Lithuania Focused on Building a World-Leading Life Science Sector
Lithuania offers a range of government support for biotech companies, including 20 years of corporate tax relief for capital investments and seven Free…
In a compact laboratory on an upper floor of the Vilnius University Life Sciences Center is a biotech startup being held up as one of Lithuania’s growing success stories. Delta Biosciences, which is using microfluidics, DNA tags, and artificial intelligence to speed up drug screening, is hoping to start approaching European venture capitalists for investment next year.
The founders present their company with the energy and dynamism of stereotypical San Francisco technology entrepreneurs. Daniel Kratkovski, one of the co-founders, has a background in finance and investment. He and co-founder, Dominykas Milašius, say they came to Vilnius from London during COVID-19, inspired by what they say is a wave of change sweeping over Lithuania—especially the biotech sector.
“If you go into any tech park cafe, or even the cafes in the old town, there’s this crazy vibe in the air,” says Milašius. “Everyone is either talking about Ukraine or building a tech startup. I haven’t seen that anywhere else.” Or, as Alexander Morris, PhD, the British co-founder of another Lithuania-based biotech startup, puts it, “There’s something here that’s lacking in other European countries, the U.K. included.”
Lithuania’s growing ambitions
Milašius is keen to highlight that his biotech startup benefits from wider trends in Lithuania. He references a statistic that 2020 is the first time since the breakup of the Soviet Union when more people have returned to the country than left. The population decreased from 3.7 million citizens in 1990 to 2.8 million in 2021.
“Lithuania is stuck on a mindset of 2.7 million [citizens],” he says. “Now we think seven million because we have a diaspora of seven million. There are massive communities in the U.K. and Switzerland, and that unlocks a lot of doors.”
Patriotism seems to be a major factor in recent developments in the nation’s biotech community, and again, it reflects wider political trends. Since Lithuania gained its independence from the former Soviet Union in 1991, the country has been asserting a vigorous national identity—even down to reconstructing the entire Palace of the Grand Dukes of Lithuania in central Vilnius in the 2000s (Figure 1).
This muscular pride in the nation has helped in building a strong technology sector in Lithuania. The government is focused on supporting four growth areas, including biotechnology and life sciences, according to Innovation Agency Lithuania, one of the government’s development agencies. Invest Lithuania, another development agency, notes Lithuania’s life science sector is the European Union’s fastest growing, contributing around 2.5% of GDP with an ambition to increase that to 5% by 2030.
Building on a long history
Lithuania offers a wide range of government support for life science companies. These include 20 years of corporate tax relief for capital investments, and seven Free Economic Zones with 0% corporate and dividend tax for 10 years or more.
Most of these programs are aimed at encouraging inward investment from large overseas life science and biotechnology companies, which makes sense as Lithuania’s largest taxpayer last year was American life science and pharmaceutical supplier, Thermo Fisher Scientific.
Thermo’s Vilnius site, which has 1,850 employees, manufactures reagents and consumables, with a focus on products for protein manufacturing, qPCR, cell therapies, next generation sequencing, and genotyping. The company has shipped a number of the first products for COVID-19 detection to China at the beginning of the pandemic and finished construction of a new 59,200 ft2 building in September 2020 for manufacturing mRNA and protein production supplies.
According to Justas Plankis, Thermo’s site leader and director of manufacturing operations, the Vilnius site was set up as an enzymology institute in the “old” Soviet Union in 1975, and became Fermentas International, a restriction enzyme manufacturer, in 1994. When Thermo Fisher Scientific bought the company in 2010 for $260 million, it was the largest business deal in Lithuanian history.
“Thermo Fisher noticed the potential [of the site] right after acquisition, and they’ve made an enormous investment [in] manufacturing expansion over the years,” says Plankis, adding that although the site is known for protein manufacturing, they’ve since added additional competencies.
From restriction enzymes to CRISPR
The presence of Thermo and the long history of protein research at Fermentas and the enzymology institute have had a visible impact on the culture and skill sets of Lithuanians in Vilnius. According to Invest Lithuania, 56% of the population has a higher degree (second in the EU) with 25% of students choosing a STEM academic discipline (again, second in the EU). For reasons that never become clear, despite asking lots of questions, almost two-thirds of Lithuanian scientists and engineers are female.
