Chee-Yeun Chung, "Target Alzheimer's," at TEDMED

Chee-Yeun Chung, a neuroscientist from Korea, was captivated by the idea that cures for neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and ALS, could be found by doing experiments on yeast cells. Conventional approaches to neurodegenerative diseases had proved problematic. However, an MIT professor, the late Dr. Susan Lindquist, saw a remarkable connection between yeast cells and the human neuron that could offer a solution. This evolutionary conservation, the scientific name for the unlikely connection, might lead to a platform for finding human cures. The promise of quickly evaluating compounds on simple yeast cells opened up the possibility of testing large numbers of potential treatments. Such massive experimentation could not be done with the much more complex human neuron. Chee was thus inspired to become a scientific co-founder of Yumanity Therapeutics, the corporate embodiment of Dr. Lindquist’s passionate vision.

With $47 million is Series A money, Yumanity has developed ultra-high throughput methods for testing the ability of large numbers of compounds to improve the functioning of yeast cells purposely afflicted with a certain defect. The defect, protein misfolding, is implicated as a cause of neurodegenerative diseases. Compounds found promising in treating yeast cells are then evaluated in human neurons in which protein misfolding is present. Yumanity has also developed methods to figure out the mechanism of action of these compounds based on yeast genetics and protein network analyses.

The result has been the discovery of promising compounds that might become cures. Yumanity believes that its progress over the past two years will justify a Series B raise.  The new money is expected to take the existing compounds to clinical trials.

Click here to read the annotated transcript.

Topics covered include:

  • Chee-Yeun Chung Bio
  • Yeast Cells as a Model for Human Neurons – The Simplest Cells Used to Model the Most Complex
  • Induce Protein Misfolding in Yeast – Test for Compounds that Alleviate Symptoms – Find Candidates to Treat Protein Misfolding in Human Neurons – Protein Misfolding Cause of Alzheimer’s Etc.
  • Take Skin Cells from a Parkinson’s Patients, turn them into Stem Cells, Make the Stem Cells into Human Neurons with Misfolded Proteins – Neurons Then Used to Validate “Treatments” Found in Yeast Tests
  • “There [were] a lot of evolutionary conservation between yeast and human neurons. And the compound worked in yeast and also worked in human neurons. So, this to us presented an amazing opportunity where we can create a drug discovery platform using yeast and human patient derived neurons.”
  • New Approaches Sorely Needed, Previous Approaches by Pharma to Find Treatments for Neurodegenerative Diseases Failed
  • Tony Coles, Yumanity CEO Raised $47 Million Series A to Maximize Freedom of Action & Long-term Support – Sanofi & Biogen Participating
  • Two Years into Series A – Promising Results Justify Series B Raise
  • The Biggest Obstacle Has Been the Chemistry – How to Make the Compounds Soluble, Stable Etc. without Compromising Efficacy
  • What Led Chee to Give Up a Safe Position in a Leading Lab to Risk Being is a Startup
  • Yumanity Hopes to Be in Clinical Trials Within 2 Years – Promising Compounds Have Already Been Identified
  • Working in Yumanity Chee Has Gained a Greater Appreciation of Focus and Team Work
  • Flexibility and Intense Communication Within the Team Have Proved Essential to Success
  • Sought Advice from Others Experienced with Startup Culture – Listened to Advice
  • Chee on Her Late Mentor Dr. Susan Lindquist
  • The Late Susan Lindquist found Her Work on the Evolutionary Conservation between Yeast and Human Neurons No Accepted by the Scientific Community, Yet She Persevered
  • Due to the Grit of Susan Lindquist, the Yeast-to-Human Neuron Platform for Drug Discovery Is Becoming a Reality

Transcript of Chee-Yeun Chung, "Target Alzheimer's" at TEDMED 

SAL DAHER: Welcome to Angel Invest Boston. Conversations with Boston's most interesting angels and founders. This is a special episode of our podcast. We are recording at the TEDMED Conference in Palm Springs, California. So, this is going to be a little different from the usual podcast, in the sense that the interviews are going to be short, and I've done much less prep here, so you guys may notice this because of scheduling things and so forth. So, it'll be more spontaneous, but I think it'll be very interesting. The person that I'm interviewing right now is Chee-Yeun Chung, the young founder of a company Yumanity. And she is based in Cambridge. Let's start off with a little bit of a biography. Chee, would you tell us a little bit about yourself.

