Gary Nabel: Well, just to take a step back, Moderna actually is delivering through mRNA almost the same gene products that we’ve managed to engineer onto the ferritin nanoparticle. I’d say for the good of the patients, it’s actually a good thing to have more than one product out there being tested because, one never knows how they will perform in the real world. I think what we like about our platform is the fact that it’s a protein platform, and we’re using adjuvants that are well described with a safety profile that looks favorable in humans. The preclinical data in non-human primates and in our animal models is very strong. And so we’re following a pretty well prescribed path with a nice set of immunogens where, I think we, and with great biomarkers when you’re looking at, viral loads and immune responses to the virus.
So we feel pretty good about our product. I really don’t want to get into the details of the alternative program, but what I will just say is the obvious, which is that they’re using a different platform. They’re using an mRNA platform that has some advantages in terms of going fast, but it has some unknowns, particularly with regard to side effects of the therapy. And, as you begin to treat more and more patients with a vaccine, those issues become more and more important. And so there’s no way to, ordain or to have a crystal ball about which will work better. But we feel pretty good about the platform that we have and the partnership with Merck, where they have, a real deep bench of experts and knowledge for how to expand the trials and how to expand the reach of this vaccine to what we would ultimately like to address, which is the cause of cancer or the cancer aspect of the vaccine.
So that’s, I think that’s the best I can do for you right now.
Yale Jen: Okay, great. That’s very helpful. That’s a lot of details here. Maybe one more in terms of the 2001. Is there any, could you give us some detail about the study design and maybe what are the targets being pursued by this tri-target antibody? Thanks.
Gary Nabel: Yes, we haven’t formally disclosed the targets, but we will disclose them in the near future, probably within the next few weeks as we line up to enroll our first patient. But what I can tell you is that we picked two cell surface markers that are found on a number of solid tumors. There actually is a list of about 13 malignancies that express these two antigens. And they include lung, breast, prostate, pancreatic, and the list goes on. There’s a fairly large number to be tested. And we will, in the initial stages, look at a variety of those tumor types. And we’ll be looking for signs of some tumor types where we might be seeing more efficacy. And then with time, if that bears out, we’ll focus more on the tumor types where we’re seeing efficacy and expand the trials in those tumor types.
Yale Jen: Okay, great. That’s very helpful. And congrats to move this program up the ground.
Gary Nabel: Thank you. We’re very excited to see it get to patients.
Operator: Thank you. And the next question comes from Yi Chen with H.C. Wainwright.
Yi Chen: Thank you for taking my questions. Just to follow up on the MDX2001, the Phase 1 solid tumor trial is an all-comer solid tumor trial, correct? And how many patients do you intend to enroll for this trial?
Gary Nabel: The trial is broken into parts. So we have the Phase 1a and then a Phase 1b. I’d say in the Phase 1a will be the group where we will look at multiple different types. And then after that point, we will begin to drill down on the ones where there’s more activity. We expect to be able to make some decisions with approximately 40 or so patients in the first. And that includes some dose escalation because we have to go slowly. And we will do that again in agnostic to the tumor type. And then when we reach what we think will be close to a therapeutic level, assuming we don’t see any side effects that would preclude further expansion, then we would treat the larger number.
Yi Chen: And just to clarify, did you say that the results from the Phase 1 trial won’t be available until 2026?
Gary Nabel: I didn’t really say when they would be available because I said probably not before next year is what I said earlier. And I would stand by that. It does take a while to get to the point where you think you’re in a therapeutic dose. And then you have to enroll sufficient patients. And then you have to follow them for a period of time. So expecting to see even early efficacy data. We certainly will have safety data, I think, before the end of this year that tells us what doses and how well tolerated it is in patients. But I don’t expect that we’ll begin to start seeing signals until well into next year.
Yi Chen: Got it. And could you give us some idea that how many oncology candidates you intend to bring into clinical stage of development before the end of 2025?
