A taste of your own medicine

This is the incredible story of how you will soon become the designer and creator of your own, personalised drugs.

But before we get to that, let’s rewind to October 5th, 1999.

This was a time when personal computing had just become mainstream. Microsoft and Bill Gates ruled the world.

One desperate (and relatively small) IT company, trying to revive itself from the edge of bankruptcy, placed a big bet.

They decided not to try and compete any longer in office software, and instead “usher in a new era of desktop video.”

Desktop video? Such a concept was unheard of. The launch press release explained this would now “allow mere mortals to easily create professional-quality movies right in their homes or classrooms,” according to the then-interim CEO, a certain Steve Jobs, as he launched something called iMovie. “This is going to be very, very big.”

1999 was, in case you hadn’t noticed, twenty years ago. It was a time when we debated whether the ‘information superhighway’ (also sometimes known as the internet) was just a fad, and whether computers would in fact suffer general meltdown thanks to the millennium bug. Nobody knew if this new-fangled ‘desktop video’ thing would go anywhere.

I mean, the 90s were an age when your home video collection consisted of only two types: either (a) major Hollywood movies featuring either Arnold Schwarzenegger or Meg Ryan, or (b) low resolution, discoloured, ‘shakycam’ footage of your last Christmas gathering. Yes, this was the glorious age of the camcorder.

Love Actually, released 2003, demonstrating the latest in home electronics.

Soon though, the world began to ponder new possibilities. “The democratisation of film has arrived. With these new tools we’ll soon see blockbuster movies emerging from teenager’s garages!” came some speculative newspaper features.

Spielberg in the garage

For a long time, this ‘home-grown director’ was the great fantasy. The next Spielberg or Scorsese would reveal themselves to the world, squinting as they opened the garage door having spent several days staring at their Mac, and presenting a 2-hour masterpiece that would rival the biggest studio productions.

Except it never happened.

Why not?

I mean, even today, it still takes more than 1000 people and a 9-figure budget to produce your average cinematic blockbuster.

Huh? Where are our garage-born Oscar-winning talents?

Well, actually, they are here. Just not in the way that you expected.

A full six years after the iMovie launch, a new website called YouTube went live, fuelled by a rapid rise in broadband connections. You could upload your video (“for free!”) and get it watched by anyone in the world. Moving pictures became instantly accessible – and shorter-form content was suddenly the format of choice.

But YouTube was just the start. Facebook gave video a more private audience, encouraging more user-generated content. This triggered a new cascade of apps combining video with social, including Instagram . And with everyone now owning a camera in their pocket, visual quality was sacrificed for instant gratification and shareability.

Vine , hosting only 6-second long looping clips, became the most popular video app within 2 months of its launch – then disappearing as quickly as it arrived. Twitch , exclusively showing live gaming video, became the fourth largest source of internet traffic by 2014. Snapchat took socialised temporary video mainstream before it pivoted to focus on user stories.

And then came TikTok .

Ever used TikTok? If not, you are (a) older than 25 and (b) probably surprised to hear it was the most-downloaded app in the US by the end of 2018, just a year after its international launch, smashing previous records held by YouTube, WhatsApp and Instagram. It makes homemade video highly addictive – so addictive that it now contains artificial measures to limit viewing after 90 minutes.

Whatever you think of TikTok, the dream of democratised video is well and truly here, with more creators than ever before. It’s just very different from how we envisaged it at the iMovie launch two decades ago.

The creation of the creator

Back in 1999, teenagers had different aspirations. They wanted to be lead singers, footballers or actors.

Those times have passed. Here in the UK, one recent survey reveals that 31% of 11-16 year olds have ambitions to become a ‘YouTuber’ (17%) or ‘Instagram influencer’ (14%).

This is where teenagers live now. The tools are powerful yet simple, so who wouldn’t feel?the apparently carefree life of a social influencer isn’t within grasp? These platforms have evolved exactly as we should have expected them to: from the era of the viewer to the age of the director.

But can you direct a drug?

