Ethan Perlstein 1-to-N

I've met so many entrepreneurial rare disease parents over the years that I’ve lost count. They have moved or are moving medical mountains to save their kids and others like them. But rare parent founders get no love from institutional players. Those days are done. Science, talent and compute are no longer limiting. Priority Review Voucher alpha makes the economics work. The missing spark is access to cure capital. That's why I’m incredibly pumped to relaunch @1000cures with my cofounder @ryan_1000cures! Ryan and I teamed up to create a “YC for Rare” that unites our biotech houses with complementary expertises, experiences and networks. 1000 Cures is an accelerator for lean startups led by parents on mission to cure pediatric rare diseases. We ride at dawn. Let’s go!

@RNAiAnalyst 🔥

I am amused by the Big Tech/AI fighting over #tradesecret theft. Would be fun for RA Capital to chime in there stating that trade secret theft is all good since it lowers the cost to consumers.

i bet the pw is 🍆🍑😩👉👌💦

dont worry for every job AI has taken a new startup will be seeded by a freshly unlocked IPO millionaire

if you raised on a SAFE, didn’t give up a board seat at seed, launched on hacker news, or took advice from a pg essay, you benefited from yc people forget what venture looked like before them. convertible debt, heavy dilution, founders swapped out for professional ceos. yc dragged the whole ecosystem toward founders, and standard capital is now doing the same to the series a. that lineage runs straight back to yc yc rejected us multiple times. i still raised on a SAFE and learned from their videos the whole time people dunk on yc for clout but every single seed founder is raising on rails they built, yc founder or not

@mhdempsey @shelbynewsad When founders need help they ask their investors. Do GPs ask their LPs for help in instances like these? Do LPs add value in this way?

Can anyone at OpenAI who follows me help me get @shelbynewsad 's account unbanned? DM me if you need. AFAIK we were merely trying to understand the limits of biosecurity of the models like 2 generations ago and it got perma-banned.

@TheFoxRadar @PRVWatch @Contrary_Res my thoughts on the PRV are pretty clear, that’s why @ryan_1000cures and I launched @1000cures besides capital, the missing ingredient in all this is the FAMCO: a personally invested operator driving a specific cure over the finish line

good catch on the PRV omission. That market incentive is definitely material, especially with recent sales still clearing in the $150-200M range. On the cost side, I agree the $1-2B figure often cited feels outdated for orphan programs. The real advantage for platforms like $PRME is the combination of lower development costs + the ability to monetize a PRV + the broader regulatory tailwinds we’re seeing. The FDA has been steadily improving timelines across multiple fronts this year (Operation TrialBlazer, the Plausible Mechanism framework, prior knowledge guidance for gene editing, expedited IND pathways, and openness to single pivotal trials in rare indications). These changes are meaningfully shortening the runway from IND to potential approval, which compounds nicely with the PRV economics. Curious what your take is on how these cumulative reforms interact with the traditional PRV incentive for gene-editing platforms targeting multiple rare diseases.

What if $PRME becomes the leading gene editing platform for rare diseases? The world has no idea what could be in the making. A generational opportunity.

95% of rare diseases have no approved treatment. When your child is getting sicker, waiting isn’t an option. ARPA-H is investing $160 million through THRIVE to accelerate personalized genetic cures for the kids who need them most. A rare diagnosis should never mean no hope for a cure. @broadinstitute @ChildrensPhila @igisci @StJude @Stanford #GEMMABio #MassachusettsGeneralHospital arpa-h.gov/news-and-event…

orphan drug development gets orphaned yet again

@Katerina_Hatzi @daphnezohar proud Promakhos investor here 👋

@daphnezohar I know angels who invest mainly in tech and occasionally in biotech made good returns in 2021 when their biotechs went public. Recursion is a good example. Why has the ecosystem been wiped out? Poor returns in recent years? Consolidation through company building?

IRR for angels and seed investors that don’t have large funds to follow/protect investment is mostly negative. That ecosystem has more or less been wiped out in biotech. Tech related thread below but pls respond w biotech stories

@silvirouskin open mic opportunity

Good news - i’m giving a talk at an awesome conference. Bad news- the talk is at 9PM , the last talk of a day that started at 9am !! I’d love to hear thoughts and ideas how to keep the audience engaged !! clearly have to spend most of my time coming up with clever jokes.

@laurencurehd @HDBuzzFeed sounds like a Huntington FAMCO needs to take control of the asset and bring it to market

Unfortunately, I have some disappointing news for you today. Roche announced today it is stopping development of two of its huntingtin-lowering ASO drugs, tominersen and RG6496. I want to share this article from @HDBuzzFeed that goes into it more, and I'm planning on doing a show this afternoon on @Help4HDI Live to discuss it more. I myself have been part of a clinical trial that was ultimately terminated, so I know how disappointing this is, and my heart is with all the participants receiving the news today. 💔 As is so well said in the article, "Every clinical trial, regardless of its outcome, teaches us something." Please also note: "Importantly, the drug appeared to do exactly what it was designed to do biologically. Participants receiving tominersen had significant reductions in levels of the expanded huntingtin protein in the cerebrospinal fluid (CSF) that bathes the brain, alongside reductions in NfL in both CSF and blood plasma, indicating brain health seemed to be improving. We did not learn the specifics yet of exactly how much each of these biomarkers changed but hopefully we will learn that in forthcoming updates. Roche also reported no new safety concerns during the study, which is good news.  However, despite these encouraging biomarker changes, people receiving tominersen did not appear to experience a slowing of disease progression compared with those receiving placebo during the span of the study. The study’s clinical endpoints, including the hoped for improvements in cUHDRS and TFC at 16 months, were not met. As a result, Roche has decided to discontinue development of tominersen." "More than 1,500 HD families have contributed to Roche’s huntingtin-lowering programmes since the first tominersen studies began over a decade ago. Although today’s news is deeply disappointing, it’s important to remember as we all digest this news that those contributions have fundamentally advanced the field. Every clinical trial, regardless of its outcome, teaches us something. Sometimes the lessons are exactly what researchers hoped to find; sometimes they reveal that a promising approach needs to be refined or that a different strategy may be needed. While this news is very disappointing, there’s no such thing as a failed study. Researchers are gaining valuable knowledge from each study, each trial participant, and each datapoint. So no effort is wasted. Every study brings the HD field one step closer to understanding how to develop treatments that truly modify the course of the disease." en.hdbuzz.net/roche-ends-two… More to come later on the podcast. #HuntingtonsDisease #raredisease #HDResearch

@ninakilbride 💯

I am that person

cure one to cure many

cure odysseys begin with a diagnosis

I'm in! Q: What am I shipping? A: Needed PKU (phenylketonuria) infrastructure that helps us harness AI, of course. My son's rare disorder & a decade-long mission. I'm really glad I find this stuff fun too.

@ninakilbride 👏🙌💪

This is frustrating to watch and I’m a Browns fan.

just did the same for my genome!