Lithuania’s most famous contemporary scientist Kavli Prize laureate Virginijus Šikšnys, PhD, chief scientist and head of the department of protein-DNA interactions at Vilnius University, who is widely credited in Lithuania to have been scooped for the discovery of the pivotal CRISPR-Cas9 gene-editing technology after Cell rejected his paper.
According to Šikšnys, CRISPR was the “logical development” of Lithuania’s history and expertise in protein production. “[Fermentas] became a big production site for restriction enzymes to be distributed all over the world. This allowed Lithuanian scientists and researchers to gain the necessary protein production skills.”
Šikšnys co-founded the gene-editing company Caszyme in 2017, which is among Lithuania’s better established biotechs. The company manufactures CRISPR-Cas proteins with different characteristics as a molecular tool the life sciences, including industrial biotech. The company says it offers a library of more than eighty Cas9 orthologs. These include smaller Cas proteins for efficient delivery by adeno-associated viruses (AAVs), which have human therapeutic applications.
Caszyme also is now developing CRISPR-Cas12 proteins, which are smaller in size and introduce a double-stranded break into DNA by a different mechanism than Cas9 with different potential applications. Caszyme has visibly outgrown its space in the biotech incubator at the Vilnius University Life Sciences Center (Figure 2) and is working to move to new premises.
A major historical inspiration
The Thermo Fisher Scientific site serves as a source of supporting science in the local community. It partners with local universities, including Vilnius University, gives guest lectures, runs internships, and collaborates with a volunteer-led mobile bioscience lab where high-school students can run simple experiments to find out, for example, whether an onion is genetically modified or not.
But the company’s role as a driver of Lithuanian biotech is a result of being “a big player within the local economic environment,” as Plankis puts it. For biotech startups, Fermentas is a major inspiration. “Every young tech entrepreneur looks at [the history of] Fermentas and hopes to do the same in the next couple of years,” Milasius says.
Both Milasius and his co-founder came to Lithuania from London. Among the factors encouraging them to relocate was the reverse of Lithuania’s historical “brain drain” with scientists joining them from the University of Geneva in Switzerland the Crick Institute, and the University of Cambridge in the U.K.
Another factor is the lower costs of founding a startup in Lithuania. Genie Biotech is fitting out its laboratory in the Centre for Innovative Medicine in Vilnius, where they’ve been for about six months, after deciding turn-key laboratory and incubator space in London was too expensive. The company, which is using Click Chemistry to develop a site-specific conjugation technology called GenieTAG, is hoping their early-preclinical-stage technology will eventually find applications in vaccine production.
The GenieTAG is a fusion protein that can be used to attach other proteins together, such as decorating a virus-like particle with parts of the SARS-CoV-2 viral protein to create a synthetic COVID-19 vaccine or—potentially—a prophylactic cancer vaccine. According to Grigorij Sutov, PhD, Genie’s CEO, the tag has robust chemistry, slowly dissociates over time for controlled drug release, and benefits from being smaller (200 Dalton) than other conjugate chemistries. “The bigger it is, the more chance of a [negative] immune response,” he says.
Creating an ecosystem
Lithuania also benefits from an emerging “biotechnology ecosystem,” according to Milašius, with companies, such as Caszyme and microfluidics instrument manufacturer, Droplet Genomics, coming onto the scene.
Delta Biosciences is using a Droplet Genomics instrument, which they cheerfully demonstrate, to run their screening tests. The aim of the company’s technology is to accelerate drug discovery by running drug candidate screening experiments in pico-sized droplets, instead of in 96-well plates. Two streams of droplets, one containing a target and the other a candidate molecule with a DNA carrier tag, are encapsulated in the same bubble on which screening experiments can be performed. According to the company, they can experiment on 500,000 droplets a day—the equivalent of one technician pipetting 50 droplets every second.
Providing a service
Like Fermentas and Thermo, many Lithuanian biotech startups appear to be service companies aiming to sell products or license out technology. For a few of them, the need to secure funding is the key driver.
According to Rytis V. Urbonas, PhD, co-founder and general manager of Sanobiotec, a Lithuanian manufacturer of minor cannabinoids for medical and well-being applications. “Our goal was making revenue and finding a product we could sell as fast as possible, as we don’t have the same possibilities as in the U.S. where you get $20 million in pre-seed funding. Here you get 200,000 Euros and, you know, you should be happy.”
