Oral teriparatide has been one of pharmaceutical drug delivery’s stubborn ambitions: take a peptide hormone that builds bone, a molecule normally injected under the skin every day, and get it through the digestive system intact and into the bloodstream.
Entera Bio thinks it is close enough to try in a registrational clinical trial.
In its November 6, 2026, third-quarter report, the company said its investigational tablet, EB613, an oral form of the parathyroid hormone fragment PTH(1-34), is preparing for a Phase 3 study of approximately 900 postmenopausal women with osteoporosis.
The first clinical site is expected to activate in late 2026, with topline results anticipated in the second half of 2028.
The company also has the money to get there, which small oral-peptide developers often do not. Entera reported $265.9 million in cash and cash equivalents at the end of September, following a July financing that generated approximately $275 million in gross proceeds. Management expects its available resources to support operations into 2030.
What Entera does not have yet is a successful Phase 3 result, evidence that EB613 prevents fractures, or FDA approval for its oral formulation.
The distinction matters. Entera has made meaningful progress on the regulatory plan and financing. The central clinical question remains unanswered.
Why Oral Teriparatide Matters for Osteoporosis
Osteoporosis is a disease of declining bone strength that increases the risk of fractures, particularly in the hip, spine and wrist.
Many osteoporosis treatments work primarily by slowing bone breakdown. Teriparatide belongs to a smaller class of anabolic medications that stimulate bone formation.
Teriparatide is the active peptide fragment PTH(1-34), corresponding to the first 34 amino acids of human parathyroid hormone. The injectable medicine Forteo received its initial FDA approval in 2002.
For eligible patients at high fracture risk, bone-building treatments can be important components of osteoporosis management. But injections create a practical barrier for some patients, particularly when treatment must be administered regularly over an extended period.
Entera’s EB613 is designed to deliver the same active hormone fragment in a once-daily oral tablet.
That is considerably harder than it sounds.
Peptide medicines are vulnerable to degradation by digestive enzymes, and the intestinal wall restricts the passage of large molecules into the bloodstream. Even when a formulation protects the molecule, consistent absorption can remain difficult.
Entera is developing EB613 using its proprietary oral delivery technology, known as N-Tab, to address these challenges.
The broader pharmaceutical industry has already demonstrated that some peptides can be formulated for oral administration, including semaglutide. But success with one peptide does not establish that a different peptide can be delivered with comparable reliability.
Each molecule has its own stability, absorption, exposure and formulation problems.
Readers interested in alternative peptide delivery approaches can also see Grey Pepper’s coverage of nasal GLP-1 peptide delivery.
The commercial attraction is obvious. A tablet that reliably reproduces the clinically meaningful effects of an established injection could remove one obstacle to treatment.
Whether EB613 can do that remains the purpose of the upcoming trial.
The pitch fits in one line: a bone-building option without a daily needle. The proof will take considerably longer.
What the FDA Agreed to for EB613 Phase 3
On June 22, 2026, Entera announced that it had received positive feedback from the FDA on its proposed registrational development plan for EB613.
The agency accepted a plan for a randomized, double-blind, placebo-controlled Phase 3 clinical trial that could support a New Drug Application if the resulting evidence is sufficient.
The primary endpoint is the percentage change from baseline in total hip bone mineral density after 12 months of treatment.
Bone mineral density, or BMD, measures the mineral content of bone and is commonly assessed using dual-energy X-ray absorptiometry, known as DXA.
In December 2025, the FDA qualified percentage change in total hip BMD at 24 months as a validated surrogate endpoint for certain osteoporosis drug-development trials.
Entera’s proposed 12-month primary endpoint is therefore important to interpret in the context of its specific FDA-reviewed plan. The company is also planning additional evidence to bridge its oral tablet to the approved injectable medicine Forteo.
The planned application would use the 505(b)(2) regulatory pathway, which allows a sponsor to rely partly on previously established findings for an approved medicine while supplying the additional evidence needed for its own product.
Entera’s program includes a scientific bridging analysis with Forteo, pharmacokinetic studies examining drug exposure and a bone biopsy substudy in a subset of participants.
The trial has also expanded since the June announcement.
The initial proposal described approximately 750 postmenopausal women. In October, Entera presented an updated design involving approximately 900 participants, and the November report repeated that target.
Participants will be randomized 2:1, with approximately 600 assigned to EB613 and 300 to placebo.
Eligible women will be between 50 and 90 years old, at least five years beyond their last menstrual period, and have a DXA T-score of -2.5 or lower at the lumbar spine, total hip or femoral neck.
The study will also examine secondary measures of bone density, including changes at the lumbar spine and femoral neck, alongside safety and drug exposure.
