Raffaele Colombo @raffcolo
ADCs, targeted therapies, chemistry, biotech, pharma. Director @ Zymeworks linkedin.com/in/raffaelecol… Vancouver, British Columbia Joined October 2022-
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@StephenVLiu It is certainly impressive! What works, works! Some questions remain...
Iza-Bren is very effective (not only in TNBC) but its profile is also very chemo-like. What’s the targeted contribution vs non-specific uptake? Iza-Bren half-life is ~1 day! What’s the correlation with EGFR expression? HER3 expression? Co-expression of both EGFR and HER3?
Impressive results from a phase 3 trial of Iza-Bren (anti-HER3/EGFR TOPO1 ADC) vs chemo in pretreated mTNBC, with improvement in PFS and OS. High rate of hematologic toxicities, including 5% febrile neutropenia. Phase 3 ongoing to confirm these results in a global population.
Not all the ADCs are identical. Known target (Nectin4) and payload (exatecan). “The EXCEED study didn’t identify a dose that was both tolerable and efficacious. Without a clear therapeutic window, development was discontinued” LY4101174 (ETx-22) came from Emergence acquisition
EXCEED #ASCO26: LY4101174 = More data on Nectin4/Topo1 ADCs in 86 patients with pretreated advanced UC . RRs 20% is lower than expected while haem tox was high. Efficacy and toxicity balance doesn’t support further development. Yesterdays data (LY405 same payload/target) has
Standing ovation for the RASolute302 trial results! @UTMDAnderson @KRASKickers #ASCO26 @RevMedicines
@phsiao4 @ChandrakanthMv @PTarantinoMD Hilarious, sac-tmt hasn’t optimized linker over Dato… maybe understand a bit of chemistry before generating AI summaries?
The Topo1 ADC tsunami in ADCs #ASCO26
Data on nectin-4/Topo-1 ADC (LY405) #ASCO26. @IyerGopa RR= 42% (n=48). RRs are maintained after prior Nectin-4 targeting but not after prior Topo1 payload exposure. Resistance is therefore mainly payload orientated. Sequencing Nectin4 ADCs requires R3 trials, but look imporant. LY405 is metabolized by CYP2D6. Absence of CYP2D6 (~10%) led to serious toxicity. Measuring CYP2D6 is straightforward but important for this drug . @OncoAlert
Don’t miss the #ASCO26 educational session on ADCs tomorrow afternoon!
Dr. Paolo Tarantino (@PTarantinoMD) will be discussing combining and sequencing #AntibodyDrugConjugates with targeted agents in tomorrow's #ASCO26 education session on #ADCs. 🗓️Saturday, May 30 ⏰ 4:45 – 5:00 PM CDT (5:45 – 6:00 PM EST) 📍 Hall D2
@Mykalt45 @PR_pharma @JacobPlieth Agree to disagree... pubs.acs.org/doi/10.1021/bc… Seagen Topo ADCs in 2009.
@Mykalt45 @PR_pharma @JacobPlieth That's completely a different topic than "didn't have the tech"... that's a development choice ("ai posteri l'ardua sentenza", cit. Manzoni)
Infographic of CD123 ADCs that have entered clinical development: 5 different payload classes, 4 discontinued! From my talk @ Joint International Conference Innovation in Oncology (x.com/FondazioneBona…) Figure updated to reflect PVEK approval! (preclinical ADCs not shown)
FDA approves pivekimab sunirine [PVEK, IMGN632] based on CADENZA trial! CD123‐targeting antibody with DGN549 payload. 15th ADC approved by FDA 20th ADC worldwide 1st CD123 ADC 1st IGN payload (similar to PBD) prnewswire.com/news-releases/…
@Mykalt45 @PR_pharma @JacobPlieth I’m sorry to correct you, but Seagen published on dual payload ADCs in 2016!
@ADC_Chemist Haha, yes, omg! just copy and paste error 😅. Thanks!
@GIMedOnc @PTarantinoMD With the caveat that, for biomarker selected, the dose was ≥2.4 mg/kg (which included patients at 3.0 mg/kg). It is clear from the numbers (9 PRs in the "high" group, but there only 7 PRs total in the 2.4 mg/kg group). And 3.0 mg/kg is not exactly tolerable and manageable
@phsiao4 @MedChemExpress Everything is made up... linker, DAR, payload, and even chemistry. Not even worth discussing what the mistakes are.
@GIMedOnc @PTarantinoMD How did you get 38% ORR???
RongzeJin-sanjingbio @RongzeJinngii
0 Followers 34 Following Founded in 2022, Hangzhou Sanjing Biotechnology Co., Ltd. focuses on nanobody R&D and services, providing nanobody and early‑stage discovery
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Publishing with Integ... @fake_journals
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