We did this to the number of APOE4 alleles, the MRI features themselves and the clinical manifestation. So, it really – we don’t see any differences, and we have shown it to a number of the ARIA experts who have also said that this is really indistinguishable.
Marc Grasso: And I think we don’t see any difference between the main study and the extension study, Myles, to your question.
Myles Minter: Okay. So, no difference from the 19% to 23% that you reported at AAIC compared to your most…?
Gary Romano: Yes. No, sorry. We are blinded to who is who in the study. But so far, we have seen very little ARIA in the long-term extension, that…
Marc Grasso: Earlier days with the extension of the study, Myles. So, to try to draw inferences from those percentages would be difficult.
Myles Minter: Thanks for the questions.
Operator: Thank you. [Operator Instructions] And our next question is coming from Neena Bitritto-Garg of Deutsche Bank. Your line is open.
Unidentified Analyst: Hi. It’s Avi Novak [ph] on the line for Nina. Thank you for taking my question. So, on the ABC technology, can you discuss how your transferrin approach differs from other transferrin-based delivery platforms? And then also on INVOKE-2, given what you know about the AL002 mechanism, which biomarkers do you see as being most likely to be correlated with improvement on CDR Sum Of Boxes or any other clinical endpoints? Thanks.
Sara Kenkare-Mitra: I can start with the ABC technology, and then Gary can address your second question. So, in terms of our BBB approach, it employs a versatile blood-brain barrier carrier technology, which uses a suite of fragments that target both TFR and CD98 heavy chain. What we found is that thus far, we are getting about ten-fold increases in brain concentrations, utilizing these multiple cargoes. I think what’s unique about our technology is that it is an adaptable technology and it’s sort of modular and is customizable based on the sort of the requirements of therapeutic affinity, valency and format, and we can match that to a variety of cargoes. We use bispecific formats, and we are also able to customize and make adaptations to the Fc portion and have been able to sort of tweak a variety of ranges of effective function as well as half-life.
And as we said in the call, our safety and efficacy studies in non-human primates thus far suggest a favorable safety and efficacy profile, even when we have Fc engagements. And we will be – by the way, we will have a webinar some – I don’t – the date is not set, but sometime this summer, which we will go into a lot more detail on our technology. So, pleased to join at that time. And I will pass it to Gary.
Gary Romano: What was that question? I am sorry. I didn’t hear it.
Unidentified Analyst: Yes. So, for INVOKE-2, and given what we know about the AL002 mechanism, which biomarkers do you see as being most likely to be correlated with improvement in CDR Sum of Boxes or more generally our…
Gary Romano: Yes. Sure. Well, again, that would be the biomarkers of Alzheimer’s pathophysiology. Most importantly, I think the tau biomarkers, both, we will have tau PET, which would be a tau PET sub-study. But we will also have plasma biomarkers on everybody in this study, the p217, and hopefully a microtubular binding region assay as well. So, this will give us a – that’s the – really the tau biomarkers are the ones that correlate most closely with clinical outcomes and really can be seen, I think as sort of summing up the effects, all these hypothetical effects of benefits of healthy microglia on slowing the disease progression.
Unidentified Analyst: Alright. Great. Thank you and congrats on the quarter.
Gary Romano: Thank you.
Operator: Thank you. [Operator Instructions] Our next question is coming from Thomas Shrader of BTIG. Your line is open.
Unidentified Analyst: Hi. Good afternoon. This is Tom on for Tom. So, for the ongoing Phase 2 progress AD study, is there a reason to perhaps stratify these patients based on baseline programming level for any possible sub-analysis in the future? Thank you.
Gary Romano: Yes. Thanks for the question. We did not do – we are not doing that. And that’s because part of the evidence in favor or in support of this mechanism is that even modest bad mutations that cause even very modest effects in pro-granulin levels, increase the risk of Alzheimer’s disease. And so, we didn’t believe that it would be necessary. And our hypothesis is that this would be effective in slowing disease progression regardless of your baseline for granulin levels. There is also animal data, which we may want to speak more to that shows that in various animal models of Alzheimer’s disease that just elevating progranulin itself is protected against disease progression.
Unidentified Analyst: Great. Thank you.
Operator: [Operator Instructions] And our next question will be coming from Ananda Ghosh of H.C. Wainwright. Your line is open.
Ananda Ghosh: Yes. Hi. Congrats on the quarter. Given the biology of TREM2 and from your own ARIA data, I think there is little doubt that experts believe – there is little doubt on the fact that the TREM2 might be involved in plaque removal. However, one question which I have, and that’s based on the latozinemab and also a lot of questions on tau biomarkers today here. Given the data from those two trials and the recent publication validating plasma pTau217, do the MRI – the tau PET abeta data along with the plasma tau biomarkers puts you into a position where you can negotiate an accelerated approval pathway, which strategically might be very similar to the QALSODY approach? So that’s the question. Thank you.
Gary Romano: Yes. Thank you. So, if I understand your question, you’re wondering whether based on changes or just – or treatment-related changes on tau PET or on tau biomarkers, could that be the basis of an accelerated approval approach?
Ananda Ghosh: Right. If there is a clear sign that there is a remarkable change in the plasma tau biomarker based on the plaque removal, is there a potential for activated approval pathway similar to QALSODY approach?
Gary Romano: Yes. I would never say no. And I would say that when we open this up and we see what we have based on the robustness of the findings, we would certainly – if we thought that it was robust enough, we would certainly consider that. We have also had questions about, well, if we see very significant amyloid lowering could that itself – could that also be? And again, I think a way of going at this differently, that’s not the original intention in this trial and – but of course, when we open it up and we see what we have, if we think that there are potential paths forward, we will certainly explore them.
Ananda Ghosh: Alright. Thank you.
Operator: Thank you. And our final question today will be coming from Graig Suvannavejh of Mizuho Securities. Your line is open.
Marc Grasso: Graig, are you there?
Operator: I would now like to go ahead and turn the call back over to Marc Grasso for final remarks.
Marc Grasso: Thank you, operator and thanks everyone for the thoughtful questions. Before we end the call, I’d just like to share that we will be participating in a number of upcoming conferences, including TD Cowen’s 44th Annual Healthcare Conference on March 5 in Boston, Leerink’s 2024 Global Biopharma Conference on March 12 in Miami, Barclays Global Healthcare Conference on March 13 in Miami, and Stifel’s C&S Days on March 19. Thank you again for your time and attention. We’ll now conclude today’s call.
Operator: This concludes today’s conference call. You may all disconnect.
