Entera Bio Ltd Announces Completion of Enrollment In Phase 2 Clinical Trial of Eb613 In Osteoporosis

"' Company Expects to Report Interim 3 Month Biomarker Data for All Enrolled Patients in Q1:21 with Final Bone Mineral Density, or BMD, Data Expected in Q2:21 "'

"' Results Expected Are Expected to Inform the Design of Potential Global Phase 3 Clinical Trial "'

BOSTON and JERUSALEM, Israel, Nov. 09, 2020 (GLOBE NEWSWIRE) — Entera Bio Ltd. (NASDAQ: ENTX), a leader in the development of orally delivered large molecule therapeutics, announced the completion of enrollment in the ongoing Phase 2 clinical trial of EB613. EB613 is an orally delivered human parathyroid hormone (1–34), or PTH, positioned as the first potential oral bone building product to treat osteoporosis patients.

The Phase 2 clinical trial of EB613 is a dose–ranging, placebo–controlled study in postmenopausal female subjects with osteoporosis, or low bone mineral density (BMD), and is being conducted at four leading medical centers in Israel. The trial was initially designed with three treatment groups including doses of 0.5mg, 1.0mg and 1.5mg. In July 2020, the Company amended the Phase 2 protocol based on a review of the 3–month interim biochemical marker and safety data from the first 80 subjects randomized. The two lower doses (0.5 mg and 1.0 mg) of EB613 were discontinued and a 2.5 mg dose of EB613 was added. The initial target enrollment was 160 subjects, with final enrollment of 161 subjects.

In August 2020, the Company announced 6–month interim biomarker and BMD data from the first 50%, or 80 patients, enrolled in this trial. The data indicated EB613 has a meaningful and positive impact on lumbar spine BMD in a dose dependent manner. EB613 generated a mean placebo adjusted increase in lumbar spine BMD of 2.15% (p = 0.08) for the 14 patients in the 1.5 mg treatment arm, as compared to the 16 patients in the placebo arm. The placebo–adjusted increase was comprised of a mean BMD increase of 1.44% in the 1.5 mg treatment arm compared to a mean decrease of 0.71% in the placebo arm. An additional analysis of BMD changes in all EB613 treatment groups showed a significant dose–dependent trend in the percentage change in lumbar spine BMD.

"There is a clear and compelling need for an oral PTH treatment that builds bone in patients with osteoporosis and we look forward to reporting the full topline results from this trial in the second quarter of 2021," stated Roger Garceau, MD, Director and Interim CEO of Entera. "We are excited that we were able to complete enrollment given the extraordinary challenges related to the COVID–19 pandemic. I would like to thank the patients for their participation and the sites and investigators for their efforts to both enroll and follow–up with the patients in the trial."

Entera expects to report efficacy results for the EB613 Phase 2 clinical trial including the full 3–month biomarker data in the first quarter of 2021, and the efficacy and safety results for the full trial in the second quarter of 2021. As of September 30, 2020, the Company had cash and cash equivalents of $7.1 million and believes its current cash position will be sufficient to fund its operations into the second quarter of 2021.

About EB613

EB613 is an orally delivered human parathyroid hormone (1–34), or PTH, program positioned as the first potential oral bone building product to treat osteoporosis patients. Teriparatide for injection (marketed under the brand name Forteo ) was approved by the U.S. in 2002 for the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture and is taken daily via a subcutaneous injection. Entera Bio completed enrollment of a 6–month phase 2 study in postmenopausal women evaluating the effects of a range of oral EB613 doses (and placebo) on bone mineral density, or BMD, of the spine and proximal femur (hip), and anticipates reporting top–line BMD efficacy and safety results for the trial in the second quarter of 2021.

About Osteoporosis

Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, which leads to greater fragility and an increase in fracture risk. Osteoporosis is also a silent disease, often displaying no signs or symptoms until a fracture occurs, leaving the majority of patients undiagnosed and untreated, representing a high unmet medical need. The debilitating effects of osteoporosis have substantial costs and osteoporotic fractures create a significant healthcare burden. An estimated two million osteoporotic fractures occur annually in the United States, and this number is projected to grow to three million by 2025. The National Osteoporosis Foundation (NOF) has estimated that eight million women already have osteoporosis, and another approximately 44 million may have low bone mass placing them at increased risk for osteoporosis. In US women 55 years of age and older, the hospitalization burden of osteoporotic fractures and population facility–related hospital cost is greater than that of myocardial infarction, stroke, or breast cancer.

