The promise of telomerase inhibitors for treating blood cancer
Posted: 8 December 2022 | Catherine Eckford (European Pharmaceutical Review) | No comments yet
Geron’s CEO Chip Scarlett discusses the company’s leading telomerase inhibitor in this exclusive interview ahead of the 2022 American Society of Hematology Annual Meeting.
Geron’s CEO Chip Scarlett spoke to EPR to explain the science behind Imetelstat, the company’s leading telomerase inhibitor candidate.
If successful, imetelstat could become the first-ever cancer treatment based on the inhibition of telomerase, helping to treat lower-risk myelodysplastic syndromes (LR MDS), which leaves many patients dependent on blood transfusions.
Here, Geron’s CEO reveals promising results of its telomerase inhibitor candidate from its Phase II trial. In early January 2023, Geron plans to announce top-line results of its Phase III clinical trial (NCT02598661) of imetelstat in LR MDS.
As a first-of-a-kind therapy, what is imetelstat and how does it work?
Imetelstat is a small oligonucleotide, comprised of a nucleic acid and a lipid moiety. The first-in-class telomerase inhibitor harnesses Nobel Prize-winning science to suppress the uncontrolled proliferation of malignant stem cells in blood cancers. It is unique from other treatments as it stops cancer at the root. This is possible because imetelstat targets telomerase, an enzyme that plays a critical role in enabling cancerous stem cells proliferation.
Geron is the first and only company to advance telomerase inhibition into Phase III clinical trials to treat blood cancers. The prior Phase II clinical trials of imetelstat in two types of blood cancers – LR MDS and relapsed/refractory myelofibrosis (MF) – yielded compelling and unique results, including evidence of disease modification in both indications. This differentiates imetelstat from other currently approved and investigational treatments in LR MDS and MF.
Why is telomerase inhibition important in treating cancer?
The approved treatments for blood cancers that patients have available to them may improve symptoms or have other beneficial effects, but the underlying disease continues to progress. This means there is still the need for treatments that can actually modify the course of the disease. The source of disease in these blood cancers are malignantly transformed, hyperproliferative stem cells in the bone marrow. When they proliferate, they crowd out normal cells in the marrow. Imetelstat however has demonstrated evidence in clinical trials that it could be disease modifying, altering the progression of disease. This is why we are excited about the potential of imetelstat and telomerase inhibition.
How can Imetelstat help treat lower-risk myelodysplastic syndromes?
We are excited about the potential of our telomerase inhibitor imetelstat to help patients with LR MDS. Despite standard of care treatment, these patients often become highly dependent on red blood cell transfusions, which require frequent costly hospital visits and can cause transfusion related complications.
… one-third of the patients in our Phase II study – who started imetelstat treatment with a pre-treatment average need of six units of red blood cells every eight weeks – went over one year without needing a single blood transfusion.”
Imetelstat has, in a LR MDS clinical trial, reduced patient dependency on blood transfusions by stopping cancer at the root. In fact, results we’ve just published in an abstract and will soon be presenting at the American Society of Hematology (ASH) Annual Meeting describe that one-third of the patients in our Phase II study – who started imetelstat treatment with a pre-treatment average need of six units of red blood cells every eight weeks – went over one year without needing a single blood transfusion. We believe this is unprecedented in the LR MDS treatment landscape.
What are the challenges of manufacturing Imetelstat?
The COVID-19 pandemic created a sizeable increase in the demand of oligonucleotide therapies such as the mRNA vaccines.”
Oligonucleotides are complex and we’ve spent over a decade working out the challenges of manufacturing imetelstat. A recent challenge for manufacturers of oligonucleotides is demand. The COVID-19 pandemic created a sizeable increase in the demand of oligonucleotide therapies such as the mRNA vaccines. Manufacturers had to invest in their facilities to increase capacity and ability to scale. The investments these manufacturers have made have the potential to benefit anyone developing oligonucleotides including Geron.
How do you predict Imetelstat will inform the emerging field of oligonucleotides?
Geron are on the cusp of demonstrating the potential of imetelstat in blood cancers through a potential positive outcome from our Phase III trial in LR MDS. With positive data, we could see the first approved medicine that works to stop the source of disease in blood cancers with a mechanism of action (MOA) based on the science of telomerase inhibition. That would put us on the path to potentially transforming the treatment landscape for LR MDS and other hematologic malignancies.
Telomerase inhibitors: the scientific rationale
Telomerase is a naturally occurring enzyme that maintains telomeres – short strands of DNA – and prevents them from shortening during cell division.
Inhibiting telomerase could help treat cancer as it helps impede the proliferative capacity of malignant stem and progenitor cells, which researchers suggests are critical in driving tumour growth and progression.
Many myeloid hematologic malignancies, or blood cancers, arise from malignant stem and progenitor cells that express higher telomerase activity and have shorter telomeres when compared to normal healthy cells. In hematologic malignancies, telomerase enables the proliferation of malignant stem and progenitor cells.¹
Dr John A (Chip) Scarlett is Chief Executive Officer of Geron.
He co-founded Covance Biotechnology Services, Inc. in 1995 and from 1991 to 1993, he headed the North American Clinical Development Center and served as Senior Vice President of Medical and Scientific Affairs at Novo Nordisk Pharmaceuticals, Inc.
Dr Scarlett received his B.A. degree in chemistry from Earlham College and his MD from the University of Chicago, Pritzker School of Medicine.
- Telomerase: Scientific rationale [Internet]. Geron. [cited 2022Dec8]. Available from: https://www.geron.com/r-d/telomerase/