Check-Cap Stock

Check-Cap Ltd. operates as a clinical stage medical diagnostics company.

The company is aiming to redefine CRC screening through the introduction of C-Scan, the first and only patient-friendly preparation-free test designed to detect polyps before they may transform into cancer to enable early intervention and cancer prevention.

C-Scan is consisted of three main components: C-Scan Cap, an ingestible X-ray scanning capsule; C-Scan Track, three miniaturized patches worn on the patient’s back for integrated positioning, control and data recording; and C-Scan View, a proprietary software to process and represent 2D and 3D maps of the inner surface of the colon. This solution has the potential to become an alternative for both physicians and patients and to increase the number of people completing CRC screening.

The company’s C-Scan Cap is swallowed and propelled by natural motility through the gastrointestinal tract and excreted naturally with no need for retrieval for data collection (during clinical trials in the U.S., the C-Scan capsule is not intended to be disposed of in the sanitary sewer system, and is therefore collected by the patient, and returned to the medical facility administering the device for further decay and disposal). The company’s C-Scan Cap employs ultra-low-dose X-rays, which allow the C-Scan system to scan the interior lining of the colon even when surrounded by intestinal content. As such, patients using C-Scan will not be required to undergo any prior bowel cleansing.

The company’s C-Scan Cap is being designed to transmit position, motility and the data it collects to the C-Scan Track that will be attached to the patient’s back. The external data recorder is being designed to enable the download of the data to the company’s C-Scan View application to allow physicians to analyze the data collected by the company’s C-Scan Cap. The C-Scan Track is being designed to provide the physician with localization data aligned with a reconstructed image. The company intends for physicians to be able to review the colon’s inner structural information.

The company initiated its first clinical studies in 2010, consisting of two single-center feasibility studies with non-scanning (no X-ray source) capsules for the purposes of measuring gastrointestinal tract activity, colon contractions and associated capsule motility, and shortening capsule transit time.

In 2013, the company initiated a multi-center prospective clinical feasibility study, designed to allow for the recruitment of 100 subjects, to establish clinical proof of concept, safety and functionality of C-Scan in patients eligible for CRC screening. Analysis conducted on the first 66 capsules swallowed by participants showed that 65 of 66 capsules swallowed were naturally eliminated, without major or minor side effects, after 62±40.7 hours. The average calculated radiation exposure was 0.06 ± 0.04 mSv (similar to a single chest radiograph). Both pedunculated and sessile polyps were detected in several patients and validated later by colonoscopy.

In September 2017, the company completed a multi-center study of C-Scan in the support of CE Mark submission. The objective of the study was to assess safety and the clinical performance of C- Scan in detecting patients with polyps. The three-center trial enrolled 66 patients, with a mean age of 59 years. Following capsule ingestion, subjects swallowed small doses of contrast agent and fiber supplements with each meal throughout capsule passage. Average capsule transit time was 52±32 hours, and the average total X-ray dose was 0.05 mSv (CT colonography effective dose is ~ 6.0 mSv). No bowel preparation, sedation, or change in diet was required. Both confirmatory colonoscopy, performed by an independent investigator, and C-Scan review, performed by a central review group, were blinded to results.

In the fourth quarter of 2017, the company initiated an interim clinical study for the purpose of introducing an advanced version of C-Scan, Version 3, which incorporated the then latest algorithms and system optimization and tailored scanning of the colon to the patient’s natural colonic movements to maximize the amount of the colon that is tracked and imaged. In March 2018, the company announced results from the interim study.

Following the company’s certification to ISO 13485:2016 by the company’s Notified Body, and completion of the company’s multi-center clinical study and achievement of compliance with the requirements of the Medical Devices Directive, in September 2017, the company submitted a request for CE marking for the marketing and sale of C-Scan in the European Union. The company received the CE Mark certification from its notified body (DEKRA - 0344) on January 9, 2018 and a renewal certificate according to MDR (EU Regulation 2017/745) was granted on January 12, 2022, which is valid until December 1, 2026. In September 2018, the company received approval from AMAR for the marketing and sale of C-Scan in Israel. Following the MDR approval the company received from its notified body according to the EU Regulation 2017/745, the AMAR approval was renewed and is valid until December 31, 2024.

