And then there was one: GRN1005 failure leaves Geron with imetelstat and $90m
This article was originally published in Scrip
The good news for Geron's investors? Now that the Menlo Park, California-based company has terminated development of GRN1005 and plans to lay off 64 of its 107 employees, it has enough cash on hand to fund its operations for two or three years.
The bad news? Geron has $90 million in investor cash to spend on its one remaining drug candidate: the telomerase inhibitor imetelstat, which failed in a Phase II clinical trial earlier this year to improve progression-free survival (PFS) in patients with metastatic HER2-negative breast cancer (scripintelligence.com, 11 September 2012).
Geron's stock price fell 23% on 4 December to $1.14 per share after the company said on 3 December that it ended a Phase II clinical trial for GRN1005 in the treatment of patients with brain metastases arising from breast cancer. An interim analysis of the GRABM-B trial revealed no intra-cranial responses among the first 30 evaluable patients in the study.
The Phase II GRABM-L clinical trial for GRN1005 also was stopped early because of difficulties enrolling the necessary number of patients with brain metastases arising from non-small cell lung cancer (NSCLC).
Geron has terminated its exclusive license for GRN1005 and will return the asset to Angiochem, a Canadian firm whose other programs are in discovery and preclinical stages. Geron's now left with imetelstat, which has shown mixed results in clinical trials this year.
Company president and CEO John "Chip" Scarlett said during a 4 December conference call with analysts and investors that Geron has a lot of confidence in imetelstat's "novel and clinically differentiated mechanism of action."
The company will report Phase II data from essential thrombocythemia (ET) patients treated with imetelstat monotherapy at the American Society of Hematology (ASH) annual meeting on 9 December. The ET clinical trial is meant to show proof-of-concept for the treatment of various hematologic myeloid malignancies and evaluate the effect of the drug on JAK2 mutations that drive hematological malignancies.
All 14 ET patients in the study were refractory to or intolerant of conventional therapies, but 100% had a hematologic response to imetelstat and 93% of had a complete response. The molecular response rate was 86% of the seven patients with a JAK2 mutation.
Geron said the top-line data exceeded the company's expectations and suggest a selective inhibition of progenitor cells responsible for malignancies, which could give imetelstat disease-modifying status for hematologic myeloid malignancies.
When Geron stopped the Phase II breast cancer study for imetelstat in September, the company also halted a Phase II NSCLC study. The end of those studies also marked the end of development for imetelstat as a treatment for solid tumors.
Now, the company says it has non-clinical data that show tumor cells with short telomeres, which control cell division, are more sensitive to telomerase inhibition caused by imetelstat than tumor cells with longer telomeres.
Geron has completed a subgroup analysis from the Phase II NSCLC study in which there was a modest, but statistically insignificant PFS improvement. Imetelstat-treated patients whose tumors had short telomeres had a clinically meaningful, statistically significant PFS increase compared to patients in the control arm (p=0.042).
The company is refining an assay to measure telomere length in individual tumor samples, which would be necessary for a Phase III-enabling clinical trial with patients whose solid tumors have short telomeres.
Imetelstat is the last great hope for Geron, which discontinued its embryonic stem cell program for spinal cord injuries in 2011 to focus its resources on oncology drug candidates (scripintelligence.com, 16 November 2011). The company agreed last month to sell its stem cell assets to BioTime in a complicated cash and stock transaction (scripintelligence.com, 16 November 2012).
With GRN1005 on its way back to Angiochem, Geron is restructuring to focus the company's capital solely on imetelstat.
Geron will reduce its operating expenses from about $65 million in 2012 to about $33 million in 2013, including $3 million in one-time costs associated with the corporate restructuring and $3 million to pay for discontinuing the GRN1005 clinical trials. That will leave the company with about $90 million in cash and investments at the end of 2012 compared to $122.1 million in cash and marketable securities at the end of 2011.
In a discussion of risks for investors in a 4 December research note, Needham equity analyst Chad Messer wrote: "Geron currently holds sufficient cash to reach projected Phase II read-outs for imetelstat, but is unlikely to have enough cash to reach commercialization."