By Joachim Boekelmann and Joshua Brumm, as part of the From The Trenches feature of LifeSciVC.
At first blush, we may seem an unlikely duo: An attorney for a global insurance company living with a rare form of muscular dystrophy and a biotech CEO who moonlights as a kids’ basketball coach combining our voices in one blog post. But over the past few months, we’ve encountered plenty of common ground.
The two of us first met on Rare Disease Day in February 2020 – back when meeting in person was still an option. On that chilly-but-sunny Saturday morning at Dyne Therapeutics’ office in Waltham, we engaged in a dynamic Q&A that shed light on the challenges and the opportunities that drew us together. 
It’s one of those common threads that we’d like to talk about now, by sharing our perspectives on hope.
Hope is essential for individuals and families living with rare muscle diseases. It’s essential for biotech companies and the people who dedicate themselves to developing new therapeutics as well. But while it’s indispensable, it is also perilous – because, in both our worlds, hope is fragile. Even as it keeps us going, it can also set us up for crushing disappointments.
It’s important to find your own balance between optimism and realism. Here’s how the two of us have managed that challenge.
Joachim’s perspective: Always take the long view
My father was diagnosed with myotonic dystrophy type 1 (DM1) in his early 40s, so from an early age, I knew that I had a 50-50 chance of carrying the disease. A genetic test confirmed I was a carrier. My symptoms began when I was in my early 30s.
DM1 causes progressive muscle weakness and myotonia, or difficulty relaxing muscles, leading to challenges walking and talking. Even simple acts like getting dressed or picking up a glass of water become difficult.
My symptoms have worsened over time; I can still walk, but very slowly, and my speech is sometimes hard to understand. DM1 is a progressive disorder, which means my muscles will continue to weaken. Far scarier than what lies ahead for me are my concerns about my son’s and daughter’s futures. Though he has not yet received a confirmed diagnosis, my son is at a particularly high risk for DM1.
Some of my first glimmers of hope came when I got involved with the Myotonic Dystrophy Foundation. I learned about the research into therapies for DM1, and I saw how some of my peers were helping to advance that work. It was empowering.
However, I soon saw the flip side of that hope. Many in our community were emotionally invested in the first-ever clinical trial of an industry-developed investigational therapy for DM1, which launched in 2014. Hopes were high that this could be the cure we had been dreaming of for so long. At the very least, we thought it could halt progression of our disease. But in 2017, the trial results came out. It was not a success. People were devastated.
You might think that this experience would make us wary of engaging with other biotechs – but for me, at least, it was the opposite. Learning that companies like Dyne, founded in 2018, are persevering in the field has been incredibly inspiring. I do try to keep guardrails around my optimism, because I know the odds of success for any one therapy are slim. But at the same time, I know that every experiment, every trial will move us forward. We will learn from our setbacks and we will keep driving toward a cure together.
I felt even more reason for hope after my wife, Mic, and I went to Dyne’s office for its Rare Disease Day event earlier this year. As I described my story to the audience of upturned faces, I was struck by the energy in the room.
Here we were on a Saturday morning and more than 50 people had come into the office to support the rare disease community and learn about my life. And they weren’t just employees asking clinical questions that might help them to solve the puzzle of DM1. It was a family affair. There were spouses and young children in the audience, all attentive, empathetic and determined to do what they could to advance our shared mission of finding new treatments for this rare and relentless disorder.
I honestly got the feeling that the researchers I talked to were inspired after hearing my story to give another 50% on top of the 125% they were already putting into their work. I don’t know how that would be humanly possible, but that’s what I felt.
I’ve reflected on that day many times since, and it always buoys my spirits. So many smart people are so determined to tackle this disease that in the long run, we can’t fail. It will take time, but I know we’ll get there.
And that’s why I have hope.
