BiomX(PHGE) - 2021 Q4 - Annual Report

FORM 10-K Cover Page This section provides key registrant information, including company details, stock listings, filer status, and market value Registrant Information BiomX Inc., a Delaware corporation, filed its 10-K annual report for the fiscal year ended December 31, 2021, with its stock listed on NYSE American - BiomX Inc. is a Delaware-registered company that submitted its 10-K annual report for the fiscal year ended December 31, 2021[2] Trading Symbols | Title of each class | Trading Symbol(s) | Name of each exchange on which registered | | :------------------ | :---------------- | :---------------------------------------- | | Units | PHGE.U | NYSE American | | Common stock | PHGE | NYSE American | | Warrants | PHGE.WS | NYSE American | Filer Status and Market Value The company is classified as a non-accelerated filer, a smaller reporting company, and an emerging growth company, with a common stock market value of approximately $120 million as of June 30, 2021 - The company is classified as a non-accelerated filer, a smaller reporting company, and an emerging growth company[7] Filer Status and Market Value Metrics | Metric | Value | | :------------------------------------------------------------------ | :-------------- | | Aggregate market value of Common Stock held by non-affiliates (June 30, 2021) | $119,922,575 | | Closing sale price of Common Stock (June 30, 2021) | $5.46 per share | | Shares of Common Stock outstanding (March 25, 2022) | 29,779,249 | Forward-Looking Statements & Risk Factors Summary This section outlines the company's forward-looking statements and summarizes key risks, including operational, financial, and regulatory uncertainties CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS This annual report contains numerous forward-looking statements regarding company operations, financial condition, and clinical development plans, which are subject to significant risks and uncertainties - Forward-looking statements cover company operations, cash flow, financial condition, clinical development plans, safety, tolerability, and efficacy of phage therapies, as well as the design, objectives, and timing of clinical studies[15] - Actual results may differ materially from forward-looking statements due to various factors described in the "Risk Factors" section, and the company undertakes no obligation to publicly revise any forward-looking statements[18] RISK FACTORS SUMMARY The company faces significant risks including unprofitability as a clinical-stage company, future funding needs, uncertainties in phage technology development, clinical trial failures, and regulatory and intellectual property challenges - The company is a clinical-stage entity, has not generated revenue from product sales, expects continued losses, and will require additional financing[21] - Phage technology development is uncertain, no phage drugs are currently approved in the US or EU, and product candidates may not demonstrate required safety and efficacy in clinical trials[21] - Key risks include the COVID-19 pandemic, regulatory uncertainties, clinical trial recruitment difficulties, competition, intellectual property reliance, and political and economic instability in Israel[22][23] PART I This part details the company's business operations, product pipeline, intellectual property, competition, government regulation, and associated risk factors ITEM 1. BUSINESS BiomX Inc. is a clinical-stage microbiome product discovery company developing phage therapies for chronic diseases, currently without approved products and primarily funded by financing and collaborations - BiomX Inc. is a clinical-stage microbiome product discovery company utilizing natural and genetically engineered phage technology to develop products targeting harmful bacteria associated with chronic diseases such as cystic fibrosis, atopic dermatitis, inflammatory bowel disease, primary sclerosing cholangitis, and colorectal cancer[26] - The company currently has no approved products, and its product candidates are still in preclinical and clinical development, generating no revenue from product sales[30] Overview BiomX develops phage therapies to target and eliminate specific harmful bacteria linked to chronic diseases, restoring microbiome balance using proprietary screening and engineering methods - The company develops phage therapies aimed at targeting and eliminating specific harmful bacteria associated with chronic diseases while preserving the rest of the microbiome[28] - Proprietary methods are used to generate and screen phage libraries, prioritizing candidates based on selectivity, potency, safety, stability, and manufacturability[28] Our Product Pipeline BiomX's pipeline includes phage therapies for cystic fibrosis (BX004), atopic dermatitis (BX005), IBD/PSC (BX003), and colorectal cancer, while the BX001 acne program was terminated due to insufficient efficacy - The company's product pipeline includes BX004 (cystic fibrosis), BX005 (atopic dermatitis), BX003 (IBD and PSC), and colorectal cancer (CRC) projects[32][37][39][42] - The Phase 2 clinical study for BX001 (acne treatment) did not show significant efficacy differences compared to placebo, leading the company to discontinue the project[45] BX004 – Treatment of Cystic Fibrosis BX004, a phage product for Pseudomonas aeruginosa infections in cystic fibrosis patients, received FDA approval for a Phase 1b/2a trial and up to $5 million in funding from the Cystic Fibrosis Foundation - BX004 aims to treat chronic respiratory infections caused by Pseudomonas aeruginosa in cystic fibrosis patients, with preclinical studies showing efficacy against resistant strains and biofilm penetration[32] - The FDA approved the initiation of BX004's Phase 1b/2a clinical trial in September 2021, with Part 1 results expected in Q3 2022 and Part 2 results in Q1 2023[34][35] - The Cystic Fibrosis Foundation provided up to $5 million in funding, with the first $3 million equity investment received on December 21, 2021[36] BX005 – Treatment of Atopic Dermatitis BX005, a topical phage product targeting Staphylococcus aureus for atopic dermatitis, demonstrated over 90% eradication in preclinical studies, with Marubeni Corporation investing $3 million and securing a right of first negotiation for Japanese licensing - BX005 is a topical phage product targeting Staphylococcus aureus for atopic dermatitis, with preclinical studies showing eradication of over 90% of Staphylococcus aureus strains[37] - The company entered an equity purchase agreement with Marubeni Corporation of Japan, issuing 375,000 shares of common stock for $3 million in gross proceeds, and granted Marubeni