Cagri Savran, "One Cell in a Billion"

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Angel Invest Boston is sponsored by Peter Fasse, top life science patent attorney.

I invested in Savran Tech back in 2017 around the time of the first part of this interview. Recently I sat down with Cağrı Savran to review the progress of his remarkable biotech startup in the last four years. Listen to the original interview followed by a recent update.

Click here to read the full episode transcript

Here are some of the topics covered:

• Çağrı Savran Bio (Çağrı Is Pronounced Cha-re)

• Accident that Took Çağrı Savran from Turkey to Indiana

• Purdue University’s Remarkable Support for the Commercialization of Faculty Inventions

• Çağrı Savran: “So, when I say "extremely rare," I mean one-in-a-billion rare.”

• Çağrı Savran: “Our technology can find those five or six or ten cells that are, among about a billion.“

• “…from a blood sample, you have a glimpse into the tumor without cutting into the person.”

• The Promise of Monitoring Cancer Treatment with a Blood Draw

• “The advantage is if you can do this with a blood sample, it gives you a chance to do this test frequently, right?”

• Applicable to the Prenatal Monitoring of the Fetus

• Savran’s Tech Is Simple, Fast and Results in High Purity and Yield – 1000 Times Faster than Typical Microfluidic Systems

• Like Alexander with the Gordian Knot, Savran Has Loosened One Constraint to Great Effect

• Bigger Scale and Faster Flow Allows the Fast Separation of Rare Cells

• Device Seems Amenable to Large Scale Usage – Handling Many Patients at the Same Time

• How the Invention Came About

• Why Çağrı Savran Founded a Company

• Purdue’s New Commercialization Policy Played a Big Role in the Decision to Found the Company

• Why Turbocharging Cell Separation Is So Important

• Other Use Cases: People Are Always Suggesting New Ones but Need to Concentrate

• Savran’s Tech Is a Game Changer because of Throughput and Parallelization

• Other Techniques Look at Pieces of DNA – Savran’s Tech Is Capable of Finding the Entire Genome

• Sal Daher Reads the Review by Spizzy Spong on iTunes and Asks for Your Review

• How Savran Landed Bigwig Advisor Ken Morse

• How Savran Found Its CEO – Patrick Rivelli

• "Oh, you have no idea how I wish that somebody would say that about me, that I'm 'quietly competent.'”

• Savran’s Choice of the Right Patent Attorney Was Crucial – Peter Fasse Helped Way Beyond Patents

• Patrick Rivelli, CEO Proposed a New Go to Market Approach

• What Makes the Savran Lab at Purdue so Productive

• Çağrı Savran Urges Fellow Academics to Bring Their Inventions to Market

• 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 and Significantly Improved the Ability to Predict Recurrence of a Breast Cancer

• 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 "One Cell in a Billion"

Guest: ÇaGrı Savran, Engineer, Academic & Founder

Sal Daher: Welcome to Angel Invest Boston, conversations with Boston's most interesting angel investors and founders. I am Sal Daher, and my goal for this podcast is to learn more about building successful new companies. The best way I can think of doing this is by talking to people who are doing it. People such as engineer, academic, and founder Çağrı Savran. Çağrı [pronounced Cha-ree], I'm honored you made time to be interviewed. Welcome.

Çağrı Savran: The honor is mine, Sal. Thank you for having me.

Çağrı Savran Bio

Sal Daher: Well, thanks for being here. Çağrı Savran is one of the top experts in the field of microfluidics, which involves moving fluids through small channels and constrictions to achieve various useful ends such as separating out or transforming cells and other types of material. The lab that Çağrı Savran set up at Purdue University has invented a technology for cell separation that promises to revolutionize the field of diagnostics. As opposed to typical microfluidic platforms that can only process tiny microliters of samples, his patented technique can process much larger milliliters of samples within minutes, thus opening up the possibility of liquid biopsies whereby cancer or other diseases might be monitored quickly based on blood samples.

Born in Turkey, Professor Savran studied mechanical engineering at Purdue University as an undergrad. He went to MIT for his Ph.D. He then returned to Purdue as a professor of mechanical and biomedical engineering. Çağrı Savran founded Savran Technologies as a vehicle to bring his groundbreaking invention to patients. Savran Tech has gotten strong interest from parties that are knowledgeable about its intended markets. Çağrı Savran is relocating the company he has founded to Boston, but he himself will continue to work at his lab at Purdue. More about that later.

How Çağrı Savran Ended up Being an Engineer

So, Çağrı, when did it dawn on you that you wanted to be an engineer and a scientist? What- what- what prompted that?

Çağrı Savran: I think, uh, uh, (laughs) well, that was really genetic. Uh-

Sal Daher: (laughs)

Çağrı Savran: Because, uh, I- I'm an engineer. My sister is an engineer. My, uh, little brother is an engineer. He goes to MIT right now, is studying electrical engineering. Our father is an engineer. Uh, our mother is a science teacher by-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Training. Uh, we have two uncles, um, that are math teachers. So, it's somewhere, um, some-

Sal Daher: (laughs)

Çağrı Savran: ... Some- some- some sort of a genetic problem in the family that makes it (laughs)-

Sal Daher: Well, I don't know if it's necessarily, ex- explicitly ... I'm sure there's a j- very s- strong genetic component, but I'm sure there's also a strong-

Çağrı Savran: Yes.

Sal Daher: ... Cultural component.

Çağrı Savran: Yes. Uh, so, uh, my dad was a big influence. Uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: I mean, he- he- he was always a very busy man, uh, traveling, uh, and following business opportunities. But when he was around, w- I was pretty amazed with how much he knew. Math questions, uh, science questions, chemistry questions, even, uh, other types of questions or problems that were not directly scientific, he always found a way to translate that into some sort of an engineering problem, and offer some sort of a solution. That was quite amazing to me. So-

Sal Daher: Uh-huh (affirmative).

Çağrı Savran: ... That w- definitely was an influence. So, he never was imposing anything or even asking for, uh, anything.

Sal Daher: No.

Çağrı Savran: But tha- that certainly influenced. And I was always good and science and, uh, math, ever-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Since I was in elementary school. It was really a natural continuation, really.

Sal Daher: Yeah. I- I ... That reminds ... My- my dad used to go through great lengths to explain all sorts of things to me. He was an engineer also, and- and- and then a mathematician. Much to my mother's chagrin, he used to explain very abstract math concepts to her, and she-

Çağrı Savran: (laughs)

Sal Daher: ... And she- she (laughs) understood nothing, but she was very understanding (laughs) and actually-

Çağrı Savran: Yeah.

Sal Daher: ... Helped him work out a lot of these things. So-

Çağrı Savran: (laughs) Yeah.

Sal Daher: ... I can understand how your dad sitting you on your ... On his lap and telling you about how this bridge works or how this works and how that works-

Çağrı Savran: Yeah-

Sal Daher: ... Inspires you.

Çağrı Savran: Definitely, yeah.

Accident that Took Çağrı Savran from Turkey to Indiana

Sal Daher: That- that- that is, that is, uh, really wonderful. Um, y- you were born in Turkey. So, how did you end up in West Lafayette, Indiana studying engineering at Purdue University?

Çağrı Savran: Yeah. So, that's actually a big coincidence. First of all, I wanted to come to the United States to study. Some of that was influenced by, again, uh, my parents sending us to language schools, uh, mostly in Europe, Switzerland and England, uh, so that we-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Could improve our English.

Sal Daher: Yes.

Çağrı Savran: Um, I'm saying "our" because it's the same with me and my siblings. It was very important to them that we, uh, were fluent.

Sal Daher: So y- your sister and now your younger brother.

Çağrı Savran: Yes, exactly. Uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... We all went to summer schools, um-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... In either Switzerland or England. And at the end of my second year in high school ... At that time, high school in Turkey was three years. Now, I think it's four years, but at time it was three ... So, right before I started my last year, I came to Harvard for its summer program. Like most universities, they offer classes during the summer, uh, but what makes Harvard summer school special is that high school students can also take college-level classes. So, I came here and I took a physics class, and, uh, that sort of gave me a glimpse of the student life, college student life here in the United States.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: And I really liked it. Then I went back to ... Obviously, summer school was over, and I went- went back to Turkey, and, uh, uh, we were having a family vacation in a- a very beautiful, um, seaside town called Ayvalık. Uh, it's right on the Aegean Sea.

Sal Daher: Oh.

