One of them may be Cy/Flu, given the precedent that exists, but there are certainly other regimens that we can think about adding on too, that exist in autoimmunity. I think the real opportunity at the end of the day is to reach autoimmunity patients, think about what regimens they’re receiving today in their daily lives, and whether or not adding a cell therapy without Cy/Flu could substantially change their lives by promoting an immune reset.
Peter Lawson: Got you. Thank you. And then quick question for Ed. Just on kind of any guidance around SG&A and R&D, just considering it has declined significantly year-over-year. Just curious what the run rate is for the ’24?
Edward Dulac: Yeah, Peter, we’re not providing guidance today, but I think if you look back at the last two quarters, and I tend to want to look at this on a cash operating expense basis. But if you look at cash operating expenses in the third quarter, I think they were about $37 million, a very similar number, about $35 million in the fourth quarter. I think that’s a reasonable baseline to carry into at least the first half of 2024. And as the prepared remarks have indicated, we obviously have essentially five ongoing programs, 819 in oncology, 819 emerging in autoimmunity, 522, 825 across a couple of different indications. So the second-half burn rate, I think is a good indicator of what at least the first half of 2024. But as we have indicated, we are at the higher dose levels of both FT576 myeloma and FT819 in oncology, and we’ll have a go/no-go decision sometime later this year.
So, there may be some puts and takes to the extent our data allows us to continue later development. We’ll provide the appropriate guidance at that time. But for the time being, that $35 million to $40 million per quarter is a reasonable run rate to assume in the first half of 2024.
Peter Lawson: Great. Thanks so much.
Operator: Thank you. Our next question comes from the line of Ben Burnett of Stifel. Your question, please, Ben.
Carolina Ibanez: Hi, good afternoon. This is Carolina Ibanez on for Ben Burnett. Thank you for taking our question. For 819 in autoimmune disease, there is this aspect that autoimmune disease patients have a stronger immune system than cancer patients, which may drive a more energetic rejection of the allogenic CAR T-cells. What’s your perspective on this? And do you think a more intense depletion regimen may end up being required, at least for 819, to ensure that a sufficient B-cell depletion can occur?
Scott Wolchko: Yeah, based on the data that we’ve seen on the oncology side, I think we’re very comfortable and as you probably are aware, we’ve continued with the standard Cy/Flu conditioning regimen, that’s been used in treating patients with autoimmunity, as well as the conditioning regimen that’s used with autologous CAR T-cell therapy. Like I mentioned, based on the translational data that we have seen, we’ve seen FT819 behave similarly to their autologous counterparts. We’ve seen a dose-dependent expansion. We’ve seen peaks in expansion that are similar to the autologous counterparts. We’ve seen persistence that’s lasted for several weeks with respect to the product candidate, and we’ve seen B-cell suppression that extends out to at least 30 days.
So given all of that, I think we’re really comfortable with the profile that we’ve seen with FT819 on oncology, and I’m very excited about its potential in autoimmunity, where at least the data that exists in patients treated to date, primarily out of the group in Germany, has suggested that a short-lived cell, in their case an autologous program. But that an autologous cell is acting very rapidly, the kinetics of depletion are occurring quickly, and that — it is actually important at some level for the cell to ultimately clear the patient, as opposed to being long-lived, so that the B-cell compartment can come back and trigger the immune reset. So in the setting of autoimmunity, we believe based on the autologous data that’s been generated to date, that a short-lived cell can have profound impact, generate the necessary depletion enable a relatively rapid immune reset.
And we’re very excited about that.
Carolina Ibanez: Okay. Understood. Thank you.
Operator: Thank you. Our next question. Please stand by for our next question. Our next question comes from the line of Andrea Tan of Goldman Sachs. Your question, please, Andrea.
Unidentified Analyst: Hi. This is Talani Usman on for Andrea Tan. Thanks or taking our questions. Firstly, could you please [Technical Difficulty] through the considerations for FT819 and B-cell malignancies and then for 576 in multiple myeloma? And the profile you’re looking to see at the higher doses to warrant further development relative to the autologous and allogenic CAT-T therapies?
Scott Wolchko: Yeah, I think, I touched on that for multiple myeloma already. I think the profile for an allogeneic cell therapy where products are approved needs to be similar to the value proposition — therapeutic value proposition that’s provided by engagers. So in lymphoma side and as well as in the myeloma side, I think the appropriate benchmark is looking at the T-cell engagers that are approved and being developed.
Unidentified Analyst: Perfect. Thank you. And then secondly, for FT522, just how are you thinking about the delta in efficacy that you’d be willing to give up to achieve better safety and tolerability through the exclusion of the chemotherapy of conditioning?
Scott Wolchko: I think that’s something we’re absolutely going to look at. I mean, I think the reality of this is, as we look at the autoimmunity space, you know, people can have an opinion on this, but I don’t think the vast majority of autoimmunity patients are going to be treated or reached at specialized academic centers that treat oncology patients. So I think it’s going to be absolutely critical in the field of autoimmunity that we reach patients where they live and breathe in the community, and that these patients are treated without intense chemotherapy conditioning. And I think that’s going to be critical for the autoimmunity space.
