When Jay Donovan Wu joined Ascendis Pharma as EVP and president, US, earlier this year, he brought with him both a wealth of experience in the rare-disease space. He also arrived with a genuine personal connection to the company’s mission and a deep belief in the importance of empathy.
In this excerpt from his podcast conversation with Kinara co-editor Chase Feiger, the former Genentech and Bain & Company exec details how his upbringing helped define his leadership style. He also goes deep on Ascendis’ TransCon technology platform, a novel delivery and discovery platform that has changed the way the company goes about its business.
(This Q&A has been edited for length and clarity. To listen to the full Kinara podcast with Jay Donovan Wu, click here.)
Chase Feiger: What drew you to Ascendis? What excites you the most about the mission?
Jay Donovan Wu: Jan Mikkelsen, our CEO, emphasizes the need to serve patients in a way where we address the greatest unmet needs. As someone who is personally and professionally invested in rare disease, that is incredibly compelling. The second part is that it’s fundamentally a science-driven company. There’s an elegant simplicity and sophistication associated with the TransCon technology, which is a proprietary drug delivery and development platform. Anytime you can marry science with unmet patient need, that’s generally a winning combination.
Feiger: How do your personal journey and the skills that you’ve garnered over the years manifest themselves in the way you lead?
Wu: I love the question around how a personal journey affects leadership, because oftentimes people assume that leadership in a professional context is perhaps different than how we show up in our personal lives. I actually think that’s fundamentally not true. They’re intertwined. I’ll share a bit more about my background and how that informs the way I show up—not just in a work context, but also in a personal context.
I grew up as a closeted gay man in the Midwest during a time when, candidly, it was challenging. And I also grew up in a very traditional Taiwanese family. For me, it shows up in three different ways. The first is that when you grow up in that kind of environment, you naturally find a way to divorce ideas from identity. You run up against people that may have very different beliefs than you do, but they’re very good people—some of them were in my own family. It creates this early appreciation that you can challenge ideas, but not people. Good people can disagree. And that informs a big part of how I show up in a professional context. Because from a challenger-mindset standpoint, how do you create an organization where there’s enough psychological safety to foster constructive debate? How can you get the controversial or less popular idea on the table, perhaps an idea from someone quieter who otherwise wouldn’t have shared it? When you have a broader range of potential ideas and solutions on the table, you generally make better decisions.
The second way I would say it shows up is probably around the relationship between time and urgency. I’m a very impatient person, and I think some of that stems from not living in an authentic manner for the first two decades of my life. I feel that I’ll probably spend the rest of my life trying to make up for lost time. My husband will say, “You’re an impatient person regardless,” and that’s probably true, but that ethos of urgency is also an element of leadership. It’s not so much about creating an unsustainable environment where we’re burning people into the ground. It’s more about: How do you work smart? How do you work efficiently so that you can find the rate-limiting step in anything that you’re doing right? Whether that’s drug development or shortening that iterative learning cycle, whether that’s trying to shave off some time from a filing timeline or trying to get product out to patients even sooner, ultimately the people who benefit most are patients.
Last but not least, and this is the one I’m actually most passionate about, is empathy. As a concept, it’s something that gets tossed around a lot these days, but for me it’s quite personal. Oftentimes I will interact with people who don’t have the same lived experience that I do, and that’s true for all of us. But when you grow up in an environment where you are constantly surrounded by folks who don’t have that lived experience, I think you have an innate appreciation for empathy. You go through life assuming that there’s more to things than meets the eye.
From a leadership and a professional standpoint, empathy is incredibly important because it naturally orients leaders from a place of curiosity. When you translate that into seeking to understand the patient experience, it’s incredibly powerful because a lot of the things that we talk about here at Ascendis are about that patient journey. Have you actually dialed the call center yourself? What are the forms that we’re asking people to fill out? Have you actually tried to fill them out? When you go through that journey, sometimes you arrive at a different appreciation for the problem that you’re trying to solve and a different solution subset to draw from.
I have a personal connection to rare disease: My brother-in-law has cystic fibrosis and he was on a therapy that I became accountable for in my previous job. Being in a situation where knowing the decisions you’re making and the discussions you’re having with your team are directly impacting patients and communities—and in this instance, my own family—gives you a different appreciation for what empathy means in a work context.
Feiger: One of the things that stands out about Ascendis is the TransCon platform. As you mentioned, it’s not just a delivery mechanism; it’s a strategic engine for how you develop and extend a line of therapeutics. Can you walk us through what TransCon enables?