Chee-Yeun Chung Bio

CHEE-YEUN CHUNG: My name is Chee-Yeun Chung, and I'm a scientific co-founder of Yumanity Therapeutics. We have two other scientific co-founders; whose names [is] Dan Tardiff and Vikram Khurana. And our company CEO is Tony Coles. And our scientific operation is guided by our CSO. His name is Ken Rhodes.

I come from Korea. I did all my undergraduate education in Korea, and I came to the United States of America to do my PhD. And while I was in California doing my PhD, I was interested in nervous system partly because my grandparents, both of them had stroke, and whole family had suffered quite a bit because of that. So, I always had an interest in neuroscience, and I studied neuroscience during my PhD and I specifically studied stroke as you can imagine.

SAL DAHER: Yes.

CHEE-YEUN CHUNG: Then I had a chance to do my post-doctorate training, and I moved to Boston, Massachusetts at Harvard Medical School where I decided to change the field a little bit. And rather than studying acute neurological disorder, which was stroke, but more chronic disorder, in this case neurodegenerative diseases, like Alzheimer's, Parkinson's, and ALS.

SAL DAHER: Okay.

CHEE-YEUN CHUNG: So, I joined the lab at Harvard Medical School to study the neurodegenerative diseases. From there, I moved on to MIT, where Dr. Susan Lindquist, she passed away last year, had a lab studying neurodegenerative diseases in yeast. And this was very fascinating, how we can learn the most complex cell in our brain from something so simple like yeast.

SAL DAHER: My goodness.

CHEE-YEUN CHUNG: And as a scientist, the things that came out of Susan's laboratory [was] very fascinating. And some of the models that were available in the field at the time was not so faithful to the disease process. But what Susan was showing through yeast was very, very interesting. And the potential of using this simple organism to do something so profound in human nervous system was just mind-blowing to me.

Yeast Cells as a Model for Human Neurons – The Simplest Cells Used to Model the Most Complex

So, I joined her lab to see if I could learn yeast genetic, and I brought some neuronal model system that I was trained in my previous post-doctoral training. And I provided that in Susan's laboratory, and from there, I had this journey of using the most simple cell to understand the most complex, but difficult system, like neurons to learn about neurodegenerative diseases.

And there I had the most bright [mind] in the laboratory who work together with me in this journey of using yeast system to make the drug discovery platform for neurodegenerative diseases. So that I was very fortunate to work with someone called Dan Tardiff, who's the yeast wizard. And also, Vikram Khurana, who's a physician neurologist himself, has a lab at medical school right now, who happened to be my husband. So, three of us were working together in this problem where Dan Tardiff was working on using yeast system to screen thousands of thousands of [compound], modeling the neurodegenerative disease process in yeast. So, what happens in neurodegenerative diseases is the protein that gets misfolded, and this misfolding protein causing toxicity. And we really believed that yeast cells can show the way in how things work in this protein misfolding toxicity, that we can really apply this finding in neurons that are so complex, nerve cells. And this evolutionary conservation is so strong that if we understand what happens in yeast, we can really apply this finding in human neurons.

Induce Protein Misfolding in Yeast – Test for Compounds that Alleviate Symptoms – Find Candidates to Treat Protein Misfolding in Human Neurons – Protein Misfolding Cause of Alzheimer’s Etc.

So, with that biological understanding, which Dr. Susan Lindquist had, we operated in this hypothesis. So, Dan Tardiff, going back -

SAL DAHER: The wizard of -

CHEE-YEUN CHUNG: The wizard of yeast genetics.

SAL DAHER: Yeast genetics, okay.

CHEE-YEUN CHUNG: He and some other people in the lab had modeled the neurodegenerative diseases in yeast cell by introducing protein that gets misfolded in this situation.

SAL DAHER: Ah, okay. So, inducing Alzheimer's in yeast cells.

CHEE-YEUN CHUNG: That's right. And inducing the process that causes Alzheimer's disease. Yeah. Or even Parkinson's disease, or ALS.

SAL DAHER: Right.

