Biotech Leaders Get It
31
Aug
2021

Meet the Climb to Fight Cancer Postdoctoral Fellow: Aleena Arakaki

/
/
0
/
,
31 Aug 2021

I’m excited to announce that the first Climb to Fight Cancer postdoctoral fellow has been selected. This is a position designed to advance the careers of young scientists from traditionally underrepresented minority groups.

Aleena Arakaki is the first recipient of this postdoctoral award. She is a Kanaka Maoli (Native Hawaiian) woman.

Aleena Arakaki, postdoctoral fellow, Fred Hutch

Before describing Arakaki’s background and research, here’s what the program is about. This fellowship was created by generous donations in February, by the alumni of the 2019 Kilimanjaro Climb to Fight Cancer expedition that I organized as a volunteer for Fred Hutch.

That campaign raised $1.6 million for cancer research. That awesome group of 27 biotech professionals formed close bonds on a trip to Africa’s highest mountain. They stayed in touch.

When the racial justice protests swept the country last year, they wanted to do more to uplift people from underrepresented minority groups in science.

Together, we raised more than $135,000 to create this program with Fred Hutch.

This program provides funding to support a postdoc position, with an added bonus. The recipient can join one of the future Climb to Fight Cancer expeditions that I organize for the biotech community.

It’s designed to be a great way for a young scientist to advance his or her research, while also building an exceptional industry network.

Arakaki received her bachelor’s in science in Cellular and Molecular Biology, with honors, from Seattle University in 2014. She went on to get her PhD at UCSD, working in the lab of Dr. Joann Trejo. Aleena’s graduate work focused on the regulation and molecular mechanisms of GPCR activation of the Hippo pathway in metastatic breast cancer.

You can read her June 2018 publication in the International Journal of Molecular Sciences, titled “GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling.” And this April 2021 paper in The Journal of Cell Sciences on “α-Arrestin ARRDC3 tumor suppressor function is linked to GPCR-induced TAZ activation and breast cancer metastasis.”

Arakaki received a prestigious HHMI Gilliam Fellowship as a grad student, and is now working as a postdoc in the Gujral Lab at Fred Hutch. She was selected by the Office of Diversity, Equity and Inclusion as a Presidential Postdoc Fellow at Fred Hutch, and her research is partially supported by the Translational Adult Glioma Grant Award from The Ben and Catherine Ivy Foundation.

Her research proposal is focused on ependymomas — cancers of the central nervous system. She’s specifically looking at YAP1 gene fusions, and whether they can be targeted with existing kinase inhibitors, including verteporfin and sorafenib combination treatment.

I’m excited to see where the research leads, and whether it will light the way for her to discover a useful new treatment for patients.

24
Aug
2021

Computation is the Backstage Enabler in Gene Editing

/
/
0
/
24 Aug 2021

Anika Gupta, correspondent, Timmerman Report

Gene editing technologies have stirred the imaginations of scientists for close to a decade.

Many companies are aspiring to disrupt chronic care models with single-dose, curative treatments for monogenic diseases. Others see gene editing becoming an increasingly important tool for rapidly recognizing novel pathogens for pandemic response.

Emboldened by the latest clinical data from Cambridge, Mass.-based Intellia Therapeutics — which delivered a first-of-its-kind successful gene editing trial in six humans with transthyretin amyloidosis — there is increasing confidence in the scientific community that gene editing is on its way to becoming a potent and enduring treatment option for many more patients.

The rhetoric can get lofty at times. But to understand the enthusiasm requires going back to first principles.

Designing and developing a gene editing system for either diagnostic or therapeutic use involves a series of sequential, iterative steps. Computation plays an integral role at various stages along the way. Increasingly, creating an effective product relies on first amassing large amounts of data, picking up on patterns, and making decisions in the context of what needs to be optimized for.

Genomic discoveries lay the groundwork for target identification

In the post-genomic era starting in the early 2000’s, when next-generation sequencing instruments made it possible to collect vast amounts of genomic data, computational biology began to provide better analyses of the emerging data sets. Software and computation have aided in the discovery of thousands of genetic variants associated with both rare and common diseases. These findings set the stage for identifying high risk genes contributing to disease that could possibly serve as potent therapeutic targets.

Sekar Kathiresan, co-founder and CEO, Verve Therapeutics

For over 15 years, folks such as Sekar Kathiresan at Mass General Hospital and the Broad Institute (now at Verve Therapeutics), tried to understand the inherited risk or resistance individuals have to coronary artery disease.

Typical workflows included isolating and statistically quantifying patient DNA variation, particularly between cases and controls.

Computational approaches have now moved beyond standard correlations of genotype with phenotype to include methods that distinguish cause from correlation (e.g., Mendelian randomization), separate polygenicity from confounding (e.g., LD Score Regression), define the contribution of specific cell types or functional regions of the genome which contribute to heritability (e.g., stratified LD Score Regression), and incorporate millions of DNA sequence variants in polygenic scoring (e.g., genome-wide polygenic scores)

Kathiresan and others asked the question: why do some people seem to be naturally resistant to heart attack? They and others critically discovered that mutations in any of eight genes—all involved in the control of blood lipids—can confer resistance to heart attack. The resistance mutation would turn off the gene in the liver, leading to lifelong low levels of any of three blood lipids (low-density lipoprotein (LDL) cholesterol, triglycerides, or lipoprotein(a)), thereby conferring protection from heart attack.

These observations led to a therapeutic hypothesis that a medicine that mimicked these natural resistance mutations could be an effective treatment for heart attack.

Now at Cambridge, Mass.-based Verve Therapeutics, Kathiresan and team are testing that hypothesis by developing an in vivo liver gene editing medicine which would mimic the protective effect of a resistance mutation.

Verve’s first program is designed to target the PCSK9 gene in the liver. With a one-time treatment, Verve seeks to permanently turn off this cholesterol-raising gene, durably lowering blood LDL cholesterol with an ultimate goal of reducing the risk of heart attack, stroke, and death from cardiovascular disease.

Towards finding editing machinery with exquisite specificity

In minimizing the “cumulative exposure” to LDL, which begins at birth, the Verve team is aided by extensive prior pharmacology around statins that has validated the benefits of a sustained lowering of LDL in avoiding heart attacks.

However, whereas lowering LDL levels by 39 mg/dl for 5 years with a statin medicine reduces heart attack risk by 22%, that same difference over a lifetime (through a DNA resistance mutation) can lower risk for heart attack by 88%, enabling near complete protection by going after the root cause in the DNA itself. 

