Mainolfi : I think it’s a positive read through from where I stand, obviously. I can’t comment on Sanofi’s decision. I think for me, if I had to share my opinion, I think it’s refreshing to see a large pharmaceutical company taking a bold move and investing in R&D. That’s all I’m going to say.

Operator: Next question will be from Marc Frahm, TD Cowen. Please go ahead.

Marc Frahm : Can you hear me now?

Nello Mainolfi : Yes.

Marc Frahm : Okay. Sorry about that. Maybe for Jared, the description of the ASH abstract in there, there’s nine nonevaluable patients, I believe. Can you describe those? How many are still on trial, and maybe along with that, the — how many should we expect where single-agent activity might actually be part of the hypothesis when we get to the ASH presentation? And I do have a follow-up there.