What changed in this filing

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Item 1. Business

2026-03-27 compared with 2025-03-28 · 192 added, 167 removed, 546 unchanged (40% of the section changed)

Entera is a clinical stage company focused on developing first-in-class oral tablet formats of peptides or protein replacement therapies.

We focus on underserved, chronic medical conditions for which oral administration of a protein therapy has the potential to significantly shift a treatment paradigm.

Our pipeline includes five differentiated, first-in-class oral peptide programs targeting PTH(1-34), GLP-1 and GLP-2:

We concentrate on underserved, chronic medical conditions for which oral administration of a protein therapy has the potential to significantly shift a treatment paradigm.

Our pipeline includes differentiated, first-in-class oral peptides targeting PTH(1-34), GLP-1/Glucagon and GLP-2:

Currently, most protein therapies are administered via frequent intravenous, subcutaneous or intramuscular injections.

In chronic diseases where patients require persistent management, these cumbersome, often painful and high-priced injections can create a major treatment gap.

From a technical standpoint, 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.

We leverage our N-Tab™ platform, which is designed to simultaneously stabilize the peptide in the gastrointestinal tract and promote its absorption into the bloodstream.

From a technical standpoint, oral delivery of peptides and therapeutic proteins is challenging due to the enzymatic degradation within the gastrointestinal tract and poor absorption into the blood stream.

We leverage our N-Tab ® platform, which is designed to simultaneously stabilize large (4kD+) hydrophilic peptides in the gastrointestinal tract and promote their absorption into the bloodstream.

EB613 Program

Our most advanced product candidate, EB613, oral PTH(1-34), is being developed as the first oral, osteoanabolic (bone building) once-daily tablet treatment for post-menopausal women with low bone mineral density (“BMD”) and high-risk osteoporosis.

Anabolic drugs are indicated for the treatment of very high-risk osteoporosis patients as first line therapy and as second line treatment in osteoporosis patients who cannot tolerate or progress on other osteoporosis drugs.

Despite the superior efficacy of anabolic drugs, existing treatments require daily or monthly subcutaneous injections and are used in a minority of very high-risk patients.

EB613 is intended to provide an oral anabolic treatment earlier in an osteoporosis patient’s journey to increase skeletal mass, reduce the risk of fracture and consequently limit the progression of the disease, and its associated disability and mortality.

A placebo controlled, dose ranging Phase 2 study of EB613 tablets (n= 161) met primary (pharmacodynamic/bone turnover biomarker) and secondary endpoints (BMD).

The highest EB613 oral PTH tablet dose (2.5 mg), produced an increase in markers of bone formation while simultaneously decreasing the markers of bone breakdown.

Significant gains in bone mineral density of the spine and hip were observed at the end of the 6-month study and there were no significant safety concerns.

In April 2024, the phase 2 data was published in the Journal of Bone and Mineral Research (JBMR).

Our most advanced product candidate, EB613 (oral teriparatide, or oral PTH[1-34]), is being developed as the first oral, osteoanabolic (bone building) tablet treatment for osteoporosis.

EB613 is being developed under a 505(b)(2) application to the listed drug, Forteo® (teriparatide SC injection, Eli Lilly), which was first approved by the FDA in 2002 for the treatment of postmenopausal women with osteoporosis at high risk of fracture and later indicated for men with osteoporosis and osteoporosis associated with sustained systemic glucocorticoid therapy.

Forteo® has been in clinical use for over 20 years with a well-established benefit-risk profile.

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 two million fractures annually in the United States.

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 bone mineral density (“BMD”) in postmenopausal women is primary estrogen deficiency, which leads to accelerated bone loss, especially in the first five to ten years after menopause.

The three approved anabolic drugs, including Forteo®, are indicated for the treatment of very high-risk osteoporosis patients as first line therapy and as second line treatment in osteoporosis patients who cannot tolerate or progress on other osteoporosis drugs.

Despite the superior efficacy of anabolic drugs, existing treatments require daily or monthly subcutaneous injections and are estimated to be used in a minority of very high-risk patients.

EB613 is intended to provide an oral anabolic treatment earlier in an osteoporosis patient’s journey to increase skeletal mass, reduce the risk of fracture, limit the disease progression, and decrease disability and mortality.

Our mission with EB613 is to democratize anabolic treatment and enable wider access to both patients and healthcare practitioners.

We have completed a comprehensive nonclinical and clinical package for the EB613 program, including three Phase 1 comparative studies with Forteo® and three Phase 2 clinical studies.

EB613 has been safely administered to a total of 270 study participants, including postmenopausal women with low BMD or osteoporosis (n=118 on EB613, n=43 on placebo), healthy volunteers, and male and female patients with hypoparathyroidism.

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.

In April 2024, Phase 2 data was published in the Journal of Bone and Mineral Research (JBMR).

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.

At 6 months of treatment, EB613 2.5mg produced comparable total hip BMD increases as those that have been reported for Forteo® at 6 months.

In September and April 2025, the effects of EB613 on trabecular and cortical bone indices based on a 3D-Shaper DXA post-hoc analysis of Phase 2 results were presented at the American Society for Bone and Mineral Research (“ASBMR”) 2025 Annual Meeting and at the 2025 World Congress on Osteoporosis (WCO-IOF-ESCEO), respectively.

The data using 3D-DXA modelling showed evidence of an early effect on both trabecular and cortical bone of the proximal femur.

Mechanistically, the findings suggest that bone strengthening and fracture resistance may occur rapidly with EB613.

In October 2025, we reported clinical data from a post-hoc analysis of our Phase 2 trial of EB613 at the 2025 North American Menopause Society (NAMS) Annual Meeting in a poster presentation titled “EB613 (Oral PTH[1-34] Tablets) Increases BMD Over Six Months in Early Postmenopausal Women with Low Bone Mass or Osteoporosis:

A Phase 2 Randomized Trial (P-66)”.

In this analysis of the Phase 2 data, EB613 produced significant and consistent gains in BMD at the spine, femoral neck and hip in women within 10 years of menopause and in women more than 10 years post-menopause.

Since 2023, we have advanced a simplified formulation of EB613 that builds on clinical experience with the multi-tablet formulation which was used in Phase 1 and Phase 2 clinical studies.

At the ASBMR Annual Meeting in September 2025, preclinical data for EB613 single tablet formulation from a cross-over pharmacokinetic mini-pig study was presented.

This pre-clinical data showed comparable PK to the multiple tablet formulation of EB613.

The preliminary results from the ongoing Phase 1b PK study (ENT-11-2023) demonstrate PK comparability between the multiple tablet formulation and the simplified single-tablet formulation of EB613 and Forteo®.

Regulatory Background

Initial approvals of drugs for the treatment of osteoporosis have required a placebo-controlled trial demonstrating reduction in the risk of fractures as the primary outcome measure in women with postmenopausal osteoporosis.

Initial approvals of drugs for the treatment of osteoporosis have historically required a placebo-controlled trial demonstrating reduction in the risk of fractures as the primary outcome measure in women with postmenopausal osteoporosis.

The regulatory requirement for using fracture as the primary efficacy endpoint is challenging due to the patient types who would need to be studied:

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In the United States, the Foundation for the National Institute of Health-American Society for Bone and Mineral Research-Study to Advance BMD as a Regulatory Endpoint (FNIH-ASBMR-SABRE, previously known as the FNIH-Bone Quality Project [FNIH-BQP], hereinafter “SABRE”) was launched in 2013.

This initiative was established as a public-private partnership with the Federal Drug Administration (FDA) to study whether change in BMD at the lumbar spine, total hip or femoral neck in a placebo-controlled trial of an osteoporosis drug was predictive of vertebral, nonvertebral, hip and all clinical fracture risk reduction.

This initiative was established as a public-private partnership with the FDA to study whether change in BMD at the lumbar spine, total hip or femoral neck in a placebo-controlled trial of an osteoporosis drug was predictive of vertebral, nonvertebral, hip and all clinical fracture risk reduction.

SABRE aims to change the framework for how clinical trials of new anti-osteoporosis drugs are conducted and to promote innovation in the field of osteoporosis.

