Two Days of MinION

London Calling Samples-34

Audience members inspecting their free MinION. Source: Nigel Chapman

Oxford Nanopore Technologies invented the MinION device – a pocket-sized DNA/RNA sequencer that is based on protein nanopores set in an electrically resistant polymer membrane. It works by passing an ionic current through the nanopores, creating a specific disruption pattern in the current that is used to identify the molecule. This is similar to the antennae of insects, and it fascinated me. So, I wrote to Oxford Nanopore expressing my wish to join its MinION Access Programme (MAP).

MAP is a community-focused access project that started in Spring 2014. Its philosophy is to enable a broad range of scientists to explore different ways MinION may be useful to them, to contribute to developments in analytical tools and applications and to share their experiences and collaborate. This year I received an invitation to submit an abstract to a conference hosted by Oxford Nanopore called “London Calling.” The two-day conference was opened by Dr. Gordon Sanghera, the CEO of Oxford Nanopore Technologies, who explained to the international audience that London Calling is the third studio album by the English punk rock band the Clash.

The first question one might have is, Does the Nanopore technology actually work? The answer is yes. All speakers, who were part of the early group of MAP users, produced sequences using MinION. Nick Loman showed that he could identify Salmonella as the source of food poisoning in just 100 minutes of sequencing. Moreover, Jared Simpson produced a complete Escherichia coli K-12 MG1655 genome assembly having 98.4% nucleotide identity compared to the finished reference genome. This means that the MinION sequencing data can be used to reconstruct bacterial genomes without the need for a reference sequence.

All of the first-wave of MAP winners utilized the first generation application-specific integrated circuit (ASIC), which has 512 channels to prepare and relay the information from each nanopore to the host laptop (read 30 bases/sec). Imagine what they could have done if they had the next generation MkII MinION device with the next generation of ASIC, which has 3,000 channels. The new method of analysis, Fast Mode, plans to increase the speed from 30 bases per second per nanopore to around 500 and the ASIC is capable of going up to 1,000!

I was also interested to see two new additions:  the PromethION, which is expected to contain 144,000 channels across 48 flow cells, each capable of running multiple separate samples yielding up to 6 Terabases per day; and the Voltrax, a device that fits on top of the MinION or the PromethION and automates the 6-12 samples preparation.

That has me thinking about how these products will be suited to sequence whole human genomes, and the applications of this in the field of genomic medicine.

When the day was over, we went to the conference dinner at the Skyloft, which had panoramic views of London. Yet this was overshadowed by the news of MinION going to space. Yes, NASA’s Astromaterials Research and Exploration Science division plans to fly a few MinIONS to the International space station. Given the confined space within the International Space Station and the necessity to conduct experiments within it, the mere size of the MinION makes it an ideal instrument to study the existence of terrestrial nucleic acids and proteins, as well as possible infectious outbreaks in space stations of the future.

Up next: Day 2 of the conference

Fahd Al-Mulla

Australia’s government and biotech

topIn our last blog post, we laid out the Australian biotech foundation and a few of its shortcomings. Here we focus on what it has done well.

Certainly biotechs can be built successfully in Australia. One company (Acrux) grew from a $20 million market cap to $500 million over 15 years, and another (Mesoblast) grew to be worth $2 billion. Australia is doing many things right.

Partially this is because the government has played its role well. Initially Australia’s government looked at biotech as a lucrative export opportunity, and it put in place a grant system and tax benefits for anyone investing in high-risk start-ups. For instance, companies with less than $20 million in turnover yearly can get a 45% tax refund on eligible R&D expenditures (more information here).

Some of the other government initiatives have been the Innovation Investment Fund (IIF), since closed; the Innovation Investment Fund-Follow-on (IIFF), also closed, and the Early Stage Venture Capital Limited Partnerships, which offer tax breaks for limited partners. Pre-Seed plans helped create the first batch of biotech entrepreneurs, and today the government still strives to make things easy – it can take just minutes and less than $1,000 to do the paperwork to set up a firm.

The government has also invested large sums in infrastructure made available to the public on a fee-for-service basis. The National Collaborative Research Infrastructure Strategy (NCRIS) program provided $542 million from 2004 to 2011 for subsidizing infrastructure in private drug discovery firms and contract research organizations (CROs). NCRIS has in some cases subsidized the cost of installing/purchasing advanced biotech infrastructure in private CROs or R&D biotechs with a CRO wing.

