FOR-46

Investigational

FG-3246; FOR46; FOR-46

Target

Membrane cofactor protein (CD46) · CD46

Sponsor

FibroGen / Fortis Therapeutics

Indication

Metastatic castration-resistant prostate cancer (mCRPC)

Target family

Other

RP2D dose

2.7 mg/kg (adjusted body weight; MTD)

Every 3 weeks (Q3W)Pooled

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

1 adverse-event term

Ocular

Any-grade

G3+

Pooled

sagittal schematic · -

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Surface subtype

Unknown

Reversibility

Reported ocular events

Ocular adverse events (overall)0%

n=56

Construct

Molecular anatomy

Antibody

Human

Linker

Peptide

Cleavable

3.7

DAR

Payload

Monomethyl auristatin E (MMAE)

Microtubule polymerization inhibitor

Linker structureC28H40N6O7

[H]OC([H])([H])c1c([H])c([H])c(N([H])C(=O)[C@@]([H])(N([H])C(=O)[C@@]([H])(N([H])C(=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N2C(=O)C([H])=C([H])C2=O)C([H])(C([H])([H])[H])C([H])([H])[H])c([H])c1[H])c([H])c1[H]

Payload structureC39H67N5O7

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

Antibody

Antibody & Fc engineering

Antibody

Anti-CD46 fully human antibody (YS5/UA20-derived)

Isotype

Origin

Human

Fc modifications

Glycoengineering

Effector silencing

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

Mc-Val-Cit-PABC

Class

Peptide

Cleavage

Cleavable

Attachment

Cysteine (interchain)

Conjugation

Cysteine maleimide conjugation

Symmetry

Symmetric

DAR (mean)

3.7

DAR homogeneity

Plasma t½

Cleavage trigger

Cathepsin B (valine-citrulline dipeptide)

Release control

N/A

Hydrophilicity mask

None

Formula

C28H40N6O7

Linker MW

572.663 Da

Linker TPSA

200.03 Å²

Linker xLogP

0.6769

ADCdb linker

LIN0SQEDQ

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

Monomethyl auristatin E (MMAE)

Class

Auristatin

Mechanism

Microtubule polymerization inhibitor

Released catabolite

Monomethyl auristatin E (MMAE)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

717.98 Da

XLogP3

2.9

logD₇.₄

TPSA

171.92 Å²

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H67N5O7

PubChem CID

11542188

ADCdb payload

PAY0FSXOW

Bioactivity note

MMAE is a sub-nanomolar antimitotic (microtubule polymerization inhibitor; tubulin-binding auristatin). ADCdb classifies the target/payload therapeutic class as Microtubule (MT). No in-vitro IC50 was listed on the ADCdb ADC page; clinical efficacy reported in the FOR-46 (FG-3246)

Dosing & regimen

Dosing

RP2D dose

2.7 mg/kg (adjusted body weight; MTD)

Schedule

Every 3 weeks (Q3W)

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Tox summary basis

dose-escalation

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

0 %

OAE grade 3+

OAE data status

documented-absent

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Surface subtype

Unknown

Grading scale

CTCAE (unversioned)

Reversibility

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

Cornea (central)

Cornea (limbal)

Conjunctiva

RPE

Retina (HPA)

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE (unversioned)Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

for-46

Approval status

Investigational

Approval year

UniProt

P15529

ADCdb ADC

DRG0QMIBK

ADCdb antibody

ANI0QNBSC

ADCdb target

TAR0JMGXV

Primary source

FOR46 Phase I FIH mCRPC, J Clin Oncol 43:1824-1834 (2025), PMID 40138611

Aliases & development codes

FG-3246; FOR46; FOR-46

Notes

FOR-46 (FG-3246, FOR46), FibroGen/Fortis. Anti-CD46 fully human IgG conjugated to MMAE via Mc-Val-Cit-PABC (maleimidocaproyl, cathepsin-B cleavable, cysteine-attached), DAR 3.7 (ADCdb DRG0QMIBK / linker LIN0SQEDQ). CD46 = membrane cofactor protein, overexpressed in mCRPC; described as an immune-modulating ADC. DOSING/TOX from Phase I FIH FOR46-001 (NCT03575819), J Clin Oncol 43:1824-1834 (2025), PMID 40138611, DOI 10.1200/JCO-24-01989: n=56, IV Q3W, start 0.1 mg/kg, MTD 2.7 mg/kg (adjusted body weight). DLTs: neutropenia (n=4), febrile neutropenia (n=1), fatigue (n=1). Most common grade >=3 AEs: neutropenia 59%, leukopenia 27%, lymphopenia 7%, anaemia 7%, fatigue 5%. No treatment-related deaths. OCULAR: Triage-confirmed inclusion. Abstract conclusion states ocular AEs were infrequent, highlighted as a possible distinguishing feature vs other MMAE ADCs. The exact ocular PT-level percentages are NOT reported in the abstract or accessible secondary coverage (full JCO paper paywalled, HTTP 403). Therefore oae_any_pct left blank rather than imputing a number; ocular_surface_subtype=Unknown. In toxicity_rows the Ocular row uses pct=0 only as a structural placeholder for 'infrequent/low' (per schema, Any-grade row required) with an explicit note that this is NOT a documented absolute zero — it reflects an explicit 'infrequent' qualitative statement, not a quantified 0%. CTCAE assumed (version not stated). Confidence: G>=3 hematologic rows tier B (primary JCO abstract). IRR ~37% (G1-2) and peripheral neuropathy ~24% (G1-2) tier C (any-grade rates from secondary clinical coverage of the same paper; not directly verified against the full AE table). Payload physchem = standard MMAE values (PubChem CID 11542188), tier C; logD7.4/pKa left blank. Linker physchem from ADCdb (tier A/B source). Antibody isotype, DAR homogeneity, Fc engineering, n at RP2D, and most ocular subfields are blank (not in accessible literature).