About IceCure Medical Ltd

IceCure Medical Ltd. (IceCure) operates as a commercial stage medical device company. The company is focusing on the research, development and marketing of cryoablation systems, disposables and technologies based on LN2 for treating tumors. The company's proprietary cryoablation technology is a minimally invasive alternative to surgical intervention, for tumors, including those found in breast, lungs, kidneys, bones and other indications. The company's lead commercial cryoablation product is the ProSense system. In addition to the company's existing lead product, the ProSense system, a single probe system, the company has developed an additional multi probe system that is expected to have the ability to freeze several tumors simultaneously or larger tumors, which the company refers to as its MultiSense system, which has not yet been commercialized. In the company's continued efforts aimed at improving its core technology, the company is focusing on developing the company's next generation MultiSense system, which the company intends to commercialize subject to regulatory approvals. The company is also in the process of developing the company's next generation single probe system. As of December 31, 2022, in the United States, the company had a broad range of regulatory approvals for its systems to treat benign and malignant tumors in the lungs, kidneys, bones, fibroadenoma (benign breast tumor) and other indications. In the United States the company's products are approved as a 'single family' known as the 'IceCure Family,' which includes the IceSense3, ProSense, and MultiSense (which has not been commercialized) cryoablation systems. Although the company's existing, 'IceCure Family' systems have regulatory approvals from the FDA for commercialization in the United States, the company has yet to receive regulatory approval for such systems for the treatment of malignant breast tumors, which requires separate approval from the FDA. The FDA classifies medical devices into one of three classes (Class I, Class II, or Class III) depending on their level of risk and the types of controls that are necessary to ensure device safety and effectiveness. The class assignment is a factor in determining the type of premarketing submission or application, if any, that will be required before marketing products in the United States. On October 18, 2022, the company requested that De Novo classification be accepted for the company's 'IceCure Family' systems for breast cancer indication. Because of this De Novo classification request, the company will be required to accept special controls imposed by the FDA, mainly on the production process and post-market monitoring. This De Novo classification request regulatory filing with the FDA for marketing authorization was based on the company's ICE3 clinical trial interim analysis of ProSense for the indication of early-stage (Luminal A T1 invasive) low-risk breast cancer in patients who are at high risk to surgery (not suitable for surgical alternatives). In Europe, China, Singapore, India, Hong Kong, Russia, Thailand, Taiwan, South Africa, Mexico, Australia, Israel, Colombia and Costa Rica, the company has approvals for either the company's ProSense or its IceSense3 systems, or, in certain countries, both products. For instance, in China, the company has approval for its IceSense3 (without the disposables). In addition, in order to generate significant revenue, the company is seeking to pursue additional regulatory approvals for the company's products for specific indications in countries where the company already has general regulatory approvals. In these countries, the company is seeking regulatory approval for the treatment of specific tumors, including those found in breast, lungs, kidneys and bones. In addition, the company is seeking regulatory approvals for its systems in other countries where there is significant potential for sales of the company's products. On October 12, 2021, the company announced the advancement of its regulatory strategy in China with the submission of an amendment to the registration certificate for the IceSense3 system, which was granted by China's National Medical Products Administration, or NMPA. On March 28, 2023, the company announced that the NMPA approved its IceSense3 disposable cryoprobes for commercial use, to be used in combination with the company's IceSense3 system console. This approval will allow the company to sell its disposable IceSense3 cryoprobes for commercial procedures. The company expects to launch its commercial sales program for the IceSense3 system in China in the second half of 2023. Growth Strategy The company's growth strategy includes the following actions: Obtaining regulatory approval for the company's ProSense and other future systems in countries within which the company does not have regulatory approval, as well as obtaining regulatory approvals for additional indications in countries within which the company already have certain approvals. Specifically, the company intends to seek to obtain FDA approval to commercialize the company's products for the treatment of malignant breast tumors. Obtaining