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In December of 2017 I interviewed Çağrı Savran, Ph.D. about plans for his startup in which I had just invested. Almost four years later I interviewed him again to review the progress of the company which is changing the way breast cancer is followed up after treatment.
Click here for full episode transcript.
Highlights:
Update on the Original Interview with Çağrı Savran, Ph.D.
In December of 2017 Savran Was Operating with Essential Components Handmade in the Lab – In October 2021 the Main Components Are Produced by a Vendor
Early Technology Was Used in a Major Clinical Trial at Indiana University School of Medicine
The Existing Technology for Capturing Circulating Tumor Cells Is Not Scalable – Savran’s Tech Is Amenable to Scale
Strategic Players in Prenatal Diagnostics Are Interested in Sequencing the Cells Captured – Savran Is Uniquely Positioned to Provide That Ability
The Basic Technology Is Like a Kitchen, the Different Assays Are Like What’s Being Prepared in the Kitchen
Savran Has Recruited a Capable and Involved Board
Sal Daher Summarizes Savran’s Progress in the Last Four Years
Transcript of, “Liquid Biopsy of Breast Cancer Update”
Guest:ÇaGrı Savran, Engineer, Academic & Founder
Sal Daher: Hey, I am here with Çağrı Savran to do an update. We first sat down in December of 2017 or other time when I first invested in the company. Now, Çağrı has been kind enough to make time from his very busy schedule to come back and give us an update on what's going on.
Welcome, Çağrı.
Çağrı Savran: Thank you very much for having me, sir.
Sal Daher: Four years later, we're still at it.
Çağrı Savran: Yes.
Sal Daher: Almost four years.
[laughter]
Çağrı Savran: Thanks to the support from a lot of people like yourself.
Sal Daher: Tell us where we were back at the end of 2017 and where we are now in October of 2021.
In December of 2017 Savran Was Operating with Essential Components Handmade in the Lab – In October 2021 the Main Components Are Produced by a Vendor
Çağrı Savran: Back at that time, our technology was at the early prototype stage. We had a working prototype, but it was more at the academic stage, if you will. For those people that haven't listened to the first podcast, this technology came out of my own academic lab at Purdue. Back at that time, 2017, early 2018 even, all the components were actually made in my academic lab. It was important that we made that transition from academic setting into a company setting. What is very important is that the key components right now are actually outsourced, that they are made by contractors, which is very important for scalability.
You don't want to be making a 100% of everything by hand because then you cannot scale it. That's very important. We have made improvements to the design. We made the system even more scalable, even simpler. We improved its performance. We have made it more streamlined, made the whole process more automated than it was before. Very importantly, we have the technology validated in a major clinical trial, a Phase 2 clinical trial. It took a number of years actually, and it involved about 200 patients. The results were published in Journal Oncology, a very high-impact oncology journal. That's very important because the study actually wasn't even directed by us.
Early Technology Was Used in a Major Phase 2 Clinical Trial at Indiana University School of Medicine
It was run by oncologists where we provided the technology to--
Sal Daher: At another university, at the medical school.
Çağrı Savran: We're very happy that that actually influenced the way oncologists were making decisions on how to look at triple-negative breast cancer patients and how to monitor--
Sal Daher: Maybe we could get a little bit of detail here. Specifically, what your technology is doing is allowing the count, to enumerate the number of circulating tumor cells in the patient's blood to check and see if there has been recurrence of this terrible form of breast cancer, triple-negative breast cancer.
Çağrı Savran: Exactly. We basically get a blood sample and we look for extremely rare tumor cells that have detached from tumors and gone into the blood circulation. In this particular case, just the count of these cells is enough to tell whether the disease is coming back or not, which was the primary goal over here because the patients had gone through chemotherapy as well as surgery and their tumors have been removed. Now, the question is, is the disease coming back or not? The oncologists that carried out the trial, they did two types of tests. They took the blood sample, they did a circulating free DNA test, which is something that they were already doing.
Sal Daher: The free DNA is the existing liquid biopsy, the state of the art.
Çağrı Savran: Exactly. That's the state of the art. Yes.
Sal Daher: The big innovation is the Savran cell capture. Instead of capturing strands of free-floating DNA, it's actually capturing circulating tumor cells.
Çağrı Savran: Exactly. They showed that if they combined the circulating free DNA tests, which was 79% accurate in predicting a relapse, with our tests, then the accuracy was improving from 79% to 90%. That 11% difference is actually very important. There's a lot of women that may not have to suffer. That was really important.