Çağrı Savran: We were having a late lunch at a, uh, very nice fish restaurant. It was kind of like late afternoon, around 2:00, 2:30. There was nobody else in the restaurant except for us and another family.

Sal Daher: Uh-huh (affirmative).

Çağrı Savran: A couple. Um-

Sal Daher: Yes.

Çağrı Savran: ... And they were an American couple.

Sal Daher: Mmm.

Çağrı Savran: Uh, for ... Who were in love with Turkey.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Were coming there all the time. So, we started talking, and they eventually asked what I wanted to do, and I said, you know, "I want to study, uh, engineering." Uh, and they said, "Oh. You know, we're from Chicago, and, uh, there's a very, uh, well-known engineering university that was, uh, the- the alma mater to some people from our family, and that's called Purdue University."

Sal Daher: Oh, okay.

Çağrı Savran: Oh. So, uh, and then my- my- my father was like, "Oh, how ... Why didn't I remember that, because I- I know this university? I, uh, I had professors that graduated from Purdue, and I read textbooks at college that were written by Purdue professors. Yeah, you should definitely, uh, apply there." And I applied, I got in, so-

Sal Daher: A- awesome.

Çağrı Savran: ... Uh, your- your (laughs)-

What Çağrı Savran Got from His Summer Jobs During College

Sal Daher: Tremendous. Y- yeah- yeah. It's- it's really a great story. So, when you were an undergrad at Purdue, you worked at Procter & Gamble and then ... For a summer, and then at NASA for a summer.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: So, what did you get out of those experience?

Çağrı Savran: So, m- each was a unique experience. They were different from each other. Um, very different. Uh, but each one, uh, gave me a unique perspective on what engineers do. Uh, in Procter & Gamble ... Procter & Gamble is a big consumer products company, as you know, and one of their big businesses is in diapers.

Sal Daher: (laughs)

Çağrı Savran: Uh, and, uh, I actually worked in an engineering, uh, group-

Sal Daher: I- I'm ... M- my family's a big consumer of that right now.

Çağrı Savran: (laughs)

Sal Daher: We have a three-year-old and a, uh ... Well, he's out of diapers now, but the-

Çağrı Savran: (laughs)

Sal Daher: ... There's ... We have a five-month-old who's a big consumer.

Çağrı Savran: Uh, uh, so, you'd be shocked to see how much science and engineering-

Sal Daher: Oh, I know. I know.

Çağrı Savran: ... Go- goes into that. And I didn't even work on the team that was designing the diapers themselves. They ... I've actually never even seen them. But they would design it, and then we would build the machine that would make the diapers. Uh, and, uh-

Sal Daher: It's- it's am- amazing science.

Çağrı Savran: Yeah.

Sal Daher: How much progress there has been made-

Çağrı Savran: Yeah.

Sal Daher: ... Since the '80s, when my kids were in diapers, and now my grandkids. The diapers, they are so superior.

Çağrı Savran: (laughs) Yes.

Sal Daher: Even though ... I mean, they were, they were amazing then, and now they're just incredible.

Çağrı Savran: Well, and, uh, absolutely. So, I worked in a group of engineers that was designing the next generation machines for making diapers, because they continuously change what the diapers are gonna be, and you've got to ... As a result, you've got to change your machines and modify the way you're ... You make them. So, it was a great experience. Uh, in NASA, it was obviously very different. Uh, it was more focused on acoustics and noise control.

Sal Daher: Yes.

Çağrı Savran: It involved a lot of noise measurements in all kinds of experimental procedures as well as exhausts-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Uh, to understand, uh, how much noise pollution is being generated by everything that was being done, basically. And it involved a lot of measurements. It involved silencer design and ordering and having them placed on exhausts so as to, uh, reduce the, uh, pollution to the environment. And it was pretty amazing, because I had a chance to see all kinds of very unique, uh, studies and experiments, um, uh, that was, uh, that was being done at NASA.

Sal Daher: So, tell us ... You've been a faculty member for 13 years at Purdue.

Çağrı Savran: Mm-hmm (affirmative).

Purdue University’s Remarkable Support for the Commercialization of Faculty Inventions

Sal Daher: Tell us about the attitude towards faculty entrepreneurship at Purdue.

Çağrı Savran: Mm-hmm (affirmative). I believe that is one of the biggest strengths of Purdue. Our president, Mitch Daniels, uh, he's a big supporter of commercialization. As soon as he started at Purdue, uh, he gave marching orders to, um, uh, help faculty members commercialize their technology. The Office of Technology Commercialization was reformed. They started programs that would make it very easy for faculty members to write patents and license them into their own companies. They started programs that would make this very easy and also very favorable.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Um, and they would give the- the IP to faculty start-ups, uh, under terms that are more favorable than the terms that they would give to anybody else. In addition, they, uh, started a program called "the Foundry," uh, where-

Sal Daher: Uh-huh (affirmative).

Çağrı Savran: ... Uh, they recruited people that would-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Teach faculty members how to prepare pitch decks, how to, um, uh, write, uh, basic business plans, uh, how to make market search. And- and you really started this program as a faculty member, and then you go to these classes. And all of it was according to your schedule. I mean, they wouldn't really ask you to come at a certain time if ... Uh, they know you're very busy, and if you can't make a certain time, then they- they adjust according to you. They just want you to do this. And in the end, uh, you deliver your pitch based on the deck that you've prepared, and you show your business plan, and you graduate from the program, and, uh, the university basically licenses the technology to your company. Uh-

Sal Daher: Wow.

Çağrı Savran: ... It's, uh, it's, uh-

Sal Daher: So, they're training the professors to be founders.

Çağrı Savran: Yes. They-

Sal Daher: Uh, that ... Uh, r- remarkable.

Çağrı Savran: Exactly.

Sal Daher: This is--

Çağrı Savran: Exactly. Exactly. And we have a new dean right now, a dean of engineering. He very recently started, and, uh, also very, very enthusiastic about, um, commercialization. And he's talking to every faculty member right now individually, every single faculty member in the College of Engineering. And I sent him an email and he responded, and he said, "Oh, I want to, I want to hear about your company." (laughs)

Sal Daher: (laughs)

Çağrı Savran: So, we met and talked about it. (laughs) It was, it was a lot of fun. There's a big push. A lot of support.

Sal Daher: That's a revelation for me. I did not know that Purdue was such a- a hotbed of entrepreneurial activity.

Çağrı Savran: Mmm.

Sal Daher: This is sort of like Steve Case's, uh, argument for the rise of the rest.

Çağrı Savran: (laughs)

Sal Daher: You know, the- the re- ... You have New York City, Boston and the Bay Area, and, well, of course, uh, Austin, Texas.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: Big centers of entrepreneurship. But everywhere else, uh, not a lot.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: Uh, and he's making a big push so- for places like Pittsburgh, which is also up and coming.

Çağrı Savran: Mm-hmm (affirmative). Mm-hmm (affirmative). Mm-hmm (affirmative).

Sal Daher: Because of CMU.

Çağrı Savran: Sure.

Sal Daher: And, uh, now, Lafayette, Indiana-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... With Purdue. This is wonderful, because there's so much to be done in this discovery that you have. So, please tell us about the invention you're- you're seeking to commercialize. Explain what is that you ... That's so remarkable about it.

Çağrı Savran: It is a device that can perform a blood test by catching extremely rare cells in blood samples.

Sal Daher: Yeah.

Çağrı Savran: “So, when I say "extremely rare," I mean one-in-a-billion rare.”

Çağrı Savran: So, when I say "extremely rare," I mean one-in-a-billion rare.

Sal Daher: Wow.

Çağrı Savran: So, if you take a blood sample, a typical blood sample ... "Typical" meaning, when you go to your doctor and they-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Do a blood test, and that- that single-

Sal Daher: The little vial, you know what-

Çağrı Savran: Yeah, that- that- that- that one tube of blood that they- they draw from you.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: That's about eight milliliters.

Sal Daher: Yes.

Çağrı Savran: Okay? So, in that eight milliliters, uh, of blood, there are over a billion cells. Uh, and the number of cells that you're looking for are maybe five or six. Maybe 10, maybe 100, but something-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Around that, among a billion.

Sal Daher: Wow.

Çağrı Savran: Right?

Sal Daher: Right.

Çağrı Savran: “Our technology can find those five or six or ten cells that are, among about a billion.“

Çağrı Savran: Our technology can find those five or six or 10 cells that are, um, among, uh, about a billion.

Sal Daher: Yes.