About Entera Bio Ltd.

Entera is a leader in the development of orally delivered large molecule therapeutics for use in areas with significant unmet medical need where adoption of injectable therapies is limited due to cost, convenience and compliance challenges for patients. The Company's proprietary, oral drug delivery technology is designed to address the technical challenges of poor absorption, high variability, and the inability to deliver large molecules to the targeted location in the body through the use of a synthetic absorption enhancer to facilitate the absorption of large molecules, and protease inhibitors to prevent enzymatic degradation and support delivery to targeted tissues. The Company's most advanced product candidates, EB613 for the treatment of osteoporosis and EB612 for the treatment of hypoparathyroidism are in Phase 2 clinical development. Entera also licenses its technology to biopharmaceutical companies for use with their proprietary compounds and, to date, has established a collaboration with Amgen Inc. For more information on Entera Bio, visit www.enterabio.com.

ForwardLooking Statements

Various statements in this release are "forward–looking statements" under the securities laws. Words such as, but not limited to, "anticipate," "believe," "can," "could," "expect," "estimate," "design," "goal," "intend," "may," "might," "objective," "plan," "predict," "project," "target," "likely," "should," "will," and "would," or the negative of these terms and similar expressions or words, identify forward–looking statements. Forward–looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Forward–looking statements should not be read as a guarantee of future performance or results and may not be accurate indications of when such performance or results will be achieved.

Important factors that could cause actual results to differ materially from those reflected in Entera's forward–looking statements include, among others: changes in our interpretation of the interim data from the ongoing Phase 2 clinical trial of EB613, the timing of data readouts from the ongoing Phase 2 clinical trial of EB613, unexpected changes in our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates; a possible suspension of the Phase 2 clinical trial of EB613 for clinical or data–related reasons; the impact of COVID–19 on Entera's business operations including the ability to collect the necessary data from the Phase 2 trial of EB613; the potential disruption and delay of manufacturing supply chains, loss of available workforce resources, either by Entera or its collaboration and laboratory partners, due to travel restrictions, lay–offs or forced closures or repurposing of hospital facilities; impacts to research and development or clinical activities that Entera is contractually obligated to provide, such as pursuant to Entera's agreement with Amgen; overall regulatory timelines, if the FDA or other authorities are closed for prolonged periods, choose to allocate resources to review of COVID–19 related drugs or believe that the amount of Phase 2 clinical data collected are insufficient to initiate a Phase 3 trial, or a meaningful deterioration of the current political, legal and regulatory situation in Israel or the United States; the availability, quality and timing of the data from the Phase 2 clinical trial of EB613 in osteoporosis patients; the ability find a dose that demonstrates the comparability of EB613 to FORTEO in the ongoing Phase 2 clinical trial of EB613; the size and growth of the potential market for EB613 and Entera's other product candidates including any possible expansion of the market if an orally delivered option is available in addition to an injectable formulation; the scope, progress and costs of developing Entera's product candidates; Entera's reliance on third parties to conduct its clinical trials; Entera's expectations regarding licensing, business transactions and strategic collaborations; Entera's operation as a development stage company with limited operating history; Entera's ability to continue as a going concern absent access to sources of liquidity; Entera's expectations regarding its expenses, revenue, cash resources, including the amount of cash and cash equivalents as of September 30, 2020 referenced above, which has not been audited or reviewed by Entera's independent registered public accounting firm and should be viewed in the context of all other available information regarding Entera's results of operations, liquidity and financial condition; Entera's ability to raise additional capital; Entera's interpretation of FDA feedback and guidance and how such guidance may impact its clinical development plans; Entera's ability to obtain and maintain regulatory approval for any of its product candidates; Entera's ability to comply with Nasdaq's minimum listing standards and other matters related to compliance with the requirements of being a public company in the United States; Entera's intellectual property position and its ability to protect its intellectual property; and other factors that are described in the "Special Note Regarding Forward–Looking Statements," "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Entera's annual and current filings which are on file with the SEC and available free of charge on the SEC's website at http://www.sec.gov. Additional factors may be set forth in those sections of Entera's Quarterly Report on Form 6–K for the quarter ended September 30, 2020, to be filed with the SEC in the fourth quarter of 2020. In addition to the risks described above and in Entera's annual report on Form 20–F and current reports on Form 6–K and other filings with the SEC, other unknown or unpredictable factors also could affect Entera's results. There can be no assurance that the actual results or developments anticipated by Entera will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Entera. Therefore, no assurance can be given that the outcomes stated in such forward–looking statements and estimates will be achieved.

