Mastodynia

40-site U.S. trial enrolling more than 300 patients could significantly change the way DCIS is treated and reduce possibly unnecessary surgery SAN FRANCISCO, Oct. 30, 2023 /PRNewswire/ -- Quantum Leap Healthcare Collaborative (QLHC) announces the enrollment launch for the Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS), a Phase 2 platform study aimed at preventing the progression of DCIS to breast cancer. The study is evaluating three investigational endocrine therapy arms: (Z)-endoxifen, a selective estrogen receptor modulator (SERM) in development by Atossa Therapeutics (Nasdaq: ATOS); HAVAH T+Ai™, a proprietary combination of testosterone (T) and anastrozole (Ai) that targets the androgen and estrogen receptor pathways in development by Havah Therapeutics; and ORSERDU® (elacestrant), the only FDA approved oral selective estrogen receptor degrader (oSERD) in development by Stemline Therapeutics Inc. (Stemline), a wholly-owned subsidiary of the Menarini Group. "DCIS indicates the very earliest, noninvasive stage of the disease, that's why it is important for us to seek out alternative therapies for DCIS patients and find ways to reduce toxicity and unnecessary surgeries. We are excited to partner with three innovative companies to explore new treatments for this large and often over-treated patient population," said Laura Esserman, MD, a lead investigator for the study and founder of QLHC. Surgery is the current standard treatment for DCIS even though many patients never progress to breast cancer, which means that patients are often over-treated with invasive procedures. This new trial, sponsored and operated by QLHC, offers DCIS patients up to six months of endocrine therapy with the intent to forego surgery and instead be monitored via long-term active surveillance, if appropriate. A key element in reducing overtreatment of DCIS is identifying biomarkers that reflect the risk of progression so that those with low-risk lesions are spared surgery. RECAST DCIS features the assessment of imaging and molecular-based biomarkers in addition to evaluating new investigational agents in this setting. The study is open to enrollment with each investigational agent arm expected to enroll up to 110 patients. The three collaborators for this trial, Atossa Therapeutics, Havah Therapeutics, and Stemline, all aim to find alternative solutions for DCIS patients and are providing different agents for assessment. Atossa's (Z)-endoxifen has the potential to mitigate breast cancer risk (by reducing the density of breast tissue); to reduce cancer cell activity before surgery; and to reduce the risk of recurrent or new breast cancer after the initial treatment. According to published studies, (Z)-endoxifen is a competitive inhibitor of ERα and represses ERα transcriptional activity (Z)-endoxifen is 100-fold more potent in anti-estrogen activity compared to other SERMs. (Z)-endoxifen also binds to and disrupts protein kinase C beta one function (PKCb1, a known oncogenic protein). The National Cancer Institute (NCI) and others have studied (Z)-endoxifen and have demonstrated promising results in the treatment of breast cancer as well as for the treatment of other solid tumors. Treatment with (Z)-endoxifen may avoid off target effects of tamoxifen and remaining metabolites potentially increasing adherence by improving the safety profile. Havah Therapeutics' HAVAH T+Ai™ combines T, the natural ligand for the androgen receptior and Ai, an inhibitor of T conversion to estradiol, to modulate the growth of abnormal breast tissues. HAVAH T+Ai™ is a proprietary combination subcutaneously delivered system to overcome hormonal symptoms by balancing hormonal irregularities in the breast, developed from more than 10 years of clinical research into hormonal regulation in women. Havah has extensive clinical experience using HAVAH T+Ai™ to address pre- and postmenopausal prevention of breast disease, and the company generated data from more than 1,000 Australian women with breast disease through an ongoing open label cohort study (more than 6,200 implants), with critical safety pharmacokinetic and early efficacy data already demonstrated. Stemline's Elacestrant (ORSERDU), was approved by the U.S. Food & Drug Administration in January 2023 for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, HER2-negative, ESR-1 mutated advanced or metastatic breast