Many of the startups interviewed seem to rely heavily on the enthusiasm and support of their founders for financing. Officials at Delta Biosciences, for example, say they were initially seed-funded by the founders. Genie Biotech reports receiving 30,000 Euros in Lithuanian government funding, but most of the “skin in the game,” as Morris puts it, remains theirs.
According to Innovation Agency Lithuania, the country is middle ranking for GDP among EU countries, with only 7% unemployment. But reputations die hard. As Karolina Makovskytė, business development manager at Caszyme says, “We’re a small company in a small country—we have to reach out to be seen.”
The post Lithuania Focused on Building a World-Leading Life Science Sector appeared first on GEN - Genetic Engineering and Biotechnology News.unemployment pandemic covid-19 vaccine preclinical vaccine production genetic dna gdp european ukraine eu china
“We Are Headed For Another Train Wreck”: Bill Ackman Blames Janet Yellen For Restarting The Bank Run
"We Are Headed For Another Train Wreck": Bill Ackman Blames Janet Yellen For Restarting The Bank Run
Yesterday morning we joked that every…
Yesterday morning we joked that every time Janet Yellen opens her mouth, stocks dump.
Yellen opens mouth and stocks dump— zerohedge (@zerohedge) March 21, 2023
Well, it wasn't a joke, and as we repeatedly noted today, while Jerome Powell was busting his ass to prevent a violent market reaction - in either direction - to his "most important Fed decision and presser of 2023", the Treasury Secretary, with all the grace of a senile 76-year-old elephant in a China market, uttered the phrase...
- YELLEN: NOT CONSIDERING BROAD INCREASE IN DEPOSIT INSURANCE
... and the rest was silence... or rather selling.
Commenting on our chart, Bloomberg's Mark Cudmore noted it was Yellen who was "to blame for the stock slump", pointing out that "the pessimistic turn in US stocks began within a minute of Janet Yellen starting to speak."
The S&P 500 rose almost 1% in the first 47 minutes after the Fed decision. Powell wasn’t the problem either: the index was 0.6% higher in the first 17 minutes after his press conference started.
Why am I picking that exact timing of 2:47pm NY time? Because that is the minute Yellen started speaking at the Senate panel hearing. The high for the S&P 500 was 2:48pm NY time and it fell more than 2.5% over the subsequent 72 minutes. Good effort.
Picking up on this, Bloomberg's Mark Cranfield writes that banking stocks globally are set to underperform for longer after Janet Yellen pushed back against giving deposit insurance without working with lawmakers. He adds that "to an aggressive trader this sounds like an invitation to keep shorting bank stocks -- at least until the tone changes into broader support and is less focused on specific bank situations." Earlier, we addressed that too:
*YELLEN: NOT CONSIDERING BROAD INCREASE IN DEPOSIT INSURANCE— zerohedge (@zerohedge) March 22, 2023
At least until spoos drop below 4K again
Looking ahead, Cranfield warns that US financials are likely to be the most vulnerable as they are the epicenter of the debate. Although European or Asian banking names may outperform US peers, that won’t be much consolation for investors as most financial sector indexes may be on a downward path.
The KBW bank index has tumbled from its highs seen in early February, but still has a way to go before it reaches the pandemic-nadir in 2020. Traders smell an opening for a big trade and that will fuel more downside. Probably until Yellen blinks.
And if Bill Ackman is right, she will be doing a whole lot of blinking in days if not hours.
While we generally make fun of Ackman's self-serving hot takes on twitter, today he was right when he accused Yellen of effectively restarting the small bank depositor run which according to JPMorgan has already seen $1.1 trillion in assets withdrawn from "vulnerable" banks. This is what Ackman tweeted:
Yesterday, @SecYellen made reassuring comments that led the market and depositors to believe that all deposits were now implicitly guaranteed. That coupled with a leak suggesting that @USTreasury, @FDICgov and @SecYellen were looking for a way to guarantee all deposits reassured the banking sector and depositors.
This afternoon, @SecYellen walked back yesterday’s implicit support for small banks and depositors, while making it explicit that systemwide deposit guarantees were not being considered.
We have gone from implicit support for depositors to @SecYellen explicit statement today that no guarantee is being considered with rates now being raised to 5%. 5% is a threshold that makes bank deposits that much less attractive. I would be surprised if deposit outflows don’t accelerate effective immediately.
