Caspian Therapeutics and Kura Oncology have presented preclinical evidence that their selective menin inhibitor KO-7246 can regenerate insulin-producing pancreatic β-cells.
Caspian Therapeutics and Kura Oncology have reported preclinical data suggesting that their menin inhibitor KO-7246 could help regenerate insulin-producing pancreatic β-cells and provide sustained improvements in blood glucose control.
The findings, presented at the 62nd European Association for the Study of Diabetes Annual Meeting in Milan, Italy, support the development of KO-7246 as a potential treatment for both Type 1 and Type 2 diabetes. The data were generated by Kura Oncology before Caspian launched in September 2026.
Menin acts as a molecular brake on the proliferation of pancreatic β-cells. Caspian is developing menin inhibitors with the aim of increasing functional β-cell mass and potentially restoring the body’s ability to produce insulin.
“Menin is a compelling target in diabetes because multiple lines of evidence, from human physiology and genetics to pharmacologic studies, point to its role in regulating β-cell mass,” said Dr Francis Burrows, Chief Scientific Officer of Kura Oncology. “KO-7246 gives us a potent, selective way to test whether menin inhibition can harness this biology to restore endogenous insulin-producing capacity in both Type 1 and Type 2 diabetes. Its potency and selectivity as a menin inhibitor, as well as its activity in a range of diabetes preclinical models, distinguish KO-7246 from earlier approaches and support its potential to become a best-in-class menin inhibitor for diabetes.”
Sustained effects in Type 1 diabetes model
In a rat model of Type 1 diabetes, KO-7246 normalised fasting blood glucose in most animals and increased stimulated C-peptide, a marker of endogenous insulin production.
Among responding animals, pancreatic islets regenerated to between 40 percent and 90 percent of levels observed in healthy controls by day 56. The improvements in glucose control and C-peptide levels were maintained for at least a month after treatment stopped, while residual β-cell proliferation was negligible.
These findings indicate that the treatment may have regenerated functional β-cell capacity rather than simply producing a temporary reduction in blood glucose.
The response also depended on the amount of residual β-cell capacity present at the start of treatment, which the companies said was consistent with the proposed regenerative mechanism.
Activity extends to Type 2 diabetes
In a mouse model of Type 2 diabetes, KO-7246 reduced fasting blood glucose while increasing insulin and C-peptide levels. Treatment also produced a 3.4-fold increase in β-cell mass.
KO-7246 showed enhanced activity when combined with semaglutide, suggesting it could potentially complement existing GLP-1-based treatments. The increase in insulin was not associated with hypoglycaemia in the model.
The companies said the findings support further investigation of KO-7246 both as a standalone treatment and alongside established glucose-lowering therapies.
Human islet findings provide further evidence
Importantly, the researchers also tested KO-7246 in human pancreatic islet models. The treatment increased β-cell proliferation and the proportion of β-cells without stimulating the growth of other islet cell types.
This provides an early indication that the regenerative effect seen in animal models may translate to human β-cell systems, although these experiments are preclinical and do not establish whether the approach will be effective or safe in patients.
The companies also compared KO-7246 with BMF-219, another menin-targeting compound in clinical development for diabetes. KO-7246 showed potent menin inhibition in biochemical and cellular assays, while BMF-219 did not show discernible activity against menin in the biochemical assay and instead inhibited several kinases.
In a Type 1 diabetes model, KO-7246 restored glycaemic control and increased β-cell mass, whereas BMF-219 produced neither effect.
Moving towards clinical development
The companies say the findings support KO-7246 as a selective menin inhibitor with potential for diabetes and other cardiometabolic diseases.
“We believe KO-7246 has one of the most comprehensive preclinical profiles reported for a menin inhibitor being developed for diabetes,” said Dr Robert Spencer, President and Chief Operating Officer of Caspian Therapeutics. “It combines bona fide menin pharmacology with durable β-cell regeneration, activity in both Type 1 and Type 2 diabetes models and potent and selective effects on β-cells in human islets.
Caspian was formed to translate this biology into potentially disease modifying medicines. We believe these data provide a strong foundation for KO-7246 to become a best-in-class menin inhibitor and for Caspian to lead the development of menin-directed therapies for diabetes and other cardiometabolic diseases. We are advancing KO-7246 through IND-enabling development toward initial clinical evaluation.”
The next major step will be to determine whether the β-cell regeneration and sustained glucose control observed in preclinical models can be reproduced in humans. Caspian is advancing KO-7246 through IND-enabling studies ahead of potential initial clinical evaluation.
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