Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Professor of Urologic Oncology at MD Anderson Cancer Center in Houston, Texas. And we are live at AUA 2025, in Las Vegas. It's a great pleasure to welcome to the studios Dr. Patrick Soon‑Shiong, who really needs no introduction. Patrick, thank you so much for taking the time and welcome.

Patrick Soon‑Shiong: Thank you for having me.

Ashish Kamat: We know that these drugs in the BCG‑unresponsive space, pembrolizumab being the first one, the nadofaragene, and then, of course, ANKTIVA ‑‑ NAI‑‑ were studied in the BCG‑unresponsive CIS population because that's what the FDA guidance was. But there's obviously papillary patients in there. And when we look at some of the guidelines that are out there‑‑ NCCN, for example‑‑ we see that the pembrolizumab and nadofaragene are listed as options for patients with papillary disease.

We haven't yet seen NAI on there. And we know that you have data on papillary patients. So could you share with us some of the data and where you think that is heading as far as getting it on the guidelines?

Patrick Soon‑Shiong: Sure. So just to give your audience‑‑ and clearly, if your urological audience will understand it, but your lay audience may not. Within nonmuscle invasive bladder cancer, the key element for these patients is to save their bladder. As you know, it's a horrific surgery‑‑ high mortality, high morbidity. And patients will do anything to save their bladder.

So one of the key pieces of data that is necessary is, how long could the patient save their bladder when given a set of therapy? We call it cystectomy avoidance rate. So we got approval for CIS with and without papillary. And we're now fighting for papillary alone without CIS. One would think it basically entails the same.

In fact, immunologically, actually, it entails with the same disease. So what we are able to show in The New England Journal of Medicine in 2022, our patients with papillary alone, without CIS, had amazing response rate, no different from our CIS patients in the sense of its immunological activity. But more importantly, the bladder‑sparing effect‑‑ 36 months.

So we cut off the data in July 2024. And we have at 36 months for papillary disease, 82% of subjects have been able to save their bladder, with over 90% of the subjects overall survival for the disease. When you look at what we call the Kaplan‑Meier plot‑‑ and I'll share with that slide‑‑ it goes all the way out to five years.

There is no data, literally, on the planet, in the industry, in the scientific literature of papillary disease alone such as that. So when we got approved in April 2024, I approached the chairman and vice chairman of the NCCN guidelines. And there's a bladder committee of peer‑reviewed scientists that make these decisions. And the reason I approached them is because the Merck product was approved by NCCN guidelines for use in papillary disease, and so was the Ferring product‑‑ while neither of them had FDA approval.

But that's how the NCCN guidelines is, so that you can give doctors the comfort that the scientists have reviewed this and there's some meaningful benefit to go and use it. And ours with the superior data, even at that time, approached the NCCN guidelines chair and committee. And they said they will look into it.

One year later, still not approved. We approached him again and said, we'll look into it. Because the time has now gone on so far, I just presented at the keynote yesterday the three‑year data. This is the only product on the market that has data that actually preserves the bladder for patients with papillary disease for three years.

This is the only product for which is submitted to the FDA, a supplemental BLA approval. Yet this is the only product that is yet to be approved by the NCCN guidelines. I think you can't say that. I can. This level of whatever motivation that may be, whether it's conflict, perceived conflict, is not in the interest of patients.

And that's why I took the liberty yesterday of putting a slide up at the end of my talk saying, we really have to ask ourselves, are we driven by conflict, perceived or nonperceived conflict, whether that conflict is driven by pharma or whatever else it's been doing? I'm not sure. I'm not going to make any judgments.

But I do know that if you follow the science, if NCCN guidelines are supposed to follow the science, and the science is published in New England Journal of Medicine, we have to then just ask the question, why? Why is it not yet approved? So I thank you for allowing me to actually have that conversation.

But I think these are the kinds of conversations which we need as a country to have a level of transparency and have a very quiet discourse. I would love to have the chairman and vice chairman, who I've called personally, sit down and explain to me today why do they feel two drugs that they've approved that‑‑ I wouldn't call it inferior. I'm not trying to compare drugs‑‑ but have different biological activities‑‑ that have not yet even reached 36 months of data duration, but deny the approval of another.

I think these are very important questions for not only the industry to ask, but there needs to be a soul searching even in academia. And I'm from academia. You're from academia. Whose interests are we about? And I think this is why I'm now speaking out on behalf of the "consumer," so to speak.

But the consumer is just a well patient until the patient becomes a patient. So I think this is the forum, and I appreciate you asking me that question.

Ashish Kamat: No, I think it's important. Because at the heart of everything we do‑‑ or it should be at the heart of everything we do‑‑ should be the patient and the patient's interest. And the patients clearly have spoken that they don't want to lose their bladder. And how we get them to that bladder‑sparing state is our responsibility to get them there in a responsible manner.

Again, just to share some light to our listening audience, when the FDA‑‑ and we and other experts advise the FDA. And then they came up with the BCG‑unresponsive paradigm for approval. It was based in CIS because it allows them to measure effect on a cancer that's left in place.

And then the papillary for a single arm was not considered approval or regulatory pathway because they said, well, you can't control for the surgeon's expertise, so you need a control arm, which is very fair. But nowhere did they say and nowhere have they said that they would not look at that data. Because as you said, the mechanism of action to prevent recurrences is exactly the same.

There's no difference in mechanism of recurrence. It's just that, from a control perspective, to keep the trial smaller, it was decided to be CIS. So I fully agree with you that these drugs, these agents that are effective in one CIS setting, well, there's no reason they should not be effective in the others. It's just a regulatory pathway that was different.

Patrick Soon‑Shiong: When you think of the patient we're talking about, these are patients who had the surgery. But these are patients who are about to get the surgery, but were BCG unresponsive already. And then they get the surgery. And if they then do recur, I don't know what they do next.

They do anything, any desperate maneuver, including chemotherapy, as you know. And that will be a subject of our next discussion. And then, sadly, they lose their bladder, which then says‑‑ I shared with you and I shared with the keynote the quantum state of the bladder.

And the quantum state of the bladder on the patient is dependent on what we, as physicians, make a decision. You can either have a healthy, competent bladder, or you have no bladder. And that paradigm across that is‑‑ so when we have now data of bladder sparing 36 months out of 82% of patients, that then says, why do we not make that opportunity available, either through NCCN guidelines or through the FDA, to all patients who desperately seek to keep their bladder?

Now, one may say, well, what's the big deal losing an organ? And you, as a surgeon, would understand. It's a horrific procedure. The quality of life not only is horrible‑‑ the infection rate, the nephritis. So it is a really big deal. So we're talking about organ‑sparing disease now.

So that's why it really upset me very much about the NCCN guidelines. Because that supposedly is a scientific analysis of comparator. I can understand if they just say, well, fine. We're not going to deal with papillary until the FDA approves it. But they've dealt with it with two other inferior‑‑ well, I wouldn't say the word inferior‑‑ I don't want to be pejorative‑‑ with less data of bladder sparing than this has.

So I've now approached the FDA. And hopefully, with the new administration, understand what you call common sense about this is all about the patients and the health of the patient. So if you really want a healthy population, you really want a patient that doesn't suffer the loss of the bladder.

Ashish Kamat: Every time you sit down and we chat, I learn so much from you. And our audience does too. Thank you so much, once again, for taking the time.

Patrick Soon‑Shiong: You're welcome. Thank you for having me.