Combination Platform Delivery In Immuno-Oncology With Syncromune's Eamonn Hobbs

Fundamental goals of immuno-oncology therapies are to generate T-cell responses and overcome immunosuppression. In this episode of Sit and Deliver, host Tom von Gunden talks with Syncromune CEO Eamonn Hobbs about using injection- and infusion-based drug-device combination therapies in targeting solid tumor cancers.

Interested in joining Tom on an episode? Contact him today.

Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Sit and Deliver, the series in which we hear about innovations and advancements in drug delivery from leading thinkers in the space. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader and your host for the series. Today I am joined by Eamonn Hobbs, CEO of Syncromune, which is a biopharmaceutical company working on immunotherapy delivery targeting metastatic solid tumor cancers.

Welcome, Eamonn.

Eamonn Hobbs, CEO, Syncromune:

Good morning. Great to be here.

Well, great to have you. It’s my pleasure. So, hopefully, I get this description right, and you can certainly elaborate and correct me if I get it wrong. But, as I understand it, Syncromune is working on a platform called SYNC-T, which is a drug and device combo platform that is used to deliver the treatment or therapy.

And as I understand it, it's basically a needle-based device that does a couple of things: one, it first lyses a portion of the solid tumor and then follows up with a drug that it delivers to selected solid tumors, looking for an immunological response.

So, I hope that I got that reasonably accurate. And, if I did, I'd be interested to hear more about that drug-device combination and the multiple mechanisms of action that occur once the SYNC-T platform is applied.

Well, thanks so much, Tom. And you got that right, indeed. SYNC-T is a very novel approach in metastatic solid tumor cancer therapies, which is very dependent on drug delivery. The mechanism of action is to optimize the likelihood of generating a T-cell-mediated response throughout the body. So, it's a locoregional therapy that is intended to generate a systemic response. We treat one selected tumor with every cycle of SYNC-T therapy.

And, as you mentioned, it's a combination drug-device therapy. The device is a proprietary needle-like system that is inserted into a selected tumor. It could be a primary [tumor site]. It could be a met [metastatic]. And that choice is made by the clinician, based on opportunity and safety. Once the needle is placed in the tumor, the tip of the needle initiates an oncolytic cycle to lyse a small part of the tumor — to rupture cell membranes, releasing the tumor antigens that are specific to that patient.

So, SYNC-T is a very personalized therapy in that we are using the patient's own antigens. Once those antigens are liberated and sitting in the tumor microenvironment, we then immediately infuse, and not inject. But it's a relatively slow, large-volume infusion into the oncolytic zone, which then mixes with the cellular debris and the tumor antigens. And the volume of the injection — the flow of the injection — carries the drug and those antigens out of the tumor microenvironment through the normal drainage pathways — the lymphatics — into the draining lymph nodes

And in the draining lymph nodes, we all know that the highest concentrations of immune system components and antigen-presenting cells and T-cells are resident, typically. So, effectively what we've done is we have synchronized the location of the three components you need to generate a T-cell response: namely, the antigens, the drug to overcome immunosuppression and be immuno-stimulating, and the cellular components — the antigen-presenting cells and T-cells.

What happens is a T-cell is educated to recognize the tumor-specific antigens. And that T-cell expands, clones, and goes systemic, generating an abscopal effect in patients that can lead to durable, complete responses. So, the clinical data is really extremely compelling.

Great. Well, thanks for the detail on how it actually works.

So, as you move forward with those developments, I'm interested in looking backward a little bit. Up to this point, where this SYNC-T platform is moving into the picture, what options would have been available for patients who were looking for treatment in the way that the patients that you're focusing on [are]? What would that experience have been like for them up to this point?

Well, there are two aspects to consider. The first one is for our lead program in metastatic, castrate-resistant prostate cancer. The options for those patients are systemic immunotherapies, which have been a major breakthrough in all solid tumors, but, unfortunately, have only generated consistent responses in 15% to 20% of solid tumor cancer patients. So, a massive, current unmet need.

In prostate cancer, the impact is far lower. Systemic immunotherapies have not panned out, even after tremendous efforts been put into testing their viability. Combinations of multiple immunotherapeutics, including multiple checkpoint blockade, have been clinically tested and have shown a dramatic increase in response rates, but unfortunately have proved to be impractical because of severe toxicities that forced the majority of patients to discontinue therapy. They were that profound. So, a very encouraging signal from a response rate perspective, but practically, not very viable, but a great clue for folks like us developing other ways of going at it.

The other way to think about it is in liquid tumor cancers, hematologic cancers. There's been a massive breakthrough with the advent of CAR T. And  SYNC-T is definitely meant to play a bit off CAR T in that everyone [has] familiarity with CAR T. What CAR T is doing is synchronizing the location of the three components you need to generate a T-cell, an educated T-cell, which can then be cloned and generate a T-cell response. But that's all done in a laboratory.

