Table 4 Tau therapeutics in phase I or reported as being in filing for IND/CTA (as of February 28, 2023)
From: The therapeutic landscape of tauopathies: challenges and prospects
Molecule type | Company name | Drug name | Indication | Route of administration | Mechanism of action |
|---|---|---|---|---|---|
ASO | Novartis AG | NIO-752 (NIO 752; NIO752; tau antagonist) | PSP | Intrathecal | ASO that acts by targeting tau/MAPT. |
Fusion protein | Proclara Biosciences | NPT-088 | AD | IV | Ig fusion protein that acts by targeting APP, ⍺-syn, prion, and tau protein and is developed based on “General Amyloid Interaction Motif” technology. Blocks aggregate formation of Aꞵ and tau. |
mAb | Aprinoia Therapeutics | APNmAb-005 (APN 005) | AD, FTD | Undisclosed | Acts as a tau protein inhibitor and is claimed to have selectivity to toxic tau species. |
H. Lundbeck AS | LuAF-87908 | AD, tauopathies | IV | Humanized mouse IgG1 mAb to p-tau protein. | |
Merck & Co | MK-2214 | AD | Undisclosed | An anti-tau mAb. | |
Ta-1505 | AD | Undisclosed | Inhibits pSer413-tau to inhibit excessive phosphorylation of tau. | ||
Prothena | PRX-005 | Phase I for AD; preclinical for CTE, FTD, PSP | Subcutaneous | The mAb functions as MAPT inhibitor. | |
Small molecule | Alterity Therapeutics | AHT-434 (PBT-434) | MSA (Ph. II); CBD, PD, PSP (Ph. I in Australia only) | Oral | Inhibitor of metal-protein interaction. Prevents cell death by inhibiting the interaction between dopamine and iron and stops the accumulation of ⍺-syn (possibly tau too). It also elevates levels of the protective protein called DJ-1, reducing the rise of oxidative stress. |
Anavex Life Sciences | ANAVEX 3–71 (AF-710B) | AD, FTD, PD | Oral | Induces a synchronized sigma-1 receptor activation and M1 muscarinic allosteric/bi-topic modulation via super-sensitization of M1mAChR, through a hypothetical heteromerization with Sig1R. Decreases Aꞵ, tau-hyperphosphorylation, GSK3beta activation, and prevents apoptosis and mitochondrial dysfunction via increased Bcl2. | |
BeyondBio Inc | BEY-2153 | AD | Oral | Acts as a tau and Aꞵ protein inhibitor. | |
Biogen Inc | BIIB-113 | AD | Oral | Protein O-GlcNAcase inhibitor. | |
Cortice Biosciences | ARC-100 (TPI 287) | AD, PSP, CBD | IV, oral | Microtubule inhibitor. Binds to tubulin and stabilizes microtubules, resulting in inhibition of microtubule assembly/disassembly dynamics, cell cycle arrest at the G2/M phase, and apoptosis. | |
Eli Lilly and Co | ACI-3024 (morphomer tau aggregation inhibitors) | AD, tauopathies | Oral | Reduction of tau aggregation. Selective binding to tau, no binding to the monomeric form of tau, and selective binding to AD brain-derived pathological tau. | |
Neurokine Therapeutics | MW-150 | AD, dementia, tauopathies | Oral | General mechanism for reducing neuroinflammation through selective inhibition of mitogen-activated protein kinase p38 (p38MAPK). | |
Oligomerix Inc | OLX-07010 (TO-0582) | AD, FTD, tauopathies | Undisclosed | Acts by targeting tau oligomer formation. | |
Revivo Therapeutics | RIV-5061 (RIV-1061) | AD; cognitive impairment in IND/CTA phase | Undisclosed | Immediate release formulation of nomethiazole. It acts by targeting APP and NFTs. The drug candidate works by inhibiting and reducing tau protein from forming PHFs. | |
Unknown | PharmacoBio (formerly Dadang & BIO Co. Ltd.) | DDNA-0101 | Dementia associated with AD (in IND/CTA) | Undisclosed | Aggregation inhibitor for tau and APP. Also prevents the hydrolysis of acetylcholine and enhances cholinergic function. Developed based on gut-brain microbiota axis platform. |
Vaccine | Vitruvian Biomedical | YM-7555, reported to be in IND/CTA filed phase | AD (in IND/CTA) | Undisclosed | DNA vaccine that comprises human Aꞵ 1–42 and human tau 379–408 sequences connected to both ends of the Fc portion of immunoglobulin. |