Geron revives imetelstat as brain cancer drug bombs out

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Geron is a ghost of its former self. With the shelving of its peptide-drug conjugate GRN1005, the California company has taken the decision to shrink its workforce to just one third of its size 13 months ago; meanwhile, its once-vaunted stem cell assets could soon be spun out into a joint venture with the regenerative specialist BioTime.

Given its relative wealth by biotech standards, Geron does not need money – it needs success. With its pipeline stripped almost completely bare through clinical setbacks, there is little optimism – shares fell 36% to 94 cents in early trading today, valuing the company at near its current cash balance. A curtailed cash burn could help it preserve its $101m cash pile; deal-making might be necessary to revive its shares, not to mention ensure an independent course.

Data poor

The group pulled GRN1005 after an interim analysis of the first 30 evaluable patients showed no sign of intracranial response in patients with brain metastases arising from breast cancer. The company said the trial had been troubled by patients’ inability to tolerate the drug, which led to a lowering of the dose.

Geron also terminated a separate study in non-small cell lung cancer brain metastases, which had difficulty enrolling patients.

The drug is a peptide linked to three molecules of paclitaxel; the conjugate was designed to allow the peptide to bind to the lipoprotein receptor-related proteins on the surface of the blood-brain barrier, assisting the paclitaxel in reaching the tumours.

With the decision to end the GRN1005 programme, the cupboard is looking empty save for imetelstat, itself a troubled asset. The telomerase inhibitor recently failed in a phase II breast cancer trial, with progression-free survival in the treatment arm shorter than in the placebo arm, and prospects look bleak in non-small cell lung cancer (Geron blow could put final nail in telomerase inhibitor coffin, September 11, 2012).

However, the company said today that it would press on with imetelstat, also known as GRN163L, in haematological disease and solid tumours with short telomeres; the former trial is supported by a small proof of concept study that showed a 100% response rate in patients with haematological myeloid malignancies, with data to be presented at the Ash medical meeting on December 9.

In solid tumours, an unplanned interim analysis in non-small cell lung cancer trial – taken after the breast cancer failure – showed a non-significant trend towards efficacy; but in patients whose tumours with short telomeres at baseline, a pre-planned subgroup, there was a statistically significant increase in progression free survival.

For all the optimism of its executive team, Geron is looking increasingly like a company without a plan B – and a questionable plan A. Given the failure in breast cancer, it will take some exceedingly good data to interest potential partners in imetelstat now, subgroup analyses notwithstanding.

In haematological malignancies new treatments are always wanted, but better treatment classes like the Janus kinase inhibitors are emerging, meaning the imetelstat will have a higher efficacy bar to clear in coming years.

Last year Geron ended all work in embryonic stem cells, and it is now negotiating with BioTime to create the joint venture, so it can be expected that these assets will soon be out of the company’s hands (Geron exits embryonic stem cell stage, November 15, 2011).

Cash rich

What it has is cash – the company estimates it will have $90m at year end, and it forecasts burn next year at $33m. Licensing in an early or mid-stage asset is well within its financial capabilities.

At its current market capitalisation, that cash pile would make it a relatively cheap acquisition for a company needing a market listing – a speculative R&D pipeline and its proprietary nucleic acid drug discovery platform would provide some hope of future growth.

After some rather damaging clinical failures, the future of Geron probably lies largely with its investors, who may believe at this point that an acquisition is the best way to create value. Any more failures with imetelstat will certainly not help the case of those wanting the company to remain independent.

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @JonEPVantage on Twitter.

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