Woman of the Week: KaliVir Immunotherapeutics’ Helena Chaye

Helena: It’s an incredibly clever organism, right? It’s so simple. Its genetic information is very small compared to any other organisms out there. It’s a very simple organism. But it has learned to work with their environment and their host cell systems to survive and to manipulate the whole system to survive. So the elegance and the simplicity and yet it’s cleverness to piggyback off of the hosts to spread itself and to propagate and to evolve, I think is really beautiful. So, yes, I love viruses.

Taren: Does that mean you have to get smarter than the viruses then, right?

Helena: Yes.

Taren: And be more elegant than the viruses. Are we on a path to do so?

Helena: That’s a very good question. So I think one of the reasons why I am what I’m doing now is really just I think the fact that we can use something as simple and clever and as elegant as viruses which can cause diseases, we can actually optimize the viruses, understand its virology and the biology, and manipulate it and switch it from being a pathogen to something that we can use to treat patients and then treat cancer.

So, yes, we are smarter than viruses in that regard. We know how to understand its biology and to utilize the biology to our benefit and advantage, and hopefully bring treatments to cancer patients. I think the more we learn about our immune system and how our immune system works in the context of cancer, we’re able to really put those two applications together to bring the cancer treatments to patients.

Taren: Well, that’s a natural lead in to my next question, which is about KaliVir’s pipeline and the technology. Can you share a little bit about what you all are doing at the company?

Helena: Sure. KaliVir is a private biotech company that’s primarily focused on discovery and development of novel oncolytic viruses. It’s a virus that’s been genetically modified to preferentially treat cancer without harming normal cells that surround the cancer in patients. These type of viruses have been in development for quite a while, I would say decades, but primarily they’re limited to by their injection to tumor, so it’s limited in terms of clinical application.

What we do at KaliVir is we focus on designing a virus that can be delivered intravenously. Our platform technology that we call VET (Vaccinia enhanced template) that allows us to design novel viruses that preferentially target cancer cells, that preferentially replicate in those cancer cells and kills them. And then we are also able to deliver therapeutic payloads, induce anti-tumor immune response that’s durable. So our platform can generate multi-mechanistic agents that can not only directly kill cancer cells, but can also activate patient’s anti-immune response for durable long-term anti-tumor activity.

We start with the most optimal strain of viruses; in our case, we use Vaccinia viruses, which have already shown that it can be delivered systemically. We engineer the virus backbone by deleting certain genes and adding new genetic sequences to enhance its natural ability to travel within the systemic system for enhanced delivery and spread within the body, the same time increasing its cancer-killing ability. We can also add therapeutic payloads to boost the anti-tumor immune response and also to synergize with other immune therapeutics and other modalities.

I think our two partnerships are examples of our flexibility and the power over this platform. We have a collaboration that we entered into Astellas a couple of years ago which is twofold. First is a license of our lead candidate for commercialization, and then second is to design a novel virus for Astellas using our backbone platform in one of our proprietary novel therapeutic payloads.

Our second partnership with Roche, which we signed earlier in 2022, is actually slightly different than Astellas in that they provide us with their proprietary payloads to express backbone, so we’re in the process of doing that right now. And I think these two partnerships really can exemplify the power and the potential of our platform and technology at our company. In addition to those, we have a current lead virus that’s called VET-TGI. It expresses TGF beta inhibitor in IL-12. We’re really excited about the potential of this candidate given our early preclinical data. We started our GMP activities in the middle of last year, and we look forward to moving this into the clinic sometime soon and start treating patients with it, which is our goal this year.

Taren: That is exciting. I love the fact that you have these two partnerships with really big companies, but yet you’re still private. Any thoughts of taking your company public?

Helena: As you know, what’s happening in the public market right now is not very good for the biotech sector. As with any startup companies, we do have these long-term visions and strategies around providing exit for investors and IPO is definitely one of them. And then in parallel there’s always the M&A activity potential. So we keep our eye on those opportunities, and when the timing is right and we have really strong data to support going into the public market we would definitely look into that as an option.

Taren: Fantastic. Thank you for sharing that. I know sometimes those are decisions that are held pretty close to the chest. So in terms of the science and where you’re going, obviously oncology is your main focus and intravenous, are you one of the only companies that is doing this kind of science right now?

Helena: So there are lots of companies actually that are involved in or that are working on oncolytic viruses, either viruses that can kill cancer cells and deliver payloads. I think one of the ones that’s approved is with Amgen; Imlygic is the first product that’s been approved. And there are multiple other companies. I would say that we’re probably the best in class in terms of understanding the biology to the Vaccinia viruses and utilizing its native biology to enhance these systemic delivery. I think it’s what we call holy grail in the space, being able to deliver the virus intravenously so we can eliminate the need for complex surgeries and have a broader application in the clinic. Lots of people are looking for that ability to deliver virus intravenously, which I think we are kind of ahead of the class in that regard.