cancer, following at least one line of endocrine therapy. For more information including full prescribing information and important safety information, please visit . About Quantum Leap Healthcare Collaborative Quantum Leap Healthcare Collaborative is a 501c(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs. Our mission is to integrate high-impact research with clinical processes and systems technology, resulting in improved data management and information systems, greater access to clinical trial matching and sponsorship, and greater benefit to providers, patients and researchers. Our goal is to improve and save lives. For more information, visit . About Atossa Atossa Therapeutics is a clinical stage biopharmaceutical company developing innovative medicines in areas of significant unmet medical need in oncology. Atossa's current focus is on breast cancer. More information is available at atossatherapeutics.com. About Havah Therapeutics Havah Therapeutics is a biopharmaceutical company developing innovative, proprietary hormonal therapies that aim to improve quality of life for women. Havah brings together a world-class team passionate about helping women live lives free from the suffering caused by breast pain, debilitating menopausal symptoms and breast cancer. More information is available at . About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit . About Stemline Therapeutics Inc. Stemline Therapeutics, Inc. ("Stemline") a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the United States, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the US and EU to date. Stemline also commercializes NEXPOVIO® in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. SOURCE Quantum Leap Healthcare Collaborative

Motiva Flora tissue expander is intended to enhance the outcomes in breast reconstruction following breast cancer and includes several proprietary innovations SmoothSilk surface technology FDA clears Motiva Flora SmoothSilk Tissue Expander. (Credit: philippe spitalier on Unsplash) Establishment Labs, primarily focused on breast aesthetics and reconstruction, has secured the 510(k) clearance from the US Food and Drug Administration (FDA) for its Motiva Flora SmoothSilk Tissue Expander. Establishment Labs is a global medical technology company that works to improve the health and wellness of women. The firm has designed the Motiva Flora tissue expander to enhance the outcomes in breast reconstruction following breast cancer. The Flora SmoothSilk Tissue Expander is said to have several proprietary innovations, including the company’s patented SmoothSilk surface technology. Compared to other implant surfaces, SmoothSilk has been demonstrated to cause the least degree of irritation and a foreign body reaction, Establishment Labs claimed. The device also includes an RFID-enabled, non-magnetic port, designated as MR Conditional by the FDA. According to the medical technology firm, Flora’s magnet-free nature prevents the interference that magnets might produce during MRI, which could increase the accuracy of radiation oncology treatment. All other commercially marketed breast tissue expanders are said to have magnets. Establishment Labs founder and CEO Juan José Chacón-Quirós said: “This is an incredibly important day in the history of Establishment Labs, as the first of our implantable technologies has been approved by the FDA. “Our SmoothSilk surface will now be available to women in the US, and this technology is transformative for our industry and patient outcomes. “Tissue expanders have seen little innovation for more than a generation, and, in partnership with breast cancer centres, Establishment Labs is creating a new standard of care in breast reconstruction.” The device has been available in Europe and other global markets since 2021 and has been assessed in multiple independent scientific publications. In a blinded head-to-head study, a patient’s breast treated with Flora reported significantly higher aesthetic and comfort scores, along with less breast pain, discomfort, and nipple sensitivity compared to other available tissue expanders on the other breast. In the first-in-human multi-centre trial of patients undergoing 3-Tesla MRI, Establishment Labs’ device did not affect the image quality of the key part of the breast MRI protocol and there were no MRI-associated complications or damage to the expander port.

