Therapeutic Programs / Pipeline Overview

Synthesis layer over the canonical by-photo corpus. This page is a program map. Per-program narrative lives on the existing topic and entity pages; this page does not re-narrate program detail. Every substantive statement links back to a topic, entity, source note, or canonical by-photo Markdown. Where the source carries Uncertain Spans (program codes, dates, exponents, dose tokens), the routing here defers to the owner page rather than hardening the value.

Overview

The corpus’s therapeutic content is distributed across four layers: (1) the GBA-PD pilot range with Pipeline of GD & GBA-PD and per- compound rows for Eliglustat, Ambroxol, Venglustat, and PR001; (2) the four aSyn-targeting program nav-roots (TAK-341 (MEDI1341), SNCA ASO (WAVE), SNCA BTV (HDO) (PFR-4067-100), aSyn programs > aSyn Propagation Suppressor / aSyn Degrader) routed through alpha-synuclein; (3) the PARKN GT (Takeshi Hioki, PFR-4249-100) AAV9-Parkin gene-therapy arc owned by parkn-gt and parkin; and (4) the NLRP3 inhibitor (Marianthi) (PFR-4231-100) small-molecule arc owned by nlrp3-inhibitor and inflammation. Two further single-page program references — TAK-071 cholinergic/muscarinic M1 PAM (note; md, with the ASO/PD power-table fragment also visible on md) and the Pipeline of LRRK2 > … > DNL201 (=GNE-7…) / DNL151 (=BIIB12…) LRRK2 row — sit in lrrk2 without a synthesis owner and are tracked here as backlog. The Pipeline-of-PD competitor inventory (Prasinezumab, Cinpanemab, Lu AF82422, ABBV-0805, Affitope PD01A / PD03A, UB-312, NPT200-11, Anle138b, ABL301, UCB0599 / minzasolmin, NITROME, AAV2-GAD / MeiraGTx, etc.) is treated as in-axis evidence inside the relevant topic and is not promoted to a program row here.

Source / Page Ownership Rules

The map follows three placement rules so that no two pages claim ownership of the same program rows.

  1. Per-program nav-root anchors a single owner. When a program has a dedicated nav_path first-entry (e.g. PARKN GT (Takeshi Hioki, PFR-4249-100), NLRP3 inhibitor (Marianthi) (PFR-4231-100), SNCA ASO (WAVE), SNCA BTV (HDO) (PFR-4067-100), TAK-341 (MEDI1341), aSyn programs, TAK-071, DNL151 (=BIIB12...), Pipeline of LRRK2), the owner is whichever existing topic/entity page narrates that program. Where two pages overlap (PARKN GT lives in both parkin and parkn-gt), the entity page is the canonical program view and the topic page delegates per-axis context.
  2. Compound-page anchors GBA-PD pilot rows. Eliglustat / Ambroxol / Venglustat / PR001 trial and biomarker rows live on the per-compound entity pages; gba-therapeutics is the strategy-comparison map across them and gba-pd is the GBA-PD problem framing. The biomarkers (GBA-PD pilot) page seeds biomarker logic and is bounded by the same 20240722_181748_181809 source range.
  3. Program matrix routes; it does not narrate. Each row in the ## Program Matrix table below names exactly one owner page and one source-coverage anchor. Per-program detail (timeline, biomarker plan, decision tree, sample-size logic, competitor landscape) lives on the owner page, not here. Boundary contradictions (e.g. PARKN GT decision-matrix scope vs Lewy- pathology Parkin row; aSyn Tier 1 source delegation) are surfaced under Uncertainties / Boundary Notes but resolution is deferred to the owner page.

