4 open chemical decisions
Lys position
v40.22 (Lys11) vs v40.9 (HomoLys11) head-to-head; v40.24 / v40.25 extra reach reads
Chain length
C16 over-covered. v40.4 reads C18:1. C20 + saturated C18 are KAN gap-fills.
Truncation
Covered on both Nle11 (v40.2 / v40.3) and HomoLys11 (v40.10 / v40.11) scaffolds.
no linked tickets
IND stages at a glance
| Stage | Open | Overdue | Done | Next due |
|---|---|---|---|---|
| Lead optimization | 12 | 0 | 0 | 2026-07-06 |
| Stability + degradation | 2 | 0 | 0 | 2026-08-14 |
| PK (methods · studies · scaling/HED · PK-PD) | 23 | 1 | 0 | 2026-06-26 |
| Safety + immunogenicity | 4 | 0 | 0 | 2026-07-21 |
| GLP / CMC outsourcing | 8 | 0 | 0 | 2026-09-08 |
| Regulatory (AU CTN) | 3 | 0 | 0 | 2026-09-15 |
Active studies (preclin.study, last 30 days)
STU-olden-dl-dmuo-st0067 · executing
NPSv40.9 1000ug vs. NPSv40.9 500ug vs. NPSv40.9 200ug vs. NPSv40.9 100ug vs. Placebo, subq, 100ul, 0.9% saline, n = 15
owner: — · updated 2026-06-24 18:48:01.219420+00:00
Accelerated LC-MS stability triage for NPS lead-lock pair
Identify rapid parent loss or route-relevant degradation liabilities in the top NPS lead-lock candidates before the 2026-07-06 decision.
owner: iris · updated 2026-06-30 02:53:17.085537+00:00
Human albumin functional-shift screen for lipidated NPS leaders
Test whether top lipidated NPS candidates preserve functional NPSR1 agonism in human albumin conditions relevant to human half-life translation.
owner: iris · updated 2026-06-30 02:23:56.962000+00:00
Lead-lock same-plate IP1 for NPSR1 107I and 107N coverage
Determine whether the apparent 107I lead candidates retain potent full agonism on both hNPSR1 107I and 107N under matched IP1 conditions.
owner: iris · updated 2026-06-30 02:22:18.429192+00:00
Overdue across all stages (4)
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-20 | Idea | 2026-06-22 | Moaraj Hasan | no vendor | pick vendor (-8d to due) | SPPS synthesis - NPS 40.9 |
| KAN-24 | Idea | 2026-06-26 | Moaraj Hasan | no vendor | pick vendor (-4d to due) | PK study design + AEC (Animal Ethics Committee) protocol (mouse single-dose IV/SC) |
| KAN-21 | Idea | 2026-06-26 | Moaraj Hasan | no vendor | pick vendor (-4d to due) | RP-HPLC purification + lyophilization (NXN + NPS) |
| KAN-16 | Idea | 2026-06-26 | Moaraj Hasan | no vendor | pick vendor (-4d to due) | Peptide Synthesis & Purification |
Compound × complete-assay coverage
"Complete" assay set: 107I IP1 · 107N IP1 · 107I FLIPR · 107N FLIPR · bArr · cAMP — same-plate, same-producer-batch.
Cells show best EC50 in nM and run count. Empty cells (—) are missing reads.
