Entera Bio Ltd.

Short bowel syndrome (SBS) is a rare and potentially life-threatening disease wherein patients are at risk of malnutrition and weight loss because of the malabsorption of essential nutrients and fluids by the small intestine. Currently, Takeda's Gattex® (#teduglutide), is the only approved GLP-2 therapy for the treatment of SBS. However, its administration as a daily subcutaneous injections are expensive and cumbersome for patients. Entera was the first to publish pre-clinical data for their oral #GLP2 peptide tablet showing significant systemic exposure, with plasma concentrations being 10x higher than that shown with subcutaneous injection #gattex®.

There is an ongoing global obesity epidemic. The economic impact of overweight and #obesity was estimated to be 2.4% of GDP in 2020, and is estimated to increase to $4.32 trillion by 2035, nearly 3% of GPD. The estimates for global levels of high #BMI suggest that nearly 3.3 billion adults may be affected by 2035, compared with 2.2 billion in 2020. This reflects an increase from 42% of adults in 2020 to over 54% by 2035. Source: World Obesity Federation Entera and partner Opko are developing an #oxyntomodulin (OXM) analogue, a naturally occurring peptide hormone found in the colon with #GLP1 and #glucagon dual agonist activity to suppress #appetite and induce #weightloss. Stimulating both of the receptors has the potential to regulate both food intake and blood glucose.

Oral delivery of therapeutic proteins is challenging due to the enzymatic degradation within the gastrointestinal tract and poor absorption into the blood stream due to the protein’s polarity and molecular weight. Entera leverages the proprietary N-Tab™ oral delivery technology, which is designed to simultaneously stabilize the peptide in the gastrointestinal tract and promote its absorption into the bloodstream. Read more about Entera's technology platform: https://lnkd.in/dJ-jh_rk

The Biomarkers Consortium’s Bone Quality Project includes partners from NIH, FDA, industry, and academia. The Project has compiled a unique database from >50 randomized trials of #Osteoporosis medications, containing data on >170,000 individual patient to apply newer techniques as potential biomarkers for bone strength. Ultimately, the goal of the Project is to seek formal FDA qualification of its surrogate endpoint biomarkers, so that it can be utilized in future clinical studies as well as in clinical practice to address osteoporosis. Entera's pending Phase 3 study for the EB613 program has been designed to meet this surrogate endpoint, making Entera one of the first programs to potentially leverage the Project's initiative. https://lnkd.in/g3XSDiz8

Entera is developing EB612 as an oral PTH replacement therapy for #hypoparathyroidism. Phase 1 PD highlights: -Increases in calcium (+3.9%), 1,25(OH)2 - Vitamin D (+73.2%) and decreases in phosphate (-20.8%) -Decreased endogenous serum PTH(1-84) -43.0% on average from baseline On safety measures, there were no TEAE of hypercalcemia reported and no serious TEAEs. The only drug-related AE was mild headache, reported in 2/15 patients. No significant findings were observed in blood and urine lab tests. All vitals were within the normal range. Data suggests that a BID (2x/day) oral administration of our unmodified PTH(1-34) peptide may provide a viable alternative for patients with #hypopara who require a peptide replacement therapy for life and are intolerant, adverse or cannot access a daily injectable product. Phase 1 poster presented at #ENDO24 here: https://lnkd.in/dMaqaFCg

Entera reported Phase 1 data of first-in-class, oral PTH(1-34) peptide EB612 for patients with #hypoparathyroidism at the Endocrine Society ENDO 2024 Annual Meeting #ENDO2024 Data reported include PK/PD and safety results from twice-a-day oral tablet EB612. #hypopara https://lnkd.in/dH9rMa89

June 1st marks World Hypoparathyroidism Awareness Day, a time to raise awareness and provide information and support on the disease. Hypoparathyroidism is a rare disease that results from the dysregulated production of parathyroid hormone. This impacts calcium levels which are correlated to healthy bone strength and development. One of the many symptoms of #hypopara is fatigue. Entera is developing the first oral PTH(1-34) peptide replacement treatment for #hypoparathyroidism

In adults with increased fracture risk, GLP-1 #semaglutide once weekly did not increase bone formation based on bone marker P-PINP. This study does not support the notion that #GLP1 may have osteoanabolic (bone building) effects in individuals without type 2 diabetes. Assessment of secondary outcomes showed that bone resorption (P-CTX) actually increased in the semaglutide group compared with the placebo group. Increased bone resorption is a natural process that occurs when bone mineral is removed at a faster rate than it can be replaced. This can lead to a decrease in bone mass, which can weaken the skeletal structure and increase the risk of fractures. In addition, the semaglutide arm had reduced bone mass in the spine and hips, and tibial cortical thickness were lower, compared with the placebo group. Study published in eClinical Medicine, part of The Lancet Discovery Science: https://lnkd.in/d5RKKsep

PTH (1-34) (teriparatide) is a peptide with the first 34 amino acids of human PTH (1-84). The effects of PTH on bone depends on the duration of exposure. Brief pulses (30-60min) of high concentrations stimulate bone formation. Mechanism of FDA approved drug for #osteoporosis Forteo® suggests that longer PTH pulses may stimulate both bone formation and bone resorption. However, continuous infusions of PTH stimulate bone resorption without bone formation.   Entera’s EB613 consistently shows an increased Cmax and shorter duration of systemic exposure optimizing the #anabolic (bone building) effect.