Participants completing the 12-month double-blind period may enter an extension study through month 24 to assess longer-term safety and the durability of the bone-density response.
The June and November announcements do not explain why the planned sample size increased from approximately 750 to 900.
FDA feedback does not guarantee regulatory approval, and the trial has not yet generated its primary results. Entera’s next task is to demonstrate that the oral treatment produces the required response with an acceptable safety profile.
What the Oral Teriparatide Phase 2 Evidence Actually Shows
Entera’s case for advancing EB613 rests partly on a randomized Phase 2 trial published in the Journal of Bone and Mineral Research in 2024.
The study enrolled 161 postmenopausal women with low bone mineral density or osteoporosis and compared four daily doses of oral PTH(1-34) with placebo over six months.
Researchers measured biochemical markers of bone formation and resorption, along with changes in bone mineral density at the lumbar spine, total hip and femoral neck.
At the highest tested dose of 2.5 mg once daily, the oral formulation produced statistically significant improvements in bone mineral density compared with placebo.
The reported placebo-adjusted increases after six months were 2.7% at the lumbar spine, 1.8% at the total hip and 2.8% at the femoral neck.
The biochemical findings also suggested activity through two related processes: stimulation of bone formation and suppression of bone resorption.
At the highest dose, markers of bone formation increased early in treatment. The bone formation marker PINP and osteocalcin rose approximately 30% within one month before returning toward baseline by month six.
Meanwhile, the bone resorption marker CTX fell below baseline by approximately 16% at month three and 21% at month six.
There were no drug-related serious adverse events reported in the study. The most commonly reported adverse events included headache, nausea and dizziness.
These results provide a meaningful human signal that oral delivery can produce measurable biological effects. They do not establish long-term safety or fracture prevention.
The company has compared the six-month total hip BMD response with historical data for injectable Forteo. That comparison is informative but is not equivalent to a randomized head-to-head clinical trial.
In October 2026, Entera presented a further post hoc analysis suggesting that women with more severe baseline bone loss may experience larger BMD gains.
Among participants treated with EB613 2.5 mg who had baseline T-scores of -2.5 or lower at the relevant skeletal site, the reported placebo-adjusted mean increases were 4.23% at the total hip and 4.22% at the lumbar spine.
Those results sound impressive, but the subgroup sizes were extremely small: six participants in the total hip analysis and nine in the lumbar spine analysis.
With numbers that small, individual responses can substantially influence the average. The analysis was exploratory and conducted after the original study, rather than serving as a prospectively established primary comparison.
Entera is using the findings to support a Phase 3 population with established osteoporosis, but they cannot independently establish that patients with lower baseline BMD respond better.
Phase 2 showed that the oral peptide can change bone-density measurements. Phase 3 must establish whether that response is convincing and reliable enough for regulatory approval.
The absence of fracture outcomes is particularly important. Bone density is a useful predictor of bone strength, but it is not the same as directly observing fewer broken bones in treated patients.
The regulatory strategy is designed to address that distinction through a validated or otherwise agreed surrogate approach and additional evidence from the established injectable drug.
Entera Has the Cash to Pursue Phase 3
For small biotechnology companies, scientific progress is only one part of the problem. Funding a large, multinational clinical trial and maintaining operations until the results arrive can be equally difficult.
Entera’s financial position changed substantially in July 2026, when the company completed an oversubscribed private placement that raised approximately $275 million before fees and offering expenses.
Investors in the transaction included existing backer BVF Partners and several healthcare-focused investment firms.
At September 30, Entera reported $265.9 million in cash and cash equivalents, alongside $6.5 million in restricted cash primarily designated for its collaboration with OPKO Health.
The company expects those resources to finance the planned EB613 Phase 3 program through topline results, support an anticipated FDA application and sustain operations into 2030.
That forecast is encouraging, but it is not a guarantee. Clinical development costs can change with recruitment speed, protocol amendments, manufacturing requirements and unexpected safety or regulatory demands.
Research and development spending increased to $4.9 million in the third quarter, compared with $1.6 million during the same period in 2025.
Entera attributed much of the increase to Phase 3 preparation and activities associated with its OPKO collaboration.
The company reported a net loss of $15.6 million for the quarter, compared with $3.2 million one year earlier.
However, the newer figure included approximately $7.5 million in non-cash charges related to the fair-value remeasurement of pre-funded warrants. Treating the entire accounting loss as cash consumed by operations would therefore be misleading.
In practical terms, the financing gives Entera room to pursue a late-stage program without immediately returning to investors for the same purpose.
