ADC TOXICITY ATLAS
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HDP-101

Investigational
HDP-101; J22.9-amanitin ADC; anti-BCMA amanitin ADC
Sponsor
Heidelberg Pharma
Indication
Relapsed/refractory multiple myeloma
Target family
TNF receptor superfamily
RP2D dose
-
RP2D
01
Multi-organ toxicity

Fingerprint & organ drill-down

Also reported
0%severity100%
0
Assessed · clear
true 0%
No data
never assessed
1 adverse-event term

Ocular

Any-grade
0%
G3+
0%
RP2D
sagittal schematic · -
↳

Tissues shaded by reported adverse-event rate.

Cornea
AE
-
Express.
0.4%
Limbus
AE
-
Express.
0.6%
Conjunctiva
AE
-
Express.
0.06%
Lens
AE
-
Express.
-
Retina / RPE
AE
-
Express.
0%
0.1 nTPM
Dominant tissue
-
Surface subtype
None
Reversibility
-
Reported ocular events
Ocular disorders0%
02
Construct

Molecular anatomy

Antibody
IgG1
Human
Linker
Peptide
Cleavable
2
DAR
Payload
HDP 30.2115 (alpha-amanitin derivative)
RNA polymerase II inhibitor (transcription inhibition; POLR2A poison)
Linker structureC22H28N4O6
CC(NC(=O)C(NC(=O)CCN1C(=O)C=CC1=O)C(C)C)C(=O)Nc1ccc(CO)cc1
Payload structureC40H58N10O11S
CCC(C)C1NC(=O)CNCC2Cc3c([nH]c4ccccc34)SCC(NC(=O)CNCC1=O)C(=O)NC(CC(N)=O)C(=O)N1CC(O)CC1C(=O)NC(C(C)C(O)CO)C(=O)N2
03
Antibody

Antibody & Fc engineering

Antibody
J22.9-ISY
Isotype
IgG1
Origin
Human
Fc modifications
Engineered cysteine introduced at position 265 for site-specific conjugation
Glycoengineering
-
Effector silencing
-
FcγR binding
Retained
C1q binding
Retained
04
Linker & conjugation

Linker chemistry

Linker profile
Linker
Mal-Val-Ala-PAB
Class
Peptide
Cleavage
Cleavable
Attachment
Cysteine (interchain)
Conjugation
Site-specific (engineered cysteine at position 265)
Symmetry
Site-specific (paired)
DAR (mean)
2
DAR homogeneity
Homogeneous
Plasma t½
-
Cleavage trigger
Cathepsin B / Val-Ala dipeptidase-mediated cleavage
Release control
N/A
Hydrophilicity mask
None
Formula
C22H28N4O6
Linker MW
444.488 Da
Linker TPSA
144.91 Ų
Linker xLogP
0.078
ADCdb linker
LIN0BSKSQ
In-vitro stability
-
05
Payload

Payload & physicochemistry

Payload profile
Payload
HDP 30.2115 (alpha-amanitin derivative)
Class
Amatoxin
Mechanism
RNA polymerase II inhibitor (transcription inhibition; POLR2A poison)
Released catabolite
alpha-amanitin derivative (HDP 30.2115)
Mechanistic subtype
Other
Stereochem / salt
-
Bystander
Partial
PAMPA rank
-
MW
919 Da
XLogP3
-4.4
logD₇.₄
-
TPSA
400 Ų
pKa
-
Charge pH 7.4
-
H-bond donors
-
H-bond acceptors
-
IC50 (HCEC)
-
Formula
C40H58N10O11S
PubChem CID
-
ADCdb payload
PAY0VZNCV
Bioactivity note
ADCdb reports HDP-101 / HDP 30.2115 cytotoxicity IC50 across 11 cell-line experiments ranging from ~0.01 nM (highest potency, U266B1 myeloma line) to >1000 nM (non-target HS-5 and U2OS lines), demonstrating selective killing of BCMA-expressing multiple myeloma cells. Mechanism: a
06
Dosing & regimen

Dosing

RP2D dose
-
Schedule
-
Route
IV
Fractionated
Yes
n at RP2D
-
Dose basis
-
Trial phase
Phase 1/2
Dose-OAE available
Yes
Tox summary basis
RP2D
07
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)
0
Keratopathy
-
Conjunctival
-
Dry eye
-
Blurred vision
-
Dominant tissue
-
Surface subtype
None
Grading scale
CTCAE (unversioned)
Reversibility
-
Target expression in eye tissues (HCA detection · HPA bulk)
Cornea (central)
0.4 %
Cornea (limbal)
0.6 %
Conjunctiva
0.06 %
RPE
0 %
Retina (HPA)
0.1 nTPM
Cross-trial comparability · source-verified
Ascertainment: Symptom-driven reportingScale: CTCAE (unversioned)Denominator: RP2D⚠ OAE rate not directly comparable across trials
08
Identity & registry

Identifiers, registry & notes

ADC id
hdp-101
Approval status
Investigational
Approval year
-
UniProt
Q02223
ADCdb ADC
DRG0WIBDT
ADCdb antibody
ANI0OBRWR
ADCdb target
PATR0QBNMQ
Primary source
ASH 2024 abstract (FIH NCT04879043), Blood 2024;144(Suppl 1):3381
Aliases & development codes
HDP-101; J22.9-amanitin ADC; anti-BCMA amanitin ADC
Notes
HDP-101 (Heidelberg Pharma) is an anti-BCMA (TNFRSF17) ADC with the fully human IgG1 antibody J22.9-ISY, a Mal-Val-Ala-PAB cathepsin-cleavable linker, site-specific conjugation at an engineered cysteine (position 265), DAR 2, and a novel synthetic alpha-amanitin derivative payload (HDP 30.2115) that inhibits RNA polymerase II — a distinct mechanism from antimicrotubule/maytansinoid ADCs. OCULAR: Triage-confirmed explicit-zero. The FIH Phase 1/2a (NCT04879043; ASH 2024, Blood 2024;144(Suppl 1):3381; also AACR 2024 CT067) states the initial four dose cohorts were well tolerated with explicit absence of hepatic/renal toxicities, infusion reactions, or ocular disorders; oae_any_pct=0, subtype None. The dose-limiting/dominant toxicity is transient thrombocytopenia (all patients in the 100 µg/kg cohort; 3 DLTs; nadir C1D5, recovery by D15), with mild transient ALT/AST elevations at the same cohort. As of July 2024, 19 patients enrolled across 20/30/60/80/100 µg/kg cohorts plus a 90 µg/kg dose-optimization cohort (premedication/split-dosing arms); RP2D/MTD not yet established, so no RP2D dose/schedule reported (left blank). Route is IV. Free amanitin payload not detected in serum (LOD 30 ng/mL); no ADA/immunogenicity. Confidence: conference-abstract granularity (Tier D) for clinical/toxicity; composition Tier B (ADCdb + preclinical PMC10802748); linker physchem from ADCdb LIN0BSKSQ; payload physchem from PubChem alpha-amanitin (CID 9543442) as proxy for the HDP 30.2115 derivative (Tier C). Linker plasma t1/2, RP2D, dosing schedule, payload logD/pKa/charge, and AE reversibility/CTCAE version left blank (not in accessible literature).