And besides what’s publicly available, there is a lot that we’ve learned on drug development of degraders in immunology, going back to preclinical, to talks, to CMC, to clinical trial strategies. So, I think that has inspired us and has driven us to take that concept in equally large clinical opportunities. I think what we — and so you will see in January, that the programs and the data that we are generating are impressive. And maybe I’ll leave it at that. With regards to 333, I think what we’ve learned for sure is that this is an extremely powerful mechanism. And it seems to be — it seems to have, at least so far in oncology patients, a good safety profile as of the data we’ve disclosed so far. And so that has probably told us that there are pathways of particular targets that will be or can be amenable to this approach even if the safety of that particular pathway or the particular target had not been previously derisked either in the clinics or through human genetics.
So maybe that, hopefully, will give you an idea of what we will be talking about in January.
Justine Koenigsberg : And just a reminder, we do not have enough time to get through the remainder of the Q. We’d like to ask that you limit it to one question.
Nello Mainolfi : Maybe I’ll try to be faster in the answers.
Justine Koenigsberg : Next question, operator.
Operator: Next from Michael Schmidt of Guggenheim. Please go ahead.
Unidentified Analyst: Hi, good morning. This is Paul on for Michael. Thanks for taking my question. Mine’s on KT-253. I just wondered if you could provide some color on the Merkel cell carcinoma patient who had a PR. Do the patient have MDM2 application or any biomarkers like CDK and 2a [ph] loss that might be related to the response? And were you able to achieve your target degradation level in this patient? And just trying to understand the activity here at level one. Thank you.
Jared Gollob: Yes. This Merkel cell patient was p53 wild type and had the Merkel polyomavirus, the majority of Merkel cell carcinoma patients have that virus in our p53 wild type. That patient had previously been treated both with chemotherapy, and in the past, with anti-PD-1 drugs, which have been shown to be effective in Merkel cell. The patient had responded initially to anti-PD-1 and then had progressed after their latest anti-PD-1 before coming on to our study. I think on the study trial on dose level one, that patient did have a very robust induction of GDF15, which as we mentioned, is the downstream biomarker of MDM2 degradation. And so that particular patient who had that has an ongoing partial response, did show clear on-target pharmacology with elevation of GDF15.
And so, we’ve been very encouraged that even at the very first dose level, we’re seeing this sort of response, a partial response in this type of solid tumor that had previously progressed after anti-PD-1. And that really sort of does so far support our mechanistic and therapeutic hypothesis about being able to affect these p53 wild-type tumors with p53 activation and pathway upregulation, with a safety profile where we’re not seeing any hematologic toxicity, which was the case for this patient as well.
Operator: Next question will be from Srikripa Devarakonda of Truist Securities. Please go ahead.
Srikripa Devarakonda : Hi, guys. Thank you for taking my question. I was at the TBD conference. And one takeaway seems to be that — or one comment, I would say, was degrader does appear to be held at a higher standard for safety than historically small molecules have been. Do you think there is now a standard established in how you evaluate safety in the field? Do you think it is case by case for each drug? And just broadly, do you expect things to continue to evolve until we see early approvals in this space?
Nello Mainolfi : No, great question. So, I don’t know. I think maybe, your comment reflects the fact that this is a new generation of medicines. And while I think it’s not really broadly appreciated that this is a new generation of medicines probably, because probably the mechanism is not fully well understood by distract observers. This is a new generation of medicines. And so, with that, obviously, you always come to the questions of the interplay between safety and efficacy. So, I think that’s probably what’s driving some of the questions. Personally, I think it’s been shown now extensively by approved drugs. There are degraders, and we’ve talked about the image that have been on the market for years, for decades. And then all the investigational drugs that have been in the clinic for years now from companies in the space, that any safety to do with a degraded program is tied specifically to their on-target and off-target safety profile.
And there is no safety that we, at Kymera, have seen that had to do with the actual technology. So obviously, if you have a well-tolerated mechanism, and you don’t have off-target activities, I think you see molecules be well tolerated. And I think that has been consistent across the industry. Now, this is an extremely powerful technology, and this is why we believe has huge potential. And so, specificity of our molecules has to be paramount. And I think that’s what I encourage, obviously, everybody to be focused on.
Operator: Next question will be from Derek Archila of Wells Fargo. Please go ahead.
Derek Archila: Thanks for taking my question. Just one. So just given the future focus on sizable I&I indications, I guess. How does that change the calculus on cash runway? And I guess, is it fair to assume that you’ll run more traditional Phase II studies to achieve proof of concept for those programs? Thanks.
Nello Mainolfi : Yes. So maybe I’ll answer the question. Bruce, if you want to add anything to it. So, I think it’s noted that through being more financially responsible, as we’ve said today, we’ve extended the runway from the second half of ’25 to now the first half of ’26. And that includes all the plans that we have for our expanding immunology pipeline. I just want to be sure that’s clear. We will develop those drugs with the goal to approve to launch registrational studies as quickly as possible, while continuing to validate that our, obviously, investment thesis is playing out also in early development. So, I think it would be a mix of validation that is needed, right, to continue to do large investments, but also an eye on path to approval in these large indications. And as you know, with the evolving landscape, it’s important, it’s extremely important
Operator: The next question will be from Chris Shibutani of Goldman Sachs. Please go ahead.
Chris Shibutani: Thank you. Many of the questions have been asked. But again, with regard to the immunology strategy imbrues, are you thinking about ultimately collaborating or partnering some of the more advanced clinical development? And part of the protein degradation was brought up quite prominently in a recent R&D presentation from a large type pharma in Bristol. And as we think about new medicines, cell therapies moving into immunology as well, if you had to guess kind of where the puck may go, and what might be unique about targeted protein degradation that will ultimately differentiate, what might that be?