clinical data (by conducting both sponsored and independent clinical trials for the company's systems) and by gaining the support of these key opinion leaders. Expanding the company's distribution network for further commercialization, which may include distribution and/or license agreements or other forms of collaborative agreements. Obtaining the relevant approvals to allow for reimbursement to end-users of the company's systems. Having cryoablation treatment included in the recommendation guidelines as a valid treatment option of certain medical associations, such as the ASBrS. Continuing research and development efforts aimed at developing the company's next generation single Probe and MultiSense systems. Completing development and obtaining regulatory approval to commercialize the company's next generation single Probe and MultiSense systems for a variety of indications, in the United States is necessary in order for the company to grow the company's business. Obtaining guidelines from relevant professional societies in the geographic territories the company operates or plan to operate. Expanding utilization and use of the company's products for breast cancer treatment by commercial sales and clinical studies around the world. Primary Indication Benign Breast Tumors Clinical Trial in Fibroadenoma (Benign Breast Tumors) The company sponsored and completed a prospective clinical trial in benign breast tumors in the Czech Republic, Israel and Germany. Between April 2009 and September 2012, data was collected from 60 procedures that were performed across four clinical sites located in Czech Republic, Israel and Germany (two sites). The IceSense3 was used to conduct the cryoablation procedures. The primary endpoint was to create an ice ball which would successfully engulf the entire tumor, as seen using ultrasound imaging. The company's inclusion criteria were patients over 18 years old with core biopsy-proven breast fibroadenoma between 0.5 cm and 3.0 cm. The expected probability of success was 88%. Malignant Breast Tumors Clinical Trials in Cancerous (Malignant) Breast Tumors The company is sponsoring trial in the United States. The company's systems and probes are being used in three clinical studies initiated by investigators for malignant breast tumors in Japan, Hong Kong and China, and the Netherlands. Based on data presented from the Kameda Medical Center in Kamogawa, Japan, since June 2006, more than 600 procedures for cancer have been performed at the Center using the company's IceSense3 cryoablation system. Multi-Site Clinical Trial of the Cryoablation System ICE3 Study - the United States In May 2014, the company initiated a multi-site clinical trial in the United States, which included participation of 19 sites in the ICE3 trial. The ICE3 trial was intended to expand the clinical base for using the company's cryoablation system for treating low-risk, small breast cancer tumors (up to 1.5 centimeters). The primary goal of ICE3 was to assess the effectiveness by the breast tumors local recurrence rates in patients who undergo cryoablation without excision for a follow-up period of five years. The inclusion criteria were patients over 65 years old with core biopsy-proven invasive ductal carcinoma with unifocal primary disease, tumor size less than 1.5 cm, Nottingham grade 1-2, estrogen and/or progesterone receptor positive and HER2 negative and breast size adequate for safe cryoablation. In February 2019, the last patient was recruited. In total, 211 patients were recruited to the ICE3 trial, 206 of whom have enrolled, and 194 undergone Cryoablation according to the study protocol. In April 2021, as part of the yearly conference of the ASBrS, the interim results of the ICE3 trial were presented. At the follow up period of 34.83 months following treatment with the company's cryoablation system, only 2.06% (four patients) experienced cancer recurrence. The 36-month local Failure Free Probability is 99.22%. At the 23rd annual conference of the ASBrS in April 2022, the company's publication titled 'Cryoablation without Excision for Low-Risk Early-Stage Breast cancer: 3-Year Analysis of ipsilateral Breast Tumor Recurrence in the ICE3 Trial' that was published in the Annals of Surgical Oncology was selected by past ASBrS president, Helen Pass, MD, Co-Director of the Stamford Health Breast Center, Chief of Breast Surgery at Stamford Hospital, and Clinical Professor of Surgery at Columbia University, for her annual presentation following a comprehensive literature review. On October 18, 2022, the company submitted a De Novo classification request regulatory filing with the FDA for marketing authorization based on the company's ICE3 clinical trial interim analysis of ProSense for the indication of early-stage (Luminal A T1 invasive) low-risk breast cancer in patients who are at high risk to surgery (not suitable for surgical alternatives), representing approximately 43,000 women in the U.S. annually. The specific indication filed is based on interim data from the company's ICE3 trial and is in accordance with discussions the company has had with the FDA, which granted ProSense Breakthrough Device Designation on March 31, 