a right of first negotiation for a BX005 license in Japan, effective after Phase 1/2 study results (expected Q4 2022)[38] BX003 – Treatment of IBD and PSC BX003, a broad-spectrum phage product targeting Klebsiella pneumoniae for IBD and PSC, showed safety and good tolerability in its predecessor's Phase 1a study, with development paused until early 2023 - BX003 is a broad-spectrum phage product developed after integrating IBD and PSC projects, targeting Klebsiella pneumoniae, which is associated with both diseases[39] - Phase 1a study of BX002 demonstrated safety, good tolerability, and delivery of high concentrations of phage to the gastrointestinal tract[40] - The company plans to pause development of the BX003 program until early 2023[41] Colorectal Cancer (CRC) The company is developing synthetic engineered phages to target Fusobacterium nucleatum in colorectal cancer tumors and deliver therapeutic payloads, with development paused until early 2023 - The company is developing synthetic engineered phages to target Fusobacterium nucleatum, enriched in colorectal cancer tumors, and plans to deliver therapeutic payloads like immunostimulatory proteins via intravenous administration[42] - The IL-15 gene payload has been successfully engineered into F. nucleatum phages[42] - The company plans to pause development of the CRC program until early 2023[42] BX001 – Treatment of Acne BX001, a topical gel targeting C. acnes for acne, showed safety and reduced C. acnes levels in Phase 1, but Phase 2 lacked significant efficacy, leading to project termination - BX001 is a topical gel targeting Cutibacterium acnes, with Phase 1 studies showing safety, good tolerability, and significant reduction in C. acnes levels[43][44] - The Phase 2 clinical study did not show significant efficacy differences compared to placebo, leading the company to discontinue the project[45] Our Strategy The company's strategy is to develop diverse phage products by precisely targeting microbiome components, optimizing natural and synthetic engineered phage combinations, and advancing clinical and preclinical studies across its pipeline - The company aims to develop diverse phage products by precisely targeting microbiome components and combining natural and synthetic engineered phages through screening, identification, and optimized combinations[46] - Investigate the clinical safety and efficacy of lead phage product candidates for CF, AD, and IBD/PSC[46] - Identify new pathogenic bacterial targets for existing and potential new indications[46] - Develop and collaborate on promoting microbiome biomarker tests based on the proprietary XMarker platform for disease diagnosis or companion diagnostics[46] - Evaluate the preclinical activity of synthetic engineered methods for delivering therapeutic payloads to CRC tumor-resident bacteria and conduct clinical assessments[46] Our Phage Discovery Platform (BOLT) The company's BOLT phage discovery platform integrates computational biology, microbiology, and synthetic engineering to rapidly develop and optimize natural or engineered phage combinations for broad host range, resistance prevention, and manufacturability - The company's phage discovery platform, BOLT, utilizes cutting-edge methods including computational biology, microbiology, and synthetic engineering to rapidly and efficiently develop natural or engineered phage combinations[47] - The BOLT platform optimizes phage cocktails for broad host range, resistance prevention, biofilm penetration, stability, and manufacturability, with optimization development expected to take 1-2 years[48] - The platform technology is derived from the expertise of scientific founders including Professor Rotem Sorek (phage genomics), Professor Eran Elinav (microbiome and human health), and Professor Timothy K. Lu (synthetic biology)[49] Manufacturing The company has developed cGMP-compliant manufacturing processes for phage product candidates, utilizing a hybrid internal and outsourced model, and moved into a new 6,500 sq ft facility in Ness Ziona, Israel, in March 2021 - The company has developed cGMP-compliant manufacturing processes for phage product candidates, designed to meet clinical study needs and regulatory requirements[50] - The company employs a hybrid model combining in-house process development and manufacturing with outsourcing to third-party manufacturing organizations[50] - In March 2021, the company moved into a new 6,500 square foot manufacturing facility in Ness Ziona, Israel, capable of producing clinical quantities of product candidates required for early clinical development[52] Intellectual Property The company protects its technology and product candidates through patents, trademarks, trade secrets, and know-how, with a portfolio covering various product candidates and platforms, typically for 20 years, subject to adjustments or extensions - The company protects its proprietary technology and product candidates through patents, trademarks, trade secrets, know-how, and licensing opportunities[54] - The patent portfolio includes owned, licensed, and co-owned patent applications covering product candidates for CF, AD, IBD, PSC, CRC, as well as bacterial target discovery and phage discovery technology platforms[56][58] - The basic term for U.S. patents is generally 20 years from the earliest non-provisional patent application filing date, and may be extended through patent term adjustment or the Hatch-Waxman Act[68] Patent Portfolio The company's patent portfolio comprises owned, licensed, and co-owned applications for CF, AD, IBD, PSC, CRC product candidates, and discovery platforms, with most applications in early examination - The company's patent portfolio includes wholly-owned patent families, international patent families co-owned with Keio University, international patent families co-owned with Yeda and Keio, and exclusive licenses from Yeda, Keio, or MIT[56] - Most of the patent portfolio targets product candidates for CF, AD, IBD, PSC, and CRC, as well as bacterial target discovery and phage discovery technology platforms[58] Cystic Fibrosis (Patent) The company exclusively owns a PCT-stage patent family covering phage combination drugs, methods of use, and patient identification for chronic Pseudomonas aeruginosa lung infections, with related US patents expected to expire in 2042 - The company exclusively owns a PCT-stage patent family with claims covering phage combination drugs, methods of use, and patient identification for treating chronic Pseudomonas aeruginosa lung infections[59] - Related U.S. patents are expected to expire in 2042, subject to change due to patent term adjustment or extension[59] Atopic Dermatitis (Patent) The