All written and verbal forward–looking statements attributable to Entera or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Entera cautions investors not to rely too heavily on the forward–looking statements Entera makes or that are made on its behalf. The information in this release is provided only as of the date of this release, and Entera undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward–looking statements, whether as a result of new information, future events or otherwise.

Q&A: How Desert Dust Storms Supply Vital Nutrients to the Oceans

A dust story in El Fasher, North Darfur. This is a natural weather phenomenon in Darfur which occurs regularly between March and July every year. It affects all aspects of daily life in the region, including airline flights. Scientists say these storms have a range of affects that are not clearly understood. Courtesy: CC By 2.0/ Mohamad Almahady, UNAMID.

A dust story in El Fasher, North Darfur. This is a natural weather phenomenon in Darfur which occurs regularly between March and July every year. It affects all aspects of daily life in the region, including airline flights. Scientists say these storms have a range of affects that are not clearly understood. Courtesy: CC By 2.0/ Mohamad Almahady, UNAMID.

By Samira Sadeque

When sand and dust storms (SDS) rage in the Sahara Desert, more than 10,000 km away in the Caribbean Sea the very same storms have a range of effects on the 1,360 species of shorefish that populate the waters there.

According to a report released last week by the United Nations Environment Programme (UNEP), each year about half a billion tonnes of nutrients, minerals, and organic inorganic matter is transferred to the oceans through SDS.

But as Dr. Nick Middleton, a fellow in physical geography at St Anne’s College at the University of Oxford and author of the UNEP report titled “Impacts of Sand and Dust Storms on Oceans”, told IPS, “our understanding of how dust affects marine waters is far from complete”. 

Though he added that the upcoming U.N. Decade of Ocean Science for Sustainable Development will be an exciting opportunity to help scientists gain a better understanding of issues such as how much dust from SDS reaches the oceans. In his interview, Middleton said that this decade is an important time to consider the ways in which SDS affect issues such as biodiversity, the climate, and food systems.

“The U.N. Decade offers exciting opportunities to improve our understanding of some of these basic issues. Nobody lives permanently in the open oceans, so historically we have had to rely on scientists on ships to take measurements when and where they are able.

“Hence, the data we have on dust in the atmosphere and deposited over the oceans is patchy and sporadic at best. The use of geostationary satellites is improving our capacity to monitor dust, but there is no substitute for taking real samples at sea,” Middleton told IPS.

And as Jian Lu, Director of the Science Division at UNEP, said in the report: “Desert dust is a principal driver of oceanic primary productivity, which forms the base of the marine food web and fuels the global carbon cycle.” 

“One of the clear messages from this report is the simple fact that many aspects of the impacts of SDS on the oceans are only partially understood,” Lu said. “Despite the limited knowledge, the impacts of SDS on oceans—their ecosystem functions, goods and services—are potentially numerous and wide-ranging, thus warranting continued careful monitoring and research.”

“Many scientists predict that as our climate warms dust storms will become more frequent in certain parts of the world where the climate becomes drier and soils will be protected by less vegetation,” Middleton added. “More dust in these places will inevitably have complex feedback effects on climate and what happens in the oceans.”

Excerpts of the interview below.

Inter Press Service (IPS): Jian Liu said in the report the impacts of sand and dust storms on the oceans are only partially understood. What are some under-reported issues about the impact of sand and dust storms on oceans?

