Hey listeners, welcome to episode 132 of Cell & Gene Podcast. If you're new here, welcome. And if you're a longtime listener, welcome back. I'm Erin Harris. So for this episode, I'm excited to be joined by Jay Hartenbach. He is the president and COO of Dianos Oncology.
Jay is a biotech leader helping drive the development of innovative immunotherapies for some of the hardest cancers to treat. He has played a key role in advancing the company's lead candidate, which we get into, DOC 1021, including helping secure FDA fast track and orphan drug designation, raising more than $30 million in financing and building collaborations with leading cancer centers to move the program forward. Before Dianos, he co-founded Medera where he continues to serve as the chairman and he also co-founded Pearland Pharmaceuticals and so he brings a strong mix of scientific, operational and entrepreneurial experience to our conversation.
Jay and I talked through a really intriguing approach to cancer treatment that converges cell therapy, immunotherapy, and personalized medicine. We talk about how Dianos is using dendritic cells in a novel way and what makes its double loaded platform different.
We talk about the toughest tumors to treat including glioblastoma, pancreatic cancer and refractory melanoma. We also get into the early clinical signals, the manufacturing challenges and the innovations behind a therapy built from fresh patient tumor material and what this all could mean for the future of cell therapy more broadly. I love my conversation with Jay and I think you will too. So check it out. Here is my conversation with Dianos's Jay Hartenbach. Enjoy.
Jay, welcome to Cell & Gene Podcast. So happy you're here. Thanks for your time and I'm thrilled to get to talk to you about Dianos Oncology and what you and the team are up to. But first before we get started, welcome and then tell us a little bit about Dianos Oncology and its mission.
Erin, thanks for having me on. Really excited to be here. Yeah. As far as Dianos goes in our mission, our focus is based around this discovery around how to use dendritic cells in a novel way to make a significant advancement in the treatment of solid tumors and a variety of different cancer indications. And that research came out of Baylor College of Medicine and ultimately progressed into some early clinical trials. And now we're fortunately in phase two clinical trials in two different indications with the goal of not only demonstrating that one, we can make a difference in these significant unmet medical needs, but do it in a safe and effective manner that doesn't compromise patient safety using this unique approach to dendritic cells like I had mentioned.
Terrific. Well, we're going to get right into it. So, Dianos is developing DOC 1021. So, we know it's a patient derived double loaded dendritic cell immunotherapy and it combines a patient's own dendritic cells with mRNA and proteins from freshly obtained tumor specimens. So okay, how from your perspective, how does this double loaded design address key limitations that have really historically restrained dendritic cell therapies in our space?
Yeah, I think you know to start the first differentiator is that we believe and what we are seeing clinically is that we're actually generating a significant immune response. Dendritic cells have somewhat the reputation that they are really safe but they are not effective and Dianos is hoping to change that narrative with DOC 1021 and this double loaded approach and we talk about this double loading a lot that's unique to us and we believe is really the secret sauce as to why dendritic cells have not worked in the past and why we're actually able to generate a very powerful immune response in general. And so Erin, I'm happy to expand on that if you'd like.
Yeah. And so when we look at prior dendritic cell therapies, you really could put them into two different groups. There's a couple that tried some really off the charts approaches, but most approaches were either taking the patient's tumor derived lysate or mRNA and loading that into the dendritic cell. And when we think about dendritic cells, they're the master regulator of adaptive immunity. And so the thought behind dendritic cells was if we can get dendritic cells to recognize the cancer as a threat then we'll get the benefits of a complete top-down immune response. And so we have that same belief and the science would show that you know if you talk to most immunologists and you ask them if you could get dendritic cells to work would that be an ideal immunotherapy modality and the large consensus if not all would say yes but it's that if. And so these single loaded approaches that were either using the tumor derived lysate or mRNA were not stimulating or activating the dendritic cell in a way that ultimately finally initiated an immune response.
