Allogene Therapeutics Inc. Q1 2023 Earnings Call

Speaker 1: of enrollment and without the need of undergoing bridging therapy, which often comes with marginal benefits, but with toxicities. Treatment consists of one time infusion of cells, pre-uphastles, and inconvenience of heading to return to the clinic for treatment again and again, and without the cumulative toxicity that often comes with lengthy chronic therapy. Aloe-car tea is unique in its ability to potentially provide a one-time, off-the-shelf product capable of achieving long-term remissions. As we march towards our goal of an ELI submission for Aloe-501A of a completion of the alpha-2 trial and evaluate manufacturing process across Aloe-BCMA candidates to achieve optimal clinical performance, I am particularly excited to welcome Tim Moore to Aloe-Gin as our new chief technical officer. Tim was my colleague at Kite and he was trusted to deliver CARTI products for every patient we enrolled in clinical studies.

Speaker 1: update on our R&D activities.

Speaker 2: Thank you David. When Alligene began this journey, the biggest question faced in the field with whether or not the safety and efficacy of an Alligene product could be comparable to approved autologous car team therapies, and in particular whether Alligar team could achieve the longer term remissions, there's a hallmark of self therapy.

Speaker 2: While data from our ongoing phase 2 trials will be required for confirmation, we strongly believe that the available data from the phase 1 alpha and alpha 2 trials will establish the feasibility of this new modality.

Speaker 2: The unique experience and track record we have across our teams derived from previous success developing autologous CAR T therapies that led to approvals in late and earlier Lyme disease gives us the confidence in our approach in clinical data.

Speaker 2: When you combine that history with nearly 200 patients we have treated with our allocarty investigational products including nearly 50 patients along with LBCL. We are in an unparalleled position when it comes to depth of understanding.

Speaker 2: Our experience now stands even further with the addition of TEM to our team. I doubt there are any better positions to ensure that our capabilities in product science that scales successfully with our advances in the clinic.

Speaker 2: Another important benefit of our experience in the field is our longstanding relationships with investigators. We recently held a meeting with many of our phase two investigators as we progressed enrollment of the Alpha 2 trial and began enrolling patients in the expand trial. As our clinical safety and efficacy data continue to mature, the more excited our investigators are of the potential.

Speaker 2: in Chicago.

Speaker 2: While the field of allogeneic CAR-T has been marred by inconsistent datasets, especially as they relate to durability response, we believe the data we presented at our R&D showcase late last year demonstrate that our CD19 allo CAR-T product candidates have the potential to provide durability that is on par with autologous therapies.

Speaker 2: We believe we have succeeded where many have fallen short by virtue of being able to control premature CAR T cell rejection.

Speaker 2: Our platform is enabled by ALO647, our anti-CD52 from multiple antibody, that permits an extended window of car, T cell, expansion and persistence.

Speaker 2: What ALO647 does cannot be reproduced even with high doses of chemotherapy that might be associated with severe toxicity. I am pleased to report that we have recently initiated the phase 2 expand trial designed to support the licensure of ALO647 as a lymphatic aging agent for ALO510A in LDCL.

Speaker 2: This study is designed to demonstrate the superiority of ALO647-containing lympho-depletion regimens over a regimen of Flucai alone. The preponderance of data we've already presented from our CD19 program point to improved clinical performance with ALO647 in terms of depth and durability of response. And our safety data studies are generally comparable to that of autologous CAR T's.

Speaker 2: We've not observed GBHD or severe ICANNs have relatively low rates of CRS, and our rates and severity of cytopinias and infections are in line with what has been reported for autologous

Speaker 2: Based on our emerging product profile, you can understand why we remain very confident in the potential outcome of both of our ongoing phase 2 trials.

Speaker 2: I'd like to next turn your attention to our Allo-316 program, where we recently had an oral presentation of our interim Phase 1 data in renal cell carcinoma at the clinical trials plenary session of the American Association of Cancer Research annual meeting.

Speaker 2: Clear cell renal cell carcinoma is the most common form of kidney cancer.

Speaker 2: The unmetvened patients with metastatic or advanced disease who have progressed on standard of care therapies, tyrosine kinase inhibitors, and immune checkpoint inhibitors is high.