These data highlight that lowering cumulative exposure to LDL cholesterol is a key to averting heart attack.

In their proof of concept in cynomolgus monkeys earlier this year in Nature, the team observed a near-complete knockdown of PCSK9 in the liver after a single infusion of lipid nanoparticles with their base editing machinery (Musunuru et al, Nature, 2021). Key to their efforts was both the on-target editing efficiency and the minimal off-target mutagenesis.

Every step in finding and testing the guide-editor pair was aided by computation. Selecting a guide sequence involved evaluating guide sequences in the gene that would be orthogonal to the rest of the genome (i.e. with minimal sequence overlap) and ensuring the sequence was identical between monkeys and humans, to allow for higher confidence that findings in this study would translate to humans.

In order to find a guide-editor pair with the “exquisite specificity” of interest, the team engaged in systematic evaluation of all possible guides that could turn off the gene; for one gene, there are a finite number of changes that can be made, limiting their search.

The readout included the fraction of ultimate reads with the A-to-G change at the target site as well as the number of sequences with any level of similarity (i.e. few mismatches) to the candidate base editor’s protospacer 20 base pair guide sequence. In evaluating different pairs, they prioritized lists of edits by each editor based on the above criteria and eventually found VERVE101: a pair that in primary hepatocytes had no editing at >100 different potential off-target sites.

Fussy editors and combinatorial challenges

Base editing relies on fusing a DNA deaminase enzyme to a Cas9 to create a single nucleotide change in a target region of the genome. It takes advantage of Cas9’s programmability to target a specific location but hijacks the process to allow for focused edits on one DNA strand by inducing an even greater change at the complementary strand that our cells then correct.

Mandana Arbab, postdoctoral fellow, David Liu Lab, Harvard University

Intuitively, the technology aims to “trick the DNA repair system into thinking the single base-edited strand is the correct one,” says Mandana Arbab, a postdoctoral fellow in David Liu’s lab at Harvard University, a pioneering group in base editing.

Key parameters researchers track to evaluate base editing machinery are the purity (the fidelity of converting one base to another desired base), efficiency (what the relative frequencies of modified genotypes are after cell targeting), and bystander editing (editing that occurs in bases near the guide RNA’s target site; different from off-target editing).

In designing and selecting which combination of deaminase and guide RNA to use, it is critical to decide what the objective is: do only a fraction of cells need to be corrected? Is sensitivity more important than specificity?

With >10 deaminases and >15 Cas proteins to choose from, trying every combination empirically is extremely resource-intensive; thus, being able to sift through the noise through computation can be invaluable. Ideally, it can cut down the time and expense of an otherwise tedious trial-and-error process and increase the probability of success in preclinical and clinical development.

Base editing clearly works, but not always as desired or expected, Arbab states. Different deaminases will be more active or processive (making many edits in one run) and will prefer certain motifs and/or contexts (some are very sequence-dependent versus others that are more agnostic), and target sequence also affects Cas protein kinetics. 

There is a logic to base editor behavior, but there are so many of them, and their higher order interactions are so complicated, that it’s usually not easy to tease apart this logic.

Design and selection of editing repertoire becomes systematic

Addressing this challenge led Arbab and collaborators to develop a machine learning-based “BE-HIVE” model (Arbab*, Shen* et al., Cell, 2020) that predicts, for one base editor at a time, which guide RNAs and target sequences it is most well-suited to edit.

Inputs to the regression trees-based model are data from a massive, diverse library of cells with the paired guide RNA and its target sequence, treated with one editor at a time. In order to predict the best deaminase + guide pairs for a given task, features such as guide RNA GC content (sequence-based), guide RNA melting temperature, cell type, nucleotide characteristics (i.e. where they fall within the enzyme’s editing window, total counts within the window), and sequence composition with motifs (which reflects where enzymes have affinity to deaminate) are inputted.

This breadth of data on guide-editor properties and effects provides a fertile ground on which ideal editors for a given task can be chosen. Referencing this “bible” of which sites are best targeted by which guide-editor pairs can save tremendous amounts of time and resources—rather than empirically discovering good matches, researchers can rely on trends that machine learning has picked up on.

Interestingly, Arbab and her colleague Max Shen found that they achieved similar model performance with about half of the initial sequences inputted (6k instead of 12k), indicating some redundancy in the patterns found and an ability to scale such approaches with even less data.

Both the web tool from the team, which allows inputting features to optimize for and returns the ideal guide-editor pair, and the dataset itself are valuable resources now available to the public.

Leveraging natural patterns to optimize engineered toolkits

Spun out of Jennifer Doudna’s lab in 2017, Brisbane, Calif.-based Mammoth Biosciences is another group pioneering gene editing, using their expanded CRISPR toolkit of Cas proteins for both diagnostics and therapeutics.

However, they have a parallel effort that enables them to lean on nature’s engineering before diving into lab-based engineering. Starting with metagenomic data collected over decades from microbes, the team uses homology-based hidden Markov models to expand CRISPR diversity and unbiased methods to look for completely novel CRISPR systems in a pool of proteins.

Their initial discovery of the Cas14 protein (Harrington et al. Science 2018) involved looking for genes that were close to CRISPR arrays, and clustering proteins with related features. In this way, they were able to identify potential new editing systems that were extremely compact compared to previously used systems.

Starting with nature’s repertoire strengthens the search process by filtering to the systems that were robust enough to make it through the funneling forces of natural selection—these are thus more likely to function well when adapted for other use cases, says Mammoth co-founder and CSO Lucas Harrington.

Computationally-guided diagnostic and therapeutic design

In parallel with being a therapeutics company, the Mammoth team mobilized this past year to develop diagnostics as well to combat the COVID-19 pandemic.

Lucas Harrington, co-founder and chief scientific officer, Mammoth Biosciences

When designing CRISPR editors for both therapeutics and diagnostics, data science comes in handy for learning intrinsic properties of CRISPR proteins, as well as different sensitivities within the ~20 base pair guides with respect to how well they might tolerate mismatches.

Testing every possible sequence (4^20 possible, for the 20 positions, each of which can be occupied by one of four bases) is impractical, says Harrington. However, pulling out trends in how guide efficacy changes by target sequence, for example, from large datasets can prioritize optimal ones for a given editing task.

When selecting for an optimal guide RNA, the team breaks up the guide sequence, giving each section precise weights based on its effect on a variety of parameters. For diagnostics, the efficacy (how fast the guides can identify target sequences) and accuracy (detecting multiple strains of pathogens but not related sequences) of guides are key.

