AVID-100

Discontinued

AVID100; AVID 100; MAB100-SMCC-DM1

Target

Epidermal growth factor receptor (EGFR; ErbB1/HER1) · EGFR

Sponsor

Formation Biologics (Forbius)

Indication

EGFR-overexpressing advanced solid tumors (SCCHN, squamous NSCLC, TNBC)

Target family

Receptor tyrosine kinase

RP2D dose

220 mg/m2 (~6 mg/kg)

Q3WRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

10 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Reversible

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

89.35%

Limbus

Express.

97.58%

Conjunctiva

Express.

93.02%

Lens

Express.

Retina / RPE

Express.

83.36%

9.4 nTPM

Off-target signature

8% corneal toxicity, yet the Epidermal growth factor receptor (EGFR; ErbB1/HER1) target is detected in only 89.35% of central cornea - toxicity is not explained by target expression.

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Reversibility

Reversible

Reported ocular events

Lacrimation increased20%

Keratitis punctate14.3%

n=7

Conjunctivitis allergic (Allergic conjunctivitis)8.3%

Dry eye4%

Lacrimation increased (Watering eyes)-

Conjunctival injection (conjunctival hyperaemia)-

Eye pain / Eye irritation-

Uveitis-

Photophobia-

Keratitis-

Per-trial detail

Adverse events by trial

AVID100 Phase 1a/2a (NCT03094169)Phase 1a/2aAVID100 20-270 mg/m^2 (all dose levels pooled) Q3W (every 3 weeks), 2-hour IV infusionn=49CTCAE MedDRA 22.0 (CT.gov sePooledCto verify

CT.gov posted results NCT03094169 (pooled serious AE across 8 arms, derived; 1/49) NCT03094169

76 adverse-event terms · 18 systems · expand a system below

General12

Fatigue

38.78%

19/49

Progression of Disease

6.12%

3/49

Mucosal Inflammation

6.12%

3/49

Pain

6.12%

3/49

Anorexia

6.12%

3/49

Dysphagia

4.08%

2/49

Dysphasia

2.04%

1/49

Uncontrolled pain

2.04%

1/49

Flu like symptoms

2.04%

1/49

Creatine Kinase increase

2.04%

1/49

Malignant neoplasm progression

2.04%

1/49

Face Oedema

2.04%

1/49

Investigations11

Infections8

Pulmonary8

GI7

Metabolic5

Dermatologic5

Ocular4

Lacrimation Increased

12.24%

6/49

Keratitis

10.2%

5/49

Dry Eye

6.12%

3/49

Conjunctivitis Allergic

4.08%

2/49

Hematologic2

Hepatic2

Musculoskeletal2

Psychiatric2

Renal2

Vascular2

Cardiac1

Immune1

Neoplasms1

Neurologic (other)1

Construct

Molecular anatomy

Antibody

IgG1

Chimeric

Linker

Non-cleavable

3.5

DAR

Payload

Lys-SMCC-DM1

Tubulin inhibitor

Linker structureC16H18N2O6

[H]C1=C([H])C(=O)N(C([H])([H])C2([H])C([H])([H])C([H])([H])C([H])(C(=O)ON3C(=O)C([H])([H])C([H])([H])C3=O)C([H])([H])C2([H])[H])C1=O

Payload structureC53H75ClN6O15S

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([C@H]1O4)C)OC(=O)[C@H](C)N(C)C(=O)CCSC5CC(=O)N(C5=O)CC6CCC(CC6)C(=O)NCCCC[C@@H](C(=O)O)N)C)\C)OC)(NC(=O)O2)O

Antibody

Antibody & Fc engineering

Antibody

MAB100

Isotype

IgG1

Origin

Chimeric

Fc modifications

Two amino-acid differences in Fc vs cetuximab

Glycoengineering

Effector silencing

Not silenced

FcγR binding

Retained

C1q binding

Retained

Target KD (nM)

