Welcome to your weekly digest of approaching clinical readouts. As make-or-break outcomes go, Neon Therapeutics is facing a pretty momentous one. This month the company will find out whether the approach it has staked its future on is viable, clinically and commercially.
Neon has built its approach around neoantigens, proteins that occur only in cancer cells owing to genetic mutations. This specificity makes them promising targets for cancer treatments. By directing the immune system towards neoantigens, using its vaccine and T-cell technology, the company hopes to be able to shrink tumours.
The big test for the technology is the 52-week readout of a phase I trial of its vaccine NEO-PV-01. The NT-001 trial is studying the personalised vaccine in combination with Opdivo in first and second-line advanced melanoma, NSCLC and bladder cancer, indicating that the company sees the future of the product as an add-on to checkpoint inhibitors, rather in competition with them.
While the primary endpoint of the 55-patient study is safety, all eyes will be on secondary endpoints of objective response rate, as well as progression-free and overall survival, though much of this data will be immature at this stage.
Eventually Neon will have to answer one big question: is NEO-PV-01 potent enough? Because NT-001 only has one arm it will be tricky to get an answer at this stage, as it could be difficult to determine what the vaccine is adding over checkpoint blockade.
Investors appear to be waiting to see some data before fully backing the company's approach: Neon's shares have lost almost three-quarters of their value since the group floated in July 2018. Some in the sellside are keeping faith, however; a
Investors appear to be waiting to see some data before fully backing the company's approach: Neon's shares have lost almost three-quarters of their value since the group floated in July 2018. Some in the sellside are keeping faith, however; analysts at Berenberg have called the technology a “game changer for immunotherapy” and have even suggested peak sales of over $3bn for NEO-PV-01 in cancer indications.
As ever it should be worth remembering that high expectations have the equally high potential to disappoint – Incyte's epacadostat, which failed when tested on top of checkpoint inhibitor, being a case in point.
Defying the odds
Like Neon, Neurotrope is taking a crack at an old disease with a new approach. The biotech company is seeking to do what many larger companies have tried and failed to do – find an effective treatment for Alzheimer’s.
After several high profile blowups, many in the industry are finally looking beyond the amyloid beta hypothesis. Neurotrope’s lead project bryostatin is a compound derived from the marine invertebrate Bugula neritina. Bryostatin is thought to be a potent activator of protein kinase C, which is thought to be involved in a number of Alzheimer’s pathways and could have the ability to regenerate synapses, potentially making it a disease-modifying product.
The obvious caveat here is that none of this has been conclusively shown in humans. Indeed, like many early-stage Alzheimer’s projects, data has so far been mixed. In a 2017 dose-finding study bryostatin failed to show any benefit in moderate to severe Alzheimer’s patients, as measured by the Severe Impairment Battery score (SIB).
It is a measure of just how desperate the industry is to find drugs that work in Alzheimer’s that Neurotrope felt confident enough to plough on with bryostatin after conducting a subgroup analysis of the data. This found that 15 out of 16 patients not on Alzheimer’s drug memantine at the time of the trial showed improvement in their symptoms over time with bryostatin.
As such, the phase II confirmatory trial due to read out in the second half has enrolled 100 moderate-to-severe Alzheimer’s patients who are not on memantine. Study participants have either received 20ug bryostatin or placebo. The primary endpoint is again the change in the SIB score at week 13.
If Neurotrope is successful in this trial investor interest will follow. But as countless companies have found in this graveyard of clinical development, a phase II hit is no guarantee of success in phase III. Unsurprisingly, the market is definitely not factoring in commercial success for bryostatin, with 2024 forecasts standing at just $209m.
|Clinical trial IDs|
|NEO-PV-01 studies (phase I)|
|NEO-PV-01 in combination with nivolumab||NCT02897765|
|NEO-PV-01 in combination with pembrolizumab and chemotherapy||NCT03380871|
|NEO-PV-01 with nivolumab and either APX005M or ipilimumab||NCT03597282|
|Phase II in moderate to severe Alzheimer's disease||NCT03560245|