Entera Bio(US:ENTX)2024-03-07 16:00Product Development - Entera's most advanced product candidate, EB613, is being developed as the first oral, osteoanabolic tablet treatment for post-menopausal women with low bone mineral density and high-risk osteoporosis, with a Phase 2 study involving 161 patients meeting primary and secondary endpoints[31]. - The FDA has concurred that a 2-year, placebo-controlled Phase 3 study with Total Hip BMD as the primary endpoint could support a new drug application for EB613, expected to initiate in 2024[31][41]. - 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, indicating a strong safety profile[33][52]. - The company is collaborating with OPKO Biologics to develop oral tablet formulations of GLP-2 and Oxyntomodulin, with in vivo PK/PD data expected in 2024[37][39]. - EB613 is positioned to potentially be the first oral anabolic treatment for osteoporosis, addressing the treatment gap where less than 10% of patients agree to injectable therapies[50][49]. - The Phase 2a trial for EB612 demonstrated a statistically significant reduction in calcium supplementation and maintenance of calcium levels above the target for hypoparathyroidism patients[41]. - The Phase 2 clinical trial of EB613 involved 161 postmenopausal women with osteoporosis, evaluating doses from 0.5 mg to 2.5 mg daily tablets[55]. - Statistically significant increases in the bone formation marker P1NP were observed at Month 1 (p<0.001), Month 2 (p<0.005), and Month 3 (p<0.05) for the 2.5 mg EB613 dose group[58]. - The 2.5 mg EB613 group showed a 2.07% increase in total hip BMD and a 2.92% increase in femoral neck BMD after six months, surpassing the increases reported with Forteo®[61]. - The Phase 2 PK/PD trial showed an average increase in serum calcium of approximately 0.3 mg/dL and a decrease in serum phosphate by 0.5 mg/dL, maintained over 24 hours[81]. - The company has developed an improved formulation of EB612 utilizing N-Tab™ Technology, optimizing its pharmacokinetic profile and potentially reducing daily dosing[83]. - The company is exploring the use of PTH(1-34) tablets for treating stress fractures in athletes, with further details expected in the second half of 2024[34]. Market Need and Financial Impact - The prevalence of osteoporosis affects approximately 10 million Americans, with an estimated 2 million osteoporosis-related fractures occurring annually, leading to significant healthcare costs[46]. - The annual cost of osteoporotic fractures in the U.S. is estimated to reach $25.3 billion by 2025, highlighting the urgent need for effective treatments[46]. - The company expects to continue incurring substantial losses for the next several years, particularly as it develops product candidates EB613 and EB612[188]. - Existing cash and cash equivalents are projected to fund operations through the second quarter of 2025, excluding capital needed for a proposed Phase 3 pivotal study for EB613[188]. - The company may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and cost-effectiveness of its product candidates[169]. - Legislative changes, including increased rebates and mandatory discounts under the Affordable Care Act, may reduce the profitability of drug products[174]. - The U.S. government and third-party payers are increasingly scrutinizing drug pricing, which could limit coverage and reimbursement for the company's products[170]. Regulatory and Compliance - The FDA is expected to provide an update on the qualification of BMD as a surrogate endpoint in 2024[72]. - The SABRE project team submitted a full qualification plan to the FDA to use treatment-related changes in BMD as a surrogate endpoint for fractures in future trials[71]. - The FDA confirmed that 400 patients exposed to EB613 would be sufficient for safety and efficacy assessments for the NDA[68]. - The FDA has a 60-day initial review period for NDA submissions, followed by a ten-month standard review or six-month priority review[120]. - The company must comply with extensive Good Manufacturing Practice (cGMP) requirements before the FDA approves any NDA or BLA[116]. - The FDA may issue a complete response letter if an NDA or BLA is not approved, outlining conditions for securing final approval[122]. - The FDA may require post-approval studies, including Phase 4 clinical trials, to assess product safety after approval[125]. - The centralized procedure for marketing authorization in the EU is mandatory for certain products, including those derived from biotechnology[146]. - The EMA's Committee for Human Medicinal Products has 210 active days to adopt an opinion on marketing authorization, which can be reduced to 150 days for accelerated assessments[147]. - Drug manufacturers must comply with cGMP regulations and are subject to periodic inspections by the FDA[127]. - The approval process for marketing outside the U.S. varies by country and