JERUSALEM, March 08, 2024 (GLOBE NEWSWIRE) — Entera Bio Ltd. (NASDAQ: ENTX), (“Entera” or the “Company”) a leader in the development of orally delivered peptides, today reported financial results and key business updates for the fourth quarter and year ended December 31, 2023.

“2023 was an inflection point for Entera, with consistent validation of our disruptive N–Tab™ oral peptide technology platform and the unveiling of our goal to advance five potential first–in–class oral peptide programs, Phase 1 through Phase 3, into the clinic by the end of 2025. Each of these programs has been carefully selected to align with our platform and our mission to develop treatments that stand to become the number one choice for patients requiring peptide therapies, in a simple and convenient tablet format. Each of these programs is expected to have important catalysts during 2024. Following our December 2023 financing, we expect to have sufficient cash to fund operations through the first half of 2025,” said Miranda Toledano, CEO of Entera.

EB613: First Oral PTH(1–34) Daily Osteoanabolic Tablets for Osteoporosis

• In March 2023, a Type D meeting between Entera and the U.S. Food and Drug Administration (FDA) re–affirmed that a placebo–controlled phase 3 study design with Bone Mineral Density (BMD) and not fracture as primary endpoint could support a New Drug Application for EB613

• In November 2023, Entera echoed the American Society for Bone and Mineral Research (ASBMR) announcement that the Strategy to Advance BMD as a Regulatory Endpoint (SABRE) team had submitted its final qualification plan to the FDA

• At the Annual ASBMR Meeting in October 2023, Entera presented the differentiated pharmacokinetic profile of EB613, versus Forteo® PTH(1–34) 20 µg which requires a daily subcutaneous injection. EB613 consistently shows an increased Cmax and shorter duration of systemic exposure versus Forteo®. Furthermore, EB613’s brief “pulsatile” action appears to simultaneously stimulate both a dual bone formation and a mild anti–resorptive effect, as compared to Forteo®

• During the fourth quarter of 2023, Entera submitted its Phase 2 manuscript for potential publication in a major medical journal related to its phase 2, 6–month, 161–patient, placebo–controlled study in post–menopausal women with low bone mass and osteoporosis which met primary and secondary endpoints

“We expect an update on the qualification process of SABRE and BMD as the surrogate endpoint for fracture in 2024. We view this as the final de–risking event from a regulatory standpoint to move EB613 to Phase 3. We believe EB613 stands as the first program to potentially avail itself of the landmark SABRE initiative which is also the first biomarker to potentially be approved as part of the 2016 21st Century Cures Act. As the first potential oral tablet osteoanabolic treatment, EB613 holds the potential to address the treatment chasm in this severe, potentially lethal disease which remains significantly undertreated despite efficacious injectable treatments. Fracture rates continue to rise globally, and we have not seen any new drugs approved for osteoporosis since 2019 due to the ethical concerns and the costs of fracture endpoint studies. Our discussions with key clinicians and patient advocacy groups and other key stakeholders in this ecosystem indicate that an oral anabolic treatment is absolutely warranted and a potential ‘game changer’ for the estimated 200 million women with osteoporosis globally. We continue to hold strategic discussions related to EB613 and look forward to initiating our pivotal phase 3 study once the final qualification of the SABRE endpoint is announced by FDA,” said Miranda Toledano, CEO of Entera.

EB612: First Oral PTH(1–34) Peptide Replacement Therapy Tablets for Hypoparathyroidism
EB612, is being developed as the first oral PTH(1–34) peptide replacement treatment for hypoparathyroidism. Entera is currently evaluating its hypoparathyroidism program with an improved formulation of EB612 using the naked PTH(1–34) peptide and new intellectual property, tailored to optimize its PK profile and the potential for reduced daily dosing. Entera is also combining its N–Tab™ platform with an alternative PTH receptor agonist in a third party collaboration. Entera expects to submit data from the Phase 1 of its next generation EB612 program using the naked PTH(1–34) peptide in the first half of 2024.

First GLP–2 Peptide Tablets for Short Bowel Syndrome
Under a collaboration agreement with OPKO Health (“OPKO”), Entera is combining its N–Tab™ technology with a proprietary long–acting GLP–2 peptide for the development of the first potential daily oral GLP–2 for the treatment of short bowel syndrome and other GI disorders such as Crohn’s and Celiac disease for which GLP–2 has relevance. Entera published pre–clinical data in May 2023 demonstrating that its oral peptide delivery platform enables gastric absorption of teduglutide (Gattex®), the only approved GLP–2 treatment, as a convenient potential tablet alternative to daily injections. Pre–IND in vivo PK data for oral GLP–2 using OPKO’s long–acting analogue is expected in the first half of 2024.

