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

Cornea

Surface subtype

Corneal (off-target)

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

Per-trial detail

Adverse events by trial

NCT01114230 (AGS-16M8F first-in-human Ph1)Phase 10.6-4.8 mg/kg (dose escalation, all levels pooled) IV q3wn=26CTCAE CTCAE v4.0PooledBto verify

Thompson, Clin Cancer Res 2018;24(18):4399-4406 PMID 29848572 / PMC6731023 / NCT01114230

6 adverse-event terms · 1 system · expand a system below

Other6

Subjects with at least 1 adverse event (overall incidence)

100%

26/26

Fatigue

46.2%

12/26

Thrombocytopenia

30.8%

8/26

Constipation

30.8%

8/26

Nausea

26.9%

7/26

Dyspnoea

26.9%

7/26

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

Reduced

C1q binding

Reduced

Target KD (nM)

0.08

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

Cell line

Hybridoma

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

Potency IC50 (nM)

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

ADA rate (%)

0 %

Target prevalence (%)

92.3 %

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

15.4 %

Blurred vision

15.4 %

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v4.0

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 · source-verified

Ascertainment: Symptom-driven reportingScale: CTCAE v4Denominator: RP2D⚠ Not comparable: symptom-driven ascertainment

Dose & schedule → ocular toxicity · ocular AE (any-grade) by cohort

0.6-4.8 mg/kg (events only at 2.4/3.6/4.8)

Q3W, IV infusion over 60 min

31%

n=26 · AGS-16M8F first-in-human Ph1

0.6-4.8 mg/kg (events at 2.4/3.6/4.8)

Q3W, IV infusion over 60 min

19.2%

n=26 · AGS-16M8F first-in-human Ph1

4.8 mg/kg

Q3W, IV infusion over 60 min

15.4%

n=26 · AGS-16M8F first-in-human Ph1

Per-cohort rates from the per-trial extraction, sorted by dose. Cross-trial comparison is subject to ascertainment / scale differences (see comparability above) — e.g. an early symptom-driven trial can read lower than a later systematic-exam trial at a higher dose.

Ocular AE grading reference — interspecialty consensus · 6 scales + dose modification

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).