Read the Full Video Transcript

Ashish Kamat: Hello everyone, and welcome to part three of this chat we're having with Dr. Soon-Shiong, eminent surgeon scientist. In part one, we talked about the mechanism and how you got to your journey from discovering the idea and bringing it to bladder cancer. In part two, we talked about the official label and the indications for bladder cancer patients. In part three, I'd like to revisit a little bit of what you did with the AUA at the forum yesterday here in San Antonio. Questions that people have: where is this drug now? Is it fully available? The partnership with the Serum Institute in India, the label indication, etc., etc. So let me ask you first, the drug has to be given with BCG and people always have this question, "Well, if I have to give this drug with BCG, where is the BCG supply shortage in this country going to go?" And I know you've taken steps to address that. So if you could share with the audience, where your thoughts are and where we're heading.

Patrick Soon-Shiong: Even during the trial, we had trouble because of the BCG shortage, as we're post-COVID and Merck has tried very hard. As you know, they are the only manufacturers, currently, of BCG. We recognize that if this drug gets approved, we have to address it on behalf of the United States and the world. And we didn't have that capacity, but the Serum Institute of India certainly had that capacity. Not only did they have that capacity, it's a magnificent organization with GMP manufacturing facilities that produced this for 20 countries in the world already, not only for TB but for bladder cancer. So we approached that institute and happily we signed an exclusive agreement, not only to bring back BCG to the United States, but to bring this next generation BCG that they're already doing phase one and two in Europe called recombinant BCG.

So we will be launching, together with the Serum Institute, the availability in the trial format of Anktiva plus BCG, and obviously the label allows Anktiva plus BCG for any BCG. But the label currently, the standard of care today in the United States is Tice BCG. We need to get the Serum Institute BCG approved through the FDA to replace or be on terms with Tice BCG. So that trial will be opening as soon as we can get that through the trial mechanism of the agency. That molecule is available to be shipped today. That BCG is available in the hundreds of thousands of doses at Serum Institute. Our Anktiva, as I shared with you in the last episode, we have over 170,000 doses if that's needed. So supply is not going to be an issue, and we plan for that. It took us many years, two years, to plan and produce and invest for that because we want to invest for success if this drug got approved.

In order to have the logistics of that easy for the urology practices, which is really difficult, we want to ensure that there's no difference in ordering, change, or workflow with that of BCG because it's mixed with BCG in real time. So we've also accomplished that, and that is really in motion. I'm happy to share with you that the first hub ordering has gone through successfully with the software, and that's at anktiva.com. If you just press that, you'll get through the logistics availability of that ordering.

Ashish Kamat: That's a very important point you bring up because the urologists, the academic centers that only may deal with bladder cancer, have that workflow set up, but we have a lot of colleagues in the community and a lot of our patients in North America actually get their care in the community. So it's very important for the community practice urologists not to have to disrupt their whole day or workflow. Could you again, educate the audience a little bit on exactly what you said, what was done in the trial, how it's mixed with the BCG, what's the actual workflow for those that are listening in and thinking, "Should I get this at my practice?"

Patrick Soon-Shiong: So the workflow for BCG, I think everybody understands the workflow for BCG, in which you actually take the BCG vial and if you look at the Tice label, you actually reconstitute it into 50 cc's and you pull it out and put it into the syringe and inject it into the Foley inject. Nothing changes, absolutely nothing changes. That's the workflow. The only difference is that as you add the BCG, you also add the Anktiva. So it's as simple as that, which is quite remarkable. So again, just to repeat, you take out the BCG and you take out the Anktiva from the fridge. If the patient doesn't show, you put it back in the fridge and it's fine and stable for 24 months. So there's no danger of thawing or re-thawing this. It's not frozen. You then reconstitute, like you normally do, you reconstitute BCG and you just add the Anktiva into that same 50 cc reconstituted volume and you put it into your syringe and inject it.