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Based on a meta-regression analysis to assess the relationship between change in total hip BMD (active-placebo) and the anti-fracture effect in randomized clinical trials for each fracture type, the SABRE group demonstrated that treatment-related change in total hip BMD is best associated with fracture reduction.

Following Type C and Type D meetings with the FDA in March 2023, we announced the FDA’s concurrence that a 2-year, placebo-controlled phase 3 (registrational) study with Total Hip BMD as primary endpoint could support a new drug application (“NDA”) for EB613;

Since the end of our Phase 2 Meeting in December 2021, we have engaged in FDA Type C, D, and A Meetings in 2022, 2023, 2024, and 2025 to obtain clarity and alignment on total hip BMD as a primary endpoint and an appropriate data package to support a new drug application (“NDA”) for EB613 under a 505(b)(2) application.

Following Type C and Type D meetings with the FDA in March 2023, we announced the FDA’s concurrence that a 2-year, placebo-controlled phase 3 (registrational) study with total hip BMD as primary endpoint could support an NDA for EB613;

however the SABRE BMD endpoint remained unqualified as a surrogate endpoint by FDA at that time.

In November 2023, the ASBMR announced that the SABRE project team had submitted its full qualification plan to the FDA for the use of BMD as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs.

In March 2024, the ASBMR announced that the FDA had communicated to the SABRE project team that a ruling to qualify the treatment-related change in bone mineral density (BMD) as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs would be provided within 10 months.

The EB613 osteoporosis clinical program has been developed under the auspices of this new approach to osteoporosis drug development.

We believe EB613 stands as the first program to potentially avail itself of the ASBMR-SABRE BMD endpoint.

SABRE is expected to provide an update on its FDA interactions and the qualification of the BMD endpoint in 2025.

EB612 Program

On the same day, we announced that we planned to continue our dialogue with the FDA and await the final qualification of the SABRE qualification and FDA’s guidance on the statistical evaluation of our BMD endpoint before initiating a Phase 3 study for EB613.

In March 2024, the ASBMR announced that the FDA had communicated to the SABRE project team that a ruling to qualify the treatment-related change in BMD as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs would be provided within 10 months.

In June 2025, as part of our scientific bridging, we received a written concurrence from the FDA that comprehensive nonclinical developmental and reproductive toxicity (DART) studies are not required given the totality of evidence generated from Forteo®, published literature, and EB613 nonclinical studies.

In May 2025, we received a written concurrence from the FDA that dedicated oral carcinogenicity studies are not warranted for EB613 given the totality of evidence generated from the literature and nonclinical studies conducted with EB613.

In July 2025, we announced that, in a written response to a Type A meeting request, the FDA agreed that an NDA filing for EB613 could be supported by a phase 3 study in women with postmenopausal osteoporosis, where change in total hip BMD is evaluated as the primary endpoint, and incidence of new or worsening vertebral fractures is evaluated as the key secondary endpoint at 24 months.

In December 2025, the FDA released the Determination for Qualification of BMD qualifying total hip BMD as a surrogate efficacy endpoint for fracture that could be used in future studies of new anti-osteoporosis therapies.

FDA’s suggested a context of use (COU):

“The percentage change from baseline at 24 months in total hip bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) can be used as a validated surrogate endpoint for the assessment of investigational therapies for postmenopausal women with osteoporosis at risk for fracture.”

In February 2026, we submitted to the FDA a clinical amendment that included the EB613 Phase 3 protocol, statistical analysis plan and open-label extension synopsis.

Our planned multinational, randomized, double-blind, placebo-controlled Phase 3 study is expected to enroll approximately 750 postmenopausal women with osteoporosis and will evaluate the percentage change in total hip BMD from baseline to month 12 as the primary endpoint.

The double-blind, placebo-controlled 12-month Phase 3 study and the scientific bridge to the listed drug, Forteo®, are planned to be submitted in support of the NDA.

We also plan to conduct an open label extension study under separate protocol in which participants on EB613 and placebo would be randomized to either EB613 for an additional 12 months, or transition to a standard anti-resorptive drug.

The extension study is expected to provide safety and efficacy data for EB613 at 24 months as a monotherapy and evaluate the sequence of 12 months of EB613 treatment sequenced to a standard anti-resorptive drug for an additional 12 months.

EB612 (PTH) Hypoparathyroidism Program

Our product candidate, EB612, is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for patients with hypoparathyroidism.

With respect to our EB612 program, we are currently testing new generations of our N-Tab™ Technology with the naked PTH(1-34) peptide to assess the effectiveness of once or twice a day dosing regimens, as well as collaborating with a third party on another peptide in this field.

The FDA and the EMA have granted EB612 orphan drug designation for the treatment of hypoparathyroidism.

Hypoparathyroidism is a rare, heterogeneous, endocrine disorder that leads to abnormally low calcium and high phosphorus levels in the blood and requires chronic PTH replacement therapy.

Today, the only approved PTH replacement treatment, YORVIPATH® (developed by Ascendis Pharma), requires patients to administer daily injections, while investigational candidates may require weekly injections.

Entera previously demonstrated proof-of-concept clinical data for its EB612 program using an unmodified oral PTH(1-34) analog in a 16-week Phase 2 study in patients with hypoparathyroidism (JBMR, 2021).

The study showed significant reduction in calcium supplement use and maintenance of serum calcium levels above the lower limit for hypoparathyroidism (>7.5 mg/dL) throughout the study.

However, the trial required a four-times-daily regimen with doses of up to 9mg daily.

In June 2024, Phase 1 clinical data for EB612 was presented at the Endocrine Society ENDO 2024 Annual Meeting.

The data reported from this Phase 1 clinical study include pharmacokinetic (PK), pharmacodynamic (PD) and safety results from the application of a new generation of Entera’s N-Tab™ technology platform and EB612, the active peptide fragment 1-34 of the N-terminal region of human parathyroid hormone (teriparatide) dosed twice a day (BID).

Significant systemic exposure was reported following both administrations of EB612 tablets.

Aside from positive PK measures, sustainable PD effects were reported, including serum levels of calcium (albumin corrected), phosphate, and 1,25(OH)2-Vitamin D (reaching +3.9%, -20.8%, and +73.2% change on average from baseline, respectively) and decreased endogenous serum PTH(1-84) (reaching -43.0% change on average from baseline).

There were no treatment-emergent Adverse Events of hypercalcemia reported.

There were no treatment-emergent Serious AEs.

The only Study Drug-Related AE was mild headache, reported in two out of fifteen subjects.

No significant findings were observed in blood and urine lab tests.

All vital signs were within the normal range.

To date, Entera’s proprietary PTH tablets have been safely administered to a total of 102 healthy subjects in Phase 1 studies and 153 patients in Phase 2 studies in osteoporosis and hypoparathyroidism, two diseases that remain underserved with the current standard of care and which disproportionately affect women.

We believe these product candidates, if approved, hold the potential to become standards of care for patients with osteoporosis and hypoparathyroidism.

Our ability to deliver our oral PTH(1-34) peptide in a simple 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 ASBMR 2023 Annual Meeting.

We believe our work to date has built the foundation for our oral PTH(1-34) tablets to potentially treat diverse patient populations, including younger men and women athletes at risk of stress fractures.

Oral GLP-2 and Oral GLP-1/Glucagon Programs in Collaboration with OPKO Health

In May 2023, the results from our oral glucagon-like-peptide 2 (GLP-2) program were published in the International Journal of Peptide Research and Therapeutics, “Oral Delivery Technology Enabling Gastro-Mucosal Absorption of Glucagon-Like-Peptide-2 Analog (Teduglutide, Gattex®) - A Novel Approach for Injection-Free Treatment of Short Bowel Syndrome.” We believe GLP-2 represents a strong candidate for our N-Tab™ technology and warrants further development as an injection-free alternative to patients suffering from short bowel syndrome and other gastrointestinal disorders where GLP-2 plays a role.

In September 2023, we entered into a research collaboration agreement (the “2023 Collaboration Agreement”) with OPKO Biologics, Inc., a subsidiary of OPKO Health, Inc.