Unidentified Analyst: Thank you.
Operator: Thank you. Our next question comes from the line of Yanan Zhu of Wells Fargo Securities. Your question, please, Yanan.
Yanan Zhu: Great. Thanks for taking our questions. So, first, I was wondering, this is a follow-up to the earlier question about tissue specificity. I was just wondering whether treating SLE would require the CAR the T-cells to traffic to additional tissues compared with treating B-cell malignancies. Do you have any thoughts on that and whether derived T cells could also traffic to those additional tissues if there is such a tissue. And my other question is about the patient population you plan to enroll in the SLE study. I was wondering whether these will be patients refractory to biologics and other treatments or could milder patients be enrolled as well? And lastly, I was just wondering if there are any competitive dynamic for patient enrollment just given how many clinical trials will be ongoing at the same time in SLE, do you think it could be — there could be some competition for enrolling patients? Thank you.
Scott Wolchko: Yeah. So just let’s start with patients, the patients to be treated. Yeah. So these are patients with active SLE, moderate to severe disease, will have — had to have multiple lines of therapy already. So I think the criteria of patients that we’re looking to enroll, I think is similar to those that have been treated to date out of the group in Germany with the autologous counterparts. So this is moderate to severe active disease. I think, certainly it’s a competitive landscape. There are over 10 autologous CAR T-cell programs that are beginning to move into autoimmunity. I think an off-the-shelf cell therapy program, even if at the same center as an autologous counterpart, certainly has some unique and distinct advantages.
We don’t have to leukapheresis a patient. Certainly, we don’t have to take a patient prematurely off immunosuppressive therapy. We have a product that is in inventory and can rapidly sort of intervene and treat patients. As we begin to show, continue to show safety and activity, I think with our off-the-shelf program, there is the potential to reach patients outside of the academic medical centers more into the community. You’ve certainly seen us do that with NK cells, where our protocols do not require hospitalization. Patients can be treated outpatients in an infusion center, and we can reach into the community. I think ultimately that will be a requirement to treat patients in autoimmunity and serve those patients well. And so we’re excited about sort of the differentiated profile of an off-the-shelf cell therapy, including in direct comparison to their autologous counterparts, which I think provides some real constraints on how an autologous cell can be delivered to patients today with autoimmunity.
Yanan Zhu: Very helpful. And the question about whether SLE might involve additional tissue specificity?
Scott Wolchko: Yeah. So without a doubt, I think there are bad-acting B-cells that are sitting within secondary and tertiary tissue. I guess, my comment on that, I’ve made comments about that earlier with respect to certainly we’ve seen from a clinical setting, 819 reach tumor cells that are in these secondary tertiary tissues and deplete CD19 positive tumor cells. I’d also note that we’ve done a significant amount of work with CAR NK versus CAR T-cells pre-clinically, and we’re very confident in essentially the homing and trafficking, and infiltration potential of our T-cell programs, iPS-derived CAR T-cell programs. And again, that’s based on some significant models we’ve done on the solid tumor side.
Yanan Zhu: Got it. Thanks for the answers.
Scott Wolchko: Sure.
Operator: Thank you. Our next question comes from the line of Gil Blum of Needham & Company. Please go ahead, Gil.
Ethan Markowski: Hi. This is Ethan on for Gil. Thank you for taking our questions. I’m just wondering, in your view, if there are any clinical results, let’s say, in B-cell lymphoma that would potentially gate FT522 from moving forward into autoimmune indications. And then for second question, I might have just missed this, but are you still expecting to have data for FT576 and multiple myeloma in the first half of this year? Thank you.
Scott Wolchko: Yeah. For 576, we’ll give an update when we complete the dose cohort at 2.5 billion cells times three doses. And so we’re looking at both Regimen A as a monotherapy and Regimen B in combination with CD38 targeted mAb. When we complete that cohort, with respect to responses, we’ll give an update on the 1 billion cell cohort as well as the 2.5 billion cell cohort. I suspect that’ll be sometime in the middle of this year, based on where we are currently in that study. As it relates to NK cells moving into autoimmunity or FT522 specifically, certainly excited by the potential for NK cells in autoimmunity. As I sort of mentioned before, we’ve seen, including with multidose regimens, super clean safety profiles across our entire class of NK cell therapies.
Whether that be in hematologic malignancies or solid tumors, we’ve been able to deliver NK cells in the outpatient setting in the community. And so I think that bodes very well for our potential to differentiate and reach patients with autoimmunity outside of the academic medical centers.
Ethan Markowski: Thank you.
Operator: Thank you. I would now like to turn the conference back to Scott Wolchko for closing remarks. Sir?
Scott Wolchko: Thank you. And thank you, everyone, for all your great questions today. Look forward to seeing you in the near future. Be well.
Operator: This concludes today’s conference call. Thank you for participating. You may now disconnect.