Dr Nick Middleton (NM): One aspect that needs more accurate assessment is the amount of desert dust transported to the world’s oceans each year. When they occur, we can see great plumes of dust above the oceans on satellite imagery, but we only have a rough idea of how much dust is involved. We estimate that anything between one billion and five billion tonnes of desert dust are emitted into the atmosphere by SDS every year on average. Two billion tonnes is the current best estimate, and 25 percent of that reaches the oceans, with all sorts of effects on marine ecosystems. However, most of these estimates come from computer models which are imperfect at simulating all the numerous processes involved in lifting, transporting and depositing dust to the sea.

We know that desert dust delivers some vital nutrients to the oceans, but our understanding of how dust affects marine waters is far from complete. For instance, dust probably has an impact on the energy balance in several oceans, affecting the circulation of heat and salt. These circulation regimes have implications for marine life, but our understanding of the details is hazy at best.

IPS: The U.N.  Decade of Ocean Science for Sustainable Development (2021–2030) is scheduled to start in 2021. What are some issues that you believe should be addressed during this time?

NM: The U.N. Decade could initiate a great leap forward in our understanding if it presided over the establishment of a network of study sites across different oceans to take long-term measurements of dust in the atmosphere and as it is deposited on the ocean surface. Buoys can be used as platforms for autonomous sampling of dust and other weather variables, and their data transmitted to researchers.

Long-term datasets are vitally important, but they cannot replace experiments conducted from ships at sea. The U.N. Decade can also promote coordinated experiments involving both atmospheric and marine measurements to address some of the processes in which desert dust is important. One such role is how iron and phosphorus carried with desert dust helps to fertilise large areas of ocean surface, and may also impact local climate.

IPS: The report establishes a link between desert dust and coral reef systems; it also suggests a potential link between disease arising from microorganisms and a decline in coral reefs worldwide. What kind of impact do sand and dust storms have on biological diversity overall, and on human life?

NM: Dust raised in SDS and transported to the oceans helps to sustain the biodiversity of large marine areas. One of the most direct effects is the incorporation of tiny dust particles into coral skeletons as they grow. Nutrients carried on desert dust particles also fuel the growth of marine microorganisms such as phytoplankton, which form the base of the marine food web.

Human society relies on fish and other products from the sea, but the fertilising effect of desert dust is also thought to have an impact on algal blooms, some of which are detrimental to economic activity and human health. Certain harmful algal blooms contain species that produce strong toxins which become concentrated up the food chain, becoming harmful to people who eat contaminated seafood.

IPS: Dust has significant impacts on weather and climate in several ways. In what ways are sand and dust storms linked to issues such as climate change? 

NM: Dust in the atmosphere affects the energy balance of the Earth system because these fine particles scatter, absorb and re-emit radiation in the atmosphere. Dust particles also serve as nuclei on which water vapour condenses, helping to form clouds, and the chemical composition of dust affects the acidity of rainfall. Dust from the Sahara is regularly transported through the atmosphere over the tropical North Atlantic Ocean where it can have a cooling effect on sea surface temperatures. In turn, the cooler sea surface changes wind fields and the development of hurricanes. A year with more Saharan dust usually translates into fewer hurricanes over the North Atlantic.

Future trends in desert dust emissions are uncertain. They will depend on changes in atmospheric circulation and precipitation – how much falls, when and where.

IPS: Are there ways in which sand and dust storms have an impact (direct or indirect) on the coronavirus pandemic? 

NM: Links between sand and dust storms and the coronavirus pandemic are quite possible, but inevitably work on such potential links at an early stage. We know that SDS are a risk factor for a range of respiratory and cardiovascular diseases, so someone exposed to both COVID-19 and air pollution from dust storms may experience particularly harmful effects. For instance, one recent study in Northern Italy established an association between higher mortality rates due to COVID-19 and peaks of atmospheric concentrations of small particulate matter. Saharan dust frequently contributes to poor air quality in Italy, but a direct causal link between desert dust and suffering from COVID-19 has not been established to date. There are numerous other factors to take into account.

We also know that many SDS source areas contribute many types of microorganisms (such as fungi, bacteria and viruses) to desert dust, and that these microorganisms are very resilient. SDS can also transport viruses over great distances (greater than 1,000 km), sometimes between continents. Long-range transport of desert dust has been linked to some historical dispersal/outbreak events of several diseases, including Avian influenza outbreaks in areas downwind of Asian dust storms.