Reneuron has seen enough in a phase II study of its lead candidate, the stroke stem cell therapy ReN001, to move it forward. But the data were not as emphatic as they might have been, so any potential acquirers or collaborators might want to stay on the sidelines until more robust results are available.
Next up is a pivotal study using sham surgery as a control, which should provide a more definitive answer on the project’s efficacy. Reneuron plans to start this in the first half of next year and it should take around two years to complete. On the company’s side is the current unmet need in patients with chronic disability caused by stroke and the fact that there are few other clinical-stage projects in this area.
Reneuron is actively looking for a partner in Japan but “other than that, we plan to develop it ourselves”, chief executive Olav Hellebø told EP Vantage. With £60m ($76m) in the bank at the end of the third quarter, Reneuron should have enough to fund the pivotal trial of ReN001 as well as its other programmes.
Investors initially sent Reneuron’s shares up 15% this morning, but ended up closing down 1%. And at around 3p, the company’s stock is well off its 2007 heyday of around 47p.
For now, caution is probably warranted, especially given previous stem cell therapy flops. The single-arm open-label phase II Pisces trial had a relatively low hurdle to clear, only needing to show an improvement in two out of 21 patients on the primary endpoint after three months. This endpoint involved part of the action research arm test (ARAT), which evaluates a patient’s grasp as measured by their ability to move a wooden block (Upcoming events – Reneuron’s time to deliver and Kadmon targets metastases, November 18, 2016).
Three of the patients achieved the minimum two-point improvement, but only one did this in the three-month timeframe, with the others meeting the threshold at six and 12 months. This means that Pisces II did not meet its primary endpoint, but Mr Hellebø argued that this is “relatively irrelevant”.
“The objective of the study was to learn as much as we can about the therapy in patients who’ve suffered a stroke and to see if there’s enough signal for us to continue development in this indication. And also to look at different potential endpoints to see what looks promising for further clinical trials.”
The treatment, which involves injecting human neural stem cells into the area of the brain damaged by stroke, did fare better on other endpoints. Seven and eight patients respectively showed a clinically relevant improvement on the Modified Rankin Scale, which measures disability and dependence, and the Barthel Index, a measure of performance in activities of daily living.
The former is well-regarded by the FDA, while the latter is favoured by European regulators, according to Mr Hellebø. It is unclear at this point which endpoint or endpoints will be used in the pivotal trial, though “we clearly show activity in measures [the regulators] like,” Mr Hellebø said.
The most common adverse events seen in Pisces II, such as headache and nausea, were related to the surgical procedure rather than the cells. One patient died of sepsis seven months after receiving ReN001, but “in the opinion of the investigator it’s unrelated to treatment or surgery”, Mr Hellebø said. “There was no infection in the brain – it was a general infection.”
Stifel analysts were upbeat about the data but still only give ReN001 a 25% chance of success, up from 15% previously. If it does get approved they see a lucrative market, forecasting sales of $3.9bn in 2026.
If it makes it that far, ReN001 will no doubt be helped by a lack of other options. “There are no treatments available for stroke patients beyond clot busters in the first three or four hours after stroke,” Mr Hellebø said. “Stroke patients are typically very frustrated because they improve a lot in the first month or two after stroke and after that they plateau. This is the first time, really, there’s some promise here.”
One potential rival to Reneuron is the Japanese cell therapy company Sanbio, whose SB623 bone marrow-derived stem cell treatment is in phase IIb with results expected in the second half of 2017. That is a much larger trial than Pisces II and also includes a sham surgery arm, putting Sanbio ahead in terms of development.
After nearly two decades working on ReN001, Reneuron has cleared an important hurdle – but it still has a lot more to do.
This story has been updated to reflect Reneuron's share price.