AGS-16M8F

Discontinued

anti-ENPP3-mcMMAF (hybridoma-derived variant)

Target

ENPP3 (CD203c) · ENPP3

Sponsor

Agensys/Astellas

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

5 adverse-event terms

Ocular

Any-grade

31%

G3+

3.8%

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

2.79%

Limbus

Express.

4.15%

Conjunctiva

Express.

5.7%

Lens

Express.

Retina / RPE

Express.

0.3 nTPM

Dominant tissue

Surface subtype

Unknown

Reversibility

Reversible

Reported ocular events

Eye disorders (any ocular AE, composite SOC)31%

G3+ 3.8%n=26

Dry eye19.2%

G3+ 3.8%n=26

Vision blurred15.4%

G3+ 0%n=26

Eye pruritus3.8%

n=26

Metamorphopsia3.8%

n=26

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 (hybridoma variant)

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

Same chemistry as 16C3F (mc-MMAF interchain Cys); hybridoma-derived predecessor with similar PK behavior in Thompson CCR 2018 (study closed before MTD reached, smaller cohort)

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 MMAF (ADCdb PAY0QLDVX, microtubule inhibitor) IC50 ~5.3-10 nM across tumor lines (SK-BR-3 5.3 nM; Hep-G2 7 nM; BT474-M1 8.8 nM; HT-29 10 nM). AGS-16C3F/AGS-16M8F ADC IC50 (ADCdb): 1.1 nM (ROSA KIT D816V), 2.73 nM (ROSA KIT D816V Gluc), 109.9 nM (HMC-1.1), 146.5 nM (HMC-1.

Dosing & regimen

Dosing

RP2D dose

1.8 mg/kg

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

31 %

OAE grade 3+

3.8 %

OAE data status

reported

Severity (weighted)

11.96

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Surface subtype

Unknown

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: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

ags-16m8f

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

anti-ENPP3-mcMMAF (hybridoma-derived variant)

Notes

Hybridoma-derived predecessor. V3.1 FLAG: Thompson 2018 abstract states study 'closed before MTD reached' — 1.8 mg/kg is nominal not formally established RP2D. n=26 is total study, not RP2D cohort. Comparable potency/PK to AGS-16C3F; differs only in production cell line (hybridoma vs CHO).