A Challenge Best Tackled Together – Bridging the ALS Therapeutic Gap with Industry Partners

March 29, 2022

Joseph Lewcock, Ph.D., Denali Therapeutics and member of the ALSRP Programmatic Panel

Dr. Teresa Dunn, Uniformed Services University of the Health Sciences
Dr. Joseph Lewcock

Joseph Lewcock, Ph.D., is Chief Science Officer and Head of Discovery with Denali Therapeutics and a member of the Programmatic Panel for the Amyotrophic Lateral Sclerosis Research Program (ALSRP). Dr. Lewcock provides critically important industry perspectives to ALSRP strategic planning, as the program takes major steps into the clinical trial funding space. We caught up with Dr. Lewcock recently and asked him a few questions.

Q: Dr. Lewcock, thank you for taking the time to chat with us. First of all, can you give us a rundown of how the ALS therapeutic development landscape has changed in recent years?
A: What we are seeing in the ALS drug development landscape now is a continuation of the more fundamental changes in the way people have approached ALS drug development over the last 5-10 years, based on advances in our understanding of the genetic contributors to ALS. Interestingly, there is a split in the types of therapeutic approaches being pursued between targeted strategies with genetic rationale and biomarkers to de-risk development, and those based on more general neurodegeneration biology that may apply to ALS. Some of the targeted approaches may have great promise, but are designed for only a genetically defined patient subpopulation of ALS patients with specific genetic mutations. Meanwhile, therapies that target neurodegeneration more broadly represent a more challenging road based on our incomplete understanding of disease mechanisms, and a lack of “predictive” biomarkers to determine which patients are most likely to respond to which therapies.

Q: What ALS therapeutic strategies are currently of greatest interest to industry?
A: One area the drug development industry is focused on is novel biomarkers of all varieties. Biomarkers are essential to determining the patient populations that may respond to a new therapy or to confirm the activity of a drug. Without effective biomarkers, clinical trial participation in ALS tends to be a catchall for all patients where an impact on specific patient subpopulation may be missed. Everyone would love to see more targeted approaches, but there is still a lot to learn about the drivers of disease outside of small genetically defined patient populations. More investment in biomarkers that bridge this gap is absolutely critical. At present, a company would have to take more risk to explore a therapeutic strategy that targets sporadic ALS, which represents ~90% of patients. A particularly promising approach is to develop a biomarker alongside a therapeutic effort from early on. Therefore, the ALSRP funding mechanisms are a great opportunity for companies to mitigate this risk.

Q: Interesting that the industry perspective is that the ALSRP is a good space to take risks in the biomarker arena. Should a certain type, or even class, of biomarker be prioritized?
A: I believe that any work on new biomarkers has potential for tremendous impact. If I had to pick one, I think predictive biomarkers that help define which patients may benefit from a particular therapeutic approach would be most valuable. This is because defining these patient subpopulations provides an opportunity to better define sporadic ALS patients that would have value well beyond the specific therapeutic candidate being evaluated. However, this type of study often falls into the so-called “valley of death” between academic labs and companies. These studies would be a great area for funding. Providing ALSRP funding for these types of exciting approaches can motivate others to invest in this important area of research. Any new information will increase our overall dataset over time and can allow us to make better decisions in the future.

Q: It seems like there is a strong argument in support of developing predictive/patient selective biomarkers for ALS. Can you tell us more about where you think the ALSRP can best serve in the push for biomarkers?
A: Because preclinical ALS models can only tell us so much, clinical biomarker research helps us learn about the mechanisms of human disease in addition to enabling effective development of new therapeutics. However, many companies aren’t pursuing this work, in part, because they do not know that there are funding mechanisms to support it. With their current funding mechanisms, the ALSRP can encourage both companies and academic investigators to pursue this important work. The NIH has mechanisms to fund later phase trials (which require biomarkers), but there is a hole before therapeutic strategies get there. The updated ALSRP funding mechanisms, particularly the new Clinical Biomarker Development Award ( and the option to include specific biomarker studies as part of a therapeutic development program, are filling this important gap.

Q: Who might be the best fit for the new ALSRP clinical mechanisms?
A: A great group to target with the new ALSRP clinical mechanisms, including the new FY22 Pilot Clinical Trial Award (, would be investigators or companies with an exciting idea that may need a bit more data in order to attract a larger private or public investment. The identification and/or validation of specific biomarkers could add a huge amount of value to a program and is something that ALSRP funding can enable. In my experience, the venture capital community are big believers in biomarker-enabled drug development, and having biomarker data along with strong scientific rationale can make all the difference in whether a novel therapy attracts adequate funding to move forward into clinical trials.

Q: How can the ALSRP best raise awareness of our funding opportunities with companies, startups, and venture funding groups in the clinical trial space?
A: Based on my experience on the Programmatic Panel thus far, there is surprisingly little overlap between the groups applying for ALSRP awards and those seeking venture funding. This makes it clear that there are some gaps in the groups that the ALSRP would like to target. For all the reasons I mentioned earlier, the ALSRP provides an opportunity for investigators to access funding to strengthen the data package supporting their approach. Improved engagement with venture groups could help private funders direct investigators to the ALSRP when appropriate.

Q: Is there a specific avenue for investigators to connect with venture capitalist collaborators?
A: The venture capital world is always on the lookout for the next great therapeutic idea. I think there are many ways that we could get the interesting projects funded by the ALSRP in front of them. This could range from adding venture representation on the ALSRP review panels to simply compiling a list of potentially interested venture firms, which funded investigators could contact should there be interest. It can be especially challenging for academic investigators to take a project to a point where it has a high chance of being funded through private investment. It would be great if the ALSRP could also facilitate connections between academics and biotech/pharma companies to create opportunities to further programs collaboratively. These types of collaborations could be valuable, not only for successfully funded projects, but by also making applicants more competitive for ALSRP funding.

Q: Any final thoughts on how to best work with industry partners to “move the needle” on our mission and have the greatest impact for ALS patients and their families?
A: One of my favorite things about the ALSRP funding mechanisms is that they are specifically designed to fill the gaps between NIH funding and private investment. This strategy provides important opportunities for projects to continue moving forward and should facilitate an improved understanding of the mechanisms driving ALS. These are critical steps to further the development of effective therapeutics for ALS and will surely have a tremendous impact. However, the real win would be to integrate these mechanisms to ensure rapid advancement of the most exciting approaches — I believe that ALS is a challenge best tackled together, and strong collaboration between government, non-profit, and private sources would set us up best for success. I am excited to see the beginnings of this now and hope we can continue to build this type of collaborative approach in the future.

For more information on all of the ALSRP’s available funding opportunities, visit our website at

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Last updated Tuesday, March 29, 2022