Product Development - Entera has two clinical stage product candidates: EB613 for osteoporosis and EB612 for hypoparathyroidism, both designed as first-in-class daily mini tablets of human parathyroid hormone (hPTH (1-34)) [35] - EB613 has completed Phase 2 trials with 118 patients, meeting both primary and secondary endpoints, and is expected to initiate Phase 3 registrational study in H2 2023 [43] - EB612 has received orphan drug designation from the FDA and EMA for hypoparathyroidism, with a Phase 1 PK study for a new formulation expected to begin in H1 2023 [43] - Entera's proprietary technology aims to deliver orally administered proteins with sufficient bioavailability, addressing the treatment gap in chronic diseases requiring persistent management [35] - Entera's strategy includes establishing global partnerships to diversify and shorten the development timeline of its product candidates [43] - The company is exploring additional products based on FDA-approved injectable protein therapeutics to leverage its technology platform [44] - Entera aims to shift the treatment paradigm for chronic conditions by developing first-in-class orally delivered therapies, potentially allowing patients to manage their conditions without injections [42] - The Phase 1 studies involved 72 healthy subjects, with no serious adverse events reported, and doses of oral PTH tablets up to 3 mg were well tolerated [60] - The Phase 2 study's results supported the selection of the 2.5 mg dose with a titration regimen for the proposed pivotal Phase 3 study of EB613 [71] - The pivotal Phase 3 study protocol aims to compare the effects of oral hPTH(1-34) daily tablets versus placebo on BMD in postmenopausal women with osteoporosis [78] - EB612 is the first oral formulation of PTH (1-34, teriparatide) hormone replacement treatment developed in a mini tablet form, with orphan drug designation granted by the FDA and EMA for hypoparathyroidism [84] - In a Phase 2a clinical trial, EB612 demonstrated a 42% reduction in median calcium supplement use and a 21% decrease in 24-hour urine calcium excretion [87] - The Phase 2 PK/PD trial showed an average increase of approximately 0.3 mg/dL in serum calcium and a 30% decrease in 24-hour urinary calcium on the day of treatment compared to baseline [87] Market Opportunity - The U.S. has an estimated 10.2 million individuals with osteoporosis, with over 2 million related fractures occurring annually, leading to costs of approximately $25.3 billion by 2025 [50] - Current anabolic therapies for osteoporosis require injections, with less than 10% of patients using these due to inconvenience and pain associated with injections [59] - The global market for osteoporosis treatments is significant, with the peak annual sales of Forteo (teriparatide) reaching $1.7 billion prior to patent expiration [47] - Approximately 200,000 people are affected by hypoparathyroidism in the US, EU, and Japan, with a significant unmet need for effective treatments [81] - The current standard of care for hypoparathyroidism involves high doses of calcium and vitamin D, which can lead to severe long-term morbidities [82] - Natpara®, an injectable PTH treatment, was recalled in 2019 and will be permanently phased out by the end of 2024, creating a market opportunity for new therapies [83] Clinical Trial Results - In the Phase 2 study, a dose of 2.5 mg EB613 daily tablets showed statistically significant increases in bone formation markers P1NP and Osteocalcin at Month 3 (p<0.05 and P<0.01, respectively) [66] - The placebo-adjusted increase in total hip BMD was 1.84% and femoral neck BMD was 2.76% for the 2.5 mg EB613 group, both statistically significant (P<0.02 and P<0.002, respectively) [69] - The FDA agreed that total hip BMD could serve as the primary endpoint for the registrational study of EB613 in post-menopausal women with osteoporosis [76] Regulatory Environment - The FDA regulates the company's product candidates under the Federal Food, Drug, and Cosmetic Act, requiring substantial time and financial resources for compliance [115] - The process for obtaining FDA approval involves multiple steps, including preclinical studies, IND application, and clinical trials [118] - Clinical trials are conducted in three phases, with annual progress reports required to be submitted to the FDA [124] - The FDA requires compliance with Current Good Manufacturing Practice (cGMP) before approving a New Drug Application (NDA) or Biologics License Application (BLA) to ensure consistent production within required specifications [127] - The FDA has 60 days to conduct an initial review of an NDA or BLA submission to determine if it is sufficient for filing, followed