| Compound | Qty | Synth | In-vitro (cell assays) | In-vivo + stability | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IP1 (107I) | IP1 (107N) | FLIPR (107I) | FLIPR (107N) | bArr (107N) | cAMP (107N) | SC actigraphy | EEG | PK plasma | PK CSF/brain | Stability (LC-MS) | |||
NPSv40.9ANCHOR · Lead candidate — HomoLys11, 1-20, -NH2 — in all three head-to-heads SF(Nω-methyl-Arg)N(Sar)VGTG(N-Me-Nle)(HomoLys)-K[(γ-E)-(C16 Pal)]-TSFQRAKS-NH2 | not tracked | mice reached | 0.00 nM · n=4 | 0.03 nM · n=6 | 0.62 nM · n=1 | 0.17 nM · n=1 | 1.47 nM · n=1 | 0.12 nM · n=1 | 0-6h: -33% sleep (NPSv41.18 500ug) 0-24h: -28% sleep (NPSv41.18 500ug) DL-HGA4-st0078 · 12 Olden runs · latest 2026-06-29 | post-lock | post-lock | post-lock | planned |
NPSv40.22Lys position · Lys11 SF(Nomega-methyl-Arg)N(Sar)VGTG(N-Me-Nle)K-K[(gamma-E)-(C16 Pal)]-TSFQRAKS-NH2 | — | queued for SPPS | 0.07 nM · n=2 | 0.21 nM · n=2 | — | — | — | — | planned | post-lock | post-lock | post-lock | planned |
NPSv40.24Lys position · HomoHomoLys11 (secondary — extra reach) SF(Nomega-methyl-Arg)N(Sar)VGTG(N-Me-Nle)(HomoHomoLys)-K[(gamma-E)-(C16 Pal)]-TS… | not tracked | queued for SPPS | 0.10 nM · n=2 | 0.25 nM · n=4 | — | — | — | — | planned | post-lock | post-lock | post-lock | planned |
NPSv40.25Lys position · Ornithine11 (secondary) SF(Nomega-methyl-Arg)N(Sar)VGTG(N-Me-Nle)(Orn)-K[(gamma-E)-(C16 Pal)]-TSFQRAKS-N… | not tracked | through HPLC | 0.27 nM · n=3 | 0.16 nM · n=4 | — | — | — | — | planned | post-lock | post-lock | post-lock | planned |
NPSv40.10Truncation · 1-13 (hypothesis: default 1-20 wins; verify) SF(Nω-methyl-Arg)N(Sar)VGTG(N-Me-Nle)(HomoLys)-K[(γ-E)-(C16 Pal)]-T-NH2 | not tracked | partial | 0.11 nM · n=4 | 0.23 nM · n=1 | — | — | — | — | 0-6h: +22% sleep (EEG NPSv40.10 100ug) 0-24h: +71% sleep (EEG NPSv40.10 100ug) DL-arPA-st0046 · 2 Olden runs · latest 2026-06-01 | — | — | — | — |
NPSv40.11Truncation · 1-12 (hypothesis: default 1-20 wins; verify) SF(Nω-methyl-Arg)N(Sar)VGTG(N-Me-Nle)(HomoLys)-K[(γ-E)-(C16 Pal)]-NH2 | not tracked | partial | 0.09 nM · n=4 | 0.30 nM · n=1 | — | — | — | — | planned | — | — | — | — |
NPSv41.1C-terminus · -OH variant of v40.9 — critical for in-vivo effect-life decision SF(Nomega-methyl-Arg)N(Sar)VGTG(N-Me-Nle)(HomoLys)-K[(gamma-E)-(C16 Pal)]-TSFQRA… | not tracked | partial | — | 0.17 nM · n=3 | — | — | — | — | 0-6h: -33% sleep (NPSv41.18 500ug) 0-24h: -28% sleep (NPSv41.18 500ug) DL-HGA4-st0078 · 2 Olden runs · latest 2026-06-29 | post-lock | post-lock | post-lock | — |
NPSv40.23Secondary · Nω,Nω-dimethyl-Arg3 — add to cell assays where we have it (lower priority) SF(Nomega,Nomega-dimethyl-Arg)N(Sar)VGTG(N-Me-Nle)(HomoLys)-K[(gamma-E)-(C16 Pal… | not tracked | queued for SPPS | 0.13 nM · n=3 | 0.55 nM · n=3 | — | — | — | — | — | — | — | — | — |
Planned SC mouse studies (@Jigisha)
| Study | Arms | Status / note |
|---|---|---|
| Lys11 SC study | NPSv40.9 · NPSv40.22 · NPSv40.24 · NPSv40.25 | @Jigisha — n≥20/group, 1-page plan, verify material first |
| Truncation SC study | NPSv40.9 · NPSv40.10 · NPSv40.11 | @Jigisha — n≥20/group, 1-page plan, verify material first |
| C-terminus SC study | NPSv40.9 · NPSv41.1 | @Jigisha — critical for finalising -NH2 vs -OH on in-vivo effect-life |
Synthesis workstream (@Nico, @Hillary)
Chemistry ask (@Nico): one clean ≥95% pure in-house batch each of v40.9, v40.22, v40.24, v40.25, v41.1.
