Entera Bio Submits Streamlined Phase 3 Protocol to Initiate Registrational Program for EB613 in Postmenopausal Women with Osteoporosis

Rhea-AI Summary

Entera Bio (NASDAQ: ENTX) submitted a streamlined Phase 3 protocol, statistical analysis plan and 12-month open-label extension synopsis to the FDA to support an NDA for EB613 (oral teriparatide).

The multinational randomized trial targets 750 postmenopausal women with total hip BMD as the primary endpoint at month 12. Entera plans to use a single-tablet Next-Gen EB613 formulation, expects FDA feedback within 60 days, to start dosing in late 2026 and aims for topline data in H2 2028.

Positive

• Primary endpoint set to total hip BMD at 12 months, shortening assessment window
• Planned 750-patient randomized, double-blind, placebo-controlled Phase 3
• Next-Gen single-tablet EB613 to enter Phase 3, eliminating extra bridging studies
• Topline results expected in H2 2028, ~one year earlier than prior timeline
• Submitted SAP and open-label extension synopsis; FDA feedback anticipated within 60 days

Negative

• NDA will rely on demonstrating total hip BMD increases comparable to Forteo to support approval
• Program still requires multi-year execution: initiation late 2026 and topline in H2 2028

News Market Reaction – ENTX

-2.99%

5 alerts

-2.99% News Effect

-16.8% Trough in 5 hr 35 min

-$2M Valuation Impact

$68M Market Cap

1.5x Rel. Volume

On the day this news was published, ENTX declined 2.99%, reflecting a moderate negative market reaction. Argus tracked a trough of -16.8% from its starting point during tracking. Our momentum scanner triggered 5 alerts that day, indicating moderate trading interest and price volatility. This price movement removed approximately $2M from the company's valuation, bringing the market cap to $68M at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Phase 3 enrollment: 750 women Primary endpoint timing: 12 months Prior endpoint timing: 24 months +5 more

8 metrics

Phase 3 enrollment 750 women Multinational randomized double-blind placebo-controlled EB613 osteoporosis trial

Primary endpoint timing 12 months Total hip BMD primary endpoint assessment in Phase 3

Prior endpoint timing 24 months Earlier development assumptions for primary endpoint assessment

Fracture risk reduction 60%–80% relative reduction Vertebral fracture risk associated with Forteo at 12 months

Phase 2 duration 6 months Placebo-controlled EB613 Phase 2 study showing hip BMD increases

FDA feedback window 60 days Expected timing for FDA response to clinical amendment

Extension study duration 12–24 months Open-label extension randomizing to EB613 or anti-resorptive agent

Topline timing Second half of 2028 Anticipated Phase 3 EB613 topline results, about one year earlier than prior plans

Market Reality Check

Price: $1.30 Vol: Volume 74,873 is below th...

low vol

$1.30 Last Close

Volume Volume 74,873 is below the 20-day average of 186,585, suggesting a subdued pre-news tape. low

Technical Shares at $1.34 are trading below the $1.98 200-day moving average and 58.39% under the 52-week high.

Peers on Argus

ENTX was down 2.19% while several biotech peers like CRVO (+6.98%) and OVID (+5....

2 Up

ENTX was down 2.19% while several biotech peers like CRVO (+6.98%) and OVID (+5.59%) moved higher, pointing to a stock-specific setup rather than a coordinated sector move.

Common Catalyst Both ENTX and peer CRVO issued clinical trial–related updates, suggesting a shared focus on development milestones rather than a broad biotech rotation.

Previous Clinical trial Reports

5 past events · Latest: Oct 23 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Oct 23	Phase 2 BMD data	Positive	-7.0%	Post-hoc Phase 2 EB613 data showing significant 6-month BMD gains in subgroups.
Aug 28	Conference data plans	Positive	-1.0%	Planned presentations of EB613 and other oral peptide data at major 2025 conferences.
Feb 19	Clinical abstracts accepted	Positive	-3.0%	EB613 Phase 2 results and 3D-DXA analysis accepted for major osteoporosis congress.
Jun 03	EB612 Phase 1 data	Positive	+2.2%	Promising Phase 1 EB612 hypoparathyroidism data with systemic exposure and PD effects.
Apr 08	Phase 2 publication	Positive	-1.8%	Publication of EB613 Phase 2 trial data in a leading bone research journal.

Pattern Detected

Clinical trial news for Entera has often been followed by negative price reactions despite generally positive clinical narratives.