CHEE-YEUN CHUNG: So, when you do that, yeast cell actually gets sick and dies. Using these phenomena, Dan Tardiff had screened thousands of thousands of compound to see which compound makes yeast cell healthier.

SAL DAHER: Right.

CHEE-YEUN CHUNG: And he has obtained some of the compounds that makes yeast cell now healthier against this protein misfolding toxicity. But we had no means to understand how this compound actually acts in the cell to make yeast cell happier. So, what he did was he used the amazing tools available in yeast cell to understand the so-called target of this compound in the cellular process.

SAL DAHER: Okay.

CHEE-YEUN CHUNG: So, by doing so, he got the compound that works and makes the yeast cell grow better, and understand how this compound makes this yeast cell better under -

SAL DAHER: What part of the yeast cells make up it interacts with -

CHEE-YEUN CHUNG: Right, in the cellular process -

SAL DAHER: Cellular process -

CHEE-YEUN CHUNG: Right. But the catch was that this now has to be validated in human neurons. Otherwise this is just a finding in yeast, and no one would buy that. So that's when my husband Vikram Khurana and I joined the force and what we did was we used neurons from [patient]. Well this technology was not available about seven years ago where. So, what we used is we used this technology called reprogramming, where we can take the fibroblast of the patient who has, let's say Parkinson's disease, and you can actually reprogram this fibroblast back into embryonic cell, like cell.

SAL DAHER: For those who are not biologists, fibroblast, would you just tell us what it is?

CHEE-YEUN CHUNG: A skin cell.

SAL DAHER: Skin cell, okay.

Take Skin Cells from a Parkinson’s Patients, turn them into Stem Cells, Make the Stem Cells into Human Neurons with Misfolded Proteins – Neurons Then Used to Validate “Treatments” Found in Yeast Tests

CHEE-YEUN CHUNG: Thank you. So, you can take the skin biopsy from the patient, and then you can add cocktails of proteins into it, and what happens is this skin cell that no longer can go back to where it was, but now with this cocktail of things that you are adding to skin cells, it can become like embryonic stem cells.

SAL DAHER: Right. Right.

CHEE-YEUN CHUNG: Once you have that, then you can force this embryonic stem cell like cells we call -

SAL DAHER: Yeah becomes a pluripotent cell.

CHEE-YEUN CHUNG: That's right. We call induced pluripotent stem cells. This cell now can be directed to become cells that we would like to study. So, then we could direct the cells become nerve cells.

SAL DAHER: Right.

CHEE-YEUN CHUNG: That way, we can make the neurons from patient when they're alive because before then, the only neurons that are available from patient is when they die.

SAL DAHER: Right, right.

CHEE-YEUN CHUNG: And donate postmortem tissue.

SAL DAHER: Neuron extraction can be painful.

CHEE-YEUN CHUNG: Yeah.

SAL DAHER: Joking.

CHEE-YEUN CHUNG: That's right. It is just simply practically impossible.

SAL DAHER: You described for us the process by which you're converting a skin cell to a pluripotent stem cell. And then you're transforming that into basically a human neuron.

CHEE-YEUN CHUNG: From the patient.

SAL DAHER: From the patient. And then you're testing the compound that Dan Tardiff has discovered, so how does that translate into a company?

“There [were] a lot of evolutionary conservation between yeast and human neurons. And the compound worked in yeast and also worked in human neurons. So, this to us presented an amazing opportunity where we can create a drug discovery platform using yeast and human patient derived neurons.”

New Approaches Sorely Needed, Previous Approaches by Pharma to Find Treatments for Neurodegenerative Diseases Failed

CHEE-YEUN CHUNG: So essentially those studies that we ended up publishing, the compound and target from the yeast cell validating patient's neuron, and the same target that the compound worked also worked in human neurons. There were a lot of evolutionary conservation between yeast and human neurons. And the compound worked in yeast and also worked in human neurons. So, this to us presented an amazing opportunity where we can create a drug discovery platform using yeast and human patient derived neurons. So, Dr. Susan Lindquist really thought that we have to try this. Because so far, the drug discovery process in big pharma to tackle neurodegenerative diseases have miserably failed.

SAL DAHER: Yes.

CHEE-YEUN CHUNG: And this, we think, is partly because we don't understand how the disease actually occurs. The process of cell dying through this protein misfolding toxicity.

SAL DAHER: Okay.