Epitope / domain

EGFR extracellular domain III

Linker & conjugation

Linker chemistry

Linker profile

Linker

SMCC

Class

Non-cleavable

Cleavage

Non-cleavable

Attachment

Lysine

Conjugation

Conventional Lys (SMCC)

Symmetry

Symmetric

DAR (mean)

3.5

DAR homogeneity

Heterogeneous

Plasma t½

Cleavage trigger

Non-cleavable

Release control

Unconditional

Hydrophilicity mask

None

Cell line

CHO

Formula

C16H18N2O6

Linker MW

334.328 Da

Linker TPSA

101.06 Å²

Linker xLogP

0.325

ADCdb linker

LIN0EBJON

In-vitro stability

Stability note

Stable in circulation; conjugated-antibody PK closely tracks total-antibody PK; serum DM1 catabolite remained low in non

Payload

Payload & physicochemistry

Payload profile

Payload

Lys-SMCC-DM1

Class

Maytansinoid

Mechanism

Tubulin inhibitor

Released catabolite

Lys-SMCC-DM1 (lysine-Neps-MCC-DM1); charged, membrane-impermeable catabolite (= same released species as trastuzumab-emtansine)

Mechanistic subtype

Tubulin-maytansinoid

Stereochem / salt

Bystander

PAMPA rank

1103.7 Da

XLogP3

-0.2

logD₇.₄

-0.5

TPSA

312 Å²

pKa

2.2 pKa

Charge pH 7.4

Zwitterion

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C53H75ClN6O15S

PubChem CID

71587969

ADCdb payload

PAY0JCIBW

Hydrophobicity · logD₇.₄

hydrophilic −2-0.5+4 lipophilic

Bioactivity note

MAB100 KD ~2 nM to EGFR ectodomain; competes with EGF; inhibits EGFR/MAPK/Akt phosphorylation

Dosing & regimen

Dosing

RP2D dose

220 mg/m2 (~6 mg/kg)

Schedule

Q3W

Route

Fractionated

n at RP2D

Dose basis

BSA

Trial phase

Phase 1

Dose-OAE available

Yes

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

8 %

OAE grade 3+

0 %

OAE data status

reported

Severity (weighted)

Keratopathy

8 %

Conjunctival

Dry eye

4 %

Blurred vision

Dominant tissue

Cornea

Surface subtype

Corneal (off-target)

Grading scale

CTCAE v5.0

Reversibility

Reversible

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

Cornea (central)

89.35 %

Cornea (limbal)

97.58 %

Conjunctiva

93.02 %

RPE

83.36 %

Retina (HPA)

9.4 nTPM

Cross-trial comparability · source-verified

Ascertainment: Systematic eye examsScale: CTCAE v4Denominator: RP2D

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

AVID100 120 mg/m^2

Q3W (every 3 weeks), 2-hour IV infusion

33.33%

n=3 · AVID100 Phase 1a/2a

180 mg/m2 (inferred)

Q3W

14.3%

n=7 · NCT03094169

AVID100 220 mg/m^2

Q3W (every 3 weeks), 2-hour IV infusion

33.33%

n=6 · AVID100 Phase 1a/2a

220 mg/m2

Q3W

33.3%

n=6 · NCT03094169

220 mg/m2

Q3W

n=25 · NCT03094169

AVID100 220 mg/m^2

Q3W (every 3 weeks), 2-hour IV infusion

n=25 · AVID100 Phase 1a/2a

AVID100 270 mg/m^2

Q3W (every 3 weeks), 2-hour IV infusion

14.29%

n=7 · AVID100 Phase 1a/2a

AVID100 20-270 mg/m^2 (all dose levels pooled)

