On October 19, 2022 IceCure Medical Ltd. (Nasdaq: ICCM) (TASE: ICCM) ("IceCure" or the "Company"), developer of minimally-invasive cryoablation technology, the ProSense System that destroys tumors by freezing, reported it submitted a regulatory filing (De Novo Classification Request) with the U.S. Food and Drug Administration ("FDA") for marketing authorization based on ICE3 clinical trial ("ICE3") 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 (Press release, IceCure Medical, OCT 19, 2022, View Source [SID1234622206]). The specific indication filed is based on interim data and is in accordance with discussions IceCure has had with the FDA, which granted ProSense Breakthrough Device Designation, enabling closer communications regarding its regulatory filing.

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ICE3 is the largest controlled, multicenter clinical trial ever performed in the U.S. for liquid nitrogen-based cryoablation of small, low-risk, early-stage malignant breast tumors. To date, 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. Final ICE3 5-year follow-up data are expected in the first half of 2024, at which time IceCure 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 age 60 and over, representing approximately 65,000 women in the U.S. annually.

The total group of Luminal A breast cancer for women in all ages, is estimated at 144,000 cases annually in the U.S. In the future, IceCure intends to explore more indications for additional sub groups that are part of the total group of Luminal A breast cancer.

Approximately 66% of the ICE3 patients were determined to be at high risk to surgery due to factors including age and co-morbidities. For these patients, their doctors, and insurers, cryoablation may offer significant benefits as compared to lumpectomy, the current standard of care, including less risk of complications, lower cost, superior cosmetic results, rapid recovery, higher physician and patient satisfaction, and the convenience of a fast and simple in-office procedure.

Data suggests the use of ProSense cryoablation in breast procedures eliminates the risk of re-excision (a second surgery). Between 14% – 20% of breast cancer surgeries result in re-excision due to the practice of requiring a margin of normal breast tissue beyond the involved malignant tissue. This is associated with greater morbidity, patient anxiety, poorer cosmetic outcomes, and increased cost.

"We are very pleased to be in a position to file for regulatory approval with the FDA in this specific breast cancer indication prior to our full study read out expected in 2024 and backed by what we believe is the most extensive data available in the field of breast cancer cryoablation. Following our pre-submission package to the FDA last year, we have been in discussions with the regulatory body regarding this two-step approach for the specific indications for which we are applying. While we await the full study read out of the ICE3 trial, we believe that our first submission makes a strong case for approval based on our interim analyses of the ICE3 data, highly favorable patient outcomes, and improved healthcare economics," stated IceCure CEO Eyal Shamir. "We hope to give women a new option that is just as effective as lumpectomy, without the risk of surgery in the U.S. and globally. If the FDA grants the De Novo Request for ProSense in breast cancer, this may support our global commercialization efforts, as doctors, distributors, and regulatory agencies around the world tend to consider a device’s FDA status in their decision-making."

IceCure is committed to making ProSense widely available and affordable upon regulatory approval by elucidating the procedure’s healthcare economics and through reimbursement and CPT codes. The Company will continue to follow the development of CMS’s new pathway for coverage of innovative new devices, Transitional Coverage of Emerging Technology ("TCET"), which is replacing the repealed Medicare Coverage of Innovative Technologies ("MCIT") rule. CMS is expected to share more about TCET with the public for comments after April 2023.

In addition, IceCure continues to work closely with the ASBrS toward a potential registry trial targeting ASBrS treatment guideline amendments following trial results.

About ICE3

ICE3 is the largest controlled multi-location clinical trial ever performed for liquid nitrogen (LN2) –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.

On October 19, 2022 Avenge Bio, Inc. ("Avenge" or the "Company"), a biotechnology company developing the LOCOcyte Immunotherapy platform for the precision administration of potent immune effector molecules to treat solid tumors, reported that three abstracts were selected for presentation as posters at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting on November 10-11, 2022, at the Boston Convention & Exhibition Center – Exhibit Hall C, Boston, MA (Press release, Avenge Bio, OCT 19, 2022, View Source [SID1234622205]).

