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Inluriyo: which tox species, and why?

imlunestrant · Estrogen receptor (SERD)
Species
Rat and cynomolgus monkey
“Repeat-dose toxicity studies were conducted with imlunestrant in rats (≤ 150 mg/kg/day) up to 6- months duration and monkeys (≤ 600 mg/kg/day) up to 3-months duration.”
✓ VerifiedFDA multi-discipline review, p. 41Source ↗
Why that species
Pharmacokinetics and toxicokinetics in rat and monkey similar enough to human to be representative
“Overall, it can be concluded that rats and monkeys are suitable non-clinical species for the safety assessment of imlunestrant. The pharmaco-and toxicokinetics are similar enough to human pharmacokinetics to be representative.”
✓ VerifiedEMA assessment report, p. 43Source ↗
Surrogate molecule
No surrogate; the clinical compound was tested
“Imlunestrant has been administered by QD oral gavage to rats for up to 6 months and to monkeys for up to 3 months.”
✓ VerifiedFDA multi-discipline review, p. 50Source ↗

Same question, other small molecules

Accrufer

ferric maltol · Iron replacement
Dog

Adquey

difamilast · PDE4 (topical)
Rat, dog and minipig

Agamree

vamorolone · Glucocorticoid receptor (dissociative)
Mouse and dog

Alyftrek

vanzacaftor, tezacaftor and deutivacaftor · CFTR
Rat and dog

Anzupgo

delgocitinib · Pan-JAK (topical)
Rat and dog (oral); minipig and mouse (dermal)

Aqneursa

levacetylleucine · Neuronal metabolism (proposed)
Rat and dog

Artesunate

artesunate · Plasmodium (antimalarial)
Rat and dog

Attruby

acoramidis · Transthyretin (stabiliser)
Rat and dog

Augtyro

repotrectinib · ROS1/TRK
Rat and cynomolgus monkey

Avmapki Fakzynja Co-pack

avutometinib and defactinib · RAF/MEK clamp; FAK
Rat and monkey (avutometinib); rat and dog (defactinib)

Ayvakit

avapritinib · KIT/PDGFRA
Rat and dog

Azstarys

serdexmethylphenidate and dexmethylphenidate · Dopamine/norepinephrine reuptake
Rat and dog (28-day); rabbit (6-month juvenile, EFD)

Balversa

erdafitinib · FGFR1-4
Rat and dog

Barhemsys

amisulpride · Dopamine D2/D3 receptor
Rat

Baxfendy

baxdrostat · Aldosterone synthase (CYP11B2)
Rat and cynomolgus monkey

Beqalzi

sonrotoclax · BCL-2
Mouse and dog

Blujepa

gepotidacin · Bacterial topoisomerases (gyrase/topo IV)
Rat and dog

Brenzavvy

bexagliflozin · SGLT2
Rat and monkey

Brexafemme

ibrexafungerp · Fungal glucan synthase
Rat and dog

Brinsupri

brensocatib · DPP1 (cathepsin C)
Rat and dog

Byfavo

remimazolam · GABA-A receptor (benzodiazepine site)
Cynomolgus monkey and minipig

Bylvay

odevixibat · IBAT
Rat and dog

Cabenuva

cabotegravir and rilpivirine · HIV-1 integrase; NNRTI
Rat and monkey (cabotegravir)

Camzyos

mavacamten · Cardiac myosin
Rat and dog

Caplyta

lumateperone · 5-HT2A / D2 receptor
Rat and dog (mouse up to 3 months)

Cardamyst

etripamil · L-type calcium channel
Rat and cynomolgus monkey

Cibinqo

abrocitinib · JAK1
Rat and cynomolgus monkey

Cobenfy

xanomeline and trospium · Muscarinic M1/M4 agonist; peripheral antagonist
Rat and monkey

