BioBoss

#24 - Per Hellsund: Co-Founder and CEO of Cybrexa

July 25, 2020 John Simboli
BioBoss
#24 - Per Hellsund: Co-Founder and CEO of Cybrexa
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BioBoss
#24 - Per Hellsund: Co-Founder and CEO of Cybrexa
Jul 25, 2020
John Simboli

Per Hellsund, co-founder and CEO of Cybrexa Therapeutics, shares his thoughts with BioBoss host John Simboli about leadership, building a culture of transparency, and Cybrexa's advances in treating the cancer tumor microenvironment.

Show Notes Transcript

Per Hellsund, co-founder and CEO of Cybrexa Therapeutics, shares his thoughts with BioBoss host John Simboli about leadership, building a culture of transparency, and Cybrexa's advances in treating the cancer tumor microenvironment.

Per Hellsund
I like to create and build things. And I think that is the reason why I'm doing this. And now I build companies

John Simboli
For Per Hellsund, one of the most important aspects of leadership is building a culture of transparency, involving everyone in Cybrexa in all aspects of the company. In Per's experience, gained through founding and growing several companies, this approach helps provide insight into what's going on at the company and builds a sense of ownership and alignment with the mission. This in turn, helps attract new employees who are passionate about Cybrexa's work and really want it to succeed.

John Simboli
Per's approach has some things in common with the concept of T-shaped skills, in which each member of the company has the depth of expertise required to excel, while also enjoying a broad working knowledge of the company as a whole. These T-shaped skills are in contrast to I- type employees, whose lack of knowledge about other areas of the company makes it hard for them to collaborate in a team environment.

John Simboli
Listen in now to hear Per's thoughts about building a culture of transparency at Cybrexa and his thoughts about leadership in biopharma.

John Simboli
I'm John Simboli. You're listening to BioBoss.

John Simboli
Today I'm speaking with Per Hellsund, President and CEO of Cybrexa Therapeutics. Welcome to BioBoss, Per.

Per Hellsund
Thanks so much for having me. I really appreciate the opportunity to talk about Cybrexa.

John Simboli
How did you find yourself here at Cybrexa?

Per Hellsund
At the core, I'm a serial entrepreneur, and prior to starting Cybrexa, back in 2010, I started an instrument company called CyVek. And at CyVek, we developed an automated microfluidic cartridge and instrument for measuring proteins in blood samples. And CyVek was sold to Bio-Techne, a public company in 2014 and after that acquisition, I decided that I wanted to go out and and start another company. So Cybrexa is the result of that initiative. Essentially started it with a clean sheet of paper and went out looking for opportunities.

John Simboli
What was that process like as a sifting? In other words, was it like I'm gping to take a year and look at 500 companies, I was kind of like, Ah, this one looks pretty interesting.

Per Hellsund
There were a parameters that we set. So I really wanted to do something in oncology. I was exposed to oncology at CyVek. That was one of the primary areas where the instrument was used, and it was used pretty broadly in cancer research. And my mother was battling cancer and my mother in law had cancer. So a lot of kind of exposure to cancer. And also, it's a large market with a lot of opportunity, both in terms of financial opportunity and the opportunity to make a difference for cancer patients. So really, we knew it was going to be something in biotech and really wanted to focus in on cancer. So we did have some parameters to work within. And eventually, I came upon this technology that was originally discovered at Yale by a famous scientist by the name of Don Engelman for targeting tumors and got excited about the technology and acquired a license to use the technology in cancer therapeutics, and then essentially launched Cybrexa in January of 2017. Acquired a facility at Science Park, which is right adjacent to Yale, and built out a team and everyone's been doing a great job and moving the technology forward ever since.

John Simboli
Several, I would say many of the founders and CEOs I've spoken with, and I think it's close to 20, at this point for this program, Per, have said something along these lines: This being a biopharma CEO, it's not for the faint of heart. So I would say, of all the things you could have chosen to do when you were thinking about venture capital, it had to be one of the more difficult ones to say, yeah. So how did you work through that?