CHEE-YEUN CHUNG: And what happened was before it was under a hypothesis that these pharma companies had worked to develop drugs. But what we wanted to do here using this simple cell and complex neurons, and marrying the two different, but very complimentary systems to come up with the drugs without any hypothesis. So, it will be an unbiased way of approaching the problem.

SAL DAHER: So, it's just the platform that enables people to experiment with all kinds of -

CHEE-YEUN CHUNG: That's right. We have -

SAL DAHER: Combinations.

CHEE-YEUN CHUNG: Right. We don't have any preconceived idea how things are happening. We just want to know what compound, and which target makes yeast cell healthy under the protein misfolding toxicity.

SAL DAHER: And then you test it on the human neuron cells.

CHEE-YEUN CHUNG: That's right.

SAL DAHER: Artificially generated.

CHEE-YEUN CHUNG: Yep.

SAL DAHER: So, we've talked about the science driving this. Perhaps we can just assume that we understand the need because the neurodegenerative diseases are a huge blight. It's been difficult to make headway against them.

What makes you believe that this could be a commercial venture? I think back of an interview that I did with my friend, colleague Patrick Rivelli. And he is a founder of two medical device companies, and exited within 11 years. It's an earlier podcast. And in that, he always talks about this crucial calculus that he does as an investor in a life science startup. Because life science startups can absorb enormous amounts of money and not produce results. 

So basically, you kind of have to work backwards from what your endpoint is, not actually becoming a drug, but actually reaching the point where a big player will take up the burden. And then work back from that. How much money is it going to take to go from where we are until then? And how much will they pay for that company at that point? And does it justify all the money that you're going to spend what you might get from a pharmaceutical company?

So, what is the crucial calculus here in Yumanity? Have you done that crucial calculus?

CHEE-YEUN CHUNG: Well to be honest, I think our CEO, Tony Coles, must have done this calculation. I'm the scientific co-founder of the company because I bring myself, and Dan Tardiff and Vikram Khurana brings the crucial technology that was created at MIT under Dr. Susan Lindquist.

SAL DAHER: Right.

CHEE-YEUN CHUNG: So, what we see here is that you're absolutely right. This is a long-haul investment. We can't say how many years that we're going to find the cure. And the exact point is illustrated in many failures that other companies have tried so far. This is not a -

SAL DAHER: No doubt, no doubt.

CHEE-YEUN CHUNG: Three-year gig.

SAL DAHER: No, no.

CHEE-YEUN CHUNG: That we can turn things around.

SAL DAHER: No, that makes sense.

Tony Coles, Yumanity CEO Raised $47 Million Series A to Maximize Freedom of Action & Long-term Support – Sanofi & Biogen Participating

CHEE-YEUN CHUNG: So that's where our CEO Tony Coles and [founders] Dr. Susan Lindquist had vision that our company is not to be turning things around within three years for example. Like a venture capitalist.

SAL DAHER: That's certainly very realistic, yes.

CHEE-YEUN CHUNG: That's right. So what Tony had other visions with is that we wanted this investor who's coming into support our company to have this understanding that this is going to be the long game. And we need to be able to have complete control over our scientific destiny and direction. So, the investors who joined our Series A for example have complete understanding of this. And we are actually devoid of venture capitalists in our Series A.

SAL DAHER: Have you completed your Series A?

CHEE-YEUN CHUNG: We have one year left, and we are now working on raising Series B.

SAL DAHER: Okay, oh wow. So, you raise your Series A with angel investors?

CHEE-YEUN CHUNG: Angel Investors was involved only in the very beginning.  But for Series A, we have six investors, Fidelity Mutual Fund being the lead investors.

SAL DAHER: Yes, okay.

CHEE-YEUN CHUNG: And we have two big pharma, who's also investing in -

SAL DAHER: Strategic players, okay.

CHEE-YEUN CHUNG: Yeah.

SAL DAHER: So, who are -

CHEE-YEUN CHUNG: Sanofi and Biogen.

SAL DAHER: Oh, Sanofi and Biogen. Okay.

CHEE-YEUN CHUNG: So, we have raised about 47 million dollars through this process.

SAL DAHER: Oh wow.

CHEE-YEUN CHUNG: Major credit goes to Tony Coles, who used to be a CEO of Onyx Pharmaceutical.

