Sam Chang: Hi, I'm Sam Chang. I'm a urologist in Nashville, Tennessee, and we have the pleasure of getting an update on the Oncuria bladder detection testing on which a lot of research has been done by Hideki Furuya, who is at Cedars-Sinai in Los Angeles. And we've asked him to give a presentation. He's got a few slides to give us an update on this important urinary detection test for different types of urothelial carcinoma.

So Hideki, thank you so much for being with us.

Hideki Furuya: Thank you very much for the opportunity. The title is "The Performance of the Oncuria-Detect Bladder Cancer Test for Evaluating Patients Presenting with Hematuria." And this presentation is to report the results from real-world clinical setting data.

As you know, there are many cases of hematuria reported; actually there are 2 million cases of hematuria reported in the US per year and 1.5 million cases undergo urine cytology, though its sensitivity is as low as 34%, and unfortunately, most patients will undergo cystoscopy afterward, which is an invasive test.

To solve these issues we would like to introduce Oncuria, which is the first and only multiplex immunoassay for the detection and management of bladder cancer. So Oncuria measures 10 urine protein biomarkers associated with bladder cancer, including A1AT, angiogenin (ANG), ApoE, CA9, IL-8, MMP-9, MMP-10, PAI-1, syndecan-1 (SDC1) and VEGF.

And there are three tests within Oncuria. The first one is Oncuria-Detect, which detects de novo bladder cancer in hematuria patients. And the second one, Oncuria-Monitor, detects recurrent cancer in patients with a history of bladder cancer. And the third one is to predict BCG treatment response. And these three tests use the same 10 biomarkers, however, they use different algorithms to calculate the risk score.

This is an overview of the Oncuria Assay. First, patients collect urine, which is completely non-invasive and then easily sent to ClearLab. And once ClearLab receives the urine sample, they process urine by centrifugation and then directly analyze the protein levels using a Luminex-based assay. No need to extract protein. And then the data will be uploaded to the portal, which immediately calculates the risk score.

So this is the study design. The objective of this study is to assess Oncuria-Detect's diagnostic performance in a real-world multi-center setting. We had 1,000 urine samples from subjects prospectively collected from seven global centers, including USA, Japan and France. And 931 subjects of the 1,000 were diagnosed with hematuria. And we had 69 disease controls collected from prostate cancer patients and renal cell carcinoma patients. So we divided these 1,000 samples into the training cohort and test cohort and then we trained the algorithm and then locked it down.

Now this is a quick overview of the results. The left side is the training cohort, the right side is the test cohort, and cases meaning detected cancer and non-cancer as the control. So as you can see, all the biomarkers except for syndecan-1 showed significantly high levels in cancer patients.

We saw the same results in the test cohort, even though we had disease controls, which showed slightly higher levels than the true controls. But still we showed significantly high levels in the cases. This is very encouraging.

But we still kept syndecan-1 because this helps to distinguish aggressive cancer.

So this is a summary of the results for distinguishing cancer. I'd like to emphasize that the NPV is really high in the total overall cohort: 96%. In this cohort we showed 76% accuracy, sensitivity of 87% and specificity of 74%, which is great. And also in this test cohort, validation cohort, we saw almost the same results.

And I'd like to highlight that in the non-muscle-invasive bladder cancer patients and also low-grade cancer patients, we still see almost the same level of NPV here and here. But with the high NPV value, we are able to effectively rule out up to 60% of patients from requiring subsequent cystoscopy.

And also, as I said, syndecan-1 along with the other biomarkers, we could identify high-grade, high-stage cancers.

Now, when we talk about bladder cancer, we are always asked, can we also use Oncuria for the detection of upper tract urothelial carcinoma? And the answer is yes. This is a pilot, I mean, this is an unpublished study and as you can see, the NPV of Oncuria is still high for bladder cancer, and this is the voided cytology data. NPV is low at 31%. And selective cytology shows high sensitivity. However, remember that this is an invasive test. That's why when we compare Oncuria and voided cytology, apples to apples, Oncuria outperforms cytology.

Let's compare with the existing tests. As I said, cytology showed low sensitivity of 48% and specifically for low-grade tumors, only 16%. And other tests, FDA-approved protein tests including NMP22, BTA test also showed low sensitivity of 25 to 36% in identifying low-grade cancer. And the newer version of them, the single-plex protein assay, ADxBladder, also showed low 50% sensitivity for the detection of low-grade tumor.

And so, to emphasize, Oncuria outperforms single-plex assays, especially for low-grade detection; Oncuria showed an NPV of 98%.

And how about the clinical impact? So in terms of clinical utility, Oncuria-Detect shows high sensitivity, 85%, and NPV 95% for ruling out bladder cancer and identified both low-grade and high-grade tumors with clinically useful performance. And healthcare impact. So we could eliminate unnecessary cystoscopy in up to 60% of hematuria patients. This could potentially save a lot of money.