First GLP–1/Glucagon Agonist (Oxyntomodulin) Peptide Tablets for Obesity
Under a collaboration agreement with OPKO, Entera is combining its N–Tab™ technology with a proprietary long–acting Oxyntomodulin (OXM) peptide for the development of the first potential daily OXM treatment for obesity and other metabolic diseases. Previously, an injectable pegylated version of this OXM peptide demonstrated significant reductions in weight loss and decreased plasma triglyceride levels with cardioprotective benefits in over 420 patients in phase 2/2B studies. Pre–IND in vivo PK data for oral OXM using OPKO’s long acting, modified analogue is expected in mid–2024.

EB613: First Oral PTH(1–34) Osteoanabolic Tablets to Treat Intense Sport and Military Stress Injuries
Entera is collaborating with leading researchers in orthopedics and sports medicine to contribute its proprietary oral PTH(1–34) tablets for an investigator sponsored Phase 2 Study seeking to treat young women and men athletes that experience stress fractures as a result of intense sports training. More details on this study are expected in the second half of 2024.

Financial Results for the year Ended December 31, 2023

As of December 31, 2023, Entera had cash and cash equivalents of $11.0 million. The Company believes that its existing cash resources will be sufficient to meet its projected operating requirements through the second quarter of 2025, which includes the capital required to fund our ongoing operations, including R&D, the completion of the Phase 1 PK study related to our new generation platform and the GLP–2/OXM collaborative research we are conducting with OPKO.

Research and development expenses for the year ended December 31, 2023 were $4.5 million, as compared to $5.8 million for the year ended December 31, 2022. The decrease of $1.3 million was primarily due to a decrease of $1.5 million in pre–clinical activity and materials costs and a decrease of $0.6 million in employee compensation, including a one–time payment made to a former employee pursuant to the terms of his separation agreement. The decrease was partially offset by an increase of $0.8 million in clinical expenses for our Phase 1 PK study related to our new generation platform and new formulations for EB612.

General and administrative expenses for the year ended December 31, 2023 were $4.4 million, compared to $7.3 million for the year ended December 31, 2022. The decrease of $2.8 million was mainly attributable to a decrease of $1.1 million in employee compensation, including a one–time payment to our former employee pursuant to the terms of his separation agreement, a decrease of $0.8 million as part of a restructuring of professional fees and other advisor expenses, a decrease in Board fees of $0.2 million due to the Board’s forfeiture of their fees for the third and fourth quarters of 2023 and a decrease of $0.7 million in D&O insurance costs.

Operating expenses for year ended December 31, 2023 were $8.9 million, as compared to $13.0 million for the year ended December 31, 2022.

Net loss was $8.9 million, or $0.31 per ordinary share (basic and diluted), for the year ended December 31, 2023, as compared to $13.1 million, or $0.45 per ordinary share (basic and diluted), for the year ended December 31, 2022.

About Entera Bio

Entera is a clinical stage company focused on developing oral peptide or protein replacement therapies for significant unmet medical needs where an oral tablet form holds the potential to transform the standard of care. The Company leverages on a disruptive and proprietary technology platform and its pipeline includes five differentiated, first–in–class oral peptide programs, expected to enter into the clinic (Phase 1 to Phase 3) by 2025. The Company’s most advanced product candidate, EB613 (oral PTH(1–34), teriparatide), is being developed as the first oral, osteoanabolic (bone building) once–daily tablet treatment for post–menopausal women with low BMD and high–risk osteoporosis, with no prior fracture. A placebo controlled, dose ranging Phase 2 study of EB613 tablets (n=161) met primary (PD/bone turnover biomarker) and secondary endpoints (BMD). Entera is preparing to initiate a Phase 3 registrational study for EB613 pursuant to the FDA’s qualification of a quantitative BMD endpoint which is expected to occur in 2024. The EB612 program is being developed as the first oral PTH(1–34) tablet peptide replacement therapy for hypoparathyroidism. Entera is also developing the first oral oxyntomodulin, a dual targeted GLP1/glucagon peptide, in tablet form for the treatment of obesity; and first oral GLP–2 peptide tablet as an injection–free alternative for patients suffering from rare malabsorption conditions such as short bowel syndrome in collaboration with OPKO Health. For more information on Entera Bio, visit www.enterabio.com or follow us on LinkedIn, Twitter, Facebook, Instagram.