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-20 | Idea | 2026-06-22 | Moaraj Hasan | no vendor | pick vendor (-8d to due) | SPPS synthesis - NPS 40.9 |
| KAN-21 | Idea | 2026-06-26 | Moaraj Hasan | no vendor | pick vendor (-4d to due) | RP-HPLC purification + lyophilization (NXN + NPS) |
| KAN-16 | Idea | 2026-06-26 | Moaraj Hasan | no vendor | pick vendor (-4d to due) | Peptide Synthesis & Purification |
Analytical QC workstream (@Mo)
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-17 | Idea | 2026-07-03 | Moaraj Hasan | no vendor | pick vendor (3d to due) | Analytical QC / Mass Spec ID |
| KAN-14 | Idea | 2026-07-03 | Moaraj Hasan | no vendor | pick vendor (3d to due) | Intact mass + full sequence confirmation MS/MS |
In-vitro potency workstream (@Stephen)
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-23 | Idea | 2026-07-17 | Moaraj Hasan | no vendor | pick vendor (17d to due) | NPSR1 IP1 EC50 assay — NPS 40.9 |
| KAN-18 | Idea | 2026-07-17 | Moaraj Hasan | no vendor | pick vendor (17d to due) | In-vitro Potency (OX2 IP1 / EC50) |
Mechanism + efficacy workstream (in-vitro target engagement, selectivity panel)
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-40 | Idea | 2026-07-15 | Moaraj Hasan | no vendor | pick vendor (15d to due) | In-vitro target engagement + selectivity panel |
| KAN-41 | Idea | 2026-08-05 | Moaraj Hasan | no vendor | pick vendor (36d to due) | In-vivo efficacy / target-engagement model (mouse) |
| KAN-42 | Idea | 2026-08-31 | Moaraj Hasan | no vendor | pick vendor (62d to due) | Mechanism-of-action omics readout + brain exposure |
| KAN-6 | Idea | 2026-08-31 | Moaraj Hasan | no vendor | pick vendor (62d to due) | Efficacy & Mechanism (cells, mouse, omics) |
Filed Iris gap-fills (review needed)
Some of these are now redundant with the 2026-06-30 state-of-the-union — see notes.
| KAN | Axis | Status / note |
|---|---|---|
| KAN-90 | Chain length | C20 lipid analog — DEFER: chain length is not a lead-lock decision per 2026-06-30 SoU (future-NPS lever) |
| KAN-91 | C-terminus | Free-acid (-OH) analog — already in flight as NPSv41.1; close as duplicate |
| KAN-92 | Chain length | Saturated C18 analog — DEFER (future-NPS lever) |
| KAN-93 | CMC | CMC + accelerated-degradation — re-scope as external-contractor work (Helena owns) |
Active engagements (3)
Populated from preclin.cro_capability — writes flow from forwarded CRO emails + Slack
@iris cro.| Vendor | Workstream | Status | Owner | CRO progress | Last engagement | Notes |
|---|---|---|---|---|---|---|
| Charles River Laboratories | glp_tox_rodent | no contract | melissa | no_contract | 2026-06-30 📧 | CRL BD contact Hank Arrington reached out to initiate CDA or MSA. Moaraj confirm |
| iHisto Inc. | histology | PO | melissa | PO live · Safety tissues shipped to iHisto Inc. (Salem, MA) | 2026-06-30 📧 | Safety tissues shipped to iHisto Inc. (Salem, MA) via UPS Next Day Air Early on |
| Charles River Laboratories | safety_pharm_ich_s7a | no contract | melissa | no_contract | 2026-06-30 📧 | CRL engaged to scope full nonclinical package including safety pharmacology as p |
Open gaps (17) — KAN tickets with no contracted vendor
| KAN | Due | Assignee | Summary |
|---|---|---|---|
| KAN-40 | 2026-07-15 | Moaraj Hasan | In-vitro target engagement + selectivity panel |
| KAN-43 | 2026-07-21 | Moaraj Hasan | In-vitro safety pharmacology (hERG, cardiovascular liability) |
| KAN-41 | 2026-08-05 | Moaraj Hasan | In-vivo efficacy / target-engagement model (mouse) |
| KAN-44 | 2026-08-10 | Moaraj Hasan | Immunogenicity / ADA assay strategy + in-silico risk |
| KAN-45 | 2026-08-31 | Moaraj Hasan | GLP tox study design + DART deferral justification |