I tell this story of video evolution to illustrate not only how viewing has evolved, but how the product has too. In 1999, we had no concept of a billion smartphone cameras or a trillion YouTube views .

A similar evolution will come to pharma, too.

A month ago, I stood on stage at eyeforpharma’s Barcelona conference and presented 5 bold predictions (read more here ). I then asked all 1500 audience members to vote on which they believed was most likely to surface in the next few years. The loser was the idea that ‘the first patient-created medicines will appear’.

The reason you can’t easily imagine a new age of patient-created medicines is because whilst you can hope for an evolution in drug development, you can’t comprehend the evolution of medicine itself. You’re locked into a world of FDA/EMA approvals, bureaucratic clinical trials, 12-year pipelines and $2bn development costs.

So it’s no wonder that it sounds crazy for a person to design and manufacture their own drug, right?

Right?

Wrong. It’s already happening.

Small is beautiful

First, consider the trendline. 2018 saw a record 61 drug approvals from the FDA. But only 26% of those approvals came from big pharma. And even more strikingly, 28 of those drugs came from companies that had never previously had a drug approved. As I often say, it is no longer necessary to be big to be innovative .

How is this possible? Despite the fact we’re working on more advanced treatments, drug design and development tools are digitising, thus becoming far more accessible. The smarter companies can also take advantage of something else made easier through technology: iterative or agile development cycles, rapid prototyping and in silico simulations – meaning small organisations can test a large number of drug candidates at low risk. Indeed, larger organisations are actually disadvantaged here: as Rachel Haurwitz, CEO of Caribou Biosciences (a leading CRISPR gene therapy biotech) explained to me: “there’s no way that a big pharma company could discover new treatments as quickly and confidently as we’re able to. It’s a different world.” You’ll hear similar sentiments amongst almost all of the new AI-led drug discovery companies.

But we already know what happens in the next chapter. Just as we saw with video, the tools of creation eventually get into the patient’s hands.

From Majmoua to Kymriah

Consider how people are already using their bodies to create personalised medicines at both ends of the sophistication spectrum. Kymriah, the first CAR-T therapy to gain approval for young leukaemia patients, requires leukapheresis (extraction of white blood cells), a 22-day offsite reprogramming of T-cells, and reinfusion back into the body at a cost of $475,000 per treatment.

It’s a complex, expensive process, but the price of newer CAR-T therapies is already dropping dramatically as supply chain efficiencies are introduced. (In my conversations with Novartis execs, we always discuss the evolution of the supply chain as just important a development as the science itself: in other words, the ability to personalise at lower costs will be the focus of investment for the future.)

At the opposite end, take a trip to a country like Egypt, and head to one of the poorest areas. Here, backstreet pharmacists will assess your condition and body type, and rather than an expensive drug that you can’t afford, they’ll give you ??????, pronounced majmoua or magmoua. Literally meaning ‘collection’, this is a packet of personalised drugs smashed into a powder designed to treat whatever ailment you have. You don’t know where the ingredient drugs came from, you don’t know if they’re expired, you don’t know if they’re licensed or counterfeit. But what matters is they’re tailored to you.

Wherever and whatever your symptoms, personalisation is what we want.

The rise of the patient hacker

Pedro Oliviera is a Portuguese innovation professor, based in Copenhagen. He is also founder of the non-profit Patient Innovation platform, which has managed to assemble more than 850 patient-created treatments or innovations, most of them through software or hardware, in under five years.

Most of these hacks or creations have come simply from patients trying to make their own lives easier. They may have never thought that others might also benefit from their innovation, but Pedro’s platform has made that possible.

And in doing so, he has become a recognised patient champion. When eyeforpharma launched the first im-patient conference , Pedro was the patient’s first choice of speaker – and finding patient innovators to fill the rest of the agenda was eye-opening .

The $20k trial is coming

BIOME is Novartis’ shiny new innovation lab in Silicon Valley. As well as working with digital health startups to quickly incubate, validate and venture-fund their products, the team has been working on a second initiative: a better way to do development.

The aim is to make clinical trials for $20,000, all in.

