- Drug Discovery is expensive and risky
- Cost and Risk can be lowered by more collaboration and sharing
- M4K Pharma is proposing Open Source Drug Discovery
- Don’t file patents and share all your data
- Academics and CRO’s start helping with development
- Data filed with regulatory package still allows you to have exclusivity
- M4K Pharma will be able to recoup costs through this exclusivity
- Trust between parties is a major issue in growing this model to more drug discovery efforts
What is M4K Pharma and Open Source Drug Discovery?
So we started M4K Pharma to launch this experiment in open source drug discovery.
M4K Pharma stands for Medicines for Kids Pharma and we are developing a drug for a very rare pediatric disease called DIPG.
What is Open Science to Owen?
- Don’t file any patents
- Share as much as possible, including results and methods as quickly as possible to as many people as possible
How is the current drug discovery model broken?
The core thesis is of open source drug discovery is that if you share data with others, they will in turn share data and resources back with you.
In the classic drug discovery model, you file patents for compounds you find, so that you have something you can commercialize further down the line and recoup your investment cost. Your Intellectual property becomes your company’s main asset. You own this asset and maximize your profit from it. This is the basis of capitalism and it works very well.
Classic model doesn’t work for rare diseases
Acknowledging how well the traditional model works, there are important limitations to this as well.
It takes about $250-500M to take a drug to market. If you have millions of potential customers, you can easily recoup that cost and pay for your drug development efforts.
But this model falls apart once you are targeting indications with small patient populations. You will either have to charge those people outrageous sums to break even or you simply won’t be able to recoup your investment. Hence most big pharma is focusing on indications that they know can be very profitable for them. Rare diseases often get ignored.
Personalized Medicine leads to much smaller disease populations
Through the human genome project we’ve learned that what we’ve thought of large indications are actually a combination of lots different much smaller patient populations. So we had been giving them very powerful drugs that often have had lots of side effects. Now we are starting to give patients much more targeted medicines with fewer side effects. So far the results are very encouraging.
So better understanding of diseases leads to more targeted drugs with smaller disease groups. However, this challenges the current drug discovery model, because the revenue potential of smaller groups is also going down.
How does open source drug discovery address this?
Because revenues are smaller for smaller patient populations, we are trying to apply the open source drug discovery model to lower the cost of developing the drug.
With M4K Pharma we’re trying to uncomfortably open. Scientists aren’t used to sharing this much information.
We are going to help you share the information through webcasts, point you to conferences and connect you with other scientists to work on this.
There are three main benefits of doing that
Through sharing this, we can collaborate with academic institutions as well as interested Contract for Research organizations and even pharma companies. We can do this much faster than other organizations can do who first need to negotiate for months about ownership, contribution and so forth.
We’re essentially outsourcing part of the work to a number of other interested parties and this can dramatically lower our cost and speed up the findings we need to make.
Access to grant funding
Because we are publishing all of our findings and work with other academic institutions, our work becomes eligible for more grant funding than traditional biotechs have access to. This can be an important additional source of capital, especially in the early stages of drug discovery.
One large pharma company has told us that one of the kinases we’ve been working with had some important off-target in a specific area. Academics from several institutions have also come forward and shared with us findings on what we shouldn’t try. Now this information is very valuable, since it may save us a lot of time we’re not spending on a dead-end.
Examples of collaboration at M4K Pharma
Here are some examples of how we are partnering with others.
Charles River is a CRO that is a start to finish drug developer. They are now encouraging their medicinal chemists to work on DIPG in some amount of their time. So they are now making molecules for us. So through our partnership with Charles River, we have increased our number of chemists by 50%.
Leverage existing knowledge
Academics out of Tufts University in Boston and out of Houston have come to us and said “We have assays for this target, we’ve been looking at it for a different use. These are the results that we’ve had. So don’t try this. And we’re happy to run a couple of assays for you”.
This means we can build directly on someone else’s research and save a ton of time and money on going down the wrong path.
What is in it for your partners? How are you able to get them to contribute to your work?
We are a great partner for academics. We encourage academic development and by working with us, scientists can generate additional findings they can publish.
CROs and Pharma
Because DIPG a fatal children’s disease, scientists at commercial entities are getting energized about being able to contribute to research that could help cure this.
