MPPE1

Data demonstrate compelling evidence of the immune-stimulatory properties linked to TLR-3 activation through Ampligen Additional commentary published discussing the potential of Ampligen and two other drugs OCALA, Fla., Aug. 20, 2024 (GLOBE NEWSWIRE) -- AIM ImmunoTech Inc. (NYSE American: AIM) (“AIM”) today announced the official print publication of the data analysis from a long-term Early Access Program (“EAP”) studying the company’s drug Ampligen® (rintatolimod) for the treatment of advanced pancreatic ductal adenocarcinoma (“PDAC”). The manuscript titled “Rintatolimod in Advanced Pancreatic Cancer enhances Anti-Tumor Immunity through Dendritic Cell-Mediated T Cell Responses,” appears in the journal Clinical Cancer Research, one of oncology’s most prestigious journals. Ampligen is a dsRNA product candidate that acts via the TLR-3 receptor present on several immune cells, epithelial cells and tumors. Researchers at the Erasmus University Medical Center (“Erasmus MC”) found that Ampligen treatment in pancreatic cancer patients enhances peripheral immune activity at the transcriptomic and proteomic levels, particularly involving type 1 conventional dendritic cells (cDC1s) and T cells. Post-Ampligen, the increased peripheral abundance of BTLA+XCR1+ cDC1s and CD4+SELL+ T cells correlated with improved clinical outcomes. Patients with stable disease exhibited pronounced overexpression of genes related to DC and T cell activation. Notably, the expression of immune checkpoints PD-L1 and PD-L2 decreased post-Ampligen across all patients. “We are grateful to the Erasmus team for their continued contributions to the advancement of Ampligen,” said AIM Chief Executive Officer Thomas K. Equels “There remains a large and growing unmet need for safe and effective treatments for pancreatic cancer. This data continues to provide us with further insight into Ampligen’s ability to improve progression-free survival and overall survival and enables us to identify cancer patients who might benefit more from Ampligen treatment than they would from other known cancer treatments.” Prof. Casper H.J. van Eijck, MD, PhD, Pancreato-biliary Surgeon at Erasmus MC and co-author of the published paper, added, “We continue to be encouraged by this data which suggests Ampligen infusions modulate PD-L1 and PD-L2 expression in the tumor microenvironment, while at the same time they upregulate Ki67+CD4+ and Ki67+CD8+ T-cells. We continue to make progress in the ongoing DURIPANC trial, which looks at the combination effect of Ampligen and AstraZeneca’s durvalumab and look forward to continuing evaluation of its potential for the treatment of pancreatic cancer.” In addition to the published manuscript, further commentary discussing the potential of Ampligen and two other drugs, referencing findings from the journal article, were published. Key highlights from the additional commentary include: Ampligen has been found to be also safely used through a systemic route.Interesting increases in cDC1 numbers and cytokines governing T-cell activation and migration are found to be upregulated.Researchers detected an important enrichment of B-cell numbers in peripheral blood from patients treated with Ampligen. B-cells correlated with long-term (>1 year) survival in a previous study. AIM is currently evaluating Ampligen as a therapy for metastatic pancreatic ductal adenocarcinoma in the Phase 1b/2 DURIPANC clinical study (NCT05927142) and as a therapy for locally advanced pancreatic adenocarcinoma in the Phase 2 AMP-270 clinical study (NCT05494697). About AIM ImmunoTech Inc. AIM ImmunoTech Inc. is an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders and viral diseases, including COVID-19. The Company’s lead product is a first-in-class investigational drug called Ampligen® (rintatolimod), a dsRNA and highly selective TLR3 agonist immuno-modulator with broad spectrum activity in clinical trials for globally important cancers, viral diseases and disorders of the immune system. For more information, please visit aimimmuno.com and connect with the Company on X, LinkedIn, and Facebook. Cautionary Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “continue,” “believe,” “potential,” “upcoming” and other variations thereon and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. Many of these forward-looking statements involve a number of risks and uncertainties. Publication of this data, and pre-clinical and clinical success seen to date, does not guarantee that Ampligen will be approved for the commercial treatment of cancers. The Company urges investors to consider specifically the various risk factors identified in its most recent Form 10-K, and any risk factors or cautionary statements included in any subsequent Form 10-Q or Form 8-K, filed with the U.S. Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Among other things, for those statements, the Company claims the protection of the safe harbor for forward-looking statements contained in the PSLRA. The Company does not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof.