That’s at least an order of magnitude less than it costs today, and would be a significant step in democratising pharmaceutical development. Co-founder Mohaned Fors gave me the low-down.

To start with, a new app, FocalView , was born from Novartis’ work in ophthalmology. Eye care is traditionally an area of low tech innovation but high need, given that clinical site visits for visually-impaired patients can be exceptionally arduous.

Working in partnership with Apple and Thread , a virtual clinical trial was developed for visually-impaired patients. Over 90% of what happens during a normal site visit has been replicated by 6 ‘Active Tasks ’ on Apple’s ResearchKit, covering sensitivity, contrast, time to adjust to brightness, etc.

The next step is to validate these Active Tasks so that the app can perform an official Phase IIb trial. Novartis is working with Medable to bring this to life, as well as realise many of the other potential benefits that this technology brings, such as the ability to gather data from trial subjects on a far more frequent basis, and feed that data directly to physicians in real-time.

The patient community is hungry for these innovations. FocalView received an enormous reception and was able to recruit trial patients around 10 times more quickly than in previous ophthalmology trials.

But this is just the start. Novartis is making its approved Active Tasks freely available to all, entirely open source, with researchers from anywhere able to build validated trials within 2-3 days. Why? Because if others can refine, enhance and add to these tools, a virtual trial will be able to deliver a lot more than it does today. And that $20k target is far more likely to be realised. Suddenly, the idea of patients being able to crowdfund their own development seems a lot closer.

Can you email me your drug?

The refinement of 3D printing technology for drugs continues, with companies like Aprecia , FabRx and Tvasta working hard on bringing it mainstream, while the FDA issued guidelines as far back as December 2017.

But the most exciting work in this area is being done by J Craig Venter (he of the first decoded human genome) and Dan Gibson, who have created what they call biological transportation , the ability to digitally send instructions to a machine and print, anywhere in the world, biological instructions for proteins and living cells, at the genetic level. The latest version of their machine, known as the DBC (Digital-to-Biological Converter ) uses digitized DNA code and converts that into biological entities, such as DNA, RNA, proteins or even viruses, all in a single unit. Personalised drug manufacture just got a lot more local.

The first digital-to-biological converter

The patient creation timeline

So let’s take a look at the possible patient creation timeline, starting with what’s possible today.

The first, perhaps obvious, step is to give patients the chance to express what matters to them. Every pharma company today performs in-person patient consultations and observations in development (though, even after all these years, it’s still patchy ) and regulators now do too: the FDA is now being praised by patient groups for recent efforts to include the voice of patients in public meetings and advisory boards on new drug applications.

But it’s still extremely opaque. Rarely is there any feedback coming back to patients from these engagements, and a one-way conversation doesn’t make for a two-way relationship.

There is a wide-open gulf in the field of Patient Reported Outcomes (PROs) and digital capture around diseases (rather than around drugs). A place for patients to clarify, rank and prioritize needs, en masse, because clearly it’s a lot less black-and-white than just ‘give me a pill that cures me without side effects’.

We also have the ability to track new endpoints using technology. In the FocalView trial from Novartis, the team was able to go a lot further than the usual measures around seeing how many lines of text a patient can read. But patients don’t just want to read; they want to interact with all parts of the world around them. So, Novartis gave their legal team a headache when they decided to enable ‘daily step count’ – not just total steps as we have already, but steps outside the home. By using geofencing, the team was able to determine whether the patient was leaving home and even going to things requiring good visual acuity such as visiting the theatre, cinema or shops. These are endpoints you can’t facilitate in real life unless you’re willing to hire a nurse to monitor the patient permanently.

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What’s possible tomorrow

There are a number of steps we can plan for patients in the near future. One of the first is the donation of patient primary biomaterial in the labs. Much of today’s ongoing laboratory research is conducted with non-disease material, although this is changing. Patient organisations have shown a willingness to donate primary human tissue for research – particularly when they feel ‘connected’ to real R&D activities, and having an open innovation approach generates the transparency that might enable this.

Eventually donations will be transformed into induced pluripotent stem cells (IPS) for long term usage of patient-specific materials.

