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The field of immuno-oncology has expanded out of all recognition over the last few years. Having co-founded one of the first cancer immunotherapy biotechs -- Immatics -- CEO Harpreet Singh has seen it all happen. He plans to take advantage of the company’s head start to tackle solid tumors with its T-cell redirecting therapies. Singh co-founded Immatics in 2000 with two fellow academics, Toni Weinschenk and Niels Emmerich, while completing a PhD in immunology at the University of Tübingen in Germany. The decision to found a company was based on discoveries made in the lab of Hans-Georg Rammensee of targets that could be used to develop a variety of T-cell-based immunotherapies for cancer. The company has gone from strength to strength since then, raising over €350M in private fundraising and partnership deals, and has several drug candidates undergoing phase I/II trials. Singh has guided the research and development at the company as CSO and MD for many years. He was also instrumental in setting up and leading the US office of the company in Houston, in collaboration with the MD Anderson Cancer Center, from 2015 until earlier this year when he became CEO. What inspired you to get into biotech in the first place? Translating scientific knowledge into something that can benefit the patients was always my primary driver. When I founded Immatics, I was a graduate in immunology and we had these exciting discoveries at the Department of Immunology in Tübingen. We were doing experiments in the lab on animal models and the real question, always, for Hans-Georg Rammensee, myself and others that were around him was, ‘How can we translate this into human beings and really create something that is of benefit?’. We formed an organization, a thinking and a mindset that was much more geared towards, ‘How do I bring this benefit to patients? How do I create a product that can be applied to as many patients as possible? How do I take this through various clinical development stages and ultimately to the market?’. In my opinion, that was a much more streamlined, ultimately successful way to develop drugs than to do it in academia where your interests are driven by aspects like publications, impact factors and grant funding. Do you have any regrets about making the jump into industry? I can assure you that when I was going out there with my colleagues and seeking money for our Series A round – this was in 2003 -- there were moments of regret... I think they called it the ‘Nuclear Winter of Venture Capital’ at that time. I think it was even worse than 2008-2009. I put my academic career to the side and rejected a number of existing offers in academia, but this was ultimately extremely successful. We managed to create Immatics and make this an excellent company that is now a global company. We have a broad clinical pipeline and a broad partner pipeline with various partners like Amgen, Roche, Genmab and MorphoSys. You may have seen that recently the ACR in San Francisco published our latest data on our first clinical trial in cell therapy. We infused patients with these cells and we saw that up to 50% of the T-cells are directed against cancer targets. That’s, at least to my knowledge, unprecedented biological levels. We also reported on some very interesting case studies where we’ve seen for the first time clinical benefit. That’s been a wonderful reward to the company, to our shareholders, to me and obviously, most importantly, to the patients that have actually benefited from the therapy. This is very early -- it’s too early for celebration, but we’ve made a very important and big step. How did you navigate the fundraising process and what did you learn from it? Everything starts with the science. Our science has always been exceptional, right from the start when it spun out from Hans-Georg Rammensee’s Lab in Tübingen. It was the only platform at that time that could actually discover so-called ‘pMHC targets’. These are small peptide fragments expressed and presented on MHC molecules on the surface of immune cells, and they allow the immune system to look inside the cell and understand the disease or the normal state. The rest comes with the people that actually are driving this forward with perseverance and persistence, and creating business plans and thinking about how to translate this basic research into something that’s applicable in human beings. But also how to bring in additional expertise into the company, because not everything can be done on your own. I think those are the ingredients to start a successful funding process. Once you’ve started that track record and you have some success, obviously that attracts more funding. We haven’t done a financing round in more than two years and the reason is that there’s no need given the interest in the pharma industry for what we are doing. What has become clear to many people out there, including the pharma industry, is that targets are the key to unlocking immunotherapy in solid cancers. We have been approached by almost every pharma company looking for such targets and they’ve scouted all over the world and have come to us and said, ‘We’ve looked at all the target-discovery companies. You are clearly the leaders globally. We’d like to engage with you.’ You’ve mentioned that you’re going to need more funding in the future. Are you thinking of going public soon? I think we’ve done the right thing in staying private up to this point. It has been, for us, the most successful pathway, a combination of doing venture capital rounds, as well as doing pharma partnerships and seeking some grants. Never at any point were things off the cards. Our shareholders, the board, the senior management and I always look at all opportunities and evaluate them carefully – how to best move the company forward. That’s something we’ll continue to do. I know you’ve had a lot of pharma partners at Immatics. What do you think makes a good partner? What makes a good partner is a common and shared interest. That’s typically the start. Then, it’s a lot about the quality of the science, the quality of Immatics’ science, but this also has to be matched by the quality of the science in the partnering organization. I think that these collaborations only work really well if there is a good match of the respective cultures, particularly if the collaboration is still at the stage where a lot of interaction is required between the teams. We look at these factors very carefully. If we don’t think that there is a good fit