Çağrı Savran: And it has very serious implications in a number of fields, cancer being one of them. For example, in cancer patients, the tumors shed individual cells into the bloodstream, okay? These are called circulating tumor cells. They get into the, uh, bloodstream, and they keep, uh, swimming around, circulating-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Uh, from one part of the body to another. In fact, it is believed that it is these cells that cause metastasis. They start from the tumor, and then they go someplace else by swimming in the blood.

Sal Daher: Wow.

Çağrı Savran: They invade that other organ, and they start to-

Sal Daher: So- so it's a way of- of the cancer spreading itself-

Çağrı Savran: Yes. Yes.

Sal Daher: ... V- via the blood.

Çağrı Savran: Yes.

Sal Daher: Okay.

Çağrı Savran: And so, it ... So, if you can catch these, uh, cells-

Sal Daher: Mm-hmm (affirmative).

“…from a blood sample, you have a glimpse into the tumor without cutting into the person.”

Çağrı Savran: ... Um, from a blood sample, you have a glimpse into the tumor without cutting into the person.

Sal Daher: Mm-hmm (affirmative).

The Promise of Monitoring Cancer Treatment with a Blood Draw

Çağrı Savran: You can count these cells and, uh, correlate that with the progress of the disease. In general, if their number goes up, that means things are getting worse. If the number-

Sal Daher: Yeah.

Çağrı Savran: ... Going down-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Things are getting better. You can sequence those cells because each cell gives you an intact genome, the entire genome. You can sequence it and find very subtle mutations that may have caused the disease in the first place. You can use them to assess responsive therapy, which is actually very important. Somebody already has cancer-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... And the- the doctor's prescribing a- a drug, and, uh, they take it and the doctor wants to know how the patient is doing. Now-

Sal Daher: So, if you have a big drop, you- you- you'd take a baseline-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... And you have, let's say, you know, 2,000 CT-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... You know, circulating tumor cells-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... Per tube of blood. And then it falls to just 10.

Çağrı Savran: Mm-hmm (affirmative). For example.

Sal Daher: Uh, for example. You know it's working-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... Or you know, you- you have a hundred and it stays at a hundred, means-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... It's not working, you need to find something else.

Çağrı Savran: That's- that's the idea.

Sal Daher: Yeah.

“The advantage is if you can do this with a blood sample, it gives you a chance to do this test frequently, right?”

Çağrı Savran: That's the idea, yes. The advantage is if you can do this with a blood sample, it gives you a chance to do this test frequently, right?

Sal Daher: Right.

Çağrı Savran: You can't biopsy someone frequently-

Sal Daher: No, no.

Çağrı Savran: ... But you can get a blood sample from them frequently.

Sal Daher: So, thus- thus the name l- "liquid biopsy."

Çağrı Savran: Exactly. Exactly. Hence the name "liquid biopsy."

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: And that's just one example. Now, I'm g-, I'm gonna give you a completely unrelated example, and that is pregnancy, okay?

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: And that's very different from cancer.

Sal Daher: Yes, it is.

Applicable to the Prenatal Monitoring of the Fetus

Çağrı Savran: But the technology that we're commercializing, uh, has a potential for a big impact in this field as well, because actually, i- it's kind of surprising. It was very similar to cancer. When a fetus is growing inside the mother, it also sheds cells into the bloodstream (laughs) just like a tumor does.

Sal Daher: Wow.

Çağrı Savran: If you can catch those cells, uh, you can have a glimpse into the, into the baby. Uh-

Sal Daher: You can learn a lot about the baby. Mm-hmm (affirmative).

Çağrı Savran: Exactly. You have, uh, access to the baby's entire genome very early into the pregnancy-

Sal Daher: Without- without employing methods such as amniocentesis and so forth that are dangerous.

Çağrı Savran: Yeah, or- or- or- or CVS. Exactly. Or CVS or, uh, an amnio, which are, uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Um, uh, valuable techniques, but they're very invasive.

Sal Daher: Yeah.

Çağrı Savran: Again, so you can do this, uh, with a blood test, and, uh, our technique, uh, enables that.

Sal Daher: That- that is w- just (laughs) ... It- It- it really is a ... As someone who has, uh, someone with, uh, cancer in- in- in his family, this for me is very exciting.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: Uh, the prospect of being able to do follow-ups. You would know what the cancer is, you know what to look for, then you can do a targeted search and see how many circulating tumor cells there are. Are you comfortable explaining what it is that makes this so different from-

Çağrı Savran: Of course.

Sal Daher: ... From, uh, previous, uh, approaches?

Savran’s Tech Is Simple, Fast and Results in High Purity and Yield – 1000 Times Faster than Others

Çağrı Savran: Yes, of course. What's special about our system is that it is rather simple, which is very robust and repeatable, and mass-manufacturable-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... And disposable. And at the same time-

Sal Daher: That's- that's my- my brother in law, Peter Fasse, who is the-

Çağrı Savran: Yeah.

Sal Daher: ... Patent attorney-

Çağrı Savran: Yes.

Sal Daher: ... From whom I learned about this opportunity.

Çağrı Savran: (laughs) Yes.

Sal Daher: You know, he's- he's at Fish and Richardson. He's a very prominent patent attorney.

Çağrı Savran: He is.

Sal Daher: He said, "Saleh, you've got to see this thing. It is unbelievably elegant. The solution is incredibly elegant." So, please.

Çağrı Savran: Yes. Uh, well, I- I'm glad he thinks that way. In addition to this, uh, rather simplicity which comes within ... With a lot of, uh, advantages in comparison with a lot of other systems, which are actually very complicated, it also is very fast. It has high throughput.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: It can, um, process a whole tube of blood within minutes.

Sal Daher: So, that's something on the order of 10 to the five? A hundred thousand faster is ... What's the-

Çağrı Savran: Yes. So, it- it's about a thousand times-

Sal Daher: A thousand times.

Çağrı Savran: ... Faster, uh, than a typical microfluidic-

Sal Daher: Did it-

Çağrı Savran: ... System.

Sal Daher: Okay.

Çağrı Savran: Uh-

Sal Daher: So, three orders of magnitude faster.

Çağrı Savran: E- e- exactly. Um-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, and I'm gonna talk about that, uh, in a, in a little bit. So, the speed throughput as well as the purity.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: That's very important. So, it's ...- these cells are very rare. You've got to be able to catch the cells that are very rare. But at the same time, you don't want to catch the cells that are not, um, relevant to you.

Sal Daher: Right, right.

Çağrı Savran: And there's many of them.

Sal Daher: (laughs) Yeah.

Çağrı Savran: There's many, many of them. Right? It's- it's- it's very important. So, our system also has a very, very high purity, um-

Sal Daher: Mm-hmm (affirmative).

Like Alexander with the Gordian Knot, Savran Has Loosened One Constraint to Great Effect

Çağrı Savran: ... So, the overall simplicity, the speed and the purity is what, uh, distinguishes us from the rest of the, uh, systems that are, that are out there. A typical microfluidic system, just like you mentioned at the beginning of the podcast, um, the whole field of microfluidics is about analyzing very tiny amounts of fluid samples. Microliters, nanoliters-

Sal Daher: Mi- microliters is-

Çağrı Savran: It's 1,000 times less than a milliliter.

Sal Daher: Than a milliliter, which is-

Çağrı Savran: And about-

Sal Daher: ... One thousandth of a- a liter.

Çağrı Savran: (laughs) Yes. Yes, exactly.

Sal Daher: So, a liter is like a quart, okay?

Çağrı Savran: Exactly.

Sal Daher: So, like, one millionth of a quart is the scale.

Çağrı Savran: It's basically 10,000 times smaller than ... A- a- approximately 10,000 times smaller than a- a tube of blood. That's about-

Sal Daher: Right.

Çağrı Savran: ... On the order of 10 milliliters.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: And the microliter will be, uh, about 10,000 times less than that. Now, um, the whole field of microfluidics is about, uh, analyzing microliters and even smaller-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Uh, amounts. So, that's the definition of microfluidics. Here's a problem. If you're looking for a rare target, okay? Like a rare cell, like a circulating tumor cell or a fetal cell-

Sal Daher: Right.

Çağrı Savran: ... You cannot find it in a microliter of blood. It just ... You just won't see anything in there.

Sal Daher: Right.

Çağrı Savran: Uh, you- you- you must be familiar ... You mu-, you must have seen some, uh, uh, some of the, uh, glucose tests, right?

Sal Daher: Yes. Yes, I think so.

Çağrı Savran: You know, it's a little finger prick here.

