TORL-1-23

Investigational

TORL 1-23; TORL1-23; TORL 1 23

Target

Claudin-6 · CLDN6

Sponsor

TORL Biotherapeutics LLC

Indication

Advanced CLDN6-positive solid tumors (ovarian, testicular, endometrial, NSCLC)

Target family

Claudin / tight-junction

RP2D dose

2.4-3.0

Q3W (every 3 weeks)RP2D

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+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

Limbus

Express.

Conjunctiva

Express.

Lens

Express.

Retina / RPE

Express.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Ocular toxicity (collective); corneal pseudomicrocysts/whorled epithelial keratopathy per case report0%

n=81

Construct

Molecular anatomy

Antibody

IgG1

Humanized

Linker

Peptide

Cleavable

DAR

Payload

MMAE (monomethyl auristatin E)

Tubulin inhibitor (microtubule disruptor)

Linker structure

structure not applicable

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

TORL-1-23-MAb (anti-CLDN6; sequence undisclosed)

Isotype

IgG1

Origin

Humanized

Fc modifications

Glycoengineering

Effector silencing

None disclosed (wild-type humanized IgG1 Fc; no silencing mutations reported)

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

Valine-citrulline (vc); vc-MMAE

Class

Peptide

Cleavage

Cleavable

Attachment

Conjugation

Symmetry

DAR (mean)

DAR homogeneity

Plasma t½

Cleavage trigger

Cathepsin B (lysosomal cysteine protease); Val-Cit (vc) dipeptide substrate

Release control

Conditional

Hydrophilicity mask

None

Formula

Linker MW

Linker TPSA

Linker xLogP

ADCdb linker

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

MMAE (monomethyl auristatin E)

Class

Auristatin

Mechanism

Tubulin inhibitor (microtubule disruptor)

Released catabolite

MMAE (free monomethyl auristatin E; released by cathepsin-B cleavage of Val-Cit, PAB self-immolation; Cys-mc-vc-PAB-MMAE intermediate)

Mechanistic subtype

Tubulin-auristatin

Stereochem / salt

Bystander

Yes

PAMPA rank

718 Da

XLogP3

4.1

logD₇.₄

2.7

TPSA

150 Å²

pKa

9.1 pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C39H67N5O7

PubChem CID

11542188

ADCdb payload

PAY0FSXOW

Hydrophobicity · logD₇.₄

hydrophilic −2+2.7+4 lipophilic

Dosing & regimen

Dosing

RP2D dose

2.4-3.0

Schedule

Q3W (every 3 weeks)

Route

Fractionated

n at RP2D

Dose basis

Trial phase

Other

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

0 %

OAE grade 3+

0 %

OAE data status

documented-absent

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v5

Reversibility

Reversible

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 v5Denominator: RP2D

Identity & registry

Identifiers, registry & notes

ADC id

torl-1-23

Approval status

Investigational

Approval year

UniProt

P56747

ADCdb ADC

DRG0KYOBC

ADCdb antibody

ADCdb target

TAR0UDQEU

Primary source

ESMO 2024 FIH Ph1 (Ann Oncol 2024 abstr 721MO; NCT05103683) + case report Am J Ophthalmol Case Rep 2025 (PMC12270602)

Aliases & development codes

TORL 1-23; TORL1-23; TORL 1 23

Notes

CLDN6-targeted ADC: fully humanized IgG1 (TORL-1-23-MAb) + cathepsin-cleavable valine-citrulline (vc) linker + MMAE payload (vc-MMAE), DAR 4 (ADCdb DRG0KYOBC). Antibody sequence, linker attachment chemistry, conjugation site/method and DAR homogeneity are NOT publicly disclosed (vc-MMAE conventionally implies maleimidocaproyl interchain-cysteine conjugation, but TORL/ADCdb list conjugate type 'Undisclosed' and no linker LIN id exists, so all ADCdb linker physchem cells are blank). FIH Phase 1 (NCT05103683, TORL123-001/TRIO-049; ESMO 2024 abstr 721MO, n=81 evaluable): 11 dose cohorts 0.2-4.0 mg/kg IV Q3W; MTD not reached and no formal RP2D declared; doses being expanded are 2.4 and 3.0 mg/kg (prophylactic pegfilgrastim added at >=3.0 mg/kg, effective for neutropenia). Headline TRAEs (overall n=81, predominantly G1-2): fatigue 42%, peripheral neuropathy 40%, alopecia 38%, nausea 31%, anaemia 31%, WBC decrease 23%, arthralgia 23%; most common G3+ TRAE neutropenia 23%. Fatigue/alopecia/arthralgia/myalgia not captured in toxicity_rows (outside the 7 tracked organ systems). Febrile neutropenia, ILD, and OCULAR toxicities were explicitly NOT observed in the trial (oae_any_pct=0). HOWEVER a separate peer-reviewed case report (PMC12270602, Am J Ophthalmol Case Rep 2025) documents the first ocular AE: bilateral whorled corneal epithelial pseudomicrocysts, decreased visual acuity, photophobia in a treated patient (dosed 4.0 then 2.4 mg/kg) -- classic MMAE off-target corneal microcystic keratopathy, partially reversible/recurrent with dose reduction + topical management. Genuine corneal off-target ocular signal exists despite the 0% trial cohort rate; ocular_surface_subtype/dominant_ae_tissue/reversibility are sourced from this case report. Source discrepancies: top escalation dose reported as 3.6 mg/kg (Medpath) vs 4.0 mg/kg (PRNewswire/case report); dose-expansion n reported as 20 (ESMO Part 2: 2.4 mg/kg n=12 + 3.0 mg/kg n=8) vs 30 (Medpath: 51 escalation + 30 expansion). Payload physchem = standard MMAE (PubChem CID 11542188), reused from the DB's canonical MMAE values. Phase 2 CATALINA-2 in platinum-resistant ovarian cancer is planned/ongoing.