Recent Company History

Over the past two years, Entera has repeatedly highlighted EB613 and EB612 clinical progress. Events such as positive EB613 Phase 2 BMD data on Oct 23, 2025 and multiple conference presentations in 2025 framed EB613 as a first-in-class oral anabolic therapy. Yet four of five tagged clinical updates saw negative 24-hour moves, averaging -2.11%. Today’s streamlined Phase 3 protocol for EB613 and earlier topline timing extend that same development storyline while confronting a history of muted or negative trading responses to clinical news.

Historical Comparison

-2.1% avg move · In the past 24 months, ENTX released 5 clinical trial updates with an average -2.11% move. Today’s E...

clinical trial

-2.1%

Average Historical Move clinical trial

In the past 24 months, ENTX released 5 clinical trial updates with an average -2.11% move. Today’s EB613 Phase 3 protocol news fits a pattern where constructive clinical developments have not consistently translated into positive next-day performance.

The clinical news flow shows progression from Phase 2 EB613 data and conference showcases toward a streamlined registrational Phase 3 design and timing for EB613, alongside Phase 1 work on EB612 for hypoparathyroidism.

Market Pulse Summary

This announcement advances EB613 into a streamlined Phase 3 program with a 12-month total hip BMD pr...

Analysis

This announcement advances EB613 into a streamlined Phase 3 program with a 12-month total hip BMD primary endpoint, enrollment of 750 postmenopausal women, and a final single-tablet formulation. It also outlines a 12–24 month open-label extension and anticipates topline data in the second half of 2028. In context of prior EB613 and EB612 updates, investors may watch FDA feedback within 60 days and enrollment progress as key execution checkpoints.

Key Terms

bmd, investigational new drug (ind) 505(b)(2), teriparatide, randomized, double-blind, placebo-controlled, +4 more

8 terms

bmd medical

"total hip BMD primary endpoint assessed at 12 months, rather than at 24 months"

Bone mineral density (BMD) is a medical measure of how much mineral — mainly calcium — is packed into a specific volume of bone, often reported as a number from a scan. Investors care because changes in BMD are common primary endpoints for drugs and devices treating osteoporosis and bone disorders; stronger effects on BMD can signal higher chances of regulatory approval, broader market use, and bigger revenue potential. Think of it as a method for checking how solid a building’s concrete is.

investigational new drug (ind) 505(b)(2) regulatory

"to the Company’s Investigational New Drug (IND) 505(b)(2) submission, to evaluate EB613"

An investigational new drug (IND) is the application that lets a company test a drug in people under regulatory oversight. A 505(b)(2) is a specific approval path that lets developers rely partly on existing safety or effectiveness data—like renovating a house using existing blueprints instead of building from scratch—so development can be faster and less costly. For investors, this can mean lower development risk, shorter timelines to market, and potentially quicker revenue if approvals succeed.

teriparatide medical

"EB613 (Oral PTH(1-34), teriparatide). Entera anticipates FDA feedback"

A man-made version of a naturally occurring hormone that stimulates new bone growth, teriparatide is prescribed to treat severe osteoporosis by encouraging the body to build stronger bone rather than just slowing bone loss. Investors track teriparatide because regulatory approvals, patent status, clinical trial results, pricing and insurance coverage directly affect drug sales, company valuations and the competitive landscape in the large market for fracture-prevention therapies.

randomized, double-blind, placebo-controlled medical

"multinational, randomized, double-blind, placebo-controlled safety and efficacy study"

A "randomized, double-blind, placebo-controlled" process is a method used to test the effectiveness of a new treatment or intervention. Participants are randomly assigned to different groups, with one receiving the real treatment and the other a fake version, called a placebo. Neither the participants nor the researchers know who is receiving which, which helps ensure unbiased results. For investors, this rigorous approach increases confidence that the findings are accurate and not influenced by guesswork or bias.

placebo-controlled medical

"EB613 achieved comparable increases in total hip BMD in its placebo-controlled 6-month"

"Placebo-controlled" describes a testing method where one group receives the actual treatment or intervention, while another group receives a harmless, inactive version called a placebo. This approach helps determine whether the real treatment has genuine effects beyond psychological expectations. For investors, understanding this ensures confidence that reported benefits are real and not influenced by bias or false perceptions.

open-label extension medical

"a clinical amendment providing a streamlined Phase 3 protocol, statistical analysis plan (SAP), and open-label extension synopsis"

An open-label extension is a continuation of a clinical trial where all participants and researchers know which treatment is being given, often after an initial blinded phase. It allows further study of a drug's long-term safety and effectiveness. For investors, it can indicate ongoing interest and confidence in a product's potential, influencing perceptions of its future value.

nda regulatory

"submitted in support of the NDA. Importantly, Entera plans to advance the final"

An NDA, or nondisclosure agreement, is a legal contract that keeps certain information private between parties. It’s like a promise not to share sensitive details, helping protect business ideas, strategies, or data from being leaked or used without permission. For investors, NDAs help ensure that confidential information remains secure, enabling trust and open communication during business discussions.

statistical analysis plan (sap) technical

"providing a streamlined Phase 3 protocol, statistical analysis plan (SAP), and open-label"

A statistical analysis plan (SAP) is a detailed blueprint that spells out, before results are seen, exactly how data from a study or trial will be checked, measured and compared. Investors care because a clear SAP reduces the chance of surprise or biased interpretation, making study results more reliable for judging a product’s safety, effectiveness or market potential—like reading a recipe before judging the cake it produces.

