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Orphan Drug Start-Up: Discussion With The Founder Of Perlstein Lab

July 28, 2014

Perlstein Lab PBC is a San Francisco-based biotech startup and public benefit corporation focused on precision orphan drug discovery. The company is building a scalable and personalized orphan drug screening platform that efficiently identifies patient-mutation-matched small-molecule drug candidates. Perlstein Lab is initially focusing on 47 related Lysosomal Storage Diseases (LSDs). Dr. Ethan O. Perlstein is the Founder and CEO of Perlstein Lab.

The Orphan Druganaut Blog had the opportunity to interview Dr. Ethan O. Perlstein about the Perlstein Lab, the startup’s mission and goals for the future, why the choice of LSDs, and the state of the orphan drug regulatory landscape.

(1)  Can you please tell us a little about the Perlstein Lab and what the mission and goals are for the future for developing orphan drugs ?

First off, thank you inviting me onto the blog! It’s auspicious timing. This week we closed a $2M seed round.

Perlstein Lab is a mission-driven biotech startup. What do I mean by mission-driven? First, we have a social mission: address the unmet needs of orphan disease patients using a drug screening approach that leaves no mutation behind. Second, we have an environmental mission: develop a sustainable R&D pipeline that minimizes carbon footprint and the destruction of higher animal models, e.g., laboratory mice. Third, we have a business mission: balance proprietary claims with openness and public engagement. We enshrined those principles in our founding corporate documents, and to our knowledge we are the first biotech benefit corporation, or B-corp.

Through our efforts to discover orphan drug candidates using primordial animal models, we hope to kickstart an orphan disease moonshot. Since 1983 and the passage of the Orphan Drug Act, the rate of orphan drug approvals has averaged 10-20 per year. At this pace, it will take another 400+ years before we have an approved drug for every orphan disease. This is unacceptable. We aim to accelerate the pace of discovery by a factor of 10X.

(2)  Why has the Perlstein Lab chosen to initially focus on 47 related LSDs ?

There is a scientific rationale and a regulatory rationale.

The scientific rationale is two-fold. First, we know the genetic basis of LSDs. Some LSDs were first described in the medical literature in the 1920s and 1930s. So compared to many orphan diseases, a fair amount is known about the underlying pathophysiology. Second, when I was an independent postdoc from 2007-2012 at Princeton, my lab studied lysosomal processes from a basic cell biology perspective. Choosing LSDs as Perlstein Lab’s initial focus meant leveraging a foundation of expertise.

The regulatory rationale is as follows. Patient advocacy groups (PAGs) are well-organized in the LSD space. In fact, some organizations go back to the Orphan Drug Act era and have built incredible resources and knowhow in the intervening decades. At Perlstein Lab, we want to engage with patients and advocates on the science of personalized drug discovery from the outset. When it comes time to interact with FDA, I believe that scientifically empowered PAGs will be more effective allies and participants in clinical trials.

(3)  Perlstein Lab is building a personalized drug screening platform ? Can you please share with us what this is, and what types of data and databases are being used to develop your drug screening platform ?

Perlstein Lab is guided by an approach called evolutionary pharmacology. What this means is we use simple model organisms (yeast, worms, flies and fish), as opposed to higher animal models (mice and rats), to do drug discovery. The study of simple model organisms over the last century has illuminated the inner workings of cells down to the level of genes. Most human genes have ancestral versions, or homologs, in simple model organisms. When the homologs of human disease genes in simple model organisms are mutated, these organisms get sick in ways that resemble patients with disease. We can then process these sick model organisms in drug screens to identify small-molecule drug candidates that reverse or correct the effects of mutation.

The personalization part comes in thanks to recent advances in genome editing, eg, CRISPR. Using genetic data available in public databases, Perlstein Lab can recreate specific patient mutations in the homologs of human disease genes. For example, the LSD Niemann-Pick C is caused by mutations in the gene NPC1. There are at least 200 NPC1 mutations known (and certainly more to be discovered). Using genome-editing, we can personalize drug discovery for every single one of those mutations. Why? There is strong evidence showing that different mutations require tailor-made drugs, e.g., the cystic fibrosis drug Kalydeco.

(4)  Are you working with any patient advocacy groups or organizations ?

Not directly at the moment, but as I said above Perlstein Lab is very interested in engaging PAGs on our science and on our mission. We try to take every opportunity to meet with PAGs at meetings. For example, I attended the annual Ara Parseghian Foundation’s Niemann-Pick C meeting last month, and I will be attending my second Global Genes Patient Advocacy Summit in September.

(5)  What do you see for the future for the orphan drug regulatory landscape ?

Great question. I think the policy inducements in place that encourage orphan drug development will remain and will likely be expanded, especially as more PAG-financed efforts advance drug candidates toward the clinic. The regulatory landscape will have to adapt to increasingly sophisticated PAGs and allied companies.

I look to the HIV/AIDS activists and their heroic efforts to accelerate antiviral drug research and approval in the late 80s and early 90s as a template for orphan disease PAGs in the 21st century. The pressure they exerted not only on regulatory agencies but also on Congress saved lives.

(6)  What would you like for the readers to know about Perlstein Lab and yourself ?

Perlstein Lab isn’t your typical biotech startup. 4/5 of our scientists are refugees from the postdocalypse. In other words, this is our first biotech startup experience. We also have deep, complementary expertise in the model organisms we’re working with. I don’t know of many biotech companies today that are hiring fruit fly geneticists (though back in day genetically-informed companies like Exelixis did just that).

We’re also different from your typical biotech startup in our online persona. Most biotech startups operate in “stealth mode,” meaning one can glean very little of substance from their company websites or blogs – if they even have a blog. I personally think that’s a huge lost opportunity. Patients and the public will make for much better partners when they’re scientifically empowered.

Thank you for your time.

For further information on Perlstein Lab please contact: Also Perlstein Lab can be followed on Twitter at @PerlsteinLab or on Facebook at @PerlsteinLabPBC.

 Logo courtesy of Perlstein Lab.

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