Cautionary Statement Regarding Forward–Looking Statements

Various statements in this press release are “forward–looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements (other than statements of historical facts) in this press release regarding our prospects, plans, financial position, business strategy and expected financial and operational results may constitute forward–looking statements. 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 the interpretation of clinical data; results of our clinical trials; the FDA’s interpretation and review of our results from and analysis of our clinical trials; 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; the potential disruption and delay of manufacturing supply chains; loss of available workforce resources, either by Entera or its collaboration and laboratory partners; impacts to research and development or clinical activities that Entera may be contractually obligated to provide; overall regulatory timelines; the size and growth of the potential markets for our product candidates; 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 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 “Cautionary Statements Regarding Forward–Looking Statements,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of Entera’s most recent Annual Report on Form 10–K filed with the SEC, as well as the company’s subsequently filed Quarterly Reports on Form 10–Q and Current Reports on Form 8–K. 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 or implied in such forward–looking statements and estimates will be achieved. Entera cautions investors not to rely on the forward–looking statements Entera makes in this press release. The information in this press release is provided only as of the date of this press release, and Entera undertakes no obligation to update or revise publicly any forward–looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law.

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JERUSALEM, Nov. 14, 2023 (GLOBE NEWSWIRE) — Entera Bio Ltd. (NASDAQ: ENTX), ("Entera" or the "Company"), a leader in the development of orally delivered peptides and small therapeutic proteins, today reported corporate updates and financial results for the third quarter ended September 30th, 2023.

"Today, after over a year of steadfast transformation and execution, Entera stands as a premier oral peptide company. It is our goal to potentially move five high value, first–in–class programs, Phase 1 through Phase 3, into the clinic by the end of 2025."

"Our disruptive and proprietary technology simultaneously inhibits gastrointestinal enzymatic degradation and consistently produces bioavailability of peptides, via a simple tablet format (around 6mm in diameter). Each of our oral peptide programs has been carefully selected based on platform alignment and our mission to successfully develop treatments that stand to become the number one choice for patients. Importantly Entera has sufficient cash on hand to enable key read–outs from our significant pipeline expansion efforts over the coming year," said Miranda Toledano, Chief Executive Officer of Entera.

"With our Phase 3 ready EB613 (oral PTH (1–34) peptide), we aim to transform the lives of osteoporosis patients, starting with the estimated 200 million women globally at–risk of fracture. We are also exploring the potential use of EB613 to accelerate stress fracture healing due to high intensity athletic or military training. Our EB612 program aimed at the development of a once–a–day (oral PTH (1– 34) peptide) replacement therapy for patients suffering from hypoparathyroidism, a disease which also disproportionately afflicts women, is being tested using a new generation of our platform. In September 2023, we announced a transformative collaboration with OPKO Health, Inc. ("OPKO") that expands our oral delivery technology across two additional peptides: GLP–2 for the treatment of short bowel syndrome, and oxyntomodulin, a dual targeted GLP–1 / glucagon agonist, for the treatment of obesity," said Ms. Toledano

"On a separate note, we would like to thank our collaborators, partners, and shareholders around the world for reaching out during the last six weeks since the war in Israel erupted to ensure the safety of our team and loved ones. Entera houses R&D, some manufacturing and key personnel across Israel, alongside our clinical, supply chain, regulatory and other functions in the U.S., UK and the EU. While our entire team at Entera is "safe" and continues to meet goals; we are all deeply affected by the current situation. Entera stands with Israel and its right to protect its diverse population of Jewish, Muslim, Druze and Christian citizens and residents. All of us are united in the protection and preservation of our heterogeneous and democratic country," said Ms. Toledano.