Speaker 2: Once patients have progressed on these two classes of drugs, there are limited options. In fact, it's estimated that 90% of patients with advanced dermatostatic RCC will die from their disease within five years.

Speaker 2: The data we presented at AACR showed that ALD-316 has the potential to make a difference for patients with RCC whose disease progressed on TKIs and immune checkpoint inhibitors. Initial results from the dose escalation portion of the trial showed that a single infusion of ALD-316 demonstrated anti-tumor activity in patients with CD70 expressing tumors.

Speaker 2: providing a 100% disease control rate, meaning tumors shrank or remain stable over a certain time period.

Speaker 2: In the 10 patients whose tumors were known to express CD70, the overall response rate was 30%, including three partial responses, meaning the size of the tumors were reduced by at least 30%.

Speaker 2: The longest partial response lasted to month 8.

Speaker 2: This is remarkable given that we're still in the dose escalation phase of the study, with most patients being treated with relatively low doses, 40 or 80 million total alkyl carate cells.

Speaker 2: As in our CD19 program, the safety profile of ALA316 to date appears generally consistent with what is seen with autologous CAR T cell therapies.

Speaker 2: With all 19 patients in the Phase I study, including nine who did not have CD-70 expressing tumors or had CD-70 expression unknown, there was a single case of grade 3-CRS, neurotoxicity, which is now to find more broadly, which generally low grade and reversible with most events being fatigue or headache. There were no cases of GVHD or ICANNs.

Speaker 2: infection-occurative aid patients and included four cases of great-three or higher infection.

Speaker 2: Great through your hire along the side of Pena was observed in three patients.

Speaker 2: One dose limiting toxicity in grade three autoimmune hepatitis was reported. This event, which has been resolved, may have been confounded by prior use of the checkpoint on the inter.

Speaker 2: One feature of Valo 316 that we are particularly excited about is the expansion of persistence of Valo 316, which we believe compares favorably with what has been reported for autologous and now too muchazi-lagen contracts, some of which bottom Lavais REGR?s a ton of

Speaker 2: Allot 316 was engineered so the anti-CD70 car can exhibit an additional function beyond cancer cell talent, avoiding premature rejection by the host immune system.

Speaker 2: Because CD70 is expressed on activated T cells, there is a potential for ALO316 to target and eradicate palo-reactive T cells in addition to CD70-positive cancer cells. This unique feature of ALO316, highlighted in the Traverse Translational Data shared at ACR, is the basis of our proprietary dagger technology.

Speaker 2: that now has become the foundation of our next generation anti-rejection approach.

Speaker 2: Dagger technology is designed to prevent early rejection of alocar T cells by suppressing host immune cells, thereby supporting CAR T cell expansion and enabling a prolonged window of persistence.

Speaker 2: We are excited by the possibility to deploy Dagger alongside cars directed at other energy targets in the same cell for the purpose of creating a novel, allogeneic car team platform for a suite of next-generation products that are less dependent on traditional chemotherapy-based lymphotoplesion.

Speaker 3: I will now turn it all over to Eric. Thank you, Zach, and good afternoon, everyone. While the market environment for biotech companies continues to present challenges, one thing remains certain. Success will ultimately be driven by a combination of scientific innovation, experience, and financial stewardship.

Speaker 3: Our scientific innovation is proving itself in the clinic. The experience of the Allogene team has never been in doubt, and in fact the addition of Tim as our CTO has only added to our strength.

Speaker 3: And lastly, we are proud that we have been and continue to be very thoughtful about how we deploy our resources.

Speaker 3: Our balance sheet remains strong as we ended the quarter with $514 million in cash, cash equivalents, and investments. We also continue to execute cost savings measures directed at preserving our balance sheet strength. We believe these efforts have extended our cash runway into Q2 of 2025.

Speaker 3: long enough to complete our pivotal trials for LO501A and prepare for a potential BLA submission. In the first quarter of 2023, our research and development expenses were $80.2 million, which includes $9.2 million of non-cash stock-based compensation expense. General and administrative expenses were $18.9 million for the first quarter of 2020.

