Scott Wolchko: At this point, we are doing a lot of work. I’m not going to disclose our strategy at this point in time. We are obviously doing a lot of work in thinking about our expansion strategy in autoimmunity. We are looking at areas where there have been clinical precedent with cell therapies, whether that be in transplant or out of the first data sets that are being generated, both out of Germany as well as the initial sort of company initiatives or company programs. So not prepared to disclose today how we think about expanding our FT819 IND into additional indications or the initial multi-indication study that we plan to submit for 522.
Li Watsek: And then maybe just wondering if you can just comment on your expectation for the patient enrollment in 819 studies. It seems like as you can dose the patients fairly quickly. And then it seems like you’re going to amend the protocol to allow some alternative conditioning regimens. So do you think that might drive sort of the traction with the site investigators?
Scott Wolchko: So specifically, we have guided to three to five patients — an update on three to five patients in the 819 study by the end of this year. We’ve also guided to — and we’ve discussed it on the call that we are looking to utilize Cytoxan only as a third potential regimen for treating patients. So cy/flu [Technical Difficulty] or cytoxan only. We do think that — and I think there’s been discussion about this that cy/flu potentially is a barrier to treating patients with autoimmunity. These patients aren’t oncology patients. They don’t deserve to be treated like oncology patients. And so I do think moving away from cy/flu is a conditioning regimen is going to be critical to really capturing the potential of cell therapy in autoimmunity, and we look to pioneer that.
Operator: The next question comes from Kara Bancroft with TD Cowen.
Greg Williams: This is Greg speaking on behalf of Tara. I’m wondering if you can give us any time line for when we can expect clinical data in lupus for 819?
Scott Wolchko: In the prepared remarks, we have guided to an update on the first three to five patients with FT819 in SLE by the end of this year.
Operator: The next question comes from Ben Burnett with Stifel.
Carolina Ibanez-Ventoso: This is Carolina Ibanez-Ventoso on for Ben Burnett. Congratulations on all your progress. On the ex-vivo data for FT819 on the pretreatment sample from the SLE patient. What do the ET Ratios shown imply about the necessary dose and cell expansion that you would need to achieve to get that deep B-cell depletion at the end of the CAR in vivo in the SLE patient?
Bob Valamehr: I’m happy to answer that question, and I’ll use some math here, so please forgive me if I start getting a little hypothetical. But — so what we show in the data is that at 2:1 ET ratio, we effectively eliminated all B cells that were in the PBMC compartment from the patient. If you were to think about the disease burden and autoimmune specifically SLE, we anticipate somewhere around 100 million to 300 million disease B cells residing within a patient. So if we’re effectively clearing around almost all cells at 2:1, but pretty much over 95% at 1:1, our current dose of $360 million falls right smack in the middle of an effective dose that we see in vitro. So to answer your question specifically, we are eliminating all T cells at 2:1 and over 90% at 1:1. And that should give us confidence that the current dose is basically on par to match that in the patient setting at $360 million.
Operator: The next question comes from Peter Lawson with Barclays.
Alex Bouilloux: This is Alex on for Peter. Just wondering if you could maybe just recap the data a little bit the ASGCT data. When you look at the preclinical and translational data for 819 versus 522, so the CAR program versus the NK cell program. Any notable differences you see in terms of tissue distribution, B-cell depletion or B-cell reconstitution?
Bob Valamehr: I can answer that question. So FT819 and FT522, obviously, are very different. FT522 not only has the ADR technology but also has the IL-15 receptor fusion. So preclinically, we see a very good biodistribution with FT522 because it very much doesn’t need antigen for expansion, doesn’t need cytokine for expansion. So we see very good biodistribution. Obviously, it has the ability to be combined with a monoclonal antibody. So we see that as well, either we enhance activity against the specific cells like, for example, targeting CD19 and CD20 at the same time or going after other cell types that have eliminated the CD19 expression and are only expressing, for example, CD38. So that multi-antigen perspective also comes in through with FT522.
The FT819 having the 1XX CAR and the track locus, it is a very potent CAR product. And so we see that when we go head-to-head against auto CAR-T in preclinical studies. So we see very potent activity within FT819, as I mentioned earlier as well. So those are the main differences in terms of behavior of the cells. We have a product that’s ADR that does not need conditioning and can go multi-antigen targeting and another product that’s very potent against CD19.