2021, enabling closer communications regarding its regulatory filing. Final ICE3 5-year follow-up data are expected in the first half of 2024, at which time the company plans to file with the FDA for a broader indication reflecting the entire study population-early-stage (Luminal A T1 invasive) low-risk breast cancer for patients aged 60 and over, representing approximately 65,000 women in the U.S. annually. ICE3 is the largest controlled multi-location clinical trial ever performed for liquid nitrogen based cryoablation of small, low-risk, early-stage malignant breast tumors without subsequently removing them. The trial began in 2014 and has completed recruitment of 206 patients (of which 194 were eligible for cryoablation) in 19 hospitals and medical centers across the U.S., including Columbia University Medical Center and Mount Sinai Beth Israel. In the company's De Novo classification request, the company has updated that there have been six cases of ipsilateral breast tumor recurrence ('IBTR') out of 194 patients, or 3.09%. The survival-based estimate for the 5-year IBTR is 4.3% with a one-sided 95% confidence level, upper bound of 8.4% for the entire study population. In the future, IceCure intends to explore more indications for additional subgroups that are part of the total group of Luminal A breast cancer. Independent Clinical Trial of the Cryoablation System - Japan Since May 2012, an independent clinical trial has been ongoing at the Kameda Medical Center in Kamogawa, Japan using the company's IceSense3 cryoablation system. So far, over 600 cryoablation procedures have been conducted using the company's cryoablation system (in addition to approximately 80 additional procedures with a different system). In addition, since May 2018, an independent investigator initiated clinical trial in Japan at the St. Marianna University School of Medicine Department of Mammary Gland and Endocrine Surgery using the company's ProSense system. The trial's purpose was conducted in breast cancer tumors of up to 1.5 cm (in their early stages). The inclusion criteria were patients with histologically-proven breast cancer at stage 0 (TisN0M0) or stage 1 (T1N0M0), between the age of 20 and 85 years, HER2 protein expression-negative status, Ki-67 positivity of less than or equal to 20% and lesion spread of 1.5 cm or less. The trial was completed after the enrollment of seven patients, in which pathology was confirmed using a vacuum-assisted biopsy. In all seven patients, there was no evidence of malignant cells, and following a monitoring period of two years, all seven patients remain disease free with no clinical and imaging evidence. The primary endpoint of this clinical trial was to expand the clinical knowledge of cryoablation of cancerous breast tumors and enable to implement this technology at the St. Marianna University Hospital as a routine procedure. Based on these results, the trial received approval from the hospital to offer cryoablation for breast cancer in a commercial setting. Independent Clinical Trial of the Cryoablation System -Hong Kong and China Since November 2018, an independent clinical trial has been ongoing at the Queen Mary Medical Center in Hong Kong and at Hong Kong-Shenzhen University Hospital in China. According to information disclosed by the primary investigator, treatments using the company's ProSense cryoablation system has been performed as of December 31, 2022 in 20 patients, out of an expected total patient pool of 150, in which each patient underwent an excision after the cryoablation to examine the ablated area by pathology. Following the first phase, the remaining patients are expected to be monitored according to the standard of care without excision. The purpose of this clinical trial is to expand the clinical knowledge of cryoablation of cancerous breast tumors. The primary endpoints were to demonstrate cryosurgery's efficacy in ablating small breast cancers, safety with low morbidity and the use of PET/MRI as an effective imaging modality to assess post-treatment responses. The inclusion criteria were patients between 18 and 70 years old with core biopsy-proven T0/T1a and b breast cancer or ductal carcinoma in situ. Other Clinical Indications The company is targeting other tissue tumor ablation for its ProSense system, in organs such as: lungs, kidneys, bones and other organs. The company's approach to these indications is to collaborate with hospitals and doctors to conduct clinical trials in order to gain additional information regarding the potential of the company's products to treat certain diseases. While the company's cryoablation products have been approved by various regulatory agencies for variety of oncology and surgical uses, the company will need to validate the company's products in specific indications, and in certain situations in order to obtain specific regulatory approvals, and/or to collect medical data, which will be required in order to successfully market the company's products for these indications. Lung Cancer Lung Cancer Clinical Trial Since November 2013, an independent clinical trial in cryoablation of lung tumors in non-small cell carcinoma or metastatic lesions has been