company exclusively owns a pre-PCT stage patent family covering phage combination drugs, methods of use, and patient identification for treating skin infections common in AD patients, with related US patents expected to expire in 2042 - The company exclusively owns a pre-PCT stage patent family with claims covering phage combination drugs, methods of use, and patient identification for treating skin infections common in AD patients[60] - Related U.S. patents are expected to expire in 2042, subject to change due to patent term adjustment or extension[60] Inflammatory Bowel Disease (Patent) The company holds multiple patent families in IBD, including exclusive, co-owned, and licensed applications, covering phage combination drugs, methods of use, and targeting pathogenic bacteria, with US patents expected to expire between 2037 and 2042 - The company holds exclusive, co-owned, and licensed patent families in the IBD field, covering phage combination drugs, methods of use, patient identification methods, and methods for treating IBD by targeting pathogenic bacteria[61][62] - Related U.S. patents are expected to expire in 2037, 2038, or 2042, subject to change due to patent term adjustment or extension[62] Primary Sclerosing Cholangitis (Patent) The company holds an exclusive license for PSC, covering bacterial strain drug combinations, methods of use, and treatment by reducing specific bacterial strain levels, with related US patents expected to expire in 2038 or 2039 - The company holds an exclusive license for PSC, covering bacterial strain drug combinations, methods of use, and methods for treating PSC by reducing specific bacterial strain levels[63] - Related U.S. patents are expected to expire in 2038 or 2039, subject to change due to patent term adjustment or extension[63] Colorectal Cancer (Patent) The company exclusively owns a PCT-stage patent family with claims covering synthetic and natural phage combination drugs and formulations for cancer treatment, with related US patents expected to expire in 2041 - The company exclusively owns a PCT-stage patent family with claims covering synthetic and natural phage combination drugs and formulations for cancer treatment[65] - Related U.S. patents are expected to expire in 2041, subject to change due to patent term adjustment or extension[65] Acne (Patent) The company co-owns an international patent family with Yeda, covering phage combination drugs, formulations, methods of use, and patient identification for acne treatment, with related US patents expected to expire in 2038 - The company co-owns an international patent family with Yeda, with claims covering phage combination drugs and formulations, methods of use, and patient identification for treating acne[66] - Related U.S. patents are expected to expire in 2038, subject to change due to patent term adjustment or extension[66] Technology Platform (Patent) The company exclusively licenses two granted US patents and multiple pending applications covering recombinant phage production in yeast, modified host range, and enhanced lysis efficiency, with related US patents expiring between 2034 and 2038 - The company exclusively licenses two granted U.S. patents and multiple pending patent applications covering the production of recombinant phages in yeast cells, recombinant phages with broader or altered host ranges, and recombinant methods for increasing phage lysis efficiency[67] - Related U.S. patents are expected to expire between 2034 and 2038, subject to change due to patent term adjustment or extension[67] Patent Term Patent terms vary by country, typically 20 years from the earliest non-provisional filing in the US, extendable via USPTO adjustments or the Hatch-Waxman Act, subject to limitations - The basic term for U.S. patents is 20 years from the earliest non-provisional patent application filing date, extendable through patent term adjustment to compensate for USPTO administrative delays[68] - The Hatch-Waxman Act allows for patent term extensions for FDA-approved drugs, up to five years or fourteen years from FDA approval, with only one extension per patent[68] Trade Secrets and Know-How Beyond patents, the company relies on trade secrets and know-how, protected by confidentiality and invention assignment agreements, but faces risks of independent development by third parties or costly, unpredictable protection outcomes - The company relies on trade secrets and know-how to develop and maintain its competitive position, protected through confidentiality and invention assignment agreements with employees, consultants, scientific advisors, contractors, and collaborators[70] - Third parties may independently develop equivalent proprietary information and technology or otherwise obtain trade secrets, potentially preventing the company from effectively protecting its trade secrets[71] Competition The biotechnology and pharmaceutical industries are highly competitive, with the company facing rivals possessing superior resources and experience, potentially developing more effective or earlier-approved products - The biotechnology and pharmaceutical industries are highly competitive, with the company facing competition from large pharmaceutical companies, specialized biotechnology companies, academic research institutions, and government agencies[72] - Key competitors include phage product development companies such as Adaptive Phage Therapeutics, Locus Biosciences, Inc., Armata Pharmaceuticals, Inc., and SNIPR Biome[73] - Many competitors possess greater financial, technical, and human resources, along with more extensive experience in product discovery, development, regulatory approval, and commercialization[74] Sales and Marketing The company plans to commercialize its drug product candidates through internal sales and marketing or third-party collaborations, having already granted Marubeni Corporation a right of first negotiation for BX005 licensing in Japan - The company plans to commercialize its drug product candidates by establishing internal sales and marketing capabilities or collaborating with third parties[76] - An equity purchase agreement has been signed with Marubeni Corporation of Japan, providing $3 million and granting them a right of first negotiation for a BX005 license in Japan[77] Government Regulation The company's product candidates are subject to stringent US FDA and international regulations covering R&D, manufacturing, approval, and commercialization, with potential for expedited designations and similar global regulatory frameworks - The company's product candidates' R&D, testing, manufacturing, approval, labeling, promotion, and sales are subject to strict regulation by the