SAL DAHER: Oh wow. Uh-huh.

CHEE-YEUN CHUNG: Which was acquired by Amgen for about 14 billion-dollar deal.

SAL DAHER: Yes. I'm sure he made that calculation because Sanofi and Biogen are coming in. Although this is another interesting thing for biotech investors to keep in mind. If a strategic player frequently doesn't look at things in terms of a return in the particular investment, they may want to have an in in the technology and they say the return for us is not that important because we want to observe this technology closely. It doesn't necessarily mean a vote of confidence. Because for them, participating in a 40 million dollar, it can be considered sort of like business development expenditures.

So, they have different economics from the way that investors, angel investors or venture investors would look at it. So actually, I would love it if Tony Coles could drop us a line or something, you know, just tell us a little bit of what they thought the economics were and where first is the size of the market or an exit, just to get an economic sense.

So basically, so you've raised 47 million from Sanofi, Biogen, and Fidelity.

CHEE-YEUN CHUNG: And Dolby family foundation and Redmile and so these are unusual maybe investors.

SAL DAHER: Yes.

CHEE-YEUN CHUNG: But certainly, really allow us to have complete control over scientific direction that we are taking.

SAL DAHER: Right.

CHEE-YEUN CHUNG: Which is critical for neurodegenerative disease drug discovery, which will be a long haul.

SAL DAHER: I think another point we can make here. Very often there are foundations that are dedicated to particular things. They also don't do strictly economical calculation. They look at this as a development expense. Basically, we have a target of illuminating neurodegenerative diseases and this looks like a promising direction to go in. Top researchers and so forth. Very good.

So, what stage are you now?

Two Years into Series A – Promising Results Justify Series B Raise

CHEE-YEUN CHUNG: So, we are two years now over from our Series A. And we have done a lot of things that we promised that we will do for our Series A. So, we really do believe that we're in a very good place to raise Series B. And potential partnership. So, we right now have done the things with yeast and human neurons to really discover the targets, the novel targets, to treat diseases like Parkinson's disease, and we are really working on making the compound more like a real drug. So, there's a lot of medicinal chemistry, and pharmacokinetic and pharmacodynamic experiments going on some of these targets that we have validated from yeast to human neurons. So, this is very, very exciting.

SAL DAHER: You're located where? Where is your lab?

CHEE-YEUN CHUNG: Lab is in Cambridge.

SAL DAHER: Ah, okay.

CHEE-YEUN CHUNG: So, we're very excited about this. And certainly, this will really help us raise Series B that could push this program into clinical proof of principle.

SAL DAHER: That is really amazing. Something that started with a yeast model, something so absurdly simple could be having lessons for human neurons. What would you say is the biggest obstacle you had to overcome to get to the point that you are at right now, where you're thinking of creating something that's almost like a drug for treatment?

CHEE-YEUN CHUNG: So, one thing I didn't really know about being a biologist was the chemistry part.

SAL DAHER: Ah.

The Biggest Obstacle Has Been the Chemistry – How to Make the Compounds Soluble, Stable Etc. without Compromising Efficacy

CHEE-YEUN CHUNG: So, this is something that we have very nice group of medicinal chemists working really hard to make the chemical properties as favorable to be a real drug. You know, there's a lot of issues with compounds. It could be solubility. It could be metabolism, stability. So, these are all the factors we're looking into and try to without losing potency or efficacy, try to really boost the solubility, stability, and all the other physical chemical properties of the compound is going to be very, very critical for us to have a real drug that could be applied in human.

SAL DAHER: Good, good. And so, were you involved in the fundraising at all?

CHEE-YEUN CHUNG: We were more as a support for scientific validation.

SAL DAHER: So, Tony Coles was the one that was putting his face -

CHEE-YEUN CHUNG: Tony. Yes, that's right. Tony -

SAL DAHER: To get the cream pies thrown at him all the time.

CHEE-YEUN CHUNG: His name goes far because of the credibility that he brings in. We have a Chief Business Officer, Paulash Mohsen, also working with Tony to raise the funding. And they've done a fantastic job doing this.