Sal Daher: Right. Right.

Çağrı Savran: A tiny amount of blood comes out.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: And the device very elegantly measures the glucose in there. But in that much blood, you could still find glucose, but you cannot find a circulating tumor cell.

Sal Daher: Too rare.

Çağrı Savran: You need ... Yes. Too rare. You need to be able to analyze-

Sal Daher: Mm-hmm (affirmative).

Bigger Scale and Faster Flow Allows the Fast Separation of Rare Cells

Çağrı Savran: ... Much larger volume of blood to be able to find anything. Okay? So, uh, that actually was the reason why we actually came up with this idea. If you look at a typical microfluidic system, uh, that is, um, specialized in analyzing microliters of a sample, fluid sample, in this case a blood sample, and if you put 10 milliliters through it-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Right? It's just gonna take a very long time.

Sal Daher: Very long time. Yes.

Çağrı Savran: Right? A very long time. So, um, we thought about this, and we said, "Well, why is this so slow?" We've got to find a solution to this.

Sal Daher: To relax some constraint here.

Çağrı Savran: E- e- exactly. You know, why- why is it so slow? And then it sort of hit me and I said, "Well, it's slow because it's microfluidic, right?

Sal Daher: (laughs)

Çağrı Savran: It's supposed to be, right?

Sal Daher: So, you kind of took the "micro" out of "microfluidics."

Çağrı Savran: Well, basically, it's a new kind of microfluidics, basically.

Sal Daher: Right.

Çağrı Savran: A high-speed microfluidics. Uh, and, uh, I mean, the device still has micro-features.

Sal Daher: Right. Mm-hmm (affirmative).

Çağrı Savran: Um, but, uh, it's ... It can handle, uh, fluids that are much bigger than micro- microliters. And it has to, uh, because-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... First of all, you've got to be able to find these rare cells, and you've got to be able to do that quickly. You can't wait for, um, 10 hours to flow just one tube of blood through a device. So, that's how we came up with this idea.

Sal Daher: So, this is the big thing, is that you are able now to ... Because of the scale-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... Of the sample-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: I mean, presumably if it takes you five minutes to run through 10 milliliters ... I mean, if you take a pint of blood, within an hour-

Çağrı Savran: Mmm.

Sal Daher: ... You might be able to run through an entire pint, in which case it can get a really fine-grained ... Extremely rare cells.

Device Seems Amenable to Large Scale Usage – Handling Many Patients at the Same Time

Çağrı Savran: Yeah. So, uh, I mean, from that perspective, you can take our, um, uh, device and you can very easily parallelize it.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, I was actually at a- a conference just a couple days ago here in- in Boston, and, uh, the consensus was that whatever device that comes out there, it has to be high throughput. It has to be-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Able to handle many patients at the same time. So-

Sal Daher: Right. Right.

Çağrı Savran: ... If you ... You know, based on what you've just said-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Um, you can imagine multiple blood samples from multiple patients being run in parallel-

Sal Daher: In parallel at the same time.

Çağrı Savran: All at the same time. Yeah, and if your system is high speed, then- then you could do that.

Sal Daher: Yeah. Yeah. That really-

Çağrı Savran: So-

Sal Daher: ... I- it changes the equation. While the patient is in the office, you can be doing tests, you know, the way that they do with glucose.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: You know, you go to your primary care physician, they- they prick your finger, and they-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... Five minutes later, they'll tell you, you know, your blood glucose level is okay.

Çağrı Savran: Yeah.

Sal Daher: Or, um, it's a tremendous-

Çağrı Savran: Yeah.

How the Invention Came About

Sal Daher: So, how did this, you know, did this thing come about? Were you, like, walking one day and a- an- an acorn fell on your head-

Çağrı Savran: (laughs)

Sal Daher: ... And you had, "Oh, this is what I'm gonna do!" Ho- how did it come about?

Çağrı Savran: Al- almost. Almost. I was actually driving.

Sal Daher: Ah.

Çağrı Savran: Uh, I was driving, and I can actually vividly remember where.

Sal Daher: So, you do science while you drive?

Çağrı Savran: Uh, y- y- o- e- (laughs)

Sal Daher: (laughs)

Çağrı Savran: I mean, the- the ideas, uh ... I- it's actually very interesting. I was thinking about this the other day, why- why that's the case. The- the- the ideas about new devices, they never come to my mind when I'm working on the device, or when I'm reading a manuscript, or when I'm in my office, or when I'm in the lab, or when I'm in the group meeting. They always come when I'm doing something totally unrelated. Either when I'm in the bathroom or when I'm, uh, driving. This idea came to my mind when I was driving. I- I can very vividly remember where I was, where exactly I was, and, uh, uh, it just popped up in my mind. I said, "Oh, this is how we're gonna do this."

Sal Daher: Uh-huh (affirmative).

Çağrı Savran: And, uh, it's working very well, at least the version that we have right now. It's generated a lot of interest. We have a lot of clinical collaborators working with us. We're analyzing their patients-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... In terms of circulating tumor cells. We're now, uh, about to start a clinical study to analyze blood samples of pregnant women, uh, to find, uh, fetal cells. Yeah.

Sal Daher: Tell us about the- the- the b-, the breast cancer, uh, work-

Çağrı Savran: Yes.

Sal Daher: ... That's being done.

Çağrı Savran: So, um, we're, uh, collaborating with an eminent breast cancer biologist at IU medical school. His name is Milan Radovich.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, he specialized in triple negative breast cancer. It's a very aggressive form of breast cancer.

Sal Daher: Milan Radovich? I wonder if he's r- related to Aleks Radovic-Moreno, who is also a biotechnologist here in Boston. But anyway, uh, this-

Çağrı Savran: (laughs) I don't, I don't know. But I'll ask him.

Sal Daher: (laughs) I- I'll- I'll- I'll ask, uh, I'll ask Aleks. Uh, but please- please continue.

Çağrı Savran: Yeah. Yeah, so, triple negative breast cancer. Just, triple negative means that the tumor cell lacks the three receptors on its surface that are-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Typically targeted. And when the cell doesn't have this, then it cannot be targeted with the, with the drugs that normally target these receptors. So, it- it's a particularly aggressive form of breast cancer, and there is a clinical study right now to find out how it can be prevented from coming back following chemotherapy and surgery.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Well, these patients go through chemotherapy as well as surgery-

Sal Daher: Right.

Çağrı Savran: ... And, uh, the early-stage patients are not metastatic. And, uh, after the chemotherapy and surgery, they're declared disease-free, because the CT scan cannot find anything.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, but then the question is, you know, is it gonna come back or not? So, right at that point they collect a blood sample from the patient, and we look at the blood sample. And in many of these patients, we actually see circulating tumor cells.

Sal Daher: Wow.

Çağrı Savran: It's, uh ... There's remnant of the disease-

Sal Daher: Despite their being declared disease-free by the normal-

Çağrı Savran: Yeah, by CT scan-

Sal Daher: ... The- the CT scan.

Çağrı Savran: Exactly, exactly. And not only that, but they give drugs to these patients, right? Even though they're declared disease-free, that they want to make sure that it doesn't come back. So, they collect another blood sample a couple weeks later, and we look at the number of CTCs, circulating tumor cells, in the blood again, and we see changes in many of these patients. Uh, in many of them, the CTC number goes down. In some of them, uh, it, uh, it does not. Uh, and we don't exactly know at the moment the- the- the outcome, because the study is still continuing, but, uh, we will find out, uh, pretty soon whether our results correlate with the actual clinical, uh, outcome of these patients.

Sal Daher: Uh, this- this is really fascinating. It's, um, uh, right at the frontier of, you know, practical science.

Çağrı Savran: Uh, but if it does it, it's gonna make a pretty big impact, because you're basically looking into the disease inside a patient, uh, that cannot be seen by a CT scan, uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... By an- other normal means, just-

Sal Daher: Much- much earlier, much earlier.

Çağrı Savran: Yeah. Yes, and- and just, and just by a blood test.

Why Çağrı Savran Founded a Company

Sal Daher: Yeah. Non-invasive and so forth. So, Çağrı, what possessed you to start a company? I mean, your dad's an engineer, you have all these engineers and teachers and scientists in your family-

Çağrı Savran: (laughs)

Sal Daher: ... Uh, g- doing this crazy thing of starting a company, it's so dangerous, it's so crazy, 'cause ... So, what got you to do that?