Under the terms of this agreement, OPKO has agreed to supply its proprietary long-acting GLP-2 peptide and certain Oxyntomodulin (OXM) analogs for the development of oral tablet candidates using our proprietary N-Tab™ technology.

In March 2024, we announced positive in vivo pharmacokinetic (PK) results from our collaborative research, combining a proprietary long acting GLP-2 agonist developed by OPKO with Entera’s proprietary N-Tab™ technology.

The program is focused on developing the first GLP-2 peptide tablet alternative for patients suffering from short bowel syndrome and additional disorders involving mucosal inflammation and nutrient malabsorption.

Currently, the only approved GLP-2 agonist, which is marketed under the name Gattex® (teduglutide), requires daily sub-cutaneous injections.

Zealand Pharma and Ironwood are developing long acting GLP-2 therapies requiring once and twice weekly injections.

Entera and OPKO completed a proof of concept (PoC) single dose pharmacokinetic study in rodents.

Oral GLP-2 tablets exhibited significant systemic exposure.

Furthermore, plasma levels achieved with the oral tablet form of the GLP-2 analogue were about 10-fold higher than therapeutic plasma concentrations reported for subcutaneously administered teduglutide (Gattex® label).

The pharmacokinetic analysis of the data obtained following the IV injections of the GLP-2 peptide showed the plasma half-life in rats to be about six times longer than the half-life reported for teduglutide in the same animal model.

This data is consistent with previously reported PK data relating to OPKO’s GLP-2 peptide’s long-acting profile, which had initially been developed as a weekly subcutaneous injection.

Given the challenging compliance rates attributed to injectable GLP-2 therapy and heterogeneity of SBS patients, we believe a daily tablet format may address a significant unmet need in treating and titrating SBS patients more effectively than injectable alternatives.

Oral GLP-1/Glucagon

The safety, pharmacokinetic (PK) and pharmacodynamic (PD) data reported from a Phase 1 clinical study supported twice a day dosing of EB612.

In December 2025, we announced new in vivo PK/PD data supporting the development of a proprietary long-acting PTH (LA-PTH) analog, which is being developed as part of a material transfer and collaboration agreement with OPKO Biologics, Inc., a subsidiary of OPKO Health, Inc.

(“OPKO”), utilizing our N-Tab ® platform.

Preclinical findings demonstrated a markedly prolonged plasma half-life and sustained elevation of serum calcium levels for more than three days following administration of a single oral These data support the development of a once-daily oral PTH tablet for patients with hypoparathyroidism .

Based on these data, in February 2026, we announced the expansion of our collaboration with OPKO to jointly advance this LA-PTH program.

We intend to accelerate pre-IND development of this program and currently expect to submit an IND application to the FDA late 2026.

For additional information regarding our collaboration agreement with OPKO, see Item 7.

Management’s Discussion and Analysis of Financial Condition and Results of Operations—Recent Developments—License and Collaboration Agreement with OPKO, contained in this Annual Report.

EB618 Program (Oral GLP-1/Glucagon)

In September 2023, we entered into a research collaboration agreement (the “2023 Collaboration Agreement”) with OPKO.

Under the terms of this agreement, OPKO agreed to supply its proprietary Oxyntomodulin (OXM) analogs for the development of oral tablet candidates using our proprietary N-Tab ® platform.

Under this agreement, we and OPKO have each agreed to be responsible for specific phases of development of the two oral peptides to the point of demonstrated in vivo feasibility.

OXM is a naturally occurring GLP-1/Glucagon dual agonist peptide hormone found in the small intestine that acts to suppress appetite, induce weight loss and has additional cardioprotective and anti-fibrotic attributes.

The program is focused on developing the first oral dual agonist GLP-1/Glucagon peptide as a potential once-daily tablet treatment for patients with obesity and metabolic disorders using the N-Tab™ platform.

The program focuses on developing the first oral dual agonist GLP-1/Glucagon peptide as a potential once-daily tablet treatment for patients with obesity, metabolic and fibrotic disorders using the N-Tab ® platform.

Currently, there are no approved dual GLP-1/Glucagon agonists available.

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The OXM agonist peptide (OPK-88006) is a GLP-1/Glucagon dual agonist peptide that has been modified to maintain its long-acting profile while increasing its potential potency.

The program combines OPKO’s (OPK-88006) and Entera’s proprietary N-Tab™ technology.

In September 2024, we jointly announced with OPKO topline pharmacokinetic/pharmacodynamic (PK/PD) results for the OXM program.

In September 2024, we and OPKO jointly announced topline PK/PD results for the OXM program.

Oral OXM exhibited significant systemic exposure across two in vivo models, a favorable PK profile and bioavailability.

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Oral OXM showed a statistically significant reduction in plasma glucose levels compared with placebo.

Additionally, in March 2025, we entered into a collaboration and license agreement with OPKO (the “2025 Collaboration Agreement”) with respect to the preclinical and clinical development and decision making related to the Oral OXM program for the treatment of obesity, metabolic and fibrotic disorders in humans.

For additional information, see Item 7.

Management’s Discussion and Analysis of Financial Condition and Results of Operations—Recent Developments—License and Collaboration Agreement with OPKO, contained in this Annual Report.

Given the scarcity of oral peptide treatments and potential safety challenges attributed to small molecule approaches, we believe oral OXM may address a significant number of patients suffering from chronic metabolic diseases

We plan to file an Investigational New Drug application with the FDA later this year.

Our goal is to develop first-in-class oral peptides and protein replacement therapies for underserved, chronic medical conditions for which a tablet treatment has the potential to significantly shift a treatment paradigm.

We are developing our product candidates to potentially become the first oral, daily tablet peptide or protein replacement therapies designed for patients to live injection-free as they actively manage their chronic diseases.

In March 2025, we entered into a collaboration and license agreement (the “2025 Collaboration Agreement”) with OPKO to collaborate with respect to the preclinical and clinical development and decision making related to the Oral OXM program for the treatment of obesity, metabolic and fibrotic disorders in humans (the “Program”).

The Program combines OPKO’s OPK-88006 analog and Entera’s proprietary N-Tab ® platform.

Under the 2025 Collaboration Agreement, we granted to OPKO an exclusive, sublicensable and non-transferable, worldwide license to certain of our intellectual property and technology solely to develop, manufacture, and commercialize any GLP-1/Glucagon dual agonist as an oral treatment form for the treatment of obesity, metabolic, cardiovascular, and fibrotic disorders in humans, and OPKO has granted to us a non-exclusive, non-sublicensable and non-transferable license to certain of its intellectual property and technology to the extent necessary for us to perform our obligations in relation to the Program, in each case subject to certain exceptions.

Under the terms of the 2025 Collaboration Agreement, we and OPKO will retain 40% and 60%, respectively, of all proceeds deriving from the Program and will be responsible for 40% and 60% of the Program’s development costs, respectively.

Following the completion of the Phase 1 stage, we may continue to fund our 40% share of the Program to maintain our right to proceeds or to opt-out (the “Opt-Out”).

If we Opt-Out, then we and OPKO will retain 15% and 85%, respectively, of all proceeds deriving from the Program, while OPKO will be solely responsible for ongoing development and commercialization funding of the Program.

In June 2025, a poster at ENDO2025 reported PK data from a mini-pig study of oral OPK-88006 (EB618), which showed plasma levels consistent with those reported in humans for the highest subcutaneous dose of Wegovy™ (semaglutide) weekly injection, a standard of care for the treatment of obesity.

As of late 2025, OPKO is planning to initiate a single ascending dose (SAD) and multiple ascending dose (MAD) Phase 1 clinical study with the subcutaneous injection formulation of OXM, with data expected by the end of 2026.

We plan to file an IND for the oral OXM tablet formulation thereafter.

This program focuses on developing the first glucagon-like-peptide 2 (GLP-2) peptide tablet alternative for patients suffering from short bowel syndrome (SBS) and additional disorders involving mucosal inflammation and nutrient malabsorption.

SBS is a rare and potentially life-threatening malabsorptive condition caused by a significant loss of functional bowel mass (secondary to congenital defects or disease-associated loss of absorption) or physical bowel mass (secondary to extensive intestinal resection).

