Live blogging from RB2015 — Rejuvenation Biotechnology Conference
Thanks to Traci Parker, I got a press pass for this year’s SENS Research Foundation Rejuvenation Biotechnology Conference — the leading event on anti-aging biotech. Below are some of the sessions that piqued my interest.
Keynote address: Open collaboration to catalyze new treatments for ageing societies
Fantastic talk by Chas Bountra, Structural Genomics Consortium Oxford Chief Scientist, Professor of Translational Medicine, Nuffield Department of Clinical Medicine; Associate Member , Department of Pharmacology, University of Oxford, visiting prof. of neuroscience at Imperial College in London
We must transform the way we discover medicines. The biggest challenge is identifying proteins we need to modulate. Too much secrecy and competition are slowing down drug discovery.
As an example, take cancer in the UK: in the next 12 months, 315,000 people will be diagnosed. That is one person every 19 seconds. Half of us in the room will get diagnosed with cancer in our lifetime. A paper published last year showed that:
- drugs available for solid tumors produced an increase in overall survival by only 2.1 months
- only 30 out of 71 drugs for solid tumors produced clinically meaningful improvements.
- in 2000, there were 69 drugs available for treating cancer. The average duration of treatment was 180 days. The average cost in UK was £3000, 20% of GDP per capita.
- in 2014: another 63 drugs for treatment of cancer, average duration 263 days, average cost £35,000 (11x increase), 140% of GDP/capita.
The way we discover drugs is too costly, too risky, and too slow:
- average cost per drug launched: $12Bn (Astra Zeneca)
- In 2003 there were 529 molecules in development for cancer (phase 1–3 clinical trials). In 2013 they looked at what happened to them: 45 made it to market, 95 were still in development, 389 have been terminated (took to the clinic and terminated). If you have a molecule that goes to phase 1, the chance of it going to market is 7%. For phase 3, the chance is 33%. 1 in 3 molecules that makes it to phase 3 makes it to market. This process is very risky.
- It’s also very slow. It took 6–30 years to take an idea into patients.
There are two causes: organizational challenges, and scientific.
Many pharma companies are all working on the same few ideas, in parallel, and in secret. 9 in 10 of them fail. Multiply that by ~20 companies around the world working on the same molecules. We are exposing patients to molecules that other groups *know* are destined for failure, because other companies don’t publish their failure data, and don’t publish quickly.
Of the top 10 companies, onedoesn’t publish the pipeline, but the other 9 companies had 168 molecules in development for cancer. 124 were overlapped. This is the level of duplication.
Another challenge: if you haven’t made progress in 6 months, you must move to something else. But this short-term deadline is hindering innovation.
We do not understand the causes of many diseases. Eg. schizophrenia — we don’ have a clue. The world’s leading expert in schizophrenia: there are 108 different types of schizophrenia based on genetics. We don’t have good biomarkers. E.g. on Alzheimer’s, we can’t ask, “is your memory better today than last month”. A lot of the animal models do not predict what happens in the clinic.
We don’t even know how some existing drugs work — e.g. paracetamol. Probably 100m people today take it, but we don’t know how it works. The biggest problem: in each of us there are 20,000 proteins. We are not good at target discovery.
Pharma companies are de-risking by buying anything late stage, and pulling out of difficult areas, e.g. psychiatry, which is phenomenally difficult.
We’ve done 5 things:
- Pool resources — the Wellcome Trust charity gave 16M pounds. Working with a consortium of 10 large pharma companies: GSK, Pfizer, Merck etc. We have $8M from these companies has given $8M plus we get access to their expertise & compound collection.
- I only work on human proteins; no rats & mice. And only on novel human proteins, that other people are not working on. For those novel proteins, we generate the purified proteins, assays, 3D structure, then generate small molecule inhibitors. For some of these we generate antibodies. These are high quality reagents AND we give them away to anybody in academia and pharma. This transparency creates a lot of trust, which is great for science.
- We work with 250 academic labs across the world. We’re crowdsourcing science on new proteins.
- When we generate these inhibitors, we look at what they do in human cells; no rodent tissues.
- Everything we do, we release to the world immediately — to reduce duplication and wastage.
