CDH11

-- TellDx CTC System can be leveraged to monitor efficacy of novel therapeutic agents— --Targeting multiple cadherins with 23C6 can ameliorate cancer metastasis-- -- TellBio has exclusive optionality to license 23C6 -- BEVERLY, Mass., Oct. 24, 2022 (GLOBE NEWSWIRE) -- TellBio, Inc., a development stage biotechnology company focused on revolutionizing the detection of cancer through its unique and proprietary circulating tumor cell (CTC) technology, TellDx, and treatment through its complementary therapeutics platform, TellRx, announces publication of data from the scientific founders that show a beneficial impact of a novel antibody targeting multiple cadherins on tumor cell dissemination in mouse models of breast and pancreatic cancer. The results were published on October 18, 2022, in Proceedings of the National Academy of Sciences (DOI 10.1073/pnas.2209563119). Greater than 10 million patients die from cancer each year and more than 90% of the deaths are attributed to metastasis. CTC are thought to be the precursors of metastasis. CTC detection using a minimally invasive liquid biopsy approach has been shown to be prognostic. Currently, there are no approved therapies that specifically target the metastatic process. As such, targeting CTCs with novel therapeutics could likely have a significant impact on cancer metastases and patient outcome. “TellBio is focused on the detection, monitoring, and treatment of cancer metastasis. These exciting data demonstrate that the TellDx platform can detect heterogenous CTCs in the metastatic setting and can be implemented in studies to achieve an earlier read on efficacy of investigational agents. Furthermore, the efficacy of 23C6 on reducing CTCs and suppressing cancer metastasis is promising,” said Pritesh J. Gandhi, PharmD, CEO, TellBio. Tumor metastasis is a multi-step process whereby cancer cells invade blood vessels through a complex process referred to epithelial-mesenchymal transition (EMT). Circulating tumor cells are heterogenous and both epithelial (CDH1) and mesenchymal (CDH11) cancer cells have been implicated in metastatic spread making them a potential therapeutic target to attenuate cancer metastasis. In this paper, authors including TellBio scientific founders, Drs Mehmet Toner, Shyamala Maheswaran, David Ting, and Daniel A. Haber of Massachusetts General Hospital Center for Cancer Research, sought to study the impact of a novel antibody (23C6) targeting multiple cadherins expressed on both epithelial (CDH1) and mesenchymal (CDH11) circulating tumor cells and the effects on metastasis in mouse models of breast and pancreatic cancer. Novel dual-cadherin antibody, 23C6, was initiated on day of inoculation and continued post-resection. Metastasis burden was assessed by CTC enrichment, with the TellDx platform that isolates live cells of both epithelial and mesenchymal lineage, and bioluminescence. Administration of 23C6 demonstrated 100-fold reduction in CTC count in pancreatic cancer model and led to significant metastatic suppression. “These data show the administration of anti-metastatic therapy with 23C6 resulted in a reduction in CTCs and inhibition of metastatic spread," said Dr. David Ting, Associate Clinical Director for Innovation at the MGH Cancer Center and an Associate Professor of Medicine at Harvard Medical School. Overall, this study underscores exquisite synergy of the TellBio platform. Enriching CTCs with TellDx and subsequent understanding of the biology of CTCs fuels the TellRx pipeline. TellBio has exclusive optionality to license 23C6 and integrate it into the TellRx portfolio. About TellBioThe Company is a development stage biotechnology company based in Beverly, Massachusetts, with the goal to revolutionize the detection and treatment of cancer through its unique and proprietary circulating tumor cell (CTC) technology and complementary therapeutics platform, TellDx and TellRx, respectively. TellBio’s vision is to free patients and their families from the tyranny of cancer via both its TellDx and TellRx platforms. TellDx is a fully functional diagnostics solution aimed at detecting viable CTCs from patient liquid biopsies. TellRx is the therapeutics platform that generates novel anti-cancer medicines by specifically targeting CTCs. The synergy of these platforms offers TellBio a unique opportunity to detect CTCs via a microfluidic diagnostic platform and target CTCs with novel therapeutics to optimize outcomes of patients with cancer. Contacts: Company: Annie Partisano | apartisano@tellbio.com For inquiries about deploying TellDx: Contact info@tellbio.com or visit tellbio.com

