RNA interference

So we have control over when a protein is expressed or turned off, questions of like, where is that most important for longevity in males compared to hermaphrodites, things like that.

And I think even though there were previous methods, other methods that allow you to specifically overexpress or knock down using RNAi, there are some added benefit of this system, which is that there's less leakiness.

Is that correct? It depends on what

protein you're targeting and what tissue.

Number three, Merck KGAA acquired Silence for approximately $1.3 billion, a 130% premium to the unaffected share price.

Silence is an RNA interference therapeutics company focused on hematology and rare diseases.

RNAi continues to attract major pharma interest.

Number four, Galderma acquired Zio Skin Health for $1.5 billion.

This is a physician-dispensed skincare, so not a drug, but it tells you something about where dermatology companies see growth.

From rare disease toward cardiology, transthyretin amyloid cardiomyopathy, or ATTRCM.

Alnylam is expanding target enrollment in TritonCM, the phase 3 for its investigational next-generation RNAI drug, Nucresirin.

The target goes from 1,750 to approximately 2,250 patients.

Alnylam says the expansion is enriched for patients with early disease, who it expects to benefit most.

Well, he read about Acuity, my company, in the Wall Street Journal.

I think we had a front page article when the Nobel Prize for RNAI was awarded.

And this little company in Philadelphia had the most advanced drug.

He had just sold his company, Ivax, to Teva, was looking for the next opportunity.

Still in neurology, Huntington's disease.

Alnylam presented early data for brezosiren, an investigational RNAi therapy.

In a randomized, double-blind, placebo-controlled phase 1b, adults with genetically confirmed Huntington's received one intrathecal dose of brezosiren or placebo.

The dose rose from cohort to cohort.

We were talking with John Maragonori about Alnylam and how it took 16 years from founding to first approval.

And there's some parallels here with both companies going through the peaks and valleys of RNAi.

And like many biotechs, both are overnight success stories that take decades.

Ali Mortazavi was the CEO of Silence when it was a £5 million market cap AIM listed company.

Don't try this at home, kids, is my advice.

But, you know, people kind of for the biotech space has changed so much.

The RNAi was such a privileged IP space.

And literal old silence at 5 million market cap on AIM had actually a foundational patent in SRNA chemistry.

I've been testing some different mite treatments.

Like in this hive here, I use the new double-stranded RNAi.

This is called Nora and I've been using it here.

And of course I've got Viroxan strips still working for us here.

Right.

So tell me, how do you decide to leave the comfort of an established pharmaceutical company such as Millennium to move to Alnylam as one of its founders, a startup built around a brand new idea, RNAi? And I remember there was a paper that Phil Sharp wrote with Tom Tushel and a few other people explaining in Drosophilia how you could do this.

So how do you go from that background in Millennium to say, I'm going to take a risk and join this new company, be one of the founders, and take an unproven technology needing proof of concept and building scientific credibility.

I'm going to do this.

And then on a personal side, I was getting remarried that same year in 2002 and about to embark in a whole new life with a wonderful new person in my life, build a family, which I did.

So it was not an easy time for me to take on the challenges of being a startup CEO, if you will.

But I really dove into the science of R&EI.

And just to explain it a little bit, The central dogma of biology is that DNA makes RNA, which then makes protein.