And also how about the reimbursement status? This test is currently clinically available and Medicare-reimbursed already, meaning that this assay is actionable.

The conclusion. Oncuria-Detect showed high sensitivity and NPV in real-world hematuria triage. Multiplex protein panel enhances the accuracy over existing tools. A promising non-invasive tool for the detection of bladder cancer.

The future direction is to test in additional cohorts including gross hematuria and microscopic hematuria. These two studies are currently running, and we just finished the gross hematuria recruitment and now we focus on the microscopic hematuria recruitment. Once we're done and then we will analyze the samples and the data and then release the results.

Thank you very much for your attention.

Sam Chang: Hideki, thank you for the presentation and overview. Whenever you have a conclusion slide about next studies, it always begs the next questions about those next studies.

So specifically as you use the training and test cohorts of different patients, if you look at that negative predictive value of basically 99% for different scenarios, but quite high, in reality, I mean you know if I take 100 people with microscopic hematuria, 99% plus will not have anything wrong.

So to me what's most appealing maybe would be the negative predictive value with the gross hematuria. If you really have data that shows the negative predictive value still is very high in gross hematuria patients, to me that's actually quite unique and would be quite helpful.

Do you know the breakdown yet of those patients with gross hematuria? How good is the negative predictive value in that cohort?

Hideki Furuya: Specifically only in the gross hematuria, yeah, we haven't done the analysis yet, I believe.

Sam Chang: Yeah, because you know they're gross and microscopic and-

Hideki Furuya: Yes, that's right.

Sam Chang: And because there are many scenarios, obviously there's some concern with female patients and delayed diagnosis with UTI and gross hematuria, but you could see how that would be helpful. You could also see people who have gross hematuria, who have a history of BPH or a history of radiation, a history of other conditions, if you could rule out, if these 10 protein changes aren't there, and we can rule out cystoscopy for almost all of them, that would also be very helpful.

So as you gather more data, we look forward to hearing more about the possibility.

Hideki Furuya: Yeah.

Sam Chang: I want to know a little bit more about the upper tract studies.

Hideki Furuya: Sorry, before we go to the next questions, let me chime in.

So, yeah, those are good questions. So the problem with the previous test, the BTA, is that the BTA test detects blood, not the antigen, to be honest, and that was our concern, too. So we did the same test, so we spiked blood into the urine sample to see if spiking blood could change the result. And actually some of the inflammatory molecules increased a little bit, however it didn't influence the actual results for detecting bladder cancer or not.

Sam Chang: Got it. Got it.

Hideki Furuya: Yeah, so that said, I think we haven't done the data analysis yet. However, I think either gross or microscopic hematuria may not affect the data.

Sam Chang: Got it. Tell me about the upper tract portion of the patients. So with these patients it looked like there was, again, pretty good negative predictive value for both low-grade and high-grade disease, which is great.

Do you know in that group, there were smaller numbers obviously, they were all only upper tract, none had bladder cancer, is that correct?

Hideki Furuya: Yes, that's correct.

Sam Chang: Okay. And it's from a voided specimen. It's not from a washing or anything like that, correct?

Hideki Furuya: Right. Yeah, that is voided urine, yes.

Sam Chang: Yeah. So again, you can see how monitoring these people with known upper tract urothelial carcinoma, we do repeat ureteroscopies many times. MRI or CT scans can be expensive. If we could monitor with a urine test saying that, "Oh, it looks like you're cleared of your disease," especially as we try to do more nephron-sparing types of treatments, laser therapies, chemoablative therapies, you can see how this test could work quite well.

As you look in the future, I know you're looking at gross and microscopic hematuria, tell me what Oncuria is looking at in terms of future studies with upper tract disease.

Hideki Furuya: Yes, upper tract cancer is, as you know, a rare cancer. So it is very difficult and may be unrealistic to open a clinical trial. However, yes, we are still interested in monitoring upper tract cancer patients.

And the good thing about this test is that it will provide not only yes or no, cancer or non-cancer, but also provide you with the risk score so you can see the increase in the risk score. So that is a good point for monitoring. So if you see an increase in the risk score then you may make a better decision.

Sam Chang: If things look quite stable, that makes everyone feel better. But if you start seeing a rise, maybe then you do your ureteroscopy or repeat invasive evaluation. Hideki, thank you for the update, especially as you gather real-world data and look at two different cohorts to really determine the effectiveness of a 10-protein panel marker.

I think the strength of this is, as you have highlighted, the ability to utilize the combination, as opposed to a single marker, which is really helpful in terms of honing in not only on the specificity but the sensitivity of this test as well. So please reach out. We look forward to future updates and look forward to perhaps even trying this as we help monitor patients and evaluate patients with not only hematuria, but with bladder cancer as well.

So thanks again, Hideki, and look forward to seeing you again soon.

Hideki Furuya: Thank you very much.