Program Matrix

The matrix below covers therapeutic programs that have either an internal program code (PFR-…), an internal program lead, or a dedicated nav_path first-entry in the corpus. Pipeline-of-PD competitor row programs (Prasinezumab, Cinpanemab, Inzomelid / NodThera / Selnoflast / Ventyx, etc.) are not promoted to rows here; they live as in-axis evidence on alpha-synuclein, inflammation, nlrp3-inhibitor, or the corresponding sections/<slug> page.

programmodality / targetowner pagesource coverage anchorKB statusnotes
PR001 (LY3884961)AAV / GBA gene therapypr001md, md, md, with PROPEL / PROVIDE / PROGRESS clinical-trial row continuation on mdentity (seed)GBA-PD pilot range; see gba-therapeutics for cross-strategy comparison.
AmbroxolPharmacological chaperone / GBA activatorambroxolmd, mdentity (seed)Source flags null mutations as not useful targets.
Venglustat (GZ/SAR402671 / ibiglustat)GCS inhibitor (SM)venglustatmd, mdentity (seed)MOVES-PD 52-week MDS-UPDRS II+III result reproduced on the entity page.
Eliglustat (Cerdelga)GCS inhibitor (SM, marketed for GD1)eliglustatmd, mdentity (seed)PD relevance marked uncertain in source summary.
PARKN GT (PFR-4249-100)AAV9 / Parkin (PRKN) gene therapyparkn-gt19 sources: see entity Source Table; topic context in parkinentity (seed)Decision matrix excludes aSyn-related biomarkers — see boundary note below.
NLRP3 Inhibitor (Marianthi) (PFR-4231-100)NLRP3 small moleculenlrp3-inhibitor11 sources: see entity Source Table; topic context in inflammationentity (seed)Series 5c (TR06798980 / TR06802042 / TR06851074) is the lead chemistry per source.
TAK-341 / MEDI1341aSyn antibody (passive immunotherapy)tak-3415 sources: see entity Source Table; topic context in alpha-synuclein § Antibody and Immunotherapy Programsentity (active)md PK/PD model and md Clinical studies anchor the program; cross-pipeline rows on md, md, md. By-nav: tak-341-medi1341.
SNCA ASO (WAVE)SNCA mRNA RNase-H ASOsnca-aso-wave1 source: see entity Source Table; topic context in alpha-synuclein § Antibody and Immunotherapy Programs / SNCA-Knockdown Programsentity (active)md Clinical plan of SNCA ASO anchors the program. By-nav: snca-aso-wave.
SNCA BTV (HDO) (PFR-4067-100)BTV-conjugated heteroduplex oligonucleotide (HDO) targeting SNCAsnca-btv-hdo1 source: see entity Source Table; topic context in alpha-synuclein § Antibody and Immunotherapy Programs / SNCA-Knockdown Programsentity (active)md Executive summary (Ryouta Maeda) anchors the program. By-nav: snca-btv-hdo-pfr-4067-100.
aSyn programs umbrella (aSyn Propagation Suppressor / aSyn Degrader)Small-molecule phenotypic-screen umbrellaasyn-propagation-suppressor1 source: see entity Source Table; topic context in alpha-synuclein § Antibody and Immunotherapy Programs / SNCA-Knockdown Programs umbrellaentity (active)md aSyn programs > aSyn Propagation Suppressor page anchors the SM Propagation Suppressor / aSyn Degrader axis. By-nav: asyn-programs.
TAK-071Cholinergic / muscarinic M1 PAMgba-pd-asyn (single source)md; related power-table fragment on mdsection-onlyNo topic synthesis; backlog candidate for an entity page. By-nav: tak-071.
DNL151 (=BIIB12…)LRRK2 kinase inhibitor (Denali / Biogen)lrrk2 (single source)mdsection-onlyNo topic synthesis; backlog candidate. By-nav: dnl151-biib12.
DNL201 (=GNE-7…)LRRK2 kinase inhibitor (Denali / Genentech)lrrk2 (single source, sub-path)md under Pipeline of LRRK2 > Summary (Schneider…) > DNL201 (=GNE-7…) > Clinical trialssection-onlyNo topic synthesis; backlog candidate. By-nav: pipeline-of-lrrk2.
GAPFREE3 / Preclinical support (MC1 PET radioligand bench)[3H]BCPP-EF saturation-binding bench on PARK2 / sPD fibroblastsparkin § Preclinical Support And MC1 PET Radioligand Workmd, md, md, md, with iPSC adjacency on mdtopic-onlyNo standalone program / entity page; the radioligand work supports the PARKN GT MC1 PET biomarker plan.