by a ten-month review period for standard applications and six months for priority reviews [131] - The FDA may designate a product for fast track review if it addresses an unmet medical need for a serious condition, allowing for greater interactions with the FDA during the review process [139] - The FDA may issue an Emergency Use Authorization (EUA) for unapproved drugs during a designated emergency, which is product-specific and subject to specific conditions [142] - The FDA may require post-approval studies, including Phase 4 clinical trials, to further assess a product's safety after approval [136] - The FDA can withdraw approval if compliance with regulatory requirements is not maintained or if new problems are discovered post-market [151] Financial Overview - The company incurred net losses of $13.1 million in 2022 and $12.2 million in 2021, with an accumulated deficit of $95.5 million as of December 31, 2022 [216] - The company expects to continue incurring substantial losses for the next several years, particularly as it develops EB613 and EB612, and anticipates significant net losses and accumulated deficits during this period [216] - Existing cash and cash equivalents are projected to fund operations into the third quarter of 2024, assuming no delays in securing additional capital or entering strategic collaborations [216] - The company has raised substantial doubt about its ability to continue as a going concern, depending on its ability to obtain additional financing [217] - The company anticipates needing substantial additional funding to support the execution of its long-term growth strategy, including a potential Phase 3 trial of EB613 and further development of EB612 [221] Collaboration and Partnerships - The company has a collaboration with Amgen, receiving an initial technology access fee of $725,000 and is eligible for up to $270 million in milestone payments [94] - The company aims to maximize the value of its product candidates by either independently commercializing them or seeking collaborations with third parties [103] Compliance and Legal Risks - The company is subject to significant legal, accounting, and compliance costs as a public company listed on Nasdaq, which may strain resources and distract management [232] - The company is subject to ongoing government regulation, and failure to comply could delay or prevent the marketing of its products [215] - Legislative changes, including increased rebates and mandatory discounts under the ACA, may reduce the profitability of drug products [201] - The U.S. government and third-party payers are increasingly scrutinizing drug pricing, which could adversely affect the marketability of the company's products [200] - The company faces significant barriers to entry for new products due to intense downward pressure on healthcare costs and pricing controls in various countries [199]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-38556 ENTERA BIO LTD. (Exact name of Registrant as specified in its charter) | --- | --- | |------------------------------------------ ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-38556 ENTERA BIO LTD. (Exact name of Registrant as specified in its charter) | --- | --- | |----------------------------------------------- ...

Entera Bio Ltd. (NASDAQ:ENTX) Q1 2022 Earnings Conference Call May 17, 2022 8:00 AM ET Company Participants Spiros Jamas - Chief Executive Officer Miranda Toledano - Chief Business Officer, Chief Financial Officer & Head of Strategy Arthur Santora - Chief Medical Officer Conference Call Participants Kalpit Patel - B. Riley Nathan Weinstein - Aegis Capital Operator Greetings, and welcome to Entera Bio's First Quarter '22 Update Conference Call. At this time, all participants are in a listen-only mode. The qu ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________to __________ Commission file number: 001-38556 ENTERA BIO LTD. (Exact name of Registrant as specified in its charter) | --- | --- | |------------------------ ...

1 Entera Bio Investor Presentation March 2022 Forward-Looking Statements 2 This presentation includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. Forward- looki ...

Entera Bio Ltd. (NASDAQ:ENTX) Q4 2021 Earnings Conference Call March 8, 2022 8:30 AM ET Company Participants Ramesh Ratan - CFO Spiros Jamas - CEO Arthur Santora - CMO Phillip Schwartz - Founder & President, R&D Conference Call Participants Kalpit Patel - B. Riley Nathan Weinstein - Aegis Capital Operator Greetings and welcome to the Entera Bio's Fourth Quarter and Year-End 2021 Earnings Call. At this time, all participants are in a listen-only mode. The question-and-answer session will follow the formal pr ...