AI-generated analysis. Not financial advice.

Phase 3 study designed with total hip BMD primary endpoint assessed at 12 months, rather than at 24 months

EB613 single tablet final commercial formulation (Next-Gen EB613) replaces multi-tablet EB613 as Phase 3 candidate, following successful bridging study

Topline data anticipated in the second half of 2028, approximately one year earlier than previously expected; Entera commits to a 12-month extension study to run in parallel with potential NDA review

TEL AVIV, March 04, 2026 (GLOBE NEWSWIRE) -- Entera Bio Ltd. (NASDAQ: ENTX) ("Entera" or the "Company"), a leader in the development of oral peptide and protein replacement therapies, today announced the submission to the U.S. Food and Drug Administration (FDA) of a clinical amendment providing a streamlined Phase 3 protocol, statistical analysis plan (SAP), and open-label extension synopsis to the Company’s Investigational New Drug (IND) 505(b)(2) submission, to evaluate EB613 (Oral PTH(1-34), teriparatide). Entera anticipates FDA feedback within 60 days.

EB613 is the first oral anabolic (bone forming) tablet treatment in Phase 3 development for the treatment of osteoporosis. The FDA submission relies on the combination of Entera’s oral peptide platform, N-Tab^®, the Listed Drug (LD) Forteo^® (teriparatide SC injection, Eli Lilly), which has been in clinical use for over 20 years with a well-established benefit-risk profile, prior FDA alignment and recent landmark regulatory recognition of total hip BMD as an acceptable primary endpoint for fracture. Entera is seeking the same indications as Forteo^®.

The planned Phase 3 trial will consist of a multinational, randomized, double-blind, placebo-controlled safety and efficacy study in 750 women with postmenopausal osteoporosis to evaluate the percentage change in total hip BMD from baseline to month 12 (rather than month 24) as the primary outcome measure. The required target enrolment for this study is significantly lower than previous development assumptions, substantially streamlining trial execution while accelerating the potential path to approval. The study is powered to demonstrate increases in total hip BMD, which are comparable with reported outcomes for Forteo^® at 12 months, which is associated with a 60% to 80% relative reduction in vertebral fracture risk. EB613 achieved comparable increases in total hip BMD in its placebo-controlled 6-month Phase 2 study, as those reported for Forteo^® at 6-months.  The 12-month phase 3 study and the scientific bridge to Forteo^® are planned to be submitted in support of the NDA.

Importantly, Entera plans to advance the final single tablet formulation of EB613 (Next-Gen EB613) directly into the Phase 3, replacing the previous multi-tablet candidate. This strategic advancement positions the Company to pursue approval and commercialization of a simplified once-daily oral anabolic therapy without the need for future bridging development between formulations.

The Company expects to initiate the Phase 3 study in late 2026, with topline results anticipated in the second half of 2028 - approximately one year earlier than previously expected.

Additionally, Entera also submitted to the FDA a protocol synopsis for a 12-month open-label extension study in which participants would be randomized to EB613 through 12 or 24 months of treatment or transition to a standard of care anti-resorptive agent. The extension study is expected to run in parallel with the NDA review.

“This submission marks a pivotal inflection point for Entera and potentially enables us to get EB613 to patients faster,” said Miranda Toledano, Chief Executive Officer of Entera. “Our goal with EB613 is to democratize anabolic treatment and enable millions of women and men to protect their bones earlier and potentially deter the catastrophic consequences of fracture. In a silent and asymptomatic disease, access and ease of administration matters.”
                                           

About EB613
Substantial evidence supports the efficacy of anabolic therapies over bisphosphonates for lowering fracture risk in osteoporosis patients at high risk. However, all available anabolic therapies are administered by subcutaneous (SC) injection and used in a minority of eligible patients. Entera’s EB613 program (oral PTH (1-34), teriparatide), is being developed as the first oral, once-daily anabolic tablet treatment for osteoporosis. EB613 completed a phase 2, 6-month, 161-patient, placebo-controlled study that met all biomarker and BMD endpoints without significant safety concerns in women with postmenopausal osteoporosis or low BMD (JBMR 2024). 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. The effects of EB613 on trabecular and cortical bone using 3D-DXA showed increases with EB613 compared with placebo in a variety of indices, including integral volumetric BMD and trabecular volumetric BMD, cortical thickness, and cortical surface BMD. Mechanistically, the findings suggest that bone strengthening, and fracture resistance may occur rapidly with EB613. Furthermore, the data are consistent with those of published subcutaneous teriparatide at the 6-month time point.