Flora is the only magnet-free and MR Conditional tissue expander cleared for the U.S. market. NEW YORK--(BUSINESS WIRE)-- Establishment Labs Holdings Inc. (NASDAQ: ESTA), a global medical technology company dedicated to improving women’s health and wellness, principally in breast aesthetics and reconstruction, announced that the U.S. Food and Drug Administration (FDA) has granted 510(k) clearance for the Motiva Flora® SmoothSilk® Tissue Expander. The Flora® SmoothSilk® Tissue Expander offers several proprietary innovations, including Establishment Labs’ patented SmoothSilk® surface technology. SmoothSilk® has been shown to produce the least amount of inflammation and foreign body response compared to other implant surfaces.1 Flora also includes an RFID-enabled, non-magnetic port, labeled as MR Conditional by the FDA. By being magnet-free, Flora avoids the interference that magnets can cause during MRI and may improve the precision of radiation oncology treatment. All other commercially available breast tissue expanders include magnets. “This is an incredibly important day in the history of Establishment Labs, as the first of our implantable technologies has been approved by the FDA,” said Juan José Chacón-Quirós, Founder and Chief Executive Officer of Establishment Labs. “Our SmoothSilk® surface will now be available to women in the United States, and this technology is transformative for our industry and patient outcomes. Tissue expanders have seen little innovation for more than a generation, and, in partnership with breast cancer centers, Establishment Labs is creating a new standard of care in breast reconstruction.” The Motiva Flora Tissue Expander has been available in Europe and other global markets since 2021 and has been studied in several independent scientific publications. Among the notable findings: In a blinded head-to-head study where patients were randomized to receive Flora in one breast and a U.S. commercially available tissue expander in the other, patients reported significantly higher aesthetic and comfort scores, as well as less breast pain, discomfort, and nipple sensitivity with Flora. Surgeons reported higher satisfaction with lower pole expansion as well as with the footprint created by Flora. The capsule tissue around the Flora expander was thinner and the peri-prosthetic fluid was significantly lower than with the comparative device.2 In the first in-human multi-center study of patients undergoing 3-Tesla MRI, Flora did not affect the image quality of the most important part of the breast MRI protocol and there were no MRI-related complications or MRI-related damage to the expander port.3 In a radiotherapy planning study comparing the dosimetric effect of traditional metallic ports to the RFID port in Flora, Flora showed better dosimetric results to the heart and lungs vs traditional metallic ports, potentially reducing side effects to these organs. The RFID port materials also reduced artifacts on CT imaging compared to the metals used in conventional expanders.4 “The technology used by the Flora SmoothSilk® Tissue Expander that enabled it to be labeled MR Conditional will have a critical impact on patients during their breast reconstruction journey, permitting them to undergo MRI, the most important diagnostic imaging modality,” said Dr. Frank G. Shellock, Director of MRI Safety and Professor of Radiology and Medicine at the University of Southern California. “Furthermore, women working in the MRI environment now have a safe option that will allow them to work in and around an MRI system during their breast tissue expansion process.” “At our breast center in Madrid, we help thousands of women each year, from annual screenings to treatment of breast cancer and breast reconstruction,” said Dr Antonio Tejerina, Plastic and Reconstructive Surgeon at the Madrid Breast Center in Spain. “After using this tissue expander in more than 180 cases over the past two years, I can confidently state that Motiva Flora is a new standard of care and the best tool to achieve an aesthetic breast reconstruction. Including and informing women about the most advanced possibilities in their treatment is the first step in helping them own their recovery.” Doloff, J.C., Veiseh, O., de Mezerville, R. et al. The surface topography of silicone breast implants mediates the foreign body response in mice, rabbits and humans. Nat Biomed Eng 5, 1115–1130 (2021). Schoberleitner I, Augustin A, Egle D, Brunner C, Amort B, Zelger B, Brunner A, Wolfram D. Is it all about surface topography? An intraindividual clinical outcome analysis of two different implant surfaces in breast reconstruction. J. Clin. Med. 2023, 12, 1315. doi: 10.3390/jcm12041315 Schiaffino S, Cozzi A, Pompei B, et al. MRI-Conditional Breast Tissue Expander: First In-Human Multi-Case Assessment of MRI-Related Complications and Image Quality. J. Clin. Med. 2023, 12, 4410. Hwang NH, Kim M, Lee NK, Lee S, Hwang J. Dosimetric effect of injection ports in tissue expanders on post-mastectomy volumetric modulated arc therapy (VMAT) planning for left-sided breast cancer. Applied Sciences. 