During the first quarter of 2018, the company initiated a multi-center, open label, home monitoring, prospective study designed to determine the performance characteristics of C-Scan system Version 3, for detecting pre-cancerous polyps compared with the fecal immunochemical test (FIT), in each case using colonoscopy as the reference method, for the purpose of collecting additional evidence of clinical effectiveness and clinical utility to support market adoption. The study included 90 evaluable patients who either had known polyps or were considered to be of average risk. Each patient ingested a C-Scan capsule and also underwent a FIT and a comparative colonoscopy performed by independent gastroenterologists, who were blinded to the corresponding test’s results. The C-Scan clinical evaluation was obtained using the evaluable patient population implementing a gender-based motility analysis and the results of both C-Scan and FIT were compared to colonoscopy. The primary efficacy endpoint of the study was sensitivity (ability to correctly identify patients with polyps) and specificity (ability to correctly identify patients with lack of polyps) of the C-Scan system compared to FIT in detecting subjects with polyps =10 mm. In July 2019, the company announced final results from the company’s post-CE approval study. The results demonstrate that C-Scan achieved a sensitivity of 76% (p=0.0005) in patients with polyps =10 mm, while FIT achieved a sensitivity of 29% (p=0.005) in patients with polyps =10 mm. C- Scan achieved a specificity of 82% in all patients, while FIT achieved a specificity of 96% in all patients. In addition, C-Scan detected all 4 patients (100%) with polyps =40 mm, while the FIT detected only 1 of the 4 patients (25%) with polyps =40mm. Overall, C-Scan achieved a sensitivity of 66% (p=0.01) in all patients, including patients with polyps <10mm, while FIT achieved a sensitivity of 23% (p<0.0001) in all patients, including patients with polyps <10mm. In total, 142 patients enrolled in the study and after factoring in technical and physiological dropouts and protocol violations, the number of evaluable patients was 90. No serious adverse events were reported, and the adverse events were mild in severity.

The company conducted pre-submission meetings with the FDA during the period of December 2016 and February 2017 for the purpose of receiving feedback on the regulatory pathway for the company’s system in the United States. The company also sought feedback on a proposed protocol for a feasibility or pilot study, the primary purposes of which is to establish the safety of the C-Scan system and evaluate user compliance and satisfaction. In December 2018, the company received from the FDA conditional approval of the company’s IDE application to initiate a U.S. pilot study of C-Scan and received final approval from the FDA in February 2019.

In April 2019, the company initiated the U.S. pilot study of C-Scan. The U.S. pilot study (NCT03735407 ) was a prospective, multi-center, open label, single arm study was designed to evaluate the safety, usability and subject compliance of the C-Scan system. The study included 28 evaluable patients, more than two thirds of whom were considered to be of average risk for colorectal cancer. Each patient ingested a C-Scan capsule and also underwent a fecal immunochemical test (FIT), as well as a comparative colonoscopy, which was performed by an independent gastroenterologist who was blinded to the corresponding test results. The study was performed at two sites, the NYU Grossman School of Medicine and Mayo Clinic, Rochester. The primary endpoint of the study was to evaluate the incidence of device or procedure related serious adverse events. Secondary endpoints included patient compliance, subject satisfaction and device and procedure related performance. Due to sample size, the study was not designed to be powered for statistical significance. In December 2019, the company announced the results of the pilot study. No device or procedure related serious adverse events (SAEs) were reported and all device or procedure related adverse events were mild in severity. In total, 45 patients enrolled in the study, of which 40 patients underwent the study procedure. 39 patients complied with the procedure and completed a questionnaire following the procedure and reported higher satisfaction with the C-Scan System procedure compared to colonoscopy. A total of 28 patients were evaluable after factoring in technical and physiological dropouts and protocol violations. Analysis of the evaluable patient results revealed agreement between C-Scan and colonoscopy in detection of polyps was consistent with data from the post-CE approval study.

