assess the potential of UDCA treatment to be beneficial in a larger patient population.)
UDCA → normalized ATP, MMP, MC1 activity (but not MC4 activity)

20231129Estrella, Heather Recent input from a clin ops pgm manager today for aVb1 program about PDE:
PDE need - next PRC interaction after PE. Want to see progression from PE.
Sharing clinical vision on how want to develop asset - ePOC options and recommendation to demonstrate efficacy in target patient population. Doesn't have to be in the indication that want to develop in...
Biomarkers - To do the ePOC study, need the biomarkers going to measure (either surrogate (if chronic indication) for efficacy or efficacy itself). For surrogates, need to understand modulation can achieve in preclinical species.
Measure biomarkers - How get to clinical assay in order to measure.
Material plan - IND-enabling activities to do at risk to ensure have GLP material for post-candidate selection.
CDP and TPP

Narrative needs to be succinct
Give options to PDE.

Pre-meetings:
Development Review Forum (DRF) - With Translational group to review clinical development plan (CDP). Need 2-weeks from end of review before pre-reads due for PDE. Ideally 3 months prior. 60-70% of PDE narrative complete -
Disease background
Target and efficacy review - evidence clinical trial will be successful.
How project human dose
Options for clinical plan
Regulatory plan
CMC plan
20231013DevyaniWe can certainly schedule NLRP3 for later in March 2024. However, I would first like to ask that this program has been delayed times now, and just want to make sure that the team is still targeting coming to PDE around CN and not later than that. At PD will still be a lot of unknowns, that's fine. The PRC wants to provide directional input at CN to allow for ample time in shaping strategy towards IND. Coming too late in the process may actually defeat the purpose of the PDE discussion. (at least 6 month CS)
deviyani Presentation: more detail than PE presentation,
Resource gap: ? this should be operational risk,
Scientific risk > operational risk,
Timeline: PDE → CE (IE EDE), OPTIONS TO Epoc, how to show Epoc, (IS therea faster one?), epoc → poc,
Earliest signal to give us confidence, what are the methods, what the sure one, different timing, readout sooner,
Pros & cons, among options team's recommendation, PRC would give direction,
Reason of pde: disconnect between pe vs ede,
To give feedback before IND,
Timeline: little bit after CN but definitely before CS,
Asset discussion x, TPP X, Focus is on early clinical plan, BM clin, CMC,, roa,
China: is there cmc problem? Number of subject? Include china on registrational trial? Prevalence difference in china?, china publishes every year on rare disease, no specific epidemiology study,
Diversity: high level, are you going to include diversity?
Digital: devices (ann Heatherington), just binary question (just a question, if you want or not),
Just say: the same as previous PE narrative,
10 pages text, figures in text, recocc, TPP, decision tree, in main text, tpp no text in appendix, appendix has to have
20 pages in total, no change from PE, can send her draft, they are messangeers, between senior leadership,
Cmd or any other section: if issue, highlight, (raise hand),
Meeting with PRC office over PDE-rough notes
January 10 2023

Generally the Pde narrative should (a) be high level only, 10pgae +~10pages of appendix (b) focus on Translational and clinical, not other topics
  • Can assume PRC members have the PE document for other sections and if no change its possible to just write "no change from PE"
  • No asset discussion
  • Within clinical and translational plan one focus is risks and mitigations, at a high strategic level
  • The second focus is ePOC options and PROs and CONs, encouraging a discussion also on options that are more exploratory and risky ("sometimes the ePOC is almost POc"), the team should have a recommendation but explore additional scenarios
Another area of focus is manufacturing (a) in case it risks the clinical plan (b) ROA considerations might also need to be discussed.

Timeline needs to be detailed only up to CDE, after that (up to ePOC can be based on assumptions) - operational details beyond high level risks are not a focus.

The context is that CDE is too close to the clinic, and doesn't allow high level discussion (and too far after PE), the idea was to have PDE (1) ~1y before IND to allow time for changes (2) before CS to influence CS

There are a few general things introduced to PRC documents - digital plan, china elevation and patient diversity plan. At the level of PDE is more like a Yes/No question -
  • when/if china will be in clinical development (should already be introduced at PE)
  • is the team planning diversity goals (and then diversity will be part of GPT topics)
  • digital tool overview - new topic, might need to consult with Anne what is desired
(no clear guidance how to introduce it, will evolve over time)

First team is going in Feb. 26 (oncology). Second is rare ( TAK-028) on March 16. DMPK-MTV will need to update on new desired date.
[20240315]
  • narrative
    • 10 pages of text including tables,
      • No figures in text section. (just say "refer to the slide #9 " for a figure)
    • 1 page Executive summary
    • (reference not allowed)
    • (appendix not allowed)
  • Slides
    • 10 pages
Neta Philip's thought? GO, Stat (to address Anne Heatherington), Epoc , AH: criteria for success? TST (Allen Cristi?)
45 minutes for PRC1, the applicable TAU Head, DDU Head, TA Franchise Head, GPL and GPM
  • • Head Global Product & Launch Strategy
  • • Head Global Clinical Operations
  • • Head Global Portfolio Strategy
  • • Head R&D Strategy & External Innovation
  • • Head Pharmaceutical Sciences
  • • Head Global Regulatory Affairs Oncology (for all Therapeutic Areas)
  • • Head of Preclinical and Translational Sciences
  • • Head Drug Safety & Evaluation
  • • Head Quantitative Clinical Pharmacology
  • • Internal rotating member
20221215 minute:Meeting with Ceri, PDE timing will be discussed with Ceri - The PDE is rescheduled from 16 Feb to 25 Apr. CS would be delayed to Q1 FY25
Email: ?
20230104 minute:Option 1 -TR098; target PDE and CS are 25th Apr and May email: O
40225 Jay (CYP7A1 ) Conditional approval, lead sequence: tox, BST is mportant recommendation, vendor selection. Feasibility, $ involved.
Budget request including asset, tox etc. "developability"
40229 Sarah Menu- associated cost: js:
Tspo petClinical trial cost involving tspo pet
Csf bmExisting assay: IL-18Vendor,
NOVEL assay
0404 Narrative
  • Narratives will now only contain text
  • Page Limit: 10 pages (no figures in within the text; tables are OK)
  • Font size: no less than 10 pt
  • Margins: no less than 1 inch
  • Template: Fit-for-purpose, 9 Narrative Frameworks available on our SharePoint
  • Do not include: Table of Contents, Appendices
Figures
  • No presentations; slides are now part of the narrative: displaying key figures/graphs/charts, thereby removing the need to duplicate information between the narrative & slides.

Uncertain Spans

locationtranscriptionuncertainty
header glyph above 20231129 row卜⊞)ㅂA 2-3 character glyph appears just above the first meeting-log table; OCR returns mixed CJK characters but the source is partly cut and may simply be a Word-internal anchor; preserved verbatim.
40225 Jay rowBST is mportant recommendationOCR returns mportant (missing leading i); preserved verbatim as printed.
40229 Sarah inner sub-tableCsf bm row continuation columnsThe right-most column of the sub-table is mostly empty in the source; preserved as empty cells.