Takeda taps Innate for a new coeliac approach

The Japanese developer is an active name in the autoimmune condition, and with its first deal over ADCs it joins others with antibody approaches.

Takeda's interest in coeliac disease has been apparent for some years, though its work so far has focused on targeting gluten with small molecules. Last week’s deal with Innate Pharma takes it into new territory – antibody drug conjugates. But others are already testing biological projects.

The Innate research deal is still preclinical, with work due to start against an undisclosed target using a panel of Innate antibodies, so its specific direction is unknown for now. Chugai and Amgen are the other big names working in coeliac disease with antibody approaches, while Pfizer also has a couple of assets in early trials, albeit at arm's length.

Only Takeda has deployed real business development efforts in this disease, with the Innate deal its fourth since 2019. The tie-up is the first with disclosed terms: the French company receives $5m up front and a promise of up to $410m in milestones, depending on progress.

The Japanese developer’s other projects are believed to work by desensitising sufferers to gluten or by degrading it. The ADC deal adds another shot on goal rather than moving away from gluten as a target; phase 2 trials are ongoing with TAK-101 and TAK-062, and TAK-227 seems to still be in active development, although plans are unclear.

Takeda's coeliac disease effort 
Project Mechanism  Status Origin
TAK-101 Gliadin inhibitor; T-cell inhibitor Ph2 fully recruited, PCD early 2024 Takeda exercised option to license project from Cour in 2019
TAK-062 (zamaglutenase) Glutenase  Large ph2 ongoing, PCD 2025 Bought via PVP Biologics in 2020
TAK-227 (ZED1227) Transglutaminase 2 inhibitor  No new trials started since Takeda bought licence; ph2a published in NEJM Bought US rights from Dr Falk Pharma and Zedira in 2022
ADC research project Against undisclosed target  Preclinical  Licensed from Innate in 2023, $5m up front
PCD=primary completion date on clinicaltrials.gov. Source: Evaluate Pharma & company statements. 

As for other industry approaches, work is still early and data some way off. Fellow Japanese developer Chugai looks to be committed, having moved a novel project into a large phase 1 trial last year.

DONQ52 is described as a multi-specific antibody covering more than 25 gluten-derived peptides, including all immune-dominant gluten peptides for coeliac disease. The MAb is said to work by directly inhibiting gluten-dependent T-cell activation; Chugai also started a large trial testing a novel digital biomarker of coeliac disease last year, which signals real interest in this disease.

Amgen and Calypso are both testing their IL-15 targeted MAbs in coeliac patients, with the former’s large phase 2b trial one of the largest ongoing coeliac studies. Data are unlikely to emerge before 2024, however. These agents are also in development in other autoimmune conditions.

Interestingly, Regeneron is running a TCR sequencing and transcriptional profiling study, which suggests that the US biotech might also be mulling antibody approaches to the disease.

A number of small private developers have ongoing early-stage efforts targeting gluten in various ways, including Immunogenx, Anokion and the Evotec spin-out Topas.

Anokion boasts Pfizer as partner of sorts, although the big pharma does not appear to have any rights over KAN-101. Pfizer injected $35m into Anokion last year and is named as a collaborator on its recently started trial. According to the private group, its project is designed to induce tolerance to gliadin, a core component of gluten, through natural pathways in the liver.

Pfizer’s Jac3/Tec inhibitor ritlecitinib, which is awaiting news on approval in alopecia, is in a small phase 2 academic trial in coeliac, with the pharma giant again listed as a collaborator.   

It will be some time before any of these projects moves into late-stage testing, a step that only one novel project has managed, in recent years at least. 9 Meters' lazarotide failed last year in phase 3. GSK also bowed out in 2022, as it abandoned work on a project bought from Sitari back in 2019.

The coeliac disease pipeline (ex-Takeda)
Project Company  Mechanism Status 
Ordesekimab Amgen/ Provention Bio Anti-IL-15 MAb Ph2 Proactive trial recruiting, PCD late 2023
TMP-502 Topas Therapeutics  Antigen targeting project Ph2 recruiting, PCD 2024
IMGX-003/ latiglutenase Immunogenx Recombinant gluten-specific protease Ph2 crossover study ongoing, PCD April 2024
Ritlecitinib Pfizer Jak3/Tec inhibitor  Ph2 recruiting, PCD January 2024 (academic sponsored)
DONQ52 Chugai MAb against human leukocyte antigen-DQ2 Ph1 recruiting, PCD 2024
KAN-101 Anokion /Pfizer Gliadin sensitizer Ph1/2 recruiting, PCD 2024
CALY-002 Calypso Biotech Anti-IL-15 MAb Ph1 recruiting, PCD Sep 2023
PCD=primary completion date on clinicaltrials.gov. Source: Evaluate Pharma & company statements. List not necessarily exhaustive. 

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