Taren: Thank you. That was a far more elegant way to answer the question I didn’t ask properly which was what differentiates you from some of the other folks that are out there, so thank you for clarifying that for me. Obviously, going into this, there are a lot of women who are sitting in top spots in biotech companies which I think is such an unusual thing considering when you look at the vast life sciences industry where there are very few women sitting in top seats at big pharma companies, but biotech seems to be a sector where women are excelling. Have you ever found that you are oftentimes the only voice in the room? And if so, how did you find your voice to talk about all the strategies and the vision for which you want to accomplish?

Helena: Yes, I did find myself as the only woman in the room often the case. I didn’t really think of that in… I guess I didn’t recognize until I’d leave the room, per se. In terms of getting my voice heard, I come very prepared. I come with plans, my vision backed up with facts and strategies. I mean, I think I walk in the room and I’m prepared. I don’t really think of myself as the only woman in the room while I’m in the room doing what I need to do and conveying the message and communicating what I need to communicate to either the boards or investors or partners. I only think of that after I leave the room, if that makes sense. I think oh, I was only one in the room.

Taren: I get it. It’s like, ‘oh, okay,’ understood. Again, but finding one’s voice is preparation is absolutely key to success in any of these interactions. How would you describe your leadership style?

Helena: I think for me to be an effective leader, I think you have to be transparent and I think you need to have trust of your people. So for me, being as transparent as possible allows us to build trust. And I’m also open to all voices. My assumption is that they know more than I do and there’s a lot that I don’t know, so I try to foster an environment where everyone is an integral part of the team and each voice matters. I do believe that leadership is not about telling people what to do but to listen and provide a vision and a path to achieving their collective goals.

So in my company, each person has an important role in that path; and for us to be successful, we need to trust each other and to build that trust. We have to have transparency and integrity in what we do. So that’s how I sort of think about my leadership style. I hope that’s true; I mean, you have to ask my staff that, but I think that’s how I approach it.

Taren: Fantastic. And obviously the work you’re doing there’s a lot of risk involved and there’s a lot of ups and downs because it’s such new science and you’re going down pathways where folks haven’t gone before. How do you keep your team motivated and buoyed when maybe things don’t go exactly as planned?

Helena: So I think it goes with what I just said about transparency. My approach to kind of outlining a plan and sort of communicating my vision or our mission or our goals is to just outline them as transparent, as open as possible, and communicating to them that, yes, we may fail and we do make mistakes and that’s okay as long as we move forward quickly. And what I do, and this is sort of my risk averse serving tendency is that I have backups to backups to backups, and I communicate those backups to my people. So if something goes wrong or if we need to pivot because, you’re right, in biotech things happen really quickly and things change quickly and we need to respond quickly. So the motivation that I provide is to have an open door and to say come and talk to me, don’t be afraid to make mistakes; when you do make mistakes, be quick and let’s sit down together and put our heads together and come up with an alternative, and here’s a backup that we laid out we talked about before so we’ll just move forward in that regard.

So I do hope that’s what motivates them is to continue to think outside the box and to be not afraid to make mistakes, I think that’s really important, and not be afraid to come forward once you make mistakes because we will make mistakes. That’s just the nature of the beast here in the science.

Taren: Absolutely. Do you consider yourself to be a role model for other women coming up through the ranks?

Helena: I didn’t until recently.

Taren: What changed for you?

Helena: We hired a senior VP of clinical operations recently, and it’s really one of our strategies this year is to build out our clinical development capabilities. One of the first thing we did was bring in a very experienced senior VP of operations. And in her joining the company, her comment was that she wanted to work with me under me to learn from me. And that was bit of a news for me because I never really think of myself in that way. So it made me sort of pause a little to say, “Well, maybe I do play that role for some.” And I also have a daughter, who’s a teenager now, and she makes comments that made me think I do have a role and a responsibility to the new generation, so next generation woman coming through the ranks in this particular sector and I take that responsibility serious; so I didn’t until recently. Like I said, I was never aware of my presence in the room as the only woman until I left the room. So I kind of operated that way in the last 20 somewhat years, but I do think that it’s an important responsibility now.

Taren: So oftentimes with children they are watching you, they are listening.

Helena: Yeah, right. I know, I have to be careful.

Taren: So do you have any particular advice that you provide to some of the folks that maybe you’re mentoring or who you’re looking at as your high potential candidates as you look to move up and build out your teams?

