This blog post is based on a conversation between Michael Watson, CEO of MEVOX and ex-president of Valera, Moderna's infectious disease spin-out, and the #CoffeeBuddies, a virtual discussion group hosted by Graham Combe and chaired by Professor Tony Sedgwick. Book to join #CoffeeBuddies on Tuesdays and Thursdays at 2.30 pm BST (GMT+1 hr) at Eventbrite.
Since the first reported cases of a mysterious outbreak of viral pneumonia in Wuhan, China, in late December, the virus, now called SARS-CoV-2, hasn't been out of the news. Human to human transmission of the infection, known as Covid-19, was confirmed on 20 January 2020.
As of 7 May 2020, there had been 3,843,153 reported cases and 265,657 reported deaths worldwide. The UK's daily confirmed Covid-19 deaths per million (rolling 7-day average) peaked at 13.89 per million on 15 April 2020, and had fallen to 8.37 per million on 7 May 2020.
All about the virus
Coronaviruses (from corona, Latin for crown or wreath) are RNA viruses with spike proteins studded all over their surface. Evolving alongside the amniotes (reptiles, birds and mammals), coronaviruses and have been around for millions of years. Coronaviruses were first identified in the 1960s, and SARS-CoV-2 is the seventh coronavirus known to infect humans. A number of coronaviruses, including B814, 229E and OC43, cause around 15% of common colds. While the new virus' origin is still not clear, it appears to be closely related to bat and pangolin viruses.
There have been a number of coronavirus outbreaks over the last two decades, including the SARS (severe acute respiratory syndrome; SARS-CoV-1) outbreak in China and Hong Kong in 2003, and the MERS (Middle East respiratory syndrome; MERS-CoV) in 2012. The pandemic in 1889-1890, which resulted in one million deaths, may have been caused by HCoV-OC43 jumping from cows to humans.
SARS-CoV-2's spike proteins bind with the human ACE2 receptor, found in lungs, kidney, heart and gut. This ties in with the symptoms of Covid-19, which include fever, cough, shortness of breath, and diarrhoea, and can worsen to cause strokes and kidney failure.
Letting go of the tiger's tail
Modelling from Neil Ferguson and the Imperial College COVID-19 Response Team suggested that, if nothing was done to mitigate the epidemic in the UK, critical care bed capacity would be exceeded in the second week of April, and deaths would peak at around 500,000 in May or June.
Controlling the tiger that is Covid-19 requires primary and secondary prevention, allied with primary and secondary treatment approaches:
The UK went into lockdown on 23 March 2020. The UK government is discussing when and how lockdown will ease, and what social intervention will look like in the future. Between the current peak and a potential secondary peak of infection as lockdown eases is a critical and narrow window for vaccine and therapeutic development. Highly effective contact tracing and case isolation could also be important in controlling new outbreaks.
Antivirals could play a role in treatment
A study of Gilead's remdesivir in 1063 hospitalized adults showed a 31% faster time to recovery in treated patients compared with placebo (p<0.001), reducing the median time for recovery to 11 days compared with 15 days. The mortality rate in treated patients was 8.0% compared with 11.6% in the placebo group (p=0.059). Remdesivir has been studied in Ebola virus disease, MERS and SARS caused by SARS-CoV-1 infection.
Designing a vaccine for primary prevention
A safe and effective vaccine will be the best way out of the current pandemic, as waiting for herd immunity would require between 60% and 80% infection in the population, with a lot of suffering and death over several years. There are over 125 Covid-19 vaccine candidates in the pipeline to date, with eight or nine in the clinic. This is expected to increase to over 25 in the clinic by the end of 2020. Approaches include nucleic acid vaccines (mRNA, DNA),inactivated or live attenuated vaccines, or viral vectored vaccines. Normally vaccine development takes over 10 years, but this outbreak has seen vaccines developed to clinical stage in record time.
Each vaccine approach has its benefits and its challenges:
Another positive for the development of a vaccine – while coronaviruses do continue to mutate, they have an RNA 'proofreading machine' that slows the evolution of the virus. According to data published on 4 May 2020, there have been relatively few mutations spotted to date.
Provided clinical trials can show a 'good enough' protection from an initial dose, or dose + booster, the SARS-CoV-2 vaccine may need to be given annually, much like the influenza vaccine.
iThis blog post is based on a conversation between Lubor Gaal, senior vice president and head of Europe at the global life science transaction firm Locust Walk, and the #CoffeeBuddies, a virtual discussion group hosted by Graham Combe and chaired by Professor Tony Sedgwick. Book to join #CoffeeBuddies on Tuesdays and Thursdays at 2.30pm BST (GMT+1hr) at EventBrite.
