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Sublin B.V. developing a first-in-class sublingual insulin-delivery formulation

Oss, January 30th, 2020 - Sublin B.V., established in 2017 in the Netherlands. Currently sublin is a late-stage preclinical phase, backed by a round A(+) investment in 2019 and a tranche of Series B1 in 2021. Sublin aims to provide diabetic patients a disruptive alternative to their multiple and daily insulin injections by developing a sublingual insulin modality (SLIM), and other sublingual antidiabetic drug formulations that are currently are only active via injection. SLIM is based on a novel formulation technology with fast-acting and long-acting insulin release properties. This completes the development route of insulin delivery modalities from injectable, dating back to the 1920’s, towards sublingual delivery now [1-5].

Sublin’s SLIM technology is intended to address the following:

  • SLIM aims to fill a large unmet gap in the antidiabetics insulin market
  • SLIM demonstrates high oral bioavailability in hyperglycemic models
  • SLIM is in late-stage preclinical development
  • Sublin BV secured Series A investments and a Series B1 tranche

The prevalence of diabetes mellitus is rising at pandemic rates, currently affecting approximately 9% of the global adult population. Back in the year 2000, over 171 million diabetics were recorded, which will rise to an estimated 585 million patients by 2035[6,7]. The International Diabetes Federation estimates that diabetes mellitus kills 5 million people each year, shedding only a light on the high co-morbidities rates and associated healthcare burden. Regarding the latter, the United States spent around $727 billion on diabetes-related healthcare costs. As an effect, the diabetes pharmaceutical intervention market indicates a CAGR of over 7.9% and a staggering insulin market CAGR of 16.9% [6,7].

​Diabetes type-I, and insulin-dependent type-II diabetes can only be treated by insulin[8–10]. At present, the diabetes market is flushed with drugs that reduce the effect and progression of early diabetes. These drugs, being e.g. inhibitors of DDP-4, SGLT2, α-glucosidase or activators of PPARγ, AMPK or GLP-1, for many patients all have one common dominator; they only aid temporarily, not being able to prevent progression into insulin-dependency after some years [11–15]. Innovations in modalities of insulin administration are largely found in injection-based devices, like pumps, patch pumps, microneedle patches and others that are being regarded as somewhat more beneficial than syringes, but as such do not circumvent the fact that insulin needs to be injected [5]. This is due to the properties of insulin, making it too large and polar to pass biological layers to reach the circulation, and oral intake results in full digestion of the protein, rendering it completely inactive.

For these reasons Sublin BV focusses resiliently on the development of orally and sublingually available insulins. Though developing orally available insulin is a daunting task, it is regarded as the “holy grail” in the area of insulin delivery. The benefits are multifold; a higher patient compliance, a lower social adversity against insulin application, no injection site adversity, and no injection phobia which poses a difficulty in part of the patient population. In addition, the potential to transport and store insulin in dried form, contrasting current cold-chain dependent insulin solutions, makes the drug product very favorable and inexpensive to transport and store for longer periods.

The SLIM formulation development is exclusively utilizing approved compounds with secured safety profiles, high insulin compatibility and a straightforward production process that is easily scalable. SLIM is moving forward towards the clinical testing within a year. Validated in vitro studies has led Sublin’s researchers to a promising formulation technology. In the preclinical efficacy testing, both rapid-acting release and long-acting release SLIM formulations lowered the blood glucose in diabetes-induced hyperglycemic study models upon sublingual application with appropriate dose-response kinetics, indicating a promising bioavailability and suitability as insulin delivery modality. Currently, Sublin B.V. is finalizing its preclinical development stage and is now moving forward towards clinical studies.

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