Helena: I don’t specifically, but how I plan out what I need to do, what goals we need to achieve in terms of if I was given a task or if I was to give someone a task, I want them to be thinking about it in a big picture as well as details. I think sometimes if you’re in a leadership position, if you’re used to being a really good project manager, you forget to step back and take a look at the big picture. So the advice that I often hear myself give to some people is, “Okay, that’s great, and you have a great project plan. You’ve thought about everything that needs to get done and all the pitfalls, but I now need you to take a step back and take a look at the entire picture and align up with the overall strategy and vision for the company. Does it meet with that?” And I think it’s a learning maturity process that need to happen and that’s what the was advice that was given to me as I was coming up and sort of learning about leadership and taking on projects is to have someone say, okay, now can you take a step back and look at the big picture and does it fit in.  And also be flexible, anticipate failures, and building flexibility and building backups.

So that’s kind of what I try to convey to some of my senior managers and project managers is to say you have this project, take a step back and anticipate what could go wrong as part of your plan. Don’t always plan for success, which is important, but you also have to think about what would happen if things don’t go the way that you’d hoped, which often is the case in biotech space. So I guess that would be the advice I’d give is to step back and take a look and think about the pitfalls that could happen.

Taren: That’s great advice, absolutely. In terms of your own career, has anybody played a particular influence on you?

Helena: There’s been actually quite a few; and one was very beginning when I started working as a brand new lawyer practicing law, a partner mentor; his name is Ken Burnett who is now retired. I came in from an academia, I was in science for 12 years…well not quite 12 maybe 10 years, and then I went to law. I knew nothing about the business world, I knew nothing about legal practice, and he made me believe that I should believe in myself. Whether he did or didn’t, it’s not relevant, but he challenged me to trust my instincts and to believe in my intellect. And he gave me the confidence to take on whatever that was presented to me in my path. And that sort of confidence that he gave me sort of changed fundamentally how I viewed myself and the path I took in my career. I took risks in my career that I don’t think I would’ve had he not given me that confidence.

And the second person is more recent and it’s a she. When I was offered this position as a CEO, I was very reluctant to take it on because I’m really a project manager, so to be the face of the company was daunting for me. And she’s the one that said, “You need to take this on. This is something that you have worked towards for, this is something that you have experienced and expertise to take on” and she gave me the confidence to do that. So I would say that they’re not mentors in the way you typically think of mentors, but they really sort of changed in the way I view myself as a professional in this sector.

Taren: Excellent. And since taking on the CEO role, what has been one of the biggest challenges that you have found yourself having to overcome or that you’re facing right now?

Helena: I don’t think it’s different from any other sector is managing people and motivating people I think is the hardest. In particular, during the pandemic, we’re having to go up there and raise money, for example, and we have supply chain issues. There are a lot of things that could go wrong, but to manage people and to keep them motivated and keep them coming in and be excited about what we do, I think is the biggest challenge. You also have a lot of different personalities come into play and you need to figure out how to really maximize their potential and to encourage them to work to their potential, to push them, but also to encourage them in a way that’s positive. I think to me that is the biggest challenge of this position is just managing people and making sure that they’re performing at their best.

Taren: Absolutely. You talked about the pandemic; as we’re coming out of the pandemic, are all your folks back in the office? Are you working in a hybrid environment? Have you figured out what works best for your organization yet?

Helena: So we were really fortunate to have been able to continue to work on site during the pandemic. We had to keep the experiments running so we did a staggered schedule. We had people come in earlier or later in the day, whatever the schedule allowed. We also placed people physically distant. We have a big 18,000 square foot facility in Pittsburgh, and we were able to spread people out so we can continue to run the core experiments which was critical for the company to keep going because without those experiments, we couldn’t have made those deals that we did in the financing we did in the last two years. So I’m forever grateful for the technicians and scientists who came in even in the height of the pandemic to keep the experiments running. We are now fully back in hundred percent. As I said, we’re entering into a different phase of the company and bringing on a drug development capability that’s really important to advance our collaboration with Roche and to advance our internal program. So nothing’s changed really pre-pandemic and during pandemic. And we are currently just going at warp speed right now trying to get everything done to advance our programs.

Taren: Warp speed is hard as we saw through the pandemic, working 24/7 to get to a solution for the virus. It’s hard to work constantly at warp speed.

Helena: It is.

Taren: How do you manage that?