Organization funds more than 130 promising research grants on lung cancer, asthma, COVID-19 and more CHICAGO, Oct. 12, 2022 /PRNewswire/ -- Lung health research is more important than ever. Never have we faced so many challenges to our lung health, including COVID-19, vaping and smoke from increased wildfires. To find solutions to alleviate the burden of lung disease, today the American Lung Association announced it awarded research grants and is now funding more than 100 innovative projects. The funded projects address a wide range of lung health topics, including asthma, COPD, lung cancer, COVID-19 and more. For its 2022-2023 funding cycle, the Lung Association funded $13.1 million for more than 130 lung health research grants. Through the Awards and Grants Program, the Lung Association supports trailblazing research, novel ideas and innovative approaches. For this round of funding, the Lung Association placed a greater focus on strategic partnerships with key organizations like American Thoracic Society and CHEST, and grants that focus on equity like the Harold Amos Scholar. "More than 34 million Americans live with lung disease, including asthma, lung cancer and chronic obstructive pulmonary disease (COPD). On top of that, we are seeing emerging lung health threats that we have never seen before. That's why the American Lung Association is investing in the top scientific minds to find better ways to reduce the burden of lung disease and investigate the long-term impacts of lung health challenges like vaping, climate change and COVID-19," said Harold Wimmer, President and CEO of the American Lung Association. "We are honored to welcome our 2023 Research Team and empower them to help us prevent lung disease and improve the lives of people living with lung disease for years to come." Research projects funded by the Lung Association are carefully selected through rigorous scientific review and awardees represent the investigation of a wide range of complex issues. Awards were given in eight different categories; ALA/AAAAI Allergic Respiratory Diseases Award, ALA/ATS/CHEST Foundation Respiratory Health Equity Research Award, Catalyst Award, COVID-19 Respiratory Virus Research Award, Dalsemer Award, Innovation Award, Lung Cancer Discovery Award, and Public Policy Research Award. A few of the recent grant awardees include: Lung Cancer Discovery Award Presented to Moumita Ghosh, PhD, from the University of Colorado Denver for his study on lung cancer titled, "Deconstructing and reconstructing the impact of the immune microenvironment." When it comes to treatment of lung cancer, early detection is critical to the success of lung cancer treatments. One potential marker that signals early lung cancer could be changes in progenitor cells, which are a type of stem cell critical for tissue repair and maintenance of a healthy lung. Dr. Ghosh's lab discovered that these cells are impaired in people with lung cancer, which coincides with an increased level of immune cells. Their study will look at epithelial progenitor cells and how their function is affected by their location relative to a tumor, as well as the presence of immune cells. This investigation could lead to new methods of early detection of lung cancer and also new targets to enhance progenitor function and slow or stop the formation of cancer. Innovation Award Presented to Aparna Sundaram, MD, from the University of California, San Francisco, for his project, titled "Mechanisms of Cadherin-11 Modulation of Force Transmission in Asthma." Dr. Sundaram's group has shown that individual smooth muscle cells in the airways are attached to the surrounding airway by tethering proteins, like an anchor. This study will examine the role of the tethering protein called cadherin-11 in coordinating neighboring smooth muscle cells to contract, and how an allergic environment may influence this action. Understanding the structure of the airways, and how the smooth muscles anchor to the airways could lead to new therapies that can block this action, and thus prevent airway narrowing in asthma. Catalyst Award Presented to Alexandra C. Racanelli, MD, PhD, from the Joan & Sanford I. Weill Medical College of Cornell University, for her project, titled "The role of endothelial derived leucine-rich 2-alpha glycoprotein-1 (LRG1) in the pathogenesis of COPD." Dr. Racanelli's lab has discovered that dysfunction of blood vessels in the lung leads to the development of the type of lung destruction found in COPD. They will use a mouse model of COPD and human lung cells to better understand how this dysfunction develops. In particular, they will focus on a specific protein called LRG1, and see if excessive levels lead to blood vessel abnormalities and eventually development of COPD. These findings could help develop new therapies targeting the impairment in blood vessels that cause COPD, and eventually improve the lives of millions of patients. The Lung Association's Nationwide Research Program includes the Awards and Grants Program, and also our Airways Clinical Research Network, the nation's largest not-for-profit network of clinical research centers dedicated to asthma and COPD treatment research. For more information about the new grant awardees and the entire American Lung Association Research Team, visit Lung.org/research-team. About the American Lung Association The American Lung Association is the leading organization working to save lives by improving lung health and preventing lung disease through education, advocacy and research. The work of the American Lung Association is focused on four strategic imperatives: to defeat lung cancer; to champion clean air for all; to improve the quality of life for those with lung disease and their families; and to create a tobacco-free future. For more information about the American Lung Association, which has a 4-star rating from Charity Navigator and is a Gold-Level GuideStar Member, or to support the work it does, call 1-800-LUNGUSA (1-800-586-4872) or visit: Lung.org. American Lung Association • 55 W. Wacker Drive, Suite 1150 • Chicago, IL 60601 1331 Pennsylvania Ave. NW, Ste. 1425 North • Washington, D.C. 20004 1-800-LUNGUSA (1-800-586-4872) Lung.org CONTACT: Jill Dale | American Lung Association P: 312-940-7001 E: Jill.Dale@Lung.org View original content to download multimedia: SOURCE American Lung Association