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Avenge’s most advanced product candidate, AVB-001, produces native IL-2 immunotherapy and is initially being studied in metastatic peritoneal cancers such as ovarian cancer. AVB-001, developed in the LOCOcyte platform, consists of proprietary engineered human cells. The cells are encapsulated in a pro-inflammatory biomaterial that are delivered to the local tumor environment and generate high, sustained concentrations of native IL-2. The encapsulated cells initiate a robust, local, and durable systemic immune response while avoiding toxicities associated with systemic immunotherapies. Avenge has additional pipeline candidates for the treatment of a wide range of cancers including pancreatic, lung and breast cancers. In July 2022, Avenge announced that Food and Drug Administration ("FDA") cleared the Investigational New Drug ("IND") application for AVB-001 for the treatment of platinum resistance ovarian cancer. The Phase 1, multicenter clinical trial is expected to be initiated in Q4 2022.

Details on Avenge’s presentations at SITC (Free SITC Whitepaper) are as follows:

Abstract #: 363
Poster Title: Localized interleukin-2 cytokine factories eradicate mesothelioma tumors via activation of adaptive and innate immune cells
Presenting Author: Samira Aghlara-Fotovat, BA (Rice University)
Location: Poster Hall C
Date: Thursday, November 10, 2022
Time: 11:40 AM-1:10 PM ET & 7:30-9:00 PM ET

Abstract #: 1095
Poster Title: IL-12-Based Cytokine Factories Modulate Tumor Microenvironment to Eradicate Pancreatic Tumors in Mice and are Well Tolerated in Non-human Primate
Presenting Author: Amanda Nash, BS (Rice University)
Location: Poster Hall C
Date: Thursday, November 10, 2022
Time: 11:40 AM-1:10 PM ET & 7:30-9:00 PM ET

Abstract #: 1094
Poster Title: Favorable preclinical efficacy and safety profile of AVB-001 a novel IL-2 cell-based immunotherapy that eradicates ovarian cancer in mouse tumor models and supports first in human clinical development
Presenting Author: Guillaume Carmona, PhD (Avenge Bio, Inc.)
Location: Poster Hall C
Date: Friday, November 11, 2022
Time: 11:55 AM-1:25 PM ET & 7:00-8:30 PM ET

The posters will be available on the Presentations and Publications section of www.avengebio.com following the conference.

About LOCOcyte Platform
Our LOCOcyte allogeneic cell-based immunotherapy platform enables potent localized modulation of the immune system which also precipitates a systemic immune response, allowing us to treat previously intractable cancers. The technology leverage three unique advantages:

Potent immune effector molecules are generated by synthetically engineering allogeneic cells creating a ready-to-use therapy,
Therapy is localized in proximity to the primary tumor site and generates innate and adaptive immune response, and
The immunomodulator trains the patient’s immune system generating a robust immune response that seeks and eradicates distal metastasis without systemic toxicity.

On October 19, 2022 SeekIn Inc, a leader in blood-based cancer early detection and monitoring technology, reported the results of pan-cancer early detection test SeekInCare were presented at The 2022 Early Detection of Cancer Conference in Portland, Oregon (Press release, SeekIn, OCT 19, 2022, View Source [SID1234622204]).

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At present, the majority of deadly cancers do not have standard-of-care screening paradigms available and the existing screenings have challenges in patient compliance due to the invasive procedures endured from the tests. As a result, most cancers are detected until they have progressed to late stages when chances of survival are much lower.

"Currently, the five-year survival rate for cancer patients in China is 39%, compared with 68% in the United States. The key to the difference in the survival rates between China and the United States is cancer screening, which reduces disease- and treatment-related morbidity, increases the likelihood of treatment success, improves quality of life, and reduces treatment cost and complexity," said Mao Mao, M.D., Ph.D., SeekIn’s founder and CEO. "SeekInCare, a blood-based pan-cancer detection approach, holds promise for identifying asymptomatic cancer patients from general population through a single blood draw."