U.S. FDA and other national regulatory authorities[78] - In the U.S., biological products require BLA approval, involving preclinical studies, IND submission, IRB approval, clinical trials (Phase 1-3), BLA submission, FDA review, and manufacturing facility inspection[80][81][82][88][89][91] - The company may obtain Orphan Drug Designation (7 years of market exclusivity), Fast Track Designation, Accelerated Approval, and Breakthrough Therapy Designation to expedite development and review processes[93][94][95][96][97] - The EU and other countries have similar regulatory processes, including Clinical Trial Applications (CTA), Marketing Authorization Applications (MAA), Orphan Drug Designation (10 years of market exclusivity), and expedited approval mechanisms (e.g., conditional marketing authorization, PRIME status)[111][112][113][114][115][120][121][122][123][125][126][127] U.S. Biological Product Development Process In the U.S., FDA regulates biologics under FDCA and PHSA, requiring BLA approval through preclinical studies, IND submission, clinical trials, and facility inspections, with non-compliance leading to sanctions - The FDA regulates drugs and biological products under the FDCA and PHSA, with an approval process that is time-consuming and resource-intensive[78][79] - Complete extensive preclinical studies[80] - Submit and have an IND become effective with the FDA[80] - Obtain IRB approval at each clinical trial site[80] - Conduct adequate and well-controlled human clinical trials in accordance with GCP requirements[80] - Submit a BLA to the FDA[80] - FDA decides within 60 days whether to accept the BLA for review[80] - FDA conducts pre-approval inspections of manufacturing facilities to assess cGMP compliance[80] - FDA may audit clinical trial sites[80] - Pay BLA review user fees (unless waived)[80] - FDA reviews and approves the BLA[80] Preclinical Studies and IND Preclinical studies involve product chemistry, formulation, in vitro, and animal research to establish therapeutic rationale and assess adverse events, with IND submission requiring these results and clinical plans, becoming effective in 30 days unless clinically halted by FDA - Preclinical studies include product chemistry and formulation assessment, in vitro and animal studies to establish therapeutic rationale and evaluate potential adverse events, and must comply with GLP regulations[81] - An IND (Investigational New Drug application) is a request to the FDA for authorization to conduct human trials, requiring submission of preclinical test results, manufacturing information, analytical data, and clinical trial plans, typically becoming effective 30 days after FDA receipt unless a clinical hold is issued[81] Clinical Trials Clinical trials involve administering biological product candidates to volunteers or patients under qualified investigators, adhering to GCP, IRB approval, and informed consent, typically progressing through Phases 1-3, with potential for post-market Phase 4, and can be halted by FDA or sponsor - Clinical trials must be conducted under the supervision of qualified investigators, adhering to FDA's GCP requirements, including informed consent and IRB approval[82] - Phase 1: Small group of healthy volunteers or patients, assessing metabolism, pharmacological actions, side effect tolerability, and safety[83] - Phase 2: Patients with the disease, evaluating proof-of-concept and dosing regimens, collecting safety, pharmacokinetic, and pharmacodynamic information, and preliminary efficacy assessment[84] - Phase 3: Large-scale, multi-center patient population, providing data to demonstrate product effectiveness, safety, and overall benefit/risk relationship, forming the basis for new drug labeling[88] - Phase 4: Post-marketing trials, gathering additional patient treatment experience, which the FDA may mandate as a condition of approval[88] - The FDA or sponsor may suspend or terminate a clinical trial at any time, and an IRB may also suspend or terminate trials at its institution[86] FDA Review Process Upon clinical trial completion, data is submitted to the FDA as part of a BLA for safety, efficacy, purity, and potency evaluation, followed by a 60-day acceptance decision, in-depth review, potential facility inspections, data audits, and advisory committee consultations, culminating in an approval letter or complete response letter - Clinical trial data is submitted to the FDA as part of a BLA to evaluate the product's safety, effectiveness, purity, and potency[89] - The FDA decides within 60 days whether to accept the BLA, and if accepted, conducts an in-depth review, with standard review targets of 10 months and priority review of 6 months[90] - The FDA inspects manufacturing facilities for cGMP compliance before approval and may audit clinical trial data or consult advisory committees[91] - The review outcome is either an approval letter (authorizing commercial marketing) or a complete response letter (identifying BLA deficiencies requiring additional data or modifications)[92] Orphan Drug Designation FDA grants Orphan Drug Designation for products treating rare diseases (fewer than 200,000 US patients), offering financial incentives and 7 years of market exclusivity upon first approval, subject to exceptions - The FDA may grant Orphan Drug Designation to products treating rare diseases (affecting fewer than 200,000 patients in the U.S.)[93] - Orphan Drug Designation provides financial incentives such as clinical trial grants, tax credits, and user fee waivers[94] - If the product is the first to be approved, it may receive 7 years of market exclusivity, but exceptions exist if there is a clinical advantage, supply issues, or if the product is deemed the same indication within a competitor's product scope[94] Expedited Development and Review Programs FDA offers Fast Track, Priority Review, and Breakthrough Therapy designations to expedite development and review of new drugs and biologics for serious or life-threatening conditions with unmet medical needs, providing enhanced guidance or faster review, but not guaranteeing approval - The FDA's Fast Track program aims to expedite the review of new drugs and biological products for serious or life-threatening conditions that address unmet medical needs[95] - Priority Review applies to products that treat serious or life-threatening conditions and offer significant improvements in safety or effectiveness[95] - Breakthrough Therapy Designation is for products treating serious or life-threatening conditions where preliminary clinical evidence suggests substantial improvement over existing therapies, offering more intensive FDA guidance[97] - These designations do not guarantee