Life Science Partners
Phacilitate: So Life Science Partners are actively investing in both immunotherapy and cell and gene therapy. What advice can you give biotechs in the space looking to engage in BEC funding?
Vincent Brichard: Immunotherapy of cancer and cell and gene treatment have both been very hot topics in recent years, as have autoimmune disorders. The main advice I would give to early biotechs is: “Don’t follow the trend just because something is a hotspot today.” It is extremely tempting to scour the biotech pipeline, or the biotech platform, for something that is (or could be) applicable to cancer immunotherapy or cell and gene therapy, even when this is actually not the core business of that particular biotech company’s technology platform.
Instead I would say: “Just focus on your core business and try and see what is going to happen there five years from now.” Cancer immunotherapy, and cell and gene therapy, are here today. Over the past three years, immunotherapy has really demonstrated that it can be a stand-alone modality in the reduction of tumour size, with the ability to induce long-lasting and sometimes complete responses.
On the other hand, we are also beginning to see the limitations of these current approaches for immunotherapy. Of course a small percentage of patients respond, but for precisely this reason we should now be focussing on the non-responders. For cell and gene therapy, important limitations are the cost of materials, manufacturing issues and questions related to autologous cell cancer; this is why other people are looking for allogeneic technologies, which seem to offer a better path to proceed along.
As I mentioned, my second piece of advice to early biotechs is to think about what is going to happen in five years from now, not just what is happening today. And a third piece of advice would be: “Focus on the unmet needs”. As I also mentioned, in immunotherapy the focus should be on the non-responders and not, for example, on some additional checkpoint inhibitors that could perhaps be used in combination therapy but which in fact offer little added benefit. Focus on populations where there is still a high unmet need! If you think about immunotherapy, or cell and gene therapy, then you will still find very broad areas where the need is not yet met.
Phacilitate: In March, LSP led the Series A financing for ERVNA immunotherapy, a product that includes off-the-shelf injectable mRNA. Dr. John de Koning said in an article that “mRNA technology is one of the hottest areas in the global biotechnology science.” How do you expect the mRNA field to fit into the immunotherapy toolbox alongside all the other existing and emerging modalities?
Vincent Brichard: mRNA technology is unique because the manufacturing part is relatively easy. The mRNA platform can be extremely flexible and extremely agile. For example, if you think about personalised medicine and a neoantigen (the antigen in an individual patient’s tumour) the mRNA technology is flexible enough to incorporate these neoantigens easily, and in a short space of time, into a personalised vaccine.
Moreover, eTheRNA technology is exciting because of the potential of the TRIMIX technology. This combines three complementary components that boost a vaccine’s effect and increase the induction of a T‑cell response.
We see in eTheRNA a possible way to modify “cold” tumours, as we say in oncology, that is, tumours that are not inflamed and have not been infiltrated by immuno-effectors. It is a way to change those “cold” tumours into “warm” tumours – meaning those tumours where you clearly have a T‑cell infiltrate. Such tumours have been associated with clinical benefit with the use of checkpoint inhibitors.
eTheRNA technology combines the advantage of delivering antigens and potentially personalised (neo)antigens from the individual patient, with the advantage of a complementary adjuvant component. This would seem to be ideal for a future combination with checkpoint inhibitors. This is a good, strong and agile platform which has been shown to be a good inducer for T-cell effectors.
Phacilitate: Are there any particular therapeutic areas or indications that LSP are actively looking to invest in? Or is it more of a technology area focus for you within the cell and gene therapy space?
Vincent Brichard: LSP is one of the oldest venture funds in continental Europe, and one of the largest. LSP has raised a fund for private Biotech investments of €250m, but we believe that globally LSP has invested well above €1bn in this technology. The drivers for LSP are not a particular area or a focus in a technology platform. The drivers of LSP are (1) very good science; (2) a perpetual push toward innovation and transformation within medicine; and (3) a good team, both on the scientific side and on the business and management side.
We think that these three conditions will enable LSP to generate new products for the future, ones that will correspond to the needs of society, and obviously to the needs of our customers; the pharma industry and the payers. So the three drivers for LSP are science, innovation and teamwork rather than a specific technology or therapeutic area.
Phacilitate: What excites you, and what worries you, about both sectors currently? Where do you see value and where do you see risks?
Vincent Brichard: Over the last three years we have seen tremendous successes in cancer treatment, and maybe a transformation in the way we see cancer and the manner in which our bodies fight against it. Immunotherapy and cell and gene therapy have outstanding success stories to tell.
For immunotherapy, the first success story was CTLA‑4 – maybe not the most exciting one, but it did establish immunotherapy. The arrival of PD1 and PDL1 in 2014 and 2015 really integrated these immunotherapeutic leader molecules into the standard of care in cancer. More importantly, not only in one type of cancer. The first cancer type on which it was tested was melanoma, but other types of cancer as well – including frequent ones such as lung cancer and bladder cancer.
For cell therapy, the compound CAR 19 was pioneered by Carl June at the University of Pennsylvania in Philadelphia. It took two decades to find a treatment that is efficacious in a disease (childhood leukaemia) where the medical need was very high. Treatment with CAR 19 led to outstanding response rates, close to 90% in fact, and with very long responses.
The only risk is actually to deliver on these promises, because everyone has seen the success stories, and everyone has been willing to develop more components mimicking the CTL4, PD1, PDL1, checkpoint inhibitors or immune stimulators or other cellular therapies mimicking CAR19. The autologous technology is labour-intensive and time-consuming. Therefore, there will be great interest in the allogeneic platform, which only requires one universal donor, where the blood can be prepared and despatched to several cancer patient recipients.
For checkpoint inhibitors, the focus should be upon the non-responder population or on immune cells that are exhausted. For cell and gene therapy the focus will probably be different in the future – the focus, and indeed the challenge, are going to be the cost of materials.
I would see less the risk, but more the challenge, that of unfolding the approach’s full value and delivering what it promises. Immunotherapy is being administered to many cancer patients and bringing a broad clinical benefit, without the requirement to select those patients that are the most likely to respond to one specific kind of molecule, or to one specific technology platform, and not to others.
Phacilitate: After the recent financing rounds, and after the success stories and failures of IPO: What are the most important lessons to be learnt from the European immunotherapy and cell and gene therapy industries?
Vincent Brichard: The take-home messages are the following. First recent years in Europe have shown success – both for immunotherapy of cancer and for cell and gene therapies. European companies have done very well, and have made a real contribution to the global effort.
So it is not only a US story, it is also a European story, which is reassuring for European investors. It means that science in Europe is really at the cutting edge.
Looking into the future, I would say that given the context that we see today on the financial markets, acquisitions or IPOs are currently not that easy. For that reason companies should not rush to enter the stock market; they should take the time to find their best window of opportunity before they get listed.
People should be aware of the financial market and should know the medical market too, i.e., the needs of both the payers and society, as well as the needs of the pharmaceutical industry – which is one of the biggest customers for Biotech. In Europe this will be the key to focussing scientific research.