Biotech’s key fourth-quarter data 

After delving into big pharma readouts Evaluate Vantage has pulled out the key fourth-quarter catalysts for biotech companies with a market cap of $1bn and up. Here, Deciphera stands out: clinical results will see whether Qinlock can move into an earlier treatment line in gastrointestinal tumours, a key revenue opportunity. 

Meanwhile, Allakos appears to be the only group targeting Siglec-8 in rare inflammatory conditions. And early data will be seen with Uniqure’s gene therapy for Huntington’s disease, an area littered with failures. 

Deciphera’s big opportunity 

Deciphera’s Qinlock, a Kit/PDGFRα kinase inhibitor, only has a fourth-line label in gastrointestinal stromal tumours, and the hope is that data from the Intrigue study could move it into second-line disease.  

Intrigue’s primary measure is progression-free survival versus Sutent. It has enrolled patients who have progressed on, or are intolerant to, first-line Gleevec, and the study has been powered to assume that Sutent will allow six months' PFS. 

So far revenues in the fourth-line setting have flattened, with $22m recorded in the second quarter. A second-line label is needed to bring a substantial uptick, and sellside consensus forecasts $1.4bn for 2026. Those numbers, from Evaluate Pharma, position Qinlock as market leader in the space. 

Stifel analysts note a 70-80% probability of success for Qinlock in Intrigue, pointing to the 10.7 months' median PFS achieved in 31 second-line patients in a separate phase 1 trial. 

Targeting Siglec 

Data on Allakos’ lirentelimab are due from two clinical studies. The company is aiming to treat rare chronic inflammatory conditions of the stomach, duodenum or oesophagus that are thought to be driven by mast cells and eosinophils. Lirentelimab targets Siglec-8, an inhibitory receptor found on these cells. 

Enigma2, a phase 3 study in eosinophilic gastritis and eosinophilic duodenitis, pits lirentelimab against placebo, and the primary endpoints are the proportion of responders, as determined by gastric or duodenal tissue eosinophil counts, and the mean absolute change in total symptom score. 

Lirentelimab has been shown to lower gastrointestinal eosinophil counts, the primary endpoint in a successful phase 2 trial. Earlier data for the change in total symptom score, however, are not as clear cut.

The latter was a secondary measure in phase 2, where the 3mg/kg dose showed a benefit over placebo, though 1mg/kg lacked statistical significance (No Enigma in mid-stage success, Allakos insists, August 5, 2019). 

Also due are results of the phase 2/3 Kryptos trial in patients with eosinophilic oesophagitis, comparing the same 1mg/kg and 3mg/kg doses against placebo. Here the primary outcomes are the proportion of patients who achieve a specific oesophageal intraepithelial eosinophil count and the mean absolute change in dysphagia symptom score. 

Both Sanofi/Regeneron’s Dupixent and Astra’s Fasenra have ongoing studies in the inflammatory conditions, and Takeda’s Eohilia, an oral suspension of budesonide, has been filed in eosinophilic oesophagitis. And, while there are several other Siglec modulators in clinical development, it looks like Allakos is the only group targeting Siglec-8. 

Huntington’s gene therapy 

Like many other CNS disorders Huntington’s disease has suffered numerous clinical setbacks, with recent examples including antisense projects from Roche/Ionis and Wave. Now data are expected from Uniqure’s gene therapy AMT-130, albeit in just four patients from the first dose cohort of a phase 1/2 study.  

AMT-130 uses an AAV5 vector that carries microRNA tailored to silence the huntingtin gene. The first cohort to report uses a dose of 6x10¹² genome copies per subject, and the therapy is delivered via MRI-guided stereotaxic infusion into the brain. 

Sham surgery is used as the control, and the primary measure is safety; data on biomarkers and imaging are also expected. In total the first cohort consists of 10 patients, and a higher dose of 6x10¹³ genome copies per subject is also being tested.  

One explanation for the failure of Roche and Wave’s projects is that they were delivered intrathecally so might not have sufficiently penetrated the deep brain tissues involved in Huntington’s. Uniqure is directly injecting AMT-130 into the relevant brain areas, which might avoid issues with biodistribution. 

Safety is obviously a key consideration in gene therapy studies, and Biomarin and Astellas have suffered recent adverse event scares with their AAV projects. Uniqure, itself no stranger to questions about gene therapy toxicities, will be hoping to avoid the same pitfall. 

The table below contains a fuller list of upcoming catalysts, with consensus forecasts from Evaluate Pharma. A look at big pharma clinical catalysts can be found here.