The team’s goal here has been: “how can we, within a matter of weeks, spin up a new test?” says Harrington. Having both the manufacturing kits and the software to prioritize guide RNAs given target sequences and co-infections to avoid has allowed for a fast response by eliminating the need for testing every possible guide.

For each new variant that appears in the population, the team simply switches out the guide they use in their test.

Where therapeutics and diagnostics diverge

As they are biochemical assays, CRISPR-based diagnostics can be developed in a controlled setting: starting with an amplicon of DNA only and no chromatin provides minimal competition from reagents. As a result, researchers can make very clean training datasets from assaying thousands of guides that capture the intrinsic properties of the proteins themselves rather than confounders.

Whereas for diagnostics, inclusion (guides that enable detection of all SARS-CoV-2 variants) and rapid development are useful, safety is the foremost goal in therapeutics. Thus, guide exclusivity is key, and the team tests every possible sequence to ensure the best possible one is chosen. The stakes are much higher when artifacts might not only limit therapeutic efficacy but also risk safety.

Looking ahead, role of computation in gene editing

Gene editing as a therapy in some ways is paradigm-changing and in others fits a traditional mold. Just like the permanence of surgeries, “in some sense, making a single base pair change in the liver to improve someone’s health is molecular surgery,” says Kathiresan.

Computation is important in every key step of the journey: from identifying new possible proteins and guide sequences as components of the editing machinery to evaluating the medicines both in the lab and in the clinic. Every new technology that generates its own kind of data will require clever analyses from which to extract key design insights to maximize the efficiency of both diagnostic and drug development.

Harrington says that the biggest challenge today remains in the data itself—specifically, extending beyond small or “dirty” datasets so that biological conclusions are reliable and not artifact-driven.

We are still at the point where scientists must ask the right questions and feed in the variables that are likely to be most informative to pattern recognition models. However, there is a consensus that patterns exist in biology, and that computers will be better at extracting them due to their ability to hold more information at once than humans (who can typically hold 4-5 sequences in their mind simultaneously).

Tools like Arbab’s that serve as community resources will be increasingly useful as each team builds off shared learnings for their disease area(s) of focus. Bridging discovery with applications will allow closing the loop, enabling more informed development of gene editing tools. This will require crews of software engineers to build out databases in a way that will be “mine-able,” as well as constant communication with wet lab scientists who can flag and curate learnings and report them upstream.

There’s a palpable optimism in the field of gene editing. The potential for one-shot, curative treatments provides clear focus and ample motivation for the long term. The advanced computational tools, shared datasets, and collaborative spirit from multiple disciplines are all there. It’s an exciting time for the field, with potential benefits for human health that could arrive faster than people would have forecasted just a few years ago.

20
Aug
2021

Giving Back and Experiencing Nature

/
/
0
/
20 Aug 2021

Sometimes we need to get away from work, and the news, to recharge our batteries. August is traditionally that time of year for me.

I just got back from the summit of Mt. Baker (elevation 10,781 ft) in the North Cascades of Washington. It was another successful mountain trip with terrific biotech people – entrepreneur Julia Owens, investor Dan Bradbury, venture capitalist Nancy Hong, and Ardem Patapoutian (Nancy’s husband and a researcher at The Scripps Research Institute).

We were guided by Lakpa Rita Sherpa, Jangbu Sherpa and Dawa Yangzum Sherpa. They are some of the most accomplished Sherpa mountain guides in the world. Lakpa and Jangbu are good friends of mine, and were part of the guiding team on my Mt. Everest summit expedition in 2018. Dawa Yangzum is famous for being the first Nepali woman to summit K2, and the only woman of color on the all-star team of mountain athletes sponsored by The North Face.

This climb was a fundraiser for the Alpine Ascents Foundation, which supports education for 55 Sherpa schoolchildren in Nepal. Together, we raised $20,000 for the cause.

There were some challenges. We ran into 50 mph winds. We had to avoid some massive crevasses. It was a long, low-visibility day on the icy glaciers of the North Cascades. But everyone made it up and down safely, and had a wonderful time. See a couple photos (that’s me and Julia Owens on the very windy summit).

This isn’t my only outdoor adventure which mobilizes the biotech community for a good cause in 2021.

Next month, I’m taking a team of 20 biotech executives and investors on the Presidential Traverse hike in New Hampshire. We’ll cover more than 20 miles, and gain more than 8,000 feet of elevation as we cross over the summits of Mt. Washington, Mt. Jefferson, Mt. Madison and more.

This Timmerman Traverse is a fundraiser for Life Science Cares. It’s an organization that supports an array of outstanding nonprofits in the Boston area who do critical work on homelessness, hunger, job training, education and more. LSC is now expanding its model to other biotech hubs — the San Francisco Bay Area, San Diego, and Philadelphia.

Life Science Cares provides a way for the biotech community to support the most vulnerable people in our communities, and help them get back on their feet.

The Timmerman Traverse team has raised more than $479,000 so far – well on our way to smashing the $500,000 team goal. I’m proud of this group of dedicated biotech leaders, and grateful for the generous support of so many people.

If you’d like to learn more about this trip and this team, watch this 3-minute video created by SVB, the lead sponsor of the Timmerman Traverse for Life Science Cares.

Doug Fambrough of Dicerna, Katherine Andersen of SVB, Alice Pomponio of the American Cancer Society, Samantha Truex of Atlas Venture, Dave Melville of The Bowdoin Group all have powerful messages about why they’re doing what they do. Art Krieg of Checkmate Pharmaceuticals and Jeb Keiper of Nimbus Therapeutics also have potent video testimonials at the end.

You can click here to see who’s on the team, and make a contribution directly to their fundraising campaign through the JustGiving.org platform.

There is tremendous capacity for good in the biopharmaceutical industry. Let’s show it.

16
Aug
2021

Vaccination and the Delta Variant: Four Steps Forward, Two Steps Back

/
/
0
/
16 Aug 2021

Larry Corey, MD

The news is all about Delta, Delta, Delta, for good reason.

The variants are forcing us to ask and answer, again, a whole set of uncomfortable questions.

Sobering findings of the past few weeks have shaken both the American and scientific psyche. People have had to re-assess their perceptions about the COVID-19 vaccines, and the re-emergence of an epidemic many thought was over. Many of us have had to come to terms with how life can sometimes just be complicated.

It’s been a scientific and emotional roller coaster. In the spring, we saw the Alpha variant, which was two times more infectious than the ancestral strain. That was followed by Beta, which was eight times more resistant to laboratory assays and to neutralization with therapeutic antibodies in the petri dish. That variant was worrisome, because it was more capable at resisting vaccines. We were lucky because it was outcompeted by Alpha – a variant that the vaccines could handle.

