Johnson & Johnson waits until the last to drop Geron
A new partnership hunt awaits Geron Corporation as it seeks to defray the costs of the phase III imetelstat programme, making Ash presentations a key moment in the biotech’s future.
Geron’s imetelstat story already has had more twists than a Hitchcock film, and today the group's partner, Johnson & Johnson, threw in another one. The big pharma decided to wash its hands of the myelodysplastic syndrome project, a decision that knocked Geron out of the billion-dollar biotech club as shares plummeted 69%.
Executives of the spurned partner put on a brave face today, highlighting coming data and committing even more money to R&D. Geron should be thankful for its $183m cash pile, as it might need to use quite a bit of this to sustain imetelstat.
Strategic review
Geron's chief executive, John Scarlett, chalked up J&J’s decision to a strategic portfolio review, and it might be difficult to fault the big pharma for making such a call. Imetelstat will need to elbow its way into the increasingly competitive myelodysplastic syndromes and myelofibrosis market, where Incyte and Novartis’s Jakafi has dominated and Celgene is looking to extend the reach of its weighty blood cancer franchise (see table below).
| A crowded field: Select pipeline projects in myelofibrosis | |||
| Product | Company | Mechanism of Action | |
| Phase III | Pacritinib | CTI BioPharma | Jak2 inhibitor |
| Pomalyst | Celgene | TNFa inhibitor | |
| Fedratinib | Celgene | Jak2 inhibitor | |
| Momelotinib | Gilead Sciences | Jak1/2 inhibitor | |
| Glasdegib | Pfizer | Smoothened homologue antagonist | |
| Phase II | NS-018 | Nippon Shinyaku | Jak2 inhibitor |
| Sotatercept | Celgene | Activin receptor 2a regulator | |
| Luspatercept | Celgene | Activin receptor 2b antagonist | |
| Imetelstat | Geron | Telomerase inhibitor | |
| RG7433 | AbbVie | BCL-2 inhibitor | |
| PRM-151 IV | Bristol-Myers Squibb | Regulatory macrophase (MREG) differentiation stimulant | |
| LCL161 | Novartis | Inhibitor of apoptosis protein (IAP) inhibitor | |
| Source: EvaluatePharma | |||
It is also difficult to blame Geron for persisting, as imetelstat is its most advanced product and the company hopes to get data from the phase II Imbark and Imerge studies onto the Ash agenda. Primary analysis of this phase II programme triggered a countdown clock for J&J to decide whether it wanted to maintain its licence.
If the data are good enough they could trigger new partnering talks. Mr Scarlett told analysts in a call today that Geron would continue alone, but is hoping to snare an ex-US commercial partner.
Digging deep
Investors therefore need to assume that the base case is for Geron to fund phase III fully, and this will see it dig more deeply into its cash reserves. The company has already told backers that it expects operating costs of $37m for 2018, 23% above the $30m in its guidance, as it adds staff and resources to complete the phase II studies of imetelstat and prepare for phase III.
Imbark is a trial in 200 high-risk myelofibrosis patients who have not responded to or have relapsed on Jakafi, looking to reduce spleen volume and myelofibrosis symptoms, similar to the endpoints used in the trials of Jakafi that earned it US FDA approval in 2011.
Geron has said that imetelstat has shown activity on these endpoints, along with other measures, and that as of January 2018 a median overall survival number had not been reached after 19 months of follow-up. This trial has no comparator arm, however.
Imerge is a phase II/III trial in low-risk myelodysplastic syndromes, trying to establish transfusion independence, along with response measures. Geron has submitted data from two cohorts of patients to Ash.
Owing to the conference’s policies Geron cannot let slip any of the data it has in house, meaning that there should be a quiet period until the presentation embargo lifts in late November. There is no doubt that the group will need a very good Ash to return to investors’ favour.