Scott Wolchko: And I think one of the comments I would just add on to that is FT819 with respect to its manufactured, phenotype has high expression of CXCR4. And so we’ve seen very good sort of homing and trafficking and infiltration of secondary and tertiary tissue in preclinical studies.
Bob Valamehr: That’s a good point.
Alex Bouilloux: And I guess does that have any implications for which type of indications you could target in the autoimmune setting?
Scott Wolchko: I mean it’s something we’re looking at. I mean we are still doing work on thinking about exactly how to expand and what indications are going to be prioritized with 819 and 522. We are prepared and now we are preparing to expand the 819 IND to consider additional indications. And obviously, we’ve discussed filing a multi-indication IND for 522. So a lot of work going on, stay tuned there on that front.
Operator: The next question comes from Yanan Zhu with Wells Fargo Securities.
Yanan Zhu: To follow up on a prior question about the bispecific literature — recent literature. Just wondering, do you have a view on depth of B-cell depletion bispecific antibody can achieve compared with cellular therapy. And do you foresee for the bispecs, if it becomes a modality, would it be repeat administration at certain time interval. Could that be viable or competitive with cellular therapy? And lastly, for 819, do you foresee the potential possibility of additional doses at a certain time interval? And whether that could be part of the product profile and whether you might even be considering looking at that in the current study?
Scott Wolchko: So forgive me, I am not an expert on the bispecific engagers. And so I can’t talk in an informative way about the depth of B-cell depletion that’s been seen or achieved with the B-cell engagers. Obviously, in the setting of oncology, the T-cell engagers have generated complete responses. So again, we are going into the field of autoimmunity, recognizing that T-cell engagers can be an attractive modality and have the potential to drive an immune reset. Whether that’s achievable, what the duration of that looks like, what the side effect of profile that looks like, how many doses, all that’s TBD. We’re very early, I think, just generally in the field of autoimmunity. That said, I think one of the potential strength of an engager is that it can be multi-dosed?
And I do think from our standpoint, as a company, we’ve always discussed the fact that an off-the-shelf cell therapy, we do think has multi-dosing potential. I think multi-dosing potential can be hindered by cy/flu conditioning, Hence, as we’ve discussed, we think it’s important to think about both 819 and 522 being developed as add-on strategies. Two standard regimens that are used today to treat patients in the community setting with autoimmune disease. And I think you will see us continue to move in that direction where we are thinking about delivering and dosing cell therapies as if they were a monoclonal antibody.
Operator: The next question comes from Bill Maughan with Canaccord Genuity.
Bill Maughan: So to follow up on this morning’s 819 data. All the PK, obviously, was positive. But thinking about translating that from an oncology patient to an autoimmune patient when antigen-dependent expansion is a key part of the PK of a CAR T-cell therapy. I was just wondering how you think about being able to translate from that — from one population to the next?
Scott Wolchko: Yes, I think there’s a lot we don’t know. With respect to how the two diseases are going to translate, I think what we have certainly seen with the PK, is that we have seen CD19 mediated expansion that is dose dependent. Certainly, the mechanism of action or one of the key mechanisms of action in autoimmunity is being able to recognize and target and eliminate CD19+ B-cells. So I don’t necessarily presume that actually the PK profiles are necessarily going to be the same in oncology versus autoimmunity. I think at the end of the day, what’s obviously critical is the kinetics and depth of B-cell depletion.
Operator: The next question comes from Ethan Markowski with Needham & Company.
Ethan Markowski: This is Ethan on for Gil Blum. So I’m just looking at the chart in the ASGCT data. And I think you guys clearly show that FT522 demonstrates deeper B-cell depletion than FT596. But it looks like FT819 graph, at least the bar graph and depletion is very similar to FT596 with themselves kind of coming back up in the mid end of the cycle. I was wondering, first, how important this complete response is? And if some sales coming back at the end is clinically relevant. And then also just from a cost savings perspective, I know you’re no longer planning to move forward in multiple myeloma and B-cell lymphoma. Just wondering if that has any impact in a positive way on near-term R&D spend?