Çağrı Savran: (laughs) Yeah. So, um, it was actually very natural. It's like, it wasn't even, like, "Should I start a company or should I not start a company?" When we first came up with this idea, actually, that was not to start a company. It was just to solve a problem.

Sal Daher: Right. Right. Right.

Çağrı Savran: That's why the idea came a- into our mind. But then, but then-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... As we, uh, saw that it was working, then we said, "Well, we've got to make this very easy so that it's, uh, mass-manufacturable, so that it's disposable, so that it can function in the hands of other people, not just in our own lab."

Sal Daher: Very important-

Çağrı Savran: And- and ... Exactly.

Sal Daher: ... That you have ... Yeah, someone with a tenth-grade education can operate it.

Çağrı Savran: Exactly.

Sal Daher: Right.

Çağrı Savran: And that it's fast and that the ... It's ... It has very high performance, it's sensi-, it's very sensitive. You can find, uh, the cells that are in there, and it's ... It rejects as much of the cells that you don't want as possible. And then, if you put all that together, what is the next step? Well, that means you've got to commercialize this, so that you can get it in the hands of people. So, it- it was a very natural step. It was like graduating from high school and then just going to college.

Sal Daher: College. (laughs)

Çağrı Savran: It's the next thing. And so-

Sal Daher: Yeah, right.

Purdue’s New Commercialization Policy Played a Big Role in the Decision to Found the Company

Çağrı Savran: That's basically how, uh, how- how it happened. And, uh, again, in no small part, uh, because of the encouragement that was given by, uh, Purdue's new commercialization-friendly ecosystem.

Sal Daher: Wow. So, this isn't a result of President Daniels' approach to-

Çağrı Savran: Exactly.

Sal Daher: ... In a, in a certain way, uh, as well.

Çağrı Savran: Exactly.

Sal Daher: Yeah.

Çağrı Savran: Exactly. And his influence on other people, too.

Why Turbocharging Cell Separation Is So Important

Sal Daher: You know, so, if you can just review again why it's so important to be able to turbocharge the, you know, cell separation the way you're doing.

Çağrı Savran: Mm-hmm (affirmative). Mm-hmm (affirmative). So, the war on cancer was declared quite some time ago, right? And what is your assessment? I mean, are we, are we winning that war, you think?

Sal Daher: Well, I think we're making ... You know, we've won battles.

Çağrı Savran: Yeah.

Sal Daher: There are ... There's a lot of treatments-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... Uh, but there are some cancers, for example, you know, the brain cancers, that are-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... Where the c- treatments have ... Leave a lot to be desired.

Çağrı Savran: Mm-hmm (affirmative). Mm-hmm (affirmative).

Sal Daher: Pancreatic cancers-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... Leave a lot to be desired.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: You know, there are some areas where a lot of progress has been made, but-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... There's still a lot to be done.

Çağrı Savran: I- I completely agree, and significant advancements have been made, but the war really hasn't, uh-

Sal Daher: No.

Çağrı Savran: ... Been won. Because, uh-

Sal Daher: No.

Çağrı Savran: ... In this country every year, about half a million people die. Uh, 500,000, approximately, maybe a little more, maybe a little less. And we're getting into 2018 right now, and another half million people will be dying. And I'm-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Not even, um ... I haven't even specified, uh, the number of patients that are living with the disease. That's-

Sal Daher: Yes.

Çağrı Savran: ... Half a million just the people that are going to die.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: We have to turbocharge something to help these people, right? You and I could be, uh, uh, well, I'm-

Sal Daher: Well, yeah, it happened, it happened in my family. Um, you know?

Çağrı Savran: Yeah, exactly. So- so, uh, so do I.

Sal Daher: It's- it's over ... Yeah.

Çağrı Savran: And, uh, um, not just cancer, but also in the field of prenatal diagnostics, for example. There are four million pregnancies in this country.

Sal Daher: Mmm.

Çağrı Savran: Just in this country alone. You've got to turbocharge the field so you can analyze as many patients in a quick amount of time, uh, some small-

Sal Daher: Let's s- speculate. Beyond- beyond the things, the applications we've talked about, what else could be out there? Let's- let's get-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... A little speculative here.

Çağrı Savran: Mm-hmm (affirmative). What else out there in the sense of ...?

Sal Daher: Yeah, y- you know, beyond a cancer diagnostic, because this is a platform.

Çağrı Savran: Yeah, I see. Yes.

Sal Daher: This is not just-

Çağrı Savran: Exactly.

Sal Daher: ... A cure for something. It's a platform that allows you to do a lot of other stuff. So-

Çağrı Savran: Exactly.

Sal Daher: ... separating cells-

Çağrı Savran: Exactly. Yeah.

Sal Daher: ... Is- is a, you know ... Any other thoughts beyond these two use cases that you mentioned?

Other Use Cases: People Are Always Suggesting New Ones but Need to Concentrate

Çağrı Savran: Yeah, of course, yeah. There's quite a bit of other fields, actually, but- but- but we have to-

Sal Daher: Yeah. The- the struggle is- is focusing, right?

Çağrı Savran: Exactly.

Sal Daher: It's e- eliminating ... Yeah, exactly.

Çağrı Savran: (laughs) And we're gonna ta- ... Uh, we're gon-, we're gonna talk about that later. But-

Sal Daher: Well, but- but anyway, let- let's ... We're l-, we're not, we're not figuring out the strategy for Savran Technologies. We're just, uh-

Çağrı Savran: Yeah, exactly.

Sal Daher: You know, gedankenexperiment here.

Çağrı Savran: Yeah, exactly.

Sal Daher: You know, mind e-, you know, mind experiment.

Çağrı Savran: Sure. There are other, um, applications such as, uh, sepsis detection.

Sal Daher: Oh, wow.

Çağrı Savran: And there are even some other, uh, applications that, uh, we haven't even touched yet, but that was brought up by, uh, some companies that have, uh, seen the technology.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, and that, uh, goes along the lines of water purification.

Sal Daher: Wow. (laughs)

Çağrı Savran: That's- that's totally different from (laughs) everything else.

Sal Daher: Yeah. So, people see the technology and say, "Oh, wow, it could be for this, it could be for that, yeah."

Çağrı Savran: "Oh, it can do this." Yeah. And then there's other people say, "Oh, you know, we can do this." And then, uh-

Sal Daher: Because it's a game-changer because of this tremendous throughput that you're-

Çağrı Savran: Exactly. Exactly. Exactly.

Sal Daher: Yeah.

Savran’s Tech Is a Game Changer because of Throughput and Parallelization

Çağrı Savran: Throughput and parallelization opportunity.

Sal Daher: Parallelization. Yeah.

Çağrı Savran: Exactly right.

Sal Daher: Yeah.

Çağrı Savran: And, uh, turbocharging. So, this entire field needs to be turbocharged, because there are patients that are waiting to be benefited, but your specific question of why the field of cell separation needs to be-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Turbocharged.

Sal Daher: Yes.

Other Techniques Look at Pieces of DNA – Savran’s Tech Is Capable of Finding the Entire Genome

Çağrı Savran: I'd li-, I'd like to say a few words about that too. Now, there are techniques right now, non-invasive techniques, that can, uh, be used in cancer diagnostics as well as in prenatal diagnostics. These techniques are also based on, um, looking at blood samples. But they look at bits and pieces of DNA in the blood sample.

Sal Daher: Right, right. Mm-hmm (affirmative).

Çağrı Savran: So, the cells that are dying, again, both in the field of cancer and both in the field of prenatal diagnostics. Even though these are very different fields, uh, from a mechanical perspective, uh, they're actually very similar.

Sal Daher: Right. Right.

Çağrı Savran: When cell, when cells die, they shed the DNA that's inside them, and then-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... You know, they're chopped up into pieces and then they're, you know, floating around in the patient's blood. So, you actually can gather information from these bits and pieces of DNA. In case of cancer, you can get some information about the tumor cells. Uh, in the case of, um, uh, prenatal diagnostics, you can get some information about the baby. But there's only few and distinct pieces of information you can get just by looking at cell-free DNA, and the reason is, that's not the only DNA that's in blood. It's-

Sal Daher: Cell-free DNA is the chopped-up DNA?

Çağrı Savran: That's chopped-up DNA.

Sal Daher: Right. Right.

Çağrı Savran: What ... Uh, so it's- it, uh ... The- the cell-free DNA that you're looking for is not the only cell-free DNA in blood.

Sal Daher: Right, right.

