ADC Programs

IKS03

Best in class CD19-directed ADC for B-cell cancers

IKS03 is currently in Phase 1 clinical trials for B-cell lymphomas.

IKS03 has been designed to deliver high anti-cancer activity with good patient tolerability. The ADC benefits from tumor-selective release and activation of ultra-potent PBD payloads for an enhanced TI.

Preclinical studies have demonstrated class leading efficacy across a wide range of B-cell cancer models and improved safety over in-clinic comparators. Phase 1 recruitment is ongoing at sites in Australia, Europe, the United States and Canada

IKS03 development status

ADC

IKS03

Target

CD19

Indication

B-cell malignancies

Research Pre-clinical Clinical

Differentiation by design

IKS03 is comprised of an anti-CD19 antibody, engineered for site-specific conjugation of PBD prodrug payloads.

A beta-glucuronide linker is used for tumor-selective payload release, whilst a second beta-glucuronide moiety improves hydrophilicity and plasma stability of the PBD prodrug.

Payload release and ADC activation requires processing by beta-glucuronidase, an enzyme overexpressed in cancer cell lysosomes, active only at acidic pH and with expression in normal tissues.

CD19 is an attractive target for B-cell malignancies

CD19 is a B-cell specific antigen which is broadly expressed in most B-cell malignancies

In normal cells, CD19 expression is limited to cells in the B-cell lineage. No significant on-target toxicity risks are therefore expected for an ADC approach.

CD19 has a wider and more consistent range of expression in B-cell cancers than other common targets such as CD20, CD79b, ROR1 and CD30 - providing enhanced therapeutic options compared with others.

Class leading profile

In preclinical studies, IKS03 is associated with class-leading TI.

Compared with the in-clinic comparator Zynlonta, (loncastuximab tesirine), IKS03 is significantly more active at lower doses after single-dose administration, with an HNSTD (in NHPs) that is approximately twofold higher.

IKS03’s advanced ADC design improves upon the high efficacy of DNA crosslinkers whilst not being associated with delayed toxicity, thus significantly increasing therapeutic index.

In addition, IKS03 is efficacious in high-grade 'triple hit', refractory and MYC-amplified lymphoma PDX models in vivo.

IKS03 has Best in class TI for CD19-targeting therapies

Drug	Payload	MED (mouse CR)	Preclinical Therapeutic Index*
Zynlonta (loncastuximab tesirine)	PBD	0.6 - 1.0 mg/kg	< 1
IKS03	proPBD	≤ 0.3 mg/kg	> 5
Polivy	MMAE	2.5 mg/kg	< 1.2

*TI = monkey HNSTD/mouse CR: IKS03 is well tolerated at 1.5mg/kg in monkeys

IKS03 is highly active in B-cell lymphoma models, including those in which Polivy is inactive or shows early relapse

Regressions are observed with single doses of 0.1-0.3 mg/kg in ABC-DLBCL, GCB-DLBCL and MCL xenograft models

Clinical trial overview

Clinical trial NCT05365659 is an open label, uncontrolled non-randomized multi-center, 2 part study assessing IKS03 in patients with non-Hodgkin Lymphoma that is either relapsed, refractory to, or intolerant of existing therapy/ies, or for which no standard of care is available.

Part I is a dose escalation 3+3 design study, with a primary objective of safety (MTD).

Part II is a dose expansion study in specified indications, with a primary objective of Objective Response Rate (ORR)

The study is being conducted in investigative sites in Italy, Spain, Australia and the US

Site Locations

United States

Baltimore, Maryland, United States, 21201

Australia

Westmead, New South Wales, Australia, 2145

Adelaide, South Australia, Australia: Royal Adelaide Hospital

Perth, Western Australia, Australia

Linear Clinical Research

Sir Charles Gairdner Hospital/Linear Clinical Research, Hospital Ave, Nedlands, Perth, WA 6009, Australia

Royal Hobart Hospital, 48 Liverpool St, Hobart TAS 7000, Australia

Canada

Montréal, Quebec, Canada, H3T 1E2; Jewish General Hospital

Italy

Milano:

La Fondazione e l'Istituto di Candiolo

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele

Istituto Europeo Clinico Humanitas

Istituto Europeo di Oncologia

Spain

Badalona, Institut Catala d’Oncologia

Madrid, Hospital Universitario Quironsalud

Salamanca, Hospital Clinico Universitario de Salamanca

Valencia, Hospital Universitari i Politecnic La Fe

Pipeline prioritization strategy

Clinically meaningful differentiation is central to our ADC design.

Iksuda only progresses ADC programs which meet our design criteria to clinical assessment. For programs directed to known ADC targets, with in-clinic and/ or on-market ADCs available, raising TI to a clinically meaningful degree is prerequisite in our decision-making.