PET aSyn — QST Specified Clinical Trial planning (Operational lead, Funding MJF, Schedule, IND, Goal, Protocol, Process, Contract, Freedom to operate, GLP-Tox)

QST Specified Clinical Trial — planning (PET aSyn vendor matrix continuation)

[20230809] CS to Check timeline to use a PET for SPAL-T-06 clinical studies, and Reach out to MJFF, to see if they would like to collaborate on SPAL-T-06 clinical studies. Paul Ito, Reach out to Yutoo to check required dataset for PET IND in US.

TakedaQST as Specified Clinical Trial
Operational lead
Estimated costTBD~80M JPY (= US 559K JPY for actual drug manufacturing cost of SPAL-T-06 1Q SPAL-T-86 IFM 5 incidung tax)
FundingMJF (full vs partial? TBD)
The SPAL trials will keep SPAL-T-06 patent. If MJFF industry consortium participants would like to use SPAL-T-06, they have to have license agreement.
Ono, Takeda, and potentially QST. (not MJF)
Takeda has announced the withdrawal from the SPAL-T-06 longitudinal study in Japan as QST and Ono Pharma before signing a contract because of no budget.
ScheduleAll the data generated by the MJFF collaboration have to be shared with MJFF industry consortium participants (e.g. Merck, Biogen) and will be public information after an embargo period. → 20231113 One set to join.

8 months in total (2-3 months for IND and 4 months to finalize protocol).

a joint research agreement 2025 fall: interim draft analysis results of data up to 12 months (at least about 10 cases) — summer of 2025
INDNOT need IND filing because of Specified Clinical Research by QST
Goal (1) Enrichment of baseline data by a larger number of subjects than in specific clinical studies of FIH; Comparison between MSA-P and MSA-C, Correlation with UMSARS, (correlation with other items, BMI, etc.)
(2) Examination of changes over time (6 months, 12 months); Correlation between SUVR change rate and UMSARS change rate in key areas of interest, etc.

[from Ono]
Protocol -Target: Patients with MSA-P or MSA-C (~10-15 patients in total)
-Entry criteria: <5 years of onset
-PET imaging points: 3 time points (0m, 6m, 12m)
live α-syn in CSF and/or plasma and NFL in plasma. Plasma sampling WITHOUT CSF should be feasible to proceed the longitudinal study in a timely manner.
Protocol-BMOno agreed to the CSF sampling in US of planned
Protocol-ToxOna has low priority of 1mo PET in an accumulation of tau in MSA seems to be important
ProtocolProtocols in Japan and US should be identical as much as possible. Dr. Higuchi is planned join discussion with MJFF and lawyers about the study in US.
Process Propose plan to MJFF consortium, make an agreement with MJFF and SPAL team, and transfer data for IND filing.
  • Research Agreement between MJFF, QST, and Takeda. Drafter should be fixed after discussion with MJFF and QST. → Then alliance team to lead.
  • License Agreement from QST, Eisai, Ono, and Takeda (Article 8 of the patent application agreement). The necessity depends on the research contract with MJFF. The agreement should be obtained easily without tough negotiation if necessary.
Contract Agreement with QST, Eisai, Ono, MJFF, and Takeda to disclose confidential information to MJFF (Article 12, from 5 of the patent application agreement). If undisclosed information is shared with MJFF, the agreement is required → The agreement would be required to share non-GLP tox and dosimetry data for IND filing in US.
Freedom to operate License Agreement 한송이라 어... 20230914 a-syn PET Pleockefelder "Freedom to operate" SPAL T-06.pdf Fushimi, Makoto

The SPAL T-06 kickoff meeting with QST about MJFF industry consortium will be held on 30/31 Jan 2024.
Attendees:
  • QST: Drs. Higuchi, Mitumi, and Hwoguchi
  • Takeda: Cristian, Paul, Manori, Koji, and Makoto
Outcome 1: to Propose SPAL T-06 longitudinal study to MJFF, Funding from MJFF, nothing from Takeda
GLP-Tox cost: approx. 8 mil yen + GLP test substance manufacturing cost.
20230706 Keep discussion with QST and Ono about SPAL-T-06 GLP tox study and longitudinal study.
Higuchi from QST: Join both discussion for US & Jap to have identical protocols as much as possible