JS PD KB

TAK-071

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TAK-071

Single-program entity page for the Takeda cholinergic / muscarinic M1 PAM (positive allosteric modulator) program TAK-071. Promoted from the therapeutic-programs Entity Backlog. The program-routing context continues to live on therapeutic-programs § Program Matrix; this page collects the program-level evidence package across the single primary source page indexed under the program nav-root. Every substantive statement links back to a source note or the canonical by-photo Markdown. Where the source carries Uncertain Spans, that uncertainty is preserved here rather than smoothed out.

Program Overview

TAK-071 is captured in source as a M1 muscarinic ACh receptor positive allosteric modulator (PAM) that specifically activates post-synaptic neurons, with no effect on M4 or other ACh receptors, with the comparator note that AChEIs increase synaptic ACh longevity. Activation of presynaptic M4 receptors then reduces synaptic ACh release. The single primary source page (20240722_181839) documents the program’s Mechanism, the TAK-071 PD Falls and cognition Timelines – Base Plan (a 2019–2029 multi-track timeline with Clinical Studies, CMC, and Toxicology rows plus a Regulatory overlay), the empty-section Timeline of TAK-071 heading that follows, and the TM of TAK-071 paragraph drawing on (20201211 TAK-071 CDP_NSRB_11Dec2020.docx) to record the program’s biomarker-exploration thinking around resting-state EEG / fMRI gait- variability correlates and a potential IIR or Takeda-sponsored biomarker study gated on study 2002 outcomes via Dr. Lewis Lipsitz, Chair of Gerontology at Beth Israel Hospital.

The same canonical photo continues into cGAS (cyclic GMP-AMP synthase, cGAMP synthase, =mb21d1) > MOA cGAS > Normal / Pathophysiology > Evidence > Borsche 2020 IL6 / PRKN / PINK1 Figure, which is out of scope for this entity and is owned by cgas-cgamp § cGAS — Senescence and the cGAS-STING Pathway and by cgas-cgamp; see Source Scope And Boundary Notes for the page-level boundary handling. The cross- program TAK-071 material on the preceding canonical photo 20240722_181835 (TAK-071 Clinical Plan, TAK-071 Cognition Result Note, TAK-071 Power Table Fragment, plus the body-embedded diagram_tak071_crossover_design.jpg figure asset) is out of scope for this entity’s Source Table because the SNCA ASO (WAVE) nav-root owns that page; it is referenced as a related boundary continuation only, with the canonical owner being snca-aso-wave.

Source Scope And Boundary Notes

This entity is a single-source program: only 20240722_181839 carries the program nav root TAK-071 as its first nav_path entry, and it is the only page indexed under tak-071. The page is fully included for the TAK-071 portion of its content; the program nav root is the first nav_path entry, so the strict “first nav_path entry == program nav root” rule applies without exception at the nav-root level.

The same canonical photo also carries unrelated cGAS / cGAMP pathway material (cGAS (cyclic GMP-AMP synthase, cGAMP synthase, =mb21d1), MOA cGAS > Normal / Pathophysiology, Evidence, and the body- embedded figure_borsche_il6_prkn_pink1_partial.jpg Borsche 2020 PRKN / PINK1 IL6 figure fragment that continues onto the following photo 20240722_181843). That cGAS material is out of scope for this entity and remains owned by cgas-cgamp (which records 20240722_181839 as a capture-order neighbour via the continues_upper_cgas_senescence_evidence related_photos entry on 20240722_181843) and by gba-pd-asyn (which retains 20240722_181839 under its TAK-071 program nav root). The Evidence Package, Key Source Interpretations, Source Table, figure-group, and uncertainty rows below cover only the TAK-071 portion of 20240722_181839; the cGAS portion of the same page is referenced via Related Pages rather than re-narrated here.

The cross-program TAK-071 material on the preceding canonical photo 20240722_181835 is not in this entity’s Source Table because the SNCA ASO (WAVE) nav root owns that page (see snca-aso-wave § Source Scope And Boundary Notes). The TAK-071 portion of 20240722_181835 covers:

  • TAK-071 Clinical Plan (visible header text TAK-071, Executive summary, Clinical plan; the leftmost heading is partly cut at the photo edge);
  • A three-row 1001 / 1002 / K-1-02 OC study study-status table with the additional design text for K-1-02 OC study (PD subjects aged 40 to ≤65 years extensible to ≤85, US-based, ≤6-week screening, two 6-week double-blind treatment periods separated by ≥3-week washout, primary gait-variability endpoint, secondary global- cognition endpoint, exploratory cued-180-turn / TUG / postural-sway / in-home / fall / MDS-UPDRS / CGI / PGI / speech / Epworth panel, FPI: 30 Nov 2020 and LPLV: 27 Feb 2023, Total screened: 106, Number of Subjects Randomized: 54);
  • The diagram_tak071_crossover_design.jpg body-embedded figure (Screening / Period 1 / Washout / Period 2 / Follow-up; N~64; Placebo -> TAK-071 7.5 mg (ages 40 ≤ 65), 5 mg (ages 66 ≤ 85) and the reverse arm; visible duration labels ≤6 weeks, 6 weeks, ≥3 weeks, 6 weeks, 14 days; Top line results: 20230321 (?));
  • TAK-071 Cognition Result Note (STV / d, STV / P, Cognition criteria 0.49 and 0.8, Js: Mean & sd 사용시 0.70, Js: LSM 사용시 0.556, Slide: 0.54, 0.62, P(effect size > 0.49) is 0.62, subjects with both periods: 36, Mean(sd) = 0.285(0.526)); and
  • TAK-071 Power Table Fragment (clipped at the bottom of the photo, with the highlighted row 0.49 / ? / ? / 36 / 36 / ? / 0.62 preserved as Uncertain Span on 20240722_181835).

That TAK-071 material is referenced as a boundary continuation only: per the SNCA ASO (WAVE) entity’s primary-owner rule, this entity does not include 20240722_181835 in its Source Table or Evidence Package. Readers seeking the K-1-02 OC study clinical-plan detail should open the canonical SNCA ASO page directly via snca-aso-wave § Source Scope And Boundary Notes. The three Uncertain Spans on 20240722_181835 that belong to the TAK-071 portion (TAK-071 row label K-1-02 OC study partial-cut, the Js: Mean & sd 사용시 / Js: LSM 사용시 Korean / English notation, and the highlighted TAK-071 power-table row 0.49 / ? / ? / 36 / 36 / ? / 0.62) are owned by the canonical page and are also surfaced by the SNCA ASO (WAVE) entity page as delegated TAK-071 uncertainty.

Adjacent material that is excluded from this entity:

  • The single SNCA ASO (WAVE) source page (20240722_181835) carries the boundary-continuation TAK-071 material described above; its primary owner is snca-aso-wave and it is referenced via Related Pages rather than re-narrated here.
  • The cGAS / cGAMP whole-section topic cgas-cgamp owns the cGAS (cyclic GMP-AMP synthase, cGAMP synthase, =mb21d1) > MOA cGAS branch of 20240722_181839 and the downstream 20240722_181843 / 20240722_181847 cGAS / cGAMP pages; it does not own TAK-071 program data.
  • The capture-order-neighbour cGAS senescence page (20240722_181843) records 20240722_181839 via its related_photos continues_upper_cgas_senescence_evidence entry and is the canonical owner for the cGAS senescence narrative; it does not carry TAK-071 program data.
  • The α-synuclein Tier 1 page alpha-synuclein does not list TAK-071 as a program-row owner; the alpha-synuclein-source-boundary Tier 2 description names TAK-071 only as a sibling-topic / sibling- entity owner (a delegation pointer for any TAK-071 mention rather than a TAK-071 program-evidence row).

The page does not appear under the Pipeline of GD & GBA-PD inherited-thread band in the nav_path (its first entry is TAK-071 — a free-standing program nav root, not a Pipeline of GD & GBA-PD > … > TAK-071 … sub-path), so the entity scope at the nav-root level is unambiguously the single nav-rooted page.