Speaker 3: We now expect a decrease in cash, cash equivalents, and investments of approximately $230 million in 2023. We expect that our full year 2023 GAAP operating expenses to be approximately $340 million, which includes estimated non-cash stock-based compensation expense

Speaker 3: expect a decrease in cash, cash equivalents and investments of approximately $230 million in 2023. We expect that our full year 2023 GAAP operating expenses to be approximately $340 million, which includes estimated non-cash stock-based compensation expense of approximately $80 million.

Speaker 3: This guidance excludes any impact from potential business development activities. With that, we will now open the call for your questions.

Speaker 3: excludes any impact from potential business development activities. With that, we will now open the call for your questions.

Speaker 4: To ask a question, please press star 11 on your phone and wait for your name to be announced. To withdraw your question, please press star 11 again.

Speaker 4: We ask that you please limit yourself to one question and one moment, please, as we compile the Q&A roster.

Speaker 4: And one moment for our first question. Our first question will come from Tyler Van Bern of TD Cowen. Your line is open.

Speaker 4: So, Mr. Van Buren.

Speaker 3: Is John on mute? I'm here. Off mute. Yep, thanks. Congrats on the progress, guys. Thanks for taking the question. As we think about the ASCO update and what we should expect, can you just help frame that a little further? You know, we've seen good durability obviously with the early patients and the majority of alloy patients have made it past 12 months.

Speaker 3: So there's a focus at ASCO on the single dose FCA 90 alloy patients and will all 12 be past 12 months at the time of cutoff, right just before ASCO.

Speaker 1: Thanks for that question. This is David Chang. Certainly, we will be updating, providing the data at ASCO. And one thing that we are really trying to do is have our data be

Speaker 1: in front of the investigator and the KOLs. Previously, we have shared the information, but that was in a corporate presentation setting. And as we are expanding the clinical studies, it has become very apparent to us that much of the information that we have communicated to our investors were not readily available.

Speaker 1: or have been made known to the academic community, clinical community. So the purpose of the ASCO presentation is to ensure that KOLs and our investigators and their teams have a chance to see our data. We know that KOLs are the best way to do that, and we know that KOLs are the best way to do that. We know that KOLs are the best way to do that.

Speaker 3: peer-reviewed format. And Tyler, this is Eric. Just in terms of the specific details, you know, we're going to have to wait until PASCO, the conference itself, we don't want to preempt the conference organizers. I do want to remind everyone that we stopped enrolling patients in the phase one study when we began.

Speaker 3: the Phase 2 program, so there won't be additional patients. But yes, we'll have additional follow-up on patients previously treated as you presumed. And obviously, we're just keen to share this update in the medical forum, as David mentioned.

Speaker 4: Thank you. One moment please for our next question.

Speaker 4: Next question will come from the Rifter of Goldman Sachs. The line is open.

Speaker 5: Hey, thanks. This is Matt on for Salveen. Could you guys give us any more details on the progress of the pivotal alpha-2 trial in particular? Have you begun treating patients and when can we expect initial data? Thank you.

Speaker 2: Thanks for that question. So the study is open to enrollment and it is progressing as expected and our guidance remains the same that we expect a complete enrollment in the first half of next year and we expect a phase two readout by the end of next year.

Speaker 4: Thank you.

Speaker 4: Thank you. One moment, please, for our next question.

Speaker 3: Our next question will come from Michael of Jeffries. Your line is open. Hey, guys, good afternoon and thanks for the update. We had 1 question and a follow up on the enrollment of alpha 2 and also the expand trial. Could you comment?

Speaker 3: on how you think about the types of patients that are getting enrolled in alpha 2 and even specifically the expand trial given that's actually a randomized study where the control arm doesn't necessarily get the 647 and if you think about how efficacy would be on that, the types of patients that would actually enroll in that trial. And the reason I ask about this is just obviously leading to the confidence around the timing of the timing, alluding to the prior question.

Speaker 3: as well as obviously other options that are out there for people in a competitive environment. So that's a complicated but I think it's important first question. And then the follow up is on myeloma. Could you comment on how you're thinking about the timing of the next update there as it relates to the manufacturing and what we're sort of waiting for when we can get some disclosure is up this year?

Speaker 2: autologous CAR-T studies. So these are patients who are in third line, whose disease is progressing, but otherwise sort of are fit and well enough to meet the eligibility criteria. So we do not expect to be measurably different in the patients that we treat in either Xpand or Alpha 2.

