ON-BOARD™ PLATFORM
ON-BOARD™ PLATFORM
Attributes & Benefits of ON-BOARD ™ Platform
HIGHLY TUNABLE PLATFORM
Tunable core hydrophobicity, core and shell functional groups – suitable for encapsulation, conjugation
LARGE UNIVERSE OF POTENTIAL DRUG TARGETS
Demonstrated ability to deliver small molecules, antibody fragments and cytokines
INCREASED TUMOR PENETRATION, EFFICACY
Unique properties provides improved penetration compared to traditional polymeric approaches
REDUCED TOXICITY
Improved therapeutic window due to limited exposure of payload to normal tissues – offers potential to improve upon discontinued, existing and developmental compounds
AVOIDS LIMITATIONS & COMPLEXITY OF ACTIVE TARGETING
Eliminates need for active targeting with mAbs/other agents that limit therapeutic utility
ONM-400: Tumor-Specific Delivery of IL-2
OMN-400 addresses shortcomings of other IL-2 product candidates:
- Highly specific tumor delivery
- High loading capacity, instantaneous IL-2 release leads to high tumor accumulation
- Effective payload “shielding” from normal tissues, avoids systemic exposure and IL-2 toxicity
ON-BOARD™ delivery avoids requirement for mutein forms of IL-2
- Low tumor concentrations achieved with WT IL-2 led to use of muteins to minimize Treg regulation
- ONM-400 provides high tumor concentrations resulting in preferential activation of T effectors over Tregs eliminating the need for muteins
- ONM-400 avoids off target binding to normal tissues eliminating need for mutein forms
- ONM-400 optimizes delivery of a commercially validated rhIL-2, reducing clinical risk
ONM-400 Delivery Enables Favorable PK and Targeted Tumor Delivery
- Distinctly different accumulation pattern for ONM-400 versus free IL-2
- ONM-400: Strong preferential accumulation in tumors over other tissues/organs
- Free IL-2: Predominantly accumulates in kidney and bladder
- Persistent tumor accumulation @ 24 hr timepoint
- ONM-400 accumulation in tumor is still seen at 24 hrs, while free IL-2 has cleared
- Significant extension of plasma half-life
- – ONM-400 t1/2 >12 h vs. free IL-2 t1/2 <0.5 h
ONM-400 Preliminary Preclinical Data
- ONM-400 shows higher response rate with more complete tumor regression vs. IL-2 alone at the same dose
- ONM400 in a preliminary study as a single agent, shows greater single agent survival benefit vs. competitors
- ONM-400: 60% of animals were tumor free at 36 days vs. 0% for IL-2
- NKTR-142 (Nektar) in vivo preclinical data indicates limited single agent efficacy
- THOR-701 (Synthorx) in vivo preclinical data indicates virtually no single agent efficacy
Application to Small Molecules: ON-BOARD™ Improves the Therapeutic Index of MCT-1 Inhibitor
- MCT-1 Inhibitor held promise as an effective broadly applicable cancer therapy; however, toxicities in Ph 1 led to its being dropped
- ON-BOARD™ micelle encapsulation significantly improves therapeutic index of MCT-1 Inhibitor alone
ON-BOARDTM/MCT-1 Inhibitor Demonstrates Efficacy, Anti-PD-1 Synergy and Improved Safety