Evidence Package

evidence areasource-captured detailsource
Mechanism — molecule / classa M1 muscarinic ACh receptor positive allosteric modulator (PAM).20240722_181839
Mechanism — TAK-071 selectivityTAK-071 specifically activates post-synaptic neurons, with no effect on M4 or other ACh receptors.20240722_181839
Mechanism — comparator / noteC?) AChEIs increase synaptic ACh longevity. Activation of presynaptic M4 receptors then reduces synaptic ACh release. (the leading C?) row marker is partly cut and recorded as Uncertain Span; see Uncertainties Carried From Source.)20240722_181839
TAK-071 PD Falls and cognition Timelines – Base Plan — figure / year axisThe body-embedded figure_tak071_timeline_base_plan.jpg is the program’s multi-track timeline; the year axis is transcribed verbatim as 2019, 2020, 2021, 2022, 2023, 2024, 2025, 2026, 2027, 2028, 2029 and the legend uses blue Clinical, green CMC/PS, cyan Tox, red triangle Regulatory (format_notes).20240722_181839
TAK-071 PD Falls and cognition Timelines – Base Plan — Follow-up to PRCFollow-up to PRC group activity Follow-up to PRC with dates / milestones PRC-PRC Memo; LDE; Ph 3 studies are placeholders; Phase3 study; markers around 10 Jul28 and 13 Jun29.20240722_181839
TAK-071 PD Falls and cognition Timelines – Base Plan — Clinical Studies rowsPD Gait ePoC 30 Nov20 - 22 Feb23; PD Ph2 Dose ranging/Ph3 Studies (2) 30 Jul24 - 31 May28; PD Long Term Safety 29 Jan25 - 22 Nov29; DDI (2) Studies for CYP3A4 14 Sep22 - 09 May23; IND/NDA Submission/Approval IND; Remove Partial CH; EOP2/EMA-HTA; hADME Study 14 Apr23 - 09 Feb24.20240722_181839
TAK-071 PD Falls and cognition Timelines – Base Plan — CMC rowsCTM for ePOC 01 Oct18 - 31 May20; DS/DP development for Ph3* 30 Aug22 - 31 Aug23; API & CTM for Ph3 (pilot scale)* 30 Aug22 - 25 Jul24; CTM for Ph3 (2nd supply) 01 Jul24 - 03 Apr25; DS/DP registration stability 01 Jul24 - 29 Oct27.20240722_181839
TAK-071 PD Falls and cognition Timelines – Base Plan — Toxicology rows26W Rat 30 Aug22 - 09 Aug23; 39W NHP 30 Aug22 - 12 Oct23; Definitive EFDs 30 Aug22 - 25 Feb23; Male/female Fertility 30 Aug22 - 27 Mar23; TG car study + DRF-SPA 28 Mar23 - 29 May25; 2 year rat car study 29 Jul24 - 27 Nov27.20240722_181839
TAK-071 PD Falls and cognition Timelines – Base Plan — footnotes*Raw material ordering and some DS/DP development begin in 2021. Initiating 6 month prior (Jan 2022) will be additional 0.8 OY.; *hADME, Asian bridging, tQT studies will be conducted after successful ePOC. LDE 1 month after DDI studies.; "Reg team is exploring fast track, and Ph3 digital tools.20240722_181839
Timeline of TAK-071 — heading## Timeline of TAK-071 heading is present in the body but carries no text under it on this page (the timeline detail above sits under the TAK-071 PD Falls and cognition Timelines – Base Plan figure rather than under this heading).20240722_181839
TM of TAK-071 — biomarker exploration(20201211 TAK-071 CDP_NSRB_11Dec2020.docx) Potential IIR or Takeda-sponsored biomarker study: Currently, there is no biomarker for the TAK-071 program, and none is used in the 2002 study. The team has interacted extensively with Dr. Lewis Lipsitz, Chair of Gerontology at Beth Israel Hospital whose research program is focused on falls in cognitively impaired elderly patients. His group has identified resting state fMRI imaging correlates of gait variability in elderly subjects. Resting state EEG or fMRI could be a useful biomarker to explore dose-response relationships in this regard to improve the choice of doses to test in the Ph2b study. A IIR or Takeda-sponsored study can be considered if study 2002 is positive.20240722_181839