PART I [Business](index=6&type=section&id=Item%201.%20Business) Entera Bio is a clinical-stage biopharmaceutical company developing orally delivered large molecule therapeutics, with lead candidates EB613 for osteoporosis and EB612 for hypoparathyroidism [Overview](index=6&type=section&id=Overview) - Entera Bio is a clinical-stage biopharmaceutical company developing orally delivered large molecule therapeutics, with a proprietary platform tested on numerous molecules[13](index=13&type=chunk) - The company's lead product candidates are EB613 for osteoporosis and EB612 for hypoparathyroidism, both oral formulations of parathyroid hormone (PTH)[13](index=13&type=chunk) - EB613 has completed a Phase 2 trial for osteoporosis and the company is preparing for a pivotal Phase 3 study. An End-of-Phase 2 meeting with the FDA was held in December 2021[13](index=13&type=chunk) - Entera entered into a research collaboration and license agreement with Amgen in December 2018 to use its oral delivery platform for inflammatory diseases[13](index=13&type=chunk) [Our Pipeline](index=8&type=section&id=Our%20Pipeline) Product Candidate Development Pipeline | Program | Target Indication | Development Stage | Partner | Next Milestone | | :--- | :--- | :--- | :--- | :--- | | **EB613 (PTH)** | Osteoporosis | Pre-Phase 3 | - | Phase 3 start H2 2022 | | **EB612 (PTH)** | Hypoparathyroidism | Phase 2 | - | Human PK/PD 2022 | | **EB613 (PTH)** | Non-union fractures | Pre-Phase 1/2 | - | Phase 1/2 | | **GLP-2** | Short bowel syndrome | Preclinical | - | Large animal studies | | **hGH** | GH deficiency | Preclinical | - | Large animal studies | | **Undisclosed** | Anti-inflammatory | Preclinical | AMGEN | Undisclosed | [Our Strategy](index=8&type=section&id=Our%20Strategy) - Advance EB613 into a pivotal Phase 3 trial for osteoporosis in 2022, following positive Phase 2 results[18](index=18&type=chunk) - Advance EB612 for hypoparathyroidism, with plans to initiate a Phase 2b/3 clinical trial after additional formulation and development activities[20](index=20&type=chunk) - Establish commercial partnerships for large-population indications like osteoporosis, while potentially retaining commercial rights for orphan indications like hypoparathyroidism[20](index=20&type=chunk) - Leverage the technology platform through collaborations, similar to the existing agreement with Amgen, to generate non-dilutive funding[20](index=20&type=chunk) - Identify and develop additional oral versions of FDA-approved injectable large molecules, such as the new research program for an oral GLP-2 analog[20](index=20&type=chunk) [Our Product Candidates](index=10&type=section&id=Our%20Product%20Candidates) - EB613 for Osteoporosis: Completed a Phase 2 dose-ranging trial with final BMD results reported in Q2 2021. An End-of-Phase 2 meeting with the FDA was held in December 2021, with Phase 3 initiation expected in 2022[24](index=24&type=chunk) - EB612 for Hypoparathyroidism: Successfully completed a Phase 2a trial (results reported 2015) and a Phase 2b PK/PD trial comparing it to Natpara (results reported Q3 2019). An improved formulation was selected in Q4 2021[24](index=24&type=chunk) - The **2.5 mg dose of EB613** was selected for the pivotal Phase 3 study based on Phase 2 results, which showed a statistically significant dose response in lumbar spine BMD and an adverse event profile similar to Forteo®[32](index=32&type=chunk)[33](index=33&type=chunk) - EB612 has received **orphan drug designation** from both the FDA and EMA for the treatment of hypoparathyroidism[20](index=20&type=chunk)[45](index=45&type=chunk) [Intellectual Property](index=21&type=section&id=Intellectual%20Property) - The company holds issued patents covering its core compositions (protein, absorption enhancer, protease inhibitor) in the U.S., Europe, Japan, China, and other jurisdictions, with expected expiration in **August 2029**[48](index=48&type=chunk) - Pending patent applications cover specific oral administration technologies and methods of treatment for osteoporosis and hypoparathyroidism, which, if issued, are expected to expire between **2036 and 2037**[49](index=49&type=chunk) - Eleven provisional patent applications were filed in **2022** covering new discoveries for oral delivery of large molecules, with potential expiration in **2043**[49](index=49&type=chunk) [Competition](index=23&type=section&id=Competition) - For osteoporosis (EB613), key competitors include established treatments like Eli Lilly's Forteo® (injectable PTH) and Amgen's Prolia® and EVENITY®[52](index=52&type=chunk) - For hypoparathyroidism (EB612), the primary competitor is Takeda's Natpara® (injectable PTH 1-84), which has orphan drug exclusivity in the U.S. (expired Jan 2022) and EU. Ascendis Pharma is also developing a long-acting PTH in Phase 3[53](index=53&type=chunk)[127](index=127&type=chunk) [Government