AGS-16C3F

Discontinued

CHO-produced successor of AGS-16M8F; anti-ENPP3-mcMMAF

Target

ENPP3 (CD203c) · ENPP3

Sponsor

Agensys/Astellas/Seagen

Indication

ENPP3+ RCC

Target family

Ectonucleotidase

RP2D dose

1.8 mg/kg

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

10 adverse-event terms

Ocular

Any-grade

85%

G3+

21%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

59%

Express.

2.79%

Limbus

Express.

4.15%

Conjunctiva

Express.

5.7%

Lens

Express.

Retina / RPE

Express.

0.3 nTPM

Off-target signature

59% corneal toxicity, yet the ENPP3 (CD203c) target is detected in only 2.79% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Ocular toxicity (any ocular sign or symptom)85%

n=34

Keratopathy (corneal events; microcysts)59%

G3+ 21%n=34

Ocular toxicity (any postbaseline ocular diagnosis)44%

n=59

Vision blurred39%

G3+ 2%n=66

Keratitis32.4%

G3+ 17.6%n=34

Keratopathy20%

n=59

Dry eye10%

G3+ 3%n=66

Cataract2%

Retinopathy2%

Keratopathy (corneal events) Grade 4-

Construct

Molecular anatomy

Antibody

IgG2

Human

Linker

Non-cleavable

DAR

Payload

Cys-mcMMAF

Tubulin inhibitor

Linker structureC10H13NO4

O=C(O)CCCCCN1C(=O)C=CC1=O

Payload structureC52H83N7O13S

CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN3C(=O)CC(C3=O)SC[C@@H](C(=O)O)N

Antibody

Antibody & Fc engineering

Antibody

AGS-16 Ab (anti-ENPP3)

Isotype

IgG2

Origin

Human

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Reduced

Linker & conjugation

Linker chemistry

Linker profile

Linker

mc (non-cleavable)

Class

Non-cleavable

Cleavage

Non-cleavable

Attachment

Cysteine (interchain)

Conjugation

Conventional interchain Cys

Symmetry

Symmetric

DAR (mean)

DAR homogeneity

Heterogeneous

Plasma t½

8.3 d

Cleavage trigger

Non-cleavable

Release control

Unconditional

Hydrophilicity mask

None

Formula

C10H13NO4

Linker MW

211.217 Da

Linker TPSA

74.68 Å²

Linker xLogP

0.5564

ADCdb linker

LIN0TAFAV

In-vitro stability

Stability note

Median t½ of total Ab after first dose 8.29 d (range 4.01–14.2) per Thompson CCR 2018 Ph1 N=58; cys-mcMMAF released payload t½ ~4 d. CHO-produced anti-ENPP3 IgG2; classical mc-MMAF chemistry

Payload

Payload & physicochemistry

Payload profile

Payload

Cys-mcMMAF

Class

Auristatin

Mechanism

Tubulin inhibitor

Released catabolite

Cys-mcMMAF

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

PAMPA rank

1046.3 Da

XLogP3

1.4

logD₇.₄

-1

TPSA

301 Å²

pKa

3.5 pKa

Charge pH 7.4

-1

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C52H83N7O13S

PubChem CID

86278355

ADCdb payload

PAY0QLDVX

Hydrophobicity · logD₇.₄

hydrophilic −2-1+4 lipophilic

Bioactivity note

Payload mechanism: MMAF is a microtubule (MT) inhibitor (ADCdb payload PAY0QLDVX therapeutic target 'Microtubule'). ADCdb cell-line cytotoxicity for the ADC: IC50 1.1 nM (ROSA KIT D816V), 2.73 nM (ROSA KIT D816V Gluc), 109.9 nM (HMC-1.1), 146.5 nM (HMC-1.2). Clinical: Phase 1 NCT

Dosing & regimen

Dosing

RP2D dose

1.8 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 2

Dose-OAE available

Yes

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

85 %

OAE grade 3+

21 %

OAE data status

reported

Severity (weighted)

40.2

Keratopathy

59 %

Conjunctival

Dry eye

50 %

Blurred vision

44 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v4

Reversibility

Reversible

Target expression in eye tissues (HCA detection · HPA bulk)

Cornea (central)

2.79 %

Cornea (limbal)

4.15 %

Conjunctiva

5.7 %

RPE

Retina (HPA)

0.3 nTPM

Cross-trial comparability

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

ags-16c3f

Approval status

Discontinued

Approval year

UniProt

O14638

ADCdb ADC

DRG0QRDUT

ADCdb antibody

ANI0JHLRK

ADCdb target

TAR0SJQDK

Primary source

Thompson CCR 2018 PMID 29848572

Aliases & development codes

CHO-produced successor of AGS-16M8F; anti-ENPP3-mcMMAF

Notes

Monotonic dose-OAE escalation 0%→100% from 0.6→4.8 mg/kg (Thompson 2018). V3.1 FLAG: full dose-cohort AE table not accessible via open web; OAE rates 85%/29%/59% retained from v2 Thompson tables but need verification from full PDF. Ph2 RCC arm (Kollmannsberger 2021) shows lower keratopathy 22%.