Per Hellsund
One of the things that we liked about this particular opportunity was that we were using a peptide, a tumor targeting peptide technology, to improve existing drugs. So to take existing drugs and move them into new patient populations. So, we kind of looked at it as as a lower risk means of getting into biopharma, where we could potentially get the multiples that you see in biopharma with a lower risk profile, and also a faster path to market, which also means that we can help people sooner. So that was part of the thinking. And I think that sort of eased some of the distress around or concerns around jumping into biopharma.

John Simboli
I know, it's often very difficult to foresee where things will go when you're starting up something but I want to ask this question, what were you hoping to achieve that could be done, you thought at Cybrexa that could not be done someplace else?

Per Hellsund
So every day, we learn more about cancer biology and the tumor micro environment in ways to leverage both to fundamentally change the course of disease. And unfortunately, we haven't cracked that code yet. But we believe that it is important that we continue to use every tool that we have at our disposal while we continue to look for new targets. So an untapped area that we're focused on is improving the therapeutic index and by doing so expanding existing drugs into new tumor types, and patient populations. So we think it's important that we leverage what we know about the effectiveness of existing drugs, and expand their use into new patient populations and applications. And through this, we believe that we can change the standard of care and ensure that we have fully exploited our existing knowledge of cancer and cancer biology. So, what we're really looking to do is be successful in taking some of these existing drugs and making them available to patients that currently don't have the option to use these drugs and in a lot of cases don't really have any viable options.

John Simboli
So when you meet someone for the first time, perhaps through your family, and they say, what do you do for a living Per? How do you answer that? I'm sure it'll vary quite a bit.

Per Hellsund
So I generally say I run a biotech in New Haven that is developing new cancer therapeutics based on groundbreaking tumor targeting technology that was developed at Yale. So we're looking to take drugs and deliver them specifically to the tumor while sparing normal tissue. So in doing so avoiding some of these horrible side effects that everyone's familiar with, that are typical of existing cancer drugs, and I really believe that we're going to change the standard of care in certain tumor types.

John Simboli
If it's a 10 year old kid in a family that says, Mr. Hellsund, what do you do each day? Not the broad answer. But how do you spend your time? How do you answer that?

Per Hellsund
A lot of what I do is around setting goals, recruiting the right people and managing the right people and creating the right culture. So I'm not a biologist, you know, my expertise in building and managing companies. So I need to make sure that we have clear objectives. And most importantly, I need to make sure that we build a culture where people are passionate about what they do and people like to come to work, I want to have a company where people are coming to work and working hard, because it's what they love to do not because they're they're worried about some repercussions resulting from bad behavior. So, I think the most important thing I do is around that, is around building culture. And setting the objectives and the mission for the company.

John Simboli
Can you remember way back when you were, you pick the year, eight, nine years old, something like that, and we all have a self image or what we wanted to be when we grew up, but we had no idea what that meant. But sometimes it connects and sometimes doesn't. Do you remember that?

Per Hellsund
I always liked tinkering with things. And I was really obsessed with motorcycles and cars. And my father was an engineer. So I think at the time, I assumed that I was going to be an engineer because that's what my father did. And I think the way this kind of translates into— and I am an engineer by training; I'm not a biologist—but I like to create and build things. And I think that is the reason why I'm doing this and now I build companies. You talked about my role and how I fit into running these companies based on my skill set and my background and that's really what I do. I build companies,

John Simboli
Did you give any consideration to going toward a big company and trying to take advantage of all the facilities and strengths and money and everything else that a big company can offer versus starting something from scratch?