About Osteoporosis
Osteoporosis is a chronic, progressive disorder in which bone resorption exceeds formation, resulting in decreased bone strength and increased susceptibility to fracture. Osteoporosis is a major and growing public health issue, responsible for over 2 million fractures annually in the US. After age 50, one in three women and one in five men will suffer an osteoporosis-related fracture in their remaining lifetime. Osteoporotic fractures lead to chronic pain, decreased quality of life, increased disability, and contribute to premature death. Studies show that up to 20-24% of hip fracture patients die within one year of the fracture. The total medical cost of osteoporotic fractures is projected to increase from $57 billion in 2018 to $95 billion by 2040, largely due to the aging population.  Postmenopausal women are at higher risk of developing osteoporosis-related fractures, particularly in the hip, spine, and wrist. The mechanism for low BMD in postmenopausal women is primary estrogen deficiency, which leads to accelerated bone loss, especially in the first 5-10 years after menopause. Forteo® (Eli Lilly) was first approved by FDA in 2002 for the treatment of postmenopausal women with osteoporosis and subsequently for treatment of men with primary or hypogonadal osteoporosis at high risk for fracture, and for osteoporosis associated with sustained systemic glucocorticoid therapy.

About Entera Bio
Entera is a clinical stage company focused on developing oral peptide and 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 a disruptive and proprietary technology platform (N-Tab^®) and its pipeline of first-in-class oral peptide programs. The Company’s most advanced product candidate, EB613 (oral PTH(1-34)), is being developed as the first oral, osteoanabolic (bone building) once-daily tablet for osteoporosis. 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 also developing the first oral Long Acting PTH(1-34) tablet as a replacement therapy for patients with hypoparathyroidism (EB612), the first oral oxyntomodulin, a dual targeted GLP1/glucagon peptide tablet for the treatment of obesity and metabolic syndromes; and the first oral GLP-2 tablet as an injection-free alternative for patients suffering from rare malabsorption conditions such as short bowel syndrome in collaboration with OPKO Health, Inc. For more information on Entera Bio, visit www.enterabio.com or follow us on LinkedIn, Twitter, and Facebook.

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 ability to establish and maintain development and commercialization collaborations; Entera's operation as a development stage company with limited operating history; Entera's competitive position with respect to other products on the market or in development for the treatment of osteoporosis, hypoparathyroidism, short bowel syndrome, obesity, metabolic conditions and other disease categories it pursues; 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 Statement 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 Entera'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.

Company Contact:
IR@enterabio.com

FAQ

What Phase 3 design did Entera Bio (ENTX) submit to the FDA for EB613 on March 4, 2026?

Entera submitted a multinational, randomized, double-blind, placebo-controlled Phase 3 in 750 women. According to the company, the trial uses total hip BMD at 12 months as the primary endpoint and includes an open-label extension synopsis.

When does Entera Bio (ENTX) expect to start the EB613 Phase 3 study and report topline data?

Entera expects to initiate the Phase 3 in late 2026 and report topline results in H2 2028. According to the company, this timing is roughly one year earlier than prior expectations.

What formulation of EB613 will be used in the Phase 3 submitted by Entera Bio (ENTX)?

Entera plans to advance the single-tablet Next-Gen EB613 directly into Phase 3, replacing the prior multi-tablet candidate. According to the company, this avoids additional bridging development between formulations.

What primary endpoint will Entera Bio (ENTX) use to support an NDA for EB613?

The submitted protocol uses percentage change in total hip BMD from baseline to month 12 as the primary outcome. According to the company, total hip BMD has regulatory recognition as an acceptable primary endpoint for fracture.

How many patients will the EB613 Phase 3 study enroll under Entera Bio's (ENTX) submission?

The planned Phase 3 is sized for 750 postmenopausal women. According to the company, this target enrolment is significantly lower than earlier assumptions, streamlining trial execution.

What is the purpose of the 12-month open-label extension submitted by Entera Bio (ENTX)?

The extension randomizes participants to EB613 through 12 or 24 months or transition to an anti-resorptive agent. According to the company, the study is expected to run in parallel with potential NDA review.