Q3W (every 3 weeks), 2-hour IV infusion

10.2%

n=49 · AVID100 Phase 1a/2a

270 mg/m2

8.3%

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

avid-100

Approval status

Discontinued

Approval year

UniProt

P00533

ADCdb ADC

DRG0OJHEN

ADCdb antibody

ANI0ABINN

ADCdb target

TAR0UYFIF

Primary source

Spira et al. AACR 2019 Abstract CT056 (Cancer Res 2019;79(13 Suppl):CT056); ESMO 2019 (Ann Oncol 2019;30(Suppl 5), S0923-7534(19)32637-7); ADCdb DRG0OJHEN

Aliases & development codes

AVID100; AVID 100; MAB100-SMCC-DM1

Notes

Anti-EGFR-DM1 ADC: antibody MAB100 + SMCC non-cleavable linker + DM1 maytansinoid; structurally analogous to trastuzumab-emtansine (T-DM1) but with a function-blocking anti-EGFR antibody engineered to spare normal EGFR+ tissue. Shares the exact ADCdb linker record LIN0EBJON (SMCC) and DM1 payload with T-DM1, so linker physchem, payload physchem (Lys-SMCC-DM1 catabolite), and chemistry fields are mirrored from T-DM1 (tier C, derived). CLINICAL: Phase 1a/2a, NCT03094169 (Formation Biologics/Forbius). Phase 1a dose-escalation n=24, cohorts 1-6 = 20/40/80/120/180/220 mg/m2 q3w (2-h IV); no cycle-1 DLTs; RP2D = 220 mg/m2 (~6 mg/kg) q3w - among the highest RP2D of any ADC in development. Phase 2a expansion at RP2D (n=25). Program discontinued for lack of efficacy. OCULAR (qualifying AE): punctate keratitis, dose-dependent - 1/7 (14.3%) at a higher Ph1a level (~180 mg/m2, dose-level inferred), 2/6 (33.3%) at 220 mg/m2 Ph1a, 2/25 (8.0%) at 220 mg/m2 Ph2a expansion (the RP2D row). Low-grade, not a DLT. EGFR is expressed on corneal epithelium, so keratitis is on-target/off-tumor mechanistically; classified ocular_surface_subtype='Corneal (off-target)' per the DB's controlled vocabulary and matching the other anti-EGFR ADC depatuxizumab-mafodotin. oae_g3plus left blank (no explicit G3+ ocular count; events characterized as low-grade). OTHER TOX: Phase 1a pooled (n=24, all G1-2): rash 66.7%, nausea 41.7% (GI row), fatigue 29.2%. Reported qualitatively WITHOUT percentages (not rowable since pct is required): infusion-related reactions (ameliorated by premedication + infusion prolongation), vomiting, headache, anorexia, mucositis, diarrhea, reversible transaminase + alkaline-phosphatase elevations (no other evidence of hepatotoxicity), elevated amylase / G2-3 lipase, hypomagnesemia, hypokalemia, reversible thrombocytopenia. Hepatic / Hematologic / Infusion are therefore reported-but-unquantified and left without summary rows. CAVEATS: DAR undisclosed by sponsor & ADCdb (dar_mean blank); dar_homogeneity='Heterogeneous (Lys)' and conjugation_method='Conventional Lys (SMCC)' are DERIVED (tier C) from the SMCC lysine-NHS-ester chemistry. Antibody isotype/origin not disclosed (likely humanized IgG1; cf. depatuxizumab). Fc engineering not disclosed (likely wild-type IgG1; effector_silencing left blank). payload_name recorded as 'Lys-SMCC-DM1' to mirror T-DM1's representation (warhead = DM1/mertansine, ADCdb PAY0JCIBW). Sponsor = Formation Biologics (Forbius); ADCdb also lists Bristol Myers Squibb - BMS acquired Forbius in 2020 for its TGF-beta assets (AVID200/300), not the AVID100 ADC. All clinical/ocular data are conference-abstract level (tier D); no peer-reviewed full paper or regulatory label exists. overall_tier=D reflects the qualifying OAE evidence; composition/adcdb cells are tier B and physchem/chemistry are tier C (derived from T-DM1).