Per Hellsund
You know, I didn't. I've never worked for a big company. I've always worked for smaller companies and the first company I started was actually started out of a small company, probably a few hundred person company. And that was in my late 20s. So I've kind of been running companies pretty much my whole career. And it's what I like to do. And at this point I can't imagine going to work for a large company. One of the things I tell people when they come for interviews is that a lot of folks are concerned about working for a startup, particularly if they've come from a big company. What I tell them in today's environment, these are different types of startups, particularly when they're run by experienced management team, they're well funded. We're not wanting for equipment or resources. And what happens is, this is my perspective, never having worked at a large company. But things move a lot faster. People get to see the results of their work sooner. And they get to be involved in a much larger portion of the business.

Per Hellsund
One of the things that is really important to me in building culture is transparency and involving everyone in all aspects of the company. So I like folks to know what we're doing, not just, if you're a biologist, you're not relegated to just learning about biology and understanding that part of the company. We'd like people to understand everything that's going on, so you get exposed to a lot more. And I think, in doing that, people have more of an ownership of the company and the mission. And you tend to attract and mentor people that are really passionate about what you're doing and really want it to succeed. And, to me, that's incredibly rewarding and exciting.

John Simboli
That sounds like your heart is in this idea of a collaborative work culture. And I imagine either where you are or previous places you probably had that opportunity to really bring someone along, perhaps introduce them to a new area or find some strength that maybe they didn't even know. Is that part of what's going on?

Per Hellsund
I think that is part of it. And I think exposing people to a different environment and kind of a new way of doing things. On a few occasions I've had folks come back to me years later and send me an email and and thank me and that's probably one of the greatest feelings I've ever had—definitely part of what draws me. and I think a lot of folks, building and running companies. Because like you said, it's not easy.

John Simboli
What's new at Cybrexa?

Per Hellsund
We're rapidly moving our lead program toward the clinic. We plan to dose our first patients early next year. And we're looking to recruit patients that have a high unmet need despite advances in immuno oncology and other new therapies such as third line, small cell lung cancer, third line non small cell lung cancer in colorectal cancer. So the program is moving along very well. We've received positive feedback from the FDA on our pre IND filing. So that means that they're supportive of our plans and onboard for us moving forward. Our plan is to file an IND by the end of this year and move into patients, as I mentioned, first part of next year. So we're in the process of going through IND-enabling TOC studies which we plan to wrap up in early December. So we'll enter a phase 1 study in advanced solid tumors. So these are patients that where there's very high unmet need, don't have many, if any options. And we've also identified several paths to market that could get there in under five years. So we're pretty excited about the possibility of moving some of these into the market fairly quickly.

John Simboli
In part of my reading, I came across the Hartford Courant article about your hope to make a truck that was both more effective in terms of reducing size of tumor but also have less of the terrifying side effects patients sometimes experience. Can you talk to me about that second part of that, how that plays into what you're trying to do?

Per Hellsund
The fundamental mechanism of our technology is fairly easy to understand. So it's a peptide that was discovered at Yale, as I mentioned, and this peptide works by leveraging the low pH or acidic environment that's present on the surface in the micro environment immediately surrounding cancer cells. And it's important to understand that this low pH environment results from fundamental cancer cell metabolism. So our targeting technology is broadly applicable across all solid tumors. So when this particular peptide comes in contact with this low pH environment, it reacts by going through a transformation where it proteinates and forms an alpha helix. You can think of it as a corkscrew, and essentially drills through the membrane of cancer cells and stays there until the cell is destroyed. So we're using this to provide intracellular delivery of small molecules, as opposed to just administering the molecule systematically, and having it go, you know, more preferentially to cancer cells, but also attacking healthy cells, we're delivering it specifically into the cancer cells and we're actually preventing it from going into healthy cells because the peptide will not translocate into these healthy cells because of the pH.