What Led Chee to Give Up a Safe Position in a Leading Lab to Risk Being is a Startup

SAL DAHER: Oh yeah, you know, 47 million is nothing to scoff at. That's very impressive. Well this is tremendous. I like to get into the psychology. So, how did you make the decision that you wanted to leave your academic post and go off to this wild venture that could fail? I mean, in your academic post, you're a successful scientist, you've done these tremendous discoveries, and a really important lab. How did you make the decision to give that up for something so uncertain?

CHEE-YEUN CHUNG: Yes, that I actually had to think over and over again for many hours and many days, many months actually. So, it turns out that I've always worked on in my academic career [develops] something that makes animals or cells better from this neurodegenerative disease process.

SAL DAHER: Yes. Okay.

CHEE-YEUN CHUNG: That has been always my research topic.

SAL DAHER: Because of your experience with your parents? And so forth, yeah.

CHEE-YEUN CHUNG: Right, but I was just doing this in an academic level about. Gene therapy was something that I was working on, or other compounds, and never ever thought that I would be able to actually take this out in an almost commercial setting. And have such a huge impact. But this opportunity just dropped on my plate because of the publication that I had with Susan and two other scientific co-founders where really was a light bulb moment where we can use this in an iterative status to discover drugs. And just the sheer size of impact that I can make by having a therapy that's not existent right now.

SAL DAHER: Right, right.

CHEE-YEUN CHUNG: That was just so appealing to me. And I jumped out of the conveyor belt.

SAL DAHER: Okay, so you overcame your reluctance. Now is Vikram Khurana your husband? Is he also involved in the venture?

CHEE-YEUN CHUNG: Yes. So, he's -

SAL DAHER: Double risk.

CHEE-YEUN CHUNG: Well the thing is, so he's actually a faculty member, assistant professor at Harvard Medical School. And he himself is a neurologist.

SAL DAHER: Right.

CHEE-YEUN CHUNG: But he is now a consultant. He did one year as a sabbatical at Yumanity to really establish the company. And now he has his own lab, but he only consults one day a week.

SAL DAHER: So, he keeps his day job in case this one blows up?

CHEE-YEUN CHUNG: Yeah. Make sure we put eggs in two different baskets.

SAL DAHER: Yes, it makes a lot of sense. I give you tremendous credit for making -

CHEE-YEUN CHUNG: We really believe in the cause. His patients are all suffering from neurodegenerative disease, so it really drives him to see anything we can do to make the situation better.

SAL DAHER: I just want to go back a little bit to what you were talking about with Tony Coles, you know what he says about when he talks to investors, explaining to them that this is not going to be a three-year trip. You're not going to be in and out, going to be acquired by Google in three years or something in a billion -dollar acquisition. It's going to be a long process. It can be very profitable, but it's certainly going to be a long hold.

I think it's important to communicate that to people who are investing, but also to communicate the opportunity. I think that there should be a whole lot more investing in biotech because people talk about changing the world. There's so many things you can do, invest in that will change the world, the environment and all that stuff. But there's nothing that will change the world as much as figuring out a way to cure Alzheimer's. I mean, the impact with that in terms of alleviating human suffering, and also alleviating societal burdens. That is a disease that's only going to grow with time as people get healthier and healthier, their more and more likely to have Alzheimer's because it's something that, their heart doesn't give out and so forth, but they'll be around. And they'll have to be taken care of. So, it's a big, big economic burden. And it's also horrible suffering for the families. I just don't think that there's enough attention given to investing in life sciences and these really hard projects, particularly projects that are well thought out and well led, such as Yumanity.

CHEE-YEUN CHUNG: Thank you.

Yumanity Hopes to Be in Clinical Trials Within 2 Years – Promising Compounds Have Already Been Identified

SAL DAHER: This is really wonderful. So, let's say you're two years in now. Looking forward, what are your expectations for the next two years?

CHEE-YEUN CHUNG: Right. So, we have this major program that we're pushing forward. We would like to really take this program into clinical trials. That will be our goal. So, we will push forward to do that. And certainly, more compounds and more targets from our drug discovery engine.

SAL DAHER: Could I have a sneak peek? Have you guys figured out some compounds that actually work you think?

CHEE-YEUN CHUNG: Well, we believe they are. So, they are certainly validated in yeast and human neurons.

SAL DAHER: Oh wow.