Cosela

trilaciclib · CDK4/6
Rat and dog

Crenessity

crinecerfont · CRF1 receptor
Rat and dog

Cypsedo

cipepofol · GABA-A receptor
Rat and dog

Daybue

trofinetide · IGF-1 tripeptide analogue
Rat and dog

Dayvigo

lemborexant · Orexin OX1/OX2 receptors
Rat and monkey

Defencath

taurolidine and heparin · Antimicrobial catheter lock
Rat (14-day IV study) and mouse (single-dose IP study)

Dojolvi

triheptanoin · Anaplerotic energy substrate
Minipig (GLP); published rat dietary study

Duvyzat

givinostat · Histone deacetylase (class I/II)
Rat and monkey (supporting 13-week mouse and 4-week dog)

Egaten

triclabendazole · Fasciola (tubulin)
Rat and dog

Ekterly

sebetralstat · Plasma kallikrein
Rat and cynomolgus monkey

Evrysdi

risdiplam · SMN2 splicing
Rat and cynomolgus monkey

Exblifep

cefepime and enmetazobactam · PBPs; beta-lactamase (enmetazobactam)
Rat and dog

Exkivity

mobocertinib · EGFR exon 20 insertion
Rat and dog

Exxua

gepirone · 5-HT1A receptor
Rat and dog

Fabhalta

iptacopan · Complement factor B
Rat and dog

Fetroja

cefiderocol · Penicillin-binding proteins
Rat and monkey

Filspari

sparsentan · Endothelin A / angiotensin II receptors
Mouse, rat and cynomolgus monkey

Fotivda

tivozanib · VEGFR1-3
Rat and cynomolgus monkey

Foundayo

orforglipron · GLP-1 receptor (non-peptide)
Rat and cynomolgus monkey

Fruzaqla

fruquintinib · VEGFR1-3
Rat and dog

Gavreto

pralsetinib · RET
Rat and cynomolgus monkey

Gemtesa

vibegron · β3-adrenergic receptor
Rat and cynomolgus monkey

Gomekli

mirdametinib · MEK1/2
Rat and dog

Grafapex

treosulfan · DNA alkylation
Rat, dog and monkey

Hernexeos

zongertinib · HER2 (mutant)
Rat and dog

Hyrnuo

sevabertinib · HER2 (mutant)
Rat and monkey

Ibsrela

tenapanor · NHE3
Rat and dog

Ibtrozi

taletrectinib · ROS1
Rat and cynomolgus monkey

Idvynso

doravirine and islatravir · NNRTI; NRTTI
Rat and rhesus monkey (islatravir), plus mouse up to 3 months

Inpefa

sotagliflozin · SGLT1/SGLT2
Rat and dog

Inqovi

decitabine and cedazuridine · DNMT (decitabine); cytidine deaminase (cedazuridine)
Mouse and cynomolgus monkey (cedazuridine); rat (decitabine)

Inrebic

fedratinib · JAK2
Rat and dog

Iqirvo

elafibranor · PPARα/δ
Rat and cynomolgus monkey (mouse up to 3 months)

Isturisa

osilodrostat · 11β-hydroxylase (CYP11B1)
Rat and dog

Itovebi

inavolisib · PI3Kα (mutant-selective)
Rat and dog

Jascayd

nerandomilast · PDE4B
Rat, minipig and cynomolgus monkey

Jaypirca

pirtobrutinib · BTK (non-covalent)
Rat and dog

Jesduvroq

daprodustat · HIF prolyl hydroxylase
Rat and cynomolgus monkey (dog in studies up to 13 weeks)

Joenja

leniolisib · PI3Kδ
Rat and cynomolgus monkey

Journavx

suzetrigine · NaV1.8
Rat and cynomolgus monkey

Kerendia

finerenone · Mineralocorticoid receptor
Rat and dog

Klisyri

tirbanibulin · Tubulin / Src
Rat and dog (oral); minipig and rat (topical)

Komzifti

ziftomenib · Menin-KMT2A
Mouse and dog

Koselugo

selumetinib · MEK1/2
Mouse, rat and cynomolgus monkey

Krazati

adagrasib · KRAS G12C
Rat and dog

Kygevvi

doxecitine and doxribtimine · Pyrimidine nucleoside replacement (TK2 deficiency)
Rat and dog (plus 4-week mouse)

