Welcome to ALS-IF on Substack!
Welcome!
We’ve spent the past 10 years working together—as scientists, investors, and founders— backing transformative biotech companies in ALS and neurodegeneration. Our core team is led by Dr. Melanie Leitner, Craig Boyce and Felix von Coerper. Our mission is personal, all three of us have been touched by ALS through colleagues, friends, and Craig’s father who was taken by the disease.
Now, we’re launching this Substack to share insights, updates, and investment perspectives—not on a set schedule, but whenever we have something exciting or thought-provoking to discuss.
This first post dives into why ALS, and why now—exploring the investment case, the scientific momentum, and how we build a high-conviction, power-law-driven portfolio.
Why ALS?
The idea of a disease specific fund was launched by three Dutch ALS patients and some early supporters more than 10 years ago. Felix had been a co-founder in the neuroscience space, and was looking for an interesting investment case. Clearly, developing drugs for ALS serves a huge unmet need and a social impact as there are still very few options available for patients, but that’s not enough to raise the large sums of capital that are needed to bring therapies to the market. We needed to find a case with high alpha, one which could offer a significant risk adjusted return to investors. As he began navigating the ALS space, Felix found and started working with Melanie, a neuroscientist with 20 years experience in cross-sector ALS research and drug development and Craig, managing director at Bain Capital with 20 years of active engagement in ALS philanthropy.
Together they concluded that ALS is actually an exceptional and differentiated business case. The market had failed to appreciate that ALS is only considered to be a rare disease because patients pass away so quickly, within 3-5 years on average, and the definition of a rare disease is based on prevalence (patients living with a disease). The incidence of the disease is actually larger, almost as large as that of MS, with a lifetime chance of getting ALS of 1:400. While ALS drug development gets all the support of a rare disease (such as high pricing, orphan drug protections, and accelerated approvals), it is actually not all that rare of a disease. So, we started to believe in an investor return potential with asymmetric upside.
In addition, therapies for ALS are also potentially relevant to other, larger neurodegenerative diseases with similar disease pathways such as Alzheimer’s (AD) and Parkinson’s (PD). Starting with a rare disease is a proven strategy for drug development, addressing unmet needs while building a foundation to scale solutions to larger indications and broader markets. ALS, in particular, presents a unique opportunity due to its rapid, measurable progression, potentially allowing for the generation of rapid efficacy data compared to more slowly progressing indications like AD and PD.
Why now?
Diving more into the case we learned something else. We realized that therapeutic areas seemingly explode out of nothing with several solutions at once, as we all experienced recently with the GLP1 obesity drugs and COVID vaccines, or some time ago with therapies for MS and HIV. But new therapies don’t come out of nowhere and don’t develop in a vacuum. Drug development is a long slow process. The science behind GLP1 drugs was developed over the last 30 years, and the scientific basis for the mRNA vaccines that were so successful against Covid was also developed years ago but was then able to leverage more recently developed technology.
It also took many years to get to the current standard of care for MS and HIV treatments. Most of the time the development starts with slow and steady but relatively incremental discovery research into causal mechanisms, followed by a (or several) key scientific insight(s) leading to increased research spending, laying the fundamentals for drug discovery. Sometimes new delivery technologies are required to enable a treatment such as ASOs for SMA. Very often a phase of tremendous innovation is triggered by one inflection point, such as the acceptance that MRI findings could both help diagnose and accurately measure treatment effects in MS.
When Melanie, Craig and Felix started, we didn’t know if we were at such an inflection point in ALS. We did see many positive signs including the discovery of the main pathology underlying ALS, the identification of multiple new genetic causes for the disease, a almost sixfold increase of research output over the previous two decades impressive innovations in clinical trial infrastructure and the development of clinical research networks and databases, and an enormous increase in research investment due to the Ice Bucket Challenge and the growth of government funding, all of which made us believe that we were close. 10 years later, we are confident that we are at a tipping point.
The industry acknowledges that the approval of Qualsody® (tofersen) based on a specific biomarker called NfL, was a pivotal event for ALS and neurodegenerative diseases. Never before had an ALS drug received accelerated approval by the regulatory bodies based on a biomarker that could predict the future efficacy of an ALS drug. With the establishment of NfL as a predictive biomarker, the risk and costs of ALS drug development dramatically decreased. We now expect that Qualsody® is the first of a new generation of drugs that will be coming over the next 10 years and that will transform ALS, and hopefully other neurodegenerative diseases, into chronically managed diseases.
What we’re doing - is this a venture-backable thesis?
In spite of the enormous progress we have seen over the past 10 years, investing in neurodegenerative disease is still risky. But the potential financial rewards are high and could provide investors with a potentially asymmetric risk / return profile. We are specifically looking for these outliers.
The current global ALS market is estimated at $1-3 billion, but we believe that it will ultimately be closer to $10 billion, if multiple therapies in combination are required to dramatically increase patient life expectancy. Our goal is to invest in companies where, in our view, the science has undergone significant de-risking while remaining positioned ahead of its largest value inflection point. The outcomes of any single investment in our portfolio can be binary: if successful, each investment has the potential to generate double-digit multiple of money returns; if not, we risk losing all or most of the investment. This is very much by design - the best performing venture funds follow this Power Law distribution of outcomes. This is precisely what makes Venture Capital a “grand slam business” –across the asset class, just 6% of the investments generate 60% of the returns.
The Road Ahead
After a decade of working together, we've witnessed the undeniable acceleration toward a tipping point in ALS therapeutics. The convergence of cutting-edge research and capital has the potential to drive life-changing breakthroughs. By backing high-conviction, de-risked science at the right inflection points, we aim to create transformative patient impact. We’re only getting started - the time to act is now.