Regulation and Product Approval](index=26&type=section&id=Government%20Regulation%20and%20Product%20Approval) - The company's products are regulated by the FDA in the U.S. and comparable authorities abroad, requiring extensive preclinical and clinical trials (Phase 1, 2, 3) to establish safety and efficacy before marketing approval[58](index=58&type=chunk)[59](index=59&type=chunk) - The company plans to utilize the **505(b)(2) regulatory pathway** for EB613 in the U.S., which allows reliance on existing data for an approved drug (like Forteo®), potentially enabling the use of Bone Mineral Density (BMD) as a primary endpoint instead of fracture reduction[30](index=30&type=chunk) - EB612 has received **Orphan Drug Designation** in the U.S. and EU, which can provide benefits like tax credits, fee waivers, and a period of market exclusivity post-approval[71](index=71&type=chunk)[81](index=81&type=chunk) - The company is also subject to healthcare laws regarding fraud and abuse (e.g., Anti-Kickback Statute), pricing and reimbursement policies, and data privacy regulations like GDPR and HIPAA[87](index=87&type=chunk)[88](index=88&type=chunk)[116](index=116&type=chunk) [Risk Factors](index=42&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant financial, developmental, and regulatory risks, including recurring losses, a substantial accumulated deficit, and a going concern warning - The company has a history of significant net losses, including **$12.2 million** in 2021, and an accumulated deficit of **$82.4 million** as of December 31, 2021[97](index=97&type=chunk) - Management and the independent registered public accounting firm have raised substantial doubt about the company's ability to continue as a going concern, with existing cash sufficient to fund operations only into the **fourth quarter of 2022**[97](index=97&type=chunk) - All product candidates, including the most advanced (EB613 and EB612), are still in development and have not yet completed the large-scale pivotal trials required for regulatory approval[96](index=96&type=chunk)[103](index=103&type=chunk) - The COVID-19 pandemic poses a risk of adversely affecting business operations, including potential disruptions to clinical trials and supply chains[96](index=96&type=chunk)[113](index=113&type=chunk) - The company is highly dependent on its ability to form collaborations for development and commercialization, and on third parties for manufacturing and conducting clinical trials[96](index=96&type=chunk)[141](index=141&type=chunk) - Risks related to its location in Israel include IIA grant restrictions on manufacturing and technology transfer, as well as potential business disruptions from political and military instability in the Middle East[167](index=167&type=chunk)[169](index=169&type=chunk) [Properties](index=83&type=section&id=Item%202.%20Properties) The company leases **622 square meters** of office and laboratory space in Jerusalem, Israel, with the current lease expiring on **June 30, 2023** - Leases **622 square meters** of office and laboratory space in Jerusalem, Israel[176](index=176&type=chunk) - The lease agreement expires on **June 30, 2023**[176](index=176&type=chunk) PART II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=83&type=section&id=Item%205.%20Market%20for%20Registrant%27s%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities.) The company's Ordinary Shares and IPO Warrants trade on the Nasdaq Capital Market, with no history of cash dividends and plans to retain earnings for operations - Ordinary Shares trade under the symbol '**ENTX**' and IPO Warrants trade under '**ENTXW**' on the Nasdaq Capital Market[177](index=177&type=chunk) - The company has never declared or paid cash dividends and does not plan to in the foreseeable future, retaining earnings for business development[177](index=177&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=84&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company reported a **$12.2 million** net loss in 2021, with an **$82.4 million** accumulated deficit, and auditors expressed substantial doubt about its going concern, with **$24.9 million** cash projected to fund operations into Q4 2022 [Results of Operations](index=90&type=section&id=Results%20of%20Operations) Comparison of Operations (Years Ended December 31) | Financial Metric | 2021 (in thousands) | 2020 (in thousands) | Change (%) | | :--- | :--- | :--- | :--- | | **Revenues** | $571 | $365 | 56% | | **Cost of Revenues** | $373 | $300 | 24% | | **R&D Expenses, Net** | $6,771 | $6,382 | 6% | | **G&A Expenses** | $5,690 | $4,851 | 17% | | **Operating Loss** | $12,217 | $11,168 | 9% | | **Net Loss** | $12,187 | $11,216 | 9% | | **Loss Per Share** | $0.47 | $0.67 | -30% | - The increase in R&D expenses in 2021 was primarily due to costs for materials, production, and preclinical activities in