Lampit

nifurtimox · Trypanosoma cruzi
Rat and dog

Lazcluze

lazertinib · EGFR (mutant-selective)
Rat and dog

Leqselvi

deuruxolitinib · JAK1/JAK2
Rat and dog

Lifyorli

relacorilant · Glucocorticoid receptor (antagonist)
Rat and cynomolgus monkey

Litfulo

ritlecitinib · JAK3/TEC kinases
Rat and dog

Livdelzi

seladelpar · PPARδ
Rat and cynomolgus monkey (also mouse and dog)

Livmarli

maralixibat · IBAT (ASBT)
Rat and dog

Livtencity

maribavir · CMV UL97 protein kinase
Rat and cynomolgus monkey (plus 13-week mouse)

Lumakras

sotorasib · KRAS G12C
Rat and dog

Lupkynis

voclosporin · Calcineurin
Rat and cynomolgus monkey

Lybalvi

olanzapine and samidorphan · D2/5-HT2A; opioid receptors (samidorphan)
Rat and dog

Lynavoy

linerixibat · IBAT
Rat and dog

Lynkuet

elinzanetant · NK1/NK3 receptors
Rat and cynomolgus monkey

Lytgobi

futibatinib · FGFR1-4 (covalent)
Rat and dog

Mayzent

siponimod · S1P1/S1P5 receptor
Rat and cynomolgus monkey

Miebo

perfluorohexyloctane · Tear film evaporation barrier
Rabbit (ocular) and rat (oral)

Miplyffa

arimoclomol · Heat-shock response amplifier
Rat and dog

Modeyso

dordaviprone · DRD2 antagonist / ClpP agonist
Rat and dog

Myqorzo

aficamten · Cardiac myosin
Rat and dog

Nereus

tradipitant · NK1 receptor
Rat and dog (plus 13-week mouse)

Nexletol

bempedoic acid · ATP citrate lyase
Rat and monkey

Nextstellis

drospirenone and estetrol · Estrogen / progestin receptors
Rat and cynomolgus monkey

Nourianz

istradefylline · Adenosine A2A receptor
Rat and dog

Nubeqa

darolutamide · Androgen receptor
Rat and dog

Nulibry

fosdenopterin · cPMP replacement (MoCD type A)
Rat and dog (juvenile)

Nurtec ODT

rimegepant · CGRP receptor
Rat and cynomolgus monkey

Nuzolvence

zoliflodacin · Bacterial topoisomerase II
Rat and dog

Ogsiveo

nirogacestat · Gamma secretase
Rat and dog

Ohtuvayre

ensifentrine · PDE3/PDE4
Rat and dog

Ojemda

tovorafenib · RAF (type II pan-RAF)
Rat and cynomolgus monkey

Ojjaara

momelotinib · JAK1/JAK2/ACVR1
Rat and dog

Olinvyk

oliceridine · μ-opioid receptor (G-protein biased)
Rat and monkey

Omlonti

omidenepag isopropyl · EP2 receptor
Rat and cynomolgus monkey

Ongentys

opicapone · COMT
Rat and cynomolgus monkey

Orgovyx

relugolix · GnRH receptor
Rat and cynomolgus monkey (mouse up to 13 weeks)

Orladeyo

berotralstat · Plasma kallikrein
Rat and monkey

Orlynvah

sulopenem etzadroxil and probenecid · Penicillin-binding proteins
Rat and cynomolgus monkey

Orserdu

elacestrant · Estrogen receptor (SERD)
Rat and cynomolgus monkey

Orzeyful

oveporexton · Orexin OX2 receptor agonist
Rat and cynomolgus monkey

Oxbryta

voxelotor · HbS polymerisation
Rat and cynomolgus monkey (also mouse)