Across the 14 program rows (4 GBA-PD pilot rows: PR001, Ambroxol, Venglustat, Eliglustat; 2 internal-program-code rows: PARKN GT, NLRP3 Inhibitor; 4 aSyn-cluster rows: TAK-341, SNCA ASO, SNCA BTV, aSyn programs umbrella; 1 single-page cholinergic row: TAK-071; 2 LRRK2 rows: DNL151, DNL201; 1 radioligand-bench row: GAPFREE3 / Preclinical support), source coverage anchors the matrix to existing topic/entity pages or to source notes for single-page programs. The KB status column distinguishes entity (seed) / entity (active) rows (have a dedicated entity page; the aSyn programs umbrella (aSyn Propagation Suppressor / aSyn Degrader), SNCA ASO (WAVE), SNCA BTV (HDO) (PFR-4067-100), and TAK-341 / MEDI1341 are the most recent active promotions, leaving all four aSyn-cluster rows on entity pages) from topic-only (Tier 1) rows (narrated inside an existing topic-level synthesis) and section-only rows (only listed by section / by-nav, no synthesis). The matrix excludes pure-competitor / external-pipeline rows; see the topic pages for the in-axis competitor inventory.

Existing Entity Pages

These entity pages are the canonical program views in the KB. Source counts and provenance totals come from each entity’s own Source Table; this page does not duplicate them.

entitytypeprogram codeprogram leadowner sectionowner topic
pr001programLY3884961 (Prevail)gba-pd-asyngba-therapeutics, gba-pd
parkn-gtprogramPFR-4249-100Takeshi Hiokiparkinparkin
nlrp3-inhibitorprogramPFR-4231-100Marianthiinflammationinflammation
tak-341program— (Takeda / AstraZeneca / MedImmune)gba-pd-asynalpha-synuclein
snca-btv-hdoprogramPFR-4067-100Ryouta Maedagba-pd-asynalpha-synuclein
snca-aso-waveprogram— (Takeda / Wave Life Sciences)gba-pd-asynalpha-synuclein
asyn-propagation-suppressorprogramgba-pd-asynalpha-synuclein
ambroxolcompound— (ABX)gba-pd-asyngba-therapeutics
venglustatcompoundGZ/SAR402671gba-pd-asyngba-therapeutics
eliglustatcompoundCerdelgagba-pd-asyngba-therapeutics

Programs Covered By Topic Pages Only

These programs are narrated inside an existing topic synthesis but do not have a standalone entity page. The owner topic carries the per-axis narrative; the by-nav indexes carry per-stem coverage.

programowner topic axisowner sectionby-nav indexsource-notecanonical
Pipeline of PD aSyn - Antibody / Small molecules / Vaccine competitor inventoryalpha-synuclein § Antibody and Immunotherapy Programs (Pipeline of PD rows)gba-pd-asynpipeline-of-pdnote, note, notemd, md, md
Pipeline of PD GT row (AAV2-GAD / MeiraGTx, UB-312, PD01A long-term, MEDI1341 SAD)clinical-pdclinical-pdpipeline-of-pdnotemd
GAPFREE3 / Preclinical support ([3H]BCPP-EF MC1 PET radioligand bench)parkin § Preclinical Support And MC1 PET Radioligand Workparkingapfree3, gapfree3-ipsc-yuya-kunisada, preclinical-supportnote, note, note, note, notemd, md, md, md, md

Entity Backlog Candidates

These programs are visible in existing KB pages but do not yet have a dedicated entities/programs/<slug>.md or entities/compounds/<slug>.md page. They are listed here as backlog only; this pass does not create any new entity pages. Promotion is gated by enough source material (or owner page narrative) to support a per-program Evidence Package and Source Table.