6 years ago started work on epigenetics proteins. One family was the bromodomain — everybody thought it was impossible to come up with a drug for it. 4 years ago we came up with the first molecule, working with GSK. The protein was put on human cancer cells and showed it increases apoptosis. In animals, the compound stopped the tumor growth. Published in Dec 2014.
We’ve given out that molecule to ~1000 labs across the world. They’ve showed it works in fibrosis and other areas. There are now 300+ publications on that protein because of this new molecule. Many of our pharma partners have started proprietary programs. There are 6 companies with 6 molecules undergoing 14 clinical studies. In 4.5 years, all this happened because we released that molecule. This is the impact we’ve had. Our academic collaborator in Harvard also secured $15M in VC funding to create a biotech lab.
My group produces a paper every 3.5 days. Many CROs would like to take the inhibitor, convert it to a molecule, and sell it to GSK. We are delighted — we want to facilitate drug discovery.
Last year we got funding from the Brazilian government to study inhibiting kinases. There are 580 different kinases in humans. There are 300 kinases that we don’t have drugs for. We’ll generate novel inhibitors for them and share them. Last year we got another £9M from the Trust. The data now is a lot more robust (larger trials). Academia can’t do anything with a gene sequence because they need an inhibitor.
We got €42M from the Euro government to build a platform of human immune cells. Last year we also got £10M to work on Alzheimer’s.
The #6 thing we’re doing: new tools + new biology = starting point for biotech. Got £11M to create a bioescalator (biotech incubator)
The final project: I believe that target validation only happens in patients. Rather than doing the same experiment 20 times in parallel and in secret, let’s identify the 9 in 10 that are garbage, and identify the promising molecule and translate it into the market.
Too much secrecy, competition, duplication and wastage. We bring together multiple clinicians, academic groups, pharma companies, patient groups and CROs. We’re funded by government, private, philantropic and charity funds. We’re working to come up with new targets so the industry can take the molecules to the markeplace. We’re trying to create a new ecosystem, which will generate more novel, more effective medicine, more quickly, and more affordably.
Let’s remember that, regrettably, all of us will be patients one day.
Q: interfering with one gene out of the 900 that cause a disease won’t do much.
A: We try to identify targets that are early in the cascade. Epigenetics hypothesis: there is one epigenetic protein that affects the transcription of one gene, which leads to 200 proteins that cause the disease.
Q: Companies take the molecules and modify them for IP reasons.
A: There is no agreement for the companies to publish failures. We’re relying on academics to publish. Our understanding of diseases is so poor we can’t predict targets. I’m happy for academics to do whatever they like with the molecules.
Q: What are the attitudes of the companies towards this collaborative and shared approach?
A: I believe the industry is in a crisis. The UK had a pretty good track record in drug discovery, but in the last 20 years, many UK companies have downsized or pulled out — sites that employed several thousand scientists. The industry is good at things that require scale and infrastructure — really big clinical studies and marketing. But they’re bad at coming up with targets in the first place. In academia, certain things are easier: access clinicians, patient materials. We’re trying to bring together the strengths of industry and the strengths of academia.
Q: How would you address the concerns of scientists with regards to patentability due to disclosure?
A: I left GSK 7.5 years ago and have been in Oxford ever since. I got sick of academics approaching every day to fund this and that. Many believe they’ve found a drug because they come up with a target. We need some humility — 9 out of 10 novel targets fail when tested in patients for the first time.
The Wellcome Trust champions pooling resources. GSK has lead the way in open innovation. Prof. John Bell, a giant in biomedical science, has really pushed this too.
Q: Michael Vassar (Metamed): why don’t we “collaborate” with cancer cells, since it’s in their interest that the host survives.
A: Cancer patients tolerate horrendous side effects because the treatment occurs at the end of life. Depression patients wouldn’t tolerate the same amount. Affordability is also high in cancer because the families put a lot of money in. In brain diseases, we have the blood-brain barrier that makes it difficult to put drugs in the brain. Brain diseases are more difficult than cancer drug discovery. Academia has to de-risk brain diseases — only then will the industry start to back it.
Q: Thoughts on the Quantified Self movement?
A: In the UK we have health records for 65M patients, from birth to death. I think the QS movement and activity trackers will completely transform the landscape.