On November 3, 2011, Cambridge MA biotech firm Verastem announced that it was filing a prospectus for an initial public offering (IPO). At that time, the company was 15 months old.

Verastem is led by Christoph Westphal, MD, PhD, a founder and the former CEO of Sirtris and a veteran entrepreneur and venture capitalist. The IPO has been underwritten by UBS, Leerink Swann, Lazard Capital Markets, Oppenheimer & Co., and Rodman & Renshaw.

On January 27, 2012, Fierce Biotech reported that Verastem had announced the previous night that its IPO raised $55 million from the sale of 5.5 million shares at $10 apiece. This price fell exactly in the middle of its expected $9 to $11 price range, and the company had even increased the offering by a million shares over what had originally been planned.

On the same day, Verastem’s stock opened at $11 a share on the NASDAQ, up from its initial public offering price of $10.

Verastem not only has Christoph Westphal as its Chairman and CEO, but is also based on science from eminent MIT researchers Robert Weinberg, Ph.D. and Eric Lander, Ph.D., and has several other well-respected academic researchers (including Nobelist Phillip Sharp, Ph.D.) plus biotech industry drug discoverers Julian Adams, Ph.D. (MIllennium’s Velcade) and Roger Tung, Ph.D. (Vertex’ Lexiva and Agenerase) on its Scientific Advisory Board. The company has had considerable fundraising success prior to its IPO, including raising $32 million in venture capital  in July 2011.

However, Verastem has not one lone drug in human clinical trials, its most advanced compounds are in the preclinical stage, and the company does not plan to file an IND until 2013! Thus Verastem has successfully gone public, in an era in which even most private biotech companies with drugs in late-stage clinical trials are finding it very difficult to do so, despite its lack of any clinical-stage drugs.

As noted in the Fierce Biotech article, Dr. Westphal as well as other venture capital funders of Verastem agreed to buy up to $16.3 million of the IPO. This in part explains the success of the IPO. As also noted by Fierce Biotech, with over 19 million common shares outstanding, the offering valued Verastem at $192 million.

We discussed Verastem in our August 2, 2011 Biopharmonsortium Blog article entitled “Development of personalized therapies for deadly women’s cancers”. Verastem focuses on discovery and development of drugs to target cancer stem cells. Its technology is based on a strategy for screening for compounds that specifically target cancer stem cells, developed by Drs. Weinberg, Lander, Piyush Gupta (MIT and Broad Institute) and their colleagues.

Cancer stem cells are best known in acute myeloid leukemia (AML), but their existence in other cancers (especially solid tumors) is controversial, as discussed in our article. Whether cancer stem cells are involved in the pathobiology of solid tumors (or a particular type of solid tumor) or not, the biology of the putative cancer stem cell phenotype can be important in certain subtypes of cancer. Cancer stem cells are characterized by the epithelial-mesenchymal transition (EMT). In the Cell paper, the researchers screened for compounds that specifically targeted breast cancer cells that had been experimentally induced into an EMT, and which as a result exhibited an increased resistance to standard chemotherapy drugs.   They identified the compound salinomycin (now being marketed as a generic veterinary antibiotic) as a drug that specifically targeted these cells, as well as putative cancer stem cells from patients.

As we discussed in our article, triple-negative (TN) breast cancer cannot be treated with standard receptor-targeting breast cancer therapeutics (e.g., tamoxifen, aromatase inhibitors, trastuzumab) but must be treated with cytotoxic chemotherapy. It is generally more aggressive than other types of breast cancer, and even treatment with aggressive chemotherapy typically results in early relapse and metastasis. However, TN breast cancer includes two experimentally defined subtypes that have gene expression signatures related to the EMT. One or both of these subtypes might therefore be expected to be sensitive to compounds that specifically target putative breast cancer stem cells. This may be true whether the cancer stem cell hypothesis applies to TN breast cancer or not. Verastem is focusing on TN breast cancer as its first therapeutic target.

Verastem’s VS-507, a proprietary formulation of salinomycin, is being developed to treat TN breast cancer. The company is also screening for additional compounds, including New Chemical Entities (NCE) that can achieve stronger intellectual property protection than a salinomycin formulation. Verastem had not chosen a lead compound as of the middle of 2011. The company is now reported to be doing preclinical studies on three of its compounds, and also plans to create diagnostic tests to identify patients that could benefit from its treatments. (As we discussed in our article, biomarker-based tests will be critical in making such therapies work.)

As one can discern from our blog article, we are intrigued by Verastem’s approach to cancer treatment, and especially its approach to TN breast cancer. The science behind Verastem’s drug discovery strategy, developed by 2011 ASCO award-winning oncogene and cancer stem-cell pioneer Bob Weinberg, is very compelling. We would love to see Verastem’s therapeutic strategy succeed.

However, as virtually all pharmaceutical and biotechnology R&D researchers well know, it is difficult to translate even the most compelling science developed by the most brilliant researchers into the clinic. Even therapeutic strategies with an excellent scientific rationale that have achieved proof of principle in the best animal models can result in clinical failure, especially with the first compound tested in proof-of-concept studies in human patients. The cancer stem cell hypothesis remains controversial. Moreover, diseases such as TN breast cancer are complicated, they may have mechanisms of resistance to a new experiential therapy that no one knows about, and our understanding of disease biology is limited.

Thus at least until Verastem’s therapies achieve proof of concept in human studies, purchase of Verastem stock is risky indeed. Moreover, there are other risks involved other than technical and clinical risk–especially competition for developing cancer stem cell-based therapies by other biotech/pharma companies. Venture capitalists (and certain knowledgeable individual investors and funds) are in the business of taking on high-risk investments for the sake of potential large rewards, but ordinary retail investors in the public markets are not. Therefore, it seems too early for Verastem to go public, even if it has founders and investors with enough clout to make an IPO successful.

Expert analysts in the IPO field, as stated in the Fierce Biotech article, are puzzled by the rationale for Verastem going public at this time. The financial news and services website “TheStreet.com” agrees. Our own sense of puzzlement is symbolized by the interobang (‽) in the title of this article.

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