Speaker 2: from the target population that was studied in the autologous CAR-T world.

Speaker 2: on the second question around myeloma. So as we've guided previously, we are focused on reviewing the manufacturing process used for Alice M15605. We expect that to be the focus of this, the remaining months of this year, and potentially resuming dosing in 2024.

Speaker 4: Thank you.

Speaker 4: One moment please for our next question. Our next question will come from Michael Schmidt of Guggenheim Securities. Your line is open. Hi, good afternoon. This is Yigui Yan for Michael. Thanks for taking our questions.

Speaker 4: Congrats on the progress on initiating EXPAND. How do you plan to allocate patients to alpha-2 and EXPAND so that the two studies won't compete each other in terms of patient involvement? And then can you talk about the powering assumption for EXPAND or what level of PFS separation you expect?

Speaker 4: fee from the two arms. Thank you.

Speaker 2: So in terms of competing for enrollment into the two studies, Alpha 2 and Xpand, we have addressed this largely operationally through the sites that we intend to open for the two programs. They're not overlapping. So, you know, if you've got one CD19 program from Allergy and Open at your center, it's going to be either Alpha 2 or Xpand.

Speaker 6: Thank you.

Speaker 1: One moment please for our next question. Our next question will come from Mark Brightonbock of Upco. Your line is open. Very good afternoon guys. Thanks for taking our question. Just to kind of set expectations on next data from the Traverse Study.

Speaker 2: Can we kind of expect dose level three and dose level four cohorts to enroll similar numbers of patients as we saw in the first two cohorts? And I guess I'm wondering if we should be expecting data from those later this year. And if they're also all going to be selected for based on...

Speaker 7: CD70 positivity and receive FCA conditioning. I know some of the patients in dose level one and dose level two cohorts did not receive FCA conditioning. Thanks for taking those questions.

Speaker 2: So as we've mentioned in the past, the dose escalation is indeed ongoing. We do expect to enroll patients to both FC and FCA arms in at least dose level three and potentially dose level four. And as far as data updates go, we are expecting to be able to share data in the second half.

Speaker 6: will come from Jack Allen of Beard. Your line is open.

Speaker 8: Great. Thank you so much and congratulations to the team on all the progress made over the quarter. A bit of an abstract question, but I do get a number of inquiries from investors surrounding the one late progressor from the FCA 90 alloy treatment cohort of the Alpha 1 Alpha 2 study.

Speaker 1: I was wondering if you had any additional thoughts as it relates to why that may be occurring with allogeneic cell therapy and any scientific context you could provide around that patient. Hi, Jack. Let me take on that question. Even in the autologous CAR T therapy setting, late progression happens.

Speaker 1: and we don't view what happened to that patient to be a unique event to the allogeneic CAR-T. I think during the course of CAR-T, we are learning a lot. Yes, we get patients who stay very stable after six months or so, but the late progression is known to occur. Thank you.

Speaker 9: to push out dagger in specific liquid and cell tumor indications. I don't know whether you have any early view on your strategy today with the next steps. How does that fit into your current plan? Thank you.

Speaker 1: Brian , that's a great question. Dagger technology, as we reveal more data, we get more excited about what we're seeing with the Dagger. And not only, you know, we are able to transfer the Dagger to another car, as we have presented earlier this year in a scientific forum.

Speaker 1: we see this really as potentially in a next generation platform. Now with that, how do we prioritize different targets with the next generation? That's a great question. And it's something that we can do across both heme targets as well as follow tumor.

Speaker 1: strategic choice of which ones to go forward first.

Speaker 6: which wants to go forward first. Thank you.

Speaker 6: In one moment for our next question, our next question will come from John Newman, a Canacol Dignity. Your line is open. Hi there team, thanks for taking my question. So, you know, I think it's interesting. Last year you showed us data at your R&D showcase.

Speaker 10: that suggested

Speaker 10: Regression-free survival on your CD19 product is basically equivalent to autologous CAR-T.

