TRPH-222

Discontinued

CAT-02-106; CD22-4AP; TRPH 222; TRPH222

Target

B-cell receptor CD22 / Sialic acid-binding Ig-like lectin 2 (Siglec-2) · CD22

Sponsor

Triphase Accelerator Corp. (SMARTag via Catalent/Redwood Bioscience)

Indication

Relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL)

Target family

Siglec

RP2D dose

7.5 mg/kg

Q3W (once every 3 weeks)RP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

3 adverse-event terms

Ocular

Any-grade

31%

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.5%

Limbus

Express.

1.1%

Conjunctiva

Express.

1.64%

Lens

Express.

Retina / RPE

Express.

1.16%

0 nTPM

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Ocular/eye disorders (composite; blurred vision and/or dry eye, epithelial keratopathy)31%

n=32

Dry eye-

G3+ 6%n=32

Blurred vision (vision blurred)-

G3+ 6%n=32

Construct

Molecular anatomy

Antibody

Humanized

Linker

Non-cleavable

DAR

Payload

Maytansine (maytansinoid derivative; ADCdb PAY0CHGPD)

Microtubule/tubulin polymerization inhibitor (antimitotic, M-phase arrest)

Linker structureC30H45N5O8

CNN(C)Cc1cc2ccccc2n1CCC(=O)N1CCC(N(CCOCCOCCC(=O)O)C(=O)CCC(=O)O)CC1

Payload structureC32H44ClN3O9

C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4(C1O4)C)OC(=O)[C@H](C)NC)C)\C)OC)(NC(=O)O2)O

Antibody

Antibody & Fc engineering

Antibody

Isotype

Origin

Humanized

Fc modifications

Glycoengineering

Effector silencing

FcγR binding

Retained

C1q binding

Retained

Linker & conjugation

Linker chemistry

Linker profile

Linker

HIPS-4AP

Class

Non-cleavable

Cleavage

Non-cleavable

Attachment

Genetic fusion

Conjugation

Site-specific SMARTag (aldehyde-tag/formylglycine + HIPS chemistry); engineered/non-natural residue

Symmetry

Site-specific (paired)

DAR (mean)

DAR homogeneity

Homogeneous

Plasma t½

Cleavage trigger

None (non-cleavable HIPS-4AP linker; payload released only by lysosomal antibody catabolism)

Release control

Unconditional

Hydrophilicity mask

Discrete-PEG-spacer

Formula

C30H45N5O8

Linker MW

603.72 Da

Linker TPSA

153.88 Å²

Linker xLogP

1.79

ADCdb linker

LIN0RJLTB

In-vitro stability

Payload

Payload & physicochemistry

Payload profile

Payload

Maytansine (maytansinoid derivative; ADCdb PAY0CHGPD)

Class

Maytansinoid

Mechanism

Microtubule/tubulin polymerization inhibitor (antimitotic, M-phase arrest)

Released catabolite

Charged amino-acid-HIPS-4AP-maytansinoid adduct (non-cleavable; cell-impermeable catabolite analogous to lysine-MCC-DM1)

Mechanistic subtype

Tubulin-maytansinoid

Stereochem / salt

Bystander

PAMPA rank

650.17 Da

XLogP3

3.28

logD₇.₄

TPSA

148.19 Å²

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C32H44ClN3O9

PubChem CID

90167111

ADCdb payload

PAY0CHGPD

Bioactivity note

ADCdb (DRG0JCWGF): Phase 1 objective response rate 22.70% (all). Preclinical xenograft tumor growth inhibition approximately 51% to 100% across cell lines. No payload IC50 reported on ADCdb/PubChem pages.