Dealmaking in the 21st century is the life blood of the pharma and biotech industries, and it relies on the in-depth knowledge of the business development teams on both sides of the deal. They need a set of skills and knowledge:
The core of dealmaking
Dealmaking is a systematic and strategic process. The business development team from the big pharma needs to know what the scientists are looking for – almost a Christmas present list – and then find out whether these assets exist in the real world. In turn, the strategic approach for biotech BDs is to know who to talk to, and what and how to pitch. It's easy, especially for new BDs, to want to talk to anyone and everyone, but it's important to provide the right people with information on the right asset.
Working and making deals pre- and post-Covid-19
Prior to the Covid-19 pandemic, there had been a shift in investments, with VCs leaning towards investments in early stage companies and assets, which is good news for European entrepreneurs. This was a change to previous years when investment had focused on much later stage research. This could be because of a historical lack of funding for preclinical and early clinical research in biotech and small pharma meaning a dearth in the current late stage pipeline. There have also been early signs of a shift towards regional investments, for example Chinese investors looking for local deals after they have been prevented from investing in the US. However, companies making deals need to be aware that local rights could potentially limit future global deals.
During the current lockdown, some companies are continuing dealmaking as normal because of projects set up prior to the outbreak, and some are taking a strategic pause. Gaal said that he is currently transacting and reaching out for assets based on conversations that kicked off during 2019. There is money available now from companies and investors, but access to this may drop long term.
Once lockdown begins to lift, and the world returns to some kind of new normal, it may reveal which were the stronger (or at least better funded) companies, and which haven't survived, much as happened after the financial crisis in 2007-2008. As with the financial crisis, share prices have dropped. This could make negotiation harder on both sides, with smaller companies looking for pre-Covid-19 value in assets to keep them afloat, and bigger companies needing to fill their pipelines but having less money in their pockets. While China is likely to remain a big market and a potential partner, there may be a shift in manufacturing away from China and into Europe.
Working in the Covid-19 space
Companies that were already working in the virology space have shifted investment into developing coronavirus vaccines, with the World Health Organisation (WHO) currently tracking the development of 76 Covid-19 vaccine projects. Of these, five are already in clinical evaluation. It is far too early to see if vaccines, or even the disease itself, provide long-lasting immunity. Success in this space could make the industry stronger, and improve the public's understanding of its importance, but if pharma and biotech are unable to come up with a prophylactic vaccine or a drug or antibody treatment, the impact in the form of falls in funding and in public trust could be seen across the industry.
There hasn't been a noticeable shift towards Covid-19 work for companies outside the field in the short term, but it's hardly surprising that it is being left to the experts in the field. However, the impact of Covid-19 as an emerging disease, and the chance of other emerging diseases in the future as a result of climate change, could mean that there will be a movement into new infections in the longer term.
The impact of success and failure in companies working in the Covid-19 space has already been seen in the value of companies. Gilead's remdesivir, touted as a potential treatment for the infection, has failed in its first randomised clinical trial, according to accidentally-published documents. The company's share value had risen in anticipation but fell when the data from the Chinese trial, revealed in error by the WHO, showed no improvement in patients' condition, and no effect on the levels of the drug in the bloodstream. There is also likely to be a coronavirus-driven effect on the value of companies currently onboarding and running clinical trials, depending on the length of delay.
The role of networking and partnering meetings in the new world
Networking is important in dealmaking, but the Covid-19 outbreak has put a dampener on face-to-face meetings now and potentially for some time to come. Digital networking is continuing, and the importance of this, particularly with people with strong existing networks, is likely to increase as the lockdown continues.
I'm starting to sort out again. The lengthening of the days is bringing back a little of the energy and attention that has been missing for half a year, through a summer of lost purpose and a winter of anniversaries. Memories, dusty as ghosts, come rising out of dented cardboard and crumpled carriers.
My first poems and stories, hand-bound into books with board fronts and backs.
Craft projects kept carefully by my parents over many years, and brought home when I cleared out their house for the last time. My parents' wills.
Love letters from my ex from before we were married. Evidence of his love in my hand where it once was in both of our hearts.
Pictures and paperwork from houses I bought with my ex, including the house in Doncaster that was to be the fresh start for a struggling marriage (I thought) and that turned out to be the step closer to its finish.
Divorce paperwork. Condensing 14 years into just a few pages. Startling in black and white.