State governments have also helped to create a few clusters. In Melbourne, for instance, the government of Victoria has supported the development of The Walter and Eliza Hall Institute of Medical Research, Burnet Institute, The University of Melbourne, Monash University, Royal Melbourne Hospital and the Royal Children’s Hospital – many of which are in close proximity to each other. Clusters allow companies to share facilities and draw a better hiring pool. Clusters also help promote collaborations, and sometimes consortia formed in a cluster may earn state government funding.

Australia has a unique system of about 60–70 public collaborative research centres. Called the Cooperative Research Centres (CRC) program, it supports end-user-driven research collaborations to address major challenges facing Australia. The CRC Program links researchers with industry to focus R&D efforts on progress towards utilisation and commercialization. In 2014–15, there were 35 CRCs in a range of areas such as healthcare, natural hazards management and the aerospace industry.

Most biotech start-ups originate from these centres, meaning the spin offs have essentially been financed by public universities. There is no regulation on who owns an invention – the scientist, their department or their organization – and thus the company founder and inventor have been able to own IP rights rather cheaply. This has changed, with most universities adopting the equal splitting of IP rights among 3 parties: the research organization, the relevant department and the inventor scientist.

Thus, some 75% of the companies that are on the stock market are university spin-offs. Yet, partnering with the institution that spun out a company is the most common collaboration for a start-up, because the university expects that money will be pumped back to it through fee-for-service work from the spinout. This is often the cheapest way to get things done for a startup, but it is hardly ideal, as academic scientists often do not feel comfortable working in a fee-for-service arrangement and being told what they should do, nor do they understand the pressure of time and the corporate work culture.

Next post: Finance

Szymon Jarosławski and Gayatri Saberwal

Acknowledgments

This article is based on interviews with 14 senior people in, or associated with, companies in Australia, whose comments have been edited for clarity and brevity. We are extremely grateful to the interviewees, who gave freely of their time and their insights.  This work was supported by a grant to GS from the Institut Merieux, France. SJ was supported by France Volontaires, France. Neither organization played any specific role in this study.

Building biotech in Australia

KoalaAustralia has grown a busy biotech sector, but what awaits bioentrepreneurs in this small, geographically isolated country? 

The Australian biotech industry was born in the 1980s, after researchers at the Walter and Elisa Hall Institute in Melbourne discovered colony stimulating factors (CSFs). However, that discovery was left unpatented, and it was Amgen that earned billions from drugs based on the technology. This was not the last mistake made by Australia’s biotech sector, but even with the larger issues that plague it today, Australia has a long list of native benefits to offer and one of the world’s more robust biotech sectors. Over a series of blog posts, we’re going to discuss what one should consider before launching a biotech in Australia.

First, the downside

Historically, the mining industry has been an important contributor to Australia’s gross domestic product (20% in 2014), so the country has a long legacy of risky investments. But in biotech’s early years, Australia’s investors often didn’t understand the risks associated with drug development, and many didn’t understand the difference between research and development – putting in just enough money to finish the research, but leaving nothing for development.

Another mistake concerned going public too early. The Australian Stock Exchange (ASX) has a low bar for listing, and thus is amenable to smaller companies. A company with a post-IPO market cap of A$10 million can list, something unseen in the US where a firm needs to be worth $100 million before listing. This sounds like a positive – a more forgiving public market – but Australian firms are forced to go public early because of a weak venture capital (VC) environment in Australia. As of 2014, Australia’s 88 ASX-listed biotechnology companies were valued at more than A$51 billion. Without suitable market caps, many of these companies are unable to raise additional funds.

The VC environment, as a percentage of GDP, is far behind the US. The Australian government is aware that private VC money is inadequate and attempted to fill the financing gap through programs such as the Innovation Investment Fund (IIF), where funding was matched by private investors, and Commercialization Australia. As of February 2014, Commercialisation Australia had invested A$213M in 503 companies, but the program was abolished in May of that year.

This shortage of angel and VC funds means that the early Australian sector is dependent on government tax breaks and R&D grants to help generate funds. That helps, but many firms fail because they lack enough money to reach a critical size, and because of a dearth of experienced managers.