| KAN-42 | 2026-08-31 | Moaraj Hasan | Mechanism-of-action omics readout + brain exposure |
| KAN-7 | 2026-08-31 | Moaraj Hasan | Safety & Immunogenicity (DART defer, ADA) |
| KAN-6 | 2026-08-31 | Moaraj Hasan | Efficacy & Mechanism (cells, mouse, omics) |
| KAN-71 | 2026-09-08 | Moaraj Hasan | GMP clinical batch manufacture (API) + batch record + CoA |
| KAN-75 | 2026-09-15 | Moaraj Hasan | Clinical protocol + synopsis (FIH SAD) |
| KAN-69 | 2026-09-15 | Moaraj Hasan | Genotoxicity battery (Ames + in vitro micronucleus) |
| KAN-74 | 2026-09-22 | Moaraj Hasan | Author Investigator's Brochure (IB) |
| KAN-72 | 2026-09-22 | Moaraj Hasan | Drug product CMC: sterile injectable formulation, fill-finish, container-closure |
| KAN-68 | 2026-09-22 | Moaraj Hasan | GLP repeat-dose toxicology study (non-rodent) - execution + report |
| KAN-73 | 2026-09-29 | Moaraj Hasan | ICH Q1A stability program on clinical API + DP lots |
| KAN-9 | 2026-09-30 | Moaraj Hasan | AU CTN Regulatory Package & Submission |
| KAN-8 | 2026-09-30 | Moaraj Hasan | GLP Outsourcing & CMC (engage on clinical lead) |
Stability + degradation
CRO progress (Drive): 📁 Manufacturing📁 Formulation
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-15 | Idea | 2026-08-14 | Moaraj Hasan | no vendor | pick vendor (45d to due) | Forced degradation study + impurity criteria |
| KAN-2 | Idea | 2026-08-14 | Moaraj Hasan | no vendor | pick vendor (45d to due) | Degradation & Stability (HF-X Orbitrap) |
PK (methods · studies · scaling/HED · PK-PD)
CRO progress (Drive): 📁 Preclinical development
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-24 | Idea | 2026-06-26 | Moaraj Hasan | no vendor | pick vendor (-4d to due) | PK study design + AEC (Animal Ethics Committee) protocol (mouse single-dose IV/SC) |
| KAN-29 | Idea | 2026-06-30 | Moaraj Hasan | no vendor | pick vendor (0d to due) | Reference standards, IS qualification + stock/working solutions |
| KAN-25 | Idea | 2026-06-30 | Moaraj Hasan | no vendor | pick vendor (0d to due) | Dose formulation, dose verification, and vehicle bridging |
| KAN-30 | Idea | 2026-07-08 | Moaraj Hasan | no vendor | pick vendor (8d to due) | Calibration curve + selectivity/specificity (ICH M10) |
| KAN-11 | Idea | 2026-07-10 | Moaraj Hasan | no vendor | pick vendor (10d to due) | 6495D MRM method dev - NPS 40.9 |
| KAN-26 | Idea | 2026-07-10 | Moaraj Hasan | no vendor | pick vendor (10d to due) | In-life dosing + serial plasma collection (0-24 h timecourse) |
| KAN-31 | Idea | 2026-07-18 | Moaraj Hasan | no vendor | pick vendor (18d to due) | Accuracy + precision validation runs (within/between-run) |
| KAN-27 | Idea | 2026-07-18 | Moaraj Hasan | no vendor | pick vendor (18d to due) | Bioanalysis of PK samples on validated 6495D method |
| KAN-12 | Idea | 2026-07-20 | Moaraj Hasan | no vendor | pick vendor (20d to due) | Plasma protein binding + blood:plasma partitioning |
| KAN-32 | Idea | 2026-07-22 | Moaraj Hasan | no vendor | pick vendor (22d to due) | Matrix effect, recovery, dilution integrity, carryover |
| KAN-35 | Idea | 2026-07-28 | Moaraj Hasan | no vendor | pick vendor (28d to due) | Cross-species in-vitro scaling inputs (clearance, binding, stability) |
| KAN-28 | Idea | 2026-07-31 | Moaraj Hasan | no vendor | pick vendor (31d to due) | Non-compartmental PK analysis + IV/SC parameter report |
| KAN-1 | Idea | 2026-07-31 | Moaraj Hasan | no vendor | pick vendor (31d to due) | In-vivo PK: mouse single-dose IV/SC (NXN 20.16 + NPS 40.9) |
| KAN-13 | Idea | 2026-08-07 | Moaraj Hasan | no vendor | pick vendor (38d to due) | In-vivo PK study report + data package of record (IV/SC) |