Helena: How do we manage that? Like I said, I’m really grateful and fortunate for our technicians and staff who are on the ground. They believe in the technology. They believe in the innovations that they’re coming up with that’s going to treat cancer patients and hopefully make a difference in their lives. I think we’re all somewhat motivated by what we do in the lab and to see that transition from the benchtop into the clinic. I think we’re all very motivated to see these programs treat patients and see how they do in the clinic. It’s a tremendous science and I think our people should take amazing pride in the work that they do. Like I said, it’s the best in class technology in using viruses to treat cancer patients. So I think we’re just kind of inherently motivated by what we do and the science behind it.

Taren: Excellent. And as you look over the next 12-24 months, you talked a little bit just a minute ago about what some of those key strategies are, what are you looking at? What is going to be a major milestone for you in the coming year to 24 months?

Helena: Taking our lead program to the clinic is our singular focus right now. Obviously, we have to continue to support our Astellas partnership and making sure those projects advance forward. We just launched our Roche partnership so we’re working really busy, working hard at making sure we deliver the virus as they requested. But in terms of internal program, get the VET3-TGI into the clinic. I did bring on Adina Pelusio, who’s our senior VP clinical operations, as a first step.

We’re also building out our own internal in-house GMP production facility which will minimize our reliance in CDMOs and hopefully that will allow us to manufacture viruses on site without having to reach out to CDMOs, which has been a pretty risky operation on our front. So we’ll be focusing on building that capability as well. We’re really transitioning from a discovery stage company and moving into a clinical drug development company, so we’re excited about that. We’ll continue to build our capabilities and hopefully see some really great data in the clinic soon.

Taren: Well, I wish you lots of success. And that is an exciting time as the company pivots now from one stage to the next stage and looking forward. Again, that’s going to change your role as CEO, right? So as the company transitions, you’re going to need to transition, I would think, and how you look at your operations, how you look at everything.

Helena: Yes, that’s correct. So I came on with KaliVir from a clinical biotech company operations. So, to me, KaliVir was actually a new experience for me in managing a discovery and research focused company, and then sort of transitioning and pivoting into clinical development is my comfort zone. So for me this is actually something that I know how to do and what I had to learn earlier was to really work with people on the ground who do discovery research and how to manage a lab in that capacity. So I’m excited to actually build out our drug development capabilities and advancing a program to the clinic. Bringing on some key critical individuals will help us to build out that capability and hopefully have some new partnerships and financings. And so I just think that I’m really well positioned for moving this company forward. I’m excited about that.

Taren: I’m excited to see what’s next for you all. I think that you’re embarking on some really fantastic science and providing hope to patients with some unmet needs, so really exciting. I’d love to continue our conversation, but we are sadly at the end of our time, so it leads me to ask our last question which is what is that WoW moment that either changed the trajectory of your career or has left a lasting impression on you? Can you narrow it down to one?

Helena: Yeah. For me, this is easy actually. As I said, I love viruses, so when I was looking for opportunities in the US – I don’t know if I told you but I’m originally from Canada – I came across the company that was using viruses to treat cancer. And when I told my friends about this, this was over 20 years ago, they said that’s just crazy, like why would FDA ever approve such a drug, using viruses that kills people. But the idea that a pathogen that can harm you can be changed or optimized to treat cancer was absolutely fascinating to me, and it brought together two things I really loved studying when I was in school which are viruses and immunology. So for me that was absolutely no-brainer and I really wanted to be part of that innovation.

And as you know, for over 20 years, I’ve stayed in that space and I’ve been part of multiple platforms in trying to develop these viruses into treatment of cancer. So I would say to those naysayers who said FDA will not approve of ours, they did approve ours for cancer, Imlygic. Now, I’m working with KaliVir who really is developing the best in class and I’m with our VET platform. So I am where exactly where I’m supposed to be from that WoW moment that I had 20 some plus years ago.

Taren: I was just going to say it sounds like you are exactly where you need to be. You took the words right out of my mouth. Talk about a perfect intersection of timing, capabilities, skill, maybe a little luck, I don’t know…

Helena: Yeah, yeah, of course.

Taren: … I think that luck favors those who are prepared. But at the same time this is just a perfect – I don’t want to use the word storm because that sounds like messy, but this is just the perfect coming together for you, and I’m excited for you.

Helena: Thank you so much. Yeah, I am too. I think I’ve landed on the right technology after 20 years of searching.

Taren: Perfect. Well thank you so much, Helena, for being part of our WoW podcast program, and I’m going to be excited to keep tracking what you all are doing and see how you progress, and wish you all the best with your current partnerships and with the technology and building out the new development program. So go get them.

Helena: Well, thank you so much. This has been really enjoyable. I appreciate the invitation and I hope that we stay in touch.

Thanks for listening to this episode of WoW, the Woman of the Week podcast. For more WoW episodes, visit pharmavoice.com.