then, we don’t engage in such a partnership. We started with Roche in 2013. This was a discovery partnership in lung, gastric and prostate cancer. This has led to a lead target that’s being developed by Roche and it’s currently moving forward in their pipeline. With Amgen and Genmab, we have two similar partnerships. We are licensing targets to both partners and then, we and the partner engage in creating binders. Amgen and Genmab create antibody-based therapeutics and we create T-receptor based therapeutics. The last one, the MorphoSys partnership is very different from the other ones. It’s less a straight licensing partnership than with Roche, Amgen and Genmab. We’ve put targets into a joint bucket from which MorphoSys is generating antibodies against, and these are shared between the two partners for further development. Editor's note: Since this interview took place, Immatics have announced another partnership with Celgene. Immuno-oncology has evolved a lot over the last 20 years and you’ve been there almost from the beginning. How do you think things have changed and how have they impacted the company? It’s a fascinating journey! If I think back when Immatics was created in academia and became operational in 2004, I remember going to a pharma company – let’s say 2006, even 2007 – and talking to them about immunology or immuno-oncology or T-cells. The typical answer was, ‘We don’t believe in that. These are T-cells. We don’t think this can work. This is like homeopathy.’ It was a very typical response at that time. If they look now at where immuno-oncology is positioned, it’s become one of the most powerful weapons in the arsenal against cancer. The perception has dramatically changed. That’s a true paradigm change that we’ve seen in oncology. I feel privileged that I had the opportunity to actually witness this development right from the start. We’ve been discovering immuno-oncology targets since the late ‘90s, so we’ve worked before the word actually existed. For us, and for me personally as well, it’s wonderful to see that what I’ve always believed in – the power of T-cells and how these can be delivered to cancer patients – is now recognized by a much broader audience and this has actually resulted in the first approved drugs. What were your biggest management lessons from the last 19 years. Is there anything that you wish you’d done better, or that you’ve learnt from? I would say one of my biggest lessons, and it keeps continuing, is how important the people are. You can have wonderful science, you can have wonderful partnerships, you can have wonderful external stakeholders, but it’s absolutely decisive what kind of people you have. The biggest lesson is that you often come in with certain assumptions about people and often these are wrong. I have really learnt through the years to be more open-minded and to listen, rather than to think what’s my preconception of that particular person, that particular group or that particular culture. Surrounding yourself with people that contradict you and think differently to you… I think that’s the only way you can actually achieve being a company that does things differently. Only if you do things differently, ultimately, will you be successful in an area where there has been so little success – ie. the treatment of solid cancers. Biotech is notorious for having very few women in senior management positions. I noticed that you have no women on your senior management team or on your board. Is this something you are hoping to change? I can tell you this has never been by design. It is also to some extent unfortunately the reflection of a gender bias that we have in our industry. This is something that I would like to change in this company. If you look at Immatics mid-level management, that’s already very well-balanced. If I look at all the middle management, I even see subjectively a bias to actually more women. That ultimate step towards senior management at Immatics has not happened yet, but I’m very optimistic given how Immatics is evolving from the inside. Do you do anything to encourage development of talent in biotech, such as mentoring? I had the privilege to benefit from wonderful mentors, whether that was as a grad student or later when I founded the company. Business angels, mentors, teachers helped me, so I always try to give back. I engage informally in giving talks to younger people who are interested in entrepreneurship. I’ve done this both at the University of Tübingen in Germany, as well as in Houston, Texas, and I do this often in collaboration with local biotech community organizations like BioRegio Stern in Tübingen. This is something I love to do, as far as my time allows. It’s wonderful to see – I’m 45, so I’m not that old. I was 25 when I created Immatics – and to some extent, I see myself in them. That’s also a wonderful experience for me. What advice would you give yourself if you could go back in time to when you started in biotech? I typically don’t think too much about it because it’s very hard to change the past, but I’m trying to focus on the future because that’s what you can change – maybe not control, but at least try to change. I don’t think I would’ve done much differently. Every step and every painful lesson that we went through had some benefit for the next step in hindsight. At an early stage, Immatics was developing a cancer vaccine. This was initially very successful, but it didn’t work out... We weren’t able to translate that wonderful science into a real effect in human beings. To give you an example, the T-cell persistence or T-cell levels that we currently induce in patients that we treat with cell therapy are around 5,000-fold higher than with cancer vaccines. What we see now with cell therapy is that up to 50% of all T-cells in some patients, or even more, are directed against cancer targets. That’s the kind of level and higher path I believe we also need to achieve in cancer. We didn’t recognize over decades that the level that we were able to induce with cancer vaccine was just too low. We were not the only ones. There were hundreds of groups and companies, even big pharma, working on cancer vaccines. If we had recognized it earlier, we may have made that shift earlier to cell therapy. I still believe cancer vaccines can work. A lot of groups are working on adjuvants and immuno-modulators that could push the T-cell levels closer to what we achieve with cell therapy and that would be a wonderful development. Design via E. Resko

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