Scaffold Therapeutics is developing oral therapies for ALS, a fatal disease with no approved treatments. The biology behind our approach also points the way to other diseases driven by the same protein, TDP‑43.
Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig's disease, progressively destroys the nerve cells that tell muscles how to move. It typically begins as weakness in the hands, feet, arms, or legs and advances until patients can no longer chew, swallow, speak, or breathe. Respiratory failure is the most common cause of death, on average within three to five years of symptom onset. In more than 97% of those patients, TDP‑43 is not properly regulated.
The two approved therapies, riluzole and edaravone, slow progression only marginally. Patients need a treatment that changes the trajectory of the disease.
The same TDP‑43 pathology manifests in other neurodegenerative diseases, so a drug that succeeds in ALS has a credible path to a much larger patient population. Scaffold is building the first phase of a platform for treating TDP‑43 driven neurodegenerative diseases.
In nearly all ALS patients, a protein called TDP‑43 becomes overactive. Our drugs act to restore normal TDP-43 activity. That same overactivity is seen in other neurodegenerative diseases, which is why a win in ALS opens doors elsewhere.
Our molecules can be taken orally and crosses into the brain and spinal cord, a challenge that has ended numerous drug discovery programs before they reach patients. Preclinical studies have demonstrated that our compounds cross the blood-brain-barrier and are safe.
A simple test on spinal fluid identifies the patients most likely to benefit and lets us measure the drug's effect directly. So even a small human trial can produce meaningful data about how well the therapy works and who will respond best to treatment.
An oral small molecule with confirmed brain exposure, demonstrated target engagement and clean early tolerability in animal studies.
Developing novel drugs to address major unmet medical needs, initially in ALS then in diseases where TDP-43 plays a central role.
The preclinical work required to file with the FDA, followed by an early‑stage trial in ALS patients.