spec sheet7 rows
ATH-1105 is an oral small molecule being developed for ALS, from the same company as fosgonimeton and on the same claimed mechanism of positive modulation of the hepatocyte growth factor system. It has completed a phase 1 and has the strongest target-validation evidence anyone in this chemical programme has produced. ⚠️ It is not, despite frequent description, an oral version of fosgonimeton. The published structure is a different chemical class entirely, and neither of its two papers mentions fosgonimeton or dihexa. The two compounds share a claimed mechanism, not a scaffold.
- Its neuroprotection disappears when MET is knocked down, which is real target-dependency evidence and is not retracted
- Extended survival in a transgenic ALS mouse model and worked alongside riluzole
- Reduced mislocalised and phosphorylated TDP-43, the protein central to nearly all ALS
- No human safety data has been published in any form
- The phase 1 has no posted registry results and the company account of it contains no numbers
Mechanism
The claimed mechanism is the same one the whole programme rests on: positive modulation of hepatocyte growth factor signalling through the MET receptor, rather than direct agonism.
⚠️ The target-dependency evidence here is better than anywhere else in this family. Knocking down MET with interfering RNA abolished the compound's protection of motor neurons [2]. That is the kind of experiment the retracted dihexa work was supposed to have provided, done properly and published in an unretracted paper.
In cells, MET phosphorylation rose against a subthreshold amount of HGF, reaching significance at 10 and 100 picomolar [1]. ⚠️ Note the shape of that result: the higher concentrations were not significant, so the response is bell-shaped rather than dose-dependent, which is characteristic of this whole series and is a weak foundation for any potency claim. No binding constant has been published.
In -challenged motor neurons the compound reduced misplaced and phosphorylated TDP-43, the protein that mislocalises in almost all ALS, and increased inhibitory phosphorylation of GSK3 beta [2].
⚠️ The structure is probable rather than confirmed. A public chemistry record describes a bicyclic pyrazino-pyrimidine-dione carrying a trifluoromethylbenzyl group, but that record is derived from patent and vendor deposits, its stereochemistry is only partly defined, and neither company paper discloses a structure, formula or chemical class. What can be said is that it is not the linear -like chemistry of dihexa.
receptor fingerprint
MET / c-Met receptor tyrosine kinaseClaimed positive modulator
TDP-43 mislocalisationReduces (downstream)
GSK3 betaIncreases inhibitory phosphorylation (downstream)
Evidencehow good the literature is
Two peer-reviewed papers and one completed phase 1 with nothing published from it.
The main preclinical result is a survival study in a transgenic mouse line carrying a mutant human TDP-43, with 20 animals per group [1]. First death moved from day 85 in untreated animals to day 129 in treated ones, and survival at day 152 was 75 percent against 35 percent. The paper reports the difference as significant.
⚠️ Two cautions about reading that as neuroprotection. It is one mouse line in one study, and a delayed-treatment arm lost the body-weight benefit. More importantly, this particular model dies substantially of gut dysfunction rather than motor neuron loss; the paper itself notes the animals need a softened diet to manage it. A survival endpoint tied to body weight in that model is genuinely hard to interpret.
A second paper found the compound worked alongside riluzole, the standard ALS drug, with the combination better than either alone in the same model [2]. That paper also carries the MET knockdown experiment, which is the most valuable result in the programme.
A phase 2 was described as planned for early 2026; no registration for one exists.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
No safety data has been published in any peer-reviewed form.
A phase 1 in healthy volunteers has been completed. ⚠️ The only public account of it is a company presentation describing a favourable safety and tolerability profile, dose-proportional pharmacokinetics and brain penetration, and containing no numbers of any kind: no participant counts, no doses, no adverse event listing, no pharmacokinetic parameters and no measurement of drug in cerebrospinal fluid. No results have been posted to the trial registry. Those claims should be read as a sponsor's characterisation, not as data.
In the animal work the compound was given daily for months without reported toxicity, but rodent tolerability is not a human safety finding.
History
The compound came forward when its developer's lead programme failed. Two weeks after the phase 2/3 of fosgonimeton missed its endpoints in September 2024, the company cut most of its staff and redirected to this molecule for ALS. It is now the neurological programme of a company that has since renamed itself and taken on a licensed breast cancer drug as well.
Subjective profileweighing the evidence above
The most interesting compound in this family, for one specific reason: its neuroprotection disappears when the MET receptor is knocked down. That is a real target-dependency experiment, it was published in 2025, and it is not retracted, which distinguishes it sharply from the mechanism evidence behind dihexa and fosgonimeton. Set against that, the efficacy data is one transgenic mouse line in a single 60-animal survival study, and the human data is a press release with no numbers in it at all. The compound is early and the case for it is a mechanism case, not an outcome case.
Resources
This entry is here for reference.
Research
- 1.ATH-1105, a small-molecule positive modulator of the neurotrophic HGF system, is neuroprotective, preserves neuromotor function, and extends survival in preclinical models of ALS
- 2.ATH-1105 mitigates multiple pathologies in ALS models both alone and in combination with riluzole
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is this just fosgonimeton in a pill?
No. The published structure is a different chemical class, and neither company paper about it mentions fosgonimeton or dihexa. What the two share is a claimed mechanism, positive modulation of hepatocyte growth factor signalling, not a common scaffold.
Why does this entry treat its mechanism more seriously than dihexa's?
Because someone knocked down the receptor and the effect went away, and that experiment is published in a paper carrying no retraction. The equivalent claim for dihexa rests on work withdrawn in 2025 for fabricated data.
Limitations of the evidence
- Efficacy rests on one transgenic mouse line in a single 60-animal survival study
- That model dies substantially of gut dysfunction, which makes a weight-linked survival endpoint hard to read as neuroprotection
- The cell response is bell-shaped rather than dose-dependent, so no potency can be claimed from it
- No binding constant exists, and the structure is depositor-derived rather than disclosed by the sponsor
- Frequently described as an oral form of fosgonimeton, which the published chemistry does not support
Adverse effects
- No human safety data has been published in any form
- The phase 1 has no posted registry results and the company account of it contains no numbers