Now Delta is here and just ripping through both of them, like a hot knife through butter. It’s replacing Beta with the same rapidity that it replaced Alpha and all the in-between variants. It’s now the dominant variant in the US, showing up in more than 90 percent of positive cases.

So, what is it about this Delta, or what I should say, many Deltas?

What we’re seeing is this scientifically fascinating, but epidemiologically disconcerting change in the virus that’s happened at an incredibly rapid pace. Delta has some new characteristics which make it a formidable foe. It’s much more infectious to others; initial viral loads in the nose seem to be somewhat higher than previous strains with more rapid spread into the lungs and other organs within the body.

It is clear that the amount of virus required to infect others is lower, making transmissibility to household and casual contacts more efficient than the other variants. The average person who contracts a Delta infection transmits the virus to between 5 and 9 other people – making this variant far more infectious than the original ancestral strain from a year ago.

Case numbers, predictably, are quickly increasing. Younger adults are being hospitalized. ICUs are filling up. Most disconcertingly, we are seeing more children being admitted in our pediatric hospitals. When we look at who’s in the hospital among adults, we see about 95 to 98% are unvaccinated. The same pattern is seen with children. COVID-19 Delta strain is a hospital epidemic of the unvaccinated.

Yes, we are now seeing outbreaks of Delta in which vaccinated people are infected, such as the one from early July in Provincetown, Massachusetts. These outbreaks involve two behaviors we’ve seen that result in super-spreader events—crowding and indoor revelry with drinking and eating and no masks. Eating, drinking, shouting, singing—spraying forth, shall we say, produce a density of unseen viral particles in the air that people inhale over and over again.

These behaviors are the food of the virus—a heavy smorgasbord of food: all advantageous to the virus. The result is that we are seeing humans get infected. For the vaccinated, this means just mild infection. But for the unvaccinated, we are seeing rapid spread of the virus to the lungs and other parts of the body.

With more than 100,000 cases a day being tallied nationwide, it’s clear we need to take some new countermeasures to slow the spread.

We’ve seen a necessary reintroduction of masking. Just when many people were ready to celebrate, or breathe a sigh of relief, many of us are now back in an anxious position. Questions that we might have thought were settled a month ago are suddenly back in play.

Will our children be able to safely go back to school? Can we safely go back to work? Will we ever be able to relax and enjoy dinner indoors again with friends, extended family, or in professional settings?

Delta is disconcerting to all of us.

Last week, I cancelled a CoVPN (COVID-19 Prevention Network) scientific meeting in October—one that I’d been eagerly planning and anticipating for months. We wanted to meet and celebrate/review the work the network has done in developing effective COVID-19 vaccines at unprecedented, record-setting pace.

The success of the program and the hard work and toil have shaped the careers of many scientists on this team. In some ways, it has shaped entire worldviews. We wanted to revel in the camaraderie of the team’s success and do so in person. But it was clear—even though the event required vaccination to attend, no one wanted to come to Seattle to celebrate with the possible risk it would carry if anyone contracted Delta and had to be quarantined away from home.

Let’s look at vaccination and Delta as it relates to the US:

  • The mRNA and Janssen vaccines both are highly effective against death and hospitalization (greater than 90 to 98%).
  • The protection from getting symptomatic COVID-19 appears to be a bit less with the Delta variant—studies show a range from 85% to 40%–and this may differ by time post vaccination. But in all studies the severity of illness is markedly less—the immune system of vaccinated persons can rapidly clear Delta. As noted above, severe disease among the vaccinated in the US with the mRNA or Janssen vaccines is rare.
  • Transmission to others from vaccinated persons can occur, but it is less than from the unvaccinated population, although we have not yet demonstrated how much less.

So, yes, one can still get infected with Delta despite being vaccinated if one doesn’t use precautions. That’s a fact. But a bigger fact is that you won’t get very sick, and you can reduce the risk of acquiring COVID-19 and spreading it if you wear a mask.

Perhaps we shouldn’t have been surprised. We understood that reducing acquisition of COVID-19 was a harder goal than ameliorating disease. But we do know the vaccines work and countless lives have been saved by them. So, the vaccines have markedly changed the dynamic of our thought process, but maybe what we need is to change our expectations.

What do I mean by that?

Well, the virus is teaching us another important lesson—its amazing speed to adapt. It’s hard to understand how a virus like this is rolling through the world. But rolling through, it is. Recent data out of Israel estimates that every six to nine days the Delta infection among its population doubles. As Israel has the highest percent vaccination rate (with Pfizer/BioNTech mRNA) of any adult population in the world, this is at first glance surprising. However, not when one recognizes that younger people are not yet vaccinated, and it’s the unvaccinated who are the main fuel for that kind of rapid spread.

Why is it so transmissible? What selective pressure is it under? Delta doesn’t have the obvious neutralization-resistant mutations. What part of the human immune response that you get from vaccination is being delayed by the Delta variant? Will boosters actually slow it down or is it really more important to focus our efforts on reaching the unvaccinated?

These are all scientific questions needing answers. As Israel has made the decision to boost its elderly population, some data about the role that boosting can play in reducing spread will be obtained.

But the boosting issue is a bit of a diversion from the main issue in our country, which is, how do we reduce the spread of this highly infectious variant? 

Do we need a national mandate for vaccination? Is it a personal choice to vaccinate or not? Or do we all have a societal obligation to not be the fuel to this ongoing forest fire? The unvaccinated in some respects are an unsuspecting accomplice to the arsonist at large—they serve as bone-dry tinder for the lighted match.

Should we rethink this?

Our body politic is focused on extreme individualism, and isn’t allowing a universal approach to public health. In such an environment where political leadership is limited, do our corporate leaders who can mandate vaccination step up to the plate?

There are some who are pointing to government action, namely through a full approval of the vaccines by the FDA. But does anyone really believe that the Emergency Use Authorization is that much different than the FDA licensing it under a full Biologics License Application? Yes, there are important steps to licensing the medication so that there is consistency from lot to lot in manufacturing. But at 400 million vaccinated and growing daily, we have ample safety and efficacy data.

So, yes, official product licensure is, to this author, not an appropriate reason to hold back mandated vaccination. We already know the vaccines are extraordinarily effective, and powerful tools for fighting back against the pandemic. Each day the documentation of the positive effect of the vaccines grows, and we understand that the virus is continuing to mutate. Cutting off the fuel to the fire is really the only way to slow down the rate of mutational alterations.

