Entera Bio Ltd. has reported encouraging new Phase 2 findings for EB613, its investigational once-daily oral osteoporosis treatment, showing greater improvements in bone mineral density among postmenopausal women with established osteoporosis than among those with less severe bone loss. The exploratory analysis found placebo-adjusted bone density gains exceeding 4% at both the total hip and lumbar spine after six months in small patient subgroups. Presented at the American Society for Bone and Mineral Research 2026 Annual Meeting, the findings support further investigation of EB613 as a potentially first-in-class oral bone-building treatment ahead of a planned Phase 3 clinical trial involving approximately 900 women.
The results could have important implications for osteoporosis treatment, particularly for patients at high risk of fractures who may benefit from anabolic therapies but face barriers associated with daily injections. Nevertheless, the findings are based on a retrospective subgroup analysis involving relatively few participants, and the ability of EB613 to prevent fractures has not yet been established.
How did EB613 improve bone mineral density in postmenopausal women with osteoporosis?
Entera Bio presented the new findings from a previously completed randomized, placebo-controlled Phase 2 study that enrolled 161 postmenopausal women with low bone mass or osteoporosis. Participants received placebo or one of four EB613 dose levels over six months, allowing investigators to evaluate changes in bone formation biomarkers and bone mineral density.
The latest analysis focused on patients receiving the 2.5 mg daily dose of EB613, examining whether baseline bone density influenced treatment response. Investigators compared women with osteoporosis, defined by a bone mineral density T-score of -2.5 or lower, against women with less severe bone loss, whose T-scores were above that threshold.
Among women with osteoporosis at the relevant skeletal measurement site, EB613 produced a placebo-adjusted bone mineral density increase of 4.23% at the total hip after six months. This result was based on six treated participants and compared with a 1.02% increase among 15 women with higher baseline hip T-scores.
At the lumbar spine, the placebo-adjusted improvement reached 4.22% among nine patients with osteoporosis, compared with 1.59% among 12 participants with less severe bone loss. Across all 21 patients receiving the 2.5 mg dose, pooled placebo-adjusted improvements reached 1.84% at the total hip and 2.72% at the lumbar spine.
These findings suggest that women starting treatment with lower bone mineral density may experience greater short-term improvements from EB613. However, the small subgroup sizes and exploratory nature of the analysis mean that the numerical differences should not be interpreted as definitive evidence that patients with more severe osteoporosis respond better.
The company also reported changes in biochemical markers associated with bone remodeling. Responses involving P1NP, a marker of bone formation, and CTX, a marker of bone resorption, appeared somewhat larger and more sustained among women meeting the osteoporosis threshold at one or more skeletal sites.
Together, the bone density and biomarker findings provide additional support for EB613’s proposed anabolic activity. They also offer a rationale for focusing the planned Phase 3 study on patients with established osteoporosis rather than a broader population that includes women with osteopenia.
Why could a once-daily oral bone-building drug change osteoporosis treatment?
Osteoporosis is a progressive skeletal disorder characterized by reduced bone strength and increased susceptibility to fractures. It is particularly common among postmenopausal women because declining estrogen levels accelerate bone loss, potentially affecting the spine, hip and other weight-bearing skeletal structures.
Treatment strategies generally fall into two categories. Antiresorptive medications, including bisphosphonates and denosumab, primarily reduce the breakdown of existing bone, while anabolic therapies stimulate new bone formation. Anabolic treatments are especially important for some patients at very high fracture risk, where building skeletal strength rapidly may provide substantial clinical benefits.
Despite their therapeutic value, currently available anabolic treatments require injection. This administration burden can complicate treatment decisions, especially for patients reluctant to self-inject or those who have difficulty maintaining injectable regimens over extended periods.
EB613 is being developed to address this challenge by delivering PTH(1-34), the active peptide represented by teriparatide, through an oral tablet. Teriparatide is an established bone-building therapy, but conventional formulations are administered by subcutaneous injection because peptide molecules are difficult to deliver effectively through the gastrointestinal tract.
Entera Bio’s proprietary oral peptide technology is intended to overcome this delivery challenge, potentially allowing patients to receive anabolic treatment without injections. If successful, EB613 could introduce another option for physicians seeking to initiate bone-building therapy in postmenopausal women at elevated fracture risk.
Felicia Cosman, professor of medicine at Columbia University, emphasized during the company’s announcement that osteoporosis treatment strategies have increasingly favored anabolic therapy before antiresorptive treatment in appropriate high-risk patients. She indicated that an oral formulation could help address practical barriers that currently limit broader use of this treatment approach.
However, convenience alone will not establish EB613’s clinical value. The oral treatment must demonstrate sufficient biological activity, reliable absorption, acceptable safety and reproducible improvements in bone density before its potential advantages can be assessed against established therapies.
What do EB613’s Phase 2 findings reveal about its mechanism and clinical potential?