preparation for the EB613 Phase 3 trial[193](index=193&type=chunk) - The increase in G&A expenses in 2021 was mainly attributed to higher share-based compensation, legal and accounting costs, and D&O insurance[193](index=193&type=chunk) [Liquidity and Capital Resources](index=91&type=section&id=Liquidity%20and%20Capital%20Resources) - The company's independent auditor has expressed substantial doubt about its ability to continue as a going concern due to recurring losses and negative cash flows[193](index=193&type=chunk)[195](index=195&type=chunk) - As of December 31, 2021, the company had cash and cash equivalents of **$24.9 million**, which is expected to fund operations into the **fourth quarter of 2022**[193](index=193&type=chunk) - In 2021, the company sold an aggregate of **4.3 million** Ordinary Shares under its ATM Programs, raising net proceeds of approximately **$25 million**[194](index=194&type=chunk)[197](index=197&type=chunk) Cash Flow Summary (Years Ended December 31) | Cash Flow Activity | 2021 (in thousands) | 2020 (in thousands) | | :--- | :--- | :--- | | Net Cash used in operating activities | $(9,063) | $(10,557) | | Net Cash used in investing activities | $(17) | $(53) | | Net Cash provided by financing activities | $25,381 | $4,051 | [Financial Statements and Supplementary Data](index=97&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section presents the company's audited consolidated financial statements, showing cash and cash equivalents increased to **$24.9 million** in 2021, a net loss of **$12.2 million**, and the auditor's substantial doubt about going concern Consolidated Balance Sheet Data (as of December 31) | Account | 2021 (in thousands) | 2020 (in thousands) | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $24,892 | $8,593 | | Total current assets | $25,329 | $9,109 | | **Total Assets** | **$25,987** | **$9,722** | | **Liabilities & Equity** | | | | Total current liabilities | $3,161 | $1,841 | | Total liabilities | $3,422 | $2,212 | | **Total Shareholders' Equity** | **$22,565** | **$7,510** | Consolidated Statement of Operations Data (Years Ended December 31) | Account | 2021 (in thousands) | 2020 (in thousands) | | :--- | :--- | :--- | | Revenues | $571 | $365 | | Gross Profit | $198 | $65 | | Total Operating Expenses | $12,415 | $11,233 | | Operating Loss | $(12,217) | $(11,168) | | **Net Loss** | **$(12,187)** | **$(11,216)** | - The independent auditor's report explicitly states that the company's recurring losses from operations and cash outflows raise substantial doubt about its ability to continue as a going concern[214](index=214&type=chunk) PART III [Directors, Executive Compensation, and Corporate Governance](index=129&type=section&id=Items%2010-14) Information for Items 10-14, covering directors, executive compensation, corporate governance, and related matters, is incorporated by reference from the company's 2022 Proxy Statement - Information regarding directors, executive officers, corporate governance, executive compensation, security ownership, related transactions, and accountant fees is incorporated by reference from the company's 2022 Proxy Statement[293](index=293&type=chunk)[294](index=294&type=chunk) PART IV [Exhibits, Financial Statement Schedules](index=130&type=section&id=Item%2015.%20Exhibits%2C%20Financial%20Statement%20Schedules) This section lists exhibits filed with the Annual Report, including corporate governance documents, material contracts, and certifications, with no financial statement schedules filed - This section contains a list of all exhibits filed with the 10-K, including the company's Articles of Association, material agreements, and required certifications[297](index=297&type=chunk)[299](index=299&type=chunk) - No financial statement schedules were filed with this report[298](index=298&type=chunk)

Entera Bio Ltd. (NASDAQ:ENTX) Q2 2021 Earnings Conference Call August 16, 2021 8:30 AM ET Company Participants Spiros Jamas - CEO Ramesh Ratan - US-based CFO Arthur Santora - CMO Phillip Schwartz – President, R&D Conference Call Participants Kalpit Patel – B. Riley Financial, Inc. Operator Good morning, and welcome to Entera Bio's Conference Call to discuss the Financial and Operating Results for the six months Ended June 30, 2021. At this time, all participants are in a listen-only mode. After the speakers ...

Entera Bio Ltd. (NASDAQ:ENTX) Q4 2020 Earnings Conference Call March 18, 2021 8:30 AM ET Company Participants Jon Lieber – US-based Chief Financial Officer Spiros Jamas – Chief Executive Officer Art Santora – Chief Medical Officer Phillip Schwartz – President-R&D Conference Call Participants Jason McCarthy – Maxim Group Calvin Hori – Hori Capital Operator Good morning, and welcome to Entera Bio's Conference Call to discuss the Financial and Operating Results for the Year Ended December 31, 2020. At this tim ...