In preparation for the company’s U.S. pivotal study, the company has continued to optimize C-Scan’s functionality and patient experience by additional clinical data collection in a study in Israel, using advanced C-Scan versions, which incorporate mainly advanced algorithms, improved detection capability and reduced energy consumption. During the current study in Israel, the company initially enrolled both average risk and high-risk patients (e.g., ‘enriched population’) and in May 2022, shifted to enrollment of only average risk patients, for the purpose of further calibration of the C-Scan system, in parallel to conducting the first stage of the U.S. pivotal study that was initiated in May 2022, as described below.

In November 2020, the company finalized its proposed U.S. pivotal study design and submitted the company’s IDE application to the FDA and in March 2021, the company’s IDE application was approved by the FDA.

In January 2022, the company submitted to the FDA an amended IDE application to amend the U.S. pivotal study design to add a first part to the study that is designed to enable further calibration of the C-Scan system and enhancement of C-Scan algorithms, specifically for the average risk U.S. population and in February 2022, the company’s IDE amended application was approved by the FDA. Following this amended IDE, the U.S. pivotal study consists of two parts. The first part is designed to enable further calibration of the C-Scan system for the average risk U.S. population, and is intended to include up to 200 patients in the U.S. The second part is a statistically powered, randomized study which will compare the performance of C-Scan to traditional colonoscopy, and is intended to include up to 800 patients. The goal of the pivotal study in the United States is to (i) demonstrate device safety as evidenced by a lack of device related serious adverse events; and (ii) provide efficacy data concerning C- Scan’s performance.

In May 2022, the company initiated the first part of the U.S. pivotal study. In December 2022, the company submitted an IDE supplement to the FDA to include enrollment of patients at age 45-75 instead of 50-75, which was approved by the FDA in January 2023. As of December 31, 2022, the company had enrolled more than 300 average risk patients as part of the company’s Israeli study and only 17 average risk patients in the first part of the company’s U.S. pivotal study, mainly as a result of slower than expected U.S. site recruitment pace, due to licensing requirements with local states associated with the X-ray technology within the company’s C-Scan capsule. The initiation of the powered potion of the U.S. pivotal study was dependent upon successful completion of the calibration portion of the U.S. pivotal study. Following the company’s internal assessment of the clinical data collected to date from the company’s calibration studies, the company has determined that the current efficacy results do not meet the company’s intention in order to proceed to the powered portion of the U.S. pivotal study. As a result, the company has adopted a plan of action that includes conducting additional clinical data analysis and approaching the FDA to make amendments to the U.S. pivotal study protocol that are expected to be part of an IDE supplement submission to the FDA, and which are subject to FDA approval. In addition, the company plans to continue conducting the company’s calibration studies, albeit at a slower pace, to collect additional clinical data and the company also implementing a cost reduction plan, in order to extend the company’s cash runway. The initiation of the powered portion of the U.S. pivotal study that was expected in mid-2023 is therefore temporarily postponed.

Following and subject to the successful completion of the company’s U.S. pivotal study and available capital, the company’s strategy is to submit a direct de novo reclassification petition for FDA approval for the marketing of C-Scan in the United States. Direct de novo reclassification typically takes at least 9 to 12 months from filing to clearance if there are no comments or disapproval from the FDA. If the FDA determines that C-Scan is not a candidate for de novo reclassification, it will require approval of the device for market through the PMA process. The PMA pathway is much more costly and uncertain than the 510(k) clearance process or de novo reclassification, and generally takes at least 12 to 18 months, or even longer, from the time the application is filed with FDA to ultimate approval if there are no comments or disapproval from the FDA.

