Skip to content
There is a great degree of renewed optimism for drug development in the neurodegenerative disease space.
“Some of that optimism has obviously come from the headline news events of the last couple of years,” explained Selina Koch, Ph.D., Executive Editor and Head of Intelligence & Research at BioCentury, who moderated the panel, Expansion of Neurodegenerative Disease Targets and Pipelines, during the 2024 Biotechnology Innovation Organization (BIO) Investor Forum.
We’ve recently seen the approval of anti-amyloid therapies and the first disease-modifying therapy for ALS. In both cases, the U.S. Food and Drug Administration showed “a willingness to accept surrogate endpoints, and, in the ALS example, to look beyond imperfect primary endpoint data,” said Koch.
This optimism not only bodes well for the burgeoning science attached to the research and development of drugs to treat neurodegenerative disease but also for investors who are interested in entering or re-entering that space.
Huntington’s disease
For Huntington’s disease, a chronic, inherited disease that causes nerve cells in the brain to deteriorate and die, research has successfully found ways to start de-risking investment.
“Huntington’s disease has always seemed to be a little bit different from the other age-related neurodegenerative diseases, in the sense that it’s monogenic,” Koch said to Beth Hoffman, Ph.D., founder and CEO of Origami Therapeutics, Inc.
“The academic concept is simple,” Hoffman responded. “We know what’s broken, we know what to fix. We know what causes the disease, and so we go after that.”
“It turns out that part of the reason that some of these proteins cause disease is because they’re actually really important,” she explained, “and their function is really important in the cell. So, our goal is really to restore normal function, or as close to normal function as possible, by selectively getting rid of the new Huntington. We do that with a small molecule that will be an oral medication that you can take once a day.”
Paul August, Ph.D., Chief Scientific Officer for ReviR Therapeutics, explained that his company takes a genetic approach.
“We’re essentially modulating and splicing mRNAs, like the Huntington gene,” he said. “Our lead program for splicing modulation is focused on HTT reduction, as well. And there we’re also combining that with a dual mechanism, where we are inhibiting the gene that is causing repeat expansions.” ReviR Therapeutics’ focus on the inhibiting aspect is based on observations that the repetitive nature of Huntington’s is like a “ticking time bomb” for patients.
As both companies exemplify, the trick to neurodegenerative R&D is to look at a problem from multiple angles. Additionally, much of the promise of the space is also a result of the fact that small molecule drugs are very much a viable option for treatment.
Amyotrophic lateral sclerosis (ALS)
ALS is a terminal, progressive neurodegenerative disease that affects the nerve cells in the brain and spinal cord. Yet, as with many neurodegenerative diseases, ALS is not just one disease but three different diseases. This fact caused research to move slowly at first, but with new breakthroughs in science and understanding, the space is transforming significantly.
“In the last 10 years or so, we’ve seen two different innovations really breaking through,” said Kasper Roet, Ph.D., founder and CEO of QurAlis Corporation.
“One is the use of human stem cell models to really assess disease targets and also to potentially identify therapeutics, and the other is genetics,” he said. “Last year, a drug was approved for 2% of the patient population. It genetically targeted SOD1, which is actually a really important proof point because it shows that you can actually do something about this disease if you have the right target.”
Precision medicine has proven to be a key element in researching and developing drugs for neurodegeneration, especially given the genetic nature of many of these diseases, as well as the growing prevalence and diversity of things like biomarkers. With these breakthroughs, as well as de-risk incentivization, in mind, QurAlis is developing small molecule drugs to treat ALS, specifically splice modulator A.
Alzheimer’s disease
Alzheimer’s disease is a brain disorder that gradually destroys memory and thinking skills, and eventually, the ability to perform everyday tasks. Given the correlation between neuroinflammation and neurodegenerative disease, there is a great deal of interest in researching drug options, and an eventual cure.
And as David Bearss, Ph.D., CEO of Halia Therapeutics, explained, databases and the rise of AI can help R&D take lightspeed leaps forward in the coming years. In Utah, where Bearss is based, the presence of a state-wide genetic database helped his company discover a suppressive gene that counteracted the presence of the Alzheimer’s gene.
On the one hand, the activating gene can trigger neuroinflammation, leading to things like Alzheimer’s. On the other, a counteracting anti-inflammatory gene, like the one Halia found, does the opposite and slows or (hopefully) halts that progress, even later in life.
“Now we’ve discovered a way to drive this to the same pathways,” Bearss explained. “We have a new way to actually turn off inducement.”
“But what we know is that neurodegenerative diseases seem to have neuroinflammation as a primary phenotype in these diseases, and we think that there’s an opportunity to explore the ability to drug this pathway,” Bearss continued. “And human genetic experiments suggest that if we can drug it, we can prevent some of these diseases, or at least, hopefully treat some of these diseases.”
Investor optimism in neurodegenerative disease
The last year has brought new breakthroughs, coupled with the improving investment landscape (and even government investment and cooperation in the space). And investor interest in neurodegenerative space is growing.
“I think that there are a couple of reasons that we see things looking a bit easier,” explained Karen Harris, Chief Financial Officer & Head of Mission Related Investments at the Alzheimer’s Drug Discovery Foundation (ADDF).
“The first is that we’ve shown that we can do FDA approvals with biomarkers and get two drugs to market,” she said. “I think that is just something that de-risks investing in Alzheimer’s, which really was a target that it seemed that most VCs just weren’t interested in. And I’m beginning to see VCs that are now coming to ADDF and saying, Show me your portfolio companies that are raising money.”
Harris also pointed out that the variety of up-and-coming biomarkers is also a big draw for investors. Not only are companies working with blood biomarkers, but they are also working with digital and vocal biomarkers—which are especially useful in the neurodegenerative space and, with the help of AI/ML programs, can indicate degeneration earlier and more accurately.
As panelists pointed out, these breakthroughs are leading to more successful clinical trials and, therefore, higher investor confidence. The space only has room to evolve—with the very real possibility that patients could get cures sooner.
