3 Companies To Watch

Part 1 of 3

Snapshot analyses of selected companies developing new life science products and technologies.

This blog will present capsules of information, knowledge, and lessons drawn from selected entrepreneurial companies embarked on the path of product development. In addition to key facts and figures, each capsule offers reasons to watch the company in its basic history and strategy, proprietary technology, and so on — along with unique challenges to its business model. A brief, exclusive interview with a top company executive is also included for an inside look at each company.

I am a natural skeptic. But this is a blog, and I am allowed that bias, as long as I allow others to counter my views, or perhaps support them. Anyone can observe the tremendous failure rates in the life sciences industry and either take them, as I do, as reason to be incredulous of attractive paradigms or, as many others, to believe in miracles before they happen. (I do believe miracles happen, just not that often, and when pressed to name one, I often resort to the polio vaccine.) From the past I have also learned that a thousand failures lead to the doorway of success — that no miracle occurs before many paths are explored, abandoned, and mined for knowledge essential for reaching the final goal. That is cold comfort for any one of the thousands of start-ups stymied or even still-born before reaching their dream, but it is also the source of invaluable lessons for the ones that live on.

Epizyme: Beyond Cancer with HMT Inhibition and Screening

VITAL FACTS

• Employees: 40; Headquarters: Cambridge, MA.

• Two venture rounds (Total $54 Million) with participation by MPM, KPCB, BCC, NEA, Amgen, and Astellas.

• $135M realized partnership funding to date:

- Celgene (To date: $90M plus research funding, plus >$160M in milestones per program, royalties)
- GSK (To date: $24M plus research payments, including $4M milestone; potential total: $630M+, royalties).
- Eisai ($10 million plus research payments, incl. $4M milestone; plus $200M+, royalties).
- Multiple Myeloma Research Foundation ($1M).
- Leukemia and Lymphoma Society ($2.6M; $7.5M).

SNAPSHOT
As I wrote in a previous report: Epizyme may appear to be yet another targeted-therapy company, but actually its small molecule histone methyltransferase (HMT) inhibitors and screening technology may have wide cancer and noncancer applications such as metabolic, inflammatory, neurodegenerative, and cardiovascular diseases. HMTs are key enzymes in activating developmental genes. Besides Epizyme is committed to developing personalized medicines “more quickly and at a lower cost than traditional approaches,” with therapeutic product programs targeting the mutant forms of HMTs DOT1L (e.g., leukemia) and EZH2 (e.g., non-Hodgkin's lymphomas) still in the preclinical stages.

LATEST EYECATCHERS
• Lead programs (DOT1L and EZH2) in pre-clinical development
• Announced transformative partnership with Celgene on April 26, through which Celgene takes ex-US DOT1L rights and a 3-year option on ex-US rights for other HMT programs for $90M upfront – Epizyme retains all US rights

WHAT’S AT STAKE
In the beginning, there was genetics. Then came epigenetics — the causes and effects of gene expression, and the biochemical pathways by which those actions occur. It was an evolutionary step in understanding when scientists first realized how genes could be switched off or on by any number of non-genetic agents, in causal chains sometimes extending to the external environment. It was no easy step; an early form of epigenetics had over-reached, and it took advanced tools and science to show how DNA dances to many different tunes. What was once heresy hence become gospel, and the life science industry was quick to see epigenetics as a vast green field for business growth. Epizyme is a company born from the knowledge that enzymes often play a key role in epigenetic transactions found in subsets of patients with cancer and other diseases. It has built a platform that combines an impressive spread of possible applications with the targeting strategy of personalized medicine. Thus it is an excellent test case for several spaces at once.

Epizyme wants the world to know that it is more than a targeted-therapy developer. Why is that important? Look at the record for the most recent trend in targeting: molecular targeted drugs like the new cancer meds sorafenib and sunitinib. Enthusiasm for molecular targeting was high amongst all circles in oncology — scientists, clinicians, regulators, even payers — until reality set in. Once on the market, the drugs proved much more limited in use due to safety, drug resistance, tumor heterogeneity, and other issues, not the least among them high prices. To Saturday cynics like me, the subsequent move to personalized medicine looked like an after-thought attempt by companies to save the new drugs from extinction by assigning them to a lower but lucrative tier of expectations. But Epizyme’s programs may, I say may, signal a second generation of targeted/PM medicines — not settling for any plausible pathway in a disease subset, but hunting down and turning off the most essential mechanisms at work in the cause and progression of multiple diseases.

Watch for parts 2 & 3 of this blog as well as a Q&A with an Epizyme executive.