Co-founder and CEO @nanograb (YC S23)
SF / London
Joined January 2012
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- Following1.7K
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Debesh Mandal retweeted
siRNAs and delivery systems are the future of medicine
Craig Mello kicking off the nephrology meeting ! @ASNKidney RNA medicines and oligo therapies will be the next generation cures for the kidney patients
Debesh Mandal retweeted
People often want to ask me if their startup idea is good, as if my opinion means anything.
I think 99% of ideas are good if the team can execute well. The problem is, 98% of teams fail at execution.
So, no need to sell me your idea, show your execution.
Debesh Mandal retweeted
Something I just told a founder: Stay as small as you can for as long as you can. People who come to visit your office should always be surprised that such an important company has so few employees.
Debesh Mandal retweeted
Anthropic gave me $30,000 in Claude credits to research my own tumor I wrote what I built since March. I’m looking for someone who can manufacture a personalized vaccine, and a hospital that can give it
Debesh Mandal retweeted
When I started my fund in 2017, I believed the founder-centric model which is the cornerstone of tech startups was going to become increasingly relevant in #biotech, where many successful companies were historically founded by tradbio funds, led by seasoned execs in their 40s or beyond.
A decade later, nearly all of our blockbuster winners at @CivilizationVC were founded by first-time entrepreneurs, with CEOs in their 30s. @BillionToOneInc @omadahealth @ForesightDx Rewrite @lemonaidhealth etc.
I didn't know then that AI would drastically accelerate this trend.
Trad bio funds will struggle to attract top AI talent to start companies with them.
Top talent wants to found and own, not follow.
The founders who will lead the future of biopharma are today's cracked AI-native engineers.
... bonus points if they've taken biology courses! 🙂🧬🚀
Debesh Mandal retweeted
Two weeks ago, @PlanetScale launched TIN. They benchmarked it against us, and it was very fast. So we spent those two weeks making ParadeDB faster without their tradeoffs.
Today, we are faster than TIN.
paradedb.com/blog/opening-a-…
Debesh Mandal retweeted
A new class of biotech buyer is emerging, as frontier AI and big tech companies acquire early-stage biology foundational platforms. How do big tech acquisitions differ from traditional pharma exits, and what are the potential implications for founders, investors and the pharmaceutical industry? nature.com/articles/s41587-0…
rdcu.be/URMEtSZqA84a
Debesh Mandal retweeted
state of frontier bio, Aug 2026:
- AI designs the protein
- mRNA tells the cell what to build
- CRISPR rewrites the DNA underneath it
- gene therapy edits the cell permanently
- protein degraders tell the cell what to delete
- chemogenetics controls which neurons fire
- stem cells rebuild the tissue that's damaged
- lab-grown tissue replaces the function entirely
- genome-editing platforms make the edits reusable
- AI agents run the research loop without waiting for a human to sleep
programmable humans incoming
timeline is very bio/acc.
Debesh Mandal retweeted
@elonmusk is right about the acceleration implication, but mRNA isn’t software.
It’s chips.
That distinction matters.
The mRNA molecule is the programmable hardware layer: a biological device that carries instructions into a cell and gets translated by the cell’s machinery.