It is true that the Delta variant has swept in like a cold, damp morning shrouded by fog. And it’s left us with a bit of a shiver. But like all days, morning turns to afternoon and the sun gets higher in the horizon and some of the fog lifts. Although Delta has taken us two steps back, a much more important step forward is to continue to vaccinate as many of our citizens as we can – here in the US and around the world.

Once we do, Delta may move itself two steps back, putting us once again two steps forward toward pre-COVID-19 normalcy.

Dr. Larry Corey is the leader of the COVID-19 Prevention Network (CoVPN) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.

9
Aug
2021

Better Cancer Drugs for Kids: Julie Grant and Sam Blackman on The Long Run

/
/
0
/
09 Aug 2021

Today we have a pair of guests on The Long Run — Julie Grant and Sam Blackman.

Julie Grant, co-founder, Day One Biopharmaceuticals; general partner, Canaan Partners

Julie is a venture capitalist – a general partner at Canaan Partners. Sam is a pediatric oncologist and drug developer. After a routine business meeting, they realized they had something in common. They both believed that the pharmaceutical industry can — and should – find a way to do a better job of developing cancer drugs for kids.

So they did what scientific entrepreneurs do. They took a gamble, and tried to figure out how to do something that hadn’t been done before. They poured a lot of time and energy into fleshing out a concept of a purpose-built precision oncology company that puts the needs of children first. That concept became San Francisco-based Day One Biopharmaceuticals. Julie is the board chair, and Sam serves as chief medical officer.

Sam Blackman, MD, PhD; co-founder and chief medical officer, Day One Biopharmaceuticals

I wrote about the company a couple times for Timmerman Report a couple times before it went public, and subscribers can go back and read those articles from May 2020 and February 2021. The company now has a market valuation of more than $1.5 billion on the day of this recording. Side note here–if Day One is successful, its work could spill over and benefit adult cancer populations as well – but I digress.

Julie and Sam are creative, tireless people committed to helping kids with cancer. I think you’ll enjoy hearing them talk about this new journey in applying science for the betterment of human health.

Before we get started, here’s a word from the sponsor of The Long Run.

“After almost half a decade of being graced by your presence, my sense of wonder and admiration for you has not waned one bit. In fact, it has only grown.”

This is an excerpt from a love letter written by Leonardo to his cells. One of several
incredible love letters written by amazing research scientists to give us a glimpse into the wonderment, the beauty, and the challenges of cell research.

Join us in this exploration of a connection like no other, part of the Love Your Cells
campaign.

Watch Leonardo read his amazing love letters at thermofisher.com/GibcoLoveYourCells.

Now please join me and Julie Grant and Sam Blackman on The Long Run.

4
Aug
2021

Tachi Yamada, Physician-Scientist-Biopharma Industry Leader, Dies at 76

/
/
2
/
04 Aug 2021

Tadataka “Tachi” Yamada, a distinguished physician-scientist who became a biopharmaceutical industry leader and a deeply respected advisor to biotech entrepreneurs, died the morning of Aug. 4. He was 76.

Tachi Yamada

Yamada died from a heart attack while exercising at home in Seattle, said his son, Takao.

“He was a special person who did things to help people. That was his North Star,” his son said.

Yamada was a rare leader with experience in several dimensions of the scientific enterprise – academia, industry, and philanthropy. He was best known for high-profile roles later in his career as the chairman of R&D at GSK, the president of the $9 billion global health program at the Bill & Melinda Gates Foundation, and then as chief medical and scientific officer at Takeda Pharmaceuticals.

Those jobs came after Yamada made an early mark as a physician-scientist, specializing as a professor of gastroenterology at UCLA and then at the University of Michigan. He was elected by peers to National Academy of Medicine in 1994, around the time he made the move to the pharmaceutical industry.

Over the past 25 years, Yamada accomplished a series of things that will last. He built up GSK’s vaccine business to combat rotavirus and shingles and other infectious diseases. He further invested in vaccines at Takeda, including vaccines for dengue and norovirus. He helped transform Takeda from a regional pharmaceutical company into a top-tier global pharma R&D enterprise, serving as an important champion of vedolizumab (Entyvio) for Crohn’s and ulcerative colitis — a blockbuster product.

More recently, as an advisor to small companies, Yamada helped launch the Philadelphia-based gene therapy company Passage Bio with longtime friend and colleague Jim Wilson of the University of Pennsylvania, as well as Florham Park, NJ-based Phathom Pharmaceuticals, a developer of gastrointestinal drugs.

Many colleagues were shocked and in mourning over the death of such a healthy and vibrant man.

Andy Plump, president of R&D, Takeda Pharmaceutical

“He was the embodiment of life,” said Andy Plump, the president of R&D at Takeda who took over when Yamada left in 2015. “He took care of himself. Ate well. Exercised, literally every day.”

As a business leader, Yamada “was really, really smart. Very sharp. Extremely experienced,” Plump said. “He was tough. He had a vision and was not shy around that vision and really driving something he believed in.”

“I’m heartbroken,” said Thong Le, the CEO of Accelerator Life Science Partners in Seattle, who recruited Yamada to join his board of directors seven years ago. “It wasn’t his time. He was still doing so many great things…no matter how complicated the situation, he got to the nub and knew what needed to be done. He’s one of those few guys with a unique mix of understanding the medical need and all the business and technology challenges that go with developing a new treatment.”

Thong Le, CEO, Accelerator Life Science Partners

Bruce Goldsmith, the CEO of Philadelphia-based Passage Bio, a gene therapy company where Yamada was chairman of the board, was in grief.

“He put a lot of faith in me as a first-time CEO. He always gave me the support I needed to work independently, to build the company independently, but that wouldn’t mean he wouldn’t give me critical comments to think about…once he decided to invest in a person…I saw a massive amount of commitment from him. When there was uncertainty, questions as there always are, he’d set aside time constantly to make sure we’d figure it out.”

Yamada’s life journey started in Japan. He was born in Tokyo on June 5, 1945, just before the end of World War II. He moved to the United States as a boy and attended Phillips Academy in Andover, Mass. before going to Stanford University, where he majored in history.

After getting his medical degree at New York University, he did his internship and residency in Richmond, Virginia, followed by a three-year stint as a major specializing in infectious diseases at the US Army Medical Research Institute of Infectious Diseases. He spent the next 20 years as an academic gastroenterologist, starting at UCLA and then building one of the nation’s leading departments at the University of Michigan.

He sought new opportunity to help patients through industry at SmithKline Beecham in 1994, starting in a non-executive director position. He quickly worked his way up, ultimately overseeing one of the industry’s major R&D engines at GSK in the early 2000s, following a megamerger with Glaxo Wellcome.