“When you’re looking at science, you don’t ask does molecule x change in disease y. You measure everything and say what is the pattern of changes with this disease.” That’s a quote from a conversation BioSpace had with Stephen Byers, Ph.D., associate director and professor of oncology at Georgetown Lombardi. Byers and his team recently published a paper in the journal Gastroenterology regarding their findings of a novel target for pancreatic cancer therapy. Pancreatic cancer is one of the deadliest forms of cancer. The five-year survival rate is a paltry 5-10%. The tumors are basically invisible to the immune system and rarely respond to chemotherapy or immunotherapy. Byers said this type of cancer is associated with an extreme form of fibrosis. That could have something to do with its failure to respond to therapies. One of the molecules his team has been working with for years is cadherin 11 protein (CDH11). It was well-established that animals without CDH11 are resistant to all fibrotic and inflammatory diseases. They reasoned it’s also involved in the genesis of pancreatic cancer. The team found that CDH11 creates an environment that is immunosuppressive, keeping the cancer hidden from the immune system. In mouse models, when they took away CDH11 from the fibrotic cells, the tumor would become invisible to the immune system and create a window to apply therapies. By “knocking out” CDH11 production in mice, they found a reduction in pancreatic tumor growth, increased responsiveness to chemo drug gemcitabine, reversed immunosuppression and a significant increase in survival rate, comparable to 6-10 years in human terms. This is considered an extraordinary find in such a deadly cancer. Byers’ team created a small molecule drug that appears to be able to penetrate the dense fibrotic material and then inhibit CDH11. The drug has two effects – reducing fibrosis and switching the environment from immunosuppressive to one that is permissive, potentially allowing chemotherapy and immunotherapies to work. While their primary target at the start was for pancreatic cancer treatment, Byers sees no reason why the drug can’t potentially be effective in all fibrotic diseases. At the beginning of their research paper, the team started out compiling loads of data from multiple angles – RNA sequencing, single cell sequencing, cytokine arrays, phospho-protein arrays and bulk multi-dimensional assays. In the later stages, Byers formed a relationship with Fluidigm, as the company set up their first “center of excellence” using their imaging platform at Georgetown. Fluidigm manufactures life sciences tools to revolutionize the way biology is researched. First focused on microfluidic devices, the company acquired DVS Sciences in 2014 to expand its offerings to mass cytometry technology as well and has been evolving it ever since. After using Fluidigm’s Imaging Mass Cytometry (IMC) technology, according to Byer, “what we found is that we really didn’t need to any of the other [tests]. We could have just done Imaging Mass Cytometry. It’s multiplex, which means you can look at multiple markers at the same time. You can measure every gene, whether it goes up or down, in every situation and you get huge amounts of data. You can use it as a discovery to figure out what molecules are important.” The work that was done in Byers’ lab is proof-of-principle for Fluidigm technology. The company’s IMC replaced the fluorescents other technologies use with metals so that the platform can look at both protein and RNA simultaneously. This gives the ability to examine individual cells in the context of the tumor. “Tools like Imaging Mass Cytometry are really powerful tools for unlocking and making new discoveries in these complex diseases,” Andrew Quong, Chief Science Officer at Fluidigm, told BioSpace. Byers made it clear that while it’s not cheap to use IMC, in the grand scheme of things its more cost effective than doing all the other technologies he had previously done. He said Fluidigm has really put in the work to make their software intuitive and “user friendly.” “Mass cytometry and single cell sequencing is what we’re going to focus on. All of the other technologies we’ve just sort of put aside,” Byers said. Byers and co-inventor Sivanesan Dakshanamurthy have launched a startup from their research to develop the small molecule, CDH11 inhibitor the team developed. Dubbed Diviner Therapeutics, the biotech is looking for investors to finance their drug through an IND and into human trials. Fluidigm is utilizing its suspension-based technology to look into the evolution and changes in the immune system that occur after infection with SARS-CoV-2. The company’s platform plus immune profiling assay is perfect for the extended-range research needed to dig into the long-term effects of the virus on the immune system.