may involve additional testing and administrative reviews[136]. - The FDA strictly regulates marketing and promotion of products, prohibiting off-label promotion[130]. - Conditional marketing authorization can be granted for products if the risk-benefit balance is positive and it fulfills unmet medical needs[148]. - A marketing authorization is valid for five years and can be renewed based on a re-evaluation of the risk-benefit balance[149]. - Orphan drug designation provides 10 years of market exclusivity, which can be reduced to six years if criteria are no longer met[151]. - New chemical entities benefit from eight years of data exclusivity and an additional two years of market exclusivity upon receiving marketing authorization[153]. - Compliance with EU pharmacovigilance rules is mandatory, with potential financial penalties for non-compliance[156]. - Manufacturing must adhere to EMA's cGMP requirements, with inspections to ensure compliance[157]. - Marketing and promotion of drugs are strictly regulated to ensure truthful and balanced information[158]. Financial Position and Risks - The company incurred a net loss of $8.9 million in 2023 and $13.1 million in 2022, with an accumulated deficit of $104.4 million as of December 31, 2023[188]. - The company faces substantial doubt about its ability to continue as a going concern due to ongoing financial losses and the need for additional capital[188]. - The company anticipates needing substantial additional funding to complete research and development, clinical trials, and regulatory filings, which may not be available on acceptable terms[191]. - The company expects to raise additional funds to support a potential Phase 3 trial of EB613 and further development of its N-Tab™ technology platform[192]. - The company has not yet demonstrated the ability to successfully complete large-scale clinical trials or obtain marketing approval for any product candidates[204]. - The Phase 2 clinical trial for EB613 was the largest trial conducted to date, highlighting the company's limited experience in large-scale clinical studies[205]. - The company may need to delay, reduce, or cease product development activities if adequate funding is not secured[191]. - Any additional equity or debt financing could be extremely dilutive to current shareholders, raising concerns about the company's ability to finance operations[189]. - The company has a limited operating history and has not generated any revenues from product sales, which may affect investor confidence[196]. - The company is in preliminary stages of developing product candidates and completing clinical trials, which are essential for generating significant revenues and achieving profitability[207]. - The company faces numerous risks and uncertainties in pharmaceutical product development, making it difficult to predict the timing or amount of increased expenses or profitability[208]. Organizational and Operational Challenges - The company has 19 employees, with 15 in Research and Development and 2 in General and Administrative roles[181]. - The company is dependent on a small number of key employees and advisors, and their loss could adversely affect business growth and product development[218]. - The company plans to expand its organization to enhance management and operational capabilities, which may pose challenges in managing growth[219]. - Patient enrollment in clinical trials is critical; delays in enrollment could materially affect research and development efforts[210]. - The company aims to leverage its N-Tab™ drug delivery technology across various product candidates, which is crucial for minimizing risk and development timelines[211]. - The success of oral PTH product candidates is vital for the company's business; failure to validate the N-Tab™ technology could limit future opportunities[212]. Cybersecurity Risks - Cybersecurity risks are increasing, and any breaches could disrupt operations and compromise sensitive data, potentially leading to significant liabilities[222]. - The company has engaged consultants to assess its internal cybersecurity programs and compliance[225]. - Significant capital and resources may be required to protect against and recover from cybersecurity incidents[225]. - Cybersecurity incidents are evolving, necessitating additional resources for protective measures and vulnerability remediation[225]. - There is a risk of public announcements regarding cybersecurity incidents that could negatively impact the company's Ordinary Shares price[225]. - The company's remediation efforts may not be successful, leading to potential service interruptions and breaches[225]. - Loss of critical or sensitive information could result in financial, legal, business, or reputational harm[225]. - The company may face challenges in maintaining relationships with third parties due to cybersecurity issues[225].