backlog candidaterationale to promoteowner / source pointersuggested entity slug
TAK-071Single Tier 1 source with Mechanism, TAK-071 PD Falls and cognition Timelines – Base Plan, Timeline of TAK-071, TM of TAK-071 headings; cross-reference power-table fragment on the SNCA ASO page.gba-pd-asyn; noteentities/programs/tak-071
isofagomineMentioned in the GBA-PD pilot summary area before eliglustat (gba-therapeutics Strategy Map row) and on adjacent GBA-PD pages. Coverage is light — promote only if cross-page evidence justifies an entity page.gba-therapeutics; md, md, md, md, md, mdentities/compounds/isofagomine
GAPFREE3 (program)Multiple nav_path first-entries (GAPFREE3, GAPFREE3 (iPSC, Yuya Kunisada), GAPFREE3 > Preclinical support, GAPFREE3 > Preclinical support > ARG); the radioligand bench supports PARKN GT MC1 PET. Owner topic narrates but does not isolate the program.parkin; note, note, noteentities/programs/gapfree3
DNL151 (=BIIB12…) / DNL201 (=GNE-7…)LRRK2 kinase inhibitor program (Denali / Biogen / Genentech). Two single-source rows with preclinical and clinical-trial headings.lrrk2; note, noteentities/programs/dnl151 (or umbrella denali-lrrk2)
AAV2-GAD / MeiraGTxListed under the Pipeline of PD > GT row on 20240722_184333 alongside UB-312 / Vaxxinity, PD01A long-term notes, and active-vs-passive-immunisation pros/cons. Currently no owner topic.clinical-pd; noteentities/programs/aav2-gad

Pipeline-of-PD competitor rows that surface inside the alpha-synuclein § Antibody and Immunotherapy Programs axis (Prasinezumab, Cinpanemab, Lu AF82422, ABBV-0805, Affitope PD01A / PD03A / ACI-7104 / VacSYn, UB-312 / Vaxxinity, NPT200-11 / Neuropore, Anle138b / MODAG / TEVA, ABL301 / ABL Bio / Sanofi, UCB0599 / minzasolmin, BIIB101 / ION464 / Ionis, NITROME) are external comparators, not internal programs. They are not entity-backlog candidates in this pass; the canonical home for their per-program detail is the same topic axis. The same applies to the NLRP3 inhibitor competitor inventory carried by nlrp3-inhibitor (Inzomelid / Inflazome / Roche, Selnoflast / RO7486967 / RG-6418, NodThera NT-0796 / NT-0249 / NT-0527, Ventyx VTX-2735 / VTX-3232, Ventus VENT-02, Novartis DFV890 / IFM 2427, Dapansutrile / Olatec, Neumora, Halia, Genali, MCC950).

Cross-topic Dependencies

Programs sit across multiple topic clusters. The dependencies below are routing pointers, not double-narration.