Palsonify

paltusotine · Somatostatin receptor 2
Rat and dog

Paxlovid

nirmatrelvir and ritonavir · SARS-CoV-2 Mpro (3CL protease)
Rat and cynomolgus monkey

Pemazyre

pemigatinib · FGFR1-3
Rat and cynomolgus monkey

Piqray

alpelisib · PI3Kα
Rat and dog

Pizensy

lactitol · Osmotic laxative
Rat and Tg.rasH2 mouse

Ponvory

ponesimod · S1P1 receptor
Rat and dog (mouse for carcinogenicity, rabbit for EFD)

Pretomanid

pretomanid · Mycobacterial cell wall / respiration
Rat and cynomolgus monkey

Pyrukynd

mitapivat · Pyruvate kinase (activator)
Rat and cynomolgus monkey

Qelbree

viloxazine · Norepinephrine reuptake
Rat and dog

Qinlock

ripretinib · KIT/PDGFRA
Rat and dog

Qulipta

atogepant · CGRP receptor
Rat and rhesus monkey

Quviviq

daridorexant · Orexin OX1/OX2 receptors
Rat and dog

Rapiblyk

landiolol · β1-adrenergic receptor
Rat and dog

Rasonque

daraxonrasib · RAS(ON) multi-selective
Mouse and cynomolgus monkey

Recarbrio

imipenem, cilastatin and relebactam · Beta-lactamase (relebactam)
Rat and monkey

Relyvrio

sodium phenylbutyrate and taurursodiol · ER stress / mitochondrial (proposed)
Rat and minipig

Retevmo

selpercatinib · RET
Rat and Göttingen minipig

Revuforj

revumenib · Menin-KMT2A
Rat and dog

Reyvow

lasmiditan · 5-HT1F receptor
Rat and dog

Rezdiffra

resmetirom · Thyroid hormone receptor β
Rat and dog (plus mouse up to 3 months)

Rezlidhia

olutasidenib · IDH1 (mutant)
Rat and cynomolgus monkey

Rezzayo

rezafungin · Fungal glucan synthase
Rat and cynomolgus monkey

Rinvoq

upadacitinib · JAK1
Rat and dog

Rozlytrek

entrectinib · TRK/ROS1/ALK
Rat and dog

Rukobia

fostemsavir · HIV-1 gp120 (attachment)
Rat and dog

Scemblix

asciminib · BCR-ABL1 (STAMP, myristoyl pocket)
Rat and cynomolgus monkey (plus 4-week dog)

Sephience

sepiapterin · Tetrahydrobiopterin precursor
Rat and marmoset monkey

Simtriyo

centanafadine · Triple monoamine reuptake
Rat and dog

Skyclarys

omaveloxolone · Nrf2 activator
Rat and cynomolgus monkey

Sofdra

sofpironium · Muscarinic receptors (topical)
Rat and Göttingen minipig

Sohonos

palovarotene · RARγ
Rat and dog

Sotyktu

deucravacitinib · TYK2
Rat and cynomolgus monkey

Sunlenca

lenacapavir · HIV-1 capsid
Rat and dog

Sunosi

solriamfetol · Dopamine/norepinephrine reuptake
Rat and dog (plus 3-month mouse)

Tabrecta

capmatinib · MET
Rat and cynomolgus monkey

Tavneos

avacopan · C5a receptor (C5aR1)
Hamster, rat and cynomolgus monkey

Tazverik

tazemetostat · EZH2
Rat and cynomolgus monkey

Trikafta

elexacaftor, tezacaftor and ivacaftor · CFTR
Rat and dog

Truqap

capivasertib · AKT1-3
Rat and dog

Tryptyr

acoltremon · TRPM8 agonist
Rabbit and dog (ocular); rat (intravenous)