Dose-escalation study to evaluate ORB-011 as single agent, with initial safety, pharmacokinetic and mechanism-based pharmacodynamic readouts Tony Fadell, inventor of the iPod, co-inventor of the iPhone, founder of Nest, and Principal at Build Collective, joins Orionis Board of Directors BOSTON & GHENT, Belgium--(BUSINESS WIRE)-- Orionis Biosciences, a life sciences company pioneering the creation of highly selective and tunable therapeutics for cancer and other diseases, today announced that the first patient has been dosed in a Phase 1 clinical trial of ORB-011, an attenuated, cis-targeted interferon immunotherapy based on the company’s A-Kine® platform. ORB-011 is the first clinical candidate to emerge from the platform, which engineers cytokines to be highly selective for specific cellular targets while avoiding the broad systemic activity and associated toxicities observed with traditional cytokine therapies. The company is also announcing the appointment of Tony Fadell to its Board of Directors. ORB-011 is a first-in-class modified interferon designed to act with a high level of precision on cDC1 dendritic immune cells, potent activators of tumor cell killing CD8+ T cells. Preclinical research has shown that selective activation of cDC1s with such conditionally active interferon molecules translates into effective antitumor activity. Targeted activation of cDC1 was also well tolerated in non-human primate studies. “The beginning of this clinical study represents a major milestone for Orionis and our A-Kine® protein engineering platform, which combines a range of redesigned immune-modulatory cytokines with targeting modules aimed at cell types of therapeutic relevance. ORB-011 has the potential to harness the therapeutic activity of interferon in a new way,” said Nikolai Kley, Ph.D., Founder, President, and Chief Executive Officer of Orionis Biosciences. “Interferons and other cytokines in our pipeline are powerful immune-activating agents. By localizing their activity to specific target cells, and exploiting communication networks across immune cells, we are evolving immunotherapies with unique translational potential.” Tony Fadell, Principal at Build Collective has joined the Orionis Board of Directors. He is the founder and former CEO of Nest, the company that pioneered the “Internet of Things.” Tony was the SVP of Apple’s iPod Division and led the team that created the first 18 generations of the iPod and the first three generations of the iPhone. Tony holds more than 300 patents and is the author of the New York Times Best-Seller “BUILD – An Unorthodox Guide to Making Things Worth Making.” “Tony is a tremendously supportive and collaborative investor, bringing a broad range of expertise and insights to countless topics important to the strategic growth and vision of our business,” said Dr. Kley. “His increased involvement will help us take Orionis to the next level and execute on our mission to bring new breakthrough medicines to patients in need.” “Orionis deploys the most powerful new foundational technologies available: Robotics plus Assay-on-Chip for high-throughput screening, generative AI for structure-based drug design...to name only a few,” said Fadell. “This is what’s needed to combat the toughest, currently undruggable diseases. I’m excited about Orionis’s focus on immunotherapies: activating and directing our natural immune system to go after cancer. I can’t think of a more worthwhile endeavor.” About ORB-011 ORB-011 is a clinical-stage, targeted interferon that is designed to specifically activate cDC1 dendritic cells, immune cells that are specialized in presenting tumor antigens to, and activating, tumor cytotoxic CD8 T cells. It achieves localized activity by a unique mechanism of induced proximity on the cell surface of cDC1s. Orionis is evaluating ORB-011 in a Phase 1 open-label dose-escalation study (NCT05947474) for patients with recurrent or refractory solid tumors amenable to medically safe serial biopsies, including, but not limited to, colorectal cancer, HR+ or triple-negative breast cancer, non-small cell lung cancer, pancreatic cancer, head and neck squamous cell carcinoma, metastatic melanoma, bladder/urothelial, gastric cancers, esophageal, renal cell, hepatic and ovarian cancers. The Phase 1 clinical trial will provide initial safety