Yamada saw a new opportunity in 2006 to take over the global health program at the Bill & Melinda Gates Foundation. The world’s largest private philanthropy was ascendant on the global stage, flush with cash from Warren Buffett, and in position influence global health priorities around fighting tuberculosis, malaria and HIV. He stayed five years before moving back to industry.

At Takeda, Yamada was able to use his accumulated experience to help position the company to make a bigger global impact.

At the time, Takeda was fragmented across four organizations – Takeda Japan, the TAP Pharmaceuticals joint venture between Takeda and Abbott, the Millennium Pharmaceuticals team in Cambridge, Mass., and Nycomed in Europe. “He started a process, a fairly challenging process, of consolidating activities,” Plump said.

Yamada worked closely with then-Takeda CEO Yasuo Hasegawa to bring the far-flung operations together, implement more disciplined decision-making processes, and step up its game in science, Plump said.

When Hasegawa stepped aside and Christophe Weber came in as the first non-Japanese CEO of the 200-year-old company, Yamada, about 70 at the time, played an important role in keeping the transition on track until it was time for Weber to bring in a new R&D chief he could work with for the next decade. “Tachi bridged between them [Hasegawa and Weber] and lit the flames of cultural change in R&D,” Plump said.

“Few people can lead in so many different capacities as he did — in academia, in the NGO world at the highest level, and two times in pharma at the highest level in R&D,” Plump said.

The last chapter of Yamada’s career was a whirlwind. He served as chairman of the board at Phathom Pharmaceuticals, Passage Bio, and Athira Pharma. He served on the boards of a number of other small companies, partly through his relationship with Frazier Healthcare Partners.

The Frazier relationship provided an avenue for him to help a number of entrepreneurs across disciplines. The work there dated back to his time at the Gates Foundation. He stepped away from Frazier during his time at Takeda to avoid conflicts, and then returned as a venture partner in 2015.

It was an opportunity to paint on a broader canvas across the startup community, and to pick the people and projects he felt passionate about.

A day after the announcement that he was leaving Takeda, Le happened to have a pre-scheduled meeting. He walked in and got straight to the point. “Hey, I saw the announcement, and I’m sure 100 people will ask you the same thing. But I need your help,” Le said.

He asked Yamada to join his board.

“He chuckled, like he always does,” Le recalled.

Then came an unequivocal answer.

I haven’t figured out what to do with my time, Yamada told Le, “but I believe in you. Of course, I’m going to help you.”

Le was a bit choked up re-telling the story, knowing how many doors Yamada opened, and how much his committed counsel helped keep things moving forward for Accelerator. “I feel like I’ve lost a mentor, and almost like I’ve lost a father,” Le said.

Yamada, for instance, played a key behind-the-scenes role in Accelerator’s successful sale of Rodeo Therapeutics to Amgen earlier this year. (TR coverage, Mar. 2021).

Jamie Topper, managing partner, Frazier Healthcare Partners

Jamie Topper, managing partner at Frazier, said the firm was eager to have Yamada re-engage the last six years. Phathom and Passage are a couple of the portfolio companies that he helped ignite.

“Tachi is a polymath. As far as I can tell, he worked 22 hours a day, 7 days a week,” Topper said. “When he was looking at an area, he read widely in that area. He would know everything from the basic science to the clinical relevance. He lived and breathed medicine his entire career. He was a man of breadth and depth. He brought a compassion for patients and the families of the patients.”

Stylistically, Yamada was poised. He could come across as mild-mannered and soft-spoken. A man who would choose his words carefully, and speak succinctly.

“One of my favorite things about Tachi is that he was always very direct. He would do it in a polite and respectful way. If he disagreed with you about something, he could disagree and it would remain civil,” Topper said.

Le, of Accelerator, spoke of that same directness. Yamada would listen carefully and absorb information. He would also suffer no fools. “He could cut the BS and get right to whatever was most important,” Le said. “It’s such an important skill in today’s world with so much information. Knowing what to focus on can mean the difference between success and failure.”

Goldsmith of Passage Bio said he was struck by a certain agility of mind.

“You can have these big strategic overarching vision conversations with him, and then these really detailed operational conversations. He could back and forth, and it was his experience that enabled him to go back and forth. We could talk about where we should go and how to get there,” Goldsmith said.

Bruce Goldsmith, CEO, Passage Bio

Not every polymath is known for personal warmth, but those who know Yamada said he radiated that, too.

Le said that when having a meeting, Yamada would often invite him to come sit down on a couch beside him, instead of from an imposing chair behind a desk.

Goldsmith said Yamada once told him, as the senior person in the company, it’s good to always show up 1-2 minutes purposely late for a meeting so that no one on the team would feel bad for showing up late and potentially irritating the boss. It was a subtlety, but it worked, Goldsmith said.

Plump recalls traveling to Japan and waking up at the hotel, jet-lagged, and heading down to the gym at some odd hour like 3 am or 4 am or 5 am. Always, he’d see Yamada already there doing his workout. Over 30 years, Yamada told him, he’d taken two days off from his physical fitness routine.

Yamada’s favorite drink was always an ice-cold green tea. It helped him stay fresh and energized for the work. He avoided alcohol. Those consistent, disciplined habits — of body and mind — were part of what made Yamada successful. Among the many bits of advice he gave his successor, Plump remembers the part about not getting worn out. “Take care of yourself,” Yamada said. “Because the things you’re going to have to do will be stressful at times.”

Another key piece of advice from Yamada: “Everyone you work with will have something positive to offer. You need to find out what that is, and position them best so they can provide that.”

The two men had many dinner meetings during the transition at Takeda, and Yamada enjoyed discussing his family and introducing them. Goldsmith noticed the same thing – no matter how focused or intense a meeting might have been, Yamada had time at the end to talk about life, family, what was new and interesting.

Plump shared one last story. Once, when he was stuck in traffic and running 30 minutes late for a meeting with Yamada, he felt terrible and apologized profusely upon arrival.

Yamada, the picture of discipline and poise, shrugged it off, and told him not to worry. Yamada had spent the time with four different newspapers open in front of him, absorbing information from different sources and perspectives.

Plump took note. There was a scientific executive always seeking to learn, always seeking to understand, always synthesizing different perspectives. A man on a quest to get to the heart of the matter, and to advance human health.

27
Jul
2021

An Industry that Depends on Diversity Should Defend It

/
/
4
/
27 Jul 2021

Paul Hastings, CEO, Nkarta Therapeutics

[Editor’s Note: I asked Paul to write in response to a biotech executive who’s marketing a new book that claims diversity and inclusion in business is “the defining scam of our time.”]

