Nov 3, 2026 · 33 min
ADC advances expose a payload innovation gap
Ep. 395 - ESMO analysis & Auchincloss proposal
The episode connects emerging drug-design questions with proposed changes to clinical trials, cross-border biotech investment, rare-disease regulation, and a bruising IPO market.
- 1ESMO first-in-human data show ADCs expanding across targets while shared payloads may contribute to resistance.
- 2Jake Auchincloss’s proposal would embed early-stage research into routine care and strengthen the FDA Oncology Center of Excellence.
- 3Treasury rules, individualized-therapy reforms, and biotech’s IPO sell-off could reshape how innovation reaches patients and investors.
Don't miss
The ADC discussion turns on whether shared payloads could drive resistance even as the field expands into new targets and bispecific formats.
The brief
ESMO’s first-in-human studies put antibody-drug conjugates at the center of the clinical landscape, but raise a sharper question: are new targets outpacing new payloads?
The analysts examine evidence that shared payloads may drive resistance, alongside new bispecific formats that could expand ADC design beyond familiar architectures.
Jake Auchincloss’s proposed clinical-trial overhaul would embed research more deeply into routine care while strengthening the FDA Oncology Center of Excellence and its major initiatives.
The conversation then tests how Treasury’s proposed COINS Act rules could constrain China-linked biotech deals, alter governance structures, and give European companies an advantage.
Janet Woodcock’s rare-disease proposals and the difficult debuts of Bambusa Therapeutics and Aspen Neuroscience widen the question from scientific novelty to workable regulation and financing.
What was said on this episode
19 statements · 8 positive · 8 negative · 1 mixed · 2 neutral
ADCs outnumbered other modalities among ESMO first-in-human studies.
“antibody drug conjugates outnumbered any other modality in the set that we found”
Listen at 2:17
ADC payload innovation is lagging behind target innovation.
“the payload innovation is really lagging behind”
Listen at 3:21
ADC payloads are the primary resistance driver in breast cancer.
“the payload is actually the primary driver of resistance, at least in breast cancer”
Listen at 4:04
Changing ADC targets while retaining payload often produces little or no response.
“when you keep the payload consistent, but you change the tumor antigen that you're targeting in a patient who's already received an ADC against the same payload, different tumor antigen, there are almost no responses, zero responses in some cases”
Listen at 4:18
Switching ADC payloads can preserve responses during sequential therapy.
“if you switch up the payload, when you're doing sequential ADC therapies, you do continue to get some responses”
Listen at 4:34
ADC payload innovation should continue progressing.
“payload innovation needs to continue progressing”
Listen at 5:22
Most products in the first-in-human dataset had first-in-class potential.
“the majority of these products in first in human trials have first in class potential”
Listen at 6:50
Bispecific antibodies had a higher first-in-class proportion than ADCs.
“the bispecific antibodies, which had a... an even higher proportion of first-in-class potential products in this data set than the antibody drug conjugates”
Listen at 8:05
Auchincloss’s legislation would substantially affect U.S. drug development if enacted.
“if something like what Representative Auchincloss has introduced is enacted, it will have a major impact on drug development in the United States”
Listen at 11:02
The proposed biobank could be the bill’s most important element, with results taking decades.
“this biobank Could be the most important thing that happens in the bill, but the results probably won't be in for a decade or even two decades”
Listen at 13:20
The bill would cost at least $7.8 billion over five years.
“my quick calculation is that the bill would cost at least 7.8 billion dollars over five years”
Listen at 16:17
The legislation would strengthen FDA’s Oncology Center of Excellence.
“the legislation puts the Oncology Center of Excellence at FDA on a much more solid footing than it is now”
Listen at 17:13
Some U.S. newco deals licensing Chinese assets may fall under COINS rules.
“new co-deals where a Western investor or US investor is launching a company in the US with an asset in license from China may fall into this scope”
Listen at 20:25
COINS restrictions may create some benefits for U.S. investors.
“this may not be all bad news”
Listen at 20:47
Some investors fear COINS rules will advantage non-U.S. companies.
“there's some of them that are, and I quoted them in the story that I wrote the other week, you know, they're very, very, very concerned that this is going to create competitive advantages for European and, well, an Asian company is also, you know, any companies that are outside the United States”
Listen at 21:55
Nearly two-thirds of disclosed newco deals included equity stakes.
“nearly two thirds of those did involve equity stakes”
Listen at 23:51
Companies will continue seeking workarounds to regulatory restrictions.
“there's always going to be workarounds”
Listen at 24:37
U.S. regulation is partly motivated by concerns over Chinese governance roles.
“Some of the concerns are about Chinese companies having governance roles in these entities.”
Listen at 26:25
Bambusa Therapeutics and Aspen Neuroscience both closed below their IPO prices initially.
“both of them closed down on their first day”
Listen at 32:14
Statements are attributed to the speaker as said on the episode and reflect their view at the time, not PodLume's. They are not advice.
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