Entera Q3 2023 Updates and Goals for 5 Oral Peptide Programs:

EB613: First Oral PTH (1–34) Daily Osteoanabolic Tablets for Osteoporosis
EB613 (oral PTH (1–34), teriparatide), is being developed as the first oral, osteoanabolic (bone building) once–daily tablet treatment for osteoporosis. Entera is prepared to initiate a pivotal phase 3 study in post–menopausal women with high–risk osteoporosis and no prior fracture. Entera successfully completed a phase 2, 6–month, 161–patient, placebo–controlled study. EB613 produced rapid dose–proportional increases in biochemical markers of bone formation, reductions in markers of bone resorption, and increased lumbar spine, total hip, and femoral neck BMD in postmenopausal women with low mass or osteoporosis and no prior fracture. In October 2022, following a Type C meeting and in March 2023 following a Type D meeting, Entera announced the U.S. Food and Drug Administration's (FDA) concurrence that a 2–year, placebo–controlled phase 3 (registrational) study with Total Hip Bone Mineral Density (BMD) as primary endpoint could support an NDA for EB613. On November 9th, 2023, Entera reported that the American Society for Bone and Mineral Research (ASBMR) announced that the SABRE (Strategy to Advance BMD as a Regulatory Endpoint) project team had submitted to its full qualification plan to FDA for the use of BMD as a surrogate endpoint for fractures in future trials of new anti–osteoporosis drugs. EB613 stands as the first program to potentially avail itself of the ASBMR–SABRE BMD endpoint.

EB613: First Oral PTH (1–34) Osteoanabolic Tablets to Treat Intense Sport and Military Stress Injuries
Entera's ability to consistently deliver its oral PTH (1–34) peptide in a simple mini tablet format with reproduceable, dose dependent pharmacokinetics and rapid biological responses across gender, age, and health status was highlighted as part of two poster sessions at the Annual Society of Bone and Mineral Research (ASBMR) 2023 Annual Meeting held on October 13–16, 2023. This work also builds the foundation for Entera's oral PTH (1–34) tablets to potentially treat diverse patient populations including younger men and women athletes at risk of stress fractures. The Company is working towards a potential Phase 2 study for EB613 in this important indication.

EB612: First Oral PTH (1–34) Peptide Replacement Therapy Tablets for Hypoparathyroidism
EB612, is the first oral formulation of PTH (1–34), as a hormone replacement treatment for hypoparathyroidism. An open–label Phase 2a multicenter Phase 2A study, evaluating the safety, tolerability and PK of EB612 in 19 patients with hypoparathyroidism, achieved its primary and secondary endpoints, including a significant reduction in calcium supplementation (42% reduction from baseline, (p=0.001), a decline of 23% (p=0.0003) in median serum phosphate levels two hours following the first dose that was maintained for the duration of the study, improvement in quality of life score and maintenance of median calcium levels above the lower target level for hypoparathyroidism patients (>7.5 mg/dL) throughout the study. There were no treatment emergent adverse events of hypercalcemia reported and no treatment–emergent serious adverse events. Entera is currently evaluating its hypoparathyroidism program with improved formulations of EB612 based on new intellectual property, tailored to optimize its PK profile and the potential for reduced daily dosing as well as by potentially combining Entera's platform with alternative PTH analogues. Updates from the ongoing PK/PD study are expected by the end of 2023.

First GLP–2 Peptide Tablets for Short Bowel Syndrome
Under our collaboration agreement with OPKO, OPKO will supply its proprietary long–acting GLP–2 peptide to combine with Entera's oral peptide platform for the development of the first potential daily oral GLP–2 for the treatment of short bowel syndrome. Treatment with Glucagon–Like Peptide–2 (GLP–2) analogs has been shown to improve the absorption of nutrients in patients with short bowel syndrome (SBS) and reduce parenteral support requirements. Teduglutide, the only approved GLP–2 analog, requires daily subcutaneous injections. In SBS patients, oral drug delivery is particularly challenging because the site of absorption, the intestine, is short and less functional. Entera published pre–clinical data in May 2023 demonstrating that its oral peptide delivery platform enables gastric absorption of teduglutide, as a convenient potential tablet alternative to daily injections. OPKO and Entera expect to update on the program in the first half of 2024.

First GLP–1/Glucagon Agonist (Oxyntomodulin) Peptide Tablets for Obesity
Oxyntomodulin is a naturally occurring peptide hormone found in the colon, with glucagon–like–peptide 1 (GLP–1) and glucagon dual agonist activity which suppresses appetite and induces weight loss. OPKO has developed several proprietary, modified OXM analogs as potential candidates for treating obesity, including an injectable pegylated peptide which demonstrated significant reductions in weight loss and decreased plasma triglyceride levels with cardioprotective benefits in a 420 patient phase 2 study. Under the collaboration agreement, OPKO will supply certain OXM analogs to combine with Entera's oral peptide platform. OPKO and Entera expect to update on the program in the first half of 2024.