Of course, there is also the donation of patient-generated data. Patients are increasingly interested in, and capable of, providing personalized data that will support research, including genomic data. But such activities have to be organized on a larger scale as the data only becomes useful in larger data sets.

But there is a huge lack of trust when it comes to data-sharing with companies, particularly in the wake of recent misuse. What’s the solution? Either the data can be made available on a disease level and not to a specific company, or we need to create fair-trade data arrangements as I have argued previously .

The real revolution will occur when data goes two ways: delivered back to the patient in the form of instructions for a personalized medicine – even if it’s as simple as, in the first instance, information about the dosage level of a patient. As drug design becomes increasingly digital, so does this possibility.

And finally, let’s not underestimate the patient scientist. As a frequent organizer of events with patient participation, I have been frequently surprised and impressed by the number of patients who have become experts in the scientific aspects of their disease, as well as the pharmaceutical organizational routines that take place. Patients can consciously participate on an intellectual level in open research, particularly in early stage pre-clinical research, such as understanding disease mechanisms and pathways, target identification, early hit finding and chemical exploration.

Bending the line

Niclas Nilsson is the Head of Open Innovation at dermatology specialist LEO Pharma, and he helped me write some of the list above. Niclas’ ambition is to ‘bend the line’, where instead of patients merely being the recipients of healthcare, to feed back into the discovery and development process, thereby making rounding out the traditionally linear pharmaceutical value chain. “We have to change the world here. And one thing is for sure; it doesn’t happen with closed doors.”

?Niclas is also very clear on what needs to change in order that this can happen. “The ownership is the hardest part for most pharma companies. We cannot control it all. Because when you have an open platform that doesn’t put business first, instead puts the science first, you can explore many things including involving patients as disease experts and scientists, having them offer their genomic sequences and biopsies, etc.

Patients want this involvement, but not if the pharma company is possessive. Patients don’t want just one company to profit from their insights; they want everyone to benefit. It’s actually not possible to have a traditional business setup if you want to maximise patient insights. And that also includes ownership of the data, which we must share fairly.”

LEO has form in this area. Already for two years, LEO’s Innovation Lab has allowed any scientist, including competitors, to test any molecule they wish in the company’s labs in vivo or in vitro, taking full advantage of skin disease models for free. No strings attached, with full return of all data back to the originator, and full verification of whether the compound works against psoriasis or other conditions. If there are signs of potential success it is entirely the choice of the originator whether they continue to work with LEO or not.

This open-minded approach will move to the next level as they provide new tools for patients. Using artificial intelligence and the company’s deep understanding of close to 2000 compounds, a computer model has been created enabling patients to upload personal information and perform tests. The accuracy is “very, very high. And it constantly improves.”

LEO’s Chief Executive Gitte Aabo further reminded me of what’s at stake: “Patients are the real experts in their own disease. They live with it 24/7/365. I get weekends and holidays, but they don’t. Nobody else is more motivated to solve their own condition. And soon they will actually be able to sit at home, design a molecule, test it and cure it.”

Motivation eats regulation for breakfast

Non-experts are adopting the tools of drug design, just as non-experts now rule the vast majority of video production. And the very nature of a treatment is changing, just as the very nature of a video has also changed. Once these two trends become mainstream, products will be developed that transcend regulation.

As a patient designer, I will one day be able to create a personalised treatment based on my own preference or my own data. I won’t care for a second whether or not that treatment works on anyone else. My primary motivation is to fix myself.

This fundamentally alters the nature of regulating, researching and developing drugs. For all the work being done to make clinical trials faster and cheaper, could one day the clinical trial itself become a relic? After all, I’m far more likely to value the idea that my treatment is personal: I care far less whether or not it has been in a clinical trial with 300 others.

Regulating self-generated medicines will be very different from how medicines are regulated today. The process will probably borrow more from the evolution of digital music from mp3 players to Napster to Spotify, or perhaps the nascent legalisation of cannabis, than from the history of medicine. One thing is for sure: once the right tools get into a patient’s hands, they will fight for their lives, irrespective of the regulations.