So, how CAR T works: blood is drawn from a patient, that blood is spun down, the T-cells are isolated, selected antigens — a very important concept with CAR T, you have to know what antigens to educate T-cells with — are introduced, along with a stimulating drug formulation in the laboratory to get the T-cells to recognize those antigens. Once those T-cells have been educated, they are then expanded, cloned into a preparation, then returned, very importantly, to the same patient. So, there's a custody of tissue with CAR T that's critically important.

The results are, from a response rate perspective, off the charts, and it has become a standard of care over the last ten years. There are toxicities associated with off-target effects, but the risk-benefit ratio is still extremely compelling.

So, the premise, the mechanism of action concept, has been validated by CAR T. Unfortunately, CAR T has not proved to be very viable in solid tumor cancers because the antigens that are associated with solid tumor cancers are extremely diverse — and not only from patient to patient. Even within a patient, they may have multiple solid tumor cancers at the same time from an antigen perspective. So, choosing the right one and trying to educate a T-cell has proven to be very challenging at that. Impractical.

And with SYNC-T, that's what we are trying to address. We're using the patient's antigen, so we really don't know what antigens have been utilized to educate the T-cells. What we're striving to do is provide all of them to the T-cells for education in each individual patient. So, the patient gets an educated T-cell that can recognize their own cancer.

So, thinking about the delivery of the treatment aspect, but then sort of flipping it to the patient side, the recipient side of it: What would you envision or what would a typical treatment regimen or experience be like [for patients] receiving their therapies via the SYNC-T approach?

Well, in each cycle of therapy — and it's a multi-cycle therapy; the cycles are four weeks apart — the SYNC-T procedure is a minimally invasive, image-guided placement of the needle under conscious sedation. It's an outpatient procedure. The patient arrives in the morning [and] is sleeping in their own bed that evening. And they tolerate the procedure extremely well.

One of the benefits of SYNC-T therapy — because it's a locoregional therapy and not a systemic therapy from the drug delivery perspective — is that we have the advantages of very low toxicities because, although the drug concentrations are extremely high in the tumor microenvironment and the draining lymph nodes, by the time the drug diffuses out into the systemic circulation, the concentrations are extremely low.

So, we are seeing toxicities that are mild, flu-like symptoms. No grade 3 or 4 immunologic toxicities at all so far. Knock on wood that continues. So, the patients tolerate it extremely well. We've seen complete responses from SYNC-T therapy in as few as 2 cycles. But we had one patient go out as far as 12 cycles and tolerate it very well. The average in our Phase 1 trial was between 5 and 6 cycles.

I’m interested in knowing — I'm assuming that there are still some challenges to be addressed or problems to be solved or questions to be answered that your folks are looking at. Can you describe a little bit about what's ahead to still be solved and addressed?

In prostate cancer, we think ] got most of the answers there. We'd love to increase the complete response rate to 100%; you're never finished. But that one looks pretty good.

In other solid tumor cancers, like metastatic lung cancer, metastatic breast cancer, there’s still work to be done. Optimizing the combination of the components in SYNC-T for breast cancer or lung cancer may be a different combination than the one we're using in prostate cancer. So, there's that.

In addition, the synchronization is accomplished via a volume of the drug being infused at a certain flow rate. And again, we think we've nailed those parameters for prostate cancer, but they may be different for optimal conditions in breast and lung cancer. We're still investigating that.

So, let's just pull it back [up] as we conclude our conversation today, Eamonn. If there's anything else you would like to say about what it looks like, when you look out over the horizon of the future state for patients: If the advances that are being worked on there at Syncromune take hold and have the effect that we assume that they will, how do you envision or what do you hope for in terms of what the patient landscape, patient population, and individual patient experience will be like in that future state?

Well, we believe that SYNC-T has a potential to be a major breakthrough for patients in that it's going to provide an answer to a massive unmet need in metastatic, solid tumor cancers, where patients have very, very few options for end-stage disease. Most of them are palliative, and not a lot going on there with regard to potentially durable complete responses, which would hopefully be able to call a cure after a certain period of time. So, a game changer.

And as everyone in cancer therapy development does, we always focus on end-stage patients and show efficacy because the risk-benefit profile is most appropriate. And as we demonstrate that, then we take the therapy and move it upstream to earlier lines of therapy. We envision that SYNC-T will march up the food chain, if you will, towards being potentially even first-line therapy, where, ironically, resecting the tumor would be the last thing you'd want to do. So, instead of a prostatectomy, you just stick a needle in the prostate and educate T-cells to kill that patient’s own cancer and be done.

I appreciate the work that's being done there at Syncromune. Eamonn, personally, I want to thank you for joining me to tell our Drug Delivery Leader audience about the work being done there. And as we close, I want to thank that audience for joining us for another episode of Sit and Deliver. And we'll see you here next time.