Sal Daher: Let's just remind the listeners that at that time; at the time of the interview, you have perfected the technology, albeit with laboratory-made devices and so forth, but your early prototype zeroed in on capturing circulating tumor cells.
Çağrı Savran: Yes.
Sal Daher: The clinical study that we mentioned was already ongoing back in 2017 at the time of the interview.
Çağrı Savran: Yes.
Sal Daher: So, your equipment was being used at another university on this clinical trial, but it was handmade in the lab, not scalable, very early days. [Savran received blind samples from IU School of Medicine and provided enumeration of circulating tumor cells in each sample] During the following year, you went out to various strategic players to try to get interests from their part during 2018 in using circulating tumor cells as a diagnostic for cancer after-treatment. Would you care to talk about the results at that point, the feedback that you got at that time?
Çağrı Savran: Sure. Several companies that we talked to at that time told us that what they were interested in at that particular time and that actually continues to this date, at least as far as those particular companies are concerned, is that they wanted to capture whole fetal cells circulating in the bloodstream of pregnant women.
Sal Daher: Right. At that time, we couldn't find strategic players who were excited about circulating tumor cells probably because it was too early but there were strategic players who were interested in capturing fetal cells because of a commercial reason. Because the noninvasive prenatal tests that were in existence were not protected by patents and therefore, our commodity item. Their cost is coming down very fast, it was becoming a profitable product that was becoming rapidly less profitable, although it's something that's used very frequently.
The Existing Technology for Capturing Circulating Tumor Cells Is Not Scalable – Savran’s Tech Is Amenable to Scale
Çağrı Savran: Yes. Let me say a couple of things about the circulating tumor cell. We realized that there was a little bit of a diminishing enthusiasm about circulating tumor cells and there were reasons for that. People just were not very excited by the available technology, the FDA-approved technology at that time. There was nothing else that was FDA-approved so the moment people heard the word circulating tumor cells, they were associating that with the experience that they had with that technology. There was a little bit of a diminishing-- That has been changing.
Sal Daher: Let's just finish the narrative here, basically, you went to talk to them about CTC, circulating tumor cells, they came back to you saying, "Can you do fetal cells?" That's where there was a pivot in the emphasis of the company.
Çağrı Savran: Exactly. What you said is exactly what happened and we decided to listen to voice of the market because the individuals that we were talking to were experts in selling tests to patients. We realized that as an opportunity and what we have is a platform technology. If you basically know what kind of an antigen you're targeting on the surface of a cell, you can potentially capture any cell you want. Without giving up on the cancer essay, we started to direct the most of our focus on developing a new essay on capturing fetal cells in blood samples of pregnant women.
The goal over there is like the holy grail, that is the reason actually why those companies were interested in that. If you can do that, then you basically have access to the whole intact genome of the baby and not only bits and pieces of DNA fragments in the blood sample which significantly limits on how many conditions you can look at. If you have a whole cell, then you have a whole cell and you have a whole intact genome, and you can potentially look at everything. That was the reason they were interested in that.
Strategic Players in Prenatal Diagnostics Are Interested in Sequencing the Cells Captured – Savran Is Uniquely Positioned to Provide That Ability
In other words, they were not only interested in catching the cells and counting them which in many cases is sufficient, and in the case of circulating tumor cells, but it was important that those cells that are captured could also be sequenced. We directed our efforts on realizing that essay, and we're still working on it.
Sal Daher: Excellent. Basically, you did an additional raise for that pivot to support the development of that and you developed the technology substantially in terms of chemistry for capturing certain types of cells that could be interesting in noninvasive prenatal testing. That whole side has advanced tremendously in those years. Then in 2020, tell us what happened in 2020 when the paper came out, the circulating tumor cell paper.
Çağrı Savran: [laughs] At that time we realized that the interest in circulating tumor cells was actually increasing again because we started getting contacted by people that were wanting tests or disposable cartridges, wanting to get instruments, even other companies that were interested in partnering potentially. We're certainly enjoying that. That didn't really change the fact that we still had a new essay to develop. We're a very small company, we have to focus but it certainly excited us, increased our excitement.
Sal Daher: The result is that you now have your negotiations with strategics in both the circulating tumor cell and the fetal cell capture, both use cases. Before, the strategics were only interested in fetal cells, before the paper and now there's interest also on the circulating tumor cell.