Key Source Interpretations

interpretationsource
TAK-071 is recorded in source as a M1 muscarinic ACh receptor positive allosteric modulator (PAM) whose target-engagement claim is specifically post-synaptic — TAK-071 specifically activates post-synaptic neurons, with no effect on M4 or other ACh receptors — with the AChEI comparator framed in the same Mechanism table as a presynaptic-M4 / synaptic-ACh-release tradeoff. The leading C?) marker on the comparator row is partly cut and is preserved as Uncertain Span rather than normalised.20240722_181839
The TAK-071 PD Falls and cognition Timelines – Base Plan is recorded as a multi-track 2019–2029 plan combining Clinical Studies, CMC, Toxicology, and a Follow-up to PRC overlay, with PD Gait ePoC running 30 Nov20 - 22 Feb23 (the same FPI–LPLV window that the SNCA-ASO-page TAK-071 K-1-02 OC study row records — see boundary continuation in Source Scope And Boundary Notes), PD Ph2 Dose ranging/Ph3 Studies (2) 30 Jul24 - 31 May28, and PD Long Term Safety 29 Jan25 - 22 Nov29. The IND / NDA milestones cell carries the placeholder string IND; Remove Partial CH; EOP2/EMA-HTA rather than dated entries.20240722_181839
The CMC track is split between CTM for ePOC (01 Oct18 - 31 May20) and the Phase-3-supply chain DS/DP development for Ph3* / API & CTM for Ph3 (pilot scale)* / CTM for Ph3 (2nd supply) / DS/DP registration stability rows; the asterisk footnotes record that Raw material ordering and some DS/DP development begin in 2021. Initiating 6 month prior (Jan 2022) will be additional 0.8 OY. 0.8 OY is preserved verbatim as Uncertain Span and is not normalised.20240722_181839
The Toxicology track records the rat / NHP repeat-dose package as 26W Rat (30 Aug22 - 09 Aug23) and 39W NHP (30 Aug22 - 12 Oct23), the reproductive/developmental package as Definitive EFDs (30 Aug22 - 25 Feb23) and Male/female Fertility (30 Aug22 - 27 Mar23), and the carcinogenicity package as TG car study + DRF-SPA (28 Mar23 - 29 May25) and 2 year rat car study (29 Jul24 - 27 Nov27); column-by-column timeline date readings should be re-checked at the canonical level (the timeline dates row is recorded as Uncertain Span).20240722_181839
The Timeline of TAK-071 heading appears as a structural header in source but the page carries no narrative under it; the visible timeline content sits under TAK-071 PD Falls and cognition Timelines – Base Plan instead. Downstream readers should not treat the empty heading as missing content.20240722_181839
The TM of TAK-071 paragraph anchors the biomarker discussion on (20201211 TAK-071 CDP_NSRB_11Dec2020.docx) and records that there is no biomarker for the TAK-071 program, and none is used in the 2002 study. The proposed exploration is Resting state EEG or fMRI as a Ph2b dose-response biomarker via the Lewis Lipsitz / Beth Israel Hospital falls in cognitively impaired elderly patients collaboration; a IIR or Takeda-sponsored study can be considered if study 2002 is positive. A IIR, study 2002, and Dr. Lewis Lipsitz are recorded as Uncertain Spans (line-wrap / page-edge readability) and should be re-checked at the canonical level rather than treated as resolved.20240722_181839
The footnote line at the bottom of the timeline records exploratory development items 0.8 OY, tQT, fast track, and Ph3 digital tools (the latter two as Reg-team strategy items); each of these tokens is recorded as Uncertain Span, preserved verbatim, and not normalised on this page.20240722_181839

Source Table

stemnav pathsource notecanonicaluncertain spansembedded images
20240722_181839TAK-071 > Mechanismnotemd112

1 source; uncertain_span_count totals 11; embedded_image_count totals 2. Of the two body-embedded figure assets on this page, only the TAK-071 timeline figure (data/processed/assets/by-photo/20240722_181839/figure_tak071_timeline_base_plan.jpg) is in scope for this entity; the second figure (data/processed/assets/by-photo/20240722_181839/figure_borsche_il6_prkn_pink1_partial.jpg) belongs to the cGAS / Borsche 2020 IL6 / PRKN / PINK1 portion of the same canonical photo and is out of scope here per Source Scope And Boundary Notes (the figure fragment continues onto the following photo 20240722_181843, which is owned by cgas-cgamp). Both figures are linked rather than re-embedded on this entity page per the 2026-04-29 body-purity decision; the figure-only embeds remain at the canonical by-photo level. The source-note nav_path TAK-071 > Mechanism is inferred from the body heading and visible nav entries (the page also includes Timeline of TAK-071, TM of TAK-071, and the start of cGAS > MOA cGAS, so the active nav highlight should be manually confirmed); the source preserves that inference and the Uncertain Spans row labelled nav path (see Uncertainties Carried From Source below).

Figure / Asset Groups In Source

sourcefigure group
20240722_181839TAK-071 PD Falls and cognition Timelines – Base Plan (figure_tak071_timeline_base_plan.jpg): multi-track 2019–2029 timeline with the legend blue Clinical, green CMC/PS, cyan Tox, red triangle Regulatory (format_notes). Preserved as a body-embedded asset because the per-row date bars are easier to inspect visually than as text alone; the per-row text rows are also transcribed in the canonical Markdown table. The Borsche 2020 PRKN / PINK1 IL6 figure fragment on the same canonical photo (figure_borsche_il6_prkn_pink1_partial.jpg) is out of scope for this entity (see Source Scope And Boundary Notes); it is owned by cgas-cgamp and continues onto 20240722_181843.