ongoing at the Kameda Medical Center in Kamogawa, Japan using the company's IceSense3 system. Based on data provided to the company, this trial is an ongoing trial, and as of December 31, 2022, more than 400 procedures have been performed using the company's cryoablation system. The peer reviewed publication also highlighted that the use of cryoablation treatment with only one needle for the majority of the patients in the trial represented an advantage in comparison to systems that use argon gas, which usually requires the use of 2-3 needles for a procedure on the same tumors size. The publication of the results of the trial in a peer reviewed publication raises the validity of using the company's products for the treatment of lung tumors. Kidney Tumors Kidney Tumors Clinical Trials In 2012, a clinical trial called ICESECRET (NCT02399124) Post Marketing Surveillance for PROSENSE™ a Cryotherapy Treatment of Renal Cell Carcinoma was initiated at Bnei Zion Medical Center in Haifa, Israel, in collaboration with the Shamir/Assaf Harofeh Medical Center in Be'er Ya'akov, Israel. Procedures were performed using the company's ProSense system for freezing and ablating kidney tumors. The recruitment for this trial is completed. On December 19, 2022, the company announced interim results data from this study for the treatment of patients with small renal masses ('SRM') who cannot be offered kidney-preserving surgery. Data were presented on December 14, 2022 at the Urological Association Conference in Eilat, Israel. The presentation titled 'Renal Mass Cryoablation - Interim Analysis ICESECRET Study' was delivered by Dr. Nasir Said of Bnei Zion Medical Center. Products Existing Products The company's ProSense system is its second generation cryoablation system consisted of two main parts, the main cryoablation console system, the company's unique disposable probe, and the associated disposable introducer (guiding needle), which is used for procedures which are not in the breast. The company's first product, the IceSense3 was initially designed for cryoablation of breast tumors. After identifying a number of additional possible applications for the use of the company's technology, such as treating lungs, kidneys and bones, and other possible applications, in 2016 the company launched its ProSense system, as well as associated disposables (which, as shown below, are inserted into the body to conduct the freezing process). Research and Development The company's strategy is to make its next generation systems more efficient and user-friendly in several aspects. The company's research and development expenses were $9,123 thousand in 2022. Regulatory Approvals The company has received a broad range of regulatory approvals for the company's products in the United States, Europe, China (IceSense3 system only), Singapore, Hong Kong, Mexico, Australia, Israel, Colombia, Costa Rica, India, Thailand, Russia, South Africa and Taiwan. Moreover, the company is pursuing additional regulatory approvals in other indications in existing countries and in other countries where there is significant potential for sales. For example, Japan (for specific approval in certain indications), China (for disposables and for the company's ProSense system, which is an upgrade to the already approved IceSense3), Brazil, Canada and the United States (for specific approval for breast cancer). The company markets its ProSense for a specific indication per the rules and medical device classification in the specific territory. The United States In the United States, the company received from the U.S. Food and Drug Administration, or FDA, 510(k) approval for the company's IceSense3, ProSense and MultiSense and the related disposables. On December 10, 2007, the company received initial 510(k) clearance for the company's IceSense3 system for ablation indications specific to urology, oncology, dermatology, gynecology, general surgery, thoracic surgery and proctology. On November 29, 2010, the company received 510(k) clearance for the company's IceSense3 system for the ablation of breast fibroadenomas under general surgery. On December 20, 2019, the company received 510(k) clearance to allow the company to market and sell the company's IceCure family (which includes Icesense3, ProSense and MultiSense) systems for the treatment of breast fibroadenomas, prostate and kidney tissue, liver metastases, tumors, skin lesions, and other indications, and treat the company's products as 'one family of products,' which means that any additional approval given by the FDA in relation to the family of products will apply automatically to the 'family' as one product, without the need for FDA approval for each separate system; provided, however, that the company expects to require individual approvals for the company's products from the FDA if the company seeks marketing approval for a new specific indication, as is the case for the use of these products for breast cancer. On December 31, 2020, the company submitted a pre-submission package to the FDA for approval of breast cancer indication, based on its ICE3 trial interim results for the company's IceCure family systems. As part of the