Engineering Next-Generation Conjugates

Welcome to the Next-Generation Conjugates track. This field is evolving rapidly beyond classical ADCs into a broader landscape of precision-delivery platforms, with exciting advances in biology, chemistry, and engineering. Today’s session will explore both the promise and the practical realities of designing conjugates that can truly translate into better medicines. Thank you for being here, and let us get started.

Conjugates are evolving beyond traditional ADCs into a broader precision-delivery toolbox. This includes bispecific and dual-payload ADCs, oligonucleotide conjugates, degrader conjugates, and other engineered formats designed to tackle complex biological challenges and expand therapeutic windows. The keynote will explore the field's future directions, highlighting key innovations and discussing how next-generation conjugates can transcend technical complexities to achieve meaningful clinical transformations. 

AbTx develops next-gen ADCs using our TheranoStick platform, generating smaller formats (FDCs) for improved tumour access, faster clearance, and enhanced cytotoxicity. Our enzymatic conjugation (transglutaminase + patented Q-Tag system) ensures site-specific payload attachment across full-length antibodies, Fabs, scFvs, and VHHs, boosting efficacy and safety.

Antibody-drug conjugates suffer from slow systemic clearance, driving off-tumour payload exposure and dose-limiting toxicity. We engineered KBA651, a compact SIRPa-based MMAE conjugate targeting CD47 as a tumour antigen, that exploits renal filtration to achieve rapid plasma clearance, reshaping the PK/PD relationship relative to IgG-based formats. The small protein scaffold enhances tumour tissue penetration and enables site-specific conjugation with superior process control. By reducing systemic exposure while preserving tumour accumulation, KBA651 decouples efficacy from toxicity. Compatible with diverse payloads, including small molecules, siRNA, and radioisotopes, and leveraging broad CD47 upregulation, this platform unlocks a new generation of targeted oncology therapeutics.

Bus2Brain is a Nanofitin-based platform enabling targeted delivery of oligonucleotides across the blood–brain barrier, overcoming key limitations of current approaches. It enables precise conjugation, multispecific design, and efficient brain accumulation, expanding the landscape of CNS delivery strategies. Supported by in vivo data, this scalable platform unlocks the therapeutic potential of oligonucleotides for central nervous system disorders.

Antibody-drug conjugates (ADCs) have shown clinical benefit across cancers, but resistance to topoisomerase and microtubule inhibitor payloads limits durable responses. Hexagon Bio is leveraging its natural product discovery platform to identify ADC payloads with novel, non-overlapping mechanisms of action and to evaluate rational combinations that may drive deeper, more durable efficacy. Hexagon Bio's first payload targets translation. Upcoming data will highlight efficacy, activity in resistant settings and a favorable non-human primate safety profile for its HER2-targeting ADC, alongside progress across a broader payload pipeline and combination strategies.

Developing ADCs with novel payloads will be critical to differentiate new assets in the clinic and allow for sequencing in the evolving treatment landscape. We will be describing a new ADC payload platform with a novel mode of action for enhanced utility in previously treated and resistant or refractory cancer patients. We will establish protein alkylation as a differentiated, next-generation payload modality with the potential to overcome resistance and expand the ADC therapeutic window, and showcase the preclinical profile of IKS073, a B7H3–targeting ProAlk ADC with potent anti-tumor activity and a compelling efficacy–tolerability balance across solid tumour models.

There is a great need for novel ADC payloads with a different mode of action. Novel payloads can be used to treat ADC-resistant patients and expand patient populations. This talk will show the discovery of a novel PLK1/BET degrader payload and its application in a TROP2-targeting degrader antibody conjugate with excellent in vivo activity and a differentiating and mild toxicity profile.

We present data of a bispecific ADC with increased tumour selectivity. By applying an AND-gate approach and our proprietary conjugation technology, our candidate addresses on-target and off-target limitations of ADCs, respectively. Consequentially, the bsADC can be armed with a highly potent PBD payload. Our candidate shows preferential killing of double target positive cells in vitro, and promising efficacy, tolerability, and pharmacokinetics in mice.