Raffaele Colombo

🎉 It's an incredible honor and privilege to be named one of the 2024 PharmaVoice 100 by @PharmaVoice, alongside so many talented and inspiring leaders in the life sciences industry! 🎉 Check out the full list of this year #PharmaVoice100 honorees here: pharmavoice.com/news/pv100-pha…

@AppleHelix biospace.com/drug-developme…

@raffcolo What article is the quoted picture from?

Have they, though? (Answer: probably not authors.elsevier.com/a/1nKG73I2OQqH…)

@JacobPlieth The #JacobPlieth effect

@raffcolo Maybe it was something I tweeted.

Anyone care to out the unnamed pharma company whose citizen's petition has apparently resulted in the FDA pausing the release of further CRLs?

Office view! 🇨🇭 🇨🇴 #FIFAWorldCup #Vancouver #roundof16

@Markuseckstein3 @KolPulseAI There are some other ADCs showing good ORR in PDAC!

Do we understand PDAC? These tumors have a particular desmoplastic stroma, are hypovascularized, and exhibit proven high osmotic pressure in their stroma. As indicated by the 0% ORR achieved by T-DXd in 2/3+ PDACs and the lack of additive value from zolbetuximab (also an antibody), this cannot be explained solely by chemoresistance. Anti-PD-1 antibodies were also inactive. There is no strong evidence for this, but antibodies probably cannot reach PDAC tumor cells. This is underscored by the 0% ORR to T-DXd, while some patients respond to small-molecule chemotherapy. How can we overcome this? Potentially with next-generation small peptide compounds or direct tumor stroma remodeling.

@oncodaily @eBioMedicine @oncodaily, we never raised questions about linker stability of T-Bren, that was your own assumption! T-Bren has a stable linker. The comment was about the surprisingly shorter PK compared to other trastuzumab topo1 ADCs, despite being stable…

Recent publication of T-Bren on @eBioMedicine: thelancet.com/journals/ebiom… Surprisingly, half-life (2.6 days) of T-Bren is relatively short compared to other topo1i trastuzumab ADCs! (PK of Topo1 T-ADC from annalsofoncology.org/article/S0923-…, updated with T-Bren)

First patient dosed in a phase 1 clinical study (HLX48-FIH101) of Henlius’ EGFR x cMET bispecific ADC. This is the 15th (!!) EGFR x cMET ADC starting clinical development.

@mmn_tk89 Payload exposure in human is often significant (and certainly not below level of quantification) for majority of ADCs. It is kind of a myth that is very low. Authors’ link for free access: authors.elsevier.com/a/1nKG73I2OQqH…

@raffcolo Dr.Colombo, Thank you for sharing insightful paper and congratulations. Do you think lower exposure level (BLQ) of free payload observed in both animal and human implies that payload can be released in tumor, but not circulation? Do we need tumor PK data for this investigation?

In our @Annals_Oncology review we collected (see supplementary figure S6) available PK of trastuzumab-based ADCs with different drug-linkers compared to "naked" trastuzumab! annalsofoncology.org/article/S0923-… (divided by payload classes)

@phsiao4 @eBioMedicine @OncBrothers

@raffcolo @eBioMedicine @OncBrothers The initial dosing is exactly like SG (1.0 mg/kg on days 1 and 8 every 3 weeks (D1D8 Q3W) (accelerated titration). Portends to short half-life . Looks like they ended up picking 4.4 mg/kg q3wk. Look forward to learning more about this new payload Ed-04

@phsiao4 @eBioMedicine @OncBrothers I think you are confusing data from Iza-Bren. Ed-04 half-life from T-Bren is 4.4 days for the 4,4 mg/kg.

@raffcolo @eBioMedicine Definitely shorter vs #tdxd (5.4-5.7 days based on the PI). We know Dxd (payload ) half life is similar length. T-Bren. Payload the free Ed-04 (payload ) half life is short 21.9 hours. Comparable to SN 38. @OncBrothers a nice review by @raffcolo

@Markuseckstein3 Higher non-specific clearance since the antibody is still trastuzumab…

What does this short half life mean ? Is it rather a bad signal or maybe even good to avoid side effects @raffcolo ?

💡🔦 Your must-read for Sunday, I promise it will change your perception on ADCs!! Exquisite review in @Cancer_Cell by @BarbaraPistill2 et al: Quoting from the abstract: 👇 «Emerging evidence indicates that ADC activity extends beyond target antigen expression alone, encompassing tumor-intrinsic features and tumor microenvironment-dependent processes. This challenges the view of ADCs as strictly targeted agents and supports their conceptualization as tumor-ecosystem-targeting therapies governed by multidimensional biological determinants» cell.com/cancer-cell/fu…

T-DXd now approved also in Europe for HER2-positive solid tumors! In USA, it received accelerated approval for this indication in April 2024. More than 2 years later now available in EU! (Type II variation application in EU was validated in Sept 2025) businesswire.com/news/home/2026…

@teamoncology Yes!! Right after I took the picture 😅

@raffcolo Looks yummy, did they have soup?

Only Hawaii has a bento for lunch at Best of ASCO!

🧬 We've been developing ADCs as targeted drugs. Biology says otherwise. • ❌ Target expression alone poorly predicts benefit • 🔀 ADC efficacy emerges from the interaction between tumor cells, TME, payload, linker, and immune biology • 🧠 Precision ADCs require multidimensional biomarkers—not better IHC • 🧪 Longitudinal biopsies, ctDNA and spatial profiling should become important parts in ADC trials • 🎯 The next generation of ADCs will be defined as much by patient selection as by molecular engineering doi.org/10.1016/j.ccel…

And FH-006 is also with a camptothecin (topo1i) payload

More than 40 bispecific ADCs in the clinic! Figure from cell.com/cancer-cell/fu… @BarbaraPistill2 @FerMosele 1 now approved by China NMPA 7 with reported clinical data thus far 3 discontinued (one more after publication) 3 additional in clinical development (not in the table)