Çağrı Savran: The DNA that you're looking for actually is a very small portion of a huge amount of native DNA in the blood sample. You have a lot of DNA that is coming from normal cells-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... And in the case of, uh, pregnancy, you have a lot of DNA that's coming from the mother. But you're not interested in that. You're only interested in the-

Sal Daher: A- and the and the baby. It's coming from the baby and the mother, and it's all-

Çağrı Savran: Baby and the mother, but- but the amount that's coming from the baby, that's ... Which is what you're interested in-

Sal Daher: Which you want, right.

Çağrı Savran: ... But that's very small.

Sal Daher: Right.

Çağrı Savran: The rest of it is ... Most of is, uh, the mother's, uh, uh, DNA.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, so, um, if there are some very subtle changes in the DNA, some deletions and very subtle changes, you can't detect those using DNA-based tests. But you can detect them using cell-based tests.

Sal Daher: Ah, okay.

Çağrı Savran: Because when you get the whole cell-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... You have access to the entire genome. You basically have no background. You don't have... It's not mixed with any other DNA if you have the whole cell. So, that's exactly why I believe and lot of scientists and clinicians believe that cell-based technologies are gonna be the way to go, and that's exactly why it needs to be turbocharged.

Sal Daher: This is so promising and tremendous. Coming up next, I will ask Çağrı Savran how he recruited the biggest of bigwig advisors to Savran. (laughs)

Çağrı Savran: (laughs)

Sal Daher Reads the Review by Spizzy Spong on iTunes and Asks for Your Review

Sal Daher: However, first I'd like to thank Spizzy Spong for this review. This is an iTunes review. “I am a first-time entrepreneur with a startup in Boston, and this podcast has been a huge resource for me. The interview with seasoned entrepreneurs, especially the episode with Kathryn Roy, are great, but it's the episodes with other angel investors that are really illuminating. It's not often you get to hear candid discussions between angels about industries, pitching, teams, et cetera. Looking forward to more episodes.”

Thanks, Spizzy Spong. That's a cute name. I love- love that name. The (laughs) ... They c-, you ... They c- come up with the funniest names.

Çağrı Savran: (laughs) Yeah.

Sal Daher: Uh, the Angel Invest Boston podcast has outstanding guests such as world expert in microfluidics Çağrı Savran, is professionally produced, has no schlocky commercials, and comes to you free. The only thing we ask in return is that you help get the word out. Please tell a potential angel or founder about us. Take a minute to review our podcast on iTunes in faithful emulation of Spizzy Spong. Sign up at angelinvestboston.com to be notified of new episodes, and of upcoming in-person free events.

How Savran Landed Bigwig Advisor Ken Morse

So, Çağrı, how did you get the biggest of bigwigs to be an advisor to your startup? Please tell us about getting Ken Morse and how he's helped you.

Çağrı Savran: So, uh-

Sal Daher: Well, tell us who Ken Morse is.

Çağrı Savran: Yeah, yeah.

Sal Daher: Yeah.

Çağrı Savran: So- so- so Ken and I go, actually, way back. Uh, when I was a Ph.D. student at MIT, I decided to take a class from-

Sal Daher: He's co-founder of 3Com, involved with all these startups. Uh, he's a big donor at MIT, and also teaches an entrepreneurship course, um.

Çağrı Savran: He used to teach an entrepreneurship l-

Sal Daher: He used to, used to teach a course.

Çağrı Savran: Yeah, entrepreneurship course at MIT.

Sal Daher: Right.

Çağrı Savran: And he's the founder of the MIT, uh, Entrepreneurship Center.

Sal Daher: Center. Right.

Çağrı Savran: And- and he managed that for quite some time. And, like I said, when I was a Ph.D. student at MIT, I decided to take a class from, uh, Sloan School of Management.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, I was doing an engineering Ph.D., but I wanted to take a class there-

Sal Daher: Right.

Çağrı Savran: ... And this was the Entrepreneurship Lab class. That was the name of the class. E-Lab.

Sal Daher: E-Lab. Right.

Çağrı Savran: And Ken Morse was teaching that.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: So, it was my first acquaintance with Ken, and he was a very energetic instructor. He, um, gave very specific lectures on pitching and negotiating and, uh, networking, as well as, uh, going through the details of case studies that, uh, were both in the, uh, uh, portfolio of, uh, MIT Sloan School of Management as well as Harvard Business School. Because-

Sal Daher: Yes.

Çağrı Savran: Uh, a third of that class was MIT, uh, MBA students, a third of it was Harvard MBA students, another third was MIT engineers, actually.

Sal Daher: Right. Right.

Çağrı Savran: It was like a mixed, uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: And they were putting ... Yeah.

Sal Daher: So, you were thinking about entrepreneurship already at that-

Çağrı Savran: Y- yeah, exactly, I was thinking about it.

Sal Daher: ... Even when you were doing your Ph.D., yeah.

Çağrı Savran: Exactly. Yeah.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, and, uh, you know, they ... It was very realistic, and they-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Were teaching you how to, um, solve some real business problems. So, ever since then, I kept communicating with Ken on and off. He was, uh, very gracious to offer some pro bono help over the phone, over (laughs) the email.

Sal Daher: (laughs)

Çağrı Savran: But when, uh, our company, um, uh, started to do, uh, very well, and it was about time for me to reach out to him, and ask whether he would be, uh, interested in officially getting involved in our company as the chairman of the Board of Advisors, and, uh, he accepted. Uh, he's, uh, like I said, a very energetic guy, and he's very pragmatic about, um, pretty much everything that's business-related. He's very connected, uh, espec-

Sal Daher: Unbelievably connected.

Çağrı Savran: ... Especially in the Boston area, and every single time I need to deal with people, basically, almost every-

Sal Daher: (laughs)

Çağrı Savran: ... Single time in the context of business, I basically, uh, ask his advice. Uh, in many cases, I actually get him directly involved, and he has been a great resource. Just having him on board has actually helped reaching out, and, uh, energizing some other key people as well.

Sal Daher: Yeah. I've gotten to know him because of my involvement with Savran.

Çağrı Savran: Yeah.

Sal Daher: So, uh, please tell us about how you brought in repeat founder Patrick Rivelli as CEO, and what he does for Savran Technologies. Uh, listeners should know that Patrick Rivelli was interviewed on this podcast in a valuable earlier episode titled "Love and Biotech Exits," because Patrick ... he had two medical equipment start-ups that he started and- and exited within 11 years. And so, he's very experienced. Uh, he was heading up MIT Angels here, and l- looking very closely at a lot of this microfluidics. Uh, he's pretty familiar with the microfluidic space.

Çağrı Savran: Yes.

Sal Daher: So anyway, so tell me that story there.

How Savran Found Its CEO – Patrick Rivelli

Çağrı Savran: Patrick was really a gift from God, I should say. (laughs)

Sal Daher: (laughs)

Çağrı Savran: Because we were looking for a CEO and, um, Patrick was introduced to us through, uh, Peter Fasse, and I believe Peter had heard about him through you, Sal, so-

Sal Daher: Yeah. Yeah, yeah, yeah.

Çağrı Savran: ... I mean, you're- you're, uh-

Sal Daher: Peter ... I mean, I first heard of Savran at one of these Sunday dinners that we have together. The whole family gets together on Sunday at a Chinese restaurant, and we talk about family things, and then once in a while, we'll talk a little bit of business. And Peter said, "Oh, you've got to, you've got to see this guy, this company is amazing, and Çağrı i- ... The inventor of the technology is just a remarkable person. Very energetic, and, uh," and so forth. And I said, "Wow, you know, I've got to meet him." He put me in touch with you-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... And then I ... Whenever I do anything in- in life sciences, I ... You know, I- I haven't, I haven't started companies in life science, I haven't started companies in any field.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: So, I always bring in somebody who knows a whole lot more than I do, uh, you know, to look it over. And that's how I brought Patrick in. Patrick is sort of my biotech guru.

Çağrı Savran: Yeah. So, we met with him. I think he first, uh, wanted to meet us and get to know us and the technology. But we didn't even have to explain too much because ... Uh, about the technology, because he already was very familiar with the field.

Sal Daher: Yes.

Çağrı Savran: Not just, uh, the field of biomedical devices in general, but very specifically, about, uh-

Sal Daher: Cell separation. (laughs)

Çağrı Savran: ... Cell separation devices. And, uh, he saw this and he was like, "Oh ..." Yeah?

Sal Daher: Well, he- he's ... He runs the Life Science Track at MIT Angels.

Çağrı Savran: Yes. Yes.