Financial Results for the Three Months Ended September 30, 2023

As of September 30, 2023, Entera had cash and cash equivalents of $7.6 million. The Company expects that its existing cash resources are sufficient to meet its projected operating requirements into the third quarter of 2024, which includes the capital required to fund our ongoing operations, including the completion of the Phase 1 PK study related to our new generation platform and the GLP–2/OXM collaborative research we are conducting with OPKO.

Research and development expenses for the three months ended September 30, 2023 and 2022 were approximately $1.4 million. For the quarter ended September 30, 2023, there was an increase of $0.4 million in clinical expenses for our Phase 1 PK study related to our new generation platform and new formulations for EB612, which was offset by a decrease of $0.3 million materials and production costs and a decrease of $0.1 million in share–based compensation expense.

General and administrative expenses for the three months ended September 30, 2023 were $1.0 million, as compared to $1.5 million for the three months ended September 30, 2022. The decrease of $0.5 million was mainly attributable to a decrease of $0.3 million in professional fees and other consultants and a decrease of $0.2 million in D&O insurance costs.

Operating expenses for the three months ended September 30, 2023 were $2.4 million, as compared to $2.9 million for the three months ended September 30, 2022.

Net loss was $2.4 million, or $0.08 per ordinary share (basic and diluted), for the three months ended September 30, 2023, as compared to $3.1 million, or $0.11 per ordinary share (basic and diluted), for the three months ended September 30, 2022.

About Entera Bio

Entera focuses on significant unmet medical needs where an oral tablet form of a peptide treatment or protein replacement therapy holds the potential to transform the standard of care. The Company's oral PTH (1–34) teriparatide mini tablets have been administered to a total of 240 subjects (153 patients) across Phase 1 and Phase 2 studies, with demonstrated bioavailability and clinical benefit across two distinct diseases. The Company's most advanced product candidate, EB613 (oral PTH (1–34), teriparatide), is being developed as the first oral, osteoanabolic (bone building) once–daily tablet treatment for post–menopausal women with low BMD and high–risk osteoporosis, with no prior fracture. A placebo controlled, dose ranging Phase 2 study of EB613 tablets (n= 161) met primary (PD/bone turnover biomarker) and secondary endpoints (BMD). Entera is preparing to initiate a Phase 3 registrational study for EB613. EB612 is being developed as the first tablet peptide replacement therapy for the treatment of hypoparathyroidism. The Company is currently conducting a phase 1 PK study of novel PTH formulations using its proprietary, next generation oral delivery platform with data expected in the second half of 2023. Entera is also developing oral GLP–2 peptide as an injection–free alternative for patients suffering from short bowel syndrome and other severe intestinal and malabsorption metabolic conditions and oral Oxyntomodulin (GLP1/glucagon) peptide for obesity in collaboration with OPKO Health. For more information on Entera Bio, visit www.enterabio.com

Cautionary Statement Regarding Forward Looking Statements

Various statements in this press release are "forward–looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. All statements (other than statements of historical facts) in this press release regarding our prospects, plans, financial position, business strategy and expected financial and operational results may constitute forward–looking statements. 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 the interpretation of clinical data; results of our clinical trials; the FDA's interpretation and review of our results from and analysis of our clinical trials; 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; the potential disruption and delay of manufacturing supply chains; loss of available workforce resources, either by Entera or its collaboration and laboratory partners; impacts to research and development or clinical activities that Entera may be contractually obligated to provide; overall regulatory timelines; the size and growth of the potential markets for our product candidates; 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 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 "Cautionary Statements Regarding Forward–Looking Statements," "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Entera's most recent Annual Report on Form 10–K filed with the SEC, as well as the company's subsequently filed Quarterly Reports on Form 10–Q and Current Reports on Form 8–K. 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 or implied in such forward–looking statements and estimates will be achieved. Entera cautions investors not to rely on the forward–looking statements Entera makes in this press release. The information in this press release is provided only as of the date of this press release, and Entera undertakes no obligation to update or revise publicly any forward–looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law.

GLOBENEWSWIRE (Distribution ID 8979236)