EB613 contains an oral formulation of parathyroid hormone fragment PTH(1-34), which stimulates bone-forming cells when delivered in an appropriate intermittent dosing pattern. The resulting anabolic activity can increase bone mineral density and potentially improve skeletal strength, making the pathway clinically relevant for treating osteoporosis.
In the original Phase 2 study, EB613 produced dose-related improvements in bone mineral density at the lumbar spine, total hip and femoral neck. The company also reported increases in biochemical markers of bone formation, alongside reductions in markers associated with bone resorption.
The latest subgroup findings add another dimension by suggesting that baseline skeletal status may influence the magnitude of treatment response. Patients with lower initial bone mineral density appeared to experience greater gains at important anatomical sites, including the hip, where fractures are associated with considerable disability and healthcare burden.
The findings are biologically interesting because successful anabolic therapy aims to rebuild bone rather than merely slow deterioration. Improvements at the total hip may be particularly relevant for evaluating treatment effectiveness, given the clinical significance of hip fractures among older adults.
Nevertheless, bone mineral density remains a surrogate measure of skeletal health rather than a direct measurement of fracture prevention. Although changes in bone density can help predict fracture risk reduction, the current EB613 findings do not demonstrate that treated patients experience fewer fractures.
The reported comparisons are also drawn from a post-hoc analysis rather than a prospectively designed trial intended to establish differences between osteoporosis severity subgroups. Such analyses can help identify potential treatment patterns but are vulnerable to statistical instability, particularly when the number of participants is small.
Consequently, the strongest interpretation is that these findings support the biological rationale and patient-selection strategy for further development. Confirmation will depend on whether similar improvements are observed in the larger, prospectively designed Phase 3 population.
How will Entera Bio’s planned Phase 3 trial evaluate EB613 safety and effectiveness?
Entera Bio has outlined a multinational, randomized, double-blind, placebo-controlled Phase 3 study intended to provide registrational evidence for EB613 in postmenopausal osteoporosis. The current design includes approximately 900 participants, with about 600 assigned to EB613 and 300 receiving placebo.
Eligible participants will be postmenopausal women aged 50 to 90 who are at least five years beyond their last menstrual period. Osteoporosis must be confirmed through dual-energy X-ray absorptiometry, with a T-score of -2.5 or lower at the lumbar spine, total hip or femoral neck.
The study’s primary endpoint will assess the change in total hip bone mineral density after 12 months of treatment compared with placebo. Secondary endpoints will examine bone mineral density at the lumbar spine and femoral neck after 12 months, alongside measurements at three and six months.
This approach will allow investigators to evaluate not only the overall magnitude of bone density improvement but also how quickly the treatment begins producing measurable effects. Repeated assessments across skeletal sites should provide additional information about the consistency and distribution of EB613’s anabolic activity.
Safety monitoring will include adverse events, vital signs, physical examinations and laboratory assessments. Investigators will also conduct pharmacokinetic substudies to characterize exposure to PTH(1-34) following oral administration, an important consideration for a peptide treatment delivered through the gastrointestinal tract.
Participants completing the initial 12-month treatment period may enter an extension study continuing through Month 24. The extension is intended to assess longer-term safety and durability of the treatment response, helping determine whether early improvements persist or change with additional follow-up.
Entera Bio previously reported positive regulatory feedback from the U.S. Food and Drug Administration concerning its proposed 12-month registrational strategy. However, the planned trial must still generate adequate evidence to support a future marketing application, and regulatory approval is not assured.
What comes next for EB613 as Entera Bio advances its osteoporosis development program?
The latest findings strengthen the clinical rationale for evaluating EB613 in women with established osteoporosis who face elevated fracture risk. By demonstrating larger bone mineral density improvements in patients with lower baseline T-scores, the exploratory analysis supports the population selected for the company’s forthcoming registrational study.
The most important question now is whether those benefits can be reproduced in a substantially larger group over 12 months. The Phase 3 study will also need to clarify the treatment’s safety profile and establish whether oral PTH(1-34) can provide sufficiently consistent skeletal effects to support its intended clinical use.
The original Phase 2 trial reported no significant safety concerns, but a six-month study involving 161 participants cannot fully characterize uncommon adverse events or the consequences of longer treatment. More extensive safety monitoring will therefore be essential as EB613 approaches potential regulatory review.
Entera Bio is positioning the therapy within an evolving osteoporosis treatment landscape that increasingly emphasizes early use of anabolic medications for appropriately selected high-risk patients. An effective oral option could potentially expand access to bone-building treatment, although its eventual clinical role would depend on comparative effectiveness, tolerability, prescribing requirements and affordability.
The company previously indicated that it was targeting Phase 3 initiation in late 2026, with top-line results anticipated in the second half of 2028. Actual timing will depend on trial activation, recruitment and execution.
For now, EB613 represents a promising but unapproved treatment candidate. Its Phase 2 findings suggest meaningful effects on bone formation and mineral density, while the forthcoming Phase 3 program will determine whether those signals are sufficiently reliable to support a potential new oral treatment option for postmenopausal osteoporosis.