CHEE-YEUN CHUNG: So, we're very excited about that. There [are] more work to be done obviously, but we have very high hopes for pushing this program to the finish line.

SAL DAHER: And what is the situation with doing a clinical trial? I mean, initially I'm sure you're going to be doing animal trials and so forth. But what's the risk profile here? Is this something that could be risky, or is it something that's pretty low risk?

CHEE-YEUN CHUNG: Risk in terms of ...

SAL DAHER: In terms of damage to, let's say you have a patient that has well established Alzheimer's. You can't diagnose it properly, but shows all the symptoms that indicate Alzheimer's. And that's unchangeable. If you're doing a trial and it's something that's unlikely to kill the patient or to harm them or make the whole thing worse, but has a chance of making them better, it makes it much easier to do a trial. What do you expect the safety profile to be of these compounds that you're coming up with?

CHEE-YEUN CHUNG: Right. Certainly, this has to be really validated. So, this will be essentially phase one clinical trial. So, we'll have to test this compound in humans, treating this compound without even touching whether it's really -

SAL DAHER: Efficacy.

CHEE-YEUN CHUNG: Efficacy of the compound. The safety profile has to be determined even before we go do more full-blown clinical trials. So, we haven't really even, we're not there yet. We're right now trying to, as I said, improve the physical chemical properties of some of the compounds that we're working on right now for very novel target for some of the indications for neurodegenerative diseases. But this time will come.

SAL DAHER: Yes.

CHEE-YEUN CHUNG: And I hope it comes. And we are really preparing for that.

SAL DAHER: Very good.

CHEE-YEUN CHUNG: And yeah. Hopefully more targets and more compounds will come with the program. We're not really one disease, one compound company. I want to stress that.

SAL DAHER: Right.

CHEE-YEUN CHUNG: We have this drug discovery platform that we put together between yeast and human patient neurons could generate so many targets and so many different diseases for -

SAL DAHER: This is addressing a class of diseases. It's not just one particular disease. There are many diseases -

CHEE-YEUN CHUNG: Right, protein misfolding diseases -

SAL DAHER: Diseases. Right.

CHEE-YEUN CHUNG: A lot of them tend to be neurodegenerative diseases.

SAL DAHER: Right.

CHEE-YEUN CHUNG: And so, we're focusing on that right now. But certainly, our platform can generate so many targets and so many different indications of protein misfolding diseases that that's where our platform is so powerful. That's why our company has this unconventional way of approaching things. And that's why I think investors [sees] the value in investing in our company because of that potential.

Working in Yumanity Chee Has Gained a Greater Appreciation of Focus and Team Work

SAL DAHER: Okay. So, two years in, other than learning more about the science, what is it about the process that you know now that you didn't know two years ago? What have you learned about the process of creating a company and so forth? Do you feel like you can answer that?

CHEE-YEUN CHUNG: So, I had no experience before being in industry at all.

SAL DAHER: Okay.

CHEE-YEUN CHUNG: So, this was a really steep learning curve for me.

SAL DAHER: Yes.

CHEE-YEUN CHUNG: But also fun ride. So, I learned a lot from my colleagues, and also our CEO and CSO, who's Ken Rhodes coming from Biogen. And being on academics, we were so focused on showing the proof of principle, but now being in industry, to setting up with a company, we had a different focus now. Our goal is very, very clear. That we have to deliver a therapy, a compound that really alleviates the toxicity that we're dealing with here.

SAL DAHER: Right.

CHEE-YEUN CHUNG: So, this very razor sharp focused goal is something that I learned that we have to have in this company to be successful. And also, creating a culture that we're a team, that we can work together as a team with one goal. But we're very flexible. We are able to pivot depending on the direction that we're going into.

SAL DAHER: Okay.

Flexibility and Intense Communication Within the Team Have Proved Essential to Success

CHEE-YEUN CHUNG: And I do think the startup culture is different from big pharma. So, startup is something that I learned that you have to very flexible. We are very interactive company. Our direction sometimes changes, depending on the data, and data comes in very quickly. This is how we made so much progress over two years. And we have to have full communication between different teams to understand where we are. And based on that, we keep evaluating our priorities, and which direction we have to go to. And our team members are very flexible in pivoting their directions, depending on the data that we get out of.