Technology

The company’s technology is based on an ingestible capsule (C-Scan Cap), which is swallowed by the patient and propelled by natural motility through the gastrointestinal tract. The company’s capsule transmits information to a receiving device (C-Scan Track) worn on the patient’s body that stores the information for off-line analysis. The company’s C-Scan Cap consists of an X-ray source and several X- ray detectors. The X-ray source is contained in a rotating radiation shield, enabling the generation of 360-degree angular scans. The collection of successive angular scans is intended to enable the virtual reconstruction of a portion of the colon’s inner surface. During movement of the company’s capsule longitudinally through the colon, successive images of portions of the colon enable the three- dimensional reconstruction of the colon. C-Scan is also intended to enable structural identification of polyps, and masses, which protrude inward into the colon, through the detection of irregularities in the topography of the colon’s inner surface.

C-Scan is intended to be prescribed to patients by physicians. Prior to capsule ingestion, patients will swallow 15ml of iodinated oral contrast medium, three times a day, combined with oral fiber, and continue to do so in order to enhance the contrast of the colon surface. The capsule is propelled by natural motility through the gastrointestinal tract. During transit, information is transmitted to the C-Scan Track, which stores the information for off-line analysis. After the company’s C-Scan Cap is expelled from a patient’s body, the C-Scan Track data will be downloaded into the company’s workstation (C-Scan View) and uploaded to a cloud-based server, through which an expert analyst will perform pre-analysis to be followed by a physician’s final interpretation that includes a findings report and a determination of whether the patient is considered average or elevated risk. Currently, the company’s internal analysts are expected to perform the complete interpretation of the data and prepare a report accordingly. The company anticipates that the company will begin involving physicians in this process upon the initiation of the statistically powered portion of the U.S. pivotal study. The company’s proprietary software is being designed to process the data and produce a two and three-dimensional visualization of the colon’s inner surface.

C-Scan consists of the following three main subsystems that together enable the generation of high-resolution 3D imaging of the colon’s inner surface, further described below: (i) an ultra- low-dose X-ray based colon scanning capsule (C-Scan Cap); (ii) C-Scan Track; and (iii) a client\server PC-based application (C-Scan-View).

The C-Scan system enables a patient-friendly, preparation free and painless evaluation of colorectal abnormalities. Using the C-Scan system, suspicious findings that may be colorectal polyps can be identified, thus assisting the physician in deciding to elevate the patient to high-risk category and refer the patient to a colonoscopy procedure. Studies have shown that the adherence of an elevated-risk patient to undergo a colonoscopy procedure is higher than that of an average risk patient.

The C-Scan system provides information for the physician, enabling him to make a ‘YES / NO’ decision for suspected presence of polyps in the colon, based on the premise that the presence of polyps in the colon is associated with the potential development of CRC. The C-Scan system is intended to be used as a preliminary tool to assist in the detecting of subjects who are at elevated risk for polyps and thus may increase the adherence of those subjects to undergo colonoscopy.

The C-Scan system is designed to evaluate the presence of polyps, without the need for fasting and prior bowel cleansing, through identifying suspects in the human colon supported by physiological data, such as measured transit time of the capsule through the GI tract.

The C-Scan system includes three main units, C-Scan Cap, C-Scan Track and C-Scan View.

C-Scan Cap

C-Scan Cap is an X-ray scanning capsule, which enables detection of suspected polyps. C-Scan Cap is ingested by the patient and propelled by peristalsis, natural motility, it passes through the gastrointestinal tract and is excreted naturally, with either no need for retrieval or required retrieval of the capsule, depending on the local agency guidance (during clinical trials in the U.S., the C-Scan capsule is not intended to be disposed of in the sanitary sewer system, and is therefore collected by the patient, and returned to the medical facility administering the device for further decay and disposal).

C-Scan Cap is designed to measure, collect and transmit structural information, and is consisted of the following components:

X-ray Source – Including radioactive material sealed in a cylindrical housing.

Collimator – Radiation shield around the source, which absorbs most of the radiation. Several radial holes enable emission of radiation in defined directions.

X-ray Sensor – Comprised several solid state X-ray detectors for measuring the scattered radiation intensity.

Tilt Sensor – Indication of capsule motion (3D acceleration).

Rotation Motor – For rotating the collimator and X-ray Source.

Compass sensor – Indication of true north (reference coordinate system).

Pressure sensor – indicating the hydrostatic pressure inside the colon.