And so this double loaded approach really came about somewhat serendipitously by our chief science officer. He was building dendritic cell vaccines for patients or for pre-clinical samples and was just trying different approaches you know loading via lysate and loading via mRNA. And he thought one day what happens if you do both at the same time? What if what happens if you load the mRNA and the lysate simultaneously? Do you get this 1 + 1 equals 2 effect or maybe even a little bit better? And what his initial experiment showed was that 1 + 1 equals 11, right? The double loaded dendritic cells were demonstrating an 11 times greater cytotoxic immune response that had been activated by those dendritic cells.
And what he ultimately discovered was by doing the double loading, we were effectively mimicking a viral infection in dendritic cells. And so we take a step back and we think about how a virus infects a dendritic cell or how the body even detects a viral infection which is through dendritic cells. You would have the virus directly infecting the dendritic cell where the mRNA would ultimately get passed and transcribed by the nucleus. But at the same time due to viral replication and cell lysis of other cells getting infected you would also have those same proteins externally of the dendritic cell. And what he also discovered is that when you do load mRNA onto these dendritic cells through this MHC class one pathway the dendritic cell starts rapidly sampling its external environment which almost confirmation of what we were doing. Right? The dendritic cell's job is not only to detect a threat but to determine the threat.
So I know that's a lot. So to get back to it, right? So by doing this double loading by loading the patient's mRNA, tumor derived mRNA into the dendritic cell and then simultaneously presenting that tumor derived lysate or proteins. The dendritic cell believes that it's being infected by a virus and that there's an active viral infection underway. And so without that two part process happening the dendritic cell would demonstrate a little cytotoxicity would would activate some T cells. We could see that in the lab but when it had that almost two-factor authentication that this is a viral infection that's what led to this profound change in the dendritic cell and this powerful anti-tumor and antiviral response that we're able to initiate.
That's fascinating. And if we want to expand on that a little bit into so you mentioned detecting the threat and attacking treating the threat as it applies to your early clinical data around glioblastoma which we certainly talk about on Cell & Gene but I don't know that we've covered it really any way at all so far on gene podcast and so I'm interested to hear more about your work with it. So what we know is that for you and your team with 88% 12-month overall survival versus roughly 60% expected with standard of care the early findings are encouraging and we know that the FDA fast track designation for cutaneous refractory melanoma. So what do these results suggest about the potential of patient derived dendritic cell immunotherapies to shift outcomes in aggressive hard to treat cancers like glioblastoma?
Yeah, I think you know a couple things and fortunately for us, we were able to treat patients outside of the phase one trial before we started our phase two trial and that 12-month survival rate has now climbed to 91% and is being supported for what we're seeing in the phase two. I think I think two things in this early clinical data that were really important for us specifically to the GBM study. One, right, that 91% 12-month survival is certainly great. In one of the patient treated cohorts, we actually saw a 24-month median survival compared to what would be significantly lower. The majority of the patients we treated had unmethylated glioblastoma. 94% of the patients had unmethylated glioblastoma which has a median survival somewhere between 12 to 15 months. And so one just shifting that survival curve significantly was really important for us.
But the other benefit we were able to see was that we were initiating an immune response that was crossing the blood-brain barrier. Unlike other cell therapies and other treatment modalities targeting GBM or many of them where they're using an intrathecal injection right directly into the brain, we're able to administer this treatment in an outpatient setting with an ultrasound guided injection that targets the deep cervical lymph node chain. And so this is a 105 minute procedure and the patient's on their way as opposed to obviously a much more significant procedure to administer. And so to that earlier point, you know, our goal is to not only change what is possible or what is believed possible as far as improving survival, but doing it in this safe manner.
And so in this clinical study in GBM and in pancreatic cancer and now in we've now just treated our first couple of patients in refractory melanoma, we're seeing the same safety profile. Those patients that they're experiencing any AEs, they're grade one and two low-grade fever, nausea, injection site reactions. You know, the low-grade fever and nausea we're somewhat attributing to the immune system simply just waking up and realizing that it's sick. And so, as much as that is obviously the result of our treatment, right, it's a good sign, right, that the immune system is building a response. And so, we're really excited about the efficacy data, really excited about the safety data and now the challenge for us is to demonstrate it on a much larger scale which is why we have these phase 2 trials underway.