Gary Nabel: I would say that we have, it will be in the range of two to four. I think very likely there will be two that will be into the clinic by next year. Then depending on some partnerships, we may have opportunities to advance another two.
Yi Chen: Okay. And for partnerships, is it likely that you will need to generate Phase 2 level proof of concept data to materialize a partnership?
Gary Nabel: You know, I think, Elias, would you like to respond?
Elias Zerhouni: No. I wanted to just clarify that it’s very different in oncology than in other areas. Because in oncology, you start with patients. You don’t need Phase 2 data to generate a partnership. You need to have a basket trial and some demonstrable result in a Phase 1, 1b, and beginning of 2. But you don’t need to do what you need to do in other areas, where you need to complete Phase 2 to attract a major partner who would like to be a strategic buyer. I don’t know if you agree with that, Gary.
Gary Nabel: Yes, I very much agree. I think that often in oncology, you can begin to see signals in Phase 1. And then in instances where you don’t, really just depends on the appetite of the partner and of our internal teams in terms of at what point we really want to make those transitions. So, I’d say the safe answer is somewhere between Phase 1 and Phase 2.
Yi Chen: Got it. Thank you.
Operator: Thank you. And the next question comes from Michael Petusky with Barrington Research.
Michael Petusky: I just want to ask about the Rayaldee and you guys have been indicating for the last few months, at least, or several months, maybe, that, we’ve got some, we think we’ve got some data. We’ve got some evidence that, the product may slow CKD progression. And I’m just curious. I mean, are your sales folks able to share this data, this evidence with a nephrologist, or are there any even kind of anecdotal reactions that, yes, this is really compelling. This may really matter. I mean, can you just give a sense of, if there’s, if there’s any sense, that this could really unlock this product, going forward? Thanks.
Elias Zerhouni: I can expand on that. I mean, it’s clear that the data that we generated this year was very telling from real-world evidence, as well as from our own data, that you could delay the onset of dialysis by six months, if not more. Now, in terms of the reception of that, we’re publishing, obviously, but presented to KOLs and nephrologists, it really makes a difference because no other therapy of secondary hyperthyroidism has shown the ability to do that. And it shows also we have the biomarkers that really indicate which patients are the ones that really will need the Rayaldee to delay the onset of their dialysis when they’re CKD-4. So, yes, the sales force is out there. Yes, it’s talking to the nephrologists who see a lot of late-stage CKDs that are likely to go into dialysis.
But we also think it’s valid for CKD-3 patients, not just 4. So, a story in evolution, I think it reinforces the point that treating secondary hyperthyroidism in this patient does have an impact on the evolution of the disease, which was one of the questions we always have, does it change outcomes? And this is the answer that we have so far. And the data has been reviewed and is going to be published.
Michael Petusky: Can I just add a follow-up to that? In terms of, okay, so you get the data published and you start talking to docs about this. I mean, how long, things sometimes seem to move much slower than they logically seem like they should in terms of changing behavior, prescribing behavior. I mean, is this the kind of thing that, it’s really a missionary effort and it’s a matter of years rather than quarters or, to really change behavior, or, if the data is that compelling?
Elias Zerhouni: Absolutely. I think that’s the right question. I mean, if you do medicine, medicine patterns and clinical guidelines take time to develop. I mean, you’re talking about a year or two before they make it to the guidelines, but, well, they’re using the guidelines now. So it’s not a rapid process. Depending on the strength and reception of the community of pathologists who deals with that, it may be faster or slower, but it’s not a matter of a quarter or two. It will take time to develop.
Michael Petusky: All right, very good. Thank you.
Operator: Thank you. And this concludes the question-and-answer session. I would like to return the floor back to Dr. Phil Frost for any closing comments.
Phil Frost: I just want to thank everybody for participating and for your very good questions and discussion. And we look forward to being together with you again at the end of next quarter.
Operator: Thank you. The conference is now concluded. Thank you for attending today’s presentation. You may now disconnect.