Ackman concluded by repeating his ask: a comprehensive deposit guarantee on America's $18 trillion in assets...
A temporary systemwide deposit guarantee is needed to stop the bleeding. The longer the uncertainty continues, the more permanent the damage is to the smaller banks, and the more difficult it will be to bring their customers back.
... but as we noted previously pointing out, you know, the math...
Math: $18 trillion in deposits, $125 billion in the deposit insurance fund. https://t.co/Zsu2RsJk41 pic.twitter.com/nb3Ypnt1gd— zerohedge (@zerohedge) March 21, 2023
... absent bipartisan Congressional intervention - which is very much unlikely until the bank crisis gets much, much worse - this won't happen and instead the Fed will continue putting out bank fire after bank fire - even as it keeps hiking to overcompensate for its "transitory inflation" idiocy from 2021, until the entire system burns down, something which Ackman's follow-up tweet was also right about:
Consider recent events impact on the long-term cost of equity capital for non-systemically important banks where you can wake up one day as a shareholder or bondholder and your investment instantly goes to zero. When combined with the higher cost of debt and deposits due to rising rates, consider what the impact will be on lending rates and our economy.
The longer this banking crisis is allowed to continue, the greater the damage to smaller banks and their ability to access low-cost capital.
Trust and confidence are earned over many years, but can be wiped out in a few days. I fear we are heading for another a train wreck. Hopefully, our regulators will get this right.
Narrator: no, they won't.
China’s Auto Industry Association Urges “Cooling” Of Price War, As Major Manufacturers Slash Prices
China’s Auto Industry Association Urges "Cooling" Of Price War, As Major Manufacturers Slash Prices
Just hours after we wrote about maniacal…
Just hours after we wrote about maniacal price cutting in the automotive industry in China, China's auto industry association is urging automakers to "cool" the hype behind price cuts.
The statement was made in order to "ensure the stable development of the industry", Automotive News Europe reported on Tuesday.
The China Association of Automobile Manufacturers even went so far as to put out a message on its official WeChat account, stating that "A price war is not a long-term solution". Instead "automakers should work harder on technology and branding," it said.
The consumer disagrees...
Recall we wrote earlier this week that most major automakers were slashing prices in China. The move is coming after lifting pandemic controls failed to spur significant demand in China, the Wall Street Journal reported this week. Ford and GM will be joined by BMW and Volkswagen in offering the discounts and promotions on EVs, the report says.
Retail auto sales plunged the first two months of the year and automakers are facing additional challenges in trying to transition their business models to prioritize EVs over conventional internal combustion engine vehicles.
Ford is offering $6,000 off its Mustang Mach-E, putting the standard version of its EV at just $31,000. Last month, only 84 of the vehicles were sold, compared to 1,500 sales in December. There was some pulling forward of demand due to the phasing out of subsidies heading into the new year, and Ford had also cut prices by about 9% in December.
A spokesperson for Ford called it a "stock clearance".
Discounts at Volkswagen are ranging from around $2,200 to $7,300 a car. The cuts will affect 20 gas powered and electric models. Its electric ID series is seeing price cuts of almost $6,000. The company called the cuts "temporary promotions due to general reluctance among car buyers, the new emissions rule and discounts offered by competitors."
Even more shocking is Citroën-maker Dongfeng Motor Group, who is offering a 40% discount on its C6 gas-powered sedan, now priced at $18,000.
Kelvin Lau, an analyst at Daiwa Capital Markets, told the Journal that automakers are also trying to get rid of 500,000 vehicles collectively stored in their inventory, most of which are older vehicles that won't meet new emissions standards.
David Zhang, a Shanghai-based independent automobile analyst, added: “Some car makers have been seeing very few sales. At this rate, the manufacturers’ production and dealership networks will collapse.”
COVID origins debate: what to make of new findings linking the virus to raccoon dogs
New reports suggest the pandemic’s origins may be linked to raccoon dogs sold at Wuhan’s Huanan Wholesale Seafood Market. A virologist explains.
The origin of SARS-CoV-2, the virus that causes COVID, has long been a topic of heated debate. While many believe SARS-CoV-2 spread to humans from an animal at Wuhan’s Huanan Wholesale Seafood Market, others have argued the virus was accidentally leaked from a lab at the Wuhan Institute of Virology.