Source Concealment Mechanism – Conceals the source inside the radiation shield.

R-T – Radio frequency transceiver device to communicate with the receiver.

Batteries – Electrical power supply for the capsule.

Memory – Data storage. The capsule should be able to store up to an hour of measured data.

C-Scan Track Coil – Transmits a continuous electromagnetic field utilized by an external localization system to track 3D position.

C-Scan Track

C-Scan Track is a small, disposable system attached to the patient’s back via biocompatible adhesive skin patches. C-Scan Track communicates with the C-Scan Cap and enables data download for analysis purposes. Both the C-Scan Track and C-Scan Capsule are equipped with an electromagnetic capability allowing for capsule position and orientation estimations through the C-Scan Track. A dedicated scan control algorithm (SCA) identifies the C-Scan Cap’s movements in the colon and, accordingly, commands the C-Scan Cap when to perform a scan. C-Scan Track also measures the transit time from capsule ingestion to excretion through radio frequency communication to a non-volatile memory device, and enable data retrieval, to an external processor.

The C-Scan Track comprised the following components:

Sticker Housings – Biocompatible and water-resistant stickers and housing integrating all functional components, attached to the patient’s back, enabling approximately five days of continuous operation.

Recorder – Consists of receiver electronics embedded software and nonvolatile memory.

Antennas – Radio frequency antennas are embedded into the sticker housings and used to communicate with the capsule.

Activation/Deactivation Circuit – Used to activate/deactivate the C-Scan Track through a specialized protocol.

UI Indicators – Provides user with vocal and vibration indication as required.

PCB – Electronics’ printed circuit boards.

Microcontroller – Runs embedded software, logic that manages the C-Scan Track and SCA.

RF Transceivers – Several transceivers used to communicate with the capsule.

TILT/Compass Sensors – To determine the patient’s body movements.

Batteries – Electrical power supply for the C-Scan Track.

Memory – Non-volatile data storage to store data acquired by the system.

C-Scan View

The C-Scan View software is a client/server-based application that enables procedure data download from the C-Scan Track, data analysis and report generation. The C-Scan View’s main functions are load and display procedure information and data; image review, enabling the user to view structural information of the colon wall; produce procedure report; and store procedure results on server.

The data from the C-Scan Track is loaded and processed to create a reconstruction model of the colon wall, which is displayed in the C-Scan View as structural information of the colon wall, as well as Whole-Gut-Transit-Time (WGTT) data. The data is analyzed by a team that includes expert analysts, who review the structural information to identify suspicious findings that are protruding or bulging on the colon wall. The analysts consider capsule’s WGTT as part of the analysis process. The gastroenterology physician reviews the analysis in the C-Scan View and generates the final report as to whether the patient is assessed to be at average or at elevated risk, determined through a combined analysis consisting of both structural analysis and transit time analyses.

C-Scan System Non-Clinical and Clinical History

The company has developed and validated the company’s capsule-based imaging modality for providing structural information on colonic polypoid lesions and masses for CRC screening. Below is a summary of the validation tests carried out by the company in the laboratory, in phantoms, animals and humans, which were designed to evaluate this new imaging modality’s performance and potential clinical value.

Non-Clinical Testing

Imaging Performance Testing

The C-Scan Cap transmits data as it transits the colon. This data consists of imaged slices perpendicular to the capsule’s longitudinal axis; slices are then reconstructed by the C-Scan View to produce 2D and 3D images of the inner surface of the colon.

Image Reconstruction

Two main characteristics of C-Scan contribute to the image reconstruction performance:

The number of photons hitting the detector per time frame.

The angular spread of the photon beam coming out of the capsule collimator.

Based on the laboratory tests performed with a previous version of C-Scan, polyps of 6 mm and larger should be visible and 10 mm polyps and larger are expected to be detected at higher sensitivity. To further enhance the visibility of 6 mm – 9 mm polyps, a new design of the collimator was successfully incorporated and tested in the company’s advanced C-Scan Cap that is expected to enable 1.5 times the number of photons to be detected by the detectors, allowing the company’s recently enhanced algorithm to improve the imaging performance.