Tryvio

aprocitentan · Endothelin A/B receptors
Rat and dog

Tukysa

tucatinib · HER2
Rat and cynomolgus monkey

Turalio

pexidartinib · CSF1R
Rat and dog

Ubrelvy

ubrogepant · CGRP receptor
Rat and rhesus monkey

Ukoniq

umbralisib · PI3Kδ / CK1ε
Mouse and dog

Utebzi

tebipenem pivoxil · Penicillin-binding proteins
Rat and cynomolgus monkey

Vafseo

vadadustat · HIF prolyl hydroxylase
Rat and dog (plus 3-month mouse)

Vanflyta

quizartinib · FLT3
Rat, dog and cynomolgus monkey

Vanrafia

atrasentan · Endothelin A receptor
Rat and dog

Veklury

remdesivir · SARS-CoV-2 RNA polymerase
Rat and cynomolgus monkey

Velsipity

etrasimod · S1P1/S1P4/S1P5 receptors
Rat and dog

Veozah

fezolinetant · Neurokinin-3 receptor
Rat and cynomolgus monkey (females)

Veppanu

vepdegestrant · Estrogen receptor (PROTAC degrader)
Rat and dog

Verquvo

vericiguat · Soluble guanylate cyclase
Rat and dog

Vivjoa

oteseconazole · Fungal CYP51
Rat and dog

Vizz

aceclidine · Muscarinic agonist (miotic)
Rabbit

Vonjo

pacritinib · JAK2/FLT3
Mouse and dog

Voquezna

vonoprazan · H+/K+-ATPase (potassium-competitive)
Rat and dog

Voranigo

vorasidenib · IDH1/IDH2
Rat and cynomolgus monkey

Voydeya

danicopan · Complement factor D
Rat and dog

Vtama

tapinarof · Aryl hydrocarbon receptor
Rat and minipig

Vyndaqel

tafamidis · Transthyretin (stabiliser)
Rat and dog

Wakix

pitolisant · Histamine H3 receptor
Rat and cynomolgus monkey (mouse up to 1 month)

Wayrilz

rilzabrutinib · BTK (reversible covalent)
Rat and dog

Welireg

belzutifan · HIF-2α
Rat and dog

Winlevi

clascoterone · Androgen receptor (topical)
Rat and minipig

Xacduro

sulbactam and durlobactam · PBPs; beta-lactamase (durlobactam)
Rat and dog (mouse for embryo-fetal development)

Xcopri

cenobamate · Sodium channel / GABA-A
Rat and cynomolgus monkey (mouse up to 13 weeks)

Xdemvy

lotilaner · Mite GABA-Cl channel
Rabbit and dog (ocular); rat and dog (systemic)

Xeglyze

abametapir · Lice metalloproteinases
Rat and minipig

Xenleta

lefamulin · Bacterial ribosome (50S PTC)
Rat and cynomolgus monkey

Xocova

ensitrelvir · SARS-CoV-2 3CL protease
Rat and cynomolgus monkey

Xpovio

selinexor · XPO1
Rat and cynomolgus monkey

Zavzpret

zavegepant · CGRP receptor
Rat and cynomolgus monkey

Zaynich

cefepime and zidebactam · PBPs; beta-lactam enhancer (zidebactam)
Rat and dog

Zegfrovy

sunvozertinib · EGFR exon 20 insertion
Rat and dog

Zenbexus

iberdomide · Cereblon (CELMoD)
Rat and monkey

Zeposia

ozanimod · S1P1/S1P5 receptor
Rat and cynomolgus monkey

Zepzelca

lurbinectedin · DNA minor groove (transcription)
Rat, dog and cynomolgus monkey

Zevtera

ceftobiprole medocaril · Penicillin-binding proteins
Rat, marmoset and dog

Zokinvy

lonafarnib · Farnesyltransferase
Rat and cynomolgus monkey

Ztalmy

ganaxolone · GABA-A receptor (positive modulator)
Rat and dog

Zulresso

brexanolone · GABA-A receptor (positive modulator)
Rat and dog

Zurzuvae

zuranolone · GABA-A receptor (positive modulator)
Rat and dog

Zycubo

copper histidinate · Copper replacement (Menkes disease)
Juvenile rat only

Summary across all 211 small molecules →