  • GBA-PD ↔ aSyn. PR001 / Ambroxol / Venglustat / Eliglustat per-compound CSF total / phospho / insoluble / proteinase-K-resistant α-syn readouts are recorded on the per-compound entity pages and on the GBA-PD pilot pages. The whole-page α-syn synthesis is the Tier 1-only alpha-synuclein; per the alpha-synuclein source boundary map, the GBA-PD pilot range is delegated to gba-pd / gba-therapeutics and the per-compound entity pages.
  • PARKN GT ↔ aSyn / Mitochondria / PET-Imaging. PARKN GT (parkn-gt) carries an aSyn PFF preclinical-model row in its in-vivo evidence table while explicitly excluding aSyn-related biomarkers from its clinical biomarker plan. MC1 PET / [18F]BCPP-EF is the program’s imaging biomarker (delegated to mitochondria for tracer mechanism context and to pet-imaging for tracer-development framework). Parkin PET TE biomarker work is delegated to the parkin § Preclinical Support And MC1 PET Radioligand Work axis.
  • NLRP3 Inhibitor (Marianthi) ↔ Inflammation / PET-Imaging / Biomarkers-Outcomes. The program’s Microglial Imaging axis ([18F]DPA714 / [18F]FEPPA, TSPO rs6971 Ala147Thr) bridges inflammation § Imaging Neuroinflammation and pet-imaging § Microglial Imaging — TSPO. The AD Assays of pyroptosis cytokine / chemokine omics axis bridges to biomarkers-outcomes. The Havrda / Katy KOL strands are owned by inflammation § Competitor / In Vivo Strategy / KOL (Havrda, Katy).
  • TAK-341 / SNCA ASO / SNCA BTV ↔ aSyn / PET-Imaging. All three aSyn-targeting programs carry a PET workstream — TAK-341 PK/PD model with MEDI1341 brain penetration 0.1 %, SNCA ASO PET SNCA ASO biodistribution plan, SNCA BTV HDO PET Development Workflow (Steps 1–4 with Paul McQuade questions). PET tracer-development context lives on pet-imaging; the program-specific PET plans live on alpha-synuclein § Antibody and Immunotherapy Programs.
  • Pipeline-of-PD comparators ↔ aSyn / inflammation / LRRK2. Cross-program comparator rows on 20240722_184324 / 20240722_184327 / 20240722_184330 / 20240722_184333 (Pipeline-of-PD aSyn-Antibody, aSyn-Small molecules, aSyn-Vaccine, GT) link cleanly into alpha-synuclein; the LRRK2 row is delegated to lrrk2.
  • GBA-PD ↔ Biomarkers-Outcomes. Biomarker-development framework, scales (UPDRS / MoCA / RBD / SCOPA-AUT), NFL, and sample-size logic for GBA-PD trials live on biomarkers-outcomes; the seed biomarkers (GBA-PD pilot) page is bounded to the same 20240722_181748_181809 source range as the GBA-PD pilot.

Compact Provenance Table

This table lists one source-coverage anchor per program row (the source most central to the program’s narrative on its owner page). It is not a replacement for the per-program Source Tables on the entity / topic pages. Cross-program coverage continues there.

programanchor stemnav path / headingsource notecanonical
PR001 (LY3884961)20240722_181809Pipeline of GD & GBA-PD > Prevail PR001notemd
Ambroxol20240722_181756Pipeline of GD & GBA-PD > Venglustat (Ibiglustat)notemd
Venglustat20240722_181800Pipeline of GD & GBA-PD > Prevail PR001notemd
Eliglustat20240722_181748Pipeline of GD & GBA-PD > Summarynotemd
PARKN GT (PFR-4249-100)20240722_182021Parkin > PARKN GT (Takeshi Hioki, PFR-4249-100)notemd
NLRP3 Inhibitor (Marianthi) (PFR-4231-100)20240722_183153Pipeline of Inflammation > Pipeline CAPS > Animal model > TM > NLRP3 inhibitor (Marianthi) (PFR-4231-100)notemd
TAK-341 / MEDI134120240722_181818Pipeline of GD & GBA-PD > TAK-341 (MEDI1341) > PK/PD modelnotemd
SNCA ASO (WAVE)20240722_181835SNCA ASO (WAVE) > Clinical plan of SNCA ASOnotemd
SNCA BTV (HDO) (PFR-4067-100)20240722_181831SNCA BTV (HDO) (PFR-4067-100) > Executive summary (Ryouta Maeda)notemd
aSyn programs umbrella20240722_181827aSyn programs > aSyn Propagation Suppressornotemd
TAK-07120240722_181839TAK-071 > Mechanismnotemd
DNL151 (=BIIB12…)20240722_183410DNL151 (=BIIB12…) > Clinical trials > Preclinicalnotemd
DNL201 (=GNE-7…)20240722_183407Pipeline of LRRK2 > Summary (Schneider…) > DNL201 (=GNE-7…) > Clinical trialsnotemd
GAPFREE3 / Preclinical support20240722_184138GAPFREE3 > Preclinical supportnotemd

Uncertainties / Boundary Notes

These are routing-level uncertainties. Per-program Uncertain Spans are owned by the source notes and the owner pages; this list captures only the cross-program / map-level boundary issues worth flagging before any downstream extraction.