Sal Daher: So, he sees all this stuff coming through, and he's-

Çağrı Savran: Exactly.

Sal Daher: ... At MIT all the time. I mean, he spends ... You know, hi his office is in ... At, uh, One Broadway, and he's at MIT all day.

Çağrı Savran: Yeah. Yeah.

Sal Daher: Uh, so he's seeing all this stuff.

Çağrı Savran: Yes. So, he saw all the technology, and he was like, he was like, "Oh, my God, this is it."

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, because the two major problems that are still waiting to be solved is, number one, throughput-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... And number two, purity. Right?

Sal Daher: Wow. Yeah.

Çağrı Savran: Both of these need to be solved, and he said, "This is it. This solves both of these. How can I be involved?" And we said, "Well, you know, we would like you to be our CEO. Uh, would you accept it?" He said, "Yes, I would," and he was (laughs)-

Sal Daher: (laughs) It was, it was such a ... You know, it was like lighting. A lightning strike.

Çağrı Savran: Yes. (laughs)

Sal Daher: Tremendous.

Çağrı Savran: For ... Definitely for us. (laughs)

Sal Daher: Yeah. Oh, he's- he's, uh, he's so, uh ... Patrick is, uh, you know, he's- he's ... So, he's a very modest person.

Çağrı Savran: He is.

Sal Daher: If you talk to him, well, you know, you have no idea-

Çağrı Savran: Exactly.

Sal Daher: What depths run there.

Çağrı Savran: Exactly. Exactly. Yes.

Sal Daher: Uh, he- he's not, he's not a bigmouth like me. But, you know, (laughs)

Çağrı Savran: Y- y- I ... (laughs) No, I (laughs)

"Oh, you have no idea how I wish that somebody would say that about me, that I'm 'quietly competent.'”

Sal Daher: It's ... That reminds me of my ... I- uh, this is a funny story. I had this, uh, boss who's become a dear, dear friend. Uh, but she is one of the most charming people you could imagine. She's unbelievably charming and scintillating, is how you'd describe her. But she's not a quiet person. She's a (laughs) very ... Very talkative and very chatty and very social and so on. And I remember, uh, when I working for her at Bank of Boston, there was a young woman there who was- was in charge of the treasury aspects of the business that we were doing. So, she asked me, "So, what do you think of Deborah?" "Well, I think she's very good, and I think she's quietly competent." And then my friend says to me, "Oh, you have no idea how I wish that somebody would say that about me, that I'm 'quietly competent.'" (laughs)

Çağrı Savran: (laughs)

Sal Daher: But she's a delightful lady, though. Uh, I mean, I would not want her to be quiet, because she's unbelievably charming.

Çağrı Savran: (laughs)

Sal Daher: Uh, so, anyway. Uh, but Patrick is, uh, is really an exce- ... I think an excellent complement, um, because he's the ... Personality-wise, he's very different, very, uh, low-key, and he's extremely knowledgeable, and, um, very energetic, very hard-working.

Çağrı Savran: And very systematic and-

Sal Daher: Systematic.

Çağrı Savran: ... Very, very calm, and, uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Like- like you said, if you didn't know him at all, if you just spend a few minutes, you never would have guessed that he's, uh, such a highly successful person, because he doesn't really talk about himself all that much. He doesn't really, uh, uh, uh, uh, brag about anything. He's just very to the point.

Sal Daher: Yeah.

Çağrı Savran: Uh-

Sal Daher: You cannot tell how tenacious he is.

Çağrı Savran: Exactly.

Sal Daher: Uh, he's-

Çağrı Savran: (laughs)

Sal Daher: ... He's just a ... Unbelievably-

Çağrı Savran: Yeah.

Sal Daher: ... Does not let things go, is very tenacious.

Çağrı Savran: Yeah.

Sal Daher: Uh, so, I- I see this and I say, "Wow, a brilliant technical founder, Çağrı Savran, brilliant and very communicative, and then a highly connected advisor like Ken Morse, and then Patrick Rivelli, a very professional, very serious CEO." He was, he was a consultant with Bain be- for many years before that, uh, and so on. It's all in the interview in "Love and Biotech Exits," uh, that I did. So-

Savran’s Choice of the Right Patent Attorney Was Crucial – Peter Fasse Helped Way Beyond Patents

Çağrı Savran: Don't forget our highly competent patent attorney, the famous patent attorney.

Sal Daher: Well, this is the thing. You see, with this kind of technology, the moat that you have that ... And Warren Buffett likes to talk about so much ... You actually have a moat here, which is, you know, the fact that this is a patented technology, and Peter Fasse, my- my- my brother-in-law would ... By the way, he's also been interviewed on this podcast ...

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: Talks about the importance of patents. You know, I work a lot in the software area, and there, it's really hard. Because software changes all the time, it's really, really hard to have a patent be effective.

Çağrı Savran: Yeah.

Sal Daher: But in the life sciences, if you don't have a patent, it's worthless. It's not a business.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: With a patent, it's ... Particularly a business if it develops really quickly ... It makes the potential for the business to be highly, highly profitable. And- and so what's your advice about finding a- patent attorneys.

Çağrı Savran: Well, uh, my advice would be to find the best that you possibly can. Find the best that you can afford, because it actually makes a big difference. Uh ... Yes.

Sal Daher: So, yeah, it's not ... You don't, you don't stint on patent attorneys.

Çağrı Savran: Yes. I mean, the best ones will, uh, will, uh, certainly cost, but it's definitely worth it, because it's not just about writing a patent and getting it prosecuted, it's al-, it's also about the strategy of patenting.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: What's gonna come-

Sal Daher: Right.

Çağrı Savran: ... Next. For example, we have multiple issued patents right now, but Peter was the one that advised us to immediately file continuations or divisionals, uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Right before these patents issues, so we can, uh, y- you know, in a sense keep the patents alive, and, uh, he also advises us, uh, very actively about patent strategy. Coming up with additional capabilities and how they should be protected. How, uh, countries should be, uh, selected, um, and-

Sal Daher: Right. And- and there's also specialization. I mean, you're ... Patrick is very familiar with microfluidics, because there's a lot of that being done around here. Peter has seen a lot of microfluidic startups as well.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: He knows the space very intimately.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: Uh, so there's this whole specialization. It points to why Boston is such a great place to start a company, because you have all these resources, you know?

Çağrı Savran: Exactly. Which also brings me to, uh, our, uh, business counsel. Uh, he's, uh, he's William Whelan-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Uh, of Mintz Levin. Uh-

Sal Daher: Yes.

Çağrı Savran: ... He's also, um, uh, very well-known, uh, in the life sciences arena.

Sal Daher: Mm-hmm (affirmative). Yeah.

Çağrı Savran: And, uh, again, I was introduced to- to them through Ken Morse.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: He knew them very well. Um, they're also based in Boston, right here.

Sal Daher: Well-

Çağrı Savran: And that it's just-

Sal Daher: ... You're ... That ... You're gonna need that, because if ... We're talk about the strategy now.

Çağrı Savran: Exactly, yes.

Sal Daher: Uh, the going forward. You know, these licensing agreements and all of ... So, he came via Ken. So, it was Ken's recommendation.

Çağrı Savran: Yes. Yes. Exactly.

Sal Daher: Yeah. Mm-hmm (affirmative).

Çağrı Savran: Yeah. We met with them, um, and, uh, they were very excited about this, and they really wanted to help-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Uh, be a part of the, be a part of the team. Uh, and there's actually multiple people there. Uh, there's, um, William Whelan, uh, and then there's also, um, John Dellapa, who's, uh, focusing on licensing, uh, deals. They work together-

Sal Daher: Yeah.

Çağrı Savran: ... In the same- same- same company.

Sal Daher: Yeah. Yeah.

Çağrı Savran: And, um, uh, it's, uh, we really have-

Sal Daher: It's- it's ... This is how special ... How they speciali- ... I mean, like, Fish and Richardson doesn't do the corporate side. They do j- just the patent stuff.

Çağrı Savran: Exactly. Exactly.

Sal Daher: And, you know-

Çağrı Savran: Yeah.

Sal Daher: ... Where- where Peter Fasse is. You know, Mintz Levin is the firm that will do licensing and, uh, and also the incorporation and all these other things.

Çağrı Savran: Exactly.

Sal Daher: They bring together all the pieces. Um, because you're not in the business of reinventing all these different wheels. Just find the people who know best how to advise you on that, but you're in the business of reinventing ... turbocharging microfluidics to make these things flow, uh, really well. So, tell us about the strategy. Originally. Savran Tech was pursuing a strategy of licensing out its technologies to various parties.