Per Hellsund
Some folks, in layman's terms, describe it as a heat seeking missile or a smart bomb where it's very targeted, very specific delivery. So what this does is it offsets these toxic side effects which, you know, GI tox is very typical. Bone marrow tox is really typical and bone marrow tox is one of the ones that usually limits the potential of these drugs. Some of these drugs will be working well on a patient, but they have to come off them because it's destroying the bone marrow, which of course, you know, compromises the immune system and becomes unsustainable. So in the case of our lead candidates, we're taking drugs that are known to be effective at killing cancer cells. We know these drugs work. But the problem is they don't have much in the way of what's called a therapeutic index, which is the delta between the amount of damage you do to cancer cells versus the amount of damage you do to healthy cells. So by targeting these drugs, we're able to make them effective, safe, and much more tolerable.

John Simboli
When you're making a presentation, and you get the chance to describe what you just described to me, obviously in some detail, and then you find after a meeting, perhaps that many of the people say yeah, okay, I got it, Per. And you're thinking, Okay, they understand where we are, we'll see if they're interested or not. A certain number will come back probably and say, Oh, thank you for telling me that it's x when in fact, that's not what you said at all. And there's just a disconnect. When people get it wrong. What do they get wrong? Then how do you help them figure it out?

Per Hellsund
I think one of the things is they don't appreciate the differentiation between other tumor targeting technology. So anytime you set an ambitious goal, like killing cancer cells without harming healthy cells there are bound to be failures and setbacks and tumor targeting is no exception. That said, we believe we're now in a new era, where ADCs and other tumor targeting technologies are coming into their own. And we're starting to see some big successes. But there are some key differentiators with our technology, one being the universality of the technology in that we're targeting this low pH environment that's universal across all cancer cells, you can essentially look at us as targeting cancer, as opposed to targeting a specific mutation or an antigen that's specific in a subset of patient populations. So I think a lot of times folks miss the value proposition that we can go much broader than ADCs and that we're not looking to compete with ADCs in the space where they're successful, we're essentially looking to go where they're not. So I think that's one of the key things that people tend to miss and I think it's really important in terms of creating value to an investor but also in terms of helping helping patients,

John Simboli
When you help them to understand that, the way you just did for me, do you sometimes get the follow up question, yeah, that sounds great Per, but you're a small company. That sounds pretty ambitious.

Per Hellsund
I don't I know that the skepticism is so much around the size of the company. But I think a lot of folks say, yeah, you know, your data, your preclinical data, data in animals looks looks great. I mean, I don't think anyone would dispute that our preclinical data demonstrating that we can preferentially target tumors and spare normal tissue in animals is very compelling. So, the question is, okay, how do we know that's going to translate into humans? So I think that's something where a lot of times folks aren't willing to take the leap or take the risk. And I I don't even know if it's skepticism, it's just folks want to see it translate into humans.

John Simboli
What can you tell me about the pipeline at Cybrexa and how it helps to differentiate the company?

Per Hellsund
One general kind of philosophy I want to mention before going to the pipeline is that in using this technology to target existing drugs, we're not looking to target these drugs solely for the purpose of reducing the adverse effects and making them more tolerable to patients and improving quality of life. Although that's great. We're really looking for opportunities where through targeting we can move these drugs into new patient populations, into patient populations that currently don't have access to them because we feel that's where we can both create the most value and help the most people. So that said, right now we're focused on cytotoxics and DNA repair inhibitors. So we have two cytotoxics. One is CBX-12, the other CBX-13. And I'll talk a little bit more about those. And then we have two DNA repair inhibitors. One is a PARP inhibitor and one is a proprietary molecule that hits three of the four primary DNA repair pathways ATM, ATR and DNA-PK

Per Hellsund
So in the case of the cytotoxics, our lead lead program is CBX-12. And we're targeting a class of drug called a topo 1 inhibitor, topoisomerase inhibitor. And the specific molecule is exitican. Now, exitican is currently being targeted by an ADC in a drug called an HER2 that was a collaboration between Daiichi and AstraZeneca was recently approved by the FDA. There's a lot of buzz about the program. It's projected to hit $3 billion in annual sales in 2024. So that particular drug is being targeted by an ADC that targets a HER2 positive antigen. So by definition, it is relegated to tumor types and patient populations that express HER2. So what we're doing is we're taking that same drug and plan to target it with our technology, which, as we've been talking about, is universally applicable across all solid tumors and go outside of HER2 positivity. So our plan is to at least initially to go where they're not; to go into patients that could benefit from these topoisomerase inhibitors, but that don't have HER2 mutations. Similarly, CBX-13 is a class of drug called a natanzine. The specific molecule is DM4, and it's a more potent version of the DM1 that's in the Roche HER2 positive breast cancer drug Kadcyla. Once again the plan is to go beyond or outside of HER2 positivity.