faster development, review, or ultimate approval, and the FDA may withdraw a designation[98] Pediatric Information Under PREA, BLAs or supplements must include pediatric safety and efficacy data, requiring sponsors to submit a Pediatric Study Plan (PSP), with FDA potentially granting deferrals or waivers for pediatric data submission - Under the PREA, a BLA or supplement must include data assessing the product's safety and effectiveness in all relevant pediatric subpopulations[100] - Sponsors must submit an initial Pediatric Study Plan (PSP) within 60 days after the Phase 2 meeting, and the FDA may grant deferrals or full/partial waivers for pediatric data submission[100] Post-marketing Requirements Post-approval, manufacturers and products remain under continuous FDA regulation, including monitoring, adverse event reporting, promotional compliance, and approval for product modifications, with potential for REMS or post-marketing studies, and non-compliance leading to severe penalties - After product approval, manufacturers and products remain subject to continuous FDA regulation, including monitoring, record-keeping, adverse event reporting, promotional and advertising compliance[101] - The FDA may require the implementation of Risk Evaluation and Mitigation Strategies (REMS) or post-marketing studies to ensure safe product use[102] - Manufacturers must comply with cGMP regulations and undergo regular FDA inspections; non-compliance may result in approval withdrawal, product recall, fines, or criminal penalties[103] Biosimilars and Exclusivity The Biologics Price Competition and Innovation Act provides a streamlined approval pathway for biosimilars, requiring demonstration of high similarity and no clinical differences to a reference product, which enjoys 12 years of data exclusivity, extendable by 6 months for pediatric exclusivity - The Biologics Price Competition and Innovation Act provides a streamlined approval pathway for biosimilars, requiring demonstration of high similarity to a reference product with no clinically meaningful differences[105] - Reference biological products enjoy 12 years of data exclusivity, and the FDA will not accept biosimilar applications for 4 years[107] - Pediatric exclusivity can add 6 months to existing regulatory exclusivity periods[108] Companion Diagnostics The company may use companion diagnostics to identify patients more accurately; these are FDA-regulated medical devices requiring PMA or 510(k) premarket notification and should be co-developed and approved with therapeutic products - The company may use companion diagnostics to more accurately identify patients, with companion diagnostics regulated by the FDA as medical devices[109] - Companion diagnostic devices require premarket approval (PMA) or 510(k) premarket notification, and for therapeutic products, should be co-developed and approved simultaneously with the therapeutic product[109] Government Regulation Outside of the United States Outside the US, the company's product candidates are subject to national regulations for clinical trials, approval, manufacturing, and distribution, with potential restrictions on bio-sourced materials and similar EU processes for CTAs, MAAs, and ATMPs - Outside the U.S., the company's product candidates' clinical trials, approval, manufacturing, and distribution are also subject to national regulations, and the use of bio-sourced raw materials may be restricted[111] - The EU has similar Clinical Trial Application (CTA) and Marketing Authorization Application (MAA) processes, including centralized and decentralized approval procedures, and specific rules for Advanced Therapy Medicinal Products (ATMPs)[112][114][115][118] Clinical Trials (OUS) Countries outside the US have similar clinical trial regulatory processes, such as the EU requiring CTA submission to national health authorities and ethics committees, with trials adhering to GCP and the Declaration of Helsinki - Countries outside the U.S. have similar clinical trial regulatory processes; for example, the EU requires submission of Clinical Trial Applications (CTA) to national health authorities and independent ethics committees[112] - Clinical trials must comply with GCP and the ethical principles of the Declaration of Helsinki, with varying requirements and procedures across countries[112] Approval Process (OUS) To sell products internationally, the company must obtain foreign regulatory approval and comply with national requirements, which vary by country, may require additional testing, and differ in timing from FDA approval, with EU MAAs processed via centralized or decentralized procedures - To market products internationally, the company must obtain marketing approval from foreign regulatory authorities and comply with their regulatory requirements, with approval procedures varying by country[113] - EU Marketing Authorization Applications (MAA) can be processed through centralized or decentralized procedures; the centralized procedure involves scientific assessment by the European Medicines Agency's (EMA) CHMP and approval by the European Commission[114][115][117] - Marketing authorizations are typically valid for five years and renewable, unless an additional renewal is decided for pharmacovigilance reasons[119] Orphan Designation (OUS) EU Orphan Drug Designation promotes rare disease drug development for conditions affecting fewer than 5 in 10,000 people in the EEA, offering fee reductions and 10 years of market exclusivity, which may be reduced or lost if standards are no longer met or superior competing products emerge - EU Orphan Drug Designation applies to life-threatening or chronically debilitating conditions affecting fewer than 5 in 10,000 people in the EEA[121] - Orphan Drug Designation provides fee reductions and 10 years of market exclusivity, but this period may be reduced to 6 years or lost if criteria are no longer met or a clinically superior competing product emerges[122] Expedited Development and Approval (OUS) The EU offers expedited approval mechanisms, including accelerated assessment (MAA review reduced from 210 days to 150 days) and conditional marketing authorization based on incomplete data, alongside PRIME status and "MA under exceptional circumstances" to support unmet medical needs - The EU has expedited approval mechanisms, including accelerated assessment (reducing MAA review time from 210 days to 150 days) and conditional marketing authorization (granted based on incomplete data, subject to subsequent conditions)[123][127] - Conditional marketing authorization is typically limited to situations with incomplete clinical data, valid for one year, and renewable until conditions are