Wu: What it stands for is “transient conjugation.” The analogy we like to use is a benign gift wrap. You’re putting a drug in a benign gift wrap to deliver it into the body, then over time the packaging goes away, allowing for a more sustained, controlled delivery. The effects it can have are actually quite profound. Oftentimes when you’re delivering a drug into the body, you’re activating certain receptors that then trigger certain downstream cascades. But the actual biological agent may not be interacting with the receptor for an extended period of time. So every time you dose, you’re activating the receptor and then it goes away. If you’re able to deliver it in a more controlled, sustained way, the time you’re activating that receptor might be extended.
You also can meaningfully cut down on potential adverse events or side effects as a result of that more controlled release. You can go into situations where patients who are used to needing an injection daily might go to a weekly basis. That ultimately gives people a chance to live their lives in a different way than they previously were able to. They can start to focus more on what they want to do, versus receiving a therapy which they might have had to get daily or even more frequently.
Feiger: How does TransCon help you choose which diseases to go after?
Wu: The beauty of the platform is that it is applicable in so many areas, so we focus on the highest unmet need. It’s not a coincidence that the area in which you’ve seen a lot of our initial development efforts take place is rare endocrine disease. Because when you think about hormones in the body, it’s a very delicate system where a little too much or not enough can have profound multi-organ effects.
Our first long-acting growth hormone therapy was launched in 2021 and then earlier this year we launched and made commercially available the first and only approved therapy for hypoparathyroidism. We also have compelling pivotal data for a new product in achondroplasia. So you can see that this is something that really has a demonstrated track record of success.
Feiger: You’re leading a company that’s investing deeply in long-term R&D while also navigating the realities of short-term commercial expectations. How do you handle the tension between the two?
Wu: There are a lot of macroeconomic trends at play currently and a lot of uncertainty for the biopharma industry as a whole. So now more than ever, we need to operate in a lean and sustainable way when scaling our Ascendis efforts, particularly during a time of growth. Ascendis is in a unique position, in that it is a scrappy biotech but it is scaling.
I look at it through the lens of, “What’s the common denominator through which we can make an apples-to-apples comparison?,” and the common denominator for Ascentis has always been patients. I know that sounds contrived, but let’s break it down a little bit. If we invest a certain amount in continued outreach for our existing products, let’s say we can impact another 10,000 patients over the next three years. But if instead we invest all or some of those chips into R&D and the long-term pipeline, maybe we could impact 15,000 patients—but six or seven years from now. It’s easy to fall into the trap of assuming if you do more of A, you’re doing less of B and therefore it’s a zero-sum game. But I’ll tell you the Ascendis R&D leaders are sometimes the biggest proponents of the investments that we make in a near-term commercial organization. And similarly, the commercial leaders are oftentimes the loudest and most staunch advocates for investments in the R&D organization.
Feiger: What does true innovation look like in biotech today? How does Ascendis define success beyond just approvals?
Wu: I have a knee-jerk reaction to that. To me, success is always, “Are you in the game of making a transformational step change, or are you in the game of making an incremental change?” Ascendis targets that transformational step change bucket. With rare diseases in particular, oftentimes these are areas in which there have been few or no advancements. Just by virtue of entering those spaces, you are seeking to make a transformational step change.
When I think about the history of the biotech industry as a whole, there are a lot of step changes you can think of. Checkpoint inhibitors in oncology. The wave of disease-modifying therapies for cystic fibrosis and spinal muscular atrophy. People look back and they’re like, “Wow, that was a transformational step change.” What we’re doing at Ascendis is very much aligned with that.
I’ll give you a tangible example: Yorvipath, the first and only product currently approved for hypoparathyroidism. Prior to that, there really weren’t many options for patients. The pill burden was just incredibly high. You heard from some patients who said they had to wake themselves up in the middle of the night, because if they didn’t take enough pills they wouldn’t feel well enough the next day. And now having an option where there’s a daily injection that actually affects the root of the issue—that actually is a transformational step change, and it’s incredibly compelling.
Feiger: Where do you see Ascendis five years from now? What’s the story you want people sharing about the company?
Wu: Five years from now—in some ways that’s not long enough. Because when I think about that transformational step change that we talked about before, that’s about legacy and lasting impact. What I hope to see, and what I do feel confident that Ascendis is already on the pathway to achieving, is when a patient living with a rare condition looks back and is able to point to a moment in time in which they thought, “I finally felt seen. I finally felt heard. I finally felt like the world around me realized that, despite this rare condition that I have, there is an option that allows me to live my life in a meaningfully different way than I could before.”
You can wait a whole lifetime for a change like this to happen and have it not happen. So when I think about Ascendis and the story I think it will tell, it’s that, given the patient-rooted nature of everything we do, Ascendis is focusing on the areas where there’s greatest unmet need and marrying high science to it so that we can create transformational step change. That’s what I hope people will remember.
