Upcoming events – Reneuron’s time to deliver and Kadmon targets metastases

Date November 18, 2016

Welcome to your weekly digest of approaching regulatory and clinical readouts. By December 5 Reneuron will report initial data for its stem cell therapy ReN001 in chronic disability caused by stroke, from a phase II trial in which only two patients have to show an improvement for it to be deemed a success. The company has been working on ReN001 for the best part of 20 years, and backers will be eager to see some real progress.

Also expected in December are data on Kadmon’s tesevatinib in metastatic lung cancer, from a phase II study in patients whose disease has spread to the brain. Kadmon’s shares have plummeted since the company’s IPO, and with lung cancer an increasingly crowded space it will likely need to look to other indications to gain value.

A long time coming

Reneuron's Pisces II trial is an open-label, single-arm study in 21 patients with motor disability due to an ischaemic stroke. ReN001 is a human neural stem cell product, and in the study 20 million CTX cells are injected into the damaged area of the brain two to three months after the stroke, with follow-up over 12 months.

The primary endpoint is a minimum two-point improvement after six months in a part of the action research arm test (ARAT) that examines a patient’s grasp, measured by moving a wooden block. If two or more patients meet the endpoint the study will be deemed a success.

The UK-based study will report interim three-month follow-up data on December 5, and if these are positive Reneuron expects to file an application to move into a pivotal phase II/III trial in the first quarter of next year, having already met US and European regulatory authorities. That trial is likely to be a single-blind study in 200-250 patients, with sham surgery as control.

Long-term phase I data in 11 patients showed a good safety profile and evidence of improvements in neurological function 24 months out.

ReN001 is Reneuron’s most advanced asset, and the company has been slaving over it for years – it took seven years to prepare the data to satisfy government agencies that the project was safe enough to start its phase I trial back in 2010. Reneuron was the first company to perform a stem cell-based clinical trial in the UK (Behind disappointment stem cell therapy showing pluripotential, October 12, 2010).

Most clinical development in stroke is in the acute setting, and there are few options of any kind for treating long-term neurological deficits. There is one potential competitor in the Japanese cell therapy company SanBio, which has started recruiting into its 156-patient phase IIb trial in chronic mobility issues due to stroke. Its SB623 therapy uses bone marrow-derived stem cells, and the study will report in the second half of 2017.

The Pisces results will determine whether ReN001 has a future, and a hit could improve investor sentiment; Reneuron’s shares are down 20% this year. Success could also revive enthusiasm in the stem cell therapy field as a whole.

Disease spread

The phase II open-label trial of Kadmon’s oral EGFR inhibitor tesevatinib in metastatic lung cancer is continuing to enrol patients with EGFR-mutant non-small cell lung cancer that has metastasised to the brain or leptomeninges, membranes that cover the brain and spinal cord.

A 300mg once-daily dose is being tested in three treatment groups, two looking at progression while on different EGFR therapy and one in brain metastases without prior therapy. The primary endpoint in patients with brain metastases is objective response rate, and in those with cancer in the leptomeninges it is improvement in symptoms compared with baseline, both at 12 months.

Data from the first seven patients in this 60-patient trial will be reported at the IASLC 17th World Conference on Lung Cancer on December 4-7 in Vienna, Austria. Additional topline data from the trial will be released early next year.

Based on initial observations, improvements in neurological symptoms and/or tumour shrinkage were seen in six patients between days 7 and 41.

There are several issues Kadmon will have to deal with. Tesevatinib will have to distinguish itself from the other marketed EGFR inhibitors, and Kadmon will also have to focus on its ability to cross the blood-brain barrier. Analysts at HC Wainwright also note that there is no standard metric for response of leptomeningeal metastases to therapy, posing a regulatory risk for the product.

Kadmon was founded by Imclone’s chief executive Sam Waksal, who was convicted and jailed in 2001 for securities fraud; it is now run by his brother Harlan Waksal. The company completed its $75m IPO in July, but floated at a 33% discount and is down 31% to date.

As well as its potential use in cancer tesevatinib is also under investigation in polycystic kidney disease, where there are limited treatment options. A phase IIa trial in the autosomal dominant form is enrolling, and a study in paediatric disease will start early next year.

Project  Trial ID 
ReN001  NCT02117635 
Tesevatinib  NCT02616393 

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @JoEPVantage on Twitter

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