Speaker 10: You've also commented previously that the percentage of patients that are actually receiving autolysis CAR T is quite low. I wondered if you could discuss just for a moment the impact that

Speaker 10: enrolling patients from the community could have here. I'm just thinking that there's gotta be some reason why these patients are actually not receiving autologous CAR T. I'm just wondering if it's because they're not suitable, or perhaps they just don't have access to these larger centers. Thanks. Thanks for that question. So,

Speaker 2: you have a short remission and then progress. And then they get started on something before they're referred to a tertiary care center where CAR T is available. And it's often those patients who are coming in with, you know, a relapse after that frontline, having received a couple of doses of additional therapy with still, still disease present. So

Speaker 2: You know, we are looking for these patients. They come from a variety of different places, and that's just one example of the types. But in general, as I said earlier on the call, these patients are very much similar to the patients that were treated in the early days with autologous therapies.

Speaker 2: patients they come from a variety of different places and that's just one example of the types but in general as I said earlier on the call these patients are very much similar to the patients that were treated in the early days with autologous therapies. Thank you.

Speaker 6: One moment for our next question. Our next question will come from Talpesh Patel of B Riley. Your line is open.

Speaker 2: Yeah, hey, good afternoon. Thanks for taking the question. Maybe one more on the data technology as you continue to sort of explore 316.

Speaker 2: Do you think that you may be able to incorporate redosing of the aloe cartes without traditional Fusai and aloe cartes?

Speaker 2: question. Thank you for asking it. In fact, it really kind of drills down on exactly what we're so excited about with the dagger technology. So as we saw at AACR, we do see very nice expansion, in fact, very impressive expansion with FC alone. So this does give us the confidence that that dagger effect is real.

Speaker 2: potentially later on following a period of durable stable disease or partial remission. And then your question around whether we would need standard lymphodepletion is a great one and it's one that we will be considering as we move through the study.

Speaker 6: Thank you. One moment please for our next question.

Speaker 6: Our next question will come from Aztika Goombodine, a tourist. Your line is open.

Speaker 9: Hey guys, thanks for taking the question. I just wanted to go back to what's coming up at ASCO. Maybe we can talk just a little bit about in kind, what kind of translational data and additional new data do you think we'll be seeing in the presentation deck? Just want to get a better sense of what you want to be showing to.

Speaker 1: the manufacturing slot and get a product? Has your idea of what your allergenic CAR T for multiple myeloma evolved? Thanks. Yes, this is Dave Chang. In terms of the ASCO presentation, you know, we...

Speaker 1: other than what is shown in the abstract. You know, we will be curtailing the comments out of respect for the organizers. But as we have said, we have stopped enrolling into the phase one, so it's the same patient as we have previously communicated at the RDS. And obviously...

Speaker 1: We will have a little longer term follow up on these patients.

Speaker 1: And the second question, since I didn't really answer your first question, I'm going to ask you a second question. On the multiple myeloma, yes, I mean, we are monitoring the situation and the number of the patients who are actually getting glocholus carti still continues to

Speaker 1: that certainly shows that alginate CAR-T with the IL-715 works in multiple myeloma.

Speaker 1: What we are doing is reviewing the manufacturing to look for an opportunity to increase the potency.

Speaker 1: in a clear as we are communicating, we do not think we can get up to the cardiectomy level unless we do something on the manufacturing to improve the potency. And that's exactly what we are doing. And our plan, if everything goes well, is to reintroduce ALOS 715 into the clinic in 2024.

Speaker 1: we are communicating, we do not think we can get up to the cardicty level unless we do something on the manufacturing to improve the potency. And that's exactly what we are doing. And our plan, if everything goes well, is to reintroduce ALOS 715 into the clinic in 2024. Thank you.

Speaker 10: We saw one unconfirmed PR and two confirmed PRs. Has that one unconfirmed PR subsequently been confirmed? Because when you talk about that 30% ORR, I assume it has been confirmed. I didn't know from the data if that person had been redosed or if any redosing is happening in this particular study.

Speaker 10: And I guess just related to that, there were two additional patients from the November update to the AACR update. Is that kind of the cadence of enrollment we should be expecting as we get set up for the second half of this year and an update from the Traverse study?

Speaker 2: The second tail that you're seeking is actually in the swim lane plot. So the two patients that did have confirmed PRs were confirmed as per resist and that third patient, with the unconfirmed, did have a period of remission before the the tumor did grow a slight amount.

