Biotech’s key fourth-quarter data 

Deciphera, Allakos and Uniqure are all set for important data disclosures.

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

Q4 clinical catalysts (excludes Covid-19 data)
Project Company  Therapy area Q4 clinical catalyst 2026e indication sales ($m) Note/Vantage coverage

Sage Therapeutics/ Biogen/Shionogi

Major depressive disorder Coral (50mg vs placebo, on top of sertraline),
Shoreline 1yr data with 50mg dose
2,299 (SBI not split out) Alongside Waterfall data Sage expects to file in MDD on PK and safety data from Coral and Shoreline (Sage depressed by Waterfall)
Deciphera 2L GIST Ph3 Intrigue  1,418* See text
Allakos Eosinophilic oesophagitis, eosinophilic gastritis/
Ph2/3 Kryptos, ph3 Enigma2 1,224 See text
Cortexyme Alzheimer's disease Final ph2/3 Gain data (mid-November) 1,222 In Feb 2021 FDA placed clinical hold on the OLE phase of Gain over hepatic adverse events 
Bridgebio Transthyretin amyloid cardiomyopathy (ATTR-CM) Topline from Part A of ph3 ATTRibute-CM 1,195 Pfizer's Vyndaqel/Vyndamax is market leader
UCB Psoriatic arthritis and ankylosing spondyloarthritis Ph3 Be optimal, Be Complete, Be Mobile1, Be Mobile 2 994 IL-17A and IL-17F MAb, already filed in psoriasis with a Pdufa in Oct 2021
Madrigal Nafld (Nash and fibrosis) Topline data from blinded arms of Ph3 Maestro-Nafld-1, possibly at AASLD in Nov

741 (Nash and Nafld numbers)

Open-label data showed resmetirom-treated pts achieved mean 53.4% reductions in liver fat content (by MRI-PDFF at week 52; p<0.0001; Maestro-Nash registrational study data Q3 2022)
Mirvetuximab soravtansine Immunogen Platinum-resistant ovarian cancer Ph3 Soraya in high FRα expression 465 All-comers study failed (Forward I); in Forward II Avastin combo yielded 50% ORR, comprising 33% in medium and 64% in high FRα expressers (After Immunogen and Sutro, Bristol buys into the folate story) 
B-Vec (KB103/
beremagene geperpavec)
Krystal Biotech Epidermolysis bullosa Pivotal Gem-3 462 Topical gene therapy (Epidermolysis bullosa gene therapies wait in the wings)
Zilucoplan UCB Generalised myasthenia gravis Ph3 Raise 389 C5 inhibitor, originated at Ra; Pdufa for Argenx's efgartigimod (anti-FcRn MAb) in MG is in Dec 2021
AMT-130 Uniqure Huntington's disease Ph1/2 biomarker and imaging data 328 See text
CTX110 Crispr B cell malignancies Ph1 Carbon update guided to 2021 243 Anti-CD19 Car-T, expecting additional data from Allogene's  ALLO-501/A likely at Ash (Crispr valuation is no match for reality)
Trofinetide (oral) Acadia Rett syndrome Ph3 Lavender 192 Analogue of the neuropeptide IGF-1 that company says can reduce neuroinflammation and support synaptic function
Ionis/Biogen ALS Ph3 Valor data in the fall 138

Biogen leads the amyotrophic lateral sclerosis hopefuls

CTX120 Crispr Multiple myeloma Ph1 topline 135 Anti-BCMA
Bempegaldesleukin + Keytruda Nektar 2L NSCLC Ph1/2 Propel, remission data from around 60 subjects 76 Underwhelmed in melanoma (Nektar again looks to bempeg to sweeten its valuation)
Nedosiran Dicerna Primary hyperoxaluria type 3 Ph1 Phyox4 due Oct  73 (PH type not split out) Phyox2 study worked in PH1, the most severe type, but not PH2; PH3 is the mildest form (Dicerna can’t catch up with Alnylam)
CTX130 Crispr Solid tumours and haematologic malignancies Ph1 topline Cobalt-Lym, Cobalt-RCC 41 Anti-CD70
Lemzoparlimab I-Mab/Abbvie r/r advanced solid tumours, lymphoma Ph1b, plus Keytruda by YE/early 2022 - Anti-CD47 licensed by Abbvie last year (Abbvie looks east for CD47)
KT-474 Kymera/Sanofi Hidradenitis suppurativa/atopic dermatitis Ph1 healthy volunteer data  - Protein degrader
(ALX148) + azacitidine
ALX Oncology Myelodysplastic syndromes Ph1 Aspen-02 - Anti-SIRPa/CD47a MAb
*Already approved in indication at different treatment line. SBI=sales by indication. Sources: Evaluate Pharma, company releases, analyst notes &

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