| KAN-33 | Idea | 2026-08-08 | Moaraj Hasan | no vendor | pick vendor (39d to due) | Stability validation (stock, bench, freeze-thaw, long-term, autosampler) |
| KAN-36 | Idea | 2026-08-10 | Moaraj Hasan | no vendor | pick vendor (41d to due) | Allometric scaling model (CL, Vss) + human PK prediction |
| KAN-38 | Idea | 2026-08-10 | Moaraj Hasan | no vendor | pick vendor (41d to due) | PK/PD biomarker + exposure-response model build |
| KAN-37 | Idea | 2026-08-21 | Moaraj Hasan | no vendor | pick vendor (52d to due) | Human starting dose: MABEL + NOAEL/BSA HED + safety factor |
| KAN-4 | Idea | 2026-08-21 | Moaraj Hasan | no vendor | pick vendor (52d to due) | Allometric Scaling & Human Starting Dose |
| KAN-34 | Idea | 2026-08-28 | Moaraj Hasan | no vendor | pick vendor (59d to due) | ICH M10 bioanalytical validation report sign-off |
| KAN-3 | Idea | 2026-08-28 | Moaraj Hasan | no vendor | pick vendor (59d to due) | Bioanalytical Method & ICH M10 Validation (6495D) |
| KAN-39 | Idea | 2026-08-28 | Moaraj Hasan | no vendor | pick vendor (59d to due) | Clinical dose-escalation scheme + projected exposure margins |
| KAN-5 | Idea | 2026-08-28 | Moaraj Hasan | no vendor | pick vendor (59d to due) | PK/PD Linkage & Dose Escalation |
Safety + immunogenicity
CRO progress (Drive): 📁 Tox Studies
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-43 | Idea | 2026-07-21 | Moaraj Hasan | no vendor | pick vendor (21d to due) | In-vitro safety pharmacology (hERG, cardiovascular liability) |
| KAN-44 | Idea | 2026-08-10 | Moaraj Hasan | no vendor | pick vendor (41d to due) | Immunogenicity / ADA assay strategy + in-silico risk |
| KAN-45 | Idea | 2026-08-31 | Moaraj Hasan | no vendor | pick vendor (62d to due) | GLP tox study design + DART deferral justification |
| KAN-7 | Idea | 2026-08-31 | Moaraj Hasan | no vendor | pick vendor (62d to due) | Safety & Immunogenicity (DART defer, ADA) |
GLP / CMC outsourcing
CRO progress (Drive): 📁 Manufacturing📁 Formulation
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-71 | Idea | 2026-09-08 | Moaraj Hasan | no vendor | pick vendor (70d to due) | GMP clinical batch manufacture (API) + batch record + CoA |
| KAN-69 | Idea | 2026-09-15 | Moaraj Hasan | no vendor | pick vendor (77d to due) | Genotoxicity battery (Ames + in vitro micronucleus) |
| KAN-67 | Idea | 2026-09-15 | Moaraj Hasan | Charles River Laboratories · no contract 📧 | no_contract | GLP repeat-dose toxicology study (rodent) - execution + report |
| KAN-72 | Idea | 2026-09-22 | Moaraj Hasan | no vendor | pick vendor (84d to due) | Drug product CMC: sterile injectable formulation, fill-finish, container-closure |
| KAN-70 | Idea | 2026-09-22 | Moaraj Hasan | Charles River Laboratories · no contract 📧 | no_contract | Safety pharmacology core battery (ICH S7A: CV, CNS, respiratory) |
| KAN-68 | Idea | 2026-09-22 | Moaraj Hasan | no vendor | pick vendor (84d to due) | GLP repeat-dose toxicology study (non-rodent) - execution + report |
| KAN-73 | Idea | 2026-09-29 | Moaraj Hasan | no vendor | pick vendor (91d to due) | ICH Q1A stability program on clinical API + DP lots |
| KAN-8 | Idea | 2026-09-30 | Moaraj Hasan | no vendor | pick vendor (92d to due) | GLP Outsourcing & CMC (engage on clinical lead) |
Regulatory (AU CTN)
CRO progress (Drive): 📁 Phase 1 trial
| Key | Status | Due | Assignee | Vendor | CRO progress | Summary |
|---|---|---|---|---|---|---|
| KAN-75 | Idea | 2026-09-15 | Moaraj Hasan | no vendor | pick vendor (77d to due) | Clinical protocol + synopsis (FIH SAD) |
| KAN-74 | In Progress | 2026-09-22 | Moaraj Hasan | no vendor | pick vendor (84d to due) | Author Investigator's Brochure (IB) |
| KAN-9 | Idea | 2026-09-30 | Moaraj Hasan | no vendor | pick vendor (92d to due) | AU CTN Regulatory Package & Submission |