The contract for the house in Litton Mill that was a river-lined retreat from the chaos and became the start of my life version 2.
Tim's tenancy agreement from the house in Dadford where things began.
Tim's statements and pay slips. Scraps of paper filled with his spidery writing. Notes left on my desk. Cards from him, loaded with so much love it spilled over the sides.
The estate agent's flier for his beloved shop, now empty, and this beautiful house, now holding only half the love it did. The place where things ended after a decade filled with sweetness.
In August, September and October I will be running two half marathons and three 10ks to In a Diabetes UK vest to support and publicise Diabetes UK. I chose this charity because my beloved husband Tim had type 2 diabetes. He was starting to lose his sight from the disease. Then he suddenly and unexpectedly died in February 2018 at the young age of 50 when his heart failed, a complication of his diabetes. The money from selling Tim's record collection has gone to Diabetes UK, and 10% of sales of his model kits on Ebay is going there too.
Diabetes UK is a brilliant charity that provides support and funds research in type 2 diabetes, and I support it so that others might not have to go through what I have.
There are also other reasons why I run. As well as raising money, running helps me live with my depression. It helps me fight grief. It keeps me fit. It shows people that not all runners have perfect runner's bodies. And it reduces my personal risk of type 2 diabetes, a vile disease.
If you would like to make a donation, please go to my Just Giving page. But I know that not everyone can, and I have asked for money a number of times over the past few years. So if you can't donate, or don't want to, can you still spread the word about Diabetes UK?
Support people you know with diabetes. If you are diagnosed with it, or with pre-diabetes, take it seriously. Type 2 diabetes steals your sight. It destroys your heart and your kidneys. It damages feeling in your hands and feet. It leads to amputations. It shortens your life. It takes you away from people you love.
Think of me or wave me on when I run at:
Leigh 10k - 11 August
Wigan 10k - 1 September
Great North Run - 8 September
Stephen Price Memorial 10k, Ashton on Trent - 15 September
Manchester Half - 13 October
BIOPROSP_19, which will be held in Tromsø in Norway 25-27 February 2019 has a program packed with #WomenInScience talking about biorefineries for marine resources, synthetic biology, marine bioactive molecules and new resources and trends in marine biotech.
BIOPROSP is the international biennial scientific conference on marine biotechnology that aims to translate basic research into industrial applications.
Come along and hear some of the key women working in the marine biotech sector.
The polar waters are cold and often rough, but the biology and geology of this region is fascinating. The ice-going research vessel, Kronprins Haakon (KPH), packed with sampling equipment and custom laboratories, is going to open up subsea research in the high north. Researchers from Centre for Arctic Gas Hydrate, Environment, and Climate UiT (CAGE) set sail in the new vessel in October 2018 with two aims: to see what the ship could to, and to transport new, high-tech equipment to an area featuring active methane release systems in the northern Barents Sea.
The wind and the waves
One of the biggest challenges faced by earlier expeditions was that they could be thrown off course by wind and waves, making it hard to collect samples in specific areas or examine certain structures and organisms more closely. Kronprins Haakon has a dynamic positioning system, allowing it to maintain itself in position and collect samples
Another challenge is crew seasickness in rough waters – this not only is very unpleasant, it means that researchers either lose time because of illness, or because the ship has to relocate to calmer waters. Kronprins Haakon has balancing tanks built into the structure of the ship, so that it can handle waves of 4 to 5 meters. This will increase the number of sailings that can be carried out in the autumn and winter months. Inclement weather also means that it's hard to lower equipment over the edge of the ship without damaging the instrument or injuring the researchers. The 'moon pool' allows equipment to be lowered through a hole in the bottom of the ship to the seabed below
Looking more closely
In this voyage, Kronprins Haakon carried a remotely operated vehicle (ROV) named ÆGIR 6000, from the Norwegian Marine Robotics Laboratory at the University of Bergen. ÆGIR 6000 is an uncrewed submersible tethered to the ship through the moon pool by a long cable, and remotely operated from the ship. The ROV explores the bottom of the ocean, carried seven cameras, and can take samples using pincers, a coring device, a gas sampler and a water sampler. ÆGIR 6000 can also map the seabed at a resolution of 5 to 10 centimeters.
The next step
Kronprins Haakon is owned by the Norwegian Polar Institute, and run and maintained by the Institute of Marine Research. In December 2018 it is heading to Antarctica in a voyage led by the Norwegian Polar Institute and the Institute of Marine Research, and will return in May 2019. After this, it has two cruises with CAGE participation scheduled for September 2019 and October 2019.