As CEO of a cell therapy company, I know that the human immune system is a pointillist masterpiece, containing trillions of B and T cells with unique antigen receptors that allow them to latch on to and neutralize endless permutations of potential threats.

Within the human body, our diversity is – quite literally – our greatest strength.

The COVID-19 pandemic, for all the tragedy it has wrought, helped ignite two long-overdue conversations in America: one about health equity and another about the value of diversity and inclusion in a time of heightened attacks against those who identify, look or love differently.

In so many ways, biopharma CEOs sit at the intersection of both this new disease and this new dialogue. I know many CEOs and industry leaders who have been championing diversity and inclusion long before it was as popular to do so, but I celebrate the current focus on addressing systemic barriers. As a an openly LGBTQ CEO and a longtime warrior in the diversity trenches, I’m endlessly proud that a growing majority of my biopharma CEO colleagues are embracing this leadership role.

Some critics don’t believe that advocating for diversity and inclusion is in the job description of biotech CEOs and dismiss our efforts as “woke” and insincere.

Here’s what I believe: To lead a company charged with creating “living” biologic medicines in 2021 is to understand, as a fundamental matter of science, the life-sustaining value of biological diversity. The value of diversity is equally self-evident when we look up from our lab benches and look out at our colleagues around the conference-room table.

To create a culture of innovation, experience as a five-time biotech CEO has taught me to insist on teams full of people with different backgrounds, experiences, perspectives and ideas. CEOs who fail to proactively seek out such synergies aren’t just “unwoke”. In my opinion, they’re asleep at the wheel.

The truth is, some biopharma leaders have hit the snooze button for far too long on diversifying clinical trials, on building inclusive leadership teams, on hiring outside of homogenous comfort zones and on assembling culturally competent teams that can understand and meaningfully connect with underserved patient populations.

Now, from the ashes of the COVID and George Floyd tragedies, progress has a chance. There is no filibuster in the biopharma C-suite. Industry CEOs have great power to effect change and be part of an industrywide effort to invest in health equity to regain public trust and affection.

We are in the midst of a paradigm-shifting global pandemic that preys on the immunocompromised, the underinsured and the unseen. Conversations are changing. Companies are engaging contract research organizations to amplify efforts to reach diverse populations. Health equity and Corporate Social Responsibility (CSR) budgets are becoming more substantial line items. Investors now demand it.

The biotech industry is charting a more compassionate, inclusive, patient-focused course, one Zoom meeting at a time. If dedicating time and resources to achieve that kind of overdue progress is “woke,” I don’t ever want to go back to sleep.

Paul Hastings is the CEO of Nkarta Therapeutics in South San Francisco.

26
Jul
2021

Career Arc of a Biotech Leader: Sue Desmond-Hellmann on The Long Run

/
/
1
/
26 Jul 2021

Today’s guest on The Long Run is Sue Desmond-Hellmann.

Sue — and I don’t say this about many people — is a biotech industry legend.

Sue Desmond-Hellmann

Sue is an oncologist and a public health professional by training. She made her name in biopharmaceuticals at Genentech from 1995-2009 — the glory days when it became the world’s most important developer of new cancer drugs.

She was part of the leadership team when the company developed the original targeted antibodies for cancer – Rituxan, Herceptin, and Avastin.

After Genentech, Sue served as chancellor of UCSF, and then worked as CEO of the Bill & Melinda Gates Foundation until January 2020.

Currently, among other things, Sue is a board member for Pfizer, and is an advisor to GV, the venture capital firm formerly known as Google Ventures.

In this episode, we talk mostly about Sue’s early career – growing up, becoming a doctor, working on the frontlines of the AIDS epidemic, and finding her way into industry. We talk some toward the end about her time at Genentech.

Before we dive in, a word from the sponsor of The Long Run.

DNA Script recently launched the SYNTAX System, the first-ever benchtop enzymatic DNA printer, which uses their proprietary enzymatic synthesis technology.

The SYNTAX System prints DNA, on-demand, right in the lab. Researchers simply import their sequences, and within hours the system synthesizes DNA oligos that can be used immediately in molecular biology and genomics workflows.

DNA Script’s enzymatic DNA synthesis emulates nature to overcome the drawbacks of the chemical-based methods traditionally used until now. Designed for fully automated, walk-away synthesis, the SYNTAX System takes less than 15 minutes to set up with no special training to operate.

With SYNTAX, researchers can accelerate discovery with DNA on-demand.

For more information on DNA Script, please visit www.dnascript.com.

 

Now please join me and Sue Desmond-Hellmann on The Long Run.

20
Jul
2021

Why We Need mRNA Vaccines in Africa, and For All Who Are Immunocompromised

/
/
2
/
20 Jul 2021

Larry Corey, MD

The HIV pandemic, and COVID-19 pandemic, are intersecting.

The relationship between the two conditions is creating an epidemiological synergy that is starting to translate into additional misery for humankind.

If we can better understand this phenomenon, we can think more clearly about how to better protect the most vulnerable populations among us – people with HIV, and millions of others who are immunocompromised. We have seen overlapping epidemics before, and can draw from that experience.

Let’s start with HIV. Individuals living with HIV have a degree of immunosuppression which varies based on their therapy and disease course. If the disease course is well controlled and fully virologically suppressed on antiretroviral therapy, there is evidence to believe that these patients are at a normal risk of acquiring and controlling COVID-19, much like others in their families and communities.

This analogy is partially accurate in that those living with HIV can, because of their medicines, have obesity, diabetes, and increased lung disease, which are all predispositions or comorbidities associated with severe COVID-19.

Importantly, there are subsets of persons living with HIV, including those who are immune deficient with low T cell counts, those with viremia due to drug-resistant HIV viral strains, those not receiving or not taking antiretroviral therapy; and the many millions we know are living with undiagnosed HIV infection, including those recently infected.

These persons are subject to acquire persistent, prolonged COVID-19 infection, akin to organ transplant recipients and severely immunosuppressed cancer patients.  

There are many causes of immune deficiency, but in many countries, HIV infection is among the most common.

A recent case report by Karim et al. from South Africa, the country with the largest percentage of the population living with HIV of any country, described a case of HIV infection in a person who had very low CD4 counts due to resistant virus and a lack of compliance who developed COVID-19. Over a period of 200 days, this patient—who was ambulatory, living in the community, and without serious symptoms—shed COVID-19. The person had mild illness early on, which is why they were observed, and because of HIV, follow-up care ensued. The investigators had samples from the patient, and they shed COVID-19 at high titers, showing the development of multi-mutational changes in the virus over time. Mutational changes that essentially recapitulated the Beta variant, which has 9 to 11 different mutational changes from the original ancestral strain.

