Biopharmconsortium Blog

Expert commentary from Haberman Associates biotechnology and pharmaceutical consulting.

Monthly Archives: January 2012

Preclinical-stage biotech Verastem goes public. Really‽

 

Salinomycin

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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As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or of other issues that are important to  your company, please click here. We also welcome your comments on this or any other article on this blog.

Forma Therapeutics enters into two Big Pharma alliances in succession for the New Year!

 

RNase/RNase inhibitor protein-protein interaction. Dcrjsr http://bit.ly/zRrlaz

We mentioned Forma Therapeutics in two previous articles on this blog. In one article, we focused on Forma’s R&D efforts in discovering small-molecule inhibitors of protein-protein interactions (PPIs).  The other article included a discussion on Forma’s efforts in cancer metabolism.

This month–January 2012–when the new year had barely started–Forma signed two new Big Pharma alliances, covering both of these areas.

On January 5, Forma announced that it had entered into an R&D collaboration with Boehringer Ingelheim, focusing on discovery and development of small molecule drugs to address oncology-relevant PPIs. Under the terms of the agreement, Forma will receive a total of $65 million in up-front payments and research funding, and could be eligible for up to $750 million in pre-commercial milestone payments for development programs resulting from the collaboration.

As with the Genentech deal in cancer metabolism that we discussed in an earlier article, the new Boehringer Ingelheim agreement provides Forma and its shareholders several opportunities to realize early return through assets developed under the collaboration. However, details of how this might occur were not disclosed. According to a January 6, 2012 article in BioWorld Today, flexibility and liquidity (without the need for a IPO or an acquisition) are importance goal of Forma’s business development activity in general. Nevertheless, Forma CEO Steven Tregay does not rule out a future acquisition, and says that large pharmaceutical companies are interested in such a deal.

On January 10, 2012, Forma announced an exclusive alliance with Janssen Biotech (a Johnson & Johnson company), in which the companies will collaborate on the discovery, development and commercialization of novel small molecule drug candidates that target mechanisms of tumor metabolism.

Under the terms of the agreement, Forma will discover and develop drugs against a panel of tumor metabolism targets. Forma may receive up to $700 million in project and milestone funding. In addition, FORMA may receive royalties on revenues from products commercialized as a result of the collaboration. Moreover, if certain milestones are achieved during the initial phase of the collaboration, FORMA will have the opportunity to co-develop and maintain North American commercial rights to one program selected by Janssen. The two companies may also expand the collaboration to include other targets, including those in areas beyond tumor metabolism.

Once again, Dr. Tregay sees the opportunity to maintain North American rights to a product resulting from the collaboration as in line with the company’s strategy to create long-term shareholder value within Forma.

In December 2011, Forma moved its operations from Cambridge MA to Watertown MA, in the process gaining double the amount of space it had before. This will allow for the company’s growth in new internal and partnered R&D projects, and for the growth in staff that this will entail.

As we discussed in earlier articles on this blog, PPIs have been considered “undruggable” targets. However, given that researchers have been able to discover and in at least one case develop small-molecule agents to address this class of targets, it is best to think of this area as a premature technology. As discussed in our July 27, 2011 article, Forma believes that it has developed a set of enabling technologies to move the PPI field up the technology curve, similar to what happened to the monoclonal antibody field in the 1990s. Apparently, several partner organizations–not only Boehringer Ingelheim, but also Novartis and the Leukemia & Lymphoma Society–agreed with Forma enough to invest in partnerships in this area.

Forma is not the only Boston-area biotech to have a major program in discovery of drugs that modulate PPIs. Ensemble Therapeutics (Cambridge, MA), has internal programs and partnerships in discovery of small-molecule compounds that target PPIs, and Aileron Therapeutics (Cambridge, MA), which we discussed in our November 27th 2009 and our August 24th 2010 blog articles, is developing peptide compounds designed to target PPIs in internal and partnered programs.

As for cancer metabolism, Forma is once again not the only Boston-area biotech to have major programs in drug discovery in this area. We have discussed Agios Pharmaceuticals, which specializes in that area, in our December 31, 2009, April 23, 2010, and November 30, 2011  Biopharmconsortium Blog articles.

In our December 22, 2010 blog article, we discussed the field of intermediary metabolism, asking “Will intermediary metabolism be a hot field of biology again?” In the 1920s through the 1950s, intermediary metabolism was a hot field of biology, but the field was eclipsed by molecular biology starting with the Watson and Crick paper in 1953. However, largely as the result of research that combines intermediary metabolism and molecular biology, metabolism is coming to the forefront of biomedicine again. In the area of cancer metabolism, researchers such as signal-transduction pioneer (and Agios scientific founder) Lewis Cantley have been combining the two fields in order to understand cancer disease pathways, with implications for drug discovery and development.

All of the companies mentioned in this article are research-stage companies, with no drug candidates yet beyond the preclinical stage. The strategies of these companies, and the compounds that have resulted from them, thus must be validated in clinical studies. Nevertheless, we are encouraged by these companies’ success so far, and the interest show in them and their science and technology platforms by large pharmaceutical companies. The success of these companies also provides an object lesson–premature technologies and neglected fields may at least in some cases provide opportunities for drug developers.

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As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or of other issues that are important to  your company, please click here. We also welcome your comments on this or any other article on this blog.