Over the past week there has been intense activity surrounding the emergence of new data relevant to this question. In particular, reports emerged that the pandemic’s origins may be linked to raccoon dogs which were being sold illegally at the market.
The excitement stemmed from a re-analysis of raw data generated as part of official investigations into the role of the Huanan Wholesale Seafood Market in the outbreak.
The team of international scientists working on this re-analysis (from North America, Europe and Australia) alerted the World Health Organization and discussed the topic in an article published in The Atlantic. And the scientists themselves have now released a report on the issue, providing greater detail.
So what can we make of their findings? Will this development shift the course of the ongoing debate? Let’s take a look.
The Huanan market
In January 2020, writing about the emergence of what we now call SARS-CoV-2, I stated the importance of understanding how this pandemic began. It remains important to determine the virus’s origins because this knowledge may help us stop the next pandemic occurring.
Even very early in 2020, it was clear that the central Chinese city of Wuhan (a major metropolis and travel hub) was the epicentre of the outbreak. Within Wuhan, the Huanan seafood market stood out as it was associated with many – but not all – of the earliest cases. Indeed, the market was closed on January 1 2020, animals were culled, and the site was disinfected.
Suspicions arose given the role that animal trade and markets had played in the emergence of the closely related SARS-CoV-1 virus (which caused SARS, a widespread outbreak of viral respiratory disease) nearly two decades earlier. Evidence emerged that the Huanan seafood market also sold live mammals, including a fox-like mammal known as a raccoon dog, that we now know are susceptible to SARS-CoV-2.
Later epidemiological and genetic analyses further focused in on the market, and even specific stalls within it, as being the origin of the pandemic.
Read more: The original Sars virus disappeared – here's why coronavirus won’t do the same
The new data
As part of the official investigations into the market, swabs were collected from various parts of the market in the two months after it shut down at the start of 2020. The scientists who undertook this research, from the Chinese Center for Disease Control and Prevention, posted their analysis as a pre-print (a study yet to be peer-reviewed) in February 2022.
In this, the team concluded that the market likely played a significant role in SARS-CoV-2’s early spread, but that they couldn’t detect the virus in samples taken directly from animals. They reported that all the virus evidence found was associated with humans, and it was therefore likely the virus had been brought into the market by humans, not animals, and so perhaps the pandemic began elsewhere.
However, prior to any official peer-reviewed publication, the raw data from this work was released on an open scientific database called Gisaid. And the group of scientists who re-analysed this data did actually find an association between SARS-CoV-2 and animals, in particular raccoon dogs in the market.
They found DNA from animals mixed in with SARS-CoV-2 in a number of samples from the market. Some positive samples contained no human DNA and mostly raccoon dog DNA. This mix of virus and animal material is consistent with an infected animal – not a human – shedding virus, which is what you might expect if SARS-CoV-2 originated from animals brought into the market. Unfortunately, samples from a living raccoon dog were either not taken or not reported, and the official investigation makes no mention of raccoon dogs.
Where to from here?
While this latest data is one additional piece of the puzzle that supports an origin of the pandemic linked to Wuhan’s animal trade, it is unlikely to provide irrefutable evidence. It’s important to note it’s also a pre-print.
Ideally, we would like animal samples from early December 2019, and to compare animal virus genomes with human ones. It will also be crucial to follow events backwards through the animal trade and farming systems to work out where the animals got the virus from in the first instance.
Further, we must bear in mind that the virus could have easily been given to a raccoon dog by an infected human, or that the association between raccoon dog DNA and SARS-CoV-2 may be coincidental.
Read more: We want to know where COVID came from. But it’s too soon to expect miracles
However, evidence is accumulating that official investigations have left a gap in their research – particularly around the role that animals like raccoon dogs and the wildlife trade played in the origins of the pandemic.
While it may be unlikely that we will ever get concrete evidence as to how SARS-CoV-2 entered the human population, we can still think pragmatically and seek to alter behaviour and practices to reduce the chance of a new pandemic. One immediate target would be food systems (encompassing farm to fork), and how to make farming and the wildlife trade safer for all, potentially by enhancing virus surveillance in animals.
Connor Bamford receives funding from Wellcome Trust, UKRI, SFI and BMA Foundation.disease control center for disease control pandemic coronavirus genetic dna spread wuhan europe world health organization
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