ADCs, targeted therapies, chemistry, biotech, pharma. Director @ Zymeworks
Vancouver, British Columbia
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🎉 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-p…
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Adding some more color.
For a DAR4 ADC with moderate stability, comparison of total antibody (TAb, green) and ADC PK (black) highlights deconjugation. SHR-A2102 illustrates this well! Green and black lines diverge.
[Original data from the paper; PK replotted for 6 and 8 mg/kg]
Pointing out a common mistake in assessing ADC stability from this recente SHR-A2102 paper.
SHR-A2102 utilized an MC-GGFG linker, which is not fully stable. Free payload concentration is NOT a right assessment of ADC stability!
(as we discussed here: annalsofoncology.org/article…)
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But don't use this method for DAR8 ADCs with moderate stability!
The reason is simple: difference between TAb and ADC PK reflects only DAR0 species.
DAR8 ADCs generate DAR2–3 species, but not necessarily DAR0.
Always better to use TAb vs. AcDrug!
See annalsofoncology.org/article…
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ADCs account for almost one-quarter of the LBAs at #ESMO26!
(23%, for a more quantitative perspective)
The #ESMO26 LBAs are out!
Multiple impactful trials in breast oncology (and beyond) to be presented in Madrid
👇 #ESMOAmbassadors
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Pointing out a common mistake in assessing ADC stability from this recente SHR-A2102 paper.
SHR-A2102 utilized an MC-GGFG linker, which is not fully stable. Free payload concentration is NOT a right assessment of ADC stability!
(as we discussed here: annalsofoncology.org/article…)
Phase 1 of SHR-A2102 in patients (N=395) advanced solid tumours published on @TheLancetOncol
Including NSCLC, HR+/HER2- BC, TNBC, ESCC, HNSCC
Tox typical of a TOP1i ADC
Interesting discussion about biomarkers (359 patients included in the analysis)!
thelancet.com/journals/lanon…
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Phase 1 of SHR-A2102 in patients (N=395) advanced solid tumours published on @TheLancetOncol
Including NSCLC, HR+/HER2- BC, TNBC, ESCC, HNSCC
Tox typical of a TOP1i ADC
Interesting discussion about biomarkers (359 patients included in the analysis)!
thelancet.com/journals/lanon…
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In July, AZD9592 (AZ's EGFR-cMET TOPO1i ADC) got discontinued due to "unimpressive PK and PD"
A patent published today reported preliminary clinical and PK data for 150+ patients (not uncommon to see in patents ahead of conference disclosures)
"unimpressive" was the right word!
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Hint of activity in HNSCC and NSCLC EGFRwt.
However, additional patients enrolled in HNSCC and NSCLC EGFRwt showed 0% and 16% ORR, respectively.
More details in the patent, including some interesting comments on dosing:
patentscope.wipo.int/search/…
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🧬 Cancer Progress 2026: remarkable gains & a rapidly evolving therapeutic frontier fueled by science
• 📉 Mortality: US cancer death rate ↓ 35% since 1991 → >4.8M deaths averted
• 💊 Innovation: 11 new anticancer therapies FDA-approved in the past 12 months—10 molecularly targeted, including the first PROTAC in breast cancer
• 🛡️ Immunotherapy: 15 ICBs now span 23 cancer types
• 📈 Survival: 5-year survival across cancers reached 71% versus 49% in the mid-1970s
cancerprogressreport.aacr.or…
#AACR
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ChosunBiz reported that BMS had halted the development of ORM-6151 (aka BMS-986497), a degrader antibody conjugate (DAC) licensed from Orum Therapeutics.
ORM-6151 = anti-CD33, GSPT1 degrader payload (SMol006), cleavable β-glucuronide linker.
biz.chosun.com/en/en-science…
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Orum's first clinical DAC, ORM-5029 (anti-HER2, same SMol006 payload, different linker [ValCit]), was discontinued last year for safety concerns: clinicaltrials.gov/study/NCT…
3rd Orum's DAC, ORM-1153, is lined up to start clinical development: clinicaltrials.gov/study/NCT…
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Raffaele Colombo retweeted
And benefit consistent across B7H3 IHC expression levels 👀 Not surprising and another reminder that target expression ≠ a simple predictive biomarker for ADCs.
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Now approved also in EU!
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Raffaele Colombo retweeted
Thrilled to spread the word about the next @AACR Targeting RAS Special Conference!
Looking forward to bringing the RAS community together again for new mechanisms, therapies & clinical advances.
Bring us your best RAS science—the new, exciting & unexpected #AACRras27
Submit an abstract by November 2 for the AACR Conference on Targeting RAS: Mechanisms, Novel Therapeutics, and Clinical Impact (Jan 28-31; San Diego), chaired by Ryan B. Corcoran, Julian Downward, Ignacio Garrido-Laguna, and @Sandra_Misale.
brnw.ch/21x5kyf
#AACRras27
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Iza-bren (Yizekang®) met primary endpoint (PFS) in a pre-specified interim analysis of the PANKU-Breast01 (aka BL-B01D1-306) trial for patients with HR+/HER2- breast cancer.
5th phase III trial to hit the primary endpoint for iza-bren!
asia.tools.euroland.com/tool…
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FDA approves daraxonrasib (Rasonque) for the treatment of adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy!
Congrats on a transformative drug!!!
fda.gov/news-events/press-an…
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