It does not reduce the clinical uncertainty. The company can afford to run the study; it still needs to produce convincing results.
The Oral Peptide Platform Beyond EB613
Entera’s longer-term ambition extends beyond osteoporosis.
The company is also developing EB612, an oral acylated PTH(1-34) candidate intended as a hormone replacement treatment for hypoparathyroidism.
Hypoparathyroidism is a distinct condition in which the body produces insufficient parathyroid hormone, disrupting calcium regulation. Although the programs share PTH-related biology, the therapeutic goals differ from those of osteoporosis treatment.
In its November report, Entera said it was conducting investigational new drug-enabling activities for EB612 with OPKO Health and targeting a Phase 1 single-ascending-dose study in 2027.
The company has also identified an oral oxyntomodulin candidate, targeting GLP-1 and glucagon receptors for obesity and metabolic disorders, and an oral GLP-2 program aimed at conditions involving impaired intestinal absorption, including short bowel syndrome.
Those programs illustrate the broader platform strategy: using oral delivery technology to replace injections of peptide medicines across several therapeutic areas.
But the November release does not provide comparable Phase 3 plans, clinical efficacy results or development timelines for the oxyntomodulin and GLP-2 programs.
They should therefore be understood as pipeline opportunities rather than established clinical products.
As Grey Pepper has explored in its coverage of peptide drug development platforms, the ability to deliver peptides through alternative routes remains an important competitive frontier.
For Entera, EB613 is the program closest to testing whether its delivery approach can support an approved medicine.
What Must Be Proven Before an Osteoporosis Pill Can Replace an Injection
Several major questions remain open.
The first is consistency of absorption. Oral peptides can be sensitive to conditions inside the digestive system, and differences in exposure between patients may influence both efficacy and safety.
Entera’s proposed pharmacokinetic studies and bridging analysis will therefore matter alongside the bone-density measurements.
The second question is whether the Phase 3 response at 12 months will be large and consistent enough to support the planned regulatory application.
The FDA’s positive feedback makes the development strategy more credible, but final acceptance will depend on the evidence submitted and the agency’s review.
Third, long-term safety and durability remain uncertain. The Phase 2 trial lasted only six months, and the planned extension is intended to provide additional information through 24 months.
Fourth, the trial is not designed primarily to measure actual fracture prevention. Its main endpoint is bone mineral density, and Entera intends to rely partly on scientific bridging to the established injectable treatment.
There is also the practical question of patient preference. An oral formulation may be more acceptable than a daily injection to some people, but convenience is not enough on its own.
A useful tablet must deliver reliable exposure, a clinically meaningful response and acceptable tolerability under real-world administration conditions.
The final commercial calculation will also depend on price, insurance coverage and competition from other osteoporosis medicines.
None of these questions can be answered by the company’s cash balance or the FDA’s agreement to a trial design.
The scheduled timeline adds another layer of uncertainty. Results are not expected until the second half of 2028, leaving substantial time for changes in the osteoporosis treatment market and for unexpected delays in development.
Entera has completed several difficult steps that small peptide developers often struggle with. It has generated controlled Phase 2 evidence, obtained feedback on a possible registrational pathway, raised substantial financing and identified the population it intends to study.
What it has not yet shown is that its daily oral PTH(1-34) tablet can satisfy the FDA’s requirements for a marketed osteoporosis treatment.
The difference between a promising formulation and a successful drug is still measured in clinical results.
Entera has secured the money and a path toward Phase 3. Whether a fragile bone-building hormone can work reliably as a tablet remains the question its 2028 results must answer.
Sources and Further Reading
- Entera Bio. Third Quarter 2026 Financial Results and Business Updates. November 6, 2026.
- US Securities and Exchange Commission. Entera Bio Quarterly Report for the Period Ended September 30, 2026.
- Entera Bio. Positive FDA Feedback on EB613 Registrational Phase 3 Study. June 22, 2026.
- Entera Bio. EB613 Phase 2 Exploratory Analysis and Phase 3 Design Presented at ASBMR 2026. October 13, 2026.
- Tripto-Shkolnik L, et al. Oral Daily PTH(1-34) Tablets (EB613) in Postmenopausal Women With Low BMD or Osteoporosis: A Randomized, Placebo-Controlled, 6-Month Phase 2 Study. Journal of Bone and Mineral Research, 2024.
- Journal of Bone and Mineral Research. Original EB613 Phase 2 Clinical Publication. DOI: 10.1093/jbmr/zjae057.
- US Food and Drug Administration. FDA Qualifies Total Hip Bone Mineral Density as a Surrogate Endpoint for Osteoporosis Drug Development. December 19, 2025.