Per Hellsund
In the case of the PARP inhibitor, the plan is to to combine that with the DNA damaging agent. So PARP inhibitors are currently relegated to patient populations that have a BRCA mutation, or more broadly some kind of homologous recombination deficiency. So the PARP inhibitor needs a defect or deficiency to exploit in order to work. So what we're going to do essentially is artificially induce that deficiency with a DNA damaging agent. And this isn't a new idea. In fact, it was the concept behind the first PARP inhibitor that ever went into a trial. But the problem is they ran into severe bone marrow tox. And in fact, all of the companies that have PARP inhibitors on the market have run phase 1 trials where they've attempted to do these combinations and they've all failed due to bone marrow tox. So our plan is to go back to that concept and our preclinical data, once again, demonstrates without question that we can combine a PARP inhibitor with a DNA damaging agent in a very high dose and not impact the bone marrow

John Simboli
I know day to day, moment to moment, you're really focused on taking these steps to get yourself to the next step and all the things you've been talking to me about. At this stage so you also occasionally find yourself sitting back and thinking, you know, if this works, I'm going to really help some people? Or dpes that come later on?

Per Hellsund
I actually think about that a lot. And in fact, my mother's still battling. metastatic breast cancer. It's been going on for seven years. And she's actually in that category of patients, she's gone through essentially all the therapies that you go through when you have metastatic breast cancer and she's kind of getting to the end of the line and having to take drugs that are more toxic and that have worse side effects. So they start out with the drugs that are the best ones and then, you know, with all these drugs, eventually, people build up resistance and they go to the next line of therapy and the next line of therapy. She's been telling me that she's holding on because she wants to be enrolled in our phase 1 trial. So we're trying to move as quickly as we can and she's hanging in there. So there's definitely that. Also last year my sister passed away from lung cancer. So that's obviously one of the areas that we're targeting. So yeah, I mean, I think I think a lot about getting these initially into the clinic and then being able to help these patients that don't have a lot of options.

John Simboli
Why did Cybrexa choose to locate in New Haven?

Per Hellsund
So one of the reasons was the technology was originally discovered at Yale by Don Engleman. But, I think beyond that there's a really nice ecosystem in New Haven. One of the things that's most important to us is being able to have access to the talent pool and this biotech ecosystem that's building in and around Yale and New Haven is attracting a lot of talent. And also, we have a lot of very talented folks here, leftover from when Connecticut was a center for biopharma, and we had all the big biotech companies. I think, probably the most important factor for us is having access to good people. I mean, that's what makes these these companies successful. And we've had really good luck in recruiting folks. And we like the New Haven biotech environment,

John Simboli
What kind of team have you set out to build to make this culture happen that you were just describing? What do you look for when you're trying to build that team?

Per Hellsund
One of the first things that I look for is passion and fit into our culture and the way we like to do things. For,me that trumps technical acumen or talent. So when I interview folks, I'm not looking to interview them about their technical abilities for the most part because, you know, generally they're in fields that I don't have any expertise. But I'm looking for attitude and passion. And whether or not they're going to fit in with the culture. And a lot of that falls on the senior leadership in terms of creating a culture where, it fosters this type of environment where people work together, where they're collaborative, where there's open communication, where people are focused on the mission and the goals of the company. Because they want the company to succeed, not because they're looking for some personal gain or trying to climb the ladder, or those other types of things. It's really important to get the right culture. And one of the things I always tell people is once you get that working, it's like the engine's running on all 12 cylinders. It makes the, the job of the CEO becomes so much easier if you have the right culture because the company kind of almost runs itself. So, that's why a lot of my effort has been on building and maintaining that culture.