pre-submission package, the company requested that the company receive approval for this indication through the 510(k) submission pathway or De Novo classification. There can be no guarantee that the FDA approves the use of any of the company's products for the treatment of this indication, and an approval could be given on a narrower indication than requested, or, even if approval is given to market the company's products, there can be no guarantee that the approval is given via the 510(k) pathway or De Novo classification, which could result in additional costs and a longer timeline until the company receives any such approval. If the company does not receive approval via the 510(k) pathway or De Novo classification, the company may seek to receive a PMA. On March 31, 2021, the company was granted Breakthrough Device Designation, or BDD, from the FDA for the company's ProSense system, for treatment for various indications, including for use in the treatment of patients with T1 invasive breast cancer and/or patients not suitable for surgical alternatives for the treatment of breast cancer. In addition, on November 24, 2021, the company submitted a pre-submission package to the FDA in which the company proposed an intended use for early-stage breast cancer and high risk to surgery for the company's ProSense system and requested a De Novo classification. Since the company was granted BDD for the company's ProSense system, the pre-submission package included a request for a sprint discussion under FDA procedures. On October 18, 2022, the company submitted a De Novo Classification Request regulatory filing with the FDA for marketing authorization based on the company's ICE3 clinical trial interim analysis of ProSense for the indication of early-stage (Luminal A T1 invasive) low-risk breast cancer in patients who are at high risk to surgery (not suitable for surgical alternatives), representing approximately 43,000 women in the U.S. annually. The specific indication filed is based on interim data from the company's ICE3 trial and is in accordance with discussions the company has had with the FDA, which granted ProSense Breakthrough Device Designation on March 31, 2021, enabling closer communications regarding its regulatory filing. On November 1, 2022, the CMS assigned payment to the company's ProSense breast cancer cryoablation procedures. The procedures were assigned as CPT Category III code 0581T to ambulatory payment classification 5091, Level 1 Breast/Lymphatic Surgery and Related Procedures. This payment assignment for the procedure went into effect on January 1, 2023, opening the potential for facilities to be paid, on a case-by-case basis, for these procedures subject to the company's receipt of FDA marketing authorization of ProSense for breast cancer. Europe In Europe, the company received Conformitè Europëenne, or CE, mark approval for its ProSense cryoablation system and its disposables with indications for use as a cryosurgical tool in the fields of general surgery, dermatology, thoracic surgery, gynecology, oncology, proctology and urology, which enable the company to sell its ProSense in order to perform procedures in the indications the company intends to such as breast cancer, Kidney, lung, bone and other indications. Russia In 2020, the company received regulatory approvals to market and distribute ProSense and disposables in Russia for use of the company's products in the treatment of benign and cancerous tumor cells through freezing in a number of organs, such as kidneys, lungs, liver and bones. Asia and Africa In Singapore, Hong Kong and South Africa, the company's ProSense system has specific approval for cryoablation of benign and malignant tumors in the breast, lung, bone and liver. China In China, the IceSense3 console has National Medical Products Administration, or NMPA (formerly the China Food and Drug Administration, or CFDA) approval. The company has received an additional five-year renewal up to June 3, 2026. On October 12, 2021, the company announced the advancement of its regulatory strategy in China with the submission of an amendment to the registration certificate for the IceSense3 system, which was granted by the NMPA. On March 28, 2023, the company announced that the NMPA approved its IceSense3 disposable cryoprobes for commercial use, to be used in combination with the company's IceSense3 system console. This approval will allow the company to sell its disposable IceSense3 cryoprobes for commercial procedures. The company expects to launch its commercial sales program for the IceSense3 system in China in the second half of 2023. Japan In Japan, the company's ProSense and disposables are not yet approved by the Japanese regulatory authority, the Pharmaceuticals and Medical Devices Agency, or PMDA. The company started to sell its products in Japan as 'experimental products' under 'private doctor importation' licenses in low quantities. Without approval from the PMDA, the company is only able to sell a limited number of ProSense systems and disposables under 'private doctor importation' licenses. Following the company's distribution agreement with Terumo, Terumo will be responsible, and bare all