Animal Testing and Tissue Equivalent Phantom Image Reconstruction

The physics of the company’s imaging modality was tested in the laboratory on phantoms with tissue equivalent material and in animals to ensure that laboratory conditions mimic real life clinical scenarios.

Following the initial proof of concept, the company performed a series of studies in order to evaluate the feasibility and preliminary safety of the company’s technology. All studies were performed in pigs ranging from 60 to 90 kg. Pigs, which are commonly used in gastrointestinal studies, were selected as the animal model for preliminary evaluation of C-Scan based on the resemblance of the porcine colon size and morphology to the human colon. However, there are marked differences between the colon of pigs and that of humans. The pig colon is much longer and has a larger diameter, in addition to other anatomical differences. In the pig model, the pressure waves of peristalsis are believed to be more frequent and shorter than in humans. As a result, colon content movement is substantially slower and more frequent in pigs than in humans. In these studies, the company did not intend to collect statistically significant data; hence, the tests were repeated a limited number of times until adequate data was collected.

The first test was performed to demonstrate imaging proof-of-concept using a wired C-Scan. This technology included all the basic features intended to be included in the clinical C- Scan, but on a larger scale due to the use of off-the-shelf components. The subsequent studies used versions of the C-Scan that integrated most of the imaging components, software and electronics of C-Scan that the company used with humans. Since off-the-shelf components were used, the animal capsules were larger and heavier than the version of C-Scan that are used clinically.

Raw data from an animal colon showing a decrease in X-ray florescence, or XRF, photon signals and an increase in Compton backscattering, or CMT, signals corresponding to the position of a polyp that was detected when the company’s C-Scan Cap passed over the polyp is shown in the image below.

Research and Development

The company incurred approximately $14.3 million in research and development expenses, net (after deducting participation by government grants) for the year ended December 31, 2022.

Intellectual Property

As of December 31, 2022, the company had 56 granted patents (not including separate validations in Europe) in main world markets, covering various aspects of the company’s technology. In addition, the company has 19 additional pending patent applications in the pipeline. The company has submitted patent applications covering the company’s technology in the United States, member states of the European Patent Organization, Australia, Brazil, Canada, China, Hong Kong, India, Israel, Japan and South Korea. The company has received patent grants for its core patent by the United States Patent and Trademark Office, as well as from the European Patent Office, Australia, Brazil, China, Hong Kong, Israel, India, Canada, South Korea and Japan. The company also filed patent applications describing the use of the company’s technology in several other medical applications.

The company’s registered U.S. Patent Number 7,787,926 discloses an ingestible capsule with a radiation source and radiation detectors that, when used in conjunction with a radio opaque contrast agent, is adapted to detect clinically relevant findings in the colon. Utilizing X-ray fluorescence and Compton back scatterings, the capsule is able to measure the distance between the capsule and the colon wall and to distinguish between gas, intestinal contents, and clinically significant findings in the gastrointestinal tract. If the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended patent term for this patent will expire on August 28, 2026.

A PCT patent application (PCT/IL2008/000163), granted in Europe, Israel, United States, Australia, India, China, Canada and Hong Kong, discloses additional features, such as a rotating collimator and improved scanning mechanisms, the capability to determine tissue density to differentiate between different types of polyps, as well as the capability to determine capsule movement in the colon. If the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended patent term for all national phases will expire on February 6, 2028, other than the U.S. patent that will expire on April 4, 2030.

Another PCT application (PCT/IL2011/000462), granted in Europe, Israel, United States, Canada, Australia, South Korea and Brazil, discloses a number of alternate fail safe concealment mechanisms that can be utilized in the capsule to ensure that the X-ray source is blocked when the capsule is not scanning and is open when it is scanning, allowing the capsule to image the colon. The fail-safe feature ensures that in the event of power failure, the radiation source is blocked and X-rays do not escape. If the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended patent term for all national phases will expire on June 9, 2031, other than the U.S. patent that will expire on July 5, 2032.