  • PARKN GT decision-matrix scope contradiction. The decision matrix on md records that aSyn-related biomarkers are not planned for PARKN GT because aSyn pathology is rarely observed in the target population, while the Lewy-pathology Kalia and Kalia table on md records Parkin as + for protein-in-LB and +/- for LB-associated-with-disease. The same contradiction is recorded on parkin and on alpha-synuclein § Parkin / PARKN GT ↔ aSyn Link; the alpha- synuclein source boundary map also flags it.
  • NLRP3 Inhibitor program-source vs nav-root scoping. Of the 11 sources on nlrp3-inhibitor, only 2 carry the program nav root as their first nav_path entry (per the entity’s Source Scope And Boundary Notes). The Havrda KOL / Katy in-vivo pages (20240722_183225, _183228, _183234, _183238, _183241) are tightly coupled to the program in content but do not reference the program nav root, so they are catalogued at the topic level under inflammation § Competitor / In Vivo Strategy / KOL (Havrda, Katy) instead. Re-check before promoting any to entity-page rows.
  • PARKN GT trailing-comma / GBA-PD-section overlap. 20240722_182103 is filed under sections/gba-pd-asyn because the discovery layer assigned it to the GBA-PD cluster from its PE I Imaging GBA / PRC1 PE narrative content, but its first nav_path entry is PARKN GT (Takeshi Hioki, PFR-4249-100) > RD DDU's PET Imaging GBA > PK/PD Strategy, so the entity page includes it. 20240722_182113 carries the trailing-comma Parkin, first nav root rather than the long PARKN GT heading, so it is not in the per-nav-root index but is included in the entity page’s Source Table. Map consumers should follow the entity-page Source Table for canonical PARKN GT scope.
  • aSyn Tier 2 / Tier 3 delegation. Per the alpha-synuclein source boundary map, 145 Tier 2 and 54 Tier 3 candidate aSyn sources are delegated to sibling topic syntheses or section pages and are not re-narrated on alpha-synuclein. This page does not promote any of them to a program row; the Pipeline-of-PD competitor inventory is the only multi-program block surfaced via the topic page, not via this map.
  • Single-source backlog risk. TAK-071, GAPFREE3, and DNL151 / DNL201 each have 1–2 source pages of evidence. Promoting any of them to an entity page should follow the parkn-gt / nlrp3-inhibitor / tak-341 / snca-btv-hdo / snca-aso-wave / asyn-propagation-suppressor / pr001 precedent (Evidence Package + Source Table + Uncertainties Carried From Source) and should preserve Uncertain Spans rather than paraphrase them. The newly promoted asyn-propagation-suppressor (1 source: the single aSyn programs > aSyn Propagation Suppressor page, sharing the upper portfolio-grid fragment with the sibling SNCA BTV / SNCA-ASO / TAK-341 program rows that are delegated out), snca-aso-wave (1 source: the single SNCA ASO (WAVE) Clinical plan of SNCA ASO page, sharing the canonical photo with TAK-071 content that is delegated out), and snca-btv-hdo (1 source: the single SNCA BTV (HDO) (PFR-4067-100) Executive summary page) are the closest precedents for a single-source aSyn-program entity, alongside tak-341 (5 sources: 2 TAK-341 nav-rooted primary pages + 3 Pipeline-of-PD cross-pipeline pages) for a small-source aSyn-program entity.
  • Pipeline-of-PD competitor scope. The competitor rows on 20240722_184324 / 20240722_184327 / 20240722_184330 / 20240722_184333 (Prasinezumab dose / weight strata, PASADENA trial-design, ABBV-0805, Affitope PD01A / PD03A, UB-312, NPT200-11, Anle138b, ABL301, UCB0599 / minzasolmin, BIIB101 / ION464, AAV2-GAD / MeiraGTx) carry several Uncertain Spans for token-list drug names and clipped result cells. Treat them as in-axis evidence, not as program rows.
  • Body-purity figure-embed boundary. Per docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md, several program pages embed only figure-only crops; mixed text-and- figure crops are kept as evidence rather than embedded. This page re-uses owner-page provenance and does not re-embed figures.