met[124][125] - EMA's "PRIME" status (Priority Medicines) aims to support and accelerate the development and approval of complex innovative medicines, offering early dialogue and scientific regulatory support[126] - "MA under exceptional circumstances" applies to products for serious diseases or unmet medical needs, allowing approval even with incomplete data, but requiring annual review of the benefit-risk balance[127] Pediatrics (OUS) The EU mandates pediatric drug testing, requiring pediatric data for new active substances or indications unless EMA grants waivers or deferrals, with PIP completion leading to pediatric rewards like SPC or market exclusivity extensions - The EU mandates drug testing in pediatric populations, requiring pediatric data for new active substances or new indications unless EMA grants a waiver or deferral[128] - Pediatric data is generated through a Pediatric Investigation Plan (PIP), and completing a PIP can lead to pediatric rewards such as a six-month extension of the SPC term or a two-year extension of orphan drug market exclusivity[129][130] Post-Marketing Requirements (OUS) Many countries impose post-marketing regulatory requirements similar to those in the US, particularly for safety monitoring or pharmacovigilance, with EU pharmacovigilance data potentially leading to post-marketing studies, and non-compliance resulting in substantial fines or license suspension - Many countries impose post-marketing regulatory requirements similar to those in the U.S., particularly for safety monitoring or pharmacovigilance[131] - EU pharmacovigilance data may lead regulatory authorities to require post-marketing safety or efficacy studies, and non-compliance can result in substantial fines, suspension, or withdrawal of marketing authorization[131] - The EU's Supplementary Protection Certificate (SPC) can extend patent terms by up to five years, with the combined patent and SPC protection period not exceeding fifteen years from the first marketing authorization[132][133] - The EU also offers regulatory exclusivity periods such as data exclusivity (8 years), market protection (2 years), market exclusivity (10 years, for orphan drugs), and pediatric rewards[135][136][138][139] Other U.S. Healthcare Laws and Compliance Requirements The company is subject to federal and state healthcare fraud and abuse laws, including anti-kickback, false claims, civil monetary penalties, HIPAA, and ACA transparency requirements, with violations potentially leading to severe criminal and civil penalties - The company may be subject to federal and state healthcare fraud and abuse laws, which impact marketing, sales, and distribution arrangements[141] - Federal Anti-Kickback Statute: Prohibits payments to induce referrals or purchases of products or services reimbursable by federal healthcare programs[142] - Federal Civil and Criminal False Claims Acts: Prohibit submitting false or fraudulent claims for payment to the federal government[142] - Civil Monetary Penalties Law: Prohibits offering remuneration to Medicare or Medicaid beneficiaries that may influence their choice[142] - HIPAA: Created federal criminal statutes prohibiting healthcare benefit program fraud or obtaining funds by false pretenses[142] - Affordable Care Act's Transparency Requirements (Sunshine Act): Requires manufacturers to report payments or transfers of value to physicians and teaching hospitals[142] - Federal government price reporting laws: Require accurate and timely reporting of complex pricing metrics to government programs[142] - Federal consumer protection and unfair competition laws: Broadly regulate market activities and activities that may harm consumers[142] - Violations of these laws may result in criminal and/or civil sanctions, including fines, imprisonment, and exclusion from federal and state healthcare programs[145] Additional Regulation The company's operations are subject to state and federal environmental and hazardous materials laws, including OSHA, RCRA, and TSCA, governing the use and disposal of biological, chemical, and radioactive substances, as well as the US Foreign Corrupt Practices Act prohibiting bribery of foreign officials - The company's operations are subject to state and federal environmental and hazardous materials laws, such as the Occupational Safety and Health Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, which regulate the use, handling, and disposal of biological, chemical, and radioactive materials[149] - The company is subject to the U.S. Foreign Corrupt Practices Act, which prohibits bribing foreign government officials to obtain or retain business, with similar rules applying in other countries[150] U.S. Healthcare Reform US healthcare reform, driven by cost control, has significantly impacted the pharmaceutical industry through the Affordable Care Act and subsequent legislation, increasing Medicaid rebates and imposing manufacturer fees, with future reforms likely to further restrict payment for medical products and services - A major trend in the U.S. healthcare industry is cost containment, with government and third-party payers controlling costs by limiting coverage and reimbursement amounts[151] - The 2010 Affordable Care Act (ACA) increased Medicaid rebates, introduced new rebate calculation methods, imposed annual fees on manufacturers, and created the Medicare Part D coverage gap discount program[151] - Subsequent legislation (e.g., the Budget Control Act of 2011, the Bipartisan Budget Act of 2015, the American Taxpayer Relief Act of 2013, and the American Rescue Plan Act of 2021) further impacted Medicare payments and Medicaid drug rebates[152][153][154] - More healthcare reform measures are expected in the future, potentially limiting payment amounts for medical products and services, thereby affecting demand and pricing for the company's products[155] Coverage and Reimbursement Commercial sales of the company's approved products will depend on third-party payer coverage and reimbursement, which may involve coverage limitations, reimbursement caps, and cost-effectiveness studies, with ex-US markets also subject to government price controls and health technology assessments - Commercial sales of the company's products (if approved) will depend on coverage and reimbursement by third-party payers (government, managed care, private insurance)[156] - Payers may limit coverage or reimbursement amounts and require expensive clinical trials to demonstrate product medical necessity and cost-effectiveness[156][159] - Countries outside the U.S. impose government controls on drug pricing and may require additional cost-effectiveness studies or health technology assessments to obtain reimbursement