SAL DAHER: Okay, Chee, what source of information, of learning that you have that you picked up these things about how startups have to be. What sources were valuable to you in this?

Sought Advice from Others Experienced with Startup Culture – Listened to Advice

CHEE-YEUN CHUNG: Well, to me, the conversations that I had from my colleagues who had experience -

SAL DAHER: Ah, okay, okay.

CHEE-YEUN CHUNG: Was the most valuable source. Also, we have connections to people who are working in venture capital, who's actually becoming a CEO in some of the companies that they're investing. So, this advice from my friends and colleagues are very valuable.

SAL DAHER: So, you listened?

CHEE-YEUN CHUNG: Uh-huh.

SAL DAHER: You were coachable and excellent.

CHEE-YEUN CHUNG: Still learning.

SAL DAHER: We're always learning.

So, Chee, tell me, is there anything else that you'd like to say that I haven't touched? Or if there's anything you want to amend? If there are things that we've talked about.

Chee on Her Late Mentor Dr. Susan Lindquist

CHEE-YEUN CHUNG: I really want to talk about my late mentor, Susan Lindquist.

SAL DAHER: Okay.

CHEE-YEUN CHUNG: She is the definition of audacity. And she actually is the one who really believed in this drug discovery platform being possible when no one else believed in her. She's a well-known protein folding biologist, professor at MIT. She believed that this biological process is evolutionarily conserved between the yeast and human neurons. And in fact -

SAL DAHER: Rather daring assumption.

CHEE-YEUN CHUNG: Not to her.

SAL DAHER: Not to her, right.

The Late Susan Lindquist found Her Work on the Evolutionary Conservation between Yeast and Human Neurons No Accepted by the Scientific Community, Yet She Persevered

CHEE-YEUN CHUNG: Being a biologist, she had this insight that this makes total sense to her, but not to many other scientists.

SAL DAHER: Right.

CHEE-YEUN CHUNG: Probably make no sense to you, but scientific community can be very open, but also can be very closed.

SAL DAHER: Yes.

CHEE-YEUN CHUNG: Because of the dogma that everyone believes in.

SAL DAHER: I can imagine. Yes. We're all human. We're not Mr. Spock.

CHEE-YEUN CHUNG: So, to Susan, this made total sense. But to other people, sometimes they wouldn't believe in it. And one of the examples was grant agency. So, whenever she talks about using yeast, studying human brain and diseases that happens in human brain, no one bought that idea. And especially NIH, where there's a scientific review process by other colleagues.

SAL DAHER: Yes, yes.

Due to the Grit of Susan Lindquist, the Yeast-to-Human Neuron Platform for Drug Discovery Is Becoming a Reality

CHEE-YEUN CHUNG: A scientist. Whenever she writes grant on this and send it to NIH, this will be horribly rejected. Whenever we actually write the paper about these incredible findings that are now being completely validated on so many levels, it will be rejected by a scientific community. And this was an incredible uphill battle. And because she had this grit to push through, and she had firm belief that this is really something that we can use, something that could be illuminary to our brain problem that we have, that we are here right now doing this. But in the very beginning, it was such a hard battle to convince the fellow scientists that this is something we should do. And I cannot stress more that because of Susan, that we are here to really push forward a drug discovery process. We don't know if this is going to work or not.

SAL DAHER: Right.

CHEE-YEUN CHUNG: We can't say. I don't have crystal ball to say, but I would like to quote her email saying "This has a tremendous potential and for [this] horrible diseases we have to give it a try."

SAL DAHER: Right.

CHEE-YEUN CHUNG: And that's exactly what we were doing.

SAL DAHER: We have to look in all the unlikely places.

CHEE-YEUN CHUNG: That's right.

SAL DAHER: And she had the perseverance to do that.

CHEE-YEUN CHUNG: Absolutely.

SAL DAHER: Chee-Yeun Chung, I'm very grateful to you at TEDMED, this environment that's very rich with lots of things going on to sit down with us and take time to talk to our audience and to explain really remarkable project that you have at Yumanity. The remarkable collaboration you've had with Professor Susan Lindquist. So thank you very much and I hope our audience enjoys this as much as I have.

CHEE-YEUN CHUNG: Thank you very much for your invitation.

SAL DAHER: Thank you. This is Angel Invest Boston. This is 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.