NPS IND dashboard

4 open chemical decisions

Lys position

Lys11HomoLysHomoHomoLysOrnithineLys12

v40.22 (Lys11) vs v40.9 (HomoLys11) head-to-head; v40.24 / v40.25 extra reach reads

KAN-87 KAN-88

Chain length

C16C18 satC18:1C20

C16 over-covered. v40.4 reads C18:1. C20 + saturated C18 are KAN gap-fills.

KAN-90 KAN-92

Truncation

1-201-131-12

Covered on both Nle11 (v40.2 / v40.3) and HomoLys11 (v40.10 / v40.11) scaffolds.

no linked tickets

C-terminus

-NH2-OH (free acid)

Only -NH2 in current queue. -OH gap-fill filed.

KAN-91

IND stages at a glance

Stage	Open	Overdue	Next due
Lead optimization	12	0	2026-07-06
04 · Stability + degradation	2	0	2026-08-14
05 · Bioanalytical (ICH M10)	9	0	2026-06-30
06 · In-vivo PK	8	1	2026-06-26
07 · Allometric scaling + HED	4	0	2026-07-28
08 · PK/PD	3	0	2026-08-10
09 · Mechanism + efficacy	4	0	2026-07-15
10 · Safety + immunogenicity	4	0	2026-07-21
11 · GLP / CMC outsourcing	8	0	2026-09-08
12 · Regulatory (AU CTN)	3	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

STU-26-NPS-20260629-003 · locked · KAN-89

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

STU-26-NPS-20260629-002 · locked · KAN-88

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

STU-26-NPS-20260629-001 · locked · KAN-87

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 (5)

Key	Status	Due	Assignee	Summary
KAN-20	Idea	2026-06-22	Moaraj Hasan	SPPS synthesis - NPS 40.9
KAN-19	Idea	2026-06-22	Moaraj Hasan	SPPS synthesis - NXN 20.16
KAN-24	Idea	2026-06-26	Moaraj Hasan	PK study design + AEC (Animal Ethics Committee) protocol (mouse single-dose IV/SC)
KAN-21	Idea	2026-06-26	Moaraj Hasan	RP-HPLC purification + lyophilization (NXN + NPS)
KAN-16	Idea	2026-06-26	Moaraj Hasan	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
Compound	Qty	Synth	IP1 (107I)	IP1 (107N)	FLIPR (107I)	FLIPR (107N)	bArr (107N)	cAMP (107N)	SC actigraphy	EEG	PK plasma	PK CSF/brain	Stability (LC-MS)
`NPSv40.9` ANCHOR · 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	planned	post-lock	post-lock	post-lock	planned
`NPSv40.22` Lys 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
`NPSv40.24` Lys 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
`NPSv40.25` Lys 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
`NPSv40.10` Truncation · 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	—	—	—	—	planned	—	—	—	—
`NPSv40.11` Truncation · 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	—	—	—	—
`NPSv41.1` C-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	—	—	—	—	planned	post-lock	post-lock	post-lock	—
`NPSv40.23` Secondary · 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	Summary
KAN-20	Idea	2026-06-22	Moaraj Hasan	SPPS synthesis - NPS 40.9
KAN-19	Idea	2026-06-22	Moaraj Hasan	SPPS synthesis - NXN 20.16
KAN-21	Idea	2026-06-26	Moaraj Hasan	RP-HPLC purification + lyophilization (NXN + NPS)
KAN-16	Idea	2026-06-26	Moaraj Hasan	Peptide Synthesis & Purification

Analytical QC workstream (@Mo)

Key	Status	Due	Assignee	Summary
KAN-17	Idea	2026-07-03	Moaraj Hasan	Analytical QC / Mass Spec ID
KAN-14	Idea	2026-07-03	Moaraj Hasan	Intact mass + full sequence confirmation MS/MS

In-vitro potency workstream (@Stephen)

Key	Status	Due	Assignee	Summary
KAN-22	Idea	2026-07-10	Moaraj Hasan	NPSR1 IP1 EC50 assay — NXN 20.16
KAN-23	Idea	2026-07-17	Moaraj Hasan	NPSR1 IP1 EC50 assay — NPS 40.9
KAN-18	Idea	2026-07-17	Moaraj Hasan	In-vitro Potency (OX2 IP1 / EC50)

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)

04 · Stability + degradation

2 open 0 done

Key	Status	Due	Assignee	Summary
KAN-15	Idea	2026-08-14	Moaraj Hasan	Forced degradation study + impurity criteria
KAN-2	Idea	2026-08-14	Moaraj Hasan	Degradation & Stability (HF-X Orbitrap)

05 · Bioanalytical (ICH M10)

9 open 0 done

Key	Status	Due	Assignee	Summary
KAN-29	Idea	2026-06-30	Moaraj Hasan	Reference standards, IS qualification + stock/working solutions
KAN-30	Idea	2026-07-08	Moaraj Hasan	Calibration curve + selectivity/specificity (ICH M10)
KAN-11	Idea	2026-07-10	Moaraj Hasan	6495D MRM method dev - NPS 40.9
KAN-10	Idea	2026-07-10	Moaraj Hasan	6495D MRM method dev - NXN 20.16
KAN-31	Idea	2026-07-18	Moaraj Hasan	Accuracy + precision validation runs (within/between-run)
KAN-32	Idea	2026-07-22	Moaraj Hasan	Matrix effect, recovery, dilution integrity, carryover
KAN-33	Idea	2026-08-08	Moaraj Hasan	Stability validation (stock, bench, freeze-thaw, long-term, autosampler)
KAN-34	Idea	2026-08-28	Moaraj Hasan	ICH M10 bioanalytical validation report sign-off
KAN-3	Idea	2026-08-28	Moaraj Hasan	Bioanalytical Method & ICH M10 Validation (6495D)