or pricing approval[161] Data Privacy and Security Laws The company is subject to various state, federal, and foreign data privacy and security laws governing personal and health-related information, with non-compliance potentially leading to substantial civil and/or criminal penalties and private litigation - The company is subject to various state, federal, and foreign laws and regulations governing the collection, dissemination, use, access, confidentiality, and security of personal information, including health-related information[162] - Non-compliance with these laws may result in substantial civil and/or criminal penalties and private litigation[162] Material Agreements The company has entered into several license agreements with Yeda, Keio, and JSR, securing exclusive rights to patent portfolios related to its phage discovery platform and IBD/PSC programs, with terms including annual fees, milestone payments, and sales royalties - The company has entered into research and license agreements with Yeda, obtaining an exclusive worldwide license for proprietary technology and research information related to its phage discovery platform, IBD, CRC, and other indications[163][164] - The company has entered into exclusive patent license agreements with Keio and JSR, obtaining exclusive worldwide sublicenses for patent rights related to its IBD and PSC programs[169][173] - These agreements stipulate annual license fees, milestone payments (up to $3.2 million combined for IBD and PSC projects), and sales royalties (low single-digit percentages), with specific provisions for intellectual property maintenance and enforcement[170][174] License Agreement with Yeda The company has an exclusive global license agreement with Yeda for its phage discovery platform, IBD, CRC, and other indications, involving annual fees, low single-digit sales royalties, and potential mid-to-high single-digit sublicense revenue, with a term extending until the last licensed patent expires or 11 years post-first commercial sale - The company entered an exclusive worldwide license agreement with Yeda, covering proprietary technology and research information related to its phage discovery platform, IBD, CRC, and other indications[163][164] - The company is required to pay an annual license fee of $10,000, low single-digit sales royalties, and potentially mid-to-high single-digit percentages of sublicense revenue[164] - The agreement term extends until the expiration of the last licensed patent or 11 years after the first commercial sale of a product, and Yeda may terminate the agreement if the company fails to meet certain diligence and development requirements[165] Exclusive Patent License Agreement with Keio and JSR Corporation for IBD The company has an exclusive patent sublicense agreement with Keio and JSR for IBD-related patents, requiring a $10,000 license fee, annual fees of $15,000-$25,000, up to $3.2 million in clinical and regulatory milestones, and low single-digit sales royalties, with a term until the last patent expires or five years post-first commercial sale - The company entered an exclusive patent license agreement with Keio and JSR, obtaining a sublicense for patent rights related to its IBD program, involving bacterial targets and phages associated with IBD[169] - The company is required to pay a $10,000 license fee, annual fees ranging from $15,000 to $25,000, clinical and regulatory milestone payments up to $3.2 million, and low single-digit sales royalties[170] - The agreement term extends until the expiration of the last patent or five years after the first commercial sale of a product, and JSR may terminate the agreement if the company fails to make payments or commits a material breach[171] Exclusive Patent License Agreement with Keio and JSR for PSC The company has an exclusive patent sublicense agreement with Keio and JSR for PSC-related patents, requiring a $20,000 license fee, annual fees of $15,000-$25,000, up to $3.2 million in clinical and regulatory milestones, and low single-digit sales royalties, with a term until the last patent expires or five years post-first commercial sale - The company entered an exclusive patent license agreement with Keio and JSR, obtaining a sublicense for patent rights related to its PSC program, involving bacterial targets and phages associated with PSC[173] - The company is required to pay a $20,000 license fee, annual fees ranging from $15,000 to $25,000, clinical and regulatory milestone payments up to $3.2 million, and low single-digit sales royalties[174] - The agreement term extends until the expiration of the last patent or five years after the first commercial sale of a product, and JSR may terminate the agreement if the company fails to make payments or commits a material breach[175] Employees As of December 31, 2021, the company had 103 full-time employees and consultants, plus 16 part-time staff, with 33 holding PhDs or MDs and 99 engaged in R&D, maintaining good employee relations and COVID-19 safety measures without pandemic-related layoffs - As of December 31, 2021, the company had 103 full-time employees and consultants, and 16 part-time employees[177] - Of these, 33 employees hold PhD or MD degrees, and 99 employees are engaged in research and preclinical development activities[177] - The company implemented COVID-19 safety measures, including masks, social distancing, and remote work, and did not lay off employees due to the pandemic[178] Corporate Information BiomX Ltd. was founded in Israel in 2015 as MBcure Ltd., and BiomX Inc., originally Chardan Healthcare Acquisition Corporation Inc., a Delaware SPAC, completed a business combination with BiomX Ltd. on October 28, 2019, making BiomX Ltd. a wholly-owned subsidiary - BiomX Ltd. was incorporated in Israel in March 2015, originally named MBcure Ltd[179] - BiomX Inc. was incorporated in Delaware on November 1, 2017, originally named Chardan Healthcare Acquisition Corporation Inc., a special purpose acquisition company[180] - On October 28, 2019, BiomX Inc. completed a business combination with BiomX Ltd. and was renamed BiomX Inc., with BiomX Ltd. becoming its wholly-owned subsidiary[183] - The company's headquarters are located in Ness Ziona, Israel, and its website is www.biomx.com[186](index=186&type=chunk) Information About Our Executive Officers The executive team comprises CEO Jonathan Solomon, CBO Assaf Oron, Chief Development Officer Dr. Merav Bassan, and SVP of Finance and Operations Marina Wolfson, bringing extensive experience in biotechnology, pharmaceuticals, and finance Executive Officers | Name | Age | Position | | :--------------- | :-- | :----------------------------------------- | | Jonathan