Debesh Mandal retweeted
The Gene Editing revolution has only just begun. Here is JD Vance describing to Joe Rogan how the first ever approved CRISPR Gene Editing therapy - $VRTX & $CRSP CASGEVY has successfully cured Sickle Cell disease. Today’s FDA approval is another milestone in this revolution! $XBI
1/@VertexPharma have announced today that the FDA has approved expanded use of CASGEVY 🧵👇- $VRTX & $CRSP first-ever approved CRISPR Gene Editing therapy for treating Sickle Cell disease and transfusion-dependent beta thalassemia, for the treatment of people ages 2 years and older with either sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT). CASGEVY is the first approved genetic therapy indicated for children as young as 2 years for both SCD and TDT which means that Approximately 5,500 additional children in the U.S. are now eligible for this one-time therapy - expanding upon a prior FDA approval in people 12 years and older. $XBI
ALT Vertex Pharma have announced today that the FDA has approved expanded use of CASGEVY - $VRTX & $CRSP first-ever approved CRISPR Gene Editing therapy for treating Sickle Cell disease and transfusion-dependent beta thalassemia, for the treatment of people ages 2 years and older with either sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT). CASGEVY is the first approved genetic therapy indicated for children as young as 2 years for both SCD and TDT which means that Approximately 5,500 additional children in the U.S. are now eligible for this one-time therapy - expanding upon a prior FDA approval in people 12 years and older. $XBI
Debesh Mandal retweeted
LNPs have become a preferred in vivo delivery method for gene editing agents, including nuclease and base editor RNAs used to treat patients suffering from a variety of genetic diseases. But while OF-02 LNP-mediated PE RNA delivery yielded robust Pcsk9 editing in Hepa1-6 cells, in vivo delivery was inefficient in mice.
2/12
Debesh Mandal retweeted
Excited to launch Upstream and announce our $3M pre-seed round
AN INBOX DESIGNED FOR HUMANS AND AGENTS
Upstream's agents sort the noise, draft replies in your exact voice, follow up at the right time, and do what you ask, like finding receipts, scheduling meetings, or writing personalized messages
Thousands of people used it in our closed beta to handle their email. Now available to everyone
How it works: 🧵
Debesh Mandal retweeted
Today, we are launching our research blog!
We’ll use it for technical notes from our work building tools for enzyme and biomolecular design.
Our first post is about The Unreasonable Redundancy of Nature's Protein Folds.
TLDR: Please don't fold more sequences (1/n)
Debesh Mandal retweeted
Inside Claude Code, you can just use "!" to execute any bash comamnd directly, i.e. typing "! git status" would work without having the agent to execute it for you.
Debesh Mandal retweeted
Opening new R&D site in Boston as folks move to China. Continue to believe US is best place in world for novel platform innovation, and UK for discovery biology.
aerska.com/news/aerska-expan…
Debesh Mandal retweeted
Health/bio is the greatest investment opportunity of this decade.
I feel like I am often too negative here (sometimes for good reason), but I want to give people a sense for why we might be 10 years away from a paradigm shift in cancer outcomes.
This year, we have proof of concept for all of the following:
mRNA vaccine success against low antigen burden cancers (i.e. PDAC): nature.com/articles/s41586-0…
Immune activation by non-specific antigens (COVID Vaccines): nature.com/articles/s41586-0…
Successful drugging of undrugable driver genes: nejm.org/doi/full/10.1056/NE…
Successful drugging of hard to drug driver genes: managedhealthcareexecutive.c… (this presentation data was admittedly noisy so I'm holding off on this for now),
Next generations target-specific CAR-T/T cell engagers: nature.com/articles/s41591-0…
Antibody-drug conjugates for more targeted therapy: nejm.org/doi/abs/10.1056/NEJ…
nejm.org/doi/full/10.1056/NE…
Melanoma mortality rates cut in half (not new but new data supporting durable treatment effect): nejm.org/doi/full/10.1056/NE…
Transformative improvements for patients with Multiple myeloma: nejm.org/doi/abs/10.1056/NEJ…
nejm.org/doi/full/10.1056/NE…
ashpublications.org/blood/ar…
GLP1s as potential anti-cancer agents (lots of mechanisms possible here, no clinical data, so hold off on any conclusions and appreciate the multiple reasons why this may not pan out-- i.e. cachexia concerns): jamanetwork.com/journals/jam…
And, of course, AI for diagnostic radiology.
Still a long, long way to go, especially for the average, non-trial-enrolling patient. But there is reason for hope in the coming years for cancers that were death sentences as recently as 5 years ago. All of this on top of proven efficacy of checkpoint inhibitors, existing antibodies and small molecules, and the emerging technologies like adoptive cell therapies and tumor-specific mRNA vaccines.