It is in additional way for them to learn about targets. Maybe there is a finding our efforts generate that will translate back to their efforts.
If we hit a roadblock with our approach to DIPG, we will have told the world that this approach didn’t work. So others don’t have to try it.
How can you make money without patents?
Once you have approval from the FDA, you can get exclusive sales rights based on the clinical data you have generated.
There is a special provision for orphan drugs. If you have developed a medicine that targets an orphan disease, the FDA will add another 2 years for a total of 7 years.
In the EU you get 10 years plus 2 years for a pediatric disease.
Exclusivity is more valuable than the patent. The moment the exclusivity expires a generics company will come and try to attack your patent.
So in certain ways, regulatory exclusivity is actually more valuable than patents. Depending on how long it took you to get your drug approved, the patent may be valid longer than the regulatory package. So you’re giving up some lifetime but keep the really strong protection for anywhere from 5 to 10 years.
So we hold back some very specific clinical data, the data that goes into your regulatory package. We copyright that. Through that, we can get granted the regulatory exclusivity which allows us to sell the medicines on the market and recoup the cost of development.
So we can share all of the science and still make money to make it financially viable.
Why isn’t everyone doing this?
Another company could use your findings and swoop past you
If you are going for a very large market, say a non-opoid pain killer, which is something we need urgently. If we put out all my research out and derisked the project extensively, there is a chance that another pharmaceutical company could come in at the last moment and swoop past us. They could create a similar molecule and use their resources to get regulatory approval before us.
So they still have to create their own compound and do all their safety approvals and so on. But their expense is mostly in the last mile, because they can build on all the research we’ve already done.
What are your biggest challenges now?
Raising money is a bottleneck for most biotech companies, as for us. We believe we can make the process cheaper through open science as mentioned above.
Working with academia does lower the cost, but their timelines aren’t as tight. If I hire a CRO, they will get back to me with results within a few months. Academics are working with an academic calendar and less resources, so it may take a year.
Contracts for collaborations
The legal templates our partners, the granting institutions, the universities and the commercial entities use are all worded like “You will keep this to yourself”. Some of them are trying to get special provisions, but in order to keep our credibility of our open source approach, we can’t make any special deals.
Ownership and central data repository
From a legal perspective, how do we make sure that we own all the data from all the collaborations? How do we set up a central data repository where we can share the data but we are the owners? Owning the data doesn’t mean we won’t share it, but we have to own the data so that we can pass the regulatory approval process and get the exclusivity.
Open Science in a commercial model
Bio2040: Have other groups approached you to learn about this model?
Many people have thought of using open science to lower
We might be the first ones to create a commercial entity that uses open science. In an academic setting there can be a tendency to spend a lot of time on a narrow area. You may see an experiment fail and then spend a lot of time trying to understand why it failed. In a commercial setting, I don’t have the time to do that, I need to simply try out the next compound.
So the necessity to stay alive in a commercial setting drives you to focus on the highest leverage activities and that is what we can bring to the open science model.
We think the M4K Pharma model is one of the most interesting we’ve come across since we started bio2040.
It is quite fundamentally challenging the current dogma of data hoarding and privacy driven route that most biotech and pharma companies engage in when it comes to drug discovery.
Open source drug discovery faces quite a few challenges, including some of them highlighted above. The biggest barriers we see to the model are
- Aligning financial incentives with more data sharing
- Trust that the partners will behave in a way that is mutually beneficial long-term
Right now, this approach is at an experimental stage and is targeting a disease with a very small patient population. We are confident as people experiment with new business models, they will come up with new ways to collaborate and share data, while creating sustainable financial models for all parties involved.
Decentralized drug discovery?
Essentially, M4KPharma is exploring something we can also call decentralized drug discovery. Different parties across different organizations can now contribute to a single cause. We believe that in the future, this way of doing drug discovery will become more and more important.
What needs to happen for this to become true?
We are looking forward to your thoughts and comments
Find out more about M4K Pharma here:
There are so many challenges in drug discovery. We are a group of entrepreneurs and scientists who want to improve things. Our first measure is to educate ourselves and the community on what the biggest bottlenecks and their underlying reasons are. This leads us to discover exciting new opportunities. Bio2040 wants to be the leading place for or entrepreneurs & academics to meet, exchange ideas and launch new ventures.
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