Josh’s perspective: An abiding commitment to deliver for patients
I’m very similar to Joachim in that family is everything to me. I think often of my grandparents, who didn’t have wealth but who nonetheless dedicated their lives to taking care of our whole extended family. That deep sense of caring has stuck with me. From an early age, I developed a strong determination to make a positive impact on people’s lives.
Before joining Dyne, I had been an executive at other biotech companies, including one that was developing cancer therapeutics. I certainly felt passionate about that work; my wonderful grandparents were taken by cancer, and I know the deep unmet need.
But at Dyne, that commitment has reached a new level. Frankly, it surprises me to recognize how deeply I feel the urgency to move our work forward successfully. As CEO, I am of course responsible to many stakeholders, including our team, our board, and our investors. I’m also responsible to the patients who are counting on us to deliver for them, and I feel that responsibility in my bones.
After I first met Joachim in February, I found myself waking up in the middle of the night thinking about how unfair it is that there are no treatments for many progressive muscle disorders. I’ve been an athlete all my life; I love playing sports and being active with my family. Yet I know Joachim and other people living with muscle disorders cannot enjoy those same activities. As their disease progresses, they will experience muscle wasting, loss of mobility and function, and many other devastating symptoms.
We need to solve this. That’s the bottom line. We need to find therapies that can halt or reverse progression. And we need them soon. Joachim saw his father’s mobility wane over time as his DM1 progressed. Now, he’s experiencing that same loss of function. If we don’t develop a therapy soon, his own children could potentially be in the same situation in a decade or two. We just can’t let that happen.
Everyone on the Dyne team feels that sense of urgency. We’ve had several conversations with people living with rare muscle disorders; every one of them inspires us and spurs us to work harder, smarter and more creatively. Many of us have tacked photos and quotes from those interactions over our desks, so whenever we hit a roadblock, we need only look up to find the motivation we need to persevere.
Our work at Dyne has been progressing well. We designed our proprietary FORCE platform to overcome the current challenges of delivering therapeutics to muscle tissue. We link an antigen-binding fragment antibody to an oligonucleotide to deliver therapeutic payloads directly and precisely to muscle. We’ve seen compelling preclinical data across our areas of focus, which include Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD) as well as DM1. We just completed a successful IPO that will provide the funding we need to advance our lead programs to the clinic.
As excited as I am about Dyne’s approach – and as confident as I am in our team – I’m also acutely aware of the hard realities of drug development. I’ve seen first-hand how difficult a disappointment in the clinic can be for everyone involved – first and foremost, for families living with these challenging diseases.
As we move our programs forward, we know we will hit obstacles. In biotech, that’s a given. Sometimes those obstacles will be beyond our control; we can’t change the basics of human biology, for instance. In other cases, we will be able to persevere and overcome them. I personally struggle at times with how to strike the right balance between hope and caution. As CEO, I need to inspire my team and convey our very real excitement and confidence to the patient community. Yet knowing that we will inevitably face hurdles, I must be sure to temper that enthusiasm, so as not to raise outsized expectations. My motto in life – which we have adopted as a core value at Dyne – is that I do what I say I’m going to do. I feel strongly that my own personal credibility and accountability are on the line when I talk to Joachim and to all our stakeholders because we live and breathe that value: We will do what we say we will do.
I work hard to keep that sense of balance in my own mind, and in all my communications with patients and their families. I want people living with rare muscle diseases to see our passion and understand that we have confidence in our approach – confidence developed based on exciting preclinical data, a commitment to scientific rigor, and the experience of an exceptional team that has proven time and again that we can persevere through setbacks, solve enormous challenges and innovate bold solutions. But as we noted earlier, hope is fragile. We have to be respectful of that hope and balance it with a realistic understanding of the road ahead.
Closing thoughts
Both of us, Joachim and Josh, share a deep dedication to family and team. We both want to impart our knowledge to the broader drug discovery community.
And yes, we both have hope. It’s guarded, but it’s strong. And that hope is a powerful force. It has allowed us both to do incredible things – and, just as importantly, it empowers us to look toward the future with courage and optimism.
