PET aSyn vendor matrix (Takeda CS 20230427, AlzForum FOSO28, MJF supported, Method comparison Smith 2023, SPAL-T-06 vs C05-05, Round 2 compound), Takeda co-owner license agreements
PET aSyn — vendor matrix continued
| AC Immune | MODAG | University of Zurich | QST | Shenzhen | Merck | Mass Gener at Brigham | |
|---|---|---|---|---|---|---|---|
| Takeda CS 20230427 |
• we are preparing to path to generate the necessary data to file an eIND in the US. • This tracer has been already studied in humans with some degree of success • although more data needs to be generated to confirm the findings. • Tomohiro 알파, Selectivity? • 20% over a-Syn fibrils against IND that AT-501 has demonstrated good binding affinity to soluble fibrils. • They have 20nM hypothesis (what is this?) • Will modify chemistry • Current rt for outcome good enough to go further? | ||||||
| QST has some candidates that are being characterized. The team plans to check SPAL-T-06, C05-05 and AC-12589 as a benchmark to make a criteria in preclinical evaluation. A next clinical candidate will be selected according to the criteria. | |||||||
| AlzForum SUS | has said that although next-generation tracers are under investigation, FOSO28 is biorigested in people with PD or DLB and MSA, Bracogger Pharmaceutica L.C., a company in Charghoo founded by its sponsors. Hideoshima Jamie Eberling Michael J Foundation Pooled (07 Aug 2023) | ||||||
| MJF supported | a-syn PET tracer dev for over a decade and has funded more than $30 million in research. It is likely that a tracer will need to be highly selective with minimal binding to other targets including other pathological proteins (Aβ, tau, TDP-43); and bind to a-synuclein with very high affinity (love or subnanomolar). FOSO28 has many promising properties but it needs further optimization before it is ready for human testing. The affinity may need to be improved and it is unclear about potential binding properties. Also it seems that the brain penetration will need to be improved (see time-activity curves in figure 7). | ||||||
| (Smith, 2023 #2537) fig2 |
In vitro studies at Tkos for a full characterization of this compound: • clinical imaging data uploaded to our internal (PACS) system. We would like to review the data and conduct our own modeling and analysis of the images generated Method 1: 2019 Krell AD brain. competition with AD binder ([3H] AD BRAIN homogenate (5%), AD binder ([3H][PiB]) IC50 IC compelition 시험기5/4 BRAIN H ([3H]PiB) (이것의 BR low selectivity 방법인듯 value였음). Method 2: ACI-12589, K data 사용한 듯. Method 3: QST: IC50 (selectivity over Aβ) brains (homogenate) | ||||||
| Current status are well described in 2018 Hsieh | |||||||
SPAL-T-06 vs C05-05
| SPAL-T-06 | C05-05 | Round 2 compound | |
|---|---|---|---|
| T-06 has rapid clearance at white matter (low background). 06 is more convenient to use for MSA. | C05-05 has higher WM background and Longer 1 from specific binding (particularly WM 1 background) | it will take about 2 y to evaluate in a clinical study |
Takeda is co-owner of this asset
- Development of αSyn related disease therapeutics at Takeda’s own company/subsidiary/joint development company/contract for: A license agreement is required between QST and Takeda. QST will not demand compensation for non implementation (Article 7 of the patent application agreement).
- Self-implementation for other in-house product development. A license agreement is required between QST, Eisai, Ono and Takeda. QST will demand compensation for non implementation (Article 7 of the patent application agreement).
- Licenses to third parties other than the above. A license agreement is required between QST, Eisai, Ono, Takeda and the license A (Article 8 of the patent application agreement).
- The procedures required for “publishing the data acquired in the above studies” will be stipulated in the above license agreement but at least a review of QST will be required.
co-owner block
- This is being developed by (1) co-owner Dr. Eiko Hiraoshi (Co Makoto Higashi).
- We do not share ownership of this tracer
- but in preliminary conversations with Ch Higashi, there seems to be paths forward to establish a licensing arrangement to the Roto.
- However, it might be too early now to put the licence on this one, on the trigger.
- MJFF industry consortium (of which we are part of) will approach to set up a clinical study of C05-05 in subjects with PD and we should be able