#AACR26 | ADC + #PARPi - finally a rational approach
AACR Annual Meeting 2026
April 17–22, 2026 · San Diego · 2418 items
After the meeting★
Medicinal chemistry beyond KRAS: CDK2, WEE1, SERD
18 people · 18 posts4 topics
Start here
KRAS is so bright it hides the other small molecules. This chapter is early chemistry off that spine: CDK2, WEE1, macrocycles, PARP with an ADC. Most of it is still Phase 1. It should not vanish from the topic list for lack of heat.
Read it as medicinal chemistry still looking for the next main card. If one lands, it will move into another direction. If not, it stays here as an early signal that did happen on the floor.
After CDK4/6 resistance, CDK2 was treated as selectivity you could not make. ECI830 is the oral molecule on the floor that cuts that wall, aimed at Cyclin E amplification. CID-078 is a cyclin A/B macrocycle; Circle Pharma reported early activity and acceptable safety at AACR.
WEE1 / PKMYT1 and PARPi + ADC are two combinations that already have a mechanism: break DNA repair or a cell-cycle checkpoint, and amplify ADC-payload damage. The 28-patient olaparib + T-DXd set is shared with the ADC chapter.
Analysis
Do not measure this chapter with the KRAS heat ruler. The right use of a Phase 1 signal is “file it, wait for expansion,” not “no Phase 3, therefore it did not happen.”
Molecules that already cross ADC or breast (olaparib, CDK2) will be read again there. What stays here is the chemistry the tumor-type chapters have not yet claimed.
Still open
- Whether CDK2 in humans can stay off CDK1 myelosuppression.
- Whether a macrocycle’s oral exposure is enough to support Phase 2.
- Whether the PARPi + ADC lung-toxicity window still holds in a larger sample.
Key readout
CID-078 · Early activity + acceptable safetyCyclin A/B macrocycle · first clinical look
Records
| Drug / trial | Readout | Setting |
|---|---|---|
| CID-078CID-078 | Early activity + acceptable safety | Cyclin A/B macrocycle · first clinical look |
| zedoresertibzedoresertib | A WEE1-path molecule on the floor | Early clinical |
| olaparib + T-DXdolaparib | Confirmed PR 42.9%, mDOR 11.2 mo | Same 28-patient set as the ADC direction |
| TRI-611TRI-611 | An early code on the floor | Phase 1 / preclinical border |
Floor
Mali Barbi, MD MSc | Breast & Gyn Oncologist@DrBarbiOncScore6060 Mali Barbi, MD MSc | Breast & Gyn Oncologist@DrBarbiOncScore6060 Same topic zedoresertib · 3 peopleCT022lunresertib#MYTHIC#WEE1I#ZEDORESERTIB#PKMYT1I#LUNRESERTIB#CCNE1Heat 2719 likes0 replies8 repostsaacr.orgScore6060 Third New Drugs on the Horizon Session: Four Preclinical Molecules
Four investigational drugs disclosed: CID-078 (Circle Pharma), AMX-883 (Amphista), JNJ-89862175 (Johnson & Johnson) and IPN01203 (Ipsen).
Same topic CID-078 · 4 peopleNo engagement yet
LUNGevity Foundation@LUNGevityScore6060 Ingo Hartung@HartungIngoScore6060 Sarah Premji, MD@SPremji7866Score6060 Moffitt Cancer Center@MoffittNewsScore6060 Moffitt Cancer Center@MoffittNewsScore6060 At #AACR26, Timothy Yap, MBBS, PhD (
Oriol Mirallas MD@DrMirallasScore6060
Ingo Hartung@HartungIngoScore6060
Other directions
- 1KRAS / RAS targeting: from platform to Phase 3
- 2PD-1 × VEGF bispecifics after ivonescimab
- 3Next-generation ADCs: payload innovation
- 4Immunotherapy: CAR-T in solid tumors, mRNA vaccines, TCR-T
- 6MRD / ctDNA / DTP: from detection to treatment decisions
- 7Platform layer: molecular glues, spatial omics, AI
- 10Breast cancer: HER2 de-escalation, MRD, TNBC
- 11Lung cancer: perioperative IO and KRAS NSCLC
- 12The rest: ovarian, HNSCC, GBM and other floor tumors