Solomon | 45 | Chief Executive Officer and Director | | Assaf Oron | 47 | Chief Business Officer | | Dr. Merav Bassan | 56 | Chief Development Officer | | Marina Wolfson | 38 | Senior Vice President of Finance and Operations | - Jonathan Solomon has served as Chief Executive Officer since October 2019, previously co-founding and serving as President and CEO of ProClara Biosciences Inc[187] - Assaf Oron has served as Chief Business Officer since October 2019, previously Executive Vice President of Strategy and Business Development at Evogene Ltd[188] - Dr. Merav Bassan has served as Chief Development Officer since October 2019, previously holding various development positions at Teva Pharmaceutical Industries Limited[189] - Marina Wolfson has served as Senior Vice President of Finance and Operations since October 2020, previously Vice President of Finance at BioView Ltd[190] ITEM 1A. RISK FACTORS The company faces numerous risks, including sustained losses as a clinical-stage entity, uncertain future financing, high-risk phage technology development, clinical trial failures, COVID-19 impacts, regulatory delays, market acceptance issues, intellectual property challenges, third-party reliance, Israeli operational risks, and common stock price volatility - The company is a clinical-stage biopharmaceutical company that has incurred continuous losses since its inception, expects to continue incurring significant expenses in the future, and will require additional financing[193][195] - Phage technology development is highly uncertain, no phage drugs are currently approved in the U.S. or EU, and product candidates may not demonstrate the required safety and efficacy in clinical trials[203][207] - COVID-19 pandemic, regulatory approval delays, insufficient market acceptance, intellectual property reliance and protection challenges, third-party collaboration risks, and political and economic instability in Israel are key operational risks[208][213][224][308][363] Risks Related to Our Business, Technology and Industry As a clinical-stage company, the company faces risks including sustained losses, future funding needs, phage technology development uncertainties, clinical trial failures, COVID-19 impacts, regulatory delays, market acceptance issues, manufacturing challenges, intense competition, and over-reliance on its BOLT platform - The company has incurred continuous losses since its inception in 2015, with an accumulated deficit of $108.5 million as of December 31, 2021, and expects to continue incurring significant expenses in the future[193] - As of December 31, 2021, the company had $63.1 million in cash, cash equivalents, and restricted cash, but will need to raise additional funds in the future to support operations and product development[195] - Phage technology development is highly uncertain, no phage drugs are currently approved in the U.S. or EU, and product candidates may not demonstrate the required safety and efficacy in clinical trials[203][207] - The COVID-19 pandemic has had and may continue to have adverse effects on the company's business, preclinical studies, and clinical trials, including delays in patient enrollment, difficulties in clinical site initiation, and supply chain disruptions[208][210] Risks Related to Government Regulation The company faces risks of regulatory approval delays or failures, with no guarantee of expedited approval even with special designations, potential loss of orphan drug exclusivity, ongoing compliance obligations post-approval, and the possibility of FDA rejecting ex-US clinical data, alongside impacts from healthcare reform and government disruptions - Even with Breakthrough Therapy or Fast Track Designation, there is no guarantee of accelerated development, review, or ultimate approval, and designations may be withdrawn[276][278][279][280] - Orphan Drug Designation may not be obtained or maintained, and even if granted, exclusivity may be lost due to competition or failure to meet patient needs[281][282][283][284] - Post-approval, products remain subject to continuous regulatory compliance obligations, including cGMP, GCP, labeling, promotion, and post-marketing studies; non-compliance may result in approval withdrawal, product recall, fines, or criminal penalties[285][286][287][288][289][290][291][292][293] - The FDA may not accept clinical trial data from outside the U.S., potentially requiring additional trials, increasing costs and time; healthcare reform and government agency disruptions may adversely affect the business[294][295][296][297][298][299][300][301][302][303] Risks Related to Our Licensed and Co-Owned Intellectual Property The company's business heavily relies on third-party licensed intellectual property, facing severe harm if licenses are terminated or restricted, and risks from patent challenges, unenforceability, or circumvention, as well as trade secret disclosure and potential infringement litigation - The company is highly dependent on intellectual property licensed from third parties; termination or restriction of license agreements would result in significant loss of rights and severely harm the business[308][309] - The patent portfolio may be challenged, deemed unenforceable, invalid, or circumvented, and patent application outcomes are uncertain, potentially failing to provide adequate competitive protection[314][315][316][318][319][320][321][322] - The company relies on trade secrets to protect its technology but faces risks of employee disclosure, independent development by competitors, and high, unpredictable costs of trade secret protection[340] - Infringement of third-party intellectual property rights could lead to litigation, damages, royalties, or inability to commercialize products; obtaining rights to third-party intellectual property also involves uncertainty[328][329][330][331][332][333][334][335][336] Risks Related to Our Reliance on Third Parties The company relies on third parties like CROs and clinical investigators for trials, risking delays or termination due to poor performance, with reduced control but retained regulatory responsibility, and complex collaborations posing threats to product development and commercialization if not maintained or established - The company relies on third parties (e.g., CROs and clinical investigators) for clinical trials; poor performance or failure to complete on time may lead to trial delays, termination, or repetition[345][347] - The company has reduced control over third-party R&D activities but remains responsible for ensuring clinical trials comply with GCP and protocols[346] - Third-party collaborations are complex; failure to maintain or establish new collaborations, or unsuc