Uncertainties Carried From Source

issuesource
Page label Page 44 of 50 — Apple Vision and PaddleOCR agree for this statusbar, but adjacent synthesized pages previously showed Page 34 of 40; the exact OCR-visible value is kept pending manual check.20240722_181839
nav_path TAK-071 > Mechanism — inferred from body heading and nav entries; the page also includes Timeline of TAK-071, TM of TAK-071, and the start of cGAS > MOA cGAS, so the active highlight should be manually confirmed.20240722_181839
TAK-071 mechanism comparator row — C?) AChEIs... row label is partly cut/unclear; the mechanism sentence is readable but the leading marker is uncertain.20240722_181839
Timeline title — PD Falls and cognition Timelines - Base Plan right edge is visible but the left/center title is slightly blurred.20240722_181839
Timeline row labels — PD Gait ePoC, TG car study + DRF-SPA, DS/DP registration stability are small text where OCR engines disagree slightly on capitalization / spelling.20240722_181839
Timeline dates — all activity date ranges are small text; copied only when legible in both image / OCR evidence. Re-check the canonical figure rather than acting on the transcribed dates.20240722_181839
Timeline footnote tokens 0.8 OY, tQT, fast track, Ph3 digital tools are small text at the bottom of the timeline; visible wording is preserved pending review.20240722_181839
TM of TAK-071 paragraph tokens A IIR, study 2002, Dr. Lewis Lipsitz are readable but line-wrapped and partly near the right photo edge; re-check the canonical paragraph for exact wording.20240722_181839

The remaining three Uncertain Spans on the canonical page belong to the cGAS / Borsche 2020 portion of 20240722_181839 (cGAS title =mb21d1 gene-symbol normalisation question, cGAS pathway tokens STING (=tmem173) / NF-kB / IRF3 / DRP1 phosphorylation narrow- column OCR fragility, and the Borsche cohort note German / Italian cohort composition right-side photo crop) and are delegated to cgas-cgamp § cGAS — Senescence and the cGAS-STING Pathway per Source Scope And Boundary Notes; they are not duplicated here. The three TAK-071-portion Uncertain Spans on 20240722_181835 (TAK-071 row label K-1-02 OC study partial-cut, the Js: Mean & sd 사용시 / Js: LSM 사용시 Korean / English notation, and the highlighted TAK-071 power-table row 0.49 / ? / ? / 36 / 36 / ? / 0.62) are owned by the SNCA ASO (WAVE) page’s primary owner snca-aso-wave and are not duplicated on this entity page either.

  • therapeutic-programs — program-routing map; this entity page is the canonical owner for the TAK-071 row that was previously listed as an Entity Backlog Candidate.
  • tak-071 — per-nav-root index for TAK-071 (1 source — the single TAK-071 > Mechanism page).
  • gba-pd-asyn — section index containing the single source used here (filed under its TAK-071 program nav root).
  • gba-pd-biology — sibling GBA- PD biology synthesis that lists 20240722_181839 in its § Source Boundary / Delegation as the TAK-071 cluster delegated to this entity.
  • cgas-cgamp — owner of the cGAS portion of 20240722_181839 (`cGAS (cyclic GMP-AMP synthase, cGAMP synthase, =mb21d1) > MOA cGAS > Normal / Pathophysiology > Evidence

    Borsche 2020 IL6 / PRKN / PINK1 Figure`); cGAS material on this page is delegated rather than re-narrated here.

  • cgas-cgamp — section index for the cGAS / cGAMP arc that the lower portion of 20240722_181839 hands off into via 20240722_181843.
  • snca-aso-wave — primary owner of the preceding canonical photo 20240722_181835, which carries the boundary-continuation TAK-071 material (TAK-071 Clinical Plan 1001 / 1002 / K-1-02 OC study rows, the diagram_tak071_crossover_design.jpg crossover diagram, the TAK-071 Cognition Result Note, and the TAK-071 Power Table Fragment); referenced from this entity rather than re-narrated.
  • source-catalog — all 447 sources in capture order (TAK-071 source is row 14).
  • nav-path-index — 376 distinct nav_paths.
  • document-outline — top-level pipeline outline.
  • tak-341 — sibling Takeda program entity (passive-immunotherapy modality; same in-house program-entity precedent).
  • snca-btv-hdo — sibling Takeda program entity (oligonucleotide modality; same in-house program- entity precedent for a single-source program).
  • asyn-propagation-suppressor — sibling Takeda program entity (small-molecule phenotypic-screen umbrella; same single-source program-entity precedent).
  • parkn-gt — sibling program entity (different modality class; same in-house program-entity precedent).
  • nlrp3-inhibitor — sibling program entity (small-molecule modality; same program-entity precedent).
  • pr001 — pilot-scope GBA gene-therapy program entity (sibling within the GBA-PD pilot).
  • Build Note, Sidebar, KB Index, Build Log — KB structure.

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