SeekInCare, a novel multidimensional cancer risk score (CRS) model, incorporating copy number aberrations (CNA), fragment size (FS), end motifs and cancer related viruses via shallow whole genome sequencing (sWGS) from cell-free DNA (cfDNA), and seven plasma tumor markers (PTMs). The case-control study included 616 stage I-IV cancer patients that cover 8 common cancers and 19 other types, and 898 healthy subjects. SeekInCare identified 419 cancer patients with 68.0% sensitivity at 98.0% specificity, resulting in an AUC (area under the curve) of 0.916. Compared with multi-cancer detection in the retrospective validation cohorts from GRAIL and Exact Sciences, SeekInCare had a similar performance if not better. Moreover, the sensitivities were 49.0%, 61.3%, 72.5% and 85.4% in stages I, II, III and IV respectively.

To further assess SeekInCare’s performance, it was evaluated in a real-world cohort consisting of 604 subjects (median follow-up time: 404 days). 12 cancer cases were detected while nine subjects tested positive but without cancer. Only one subject was tested negative and subsequently diagnosed with stage I thyroid cancer. Thus, SeekInCare achieved 92.3% sensitivity, 97.7% specificity, 57.1% PPV and 99.7% NPV in the real-world cohort. These data demonstrated that the performance of SeekInCare is similar to the data generated by GRAIL and Johns Hopkins University in prospective setting.

"There are different technical approaches for blood-based pan-cancer/multi-cancer early detection. These clinical studies demonstrated the solid performance of our technology," said Dr. Mao, "In addition, SeekInCare had received CE-IVD Mark approval which represents a significant milestone for SeekIn in bringing SeekInCare test to the other countries besides China, allowing more people to access the cutting-edge, convenient, non-invasive and cost-effective cancer early detection technology."

On October 19, 2022 City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that the first patient to receive its novel, promising cancer medicine AOH1996 is doing well (Press release, City of Hope, OCT 19, 2022, View Source [SID1234622203]). The Phase 1 clinical trial testing the safety of a potentially cancer-stopping therapeutic developed by City of Hope in people with reoccurring solid tumors is expected to continue for the next two years. The investigational pill has been effective in preclinical research treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers.

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Linda Malkas, Ph.D., professor in City of Hope’s Department of Molecular Diagnostics & Experimental Therapeutics, has been working on the research and subsequent discovery and development of AOH1996 for 20 years. AOH1996 is named after Anna Olivia Healey, a young girl born in 1996 who unfortunately was not able to beat cancer. AOH1996 is exclusively licensed by City of Hope to RLL, LLC, a biotechnology company that Malkas co-founded.

Malkas believed that proliferating cell nuclear antigen (PCNA), which plays an essential role in the replication and repair of cells, would be a less toxic cancer therapy that targets mutated cancer cells while leaving normal cells alone. The treatment has been shown in preclinical research to target PCNA and inhibit the growth and spread of a broad range of human cancer cells. The research protocol notes that AOH1996 is not toxic to healthy cells and that treatment with this medicine both pauses cell DNA synthesis and inhibits DNA repair, leading to a type of cell death known as apoptosis in the cancer cells.

"Imagine cancer as the water filling up a bathtub. Left unchecked, the tumors or water will eventually overflow and damage other parts of your home. The treatment my team at City of Hope created is akin to a watchful homeowner who shuts the water off — stopping the spread of tumors to other parts of the metaphorical house — and then drains the tub, eliminating the cancer," said Malkas, co-investigator in the trial and the M.T. & B.A. Ahmadinia Professor in Molecular Oncology.

Vincent Chung, M.D., added, "By targeting PCNA, we are inhibiting the complex machinery to stop cellular growth and proliferation. This is a new way of trying to kill cancer cells or at least to slow it down." He is a research professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and principal investigator in the clinical trial.

The Phase 1 clinical trial is open at City of Hope Los Angeles. Its objective is to determine the maximum tolerated dose of the investigational pill, AOH1996, and to evaluate the medicine for preliminary efficacy. Eligible patients include adults with solid tumors who have not found standard treatments effective. Participating patients will be asked to take the medication in pill form twice a day.

"Since many patients’ cancers become resistant to our standard therapies, we need new therapeutics with new mechanisms of action — for example, non-cross resistant. AOH1996 is just that kind of new therapy," said Daniel Von Hoff, M.D., of the Molecular Medicine Division at the Translational Genomics Research Institute, part of City of Hope, and an advisor on the study. "Congratulations to Dr. Malkas and the City of Hope team on this new invention."