So from the nurse and from the pharmacy workflow, nothing changes. From the urology workflow, nothing changes. You put it into the bladder, you hold it there for two hours, and you send the patient home. So that's what was exciting because what we are really doing is activating the immune system inside that bladder. By the way, what's also exciting, our PK shows it doesn't go through the bladder wall. So there's no systemic absorption, meaning it's a completely local effect. And that's why the adverse events are no different from that of BCG. Some may say it even alleviates some of the BCG adverse events, but that's not what we've said in the label. So the grade three, four adverse events are 0% to 3.4%. 0% grade three with all the urinary frequency, etc. That's in the label. And for a practicing urologist in the community, we've not changed anything.

Ashish Kamat: And that's very important. And also what you mentioned about the fact that if you thaw it and it doesn't get used, you can put it back and it's stable because some of the practices will always be thinking about cost and how to save precious healthcare dollars. So that's a very important point you brought up.

Patrick Soon-Shiong: Well, it's not frozen, so it doesn't need to be thawed. So this is exciting. You just pull it out of the fridge, if the patient doesn't show, you leave it back in the fridge or you needn't take it out and it's stable there for 24 months.

Ashish Kamat: Exactly, exactly. The other point I wanted to ask you about, and it has something to do with the whole issue nowadays, there's a BCG shortage in the country. And I know this wasn't part of the label, but from a mechanistic standpoint, if a urologist were to want to use a reduced dose of BCG with the drug, do you have any sense as to whether that's okay for them to do to save the BCG?

Patrick Soon-Shiong: Yeah, it's not in the label, but I can tell you some of the science, and we did a planned subgroup analysis in terms of how much BCG the patient received, less than 12 and greater than 12, and published in the New England Journal of Medicine. And again, I want to emphasize it's not in the label, but it was a planned subgroup analysis of that subgroup. There was no difference in either CR or duration response. So that's the good news because it's an immunological stimulant. What I'm really excited about is the potential that the Serum Institute's next generation recombinant BCG is even more potent, more immunogenic, and even, according to them from the phase two data in Europe, safer than the current BCG. So yes, I think the combination of the synergistic effect of the BCG giving you the CD4, CD8 T cells, and then our Anktiva proliferating that as well as giving NK cells, is really, really exciting as this next immunotherapy generation for bladder cancer.

Ashish Kamat: Yeah, and the recombinant BCG that they've had, we've seen the phase one, phase two studies coming out of Europe and everyone's been anxiously awaiting some way for them to be able to hopefully come in and get studied here. So that's a big push and a big benefit for our patients. It's appropriate that this is May, this is Bladder Cancer Awareness Month, and there's so much activity going on, not just with the approval of the drug, but also with your efforts to get more BCG into the US approved by the FDA. In closing, I would love for you to share with me and our audience your thoughts on where this or the company is going next in urology.

Patrick Soon-Shiong: Well, I think, as you could see, you understand that T cell is used for all tumor types. So within the bladder world, we are going to muscle invasive next. We are looking at a bladder sparing opportunity, trying to transform truly bladder sparing. If we can capture patients in muscle invasive before they metastasize and create a complete response there, then we're going to go into metastatic disease, which is the same. All within the bladder world. Within the prostate world, to me, that's one of the most exciting areas that we're going to go right now because one of the areas is basically active surveillance and patients who, let's say, had a prostatectomy, they can get radiation if their PSA goes up. We don't know where the cell is, but this is exactly where we can activate that natural killer cell. And then thirdly, the BCG, getting the recombinant BCG.

What I've learned, and I didn't know this, is that all the current Pasteur strains, Connaught strains, Danish strains of BCG sit inside the cell and really stimulate mainly CD4 T cells, and a little bit of CD8. What this recombinant has done, they've taught this BCG to not only make CD4s but actually get out within that cell to make high doses of CD8 T cells. Now, that to me, was why the biological basis of increased immuno stimulation. So to me, I think hopefully at the next AUA, this recombinant BCG, we will study it, show it. Hopefully at the next AUA, we'll actually have some data on the muscle invasive bladder cancer and hopefully we will actually show some data on prostate cancer.

Ashish Kamat: Excellent. Looking forward to it. Thank you so much for taking the time, Doctor.

Patrick Soon-Shiong: Thank you for having me.