Speaker 2: that put that patient out of the sort of resist PR definition. And that the scan was, came just after that occurred. So we weren't unable to confirm that remission per resist. But there was a period of durable reduction in tumor burden over 30% consistent with resist.

Speaker 2: We did retreat to patients. Again, that data is in the swim lane plot. You can go review those and both of those patients did experience a period of disease control following the retreatment. Finally, the question on the cadence of enrollment. So as we've discussed, the protocol was amended recently to only.

Speaker 2: significant increase in the patient enrollment.

Speaker 6: Thank you. One moment please for our next question.

Speaker 6: Our next question will come from Jason Gilberry of Bank of America Securities. Jim what is your intention of hitting United States u.s.cal?

Speaker 11: Hey guys, thanks for taking my question. Just to follow up on the BCMA front, if you get the potency where you feel like you need to be from a competitive standpoint, I'm just curious how open you guys are to partnership like others on the autologous side have.

Speaker 11: explored from a cost sharing perspective? Or do you feel like with the allogeneic approach, development through to marketability wouldn't be as cost prohibitive as the autologous counterparts? And if I could squeeze a follow up in, when would you expect to complete enrollment of the EXPANDS study? Thanks. Okay, let me, on the DCMA, in the question around the partnership, which is really what you're getting into. You know, a year or two years ago, we would not have taken this approach. But right now at AllerGen, we have three clinically.

Speaker 1: validated programs that we are not fully able to invest. Earlier this year, we made a very strategic choice to focus on the execution of the pivotal study in non-hatch lymphoma with IL-501A, and the both PCMA and 316, we are...

Speaker 1: trying to advance that with some unlimited resource. In that situation, we are definitely looking into opportunity to bringing a partner who are committed in advancing the Algenne CART and together in hoping to accelerate the program such as PCMA.

Speaker 1: where we not only have the LEAD program that has shown the proof of concept, but also the potential to bring the next generation technologies, such as the one that includes the Dagger technology, or the TurboCar, which we have not been able to complete the phase one study in.

Speaker 3: On the expand trial, Jason, we just recently initiated that trial. So it's a little bit too early to say how enrollment is proceeding at this point in time, but it's still our goal to have the results from the expand study at roughly the same time we have the results from the altitude trial.

Speaker 6: Thank you. One moment, please, for the next question.

Speaker 6: Our next question will come from William Pickering of Bernstein. Your line is open.

Speaker 11: Hi, thank you for taking my question. I want to confirm I heard you correctly earlier in the call that you expect to read out the pivotal trial before the end of 2024 and is the duration of follow-up that will be reported in that sufficient to file. And if I may, on the partnership comments, you just made, David, is that specific to BCMA or is-

Speaker 3: of 2024 is a good timeline to think about.

Speaker 1: The second question around the partnership, we are not specific to one particular program. Given that we have what we consider as three viable programs, partnering on one of them, certainly we're not going to partner on all three of them, but partnering on one or two will allow us to advance the overall.

Speaker 6: One moment, please, for our next question. Our next question will come from Luca Isi of RBC Capital. Your line is open. LUCAS ISI. Oh, great. Thanks so much for taking my question. I'm going to be here for a quick one. You're lowering your cash for guidance for the year, I think about $20 million, if I'm not mistaken, so I wonder if...

Speaker 12: How do we go?

Speaker 12: What do you, uh-

Speaker 12: You look up.

Speaker 12: If you could please sound like your line went mute, could you please unmute your line? Operator, maybe we can get him back in the queue. Let's move on. Hold on a moment.

Speaker 12: If you could please sound like you're on line one mute. Could you please unmute your line? Operator, maybe we can get him back in the queue. Let's move on. One moment. And one moment for our next question.

Speaker 6: Our next question will come from Sammy Coleman of William Blair. Your line is open. Hi, there. Thanks for taking my questions. I have a couple on the EXPAND trial. I noticed that in your 10Q it stated that a couple of the clinical trial sites have declined to participate because of its randomized design. So, I guess I was curious if that sentiment or hesitation was also echoed by patients that some patientsgrove might've took this route or that several other handlers took this route. Was there another processor? No. things wont actually coincide, right? No.