Malkas said other targeted therapies, like checkpoint inhibitors, that inhibit the growth and spread of cancer have helped innumerable cancer patients, adding that perhaps one day AOH1996 will be a U.S. Food and Drug Administration-approved inhibitor that could be used in combination with existing therapies to both enhance cancer-killing effects as well as decrease side effects related to lifesaving cancer treatments.

With the infrastructure and support of City of Hope, Malkas was able to commercialize her basic research, moving her promising laboratory discovery into a clinical trial for people who need the therapies of tomorrow today. City of Hope provided structure, experts and even GMP (good manufacturing practice) facilities to manufacture her medicine.

City of Hope is devoted to supporting research and development and has infrastructure that is tailor-made to accelerate innovations from the lab to patients. This system includes everything ranging from funding support to access to counsel from internal and external drug development specialists. City of Hope’s R&D apparatus leverages the combination of its fundamental strength in basic science and its patient-care focus as a comprehensive cancer center.

Individuals interested in this clinical trial should review the eligibility requirements at clinicaltrials.gov. If they believe they are eligible, they can call 626-218-1133 or visit City of Hope’s clinical trials webpage.

On October 19, 2022 The American College of Radiology (ACR) reported that is set to launch the Contrast-Enhanced Mammography Imaging Screening Trial (CMIST) in collaboration with the Breast Cancer Research Foundation (BCRF) and GE Healthcare (Press release, American College of Radiology, OCT 19, 2022, View Source [SID1234622202]). The trial will determine whether contrast-enhanced mammography improves breast cancer detection and reduces false-positive exams in women with dense breasts.

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Left: Recombined image of the CEM exam showing iodine uptake, Right: Standard digital mammogram
Left: Recombined image of the CEM exam showing iodine uptake, Right: Standard digital mammogram
About 43 percent of women aged 40 to 72 have dense breasts, which can make detection of breast cancer more challenging when using mammography alone. The CMIST study seeks to determine if contrast-enhanced mammography (CEM) provides more accurate cancer detection compared to digital breast tomosynthesis (DBT) in women with dense breasts.

CEM combines mammography and vascular-based screening methods in a simple and quick procedure to highlight areas of unusual blood flow patterns that may indicate malignancy. Early studies of CEM in screening women with dense breasts have shown the potential benefit of CEM in the detection of breast cancer.

"In the fight against breast cancer, unfortunately it is all too common for women with dense breasts to face an agonizing wait for answers," says Catherine Lezy, General Manager for Mammography at GE Healthcare. "We know that CEM technology can be a game-changer in helping improve breast cancer outcomes. I’m excited that both GE Healthcare’s Senographe Pristina mammography system and SenoBright HD CEM technology, together with GE Healthcare Pharmaceutical Diagnostics contrast media will be used to further evaluate the clinical benefits of CEM. We hope that this will help clinicians feel more confident in their diagnosis and help patients get the answers they deserve."

The planned study will be managed by the American College of Radiology Center for Research and Innovation, with support from the Breast Cancer Research Foundation and GE Healthcare, under the supervision of Principal Investigator Christopher Comstock, MD, FACR, FSBI, Director of Breast Imaging Clinical Trials, Memorial Sloan Kettering Cancer Center, who said: "The CMIST Trial can help determine if contrast-enhanced mammography can provide a more sensitive and specific method for breast cancer screening in women with dense breasts, finding many cancers missed with our current methods."

"Through CMIST, we hope to gain increased understanding of the potential role of contrast mammography for women with dense breasts with the goal of developing more individualized breast imaging strategies." said Etta Pisano, MD, FACR, American College of Radiology Chief Research Officer.

"Given recent trends in the rising incidence of breast cancer, it is a key imperative to improve current diagnostic tools," said Dorraya El-Ashry, PhD, Chief Scientific Officer of the Breast Cancer Research Foundation. "We know that early detection is a key determinant of survival and improving diagnostic technology for women with dense breasts will undoubtedly save lives."

As the world observes Breast Cancer Awareness month throughout October, women are encouraged to ‘Don’t Skip’ their annual mammogram – where they can learn more about their own risk factors, including breast density, and consider the best care options with the help of their physician. Click here to learn more.