John Simboli
And I do also understand that there can be advantages in being in New Haven compared to some other places in terms of retention. It's it's a good lifestyle. People may want to stick around a little while that can be nice, too.

Per Hellsund
I think New Haven has a lot of the similar attributes to some of the larger biotech communities like Boston, New York and California. We've got the proximit to Yale that's got its own kind of culture and creates a certain type of environment that folks like. We've got UConn as well. But then I think beyond that, because it's smaller, both in terms of size and it's just it's more contained. It seems to be a more tight knit group than I think you'd see in some of the larger biotech centers.

John Simboli
Being located in New Haven, how does that affect your ability to bring in capital and access investors that you would like to talk to?

Per Hellsund
Even though most of the big VCs, particularly, you know, the so called Blue Chip VCs are located in Boston, New York, in California, I don't see it as a as a significant disadvantage there, particularly Boston and New York. It was an easy commute, prior to COVID-19. But you can still access these folks easily by phone and everything's being done by video conference. And you're seeing significant investment in New Haven companies and both private investment and there are a number of companies that have gone public recently, a few of which, you know, reached multi billion dollar valuation. So you look at look at Arvinas and you look at Biohaven. So, I don't see that as a disadvantage. I thought that it might be, but as we started going out and aggressively looking to raise money from institutional investors, I don't, I don't see that as an as an issue at all.

John Simboli
What can the biopharma community learn from this experience of dealing with COVID and how our community does its work, what it wants to do to help out in the future?

Per Hellsund
We've been very fortunate in that we've been able to continue on and have not missed or delayed any of our significant milestones. So we have a creative team. We came up with ways to continue the work in the lab safely. And do social distancing and communicate from home. So I think I'm fortunate that we were able to continue on and a lot of that goes out to having great people that wanted to continue to work and figured out a way to do it safely.

John Simboli
If you were thinking about where the biopharma industry needs to turn its attention in the coming years, what would you be thinking? I know one person I spoke with recently said he's very interested in the idea of democratization and making drugs affordable in countries other than in North America and Europe. Is there a series of issues that you're thinking about right now, in terms of the future and what you want to put your energy into?

Per Hellsund
There's still a lot of work that needs to be done in oncology. I mean, we've made we've made advances but we're nowhere near having a cure or even having drugs that can turn it into a chronic kind of treatable illness. I think continuing to study the underlying cancer biology and how it works, is really important. I mean, what we're focused on,, I think we talked about this before, but you know, looking at what do we know today? And how can we leverage that and how can we take existing therapies and existing knowledge and move those into patients and create therapies for the for folks that currently don't have options.

John Simboli
Thanks for speaking with me today Per.

Per Hellsund
Thanks, John. It's been my pleasure. I really appreciate the opportunity to talk about Cybrexa and tell the story.

John Simboli
While my work with leaders in the biopharma community puts me in touch with founders and CEOs around the world, my company's home base in the New York/Boston corridor gives me a close up view of what Per calls the New Haven ecosystem. Per's description of the Cybrexa origin story provides insight into this New Haven ecosystem: technology originally discovered at Yale University, the talent pool that springs from Yale and the large pharma companies who had built significant research facilities in Connecticut; and the nearby University of Connecticut campuses and Technology Incubator Program. And then there's the attractive lifestyle. A US Census Bureau Report placed in New Haven among the top areas where millennials have chosen to locate. But Per's leadership role and the work of Cybrexa are much more than a story about the New Haven ecosystem. Per's focus is squarely on patients and changing the standard of care they receive for certain tumor types. Sadly, one in two people in the US are diagnosed with cancer during their lifetime. And Per knows how much work remains to be done.

John Simboli
I'm John Simboli. You're listening to BioBoss.