2022, 12 (13), 6461. doi:10.3390/app12136461 About Establishment Labs Establishment Labs Holdings Inc. is a global medical technology company dedicated to improving women’s health and wellness through the power of science, engineering, and technology. The Company offers a portfolio of Femtech solutions for breast health, breast aesthetics and breast reconstruction. The over three million Motiva® devices Establishment Labs has delivered to plastic and reconstructive surgeons since 2010 have created a new standard for safety and patient satisfaction in the over 85 countries in which they are available. The Motiva Flora® tissue expander is used to improve outcomes in breast reconstruction following breast cancer and it is the only regulatory-approved expander in the world with an integrated port using radio-frequency technology that is MR conditional. Mia Femtech™, Establishment Lab’s unique minimally invasive experience for breast harmony, is the Company’s most recent breakthrough innovation. These solutions are supported by over 200 patent applications in 25 separate patent families worldwide and over 50 scientific studies and publications in peer reviewed journals. Establishment Labs manufactures at two facilities in Costa Rica compliant with all applicable regulatory standards under ISO13485:2016 and FDA 21 CFR 820 under the MDSAP program. In 2018, the Company received an investigational device exemption (IDE) from the FDA for Motiva Implants® and began a clinical trial to support regulatory approval in the United States. Please visit our website for additional information at . Establishment Labs' Motiva silicone gel-filled implants are currently not approved for commercial distribution in the United States. The Company’s implants are undergoing PMA clinical investigation pursuant to U.S. FDA regulations for investigational medical devices. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). You can find many (but not all) of these statements by looking for words such as “approximates,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “intends to,” “would,” “will,” “may” or other similar expressions in this press release. Any statements that refer to projections of our future financial or operating performance, anticipated trends in our business, our goals, strategies, focus and plans, including related product development and commercialization and regulatory approvals, and other characterizations of future events or circumstances, including statements expressing general optimism about future operating results, related to the company’s performance are forward-looking statements. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995. We caution investors that any forward-looking statements presented in this report, or that we may make orally or in writing from time to time, are expressions of our beliefs and expectations based on currently available information at the time such statements are made. Such statements are based on assumptions, and the actual outcome will be affected by known and unknown risks, trends, uncertainties, and factors that are beyond our control. Although we believe that our assumptions are reasonable, we cannot guarantee future performance, and some will inevitably prove to be incorrect. As a result, our actual future results and the timing of events may differ from our expectations, and those differences may be material. Factors, among others, that could cause actual results and events to differ materially from those described in any forward-looking statements include risks and uncertainties relating to: our ability to successfully, timely and cost-effectively develop, seek and obtain regulatory clearance for and commercialize our product offerings; the rate of adoption of our products by healthcare providers or other customers; the success of our marketing initiatives; the safe and effective use of our products; our ability to protect our intellectual property; our future expansion plans and capital allocation; our ability to expand upon and/or secure sources of credit or capital; our ability to develop and maintain relationships with qualified suppliers to avoid a significant interruption in our supply chains; our ability to attract and retain key personnel; our ability to scale our operations to meet market demands; the effect on our business of existing and new regulatory requirements; and other economic and competitive factors. These and other factors that could cause or contribute to actual results differing materially from our expectations include, among others, those risks and uncertainties discussed in the company’s annual report on Form 10-K filed on March 1, 2023 and in the company's quarterly report on Form 10-Q filed on August 9, 2023, which risks and uncertainties may be updated in the future in other filings made by the company with the Securities and Exchange Commission. The risks included in those documents are not exhaustive, and additional factors could adversely affect our business and financial performance. We operate in a very competitive and rapidly changing environment. New risk factors emerge from time to time, and it is not possible for us to predict all such risk factors, nor can we assess the impact of all such risk factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. We are not undertaking any obligation to update any forward-looking statements. Accordingly, investors should use caution in relying on past forward-looking statements, which are based on known results and trends at the time they are made, to anticipate future results or trends. View source version on businesswire.com: Contacts Investor/Media Contact: Raj Denhoy 415-828-1044 rdenhoy@establishmentlabs.com Source: Establishment Labs Holdings Inc. View this news release online at: