Zachary Klaassen: Hi, my name is Zach Klaassen, Urologic Oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on UroToday by Dr. Jason Hafron, who is a urologist and chief medical officer at the Michigan Institute of Urology and Solaris Health. Jason, thanks for joining us on UroToday.

Jason Hafron: Yeah, thanks Zach. Thanks so much for having me, I really appreciate it.

Zachary Klaassen: We're going to talk today about SYNC-T Therapy, SV-102, combination therapy, really a cool methodology for improving mCRPC patients. We'll talk about some phase one data presented at ASCO 2025, an exciting phase two trial, I know you're heavily involved with, and just the mechanism of detail for this new therapy and really how it fits into the urologist workflow.

So, I know you have your slides up, so why don't you walk our listeners through those points.

Jason Hafron: Yeah, thanks Zach. I think cool is the right description, because this is really exciting technology and an exciting trial to be a part of. And I think it starts with the mechanism of action. SYNC-T synchronizes antigens, and using a novel drug combination stimulates the immune system to fight the prostate cancer. So, it basically works in three steps.

The first step is that you freeze a small part of the tumor, could be in the prostate, it can be in any soft tissue anywhere in the body. It's about a three-minute freeze, and that releases these antigens. And once the antigens are released through a proprietary device, you slide essentially a sheath into the cryolysis zone and deliver this immune cocktail that stimulates an antigen or immune response. And that localized immune response then creates a systemic immune response that can treat metastatic disease. So, it's this concept of same time, same place. SYNC-T synchronizes the location of the antigens, the drug and the immune cells to create a systemic T-cell antitumor response.

The advantages are that you avoid a lot of the toxicity associated with checkpoint inhibitors and you're essentially taking a cold tumor, prostate cancer we know is pretty cold immunotherapeutic responses, and making it active with this personalized response. So, like you said, cool, exciting, it's very novel mechanism of action.

Here's the cocktail. This is what's infused into after you freeze the tumor site. Basically it's anti-CTLA-4, anti-PD-1, so you get this immune checkpoint stimulation and then there's also these co-stimulators, the two drugs at the bottom. And again, those are infused right after you freeze the tumor. It's a three-minute infusion and that creates the systemic response that creates the T-cell response to fight the cancer.

The cool thing too about this procedure is it involves the urologists. We're very familiar with many of these procedures. We employ commonly used MR and transrectal ultrasound for probe placement in the prostate. This works if the patient has an intact prostate, has a localized recurrence in the prostate. You placed a small cryoprobe, similar to cryoablation we would do for focal or whole gland, and this ICESPHERE cryoablation needle targets about a 10 millimeter ice ball. So, it's a few minute ice ball freeze, followed by a passive thawing.

Once the ice ball is thawed adequately, you slide this small sheath right into the ice ball or the melted ice ball, that will deliver that immune cocktail or the drug therapy. It's quick, it's easy, it's right up our alley. It's nice that urologists can stay involved in these advanced prostate cancer patients. If there's not a prostate, there was a previous surgical resection, if there's no disease in the prostate, then you get to work with your interventional radiologist where you can identify soft tissue targets. Same apparatus, same device, that they freeze a small part of a lymph node or any soft tissue that's available and then infuse the cocktail right into that melted cryolysis zone.

So, cool in mechanism action, cool that the urologist can stay involved in advanced therapies and, again, giving that personalized immune reaction to turn on this cancer, so that can be immune responsive.

The part that got me really excited when this company came to me a couple of years ago was this phase one data that was recently presented at ASCO. I don't know about you Zach, you see a lot of trials, but this was some pretty impressive numbers. Granted, it's phase one, we can't go too crazy. It's 15 patients, but you look at what they did in these 15 patients, there was a 53% complete response rate, which is eight patients. Let's be realistic here, but those are still a pretty strong signal in early phase disease. 33% or five patients had a partial response too, two patients, or 15%, had stable disease and no one showed progressive disease while on trial. So, the overall response rate was 87% in this previously treated, not heavily treated, early mCRPC patient population, which was very appealing and got me excited, and that's the reason why we're participating in this trial.

The safety profile was also very impressive. There was, again, 15 patients, we got to be mindful of where we are, it's phase one, but there were no grade threes or fours, mostly grade ones and twos. The grade three and four, there were two, I'm sorry, there was one spinal cord compression, and one urinary retention. And if you look at immune-related AEs there was hepatitis in one, and then there was one with hypothyroidism or endocrinopathy.

So, not a lot of immune AEs and overall pretty well tolerated for 15 patients. Most of the infusions, and this is what we've seen in some of the trials, is you get these flu-like symptoms, like a fever or a little fatigue at the time of infusion that goes away after a few days. So, respectable AE profile, very appealing.

And here's a case, this is a real patient that was treated... Not my patient, but was treated in phase one. And you see this complete response. You can see pre-therapy, May, 2023, the coronal of the PSMA PET, you can see multiple extensive bony lesions greater than 50. Post-therapy. December, 2023, you see complete resolution. So, you've seen this response in some of the early patients, that gets you excited and makes you want to just offer this to your patients and really test this to see if this is really true. So, it's complete resolution of 50 bone lesions.

The other thing, the way this works is that you get monthly treatments. You can do up to 12 treatments average, and this phase one was six. So, every month you monitor the patient, you bring the patient back for treatment. Again, you're trying to create that systemic immune T-cell response to go attack the cancer.

So, bottom line, phase one data conclusions, we see some highly encouraging clinical activity. A significant portion of the patient's achieved a complete or near complete response with resolution of bone metastasis. Saw no significant grade three or grade four autoimmune adverse events in this pilot study. Overall, systemic drug exposed after SYNC-T intratumoral infusion is significantly lower than IV infusion, and this further warrants further studies, and that's what I want talk to you about today is really our next phase, or phase two data where I've been involved with.

This is the phase two trial. It's now enrolling. We've treated a handful of patients to date. Part one is up to 18 subjects rolled across three cohorts. It's a traditional three plus three dose escalation rule, and then part two will be 52 subjects randomized one-to-one with two doses from dose escalation. So, we completed cohort one, which was a lower dose than what was done in phase one. Now cohort two is the dose that was published or presented at ASCO. Dose three is a little higher than what was done in the phase one, just required by the FDA.

So far, happily, things are going well. Patients are tolerating this well. But obviously we have to complete the trial to know exactly what's going on. The key eligibility criteria, what's required is all male subjects with advanced or metastatic histologically or cytologically confirmed adenocarcinoma prostate that is measurable by RECIST version 1.1, they have to have a serum testosterone less than 0.5 nanograms per milliliter at screening if on anti-hormonal therapy. Progression after receipt of greater than one approved second generation androgen receptor pathway inhibitors, and with or without a prior course of taxane therapy, or have not responded or progressed after standard therapies, or whom no standard therapy exists or is not available, no more than three prior lines of therapy able to undergo general anesthesia or conscious sedation.

Basically what we are looking is ARPI failures, early mCRPC. Generally you want to have an intact immune system, you want the patient to have a good performance status. It's not being evaluated as a late stage treatment, more of an early mCRPC option. The cool thing too is that we get to work in a multidisciplinary team. We work closely with the interventional radiologists. We review each case, identify the ideal target. Obviously we're working with our medical oncologists very closely as well, so we developed this collaborative team to identify what is the ideal treatment for the patient? What is the ideal target? And it's a balance between the urologist and the interventional radiologists to find the best place to freeze the tumor and deliver the therapy during these procedures.

So, SYNC-T has some clear advantages, and it's designed to address current treatment challenges or unmet needs. The cool thing again is it creates this personalized insight to cancer therapy for tumor antigen recognition. You create a small personalized immune response within the actual tumor, uses a multi-target approach. The cocktail has four drugs within it to address multiple immune suppression mechanisms simultaneously, and it employs local regional targeting that allows for lower dose administration, high local concentrations, less systemic exposure and reduced toxicity. We're getting the drug right into the tumor where it needs to be, not circulating it through the entire body. And it focuses on reversing immune suppression in the tumor microenvironment and tumor draining lymph nodes, to create a systemic anti-tumor response and defend with immune memory.

Summary. It's a unique approach to overcome current limitations of combination systemic checkpoint inhibitors specifically. Prostate cancer is historically a cold immune tumor and avoids the toxicity. It's minimally invasive routine outpatient procedure that can be performed by urologists or interventional radiologists. Excellent safety profile to date, only two grade three AEs, urinary retention and pre-existing spinal cord compression.
And we hate to get too excited, but there was some very impressive phase one data with over 85% objective response rate, 53% complete response rate, and a 33% partial response rate. So, the take-home message here is that SYNC-T therapy, SV-101, is a promising novel in situ therapy, employing a procedure that integrates seamlessly into standard urologic practice, that has demonstrated the potential to effectively combine multiple immunotherapies while avoiding major systemic autoimmune side effects in patients with mCRPC.

The trial is enrolling, we are still looking for trial sites. Please email us below if you're interested, or go online, or you can use the QR code on your screen to get more information.

Zachary Klaassen: So Jason, absolutely you're right. We saw this data presented at ASCO 2025, an oral presentation, and really impressive results. I think you nailed it, when you see 87% objective response rate, again, 15 patients, but this is something where we're now seeing urologists continuing to move through the advanced prostate cancer space.

Just a couple of quick follow-up questions. I know one thing I want to point out too, FDA designated breakthrough therapy as well, so this helps move things along quickly. Can you tell us, just in your experience already, is this something where majority you're targeting the prostate? How many soft tissues so far? What's the breakdown? I know you mentioned the multi-collaborative aspect with interventional radiology and med-onc as well.

Jason Hafron: Yeah, it just depends on the history. If they have an intact prostate, the researchers or the sponsor's telling us to use it as much as possible. So, they really want the prostate to be used. And most of the study was ex-US and most of these patients had surgical resection. The US we're going to see a lot of radiation, more radiation failures. So, they want us to hit the prostate, and we can hit the prostate as long as there's active tumor. So, four-ish times you want to go to the prostate, look for the systemic response and then move on to soft tissue if it's still there.

Zachary Klaassen: Okay, perfect. And in terms of just the workflow you mentioned, urologist being involved, are you doing this in your ASC operating room? How are you doing the procedure itself?

Jason Hafron: We do it in our ASC.

Zachary Klaassen: Yeah.

Jason Hafron: There was significant concern delivering this cocktail afterwards and monitoring, even within the confines of a phase one trial. But these patients have done, knock on wood, remarkably well. Because of the trial we had to monitor them, but we monitor them for an extended period and then send them home. But really the monitoring, if you were doing this clinically at this point, I would monitor them like a normal outpatient procedure and send them home, warning them you might get fevers and chills, but that's normal, that's good in a sense.

So, it works well to the urology workflow that it doesn't have to be this elaborate procedure that requires monitoring or this crazy immune reaction that's going to happen that a urologist, or can't be managed as an outpatient.

Zachary Klaassen: Yeah, no. Wonderful. Great presentation. Thanks for joining us. I'm glad you provided that QR code in the email, so if people want to get involved, they can reach out to the site and use those links to do that. So, thank you for joining us on UroToday, Jason.

Jason Hafron: Yeah, my pleasure. Always great to be here.