costs of obtaining regulatory approval for breast cancer from the PMDA to sell the company's products in Japan. Thailand In Thailand, the company's products have the Ministry of Public Health approval for the company's ProSense console and associated disposables to treat malignant breast tumors and other intended uses. Israel In Israel, the company has received the Medical Devices and Disposables, or AMAR, authorization for use of the company's freezing technology for freezing of benign and malignant tumors, including and among others, breast, lungs, bones, kidney and other indications, which enable the company to market its products and will allow doctors in Israel to use the company's product for those indications listed above. Taiwan In 2020, the company received regulatory approvals to market and distribute ProSense and disposables in Taiwan for use of the company's products in the treatment of benign and cancerous tumor cells through freezing in a number of organs, such as kidneys, lungs, liver and bones. India In 2020, the company received regulatory approval to commercialize its disposables in India, where the company's systems themselves do not require regulatory approval before commercialization; however, as part of Voluntary Registration for CDSCO India, coming into force October 2023, related documents of ProSense were submitted. Intellectual Property The company's intellectual property portfolio consists of 30 issued patents (17 in the United States, 7 in Europe, 5 in China and 1 in Hong Kong). In addition to the company's issued patents, the company has one patent application (application No. 16/785,686), which the company filed with the U.S. PTO in February 2020 for a cryogenic pump, a utility patent, with claims drawn to a machine and to process, which has an expected expiration date of February 10, 2040. The company's patent number 8083733 relating to cryosurgical instrument with enhanced heat exchange expired in 2019 and the company's patents number 7137978, 7481806 and 7731711, relating to Cryosurgical instrument and its accessory system are scheduled to expire in 2023. These patents are not used, and are not expected to be used, by the company for the development of the company's technology and products and the company does not expect the expiry and pending expiry to influence the company's business. In addition, the company has a number of other trademarks in the United Kingdom that the company intends on abandoning. Suppliers The primary suppliers for the company's ProSense system and disposables are Resonetics Israel LTD, J.H. Avidan LTD, and Concept Group LLC. Government Regulation The Federal Food, Drug and Cosmetic Act, or FDCA, and FDA regulations establish a comprehensive system for the regulation of medical devices intended for human use. The company's products include medical devices that are subject to these regulations, as well as other federal, state, local and foreign, laws and regulations. All of the company's medical device products sold in the United States are subject to regulation as medical devices under the FDCA, as implemented and enforced by the FDA. Further, the advertising and promotion of the company's products in the EU and the EEA is subject to the laws of individual EU and EEA member states implementing the EU Medical Devices Directive, Directive 2006/114/EC concerning misleading and comparative advertising, and Directive 2005/29/EC on unfair commercial practices, as well as other EU and EEA member state laws governing the advertising and promotion of medical devices. The company is in the process of implementing the new MDR (Medical Device Reporting) requirements to conform with the European requirements. The company has received AMAR approval in Israel. In addition, the company received approval from the MedCert Zertifizierungs und Prufungsgsesellschaft fur die Medizin GmbH of Germany, and is entitled to print the CE Mark on the company's products, after having examined the EU Technical File for each new product. In the United States, the company's activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including the Centers for Medicare & Medicaid Services (CMS), other divisions of the United States Department of Health and Human Services (e.g., the Office of Inspector General), the United States Department of Justice and individual United States Attorney offices within the Department of Justice, and state and local governments. The applicable laws and regulations include the federal Anti-Kickback Statute, the False Claims Act, and the Health Insurance Portability and Accountability Act of 1996, or HIPAA. The company continues to evaluate the effect that the Affordable Care Act has on the company's business. The Foreign Corrupt Practices Act obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations. Competition The company's primary direct competitors also include other cryoablation companies, such as Galil Medical Ltd., part of Boston Scientific Corporation, EndoCare, Inc., part of Siemens Healthineers AG, and Hygea Medical Technology Co. Ltd. for interventional radiology. History IceCure Medical Ltd. was founded in 2006. The company was incorporated in Israel in 2006.