06 · In-vivo PK

8 open 1 overdue 0 done

Key	Status	Due	Assignee	Summary
KAN-24	Idea	2026-06-26	Moaraj Hasan	PK study design + AEC (Animal Ethics Committee) protocol (mouse single-dose IV/SC)
KAN-25	Idea	2026-06-30	Moaraj Hasan	Dose formulation, dose verification, and vehicle bridging
KAN-26	Idea	2026-07-10	Moaraj Hasan	In-life dosing + serial plasma collection (0-24 h timecourse)
KAN-27	Idea	2026-07-18	Moaraj Hasan	Bioanalysis of PK samples on validated 6495D method
KAN-12	Idea	2026-07-20	Moaraj Hasan	Plasma protein binding + blood:plasma partitioning
KAN-28	Idea	2026-07-31	Moaraj Hasan	Non-compartmental PK analysis + IV/SC parameter report
KAN-1	Idea	2026-07-31	Moaraj Hasan	In-vivo PK: mouse single-dose IV/SC (NXN 20.16 + NPS 40.9)
KAN-13	Idea	2026-08-07	Moaraj Hasan	In-vivo PK study report + data package of record (IV/SC)

07 · Allometric scaling + HED

4 open 0 done

Key	Status	Due	Assignee	Summary
KAN-35	Idea	2026-07-28	Moaraj Hasan	Cross-species in-vitro scaling inputs (clearance, binding, stability)
KAN-36	Idea	2026-08-10	Moaraj Hasan	Allometric scaling model (CL, Vss) + human PK prediction
KAN-37	Idea	2026-08-21	Moaraj Hasan	Human starting dose: MABEL + NOAEL/BSA HED + safety factor
KAN-4	Idea	2026-08-21	Moaraj Hasan	Allometric Scaling & Human Starting Dose

08 · PK/PD

3 open 0 done

Key	Status	Due	Assignee	Summary
KAN-38	Idea	2026-08-10	Moaraj Hasan	PK/PD biomarker + exposure-response model build
KAN-39	Idea	2026-08-28	Moaraj Hasan	Clinical dose-escalation scheme + projected exposure margins
KAN-5	Idea	2026-08-28	Moaraj Hasan	PK/PD Linkage & Dose Escalation

09 · Mechanism + efficacy

4 open 0 done

Key	Status	Due	Assignee	Summary
KAN-40	Idea	2026-07-15	Moaraj Hasan	In-vitro target engagement + selectivity panel
KAN-41	Idea	2026-08-05	Moaraj Hasan	In-vivo efficacy / target-engagement model (mouse)
KAN-42	Idea	2026-08-31	Moaraj Hasan	Mechanism-of-action omics readout + brain exposure
KAN-6	Idea	2026-08-31	Moaraj Hasan	Efficacy & Mechanism (cells, mouse, omics)

10 · Safety + immunogenicity

4 open 0 done

Key	Status	Due	Assignee	Summary
KAN-43	Idea	2026-07-21	Moaraj Hasan	In-vitro safety pharmacology (hERG, cardiovascular liability)
KAN-44	Idea	2026-08-10	Moaraj Hasan	Immunogenicity / ADA assay strategy + in-silico risk
KAN-45	Idea	2026-08-31	Moaraj Hasan	GLP tox study design + DART deferral justification
KAN-7	Idea	2026-08-31	Moaraj Hasan	Safety & Immunogenicity (DART defer, ADA)

11 · GLP / CMC outsourcing

8 open 0 done

Key	Status	Due	Assignee	Summary
KAN-71	Idea	2026-09-08	Moaraj Hasan	GMP clinical batch manufacture (API) + batch record + CoA
KAN-69	Idea	2026-09-15	Moaraj Hasan	Genotoxicity battery (Ames + in vitro micronucleus)
KAN-67	Idea	2026-09-15	Moaraj Hasan	GLP repeat-dose toxicology study (rodent) - execution + report
KAN-72	Idea	2026-09-22	Moaraj Hasan	Drug product CMC: sterile injectable formulation, fill-finish, container-closure
KAN-70	Idea	2026-09-22	Moaraj Hasan	Safety pharmacology core battery (ICH S7A: CV, CNS, respiratory)
KAN-68	Idea	2026-09-22	Moaraj Hasan	GLP repeat-dose toxicology study (non-rodent) - execution + report
KAN-73	Idea	2026-09-29	Moaraj Hasan	ICH Q1A stability program on clinical API + DP lots
KAN-8	Idea	2026-09-30	Moaraj Hasan	GLP Outsourcing & CMC (engage on clinical lead)

12 · Regulatory (AU CTN)

3 open 0 done

Key	Status	Due	Assignee	Summary
KAN-75	Idea	2026-09-15	Moaraj Hasan	Clinical protocol + synopsis (FIH SAD)
KAN-74	In Progress	2026-09-22	Moaraj Hasan	Author Investigator's Brochure (IB)
KAN-9	Idea	2026-09-30	Moaraj Hasan	AU CTN Regulatory Package & Submission

NPS — IND process tracker

4 open chemical decisions

IND stages at a glance

Active studies (preclin.study, last 30 days)

Overdue across all stages (5)

Compound × complete-assay coverage

Planned SC mouse studies (@Jigisha)

Synthesis workstream (@Nico, @Hillary)

Analytical QC workstream (@Mo)

In-vitro potency workstream (@Stephen)

Filed Iris gap-fills (review needed)

04 · Stability + degradation

05 · Bioanalytical (ICH M10)

06 · In-vivo PK

07 · Allometric scaling + HED

08 · PK/PD

09 · Mechanism + efficacy

10 · Safety + immunogenicity

11 · GLP / CMC outsourcing

12 · Regulatory (AU CTN)