A Glimpse at Drug Discovery’s Future from H3 Biomedicine CEO Markus Warmuth
October 5th, 2012
Posted by Shane Climie, Ph.D.
As many of you know, R&D progress in drug discovery has been a challenge for “big pharma” and biotech firms alike. The costs and risks are enormous, and the rewards are increasingly elusive. For many young firms, the “valley of death” is a very real obstacle as cash burn rates exceed the pace of successful delivery of new drugs to market. What can startups (and larger companies) do? Markus Warmuth, CEO of Cambridge, Massachusetts-based H3 Biomedicine, talked with us about his company’s strategies for giving drug discovery a much-needed boost.
H3 Biomedicine Inc. is a privately held, uniquely structured oncology discovery enterprise. H3 is applying the expertise of leading scientists to the integration of insights from cancer genomics with innovative capabilities in synthetic chemistry and tumor biology to discover patient-based, genomics-driven, small molecule drugs, which represent the most promising current opportunity in cancer therapeutics. H3 Biomedicine will achieve its goals through a unique relationship with the pharmaceutical company Eisai Inc. Eisai has pledged up to $200 million in research funding to H3 Biomedicine, as well as additional support for the clinical development of H3 Biomedicine programs.
Q: What does H3’s drug discovery approach say about the current healthcare economic climate?
Warmuth: Our scientific operation and implementation of strategy is starting at a time when there’s a lot of genomic information becoming available from large numbers of cancer patients. There’s The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). It’s an absolutely fantastic time for drug discovery using a human biology or genome based approach. Now that we have genomic information available through public portals on 5,000 or more patients, we can be very systematic.
For financing, our company is based on a very different model from most companies within the small-sized biotech sector. Because we are funded by Eisai, we are less focused on short-term success and exit strategies. Human biology is very complicated; you can’t resolve issues in 3-5 years – so we are fortunate to have the ability to take a longer term approach to oncology drug discovery.
Q: How does your model let you innovate?
Warmuth: We are looking at a 6- to 8-year trajectory. This gives us time to dig deeply into genomic information, and to create biological hypotheses. On the discovery end, it prepares us to find the right chemicals to address genetic changes. We can take a detailed look at the chemical space and enzyme structure/function, and marry that with human biology. It’s relatively easy to come up with compounds, but we don’t want to ignore the question of whether a particular kinase is biologically relevant—whether an inhibitor of that kinase is more than just an interesting chemical, and whether it actually has a beneficial effect in vivo.
Q: What does it mean to you as CEO to have the luxury to innovate?
Warmuth: It’s key to have the right tools to test the hypothesis. The advantage of genomics data (and access to genomics databases) – the way it is generated by TCGA and ICGC – is that we have consistent, multilayered data from many different patients. We have information on normal tissue but also disease-related RNA sequencing data, which allows us to measure gene expression but also delivers insights into alternative gene splicing, SNP arrays to get into gene copy number changes, and so on. With this, we can start to do some really cool biological networking exercises. We do, however, need to set up new models—cell lines do not enable the same level of analysis as human samples and related genetic analyses.
Q: Why is cancer the preferred disease state for H3?
Warmuth: It’s an obvious starting point. It’s the disease with the most genomic and mechanistic information available at this point, in part because cancer tissue is more accessible than tissue related to other disease areas (compared to neuroscience, for example). Other disease areas may be catching up; there are large-scale SNP genotype and other genomic studies advancing rapidly for many other human diseases. We’re using that genetic and genomic information to drive multiple disease/discovery hypotheses.
Q: I believe that cancer is on the leading edge of drug discovery. Do you agree?
Warmuth: I certainly agree. In the areas of understanding human disease biology, relating to genetic and epigenetic changes, signaling pathways and changes in tissue, cancer is well ahead. If you think about it, cancer is probably the disease where the diseased tissue changes most, compared to normal tissue.
We’ll share more from our discussions with Dr. Warmuth in a future post on new directions in target validation, the value of open-source genomics data, and how H3’s discovery strategy differs from that of big pharma. In the mean time, you can read about H3’s most recent news announcement here.
What do you think of H3’s model? How have advances in genomics affected your product development strategies? Is there a way to digitize this new biological knowledge, or even create tools to help uncover other biological trends? Please share your thoughts with us here.
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