Asco 2016 – Ganymed applies for unicorn title with gastric data

Ganymed Pharmaceutical has made itself a candidate to be the next big private oncology takeout with promising data from its targeted antibody released at Asco.

The German group’s IMAB362 showed significant benefit in delaying disease progression and overall survival compared with chemotherapy alone in biomarker-identified patients with gastric tumours. If a billion-plus-dollar takeout awaits Ganymed, as happened with the similarly positioned Stemcentrx, it would be a decent return for the venture investors who have piled in $227m over 14 years (AbbVie caps week of cancer deals with huge Stemcentrx takeout, April 29, 2016).

New target

IMAB362, or claudiximab, is a first-in-class project targeting claudin-18.2 and is the only one known to be in development, activating an immune response to the cells to which the agent binds. Claudin-18.2 is a tight junction protein differentiated to gastrointestinal cells and not known to be expressed in healthy tissue, making it a useful target; Ganymed says the protein is expressed in up to 80% of gastrointestinal adenocarcinomas and 60% of pancreatic tumours.

The phase II trial in 161 patients with gastric or gastroesophageal junction cancers tested IMAB362 and chemotherapy against chemotherapy alone in patients with a specific minimal level of claudin-18.2 expression, as validated by Ganymed’s own CE-marked diagnostic assay. None of the patients had been treated for metastatic disease before, and were ineligible for Herceptin because they did not express HER2, which is present in only 15% of this patient group.

Disease-free progression was significantly higher in the patients taking IMAB362, 7.9 months to 4.8 months for the patients taking chemotherapy, along with overall survival, 13.2 months versus 8.4 months.

A pivotal study is planned to begin in 2017.

Looming threat

As seemingly with all things in oncology, Ganymed needs to operate with the knowledge that another immunological approach, PD-1 inhibition, is quickly moving in this space. A phase III trial of Bristol-Myers Squibb’s Opdivo is already under way in inoperable gastric cancer thanks to Japanese partner Ono Pharmaceutical, while Bristol itself plans a pivotal study in the adjuvant setting.

Pfizer and Merck KGaA, meanwhile, are testing avelumab in front-line use, and Merck & Co is testing Keytruda in patients who have progressed on platinum based chemotherapy. All of these trials appear likely to read out before Ganymed can complete its phase III trial.

What IMAB362 has on its side, however, is biomarker driven treatment, and indeed, the patients in the phase II trial with the highest levels of claudin-18.2 expression saw greater survival while treated with this agent – 13.7 months.

By comparison, PD-1 expression remains a controversial topic as a biomarker, but Opdivo has so far been approved as an all-comers drug in its biggest indication, non-small cell lung cancer. Thus Ganymed, and any possible partner or acquirer, will be acutely aware of how the market may shift between now and IMAB362’s potential approval.

This makes it a distinctly different situation than with StemCentrx, which was developing an agent in small-cell lung cancer, a condition for which there has been little progress for years and thus resulted in its massive takeout. Still, with advanced stage assets like IMAB362 a precious commodity in oncology, it would be surprising to see Ganymed advancing into phase III next year solo.

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To contact the writer of this story email Jonathan Gardner in Chicago at [email protected] or follow @ByJonGardner on Twitter