Do you think that we’re going to get an explosion of DisCos, both in and out of longevity space? And do you think all DisCos are going to just grow up and become new Novartises and Genentechs or do you think that some of them are going to be bought by mega pharmas?
- I think that this model will over time replace the single asset model, but not platforms. So the companies that will be going public in the near future are most likely going to be either DisCos or big platforms. DisCo doesn’t replace the platform model. Are each of them going to be the next Novartis? No, lot of them that are not in the longevity space will make their bacon by maturing a program through Phase 2 clinical trials and doing M&A to partner that program to big pharma company and then reinvest that their early stage R&D capabilities. We might do that with Cambrian from time to time as well, but I think that if we have the space not to do that, it is better because the value really comes in the 15-20 year timeframe as opposed to the 5-10 year timeframe.
Are most of your companies platforms or single asset companies?
- Most of them are single assets, not platforms. But it depends on how you define a single asset, we have a conservative view of that – for us a single asset means it is utilizing one set of scientific discoveries and even if there are multiple shots at the goal, if the scientific discovery turns out to be not true, they all fail.
Can you join a DisCo as an individual contributor, do you need a big team, or how does that work?
- If you’re asking whether we are hiring then yes, constantly. DisCos tend to be big companies because of all the different functions that we are covering. Working at a DisCo for an individual in the end is not that different from working at a different biotech. The difference is where people contribute – Cambrian has 4 different teams – Ventures team (inhouse VC – finding scientists, forming new teams), R&D team (advancing from hit to lead, and other stages, etc.), Operations team (everything else that it takes to build a biotech company), Individual group teams. So there is an opportunity to get involved in any of those pieces. All that in total makes about 105 people on our payroll right now, and we started 2 years ago.
How do you distribute value/recognition among the scientific founders if an individual drug program is a success or fail in the DisCo model?
- Individual success sits with the scientist in the DisCo model much longer than in the standard biotech model approach that can pivot around all over the place or get absorbed into an R&D company, because they own larger stakes in their assets compared to the standard model.
- Regarding the recognition, it’s much more about the culture of the organization. When building a DisCo, it’s important to build a culture about celebrating forming useful hypotheses worth testing and celebrating even if the test fails. “It’s really great that we did that because now we know that this doesn’t work.” Then the whole team feels like they are advancing something bigger.
Is there an example of a DisCo in another sector than longevity, that was formed longer ago (>5y, ideally >10y) and has grown and prospered in the way you foresee for Cambrian etc?
- BridgeBio is my favorite mature example of this model (founded in 2015). When I talked to investors like Cambrian, I pitched it as BridgeBio but for longevity. If you look at the evolution of this model, a lot of it was an evolution of the model started even earlier than 2015. Companies like Nimbus therapeutics, some of them evolved from IP holding companies into these hub and spoke models. And then it merged with Third Rock Ventures and Flagship Pioneering approach. They are some of the most consistent VC funds in the biopharma world and they incubate companies inhouse, put a lot of capital into them (usually all the seed and series A rounds – like $50M) before they let anybody else in, and then let them fly out. And it was a sort of natural progression because it was just so expensive to build the structure around a new company every time for each asset.
Thoughts on acquiring companies to exploit potential synergies with different combinatorial therapies for single interventions (cell therapy+senolytic for osteoarthritis)? It would be difficult to do that for single asset companies, but it seems more suitable to do for DisCos.
- You hit a nail on the head here. In 15-20 year timeframe combinations are going to be the most important thing. In general as we get more and more drugs approved as single agents, then the next bridge is biomarker enabled single agent clinical trials in multimorbidity risk prevention – slowing aging trials. The effect we are going to see from single agents would be hopefully significant (5 years of healthy lifespan extension would be a massive boost already), but there is not going to be a single silver bullet for aging. In order to get really large effect sizes, we will have to think about combinations as early as possible. And we will be trying to do trials with combinations and combinatorial studies in animals later once we get to the scale. The ITP that the NIH is running have already started to do some very preliminary work on that, like rapamycin and metformin – which actually works better together than any of them individually. And I hope that as we get to patented and more potent drugs, we will see more accentuated synergies.
Why do your candidate drugs must target particular aging hallmarks? Would it be better that they target the biological age? Targeting a particular damage form may be misleading, as aging is the reflection of many damage forms. The biological age may reflect these many damage forms, whereas it is much harder to do with hallmarks.
- Agree, as I said, hallmarks are a useful guideline for us to classify the biotechs we are evaluating, but it’s not something that is required. If we had a drug that we see can slow epigenetic aging, that alone is interesting for us as well.