Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C]-DNL343
DNL343 · 2 trials · 1 indication
Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each of 12 questions assessing distinct functional ability is scored from 4(normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function. Note that only participants who survived to their Week 24 visit contribute to the estimate.
The Mortality Rate, presented as mean deaths per month, was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row.
| Arm | Type | Description |
|---|---|---|
| DNL343 | EXPERIMENTAL | - |
| Matching Placebo | PLACEBO_COMPARATOR | - |
| DNL343 (High Dose) | EXPERIMENTAL | - |
| DNL343 (Low Dose) | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| DNL343 | DRUG | DNL343 is administered orally once daily per day for 24 weeks. |
| Matching Placebo | DRUG | Matching placebo is administered orally once daily per day for 24 weeks. |
| Placebo | DRUG | Oral repeating dose |
Inclusion Criteria: * No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT NCT04297683). Exclusion Criteria: * The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol (NCT NCT04297683). 1. Diagn...
DNL343 is an investigational small molecule being developed for the treatment of amyotrophic lateral sclerosis (ALS), a progressive neurological disease. It is not approved for any indication and remains in clinical development. Denali Therapeutics is evaluating it in ALS patients, including through the HEALEY ALS Platform Trial.
DNL343 targets eIF2B, a protein that regulates protein synthesis under cellular stress. In ALS, stress pathways can impair eIF2B activity, and DNL343 is designed to act on this target. The compound is a small molecule developed by Denali Therapeutics.
DNL343 is being developed by Denali Therapeutics Inc., which trades on the Nasdaq under the ticker DNLI. The company is advancing the small molecule for amyotrophic lateral sclerosis. The HEALEY ALS Platform Trial regimen for DNL343 was conducted in the United States.
DNL343 is in Phase 1 development, with a Phase 2 regimen conducted within the HEALEY ALS Platform Trial. It is investigational and has not been approved by the FDA. Both listed trials for DNL343 have completed, and no trials are currently active.
DNL343 has been studied in two completed trials. NCT05842941 was the HEALEY ALS Platform Trial Regimen G, a Phase 2 placebo-controlled study that enrolled 249 participants in the United States. NCT05006352 was a Phase 1 study of safety, pharmacokinetics, and pharmacodynamics in 29 participants in the United States and the Netherlands.
Yes. [14C]-DNL343 refers to a carbon-14 labeled form of DNL343 used in clinical research, typically to study how the drug is absorbed, metabolized, and eliminated. Both names refer to the same Denali Therapeutics compound being developed for amyotrophic lateral sclerosis.