ViewPoints: Stemcentrx willing to let its oncology data do the talking

In a day and age when just about any cancer drug developer able to spell ‘xenograft’ is rushing to get in on the immuno-oncology craze, and can’t wait to tell you about their latest and greatest discovery, Stemcentrx stands out from the crowd – not only for its productivity and blue-chip investor base, but the way in which the company has moved a host of antibody-drug conjugates (ADCs) targeting cancer stem cells (CSCs) into the clinic while uttering nary a peep about its progress.

Stemcentrx finally came up for air last month when it presented results from a Phase I/II trial of its lead programme, which investigators praised as the biggest breakthrough in decades in the small-cell lung cancer space, though given the company’s typically understated fashion one would be hard-pressed to know about the achievement unless you were a physician in attendance at the medical conference.

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Stemcentrx has been around since 2008 but has kept a remarkably low profile, which sounds like a red flag in a resource-intensive industry like biotech where CEOs are typically keen to tout most any accomplishment in the hopes it will make raising their next dollop of cash all the less difficult.

The company’s willingness to remain mum is likely a reflection of its founders’ dispositions – who, as one would expect, declined to comment for this story – yet Stemcentrx’s ability to do so likely speaks to both the early promise of its CSC technology platform and the faith its deep-pocketed venture capitalists have in the organisation’s ability to mine it for intriguing ADC candidates.

Thus far the company appears to be making good on this conviction from investors as its efforts have generated five ADCs that have moved into human testing, as well as a partnership with Pfizer. The company’s minimalist website does not go into great detail on the technology that was used to discover and engineer the candidates, though what is known is that they each address novel targets identified as present on CSCs specific to particular tumour types.

Stemcentrx is, of course, far from the first drug developer to embark on a mission to discover therapeutics targeting CSCs. Companies like OncoMed, Stemline and Verastem have all made names for themselves in the same space, and leveraged early promise into fruitful IPOs and in some cases big-money partnerships (such as one involving OncoMed and Celgene), though several programmes have run into problems. Just this week Verastem shares shed 45 percent after it stopped a pivotal study of its lead product, VS-6063, after seeing insufficient efficacy in patients with mesothelioma.

Investors including Founders Fund, Fidelity, Capital Group, Sequoia Capital and Artis Ventures are apparently convinced Stemcentrx may be on a different trajectory from its fellow CSC companies as they have reportedly provided it with as much as $500 million in financing, including a recent $250 million round, at an eye-popping valuation of $5 billion. Interestingly, that would put Stemcentrx’s current value at more than the market caps of Stemline ($160 million), Verastem ($200 million) and OncoMed ($440 million) combined, as of September 29.

A company that few have heard of developing agents about which little is known being worth multiple billions of dollars may seem a little far-fetched – though Celgene did recently agree to pay up to $2.6 billion to license a product from little-known Nogra Pharma – but the first real look at data supports the notion that Stemcentrx may indeed be onto something.

This weekend, investigators presented preliminary results from a Phase I/II trial showing that rovalpituzumab tesirine (or Rova-T), an ADC that delivers a cytotoxin directly to CSCs expressing DLL3, achieved a 64-percent objective response rate in relapsed/refractory patients with SCLC who were sensitive to front-line chemotherapy and positive for DLL3 expression. What’s more, the agent generated a 45-percent objective response rate in DLL3-expressing patients when given as third-line therapy.

While the data are still early, physicians clearly like what they see. David Carbone, a professor of internal medicine at Ohio State University, referred to the results as “the most exciting breakthrough in small-cell lung cancer in three decades,” as the agent’s activity compares extremely favourably versus the single-digit response rates achieved on topotecan, the current standard of care for SCLC.

M. Catherine Pietanza, assistant attending physician at Memorial Sloan Kettering Cancer Center and lead investigator on the Phase I/II study, noted that one of the most encouraging aspects was the finding that DLL3 could be used as a biomarker for identifying patients most likely to respond to therapy with Rova-T, which is a first in the SCLC setting.

The results suggest that Stemcentrx may quietly be on the right path. The company has four additional programmes in human testing, including an ADC targeting EFNA-4 partnered with Pfizer that has demonstrated activity in ovarian, non-small-cell lung cancer and triple negative breast cancer. It is also thought to have a handful of additional candidates headed towards the clinic, and plenty of novel targets available for use in discovery.

Needless to say, when Stemcentrx is ready to talk, it seems like that there are likely to be a lot of people – patients, physicians and potential partners alike – interested in listening.

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