A Double-blind, Placebo-controlled, Randomised, Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KBP-089 in Patients With Type II Diabetes

KeyBioscience is developing KBP-089, a dual activator of both the amylin and calcitonin receptors, for the treatment of type II diabetes mellitus, using a subcutaneous injectable mode of administration.
This is a double-blind, placebo-controlled, randomised, multiple-ascending dose phase I trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of KBP-089 in patients with type 2 diabetes, who are on stable therapy with metformin.
Subjects will receive daily subcutaneous injections in the abdomen over a period of 28 days. The planned maximum doses of KBP-089 to be investigated in the trial are 20 µg in cohort 1, 60 µg in cohort 2, and 150 µg in cohort 3. For cohort 1, the dose is planned to be escalated every 7 ±1 days, and for cohort 2 and cohort 3, every 3 days. Doses may be modified according to individual tolerability, but the dose regimen will not exceed 28 days.
The IMP is administered by daily subcutaneous injections taken in the morning before breakfast.
The trial is performed in Germany and at least 36 patients will be enrolled in the trial. The trial will be randomised 1:1:1 between maximum doses of KBP-089 of 20 µg, 60 µg, 150 µg and placebo. Within each of the three cohorts, 12 patients will be randomised 3:1 to KBP-089 and placebo.

开始日期2018-04-17

申办/合作机构

KeyBioscience AG

[+3]

NL-OMON43278 / CompletedN/A

A Randomised, Double-blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of KBP-089 in Healthy Adult Male Volunteers - FIH study of KBP-089

开始日期2016-10-21

申办/合作机构

KeyBioscience AG

100 项与 DACRA-089 相关的临床结果

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100 项与 DACRA-089 相关的转化医学

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100 项与 DACRA-089 相关的专利（医药）

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项与 DACRA-089 相关的文献（医药）

2021-12-01·BMC Endocrine Disorders4区 · 医学

The dual amylin and calcitonin receptor agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile

4区 · 医学

ArticleOA

作者: Henriksen, Kim ; Larsen, Anna Thorsø ; Karsdal, Morten Asser ; Gydesen, Sofie ; Sonne, Nina

AbstractBackgroundWeight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest.MethodsIn this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats.ResultsIncreasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 μg/kg/day) and 7% (at 400 μg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon.ConclusionDACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.

2017-11-01·American Journal of Physiology-Endocrinology and Metabolism2区 · 医学

Optimization of tolerability and efficacy of the novel dual amylin and calcitonin receptor agonist KBP-089 through dose escalation and combination with a GLP-1 analog

2区 · 医学

Article

作者: Karsdal, Morten Asser ; Gydesen, Sofie ; Henriksen, Kim ; Hjuler, Sara Toftegaard ; Hellgren, Lars I. ; Andreassen, Kim Vietz

Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study we investigated how to optimize tolerability while maintaining efficacy of a novel, highly potent dual amylin and calcitonin receptor agonist (DACRA), KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in high-fat diet (HFD)-fed rats. KBP-089 potently activated both the amylin and calcitonin receptors in vitro and demonstrated a prolonged receptor activation as well as a potent reduction of acute food intake. HFD rats dosed every day or every second day obtained equal weight loss at study end, albeit with an uneven reduction in both food intake and body weight in rats dosed every second day. In a 4-fold dose escalation, KBP-089 induced a transient reduction in food intake at every escalation step, with reducing magnitude over time, and the following treatment with 2.5, 10, and 40 µg/kg resulted in an ~15% vehicle-corrected weight loss, a corresponding reduction in adipose tissue (AT), and, in all treatment groups, improved oral glucose tolerance ( P < 0.01). Twofold and linear escalations suppressed body weight evenly with no significant reduction in food intake at either escalation step. KBP-089 (1.25 µg/kg) and liraglutide (50 µg/kg) reduced 24-h food intake by 29% and 37% compared with vehicle, respectively; however, when they were combined, 24-h food intake was reduced by 87%. Chronically, KBP-089 (1.25 µg/kg) and liraglutide (50 µg/kg) lowered body weight 8% and 2% in HFD rats, respectively, whereas the combination resulted in a 12% body weight reduction. Moreover, the combination improved glucose tolerance ( P < 0.05). In conclusion, DACRAs act complementarily with GLP-1 on food intake and body weight. Furthermore, on escalation, KBP-089 was well tolerated and induced and sustained a significant weight loss and a reduction in AT in lean and HFD rats, underscoring the potential of KBP-089 as an anti-obesity agent.

项与 DACRA-089 相关的新闻（医药）

2024-10-10

·EndPoints

Eli Lilly inks another obesity pact, doubling down on small Swiss partner

Eli Lilly is returning to KeyBioscience, a nimble Swiss biotech, seven years after originally linking arms with the startup to work on dual amylin calcitonin receptor agonists for obesity and other conditions. The world’s largest drugmaker by market capitalization will pay up to $1.4 billion to keep working with KeyBioscience on the potential new class of treatments also known as DACRAs. The companies didn’t say how much money was involved in the upfront payment. The tie-up includes an asset that is slated to enter Phase 2 testing by year’s end in people with obesity and osteoarthritis, the companies said Thursday morning. KeyBioscience said it will run the trial, which will include 600 people and look for both body weight reductions and changes in OA pain. Already one of the two GLP-1 leaders in the obesity drug landscape, Lilly continues to place further bets on other mechanisms of action and areas of research. It’s forged obesity pacts applying insights from the “ dark genome ,” the hibernation of the 13-lined squirrel and other areas. Beyond its hallmark tirzepatide franchise, the drugmaker has at least five other experimental medicines in late-stage or Phase 2 testing for obesity. If KeyBioscience follows through with its projected timeline, it could expand Lilly’s obesity pipeline to half a dozen drugs in mid- or late-stage trials by the end of 2024. KeyBioscience’s researchers think the dual agonists can help tamp down on body weight, control glucose levels and improve insulin action. Lilly already has an amylin receptor agonist known as eloralintide in Phase 2 for obesity. The Lugano, Switzerland-based biotech, which is a subsidiary of Danish drug developer Nordic Bioscience, had originally teamed with Lilly in 2017 for $55 million upfront. That pact included DACRAs known as KBP-042, KBP-089 and KBP-056. Lilly removed a Phase 2 of KBP-042/DACRA-042 for type 2 diabetes from its pipeline in the fourth quarter of 2018. Meanwhile, a study of KBP-089 for type 2 diabetes was terminated in 2020. On its website, KeyBioscience says in December 2019 it “reevaluated” its approach, which led to the “abandonment of once-daily injectable DACRAs” and switched to long-acting formulations that could be administered once a week. That pivot led to KBP-336, according to the biotech’s website. The drug entered human studies in the fall of 2021. A Phase 1b was completed in the spring of 2023. It wasn’t immediately clear if KBP-336 is the soon-to-be Phase 2 asset that KeyBioscience highlighted in Thursday’s press release. Editor’s note: This story was updated to include more details on the status of KBP-042 and KBP-089.

临床2期临床1期

100 项与 DACRA-089 相关的药物交易

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