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: And then Patrick Rivelli came on as CEO and advocated a hybrid technology. Uh, would you care to talk about that?

Çağrı Savran: So, this is a platform technology, like you previously mentioned.

Patrick Rivelli, CEO Proposed a New Go to Market Approach

Sal Daher: But I ... Um, what I meant, I meant to say, a hybrid approach.

Çağrı Savran: A hybrid approach, yes.

Sal Daher: Approach to-

Çağrı Savran: Yes.

Sal Daher: ... To taking the technology to market, I should say.

Çağrı Savran: Yes, yeah. To ... So, the technology itself is a platform technology. It can be-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Applicable to multiple fields of use.

Sal Daher: Right.

Çağrı Savran: Uh, there's a- a number of fields that we have identified. There's, uh, two that we are focusing on right now, but there's only one that we ourselves can develop. Uh, we've got to focus on one.

Sal Daher: Absolutely.

Çağrı Savran: Uh, uh, we can't do all of these, uh, on our own, uh, there could be other fields of use that we haven't even thought about right now.

Sal Daher: You're gonna discover when you bump into people-

Çağrı Savran: Yeah, exactly.

Sal Daher: ... Because, "Oh, it could be used for this, it could be used for that."

Çağrı Savran: (laughs)

Sal Daher: Yeah, it's- it's-

Çağrı Savran: Yeah, ex- exactly.

Sal Daher: Yeah.

Çağrı Savran: So, in the very beginning we were thinking, "Oh, you know, let's, uh, you know, do a little bit of development and then just license out every single one of these. And then, uh, we realized that it may be, uh, uh, better if we develop in one of these fields on our own. Then we can directly reflect our own experience and our own, uh, passion, our own energy-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Onto it, and, uh, maximize the chance of success while still being able to license in other fields of use where we would love to focus, but we just cannot because it's just too much for us. We're-

Sal Daher: You cannot do everything.

Çağrı Savran: Exactly. That was Patrick's suggestion. Ken, uh, was a supporter of that as well.

Sal Daher: Yes.

Çağrı Savran: And so was I. Uh-

Sal Daher: Yeah, yeah, I know.

Çağrı Savran: ... So then, that's- that's-

Sal Daher: It made ... It makes perfect sense.

Çağrı Savran: And that's the approach that we're pursuing right now.

What Makes the Savran Lab at Purdue so Productive

Sal Daher: Excellent. Excellent. So, in your 13 years at Purdue, you've built an amazingly productive lab. Please explain the interactions that made that possible.

Çağrı Savran: There are so many interactions that I- I think it would take a lot of time f- to explain every single one of them, but I'm gonna explain the ... Maybe a few key interactions.

Sal Daher: Right.

Çağrı Savran: So, I'm an academic, and I run an academic lab, and I have a very competent, uh, uh, team of, uh, uh, academics in my lab. I have a highly competent, research scientist. His name is Dr. Chun-Li Chang. He's been with me for quite some time. He's very passionate, uh-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... About the technology, and, uh, he's, um, very hard-working, and my students are also e- exceptional researchers. So, um, I'm primarily an academic. I'm not primarily a businessman. My job is to be an academic, and so the first thing I've got to worry about is education of my students-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Um, and, uh, the academic output of my lab. Every advisor has a different approach. My approach is more to, um, let the students discover their own potential-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... And then I will basically enable them to push their potential to the fullest extent. Okay. So, uh, uh, interaction with the students is very, very important.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: That's- that's number one, because it's really, um, uh, they're the ones that did all the experiments that then led to the patents, which-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... Then provoked Purdue to, uh, uh, encourage me to start a company and support it, and it's ... Then he- here we are. In addition to that, there has been a tremendous help from my clinical collaborators. Now, at Purdue, we don't have a medical school, and it's very important to have collaborations with clinicians because this is a clinical device, right?

Sal Daher: Right. Right. Right.

Çağrı Savran: And it's not very easy to, uh, um, to just, um, knock on a clinician's door and say, "Hey, you know-"

Sal Daher: (laughs).

Çağrı Savran: "... I'm, you know, I'm- I'm building devices, um, do you-"

Sal Daher: Yes.

Çağrı Savran: "... Do you want to work together?" I mean, they're dealing with some very, uh, difficult scenarios, with difficult situations. People that are about to die, uh, people that are suffering. Somebody really needs to, uh ... Someone that knows them really needs to facilitate that interaction, and the, and- and the, and the introduction. And, uh, we have a, um, a person like that, again, just appeared. I did not know her. She found me. Uh, her name is Marietta Harrison. She's, uh, an administrator at Purdue. She's a scientist as well.

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: Uh, and, uh, she really, uh, found out about our technology, and she reached out to me. She said, "I- I have to introduce to- to these clinicians, because you can't test your device without them." And she was running the, uh, Oncological Sciences Center. So, uh, uh, when she went in to, you know, ask them to meet me, uh, they were more (laughs) ... They, uh, it was easier for them to uh, um, accept my phone call. Uh-

Sal Daher: Mm-hmm (affirmative). Sure. Sure.

Çağrı Savran: ... Rather than me cold-calling them.

Sal Daher: Mm-hmm (affirmative). Sure.

Çağrı Savran: Uh, but, uh, uh, I- I- every single time I, uh, you know, remember how this whole thing was, uh, was- was born, I really want to, uh, uh, thank her over and over again. Without- without her introductions, it would have been very difficult. Like I said, we don't have a medical school on campus.

Sal Daher: So, basically, you're saying the ecosystem at Purdue enabled you to make all these connections, which can then make your lab effective.

Çağrı Savran: Yes.

Sal Daher: So, it's m- beyond encouraging entrepreneurship. It's also encouraging collaboration with the medical school at- at University of Indiana and, uh, and-

Çağrı Savran: Mm-hmm (affirmative).

Sal Daher: ... All these other connections, which is so important in science.

Çağrı Savran: Yes. We don't have a medical school at Purdue, and the closest one is at, um, Indianapolis, uh, as you mentioned, Indiana University, School of Medicine. So, um, we've been going there, m- sometimes multiple times a week (laughs)-

Sal Daher: Mm-hmm (affirmative).

Çağrı Savran: ... To- to give blood samples that are collected by our clinical collaborators.

Sal Daher: Yes. Yes.

Çağrı Savran: ... In their, uh ... Under their IRB protocols.

Sal Daher: Yes.

Çağrı Savran: Um, uh, so that we can test our devices. And without that, the device would be there, but we wouldn't have a chance to test it. That certainly was enabling.

Sal Daher: Excellent. Now, uh, Çağrı, is- is there anything else we've not touched on that you'd like to say to our audience?

Çağrı Savran: I think we touched on, um, uh, pretty much everything, Sal. Uh, but I would really like to tell the audience that, uh, they should continue listening to Sal's podcasts.

Sal Daher: (laughs)

Çağrı Savran Urges Fellow Academics to Bring Their Inventions to Market

Çağrı Savran: And, uh, uh, and, uh, I really would like to encourage, uh, all of my, uh, fellow, uh, faculty colleagues to, uh, seriously consider commercializing their technologies. Uh-

Sal Daher: Hear, hear.

Çağrı Savran: Yes. And get it, get it, uh, get it out of the lab in the hands of people, because, uh, the world really needs their technology.

Sal Daher: This is really important, I think, what you're saying here. The other day, I was listening to a podcast. This is a conversation between two economists. And the economist who was being interviewed was saying, "You know, it's really important for us, in addition to publishing papers, to actually get out there and get our papers read." Uh, so, if you're a scientist, it's important not just to get your papers read, but get your technology out so that it affects people.

Çağrı Savran, I am exceedingly grateful to you for participating and helping make this a great interview.

Çağrı Savran: Thank you very much, Sal. It was a, it was a great pleasure.

Sal Daher: It's awesome that you could be here.

Çağrı Savran: Thank you.

Sal Daher: I'd like to invite our listeners to enjoy this podcast, to review it on iTunes. This is Angel Invest Boston, conversations with Boston's most interesting angels and founders. I'm Sal Daher.

I'm glad you were able to join us. Our engineer is Raul Rosa. Our theme was composed by John McKusick. Our graphic design is by Katharine Woodman-Maynard. Our host is coached by Grace Daher.

Update on the Original Interview with Çağrı Savran, Ph.D.

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.