Dosing & regimen

Dosing

RP2D dose

7.5 mg/kg

Schedule

Q3W (once every 3 weeks)

Route

Fractionated

n at RP2D

Dose basis

TBW

Trial phase

Phase 1

Dose-OAE available

Partial

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

31 %

OAE grade 3+

6 %

OAE data status

reported

Severity (weighted)

13.5

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE (unversioned)

Reversibility

Reversible

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

Cornea (central)

0.5 %

Cornea (limbal)

1.1 %

Conjunctiva

1.64 %

RPE

1.16 %

Retina (HPA)

0 nTPM

Cross-trial comparability

Ascertainment: Monitoring unknownScale: CTCAE (unversioned)Denominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

trph-222

Approval status

Discontinued

Approval year

UniProt

P20273

ADCdb ADC

DRG0JCWGF

ADCdb antibody

ADCdb target

Primary source

TRPH-222 Phase 1 R/R B-NHL: EHA 2022 P1152 (HemaSphere; PMC9430507) + ASH 2020 (Blood 136 Suppl 1:41, abstr 142859) + Triphase PR 2022-02-22; NCT03682796. Composition/physchem from ADCdb DRG0JCWGF / LIN0RJLTB / PAY0CHGPD.

Aliases & development codes

CAT-02-106; CD22-4AP; TRPH 222; TRPH222

Notes

TRPH-222 (CAT-02-106) = humanized anti-CD22 maytansinoid ADC built with Catalent/Redwood SMARTag site-specific conjugation (genetically encoded aldehyde tag/formylglycine + HIPS chemistry), non-cleavable HIPS-4AP linker, DAR 2 (homogeneous). Sponsor Triphase Accelerator; Phase 1 only, program terminated. Antibody name and isotype are undisclosed (humanized anti-CD22; engineered aldehyde-tagged IgG, isotype not confirmed in accessible sources) -> left blank. Clinical: Phase 1 dose-escalation + expansion in R/R B-NHL, n=32 (15 indolent / 17 aggressive; 22 escalation 0.6-10 mg/kg, 10 expansion at 7.5 mg/kg), IV Q3W; NCT03682796. RP2D not formally declared; expansion/recommended dose 7.5 mg/kg. DLTs: Gr3-4 transaminase elevation (4.2 and 10 mg/kg) and Gr3 thrombocytopenia (4.2 mg/kg). Treatment-related SAEs (thrombocytopenia + pyrexia) in 6.3% at 7.5 mg/kg. Grade>=3 AEs more prevalent at doses >=7.5 mg/kg. Ocular (STRONG INCLUDE): off-target maytansinoid epithelial keratopathy. Published grade>=3 ocular = dry eye 6% and blurred vision 6% (Tier B, EHA 2022 P1152 / Triphase PR). Any-grade ocular ~31% (~10/32; grade 1-2 blurred vision and/or dry eye, onset cycles 1-3, doses ~2.0-10 mg/kg) per curator reading of the EHA poster (Tier C; per-PT all-grade splits not separately published). Reversible to <=Gr1 with dose interruption/reduction +/- lubricant eye drops; 1 patient discontinued for Gr3 dry eye + blurred vision. CD22 is not expressed in ocular surface tissue, so this is off-target corneal epitheliopathy (classic DM/maytansinoid class effect); subtype = Corneal (off-target), with blurred vision/dry eye as downstream manifestations. Physchem: linker HIPS-4AP (LIN0RJLTB) C30H45N5O8, MW 603.72, TPSA 153.88, xLogP 1.79 (ADCdb computed); SMILES shows discrete PEG2 spacer + dicarboxylic-acid hydrophilizing arms (hydrophobicity masking = Discrete-PEG-spacer). Payload (PAY0CHGPD) is the TRPH-222 maytansinoid derivative C32H44ClN3O9, MW 650.17, xLogP 3.28, TPSA 148.19 (ADCdb computed, Tier C); logD7.4/pKa/charge not available. Non-cleavable maytansinoid -> minimal/no bystander effect (charged, cell-impermeable amino-acid-linker-maytansinoid catabolite, analogous to lysine-MCC-DM1). No reported pulmonary/ILD, infusion, GI, or peripheral-neuropathy grade>=3 signal in accessible sources (not fabricated). CTCAE version not stated. Derived columns (dna_damage subtype, stability cond/uncond, FcgammaR/C1q, severity, HCA/HPA) intentionally left for downstream computation.