Speaker 6: And if this will impact enrollment in the trial at all, also when can we expect data from that trial? And if that trial ends up not being statistically significant, would you still submit a BLA for ALO 501A with just using cyclo? Thank you. Thanks, Sammy. Some terrific questions there.

Speaker 2: So I'll start with the last one. So we're going to run alpha 2 the way that we're treating patients. And we're very confident in that study's ability to demonstrate a benefit for patients who meet the eligibility criteria. With respect to how Expand is enrolled.

Speaker 2: merit of this trial and so we're obviously very excited to participate with those studies with those with those investigators in those sites.

Speaker 2: As far as the data availability goes, as Eric mentioned previously, we are targeting data availability from expand at roughly the same time as Alpha 2. Thank you. One moment please for the next question.

Speaker 11: Great. So, maybe a quick one. Eric, you're lowering your cash-burn guidance for the year by $20 million, so, if I'm not mistaken, so I'm wondering if you can expand to where some of those savings are coming from. And then second, on CD70, in the past you've spoken about tumor types beyond renal cell carcinoma, either as monotherapy or combination with checkpoint and in-situ. Okay. I think we're losing...

Speaker 3: Let me answer your first question, and I'm not sure we heard your second, but with regard to our cash burn guidance for 2023, that's correct. We've lowered our cash burn target from 250 to 230 million dollars.

Speaker 3: We continue to just be very very mindful of everything that we spend our resources on You can imagine that any any dollar spend going down to relatively low dollar amounts gets a second look these days given the nature of the capital markets raising environment and

Speaker 11: and our need to focus on our highest priority items. So, you know, across the board, we've investigated all of our spend and we've been able to tighten our belts a little bit. And the second question I think was really related to what else are we gonna do with CD70 program besides the renal cell cancer.

Speaker 1: As we have previously talked about, the potential of using CD70 outside renal cell cancer, such as CD70 positive solid tumors or hematologic malignancies, where CD70 expression is known to be pretty high. That includes T-cell leukemia lymphoma.

Speaker 1: as well as large B cell lymphoma. And then, you know, third thing, which is testing alginate CAR-T together with immune checkpoint inhibitor. All those are still under consideration. The goal this year is really trying to get to the lymphoid depletion as well as cell dose.

Speaker 1: where we can start expanding the cohort to those different considerations that we just discussed.

Speaker 1: we can start expanding the cohort to those different considerations that we just discussed. Thank you. And one moment, please, for our next question.

Speaker 11: Our next question will come from Ben Burnett of STIFO. Your line is open. Excellent. Thank you very much. I guess also a question regarding the ALO316 program, following up on an earlier question about CD70 positivity. You disclosed some, I think, interesting results showing a correlation or a trend of greater tumor reduction with higher CD70 expression.

Speaker 2: I think it was referred to maybe as an age score. So, I guess given this, have you defined what level of CD70 expression constitutes as sort of positive in this case, like CD70 positive? Is it just anything with any amount of CD70 expression? Is there a certain threshold that you're looking for? And if so, would that threshold be used to select patients?

Speaker 1: patients using the, you know, sort of the investigation in vitro diagnostic assay is to ensure that we do not involve any CD negative, you know, renal cell carcinoma patients with CD negative renal cell carcinoma. At the cut point, you know, we'll be further defined as we gain more clinical experience. dean.

Speaker 2: of that particular figure that we shared at ACR was that it really does show that this is likely an on-target effect. So, you know, anytime you're giving lymphoid depletion, there's a question of whether that might be playing a role. But the fact that we did see preliminary evidence that the higher the expression of CD70, the deeper the response gave us a lot of enthusiasm that this is a truly active agent in this disease.

Speaker 1: Thank you. That concludes our question-and-answer session. I would like to turn the conference back over to management for any additional comments. Well, thank you, and thank you for joining the call today. We continue to believe that our success across multiple clinical programs, the ability to attract top-tier talent.

Speaker 1: and financial stewardship to whether the challenging external market environment paves the way towards to bringing a new generation of CAR T products to patients. And we look forward to seeing you next at ASCO. Operator, you may now disconnect.

Speaker 12: Thank you. This concludes today's conference call. Thank you all for participating. You may now disconnect and have a pleasant day.