Head to New research vessel Kronprins Haakon is changing what we know about polar waters to learn more.
The marine environment is a place of amazing diversity. The ocean covers more than 70% of the earth's surface, creating a three-dimensional world populated by microscopic plants, algae, invertebrates and fungi through to fish, birds and mammals.
The habitats, from near shore to deep sea and trenches, and from tropical to polar, are largely untapped resources for biotechnology. Despite many decades of research in the marine environments, there are still opportunities for applications across all the different shades of biotechnology. BIOPROSP, held every two years, has a focus on the exploitation of biotechnology in marine environments.
BIOPROSP_19, held in Tromsø, the capital of the Arctic world, will focus on:
BIOPROSP_19 will take place between 25 and 27 February 2019, at UiT The Arctic University of Norway. Over the past 14 years has grown beyond marine bioprospecting to cover the breadth of marine biodiscovery and biotechnology, and the application of marine bioactive molecules.
I've just bought a new shredder, and now my office carpet looks like it's been hit by a cellulose snowstorm. I'm going through a huge box of papers and getting rid of anything older than five years.
There's a satisfaction of pushing sheets of paper into its tooth-lined maw, and filling paper sacks with shreddings for recycling. It is making me think of things that are no more. Cars, houses, cats, jobs. And marriages.
There's a lot of Tim's paperwork in here. Payslips, bank statements, bills, receipts, car documentation. And always the challenge of seeing his writing. I can't keep it all but there is part of me that feels guilty getting rid of it, as if I am erasing him.
There are some things I'm keeping, though. An old driving license. His invitation to his cousin's 21st birthday party. The receipt from a wonderful; holiday in the Loire Valley. Notes that he left on my desk. It's a balance between preservation and decluttering, and the most valuable things there are I still have. My memories of him.
I've lived with depression for many years – since my teens at the very least. And it's not as a result of anything. No childhood trauma, no lack of love. It's worsened by stress, but not caused by it, and no amount of tree hugging or walking barefoot in the grass, or eating clean will cure it. It just is. I have had counselling and CBT, I take medication, and I run. And together they help me manage it.
Depression comes in waves. I can feel when it's coming on, the slide down. It's sometimes triggered by something small like a squabble on social media, or not being able to do something I should be able to do perfectly well, or actually nothing specific at all. And I know it's on its way, and I know I need just to ride it out, keep doing what I'm doing, until I feel the start of the climb up.
When I'm low, all the colour seeps out and it feels like the world has become black and white. Sounds are muffled and my brain fogs. I'm very good at putting a mask on, and I can work and function perfectly well. Before I was first formally diagnosed I assumed that I couldn't be clinically depressed, because I got out of bed, kept myself clean and tidy, and went to work every day where I met my deadlines perfectly adequately. After all, everyone knows that people with depression can't get out of bed.
The day that the gym being closed unexpectedly left me sobbing, curled up in a ball on the floor in the corner behind my bed, should have told me something was wrong. It took a wonderful and kind friend who made me go to the doctor, and a gentle GP and patient counsellor, to make me realise that not only was there something wrong but that it could be faced up to, and it could even be fixed. Or at least managed.
I am now in a slightly more complicated world, seven months on after losing my beloved Tim. Tim understood depression. He understood that it couldn't be fixed, but that it could be contained with care and the wave surfed. He would hold me while I cried, hug me when I just felt melancholy, and then make me laugh at the ridiculousness of it all at just the right moment. And now he's gone. And so I live with depression and grief.
Whereas depression is a world without colour, and smells and tastes of mud, grief is a different thing. It is greeny-yellow, and tastes bitter. It is sharper-edged than depression. And while both come in waves, grief waves I can't see coming. They crash in out of nowhere, sweep me off my feet, and leave me breathless and gasping. They are triggered by the smallest things – while I can put my big girl pants on and be 'brave' for a birthday or an anniversary, I can't prepare myself for opening a box and finding the piece of paper that he left on my desk with yellow roses, celebrating the anniversary of our first kiss. Or the realisation that now a load of washing contains only my clothes, not both of ours. Or seeing the half-made Airfix model or the half-read book.
Some days they are both there, and I can visualise the colours, intertwining but separate. I know the difference between the two. Those days are hard.
I feel that I should be able to wrap this up with a neat conclusion. An answer. A solution. Something bright and hopeful. But really, like so many things in this year of firsts, it is what it is. I'm not brave. I'm not wonderful or amazing. I am just me, dealing with each day as I can. One foot in front of the other and one breath at a time.