Simon Burns

CEO @vialtrials. Reimagining drug development for hyperscale.

[Blake Byers @byersblake]

Over the summer, we achieved more drug development milestones than in the rest of @newlimit history. We scaled our manufacturing processes, ran our first large animal model studies, and engaged productively with regulators. Our pipeline of reprogramming payloads continued to grow, hitting new all time highs for both the quality of our best payloads and the quantity of payloads we explored.

>2X stronger regenerative rescue in old hepatocytes

+2 payloads rescue multiple functions in old hepatocytes

+8 payloads restore function in old endothelial cells, +5 in hepatocytes

314X scale up of therapeutic manufacturing, 13X quality improvement

2.5X improvement in endothelial cell age prediction accuracy

>5000 payloads tested (during just the summer) for effects on cell age (all time high!)

5X improvement in data efficiency from transfer learning

[Simon Burns @SimonBurns_]

@jb_michel @rynorhn +1

[Simon Burns @SimonBurns_]

@spisallyouneed let's go!! 🚀

[Simon Burns @SimonBurns_]

@Lawbitrage @Biohazard3737 Large China component of trial right?

[Simon Burns @SimonBurns_]

@RPavuluri Banyan Bio (partnered with Icon) and CinRX (fund associated with Medpace)

[Simon Burns @SimonBurns_]

@josiezayner This is incredible 👏

[Simon Burns @SimonBurns_]

@Mykalt45 @spARKbyARK @ARKInvest @CathieDWood Love to see it - back in ADCs?

[Simon Burns @SimonBurns_]

More here: https://t.co/TwXM0YprvQ

[Simon Burns @SimonBurns_]

We dosed the first asthma patient for Vial's IL-13 x TSLP bispecific antibody.

This is a major milestone for the program and an even larger milestone for AI accelerating scientific discovery.

The program is the first program to use AI models and organ-on-a-chip technology to skip animal trials entirely saving $2M+ and ~1 year of development time.

[Vial @VialTrials]

Vial has dosed the first patient with asthma in the Phase 1b study of Vial's IL-13 x TSLP bispecific antibody.

Following a positive Phase 1a, Vial's IL-13 x TSLP takes its ultra-long-acting profile into patients, with potential across asthma and other inflammatory diseases.

[Simon Burns @SimonBurns_]

@damirbecirovic @bubbleboi Say more! Thinking is Pharma will in-license the best and their commercial footprint isn’t at threat?

[Simon Burns @SimonBurns_]

@MartinBJensen Definitely many such cases! Ionis’s pipeline example of advancing programs for rare and their n-lorem foundation for the programs that aren’t economic is a great example of the phenomenon in action (granted many are ASOs but RNA tx generally)

[Simon Burns @SimonBurns_]

One under-appreciated aspects of siRNAs is given how high the rate of clinical success has been (Alnylam claims ~6X higher than industry standard Phase I to approval rate), companies have been able to make the math work to support ultra-rare development

[Jacob Trefethen @JacobTref]

I believe that 1) siRNA will change medicine, with new treatments for tens of diseases, 2) tens of millions of people will take an siRNA drug in the 2030s, with some chance of >100M people, and 3) I will have taken at least one siRNA drug within a decade.

I have never worked on siRNA, and I also don't think of myself as a hypester. So, why the confidence? There's the technical answer, then the structural answer.

The technical answer is that siRNA has several attractive properties as a drug modality, and enough of the chemistry problems have been solved that I'm confident more drug approvals are on the way (though there are many important unsolved problems left, e.g. in delivering siRNA to organs other than the liver). The four most attractive properties are that with siRNA you can reduce production of previously undruggable proteins by going after the RNA that codes for them; they’re “programmable” to a gene/protein you’re going after; siRNA can last long, with slow release inside cells; and siRNA drugs have the potential to be relatively cheaply made and self-administered.

The structural answer, I believe, is biotechnology’s combination of long timelines with particularly un-juicy, hard-to-remember concepts. If something takes 20 years, you can often spot it 10 years in -- but when it’s an acronym and involves chemical conjugation steps, it’s hard to remember to care. Many important ideas in biology are messy and technical and, unless you've caught the bug (intellectual or literal), boring. That means there are many important secrets lying in plain sight, as per @nayafia's last book.

While disagreements and unknowns remain, it is not particularly controversial among scientists that siRNA holds a lot of promise (alongside some realised promise already!) -- and, yet, most people who will benefit from siRNA drugs in the 2030s have never heard of it.

(PS: given my job involves stewarding charitable dollars related to science, I don’t invest in individual pharma/biotech stocks personally; this post isn’t about the financial prospects of particular companies.)

[Simon Burns @SimonBurns_]

@JacobWitten1 @MartinBJensen When it comes to indication selection, usually a few hundred patients globally isn’t enough to justify advancing a program. However, when the PoS is so high you can underwrite a lot smaller pt size

[Simon Burns @SimonBurns_]

@ChaosBioVC +1

[Simon Burns @SimonBurns_]

@itchdoctor @NobelPrize Dermatology went too long without siRNA programs being advanced! Kudos to you and looking forward to seeing clinical data from the JAK1 siRNA

[Simon Burns @SimonBurns_]

@VialTrials @scottkahan @scottkahan Thank you for spending time with us at Vial to share your thoughts on the incretins space, next generation therapeutics and where Vial's INHBE siRNA may fit within the future standard of care!