Lessons Learned on Preparing to Weather the Inevitable Challenges in Biotech

Posted September 15th, 2022 by Josh Brumm, in Biotech financing, Biotech startup advice, From The Trenches

By Joshua Brumm, CEO of Dyne Therapeutics, as part of the From The Trenches feature of LifeSciVC

By all accounts, 2022 did not start according to plan for the biotech industry. The U.S. economy and growth stocks struggled with the broader biotech index down by more than 45 percent through the first half of the year.

Throughout my career in biotech, I have learned that this industry is filled with twists and turns and, at times, setbacks. However, there are some key strategies that you can employ to best prepare for uncertainty in our business. Building an early position of strength is key to overcoming challenges that others may find insurmountable.

At Dyne, over the past couple of years we invested in thoughtful planning for our global clinical and regulatory strategy, conducted comprehensive preclinical studies to understand our candidates, put in place our manufacturing network, all to be prepared to conduct our first clinical trials this year.  Just last week we announced the first patient was dosed in our DELIVER trial evaluating DYNE-251 for the treatment of Duchenne muscular dystrophy (DMD) mutations amenable to skipping exon 51. We also announced we initiated our DYNE-101 ACHIEVE trial in myotonic dystrophy type 1 (DM1). While we were able to stay on track, the path to getting us to these significant milestones wasn’t a straight line – it rarely is.

For example, in January we received a clinical hold letter from the U.S. Food and Drug Administration on our Investigational New Drug (IND) application to initiate the DYNE-251 DELIVER trial. That hold has since been lifted and cleared. The planning and strategy we had in place allowed us to navigate the hold to dose the first patient while meeting our timelines. Furthermore, we are in a very strong position to deliver meaningful data in the DELIVER study.

Here are a few key lessons I’ve learned to navigate uncertainty and have leveraged in building Dyne for long-term success:

#1: Invest time in planning

You can’t execute on your strategy across all dimensions, R&D and product strategy, manufacturing, organization and culture, regulatory requirements and financing without a plan. While it may seem rudimentary, a well thought out plan helps ensure your team can weather storms and is prepared to deal with adversity.

At Dyne, our detailed planning process starts in June and is led by our Chief Operating Officer Susanna High and her team. During our planning cycle, each function presents its strategy to the leadership team where we collectively review, discuss and challenge ideas. I firmly believe that everyone brings a unique experience and lens to Dyne, and it’s during this process I encourage all Dynamos to speak up and ask questions. From a cultural standpoint, we call this “one mission, no ego,” one of our core values that can be seen in action during our discussions.

The COVID-19 pandemic and its impact on our business and employees, along with the operations of our stakeholders and partners (i.e., CDMOs, service providers, regulatory authorities); and our own regulatory setback, are a few of the challenges we endured. Given the complex nature of global clinical development, the strong foothold of our strategic plans positioned our team to overcome these obstacles.

Perhaps most important, the impact of planning is directly tied to our most significant stakeholder—patients. Having a sound global clinical development strategy prepares us to get to patients more quickly. Beyond this, a well-thought-out plan provides a sense of calm allowing for the ability to be proactive as opportunities for acceleration present and allows room to dream and build.

#2: Drive toward meaningful clinical data

Advancing two programs to the clinic was a tremendous moment for the company and the DMD and DM1 communities.

The most important thing biotech companies can do when conducting clinical studies in arguably all therapeutic areas is to start at safe, yet pharmacologically active doses – or doses that are therapeutic. This enables you to drive to meaningful clinical data as soon as possible which for Dyne includes evaluating key biomarkers of splicing in DM1 and dystrophin expression in DMD.

How do you make this happen? Again, it all starts with planning. First, it requires a commitment to scientific rigor and evaluating your candidates in multiple well-validated models – models that you may even have to create if they don’t exist. For example, in DM1 we developed a novel disease model (hTfR1/DMSXL) that enabled us to evaluate DYNE-101 and demonstrate an impact on reducing nuclear foci and DMPK RNA, leading to splicing correction. Generating robust preclinical data to share with global regulators supports alignment on your trial design. It’s also important early on to engage with advocacy groups, patients, caregivers and key thought leaders and incorporate their perspectives.

This planning and engagement is reflected in our study designs. Both our ACHIEVE and DELIVER trials are Phase 1/2 global, multiple ascending dose clinical trials that are designed to be registrational. Importantly, these trials are also evaluating our product candidates in patients living with these diseases versus beginning with healthy volunteers. This allows us to understand quickly whether we are having an impact on key biomarkers that can transform the lives of patients. And since we are starting at what we believe are therapeutic dose levels, this provides the opportunity to report meaningful clinical data in the second half of 2023, which is roughly a year from starting the studies.

Duchenne is a 100% fatal disease, and the current options just aren’t good enough. In DM1, patients have waited far too long for an approved therapy. Every day is critical for patients and their families, and it’s important that our studies are designed to help ensure we can drive to potential benefit as quickly and safely as possible.

We feel a tremendous sense of urgency to bring potentially transformative therapies to patients. A commitment to our core values of “fearless innovation” and “delivering for patients” motivated the team to think bigger (pharmacologically active doses, biomarker development, patients rather than volunteers, global trial sites) in our comprehensive development strategy and to be well-positioned to execute in the clinic.

#3: Take advantage of financing windows

We have been thoughtful as a company to avoid the capital treadmill. In biotech one never really gets completely off the financing treadmill, but it is possible to build a position of strength while preserving financing options to manage changing market conditions.

In September 2020, we announced the closing of our IPO raising ~$268 million, and four months later raised ~$168 million via a follow-on offering. Many questioned the timing of that follow-on offering.

Fast-forward to today, with rapidly rising interest rates and inflation, access to new capital in the public markets has become very difficult. Looking in the rear view, seizing the moment to have capital on our balance sheet has made a huge impact. Yet, capital is not just equity or debt financings, it could mean pulling other levers such as portfolio optimization, licensing or partnership opportunities. While we have chosen to preserve the ownership rights to our programs, we recently made the decision to extend our cash runway by refining our focus on our co-lead clinical programs. As a result, we are deferring our IND submission for our facioscapulohumeral muscular dystrophy (FSHD) program that we had planned for the second half of this year, and the associated manufacturing and clinical spend. However, Dyne remains fiercely committed to the FSHD community and, in time, delivering a therapy for people living with a disease that has no approved treatments.

Our strong capital strategy has given Dyne operating flexibility as we transitioned from a research-stage to now a clinical-stage organization. Now, with cash on our balance sheet expected to provide runway through 2024, we are well positioned to deliver the meaningful clinical data I mentioned above in both programs that is anticipated in the second half of 2023 – well within our runway.

#4: Don’t stop dreaming

As I wrote at the beginning of this post, the markets have not been kind to the biotech sector this year and there are innate challenges of leading and building a biotech company. Most of us go into our industry with a dream and vision for addressing even the most difficult unmet patient needs. Unfortunately, dreams can easily be crushed in this business for a variety of reasons that are often out of our control. As CEO, it’s my job to foster an environment where we encourage dreams. But dreams without goals are just dreams, and in the biotech industry it is critical to set goals.

At Dyne, I often reference a quote I like from a famous entrepreneur and company builder who said, “If you give yourself 30 days to clean your home, it will take you 30 days. But if you give yourself 3 hours, it will take 3 hours.” In other words, you need to set stretch yet achievable goals for your lofty dreams and build an environment that fosters flawless execution against your plan. For us, every lofty, yet achievable goal and every plan we establish is about never losing sight of our mission to transform patients’ lives.

While we are very focused on the clinic, we are also mindful of our scientists and researchers, who are entrepreneurs at heart, and the essential work they are doing to leverage the full potential of our FORCE™ platform beyond our initial programs. As part of that, it’s important that we set aside even a small amount of time on those “dream big” projects that involve thinking creatively about where we could we go in the future.

Just three years ago we dreamed of transitioning from a research company to a clinical-stage organization and we did it! Dyne 1.0 – chapter complete. What’s next? Dyne 2.0 – delivering meaningful clinical data and the inevitable challenges that come with executing in the clinic. The new chapter we’re embarking on will no doubt present challenges and opportunities, and you can be sure we will have a plan to help us navigate through them.

When I reflect about all the crucial work our Dynamos have achieved especially over the last year, I am filled with a tremendous sense of pride. As I look ahead, I’m confident and resolute as I know Dynamos will continue to dream and win for patients.


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