This is a single case, but it’s important because it illustrates a broader issue at work in our communities.

Individual patients living with HIV and compromised immune systems who have this prolonged shedding pattern can result in the kind of mutational changes that lead to germination and spread of variants of concern.

This case is illustrative because it’s not rare. Out of the estimated 38 million people living with HIV worldwide, South Africa alone has more than 16 million. In South Africa, that means one out of every four of its 65 million people are living with HIV.

So okay, the two epidemics are intertwined, what’s the concern? The concern is that these people will suffer more serious COVID-19 cases and that they may serve as the potential unwitting source of super-spreading events of new variants through household and community contacts.

As the greatest population of persons living with HIV is in sub-Saharan Africa, where vaccination rates are currently less than 2% of the populace, this continual reservoir of variant generation is and should be of concern to all of us. We need to recognize that we do not have a demonstrably effective vaccine against COVID-19 among persons living with HIV. People with immunocompromised profiles weren’t included in the well-controlled vaccine studies of the past year, when speed of enrollment was of the essence (see June 29 article in Timmerman Report).

While we lack comprehensive data, we have good reason to be concerned about vaccine efficacy in immunocompromised groups. The data that we have from the Novavax study in South Africa showed absolutely no efficacy against COVID-19. In the Ensemble Johnson & Johnson (J&J) study, too few cases were acquired to adequately evaluate the effectiveness of the one-dose J&J vaccine. And in the Moderna trial, no cases of COVID-19 were reported in the 150 HIV+ recipients who received vaccination. The reason for the lack of efficacy of the Novavax vaccine is puzzling and worrisome, as the post-vaccination binding antibody titers were well above natural infection and in the range associated with reasonable efficacy (median 33,000).

So, what’s going on here? The answer is, I don’t know the reason for lack of effectiveness, but I do know that the mRNA vaccines offer the most immediate solution to this major hole in the public health control of COVID-19 variants.

The data suggest that we need to take our most potent vaccines—mRNA or perhaps two doses of the J&J vaccine or a heterologous “mix-and-match” prime-and-boost with one of the vaccines being an mRNA vaccine—into areas of the world where there is HIV.

We need to urgently take steps to evaluate if our best vaccine regimens are able to effectively prevent acquisition of COVID-19 in all persons living with HIV, but especially among those with uncontrolled HIV.

This is the kind of urgent, heavy lifting that only the US government can do in an emergency.

The tale of these two intersecting epidemics needs a better ending than what we—as a global community—are currently creating. The Delta variant epidemic is rapidly illustrating that chasing variants is not a successful strategy. The Delta variant has swept through countries like the UK, Israel, and South Africa in four to eight weeks and is approaching the predominant variant in the United States at a speed that even with RNA technologies, we cannot keep up. Our approach must be to slow down the generation of these rapidly doubling super-spreading micro-epidemics of infection among unvaccinated persons.

The equation today among those unvaccinated individuals is not whether you will get COVID-19 infection but when you will get it. Slowing it down requires our best vaccine strategies. It’s certainly not too late. But we need both studies and implementation of our most potent vaccines and vaccine regimens to be applied to all of our immunosuppressed populations, the largest of which is HIV, for us to have a globally effective strategy.

Dr. Larry Corey is the leader of the COVID-19 Prevention Network (CoVPN ) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.

19
Jul
2021

Investing at the Nexus of Biology & Technology: Jenny Rooke on The Long Run

/
/
0
/
19 Jul 2021

Today’s guest on The Long Run is Jenny Rooke.

Jenny is the founder and managing partner of San Francisco-based Genoa Ventures.

Jenny Rooke, founder and managing partner, Genoa Ventures

I’ve been wanting to invite Jenny on the podcast for a while. Back in 2018, I profiled her as one of “Nine VCs Who Matter, But You Never Read About.”

As I wrote then:

“VCs take on lots of different types of risk. There’s biology risk (something can’t be reproduced from mice to humans). There’s management risk (sometimes you back bad executives). There’s market risk (maybe the market won’t buy what you’re selling at your preferred price). There’s syndicate risk (your co-investors might run out of money or lose faith, forcing you to prop up portfolio companies if you want to keep them alive to the next milestone).

What you seldom see are VCs who shoulder a more profound type of risk, not just by starting their own firm, but by starting a venture firm with an unproven business model.

She started her firm by building the largest life science syndicate on AngelList, not by going to the usual big pension and endowment funds that typically invest in VC funds as limited partners.”

Here’s how she describes her approach:

“I’m particularly motivated by novel research platforms because part of what surprised me about lab work was how manual, and slow, and low through-put a lot of available tools were for doing science, so when I see companies that are trying to develop new tools that make more and better data for researchers that gets me excited.”

How’s it going so far?

Like any early-stage VC, it takes a while to build a track record.

Two of Jenny’s big investments from the early days of Genoa are emerging – Emeryville, Calif.-based Zymergen, an industrial biotech company, and Berkeley, Calif.-based Caribou Biosciences, a company that uses CRISPR editing for cell therapies.

Zymergen went public in April, and now has a market valuation of $4 billion. Caribou Biosciences recently filed IPO paperwork to raise up to $100 million.

It took a lot of guts and creativity to do what Jenny has done, and continues to do.

Before diving into her story, a word from the sponsor of The Long Run.

DNA Script recently launched the SYNTAX System, the first-ever benchtop enzymatic DNA printer, which uses their proprietary enzymatic synthesis technology.

The SYNTAX System prints DNA, on-demand, right in the lab. Researchers simply import their sequences, and within hours the system synthesizes DNA oligos that can be used immediately in molecular biology and genomics workflows.

DNA Script’s enzymatic DNA synthesis emulates nature to overcome the drawbacks of the  chemical-based methods traditionally used until now. Designed for fully automated, walk-away synthesis, the SYNTAX System takes less than 15 minutes to set up with no special training to operate.

With SYNTAX, researchers can accelerate discovery with DNA on-demand.

For more information on DNA Script, please visit www.dnascript.com.

Now please join me and Jenny Rooke on The Long Run.

1 … 26 27 28 29 30 … 79

Get In-depth Biotech Coverage with Timmerman Report.

Individual Subscription

Group Subscription

Or: Sign in to your account

Your account

What Readers Are Saying

testimonial
testimonial
testimonial

View More Testimonials ➛

Twitter