In another PCT patent application (PCT/IL2008/000765), which was granted in the United States, Europe, Israel and Japan, the company discloses an imaging catheter that utilizes X-ray fluorescence, Compton back scattering and electron back scattering. The imaging catheter is designed for use in cardiac applications, as well as intra-operative imaging applications, such as imaging inside blood vessels where optical imaging cannot be performed because of obscuring circumstances. If the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non- extended patent term for all national phases will expire on June 4, 2028, other than the U.S. patent that will expire on July 28, 2028.

In addition, during the year 2022 the company was granted two new patents:

‘Position Estimation of Imaging Capsule in Gastrointestinal Tract’ granted in Israel, covering C-Scan's proprietary tracking technology, which enables real time tracking of the capsule and its activation when it moves throughout the colon. This functionality allows for optimal scanning along the gastrointestinal (GI) tract while maintaining low energy consumption during the procedure. The patent also covers the capsule positioning data recording utilized by the C-Scan analysis suite, which enables gastroenterologists to make a clinical decision and generate a report with their diagnosis and recommendations. Corresponding patents were granted in Japan, China, Europe and the United States.

‘System and method for polyp detection through capsule dynamics’ granted in Japan. This patent was submitted following analysis of hundreds of patients that showed that certain capsule dynamic properties correlate with increased likelihood for the presence of polyps. Corresponding patents were filed in Europe and the United States.

In addition to patent protection, the company relies on trade secrets, including unpatented know-how, technology innovation, drawings, technical specifications and other proprietary. The company also relies on protection available under trademark laws, and hold the following registered trademarks in the United States and Hong Kong: ‘CHECK CAP’, CHECK CAP (logo), ‘C-Scan’ and C-Scan (logo) and the following registered trademarks in the European Union: CHECK CAP (logo), ‘C-Scan’ and C-Scan (logo), and the following trademark applications are pending in China: ‘CHECK CAP’, CHECK CAP (logo), ‘C-Scan’ and C-Scan (logo).

In March 2021, the company entered into an exclusive license agreement with the University of Missouri with respect to certain patents held by the University of Missouri that the University of Missouri claimed included background intellectual property in C-Scan.

Environmental Health and Safety Matters

The company is subject to environmental health and safety laws and regulations in Israel, governing, among other things, the use of radioactive materials, including the Israeli Radioactive Elements and their Products, Regulation, 1980, the Hazardous Substances Law, 5753-1993 and regulations thereunder, including the Licensing of Business Regulations (Disposal of Hazardous Substances), 5750-1990, the Israeli Work Safety Regulations (Occupational Safety and Health of Ionizing Radiation Practitioners) 1992-5753 and Women Employment Regulations (Work with Ionizing Radiation), 1979-5739. The company’s research and development activities, including the company’s production activities, require (and its contemplated commercial activities will require) permits from various governmental authorities, including Israel’s Ministry of Environmental Protection, Israel’s Ministry of Health, local municipal authorities and the NRC and Agreement State regulators. The Ministry of Environmental Protection and the Ministry of Health conduct from time to time periodic inspections in order to review and ensure the company’s compliance with the various regulations.

C-Scan is a medical device subject to extensive regulation by FDA and other U.S. federal and state regulatory bodies. To obtain 510(k) clearance, the company must submit a premarket notification, or 510(k) notice, demonstrating that the proposed device is substantially equivalent to a previously cleared 510(k) device or a device that was in commercial distribution before May 28, 1976 for which the FDA has not yet called for the submission of premarket approval applications.

The company’s manufacturing processes are required to comply with the applicable portions of the QSR, which cover the methods and the facilities and controls for the design, manufacture, testing, production, processes, controls, quality assurance, labeling, packaging, distribution, installation and servicing of finished devices intended for human use.

C-Scan and the company’s operations are also subject to regulation by AMAR, which is responsible for the registration of medical devices in Israel, issuance of import licenses and monitoring of marketing of medical equipment.

History

Check-Cap Ltd. was founded in 2004. The company was incorporated in 2004.