Çağrı Savran: Exactly. At the moment, we also have parties that are about to start clinical trials approaching us wanting to collaborate on those clinical trials.
Sal Daher: More of the original use of the circulating tumor cell?
Çağrı Savran: Exactly. The advantage is that we're able to use the same technology for any kind of essay with the condition that you got to change the reagents that you use. The underlying technology is the same but the reagents that you use are different.
The Basic Technology Is Like a Kitchen, the Different Assays Are Like What’s Being Prepared in the Kitchen
Sal Daher: I like to comparison to having your kitchen set up. The technology is your kitchen, the range--
Çağrı Savran: All the utensils in the kitchen, yes.
Sal Daher: They're all set up and what's changing is what's being cooked. One day it's tapioca, the other day it's steak. [laughs] You've perfected the cooking of steak, and now you have to change the chemistry for tapioca.
Çağrı Savran: Maybe something other than tapioca but yes, that's a good example.
[laughter]
Savran Has Recruited a Capable and Involved Board
Sal Daher: I like that tapioca. Oh, there's another thing that you're forgetting Çağrı, an important step that happened in the past nearly four years. Is that at the time that I invested? The board was you and there were basically two people on the board. Now you have a board composed of four people soon to be five, four of which are outside people, non-executive people in the company. Some representing investors, some are just industry experts and you were able to recruit someone with an oncology background, who developed cancer therapeutic. That's Jeff Behrens and also Nina Altomare, who has a prenatal background and understands that space.
From an investor's perspective, and I'm on the board as a representative of early investors in the company. For me, that is really important.
Çağrı Savran: Thanks for mentioning that and also, we have significantly bolstered our IP portfolio. I think that at the time when you first invested, we have so many patents right now, we've got to go back and check the dates and all that but I think at the time you invested, we had some US patents and I believe our European patent was also issued at that time. Now we have multiple, many more US patents and subsequent European patents. Very recently, we also had our Chinese and Japanese patents allowed.
We're very happy about that.
We filed continuation patents and not only that, but we not only increase the coverage like the technical coverage of the patents but also geo coverage of the patents and the multiple countries that we were not covered before. We're also very happy about that.
Sal Daher Summarizes Savran’s Progress in the Last Four Years
Sal Daher: Now I want to see if I'm an A student, or B student. Let's recap. Back in 2017, you're using equipment made in your cleanroom in the lab at Purdue University, and it was all very primitive, not automated in any way. Now you have microfluidic chips that you're using are made by a vendor, the process is semi-automated. There's a manifold that feeds the reagents. There's a computer program that controls it, and you are now looking forward actually to the next step, which is fully automated multiplexed system. That's the thing that you're excited about in the future.
Back then you had the circulating tumor cell capture, pretty much zeroed in, although you were using very early equipment. You could doit, the chemistry was there but you had this dream of perhaps using for fetal cell capture. Now you've done a lot of work on fetal cell capture. You've managed to successfully capture a certain type of cell that's useful in that and you are now developing the chemistry for capturing another cell that is of interest. That side of technology has progressed a lot. The company has acquired a serious board of outside people, and it has grown its intellectual property. At the time, your staffing was-- I think you had one scientist at the time.
Çağrı Savran: Yes, and now we have three.
Sal Daher: Excellent. Three, and one use case that’s pretty developed and another use case that is where you've made a lot of progress.
Çağrı Savran: Yes. A plus.
Sal Daher: Okay, thank you. No, no, no, A plus would have been if I'd been more succinct. This is A-minus but I remembered everything at least.
Çağrı Savran: If you say so, okay.
[laughter]
Sal Daher: All right, Çağrı, anything else you want to add on that?
Çağrı Savran: No, I think you've done a great job of summarizing it. We're working very hard, still a lot of work to do and we're pushing full steam ahead.
Sal Daher: I can tell you that the board is very happy with the progress that you've made. Oh, the other thing. You're now a company that does quarterly updates so it's not a software company guys. Software companies have to do monthly updates because they change every month. Biotech startups, quarterly updates are fine. We have quarterly board meetings and then quarterly updates. We have growth in governance, growth in IP, growth in the technology, growth in staffing. You're cooking with gas Çağrı.
Çağrı Savran: Thank you very much.
Sal Daher: Whether it's steak or tapioca.
[laughter]
Çağrı Savran: Thank you.
Sal Daher: Thanks a lot for making time.
Çağrı Savran: Thanks a lot for having me.
Sal Daher: This is Angel Invest Boston, I'm Sal Daher.