Australia also suffers from too many tiny biotechs. The vast majority of university technologies would be better off licensed out, rather than formed into a start up. These small biotechs are often left floating, poorly capitalized and without strategic direction. Many would benefit from merging, but that’s not as common as it should be, as management often doesn’t have great vision and are more concerned with the continuity of their salaries than the firm itself.

Australian bioetchs often suffer from unfocused development, in that they do not ask the go-or-no-go questions early enough. The reason, it’s been suggested, is that if a CEO doesn’t have shares in a company, he or she won’t have a wholehearted interest in its success, and thus considering shutting down the company simply imperils the CEO’s job. Yet another aspect is that those very small companies are founded on a single invention, which means that ending a project basically ends the company. Furthermore, given the full disclosure requirements of public companies, announcing the stoppage of projects would likely crush a company’s stock price. So companies soldier on and drag out their failure. Millions of dollars have been wasted this way in Australia.

There is another issue: for an industry to be viable long-term, of course, shareholders must make money, but even when this does happen in Australia, there haven’t been enough success stories to encourage reinvestment, so money is rarely recycled. Often, if a company fails, the CEO cannot raise funds for another.

It’s true there are a handful of good firms with nice stories, such as Mesoblast, Sirtex Medical, Impedimed and Clinuvel Pharmaceuticals, but medium-cap Australian stocks have been pounded on the exchange (Table 1), even as stocks in the US have flourished. So while Australia has companies that are providing employment and are profitable, it has room to improve.

Next post: what Australia has done well

Szymon Jarosławski and Gayatri Saberwal

 

Table 1. Market damage in 2014 (Go here for this article by Mark Pachacz in full; it has been excerpted below.)

Pharmaxis, which at its peak had a market value in excess of $900 million, saw its stock fall by more than 50% in 2014, as the company’s lead product for the treatment of cystic fibrosis failed to gain substantial market traction in Europe.
Acrux’s share price fell by 55% in 2014, amid concerns emerging about the use of testosterone products and the inability of the company’s product to secure a more substantial market share in the US through its partner, Eli Lilly.
QrxPharma received a red light once again from the US Food and Drug Administration for its pain combination therapy. Its share price plummeted by 98%.
Alchemia’s shares fell 85% after its Phase III cancer trial showed no benefit over placebo.

 

Acknowledgments

This article is based on interviews with 14 senior people in, or associated with, companies in Australia, whose comments have been edited for clarity and brevity. We are extremely grateful to the interviewees, who gave freely of their time and their insights.  This work was supported by a grant to GS from the Institut Merieux, France. SJ was supported by France Volontaires, France. Neither organization played any specific role in this study.

Annual private biotech feature

specialists

Image source: Ridge Carpenter

2014 was a great year for private biotech. Venture capital (VC) investment into the biotech sector as a whole—from recent startups all the way to enterprises in late-stage financings—jumped to a record $9 billion. The number of series A financing rounds also remained strong. These trends held true for the subset of private companies that Nature Biotechnology considers in its annual survey. Data from Dow Jones show that money from combined exits (initial public offerings [IPOs] and buyouts) for private investors reached mythic levels last year—a 78% increase over an already strong 2013. Although the number of overall VC rounds into innovative biotech did not expand from 2013’s totals, the total amount invested did, and the global count of private biotech companies jumped from 1,133 in early 2013 to 1,361 as 2014 began.

VC investing across all industries in 2014 reached the highest level in more than a decade—$48.3 billion went to more than 4,300 deals, according to The MoneyTree Report from PricewaterhouseCoopers and the National Venture Capital Association, powered by data from Thomson Reuters. But biotech has been one of the top performing sectors. Much of this fervor is attributed to the hot biotech IPO market—a receptivity so robust it’s less a window and more a hole blasted through the wall—as a strong IPO market tends to draw in VC funding. When its IPO market whirred to life 2.5 years ago, a needful industry warily wondered how long it would last. Now the question is, when the eventual correction comes, how will it affect private investment in biotech?

Excerpted from our annual feature gauging the health of the private biotech sector, included in the May issue (out 5/12/2015). Click image to enlarge.