Approximately 30,000 patients across the United States and EU are living with SBS.

SBS patients have a reduced ability to absorb nutrients and fluids and are at risk of malnutrition, unintended weight loss and additional symptoms due to the loss of essential vitamins and minerals.

SBS is the most common cause of chronic intestinal failure, accounting for approximately 75% of chronic intestinal failure cases in adults and 50% of such events in children.

Currently, the only approved GLP-2 agonist, which is marketed under the name Gattex® (teduglutide), requires daily sub-cutaneous injections.

Zealand Pharma and Ironwood are developing long-acting GLP-2 therapies requiring once and twice weekly injections.

In May 2023, the results from our oral GLP-2 program were published in the International Journal of Peptide Research and Therapeutics, “Oral Delivery Technology Enabling Gastro-Mucosal Absorption of Glucagon-Like-Peptide-2 Analog (Teduglutide, Gattex®) - A Novel Approach for Injection-Free Treatment of Short Bowel Syndrome.” We believe GLP-2 represents a strong candidate for our N-Tab® platform and warrants further development as an injection-free alternative to patients suffering from SBS and other gastrointestinal disorders where GLP-2 plays a role.

In late 2023, Entera and OPKO completed a proof of concept single dose pharmacokinetic study in rodents.

Oral GLP-2 tablets exhibited significant systemic exposure.

Furthermore, plasma levels achieved with the oral tablet form of the GLP-2 analogue were approximately 10-fold higher than therapeutic plasma concentrations reported for subcutaneously administered teduglutide (Gattex® label).

The pharmacokinetic analysis of the data obtained following the IV injections of the GLP-2 peptide showed the plasma half-life in rats to be approximately six times longer than the half-life reported for teduglutide in the same animal model.

This data is consistent with previously reported PK data relating to OPKO’s GLP-2 peptide’s long-acting profile, which had initially been developed as a weekly subcutaneous injection.

In September 2025, pharmacokinetic data from a mini-pig study of OPK-8801003, our oral GLP-2 analog developed in collaboration with OPKO, were presented at the 47th European Society for Clinical Nutrition & Metabolism (ESPEN) Congress.

The data demonstrated a plasma half-life of approximately 15 hours (approximately 18 time longer than teduglutide), which has a half-life of only 0.85 hours in the same species.

Oral administration achieved peak plasma levels of ~200 ng/mL and maintained systemic exposure (AUC ≈ 2 h•μg/mL) for over 24 hours with low variability, supporting once-daily oral dosing.

Our goal is to develop first-in-class oral peptides and protein replacement therapies for ignored, underserved, chronic medical conditions for which a tablet treatment has the potential to significantly shift a treatment paradigm.

We are developing our product candidates to potentially become the first oral, single daily tablet peptide or protein replacement therapies designed to expand access for patients and healthcare practitioners.

We aspire to continue to validate our platform across a variety of additional high value therapeutic proteins.

Our strategy to achieve these goals includes:

• Advancing EB613, Potentially the First Daily Anabolic PTH(1-34) Tablet Treatment into Phase 3 for the Treatment of Post-Menopausal Women with Low Bone Mass and Osteoporosis :

Our six-month placebo-controlled Phase 2 double-blind, dose-ranging trial of EB613 in 161 patients with low bone mass and osteoporosis met both primary and secondary endpoints was selected for oral presentation at the ASBMR annual conference in 2021 and published at JBMR in March 2024.

Based on the outcomes of our FDA meetings, we believe that EB613 may be the first osteoporosis program to be permitted by FDA to pursue a placebo controlled, BMD endpoint registrational Phase 3 study to support an NDA.

We view this potential outcome as testament to the treatment gap and unmet need for a viable alternative to treat the millions of osteoporosis patients who, despite current guidelines and availability of highly efficacious injectable anabolic agents, remain undertreated.

We are preparing to initiate a Phase 3 registrational study for EB613 pursuant to the FDA’s qualification of a quantitative BMD endpoint, which we currently expect to occur in 2025.

• Advancing the First Daily PTH(1-34) Peptide Replacement Tablet Therapy for the Treatment of Hypoparathyroidism:

• Advancing EB613, Potentially the First Oral Anabolic (Bone Building) Tablet, into Phase 3 for the Treatment of Osteoporosis:

Building on our historical alignment with the FDA in July 2025 and the FDA’s 2025 broad qualification of BMD as a regulatory endpoint for anti-osteoporosis drugs, we submitted a clinical amendment to the FDA in February 2026, providing a streamlined Phase 3 protocol.

We believe that EB613 may be the first osteoporosis program to be permitted by FDA to pursue a placebo controlled, BMD endpoint registrational Phase 3 study in support of an NDA.

We view this potential outcome as a testament to the treatment gap and unmet need for a viable alternative for the millions of osteoporosis patients who, despite current guidelines and availability of highly efficacious injectable anabolic agents, remain undertreated.

Entera currently retains global rights to EB613.

• Advancing Potentially the First Oral LA-PTH Analog as a Once-Daily Tablet for Patients with Hypoparathyroidism as part of our Collaboration with OPKO:

In 2015, we successfully completed a Phase 2a four-month trial in 19 patients with hypoparathyroidism, which demonstrated clinical benefit, including a statistically significant reduction in calcium supplementation, maintenance of calcium levels above the lower target level for Hypoparathyroidism patients (>7.5 mg/dL) throughout the study and statistically significant rapid decline in median serum phosphate levels two hours following the first dose, which was maintained for the duration of the study.

The FDA and the European Medicines Agency (“EMA”) have granted EB612 orphan drug designation for the treatment of hypoparathyroidism.

In addition, we continue to collaborate productively with a third party on the oral tablet development of another PTH replacement treatment for hypoparathyroidism.

• Identifying and Developing Potentially High Value Oral Peptides in Collaboration with Strategic Partners such as our Oral GLP-2 and Oxyntomodulin (Oral GLP-1/Glucagon ) Programs with OPKO:

We intend to leverage our N-Tab™ platform by applying it to the development of additional, currently approved injectable peptides and therapeutic proteins with known mechanisms of action and established safety profiles.

We believe this will allow us to advance our product candidates more efficiently and predictably through the research and clinical development cycle.

For example, in collaboration with OPKO, we are focusing on the development of the first oral OXM, a dual targeted GLP1/glucagon peptide, in tablet form for the treatment of metabolic disorders and the first oral GLP-2 peptide tablet as an injection-free alternative for patients suffering from rare malabsorption conditions, such as short bowel syndrome.

Both these peptides have well characterized pre-clinical PK/PD and toxicology.

In 2025, we were testing the development of a proprietary LA-PTH analog utilizing our N-Tab ® platform and preclinical findings demonstrated a markedly prolonged plasma half-life and sustained elevation of serum calcium levels for more than three days following administration of a single oral.

These data support the development of a once-daily oral PTH tablet for patients with hypoparathyroidism.

We currently expect to submit an IND application to the FDA in late 2026.

We and OPKO each own 50% of the rights related to the LA-PTH hypoparathyroidism EB612 program.

Our development expenses through Phase 1 are expected to be funded from the $8 million in proceeds received as part of OPKO’s equity investment in Entera in 2025.

• Identifying and Developing Additional High Value Oral Peptides in Collaboration with Strategic Partners such as our Oxyntomodulin (Oral GLP-1/Glucagon) and Oral GLP-2 Programs:

We intend to leverage our N-Tab ® platform by applying it to the development of additional, proprietary peptides and therapeutic proteins.

In collaboration with OPKO, we are currently focusing on the development of the first oral OXM, a dual targeted GLP1/glucagon peptide, in tablet form, for the treatment of metabolic disorders and have completed a proof of concept for an oral GLP-2 peptide tablet as an injection-free alternative for patients suffering from rare malabsorption conditions, such as short bowel syndrome.

We and OPKO own 40% and 60%, respectively, of the rights related to the OXM EB618 program.

• Establishing Select Global and Regional Development and Commercial Partnerships :

Our N-Tab™ Technology platform and intellectual property are designed to generate a pipeline of product candidates across various therapeutic indications.

Our N-Tab ® platform and intellectual property are designed to generate a pipeline of product candidates across various therapeutic indications.

We intend to explore opportunities to diversify and shorten the preclinical and clinical development of these candidates in a capital-efficient manner, including selectively pursuing research and clinical development partnerships with biopharmaceutical companies with specific domain expertise as well as with biopharmaceutical companies with proven commercial footprints to de-risk our late-stage programs.

Parathyroid hormone (PTH) is an 84-amino acid hormone that regulates calcium and phosphate homeostasis and bone metabolism in the body.

In healthy individuals, PTH is generally produced at very low basal levels, at a blood concentration of 15 - 25 pg/mL.

On top of the basal PTH levels, there are physiological pulses two to three times per day that result in transient increases in PTH levels reaching up to 65 pg/mL.

The changes in PTH secretion are in response to ionized calcium concentrations in the blood resulting from the entry of calcium from nutrients in the intestine and resorption of calcium from bone.

PTH in Osteoporosis

The effects of PTH on bone depends on the duration of exposure.

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Forteo® requires a daily subcutaneous injection.

First Daily Osteoanabolic Tablet Treatment for the Treatment of Osteoporosis

Potentially the First Oral PTH(1-34) Anabolic Tablet Treatment for Post-Menopausal Women with Osteoporosis

EB613 is the first once daily PTH(1-34, teriparatide) tablet treatment and has the same amino acid sequence as Forteo ® (teriparatide daily subcutaneous injection), a leading anabolic agent which has been marketed for 24 years and achieved peak annual sales of $1.7 billion prior to patent expiration in 2018.

Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, which leads to greater fragility of bones and an increase in fracture risk.

Osteoporosis is a serious condition that can result in pain, permanent disability, loss of independence and often death.

One in three women over age 50 will develop osteoporosis, and one in two women aged 50 and older will develop an osteoporosis-related fracture.

Osteoporosis is most frequently associated with menopause in women, aging in both women and men and glucocorticoid steroid use (greater than three months).

Osteoporosis is a chronic, progressive disorder in which bone resorption exceeds formation, resulting in decreased bone strength and increased susceptibility to fracture.

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 five to ten years after menopause.

The bone remodeling cycle can be separated into two distinct processes:

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and (ii) bone formation, where cells called osteoblasts are responsible for bone matrix synthesis and subsequent mineralization of the bone.

In healthy individuals, bone resorption is matched by new bone formation.

In healthy individuals, bone resorptions matched by new bone formation.

Osteoporosis develops as the balance between bone resorption by osteoclasts and bone formation by osteoblasts is not maintained, and not enough bone tissue is formed, leading to frail and fracture-prone bones.

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women 55 years of age and older, the hospitalization burden, including hospital costs of osteoporotic fractures, is greater than that of myocardial infarction, stroke, or breast cancer.

Furthermore, it estimated that the number of fractures in the United States due to osteoporosis will rise to three million by 2025, resulting in an estimated $25.3 billion in costs each year.

Worldwide, osteoporosis affects an estimated 200 million women, according to the International Osteoporosis Foundation (the “IOF”) and causes more than 8.9 million fractures annually, which is equivalent to an osteoporotic fracture occurring approximately every three seconds.

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and romosozumab (an antibody that inhibits sclerostin and also inhibits bone resorption, Evenity®).

It is estimated that less than 10% of currently treated osteoporosis patients agree to injectable osteoanabolic treatment despite guideline recommendations, their efficacy versus the anti-resorptives and the approval of lower cost generics.

According to surveys with osteoporosis practitioners including primary care, gynecology, endocrinology and rheumatology, we estimate that less than 15% of currently treated osteoporosis patients agree to or have access to injectable osteoanabolic treatment despite guideline recommendations, their efficacy versus the anti-resorptive drugs and the approval of lower cost injectable generics.

There are currently no FDA-approved oral anabolic treatments for osteoporosis.

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Phase 1 Safety, PK and PD Data for Oral PTH(1-34) Tablet Programs

Our Oral PTH(1-34) tablet candidates, including EB613 and EB612, have been administered collectively to a total of 102 healthy subjects in three Phase 1 studies.

In the first two cohorts of a 2023 phase 1 study evaluating the current EB613 formulation, Forteo and new formulations for EB613 and EB612, 30 healthy subjects were administered various doses (PTH(1-34) 1.5 mg – 2.5 mg) and regimens (QD or BID) of oral PTH.

No drug-related severe adverse events (SAEs) were reported, and four subjects reported four mild adverse events (AEs) of nausea (N=1), palpitation (N=1), and headache (N=2).

These AEs are consistent with those reported with injectable PTH analogs.

Across Phase 1 studies, the PK profile of EB613 daily tablets was characterized by a rapid increase in plasma PTH(1-34) levels, with peak concentrations of the drug observed within 30 minutes after dose, and a rapid decline thereafter.

We have completed a comprehensive nonclinical and clinical package for EB613, including three Phase 1 studies and three Phase 2 clinical studies.

In the clinical development program, EB613 has been administered collectively to a total of 270 subjects in Phase 1 (n = 117) and Phase 2 (n = 153) studies.

EB613 was well-tolerated, and no new drug-related adverse events (AEs) were identified in the Phase 1 and Phase 2 studies, at doses of up to 9 mg daily.

Across Phase 1 studies, the PK profile of EB613 has been characterized by a rapid increase in plasma PTH(1-34) levels, with peak concentrations of the drug observed within 30 minutes after dose and a rapid decline thereafter.

The blood half-life of PTH(1-34) in humans is less than five minutes (see Forteo® USPI).

Due to this very short elimination time and a short absorption phase, PTH(1-34) levels decrease below limit of quantitation within two hours after drug administration.

Due to this very short elimination time and a short absorption phase, PTH(1-34) levels decrease below the limit of quantitation within two hours after drug administration.

As a result, no drug accumulation is expected with once daily tablet dosing.

EB613 Phase 2 Study in Post-Menopausal Women with Low Bone Mass and Osteoporosis

The Phase 2 clinical trial of EB613 was a dose-ranging, placebo-controlled, double-blind study in 161 postmenopausal women with osteoporosis or low BMD conducted at four leading medical centers in Israel.

This Phase 2 clinical trial of EB613 was a dose-ranging, placebo-controlled, double-blind study in 161 postmenopausal women with osteoporosis or low BMD conducted at four leading medical centers in Israel.

The trial evaluated 0.5 mg to 2.5 mg daily tablets on BMD, pharmacodynamic bone markers, including P1NP and Osteocalcin-bone formation markers, CTX - a bone resorption marker, and various safety endpoints.

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A statistically significant decrease also occurred in Serum CTX (marker of resorption) from baseline to Month 6 (p<0.01).

The decrease in bone resorption (CTX) resulting from EB613 daily tablets was unanticipated based on historical results from subcutaneously daily injectable PTH, Forteo®;

and indicates a potential dual mechanism of action for EB613 which seems to induce bone formation and decrease bone resorption, with a lower rate of bone turnover.

The decrease in bone resorption (CTX) resulting from EB613 daily tablets indicates a potential dual mechanism of action for EB613 with preferential stimulation of ostoblastic activity over osteoblastic activity.

Bone Mineral Density

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Increases in TH (2.07%) and FN (2.92%) BMD in the 2.5 mg EB613 daily tablet titrated group were greater than those previously reported with Forteo® at six months (0.1% and 0.3%) (Leder, 2015).

The increases in proximal femoral BMD (TH and FN) and cortical bone after six months of EB613 daily tablet treatment were unanticipated given that the reported subcutaneous Forteo® injection increases are typically small and not significant at six months.

The results of the Phase 2 study supported the selection of the 2.5 mg dose with a titration regimen to be used in the proposed pivotal Phase 3 study of EB613.

FDA End of Phase 2 Meetings (EOP2)

After successful completion of the Phase 2 dose ranging study of EB613, we held an end-of-Phase 2 meeting at the end of 2021 with the FDA to discuss various aspects of our nonclinical and clinical development plan.

The meeting focused on the potential use of a 12-month non-inferiority head-to-head study versus Forteo® phase 3 study design to support an NDA under the 505(b)(2) regulatory pathway.

We requested an additional EOP2 meeting with the FDA to seek agreement on the specifications and control of the drug substance, drug product and excipients to support the Phase 3 study and eventual product registration.

The meeting request was granted, and we received a written response from the FDA towards the end of the first quarter of 2022, confirming that the specifications for the drug substance, excipients and drug product appear reasonable and that final determination on the adequacy of the proposed excipients and drug product specification will be made during the NDA review.

The FDA also provided guidance regarding the proposed process scale-up, process qualification approach and stability plan for EB613.

Early in the first quarter of 2022, Entera received additional EOP2 minutes from the FDA, suggesting that a non-inferiority head-to-head study versus Forteo® Phase 3 design may not be favorable to the success of the program and potential approvability of EB613 given EB613’s PK profile, PD (biomarker) profile and BMD outcomes from the phase 2.

The FDA also commented on a possible exploration of a placebo-controlled phase 3 study and a potential Total Hip (TH) BMD endpoint given recently published 24-month Surrogate Threshold Effects (STEs) by the SABRE project team that are considered associated with fracture risk reduction and the SABRE ongoing qualification process with FDA of the BMD endpoint as a surrogate for fracture.

FDA Type C Meeting

In October 2022, we announced the successful conclusion of our Type C meeting with the FDA and the FDA’s concurrence that a single Phase 3 placebo-controlled study with a BMD endpoint could support a NDA submission of EB613.

The FDA also agreed (i) that TH BMD could serve as the primary endpoint for the registrational study of EB613 in post-menopausal women patients diagnosed with osteoporosis, (ii) with the proposed 2:1 randomization (EB613 vs.

placebo) design and (iii) that 400 patients exposed to EB613 would be sufficient to support both the safety and efficacy assessments for the NDA.

Furthermore, the FDA agreed with our proposed enrollment of post-menopausal women diagnosed with osteoporosis based on a BMD T-score of ≤-2.5 to -3.0 and no major fracture history.

This patient population is consistent with that studied during our Phase 2 six-month dose ranging study of EB613, which met all primary and key secondary endpoints of biochemistry and BMD.

FDA Type D Meeting

In February 2023, we announced that a Type D meeting protocol review had been accepted by the FDA to provide responses by March 30th, 2023.

The pivotal, Phase 3 study protocol is entitled “A 24-Month Phase 3, Randomized, Double-Blind, Global Multicenter Study Comparing the Effects of Oral PTH(1-34) (EBP05[EB613]) Daily Tablets vs.

Placebo on Bone Mineral Density (BMD) in Postmenopausal Women with Osteoporosis.” The objective of the Type D meeting review was to confirm that the protocol met the FDA’s expectations, including the analysis of the primary endpoint and the population PK evaluations, ahead of potential initiation of the Phase 3 study.

In April 2023, we reported that the FDA would not be opposed to Entera initiating the Phase 3 study under the proposed SABRE endpoint and that the Company’s proposed PK sampling scheme seemed reasonable.

On the same day, we announced that we plan to continue our dialogue with the FDA and await the final qualification of the SABRE criteria and their guidance on the statistical evaluation of our BMD endpoint before initiating a Phase 3 study for EB613.

In November 2023, we announced that the SABRE project team has submitted to the FDA its full qualification plan to use the treatment-related change in BMD as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs.

BMD is the first surrogate endpoint undergoing qualification by the FDA under the 21st Century Cures Act which was signed into law on December 13, 2016, to help accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently.

In March 2024, ASBMR announced that the FDA had communicated to the SABRE project team that a ruling to qualify the treatment-related change in bone mineral density (BMD) as a surrogate endpoint for fractures in future trails of new anti-osteoporosis drugs would be provided within 10 months.

In September 2024, we presented new comparative pharmacological data for EB613 at the ASBMR 2024 Annual Meeting in Toronto.

An update on FDA’s potential the qualification of BMD as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs by SABRE is expected in 2025.

First Daily PTH Replacement Therapy Tablets for the Treatment of Hypoparathyroidism

Hypoparathyroidism is a rare condition in which the body either fails to produce sufficient amounts of PTH or the PTH produced lacks normal biologic activity.

At 6 months of treatment, EB613 2.5mg produced comparable total hip BMD increases as those that have been reported for Forteo® at 6 months.

Furthermore, in a post hoc analysis using FDA-approved 3D-DXA, EB613 showed early effects on both trabecular and cortical bone of the proximal femur.

The outcomes were comparable with those reported for Forteo and Tymlos on cortical bone indices at 6 months.

First Oral Long-Acting PTH(1-34) Peptide Tablet for the Treatment of Hypoparathyroidism

Hypoparathyroidism is a rare condition in which the body either fails to produce sufficient PTH or the PTH produced lacks normal biologic activity.

Individuals with a deficiency of parathyroid hormone may exhibit hypocalcemia and hyperphosphatemia.

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Although calcium and vitamin D can help alleviate hypocalcemia, their chronic use can result in many serious side effects.

Hypoparathyroid patients often need to take large doses of calcium throughout the day in order to maintain serum calcium near the lower limit of the normal range.

Moreover, ordinary vitamin D is generally insufficient, as the body cannot produce adequate quantities of 1,25-dihydroxy vitamin D, the active hormone derived from vitamin D.

Drugs like calcitriol and alfacalcitol must often be prescribed to stimulate calcium absorption.

If excess calcium is absorbed, it then falls upon the kidneys to dispose of excess calcium.

Endogenous PTH normally regulates renal calcium excretion, but this regulation is defective in patients with hypoparathyroidism.

Over many years of treatment, kidney stones may develop, and kidney failure may ultimately occur due to either kidney stones or deposition of calcium phosphate in kidney tissue (called nephrocalcinosis).

Despite the use of calcium and vitamin D supplements and other medications, many patients with hypoparathyroidism continue to experience physical and cognitive symptoms.

An injectable form of full length human PTH (1-84) marketed under the name Natpara®, was approved for the treatment of hypoparathyroidism in 2015.

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A long acting once weekly injectable PTH peptide prodrug (MBX2109) developed by MBX Biosciences, Inc.

is in Phase 2 clinical testing with topline data expected in Q3 2025.

Finally, oral small molecule PTHR1 (SEP786) developed by Septerna Inc, discontinued a Phase I trial in February 2025 due to safety.

Our product candidate for hypoparathyroidism, EB612, is the first oral PTH (1-34) hormone replacement treatment developed in a tablet form.

The FDA and the EMA have granted EB612 orphan drug designation for the treatment of hypoparathyroidism.

We believe that EB612 may have inherent advantages compared to injectable forms because this is a protein replacement therapy requiring long term use, and we believe that patients have a preference for oral medication, and our tablets may enable more flexibility for titration and more individualized treatment in this heterogeneous disease.

reported positive Phase 2 topline data in 2025.

Finally, oral small molecule PTHR1 5(SEP786) developed by Septerna Inc, discontinued a Phase I trial in February 2025 due to safety and is expected to advance another small molecule into Phase 1 in 2026.

Our current product candidate for hypoparathyroidism, EB612, is the first oral long acting PTH(1-34) hormone replacement treatment developed in a tablet form.

We believe that EB612 may have inherent advantages as compared to injectable and small molecule approaches in terms of potential superior safety and flexibility to provide more individualized treatment in this heterogeneous disease.

Phase 2a Clinical Trial

In 2015, we successfully completed a multicenter Phase 2a clinical trial of EB612 in hypoparathyroidism patients.

In 2015, we successfully completed a multicenter Phase 2a clinical trial of an older, multitablet formulation of EB612 in hypoparathyroidism patients.

This study demonstrated the safety and tolerability of EB612 administered four times daily for 16 weeks to patients with hypoparathyroidism.

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The study achieved its primary and secondary endpoints, including a reduction in calcium supplements, reductions in serum phosphate and 24-hour urine calcium excretion, maintenance of ACa within the reference range, and an improvement in quality of life.

Specific results of this trial included:

Phase 2 PK/PD Clinical Trial

We initiated a two-part Phase 2 PK/PD trial in 2014.

This trial was designed to provide a bridge from our completed Phase 2 study, which was conducted prior to the marketing approval of Natpara, and to allow us to better understand the relative strength and dose of EB612 as compared to the then marketed product, Natpara.

The relevant endpoints for the PK/PD trial included an examination of levels of PTH(1-34), PTH(1-84) (Natpara), serum calcium, serum phosphate, urinary calcium and urinary phosphate.

In November 2018, we announced the completion of part I of this Phase 2 PK/PD trial which showed (i) an increase in the serum calcium by an average of approximately 0.3 mg/dL over baseline, with such increase maintained over a 24-hour period;

(ii) a decrease in serum phosphate by an average of 0.5 mg/dL below baseline with such decrease maintained over a 24-hour period;

(iii) an increase in average levels of serum active vitamin D of approximately 90% on the day of treatment as compared to baseline;

and (iv) a decrease in average levels of 24-hour urinary calcium of approximately 30% on the day of treatment as compared to baseline.

The concentration of PTH(1-34) in blood after administration of EB612 in the trial was sufficient to produce the observed pharmacodynamic effects and did not induce hypercalcemia.

No serious adverse events were reported.

The second part of the PK/PD trial evaluated a variety of dosing treatment regimens with a high and low dose of EB612 as well as Natpara with patients also receiving calcium supplements and either alfacalcidol or calcitriol.

There were no treatment-emergent adverse events of hypercalcemia, as well as no treatment-emergent serious adverse events reported in the trial.

In September 2019, we presented the results of Part 2 at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting.

Planned Additional Clinical Development and Regulatory Pathway

We have since developed a new generation of EB612 based on new intellectual property of our N-Tab™ Technology, which we have designed to optimize its PK profile and the potential for reduced daily dosing.

We have since developed a new generation of EB612 based on new intellectual property of our N-Tab ® platform, which we have designed to optimize its PK profile and the potential for reduced daily dosing.

We initiated a PK study in May 2023, which tested various potential drug candidates based on our new platform, including several which could be developed for the treatment of hypoparathyroidism.

In April 2024, we submitted pharmacokinetic (PK) and early PD Data from a Phase 1 study evaluating an unmodified PTH(1-34) peptide and a new generation of Entera’s N-Tab ® platform to the Endocrine Society Annual Meeting (ENDO 2024).

In June 2024, we presented Phase 1 clinical data at the ENDO 2024 Annual Meeting, that supports potentially moving the BID (twice-daily) tablet dose to Phase 2 development in patients with hypoparathyroidism.

Additionally, we are also collaborating with a third party to combine our N-Tab™ Technology with another peptide for hypoparathyroidism.

In June 2024, we presented Phase 1 clinical data at the ENDO 2024 Annual Meeting, supporting a BID (twice-daily) tablet dose to Phase 2 development in patients with hypoparathyroidism.

In December 2025, we announced new in vivo PK/PD data supporting the development of a proprietary LA-PTH analog utilizing our N-Tab ® platform in partnership with OPKO.

Preclinical findings demonstrated a markedly prolonged plasma half-life and sustained elevation of serum calcium levels for more than three days following administration of a single oral tablet, in contrast to unmodified PTH(1-34) controls, which showed no calcium response.

These data support the development of a once-daily oral PTH tablet for patients with hypoparathyroidism.

Intellectual Property

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As of March 23, 2026, our global patent portfolio included issued patents and patent applications.

We believe that the granted patents as well as certain of the pending claims contained in our patent applications, if issued in substantially the same form, would cover our proprietary technology platform (N-Tab™) and the candidates used in various pipeline programs as indicated in the following table:

We believe that the granted patents as well as certain of the pending claims contained in our patent applications, if issued in substantially the same form, would cover our proprietary platform (N-Tab ® ) and the candidates used in various pipeline programs as indicated in the table below.

In addition, during 2025 we further strengthened the patent protection for our EB612 and GLP1/Glucagon product candidates through the in-licensing of composition-of-matter patent applications from OPKO.

The composition-of-matter patent applications relating to EB612 and GLP1/Glucagon are expected to expire in 2046 and 2045, respectively, not considering any patent term extensions that may be obtained.

Subject Mater

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Issued patents and any patent that may issue from the pending patent applications are currently expected to expire by the Nominal Patent Term as noted in the above table, assuming national phase filings are timely effected.

The nominal patent term does not include potential patent extension and/or patent term addition when applicable.

The nominal patent term does not include potential patent term extension and/or patent term adjustment when applicable.

The term of individual patents depends upon the legal term for patents in the countries in which they are granted.

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The patent term extension period is generally one-half the time between the effective date of the IND and the submission date of the NDA for the product, plus the time between the submission date of the NDA and the approval of the application.

Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent.

Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted within 60 days of regulatory approval of the approved drug and prior to the expiration of the patent.

Only those claims covering the approved drug, a method for using it or a method for manufacturing it may be extended.

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However, the length of any extension, if granted, could be less than we request.

In December 2025 an opposition was filed by an anonymous entity against our European patent EP3256113 ('113 patent).

The granted claims of the '113 patent are directed to an old-generation product that is not currently under development.

Trade Secrets

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Commercialization Strategy

We hold global rights to our internally developed product candidates (including EB613 and EB612), and intend to maximize the value of these candidates commercially with strong partners that have the requisite commercial infrastructure within a specific therapeutic indication, target or geography.

In relation to Oral GLP-1/Glucagon , under the terms of the 2025 Collaboration Agreement, OPKO and Entera hold 60% and 40% pro-rata ownership interests, respectively, in the program and be responsible for 60% and 40% of the program’s development costs, respectively.

We hold global rights to our internally developed product candidate EB613 and intend to maximize the value of EB613 with strong partners that have the requisite commercial infrastructure to successfully launch a candidate that we believe has the potential for significant sales.

In relation to EB612, under the terms of the A&R Collaboration Agreement, OPKO and Entera each hold 50% ownership interests in the program and development costs will be shared equally between the parties.

Following the completion of the Phase 1 stage, we have the option to continue to fund our 50% share to maintain our pro-rata ownership interest in the program.

Should we opt-out, we will retain a 15% ownership interest in the Oral OXM program, while OPKO will retain 85% and be responsible for ongoing development activities and funding of the program.

Should we opt-out, we will retain a 15% ownership interest in the program, while OPKO will retain 85% and be responsible for all ongoing development activities and funding of the program.

In relation to EB618 (Oral GLP-1/Glucagon), under the terms of the A&R Collaboration Agreement, OPKO and Entera hold 60% and 40% pro-rata ownership interests, respectively, in the program and be responsible for 60% and 40% of the program’s development costs, respectively.

Following the completion of the Phase 1 stage, we have the option to continue to fund our 40% share to maintain our pro-rata ownership interest in the program.

Should we opt-out, we will retain a 15% ownership interest in the Oral OXM program, while OPKO will retain 85% and be responsible for all ongoing development activities and funding of the program.

Our Oral GLP-2 program is governed by a 2023 MTA and Collaboration Agreement which we have shared responsibilities.

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While we believe that our technology, knowledge, experience and scientific resources provide us with competitive advantages, we face competition from many different sources, including large pharmaceutical, specialty pharmaceutical, biotechnology, and generic drug companies and academic and government institutions.

We believe that the key competitive factors that will affect the development and commercial success of our product candidates for osteoporosis, hypoparathyroidism and any other product candidates that we develop, are the efficacy, safety and tolerability profile, convenience in dosing, product labeling, price and availability of reimbursement from the government and other third-parties.

We believe that the key competitive factors that will affect the development and commercial success of our product candidates are their efficacy, safety and tolerability profile, convenience in dosing, product labeling, price and availability of reimbursement from the government and other third-parties.

Our commercial opportunity could be reduced or eliminated if our competitors have products that are better in one or more of these categories.

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Such a non-Israeli interested party is required to sign an undertaking towards the IIA in which it undertakes to comply with the Research Law.

Notice or undertaking to the IIA may not be required in respect of purchase of Ordinary Shares in standard acquisition or trading in the stock exchange following to an IPO that was approved by the IIA.

Notice or undertaking to the IIA may not be required with respect to the purchase of Ordinary Shares in standard acquisition or market purchases following an initial public offering (IPO) that was approved by the IIA.

If we fail to comply with the Research Law, we may be forced to return the grants and/or be subject to other payments to the IIA, monetary fines and/or criminal charges.

OPKO Collaboration and License Agreements

2023 Collaboration Agreement

In September 2023, we entered into the 2023 Collaboration Agreement with OPKO Biologics.

Under this agreement, we and OPKO have each agreed to be responsible for specific phases of development of the two oral peptides to the point of demonstrated in vivo feasibility.

2025 Collaboration Agreement

In March 2025, we entered into the 2025 Collaboration Agreement with OPKO and OPKO Biologics to collaborate with respect to the preclinical and clinical development and decision making related to the Oral OXM program for the treatment of obesity, metabolic and fibrotic disorders in humans (the “Program”).

The Program combines OPKO’s proprietary long-acting oxyntomodulin (OXM, dual targeted GLP-1/Glucagon agonist, OPK-88006) analog and Entera’s proprietary N-Tab ® technology.

Under the terms of the 2025 Collaboration Agreement, we and OPKO will retain 40% and 60%, respectively, of all proceeds deriving from the Program, and will be responsible for 40% and 60% of the Program’s development costs, respectively.

Following the completion of the Phase 1 stage, we may continue to fund our 40% share of the Program to maintain our right to proceeds or to opt-out (the “Opt-Out”).

In connection with the execution of the 2025 Collaboration Agreement, we issued and sold to OPKO an aggregate of 3,685,226 Ordinary Shares for a purchase price of $8.0 million, the proceeds of which we have agreed to use solely to fund our development cost obligations under the 2025 Collaboration Agreement, subject to the expiration or termination of the agreement.

A&R Collaboration Agreement

In February 2026, we entered into an amended and restated collaboration agreement with OPKO (the “A&R Collaboration Agreement) which amends and restates the 2025 Collaboration Agreement to expand the scope of the agreement to include the collaboration with respect to the preclinical and clinical development of a daily LA-PTH for the treatment of hypoparathyroidism and other indications in addition to the original oral dual agonist GLP-1/glucagon peptide program.

Development costs incurred by the parties with respect to the development of the LA-PTH program will be shared equally between the Company and OPKO.

Oramed Patent Transfer Agreement

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Under the terms of the Patent Transfer Agreement, we agreed to pay Oramed royalties equal to 3% of our net revenues generated, directly or indirectly, from our exploitation of the assigned patent rights, including the sale, lease or transfer of the assigned patent rights or sales of products or services covered by the assigned patent rights.

On March 27, 2025, we entered into a Novation Agreement with Oramed, and Oramed NewCo Inc.

("Oramed NewCo") pursuant to which Oramed NewCo replaced Oramed as a party to the Patent Transfer Agreement.

Under the Novation Agreement, Oramed NewCo assumed all of Oramed's rights and obligations under the Patent Transfer Agreement accruing on or after the effective date, Oramed was released from any obligations and liabilities owed to us under the Patent Transfer Agreement accruing or arising after such date, and we were released from any obligations and liabilities owed to Oramed accruing or arising after such date.

All other provisions of the Patent Transfer Agreement remain in full force and effect.

Manufacturing

We do not own or operate facilities for large scale product manufacturing, storage and distribution, or testing, nor do we expect to in the future.

Our current facility is limited to small-mid scale manufacturing, storage and distribution of materials and oral drug formulations for clinical studies.

Our current facility is limited to small-mid scale manufacturing, storage and distribution of materials and oral drug formulations for early stage clinical studies.

Our facility has ISO:9001:2015 quality management systems accreditation from The Standards Institution of Israel for the production and development of functional excipients and oral drug formulations to be used in clinical trials.

The facility includes a dedicated Class D clean room for tablet production and a dedicated chemical synthesis room designed to meet ISO 8 specifications.

Our manufacturing activities include the chemical synthesis of one of our non-active but functional drug components in our facility.

In addition, we have a contract with a contract manufacturing organization, to produce and supply tablets for trials performed worldwide, including formulation and production of the final drug, packaging, storage and distribution.

The manufacturer’s facility is an FDA/EMA inspected-GMP site and we expect future clinical studies with our oral PTH (1-34) tablets, as well as the potential commercial supply, if approved, will be provided by the same subcontractor.

This contract is not exclusive and we may enter into additional contracts.

In addition, we have agreements with contract manufacturing organizations, to produce and supply tablets for clinical trials performed worldwide, including formulation and production of the final drug, packaging, storage and distribution.

The manufacturers’ facilities are FDA/EMA inspected-GMP sites and we expect future clinical studies as well as the potential commercial supply, if approved, will be provided by the same subcontractors.

These agreements are not exclusive and we may enter into additional contracts.

Our research and development team supports the manufacturing activities and develops/optimizes analytical methods used by the contract manufacturer in order to meet regulatory requirements for our clinical trials.

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Certain medicinal products, including products developed by means of biotechnological processes must undergo the centralized authorization procedure for marketing authorization, which, if granted by the European Commission, based on the opinion of the EMA, is automatically valid in all EU member states.

Sponsors may elect to file an MAA through the centralized procedures for other classes of products.

Sponsors may elect to file an MAA through the centralize procedures for other classes of products.

The centralized procedure is mandatory for certain types of products such as, medicines derived from biotechnology processes such as genetic engineering, advanced-therapy medicines such as gene-therapy or tissue engineered medicine, orphan medicines, and medicinal products containing a new active substance indicated for the treatment of HIV, AIDS, cancer, diabetes, neurodegenerative disorders, autoimmune and other immune dysfunctions, and viral diseases.

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• the federal False Claims Act imposes civil penalties, and provides for civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

• the Civil Monetary Penalty Act of 1981 imposes penalties against any person or entity that, among other things, is determined to have presented or caused to be presented a claim to a federal health care program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent, or offering or transferring remuneration to a federal health care beneficiary that a person knows or should know is likely to influence the beneficiary’s decision to order or receive items or services reimbursable by the government from a particular provider or supplier.

These penalties include monetary fines ranging from $2,670 and $127,973 per violation and exclusion from participation in a federal health care program such as Medicare and Medicaid, meaning that items and services provided by excluded entities are not directly or separately billable to federal health care programs.

• the Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any health care benefit program or making false statements relating to health care matters.

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• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information that is stored or transmitted electronically;

the Physician Payments Sunshine Act, created under the Affordable Care Act, and its implementing regulations, which require specified manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to payments or other “transfers of value” made to physicians.

• the Physician Payments Sunshine Act, created under the Patient Protection Affordable Care Act (the Affordable Care Act), and its implementing regulations, which require specified manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to payments or other “transfers of value” made to physicians.

All such reported information is publicly available;

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Further, on August 16, 2022, Congress enacted the Inflation Reduction Act allowing CMS to negotiate directly with drug manufacturers to lower the price of some of the costliest drugs under the Medicare program, as well as requiring drug manufacturers to provide Medicare with a rebate if the price of drugs increases faster than the rate of inflation.

In 2025, HHS began implementation of “Most Favored Nation” drug pricing by setting the Medicare price of single-source brand drugs without generic or biosimilar competition to the lowest price available in wealthy countries with aper capita GDP of at least 60% of that in the United States.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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Prescription drugs and biological products advertisements that are in violation of these requirements will be included on a public list.

On September 9, 2025, the FDA began requiring pharmaceutical advertisements to include full safety warnings during direct-to-consumer advertisements, instead of footnoting such information.

Additionally, the FDA expanded its oversight on social medial promotional activities, including influencer partnerships, algorithm-driven targeted advertising, and AI-generated health content, to ensure compliance with the FDA’s advertisement requirements.

The FDA has indicated it will begin enforcement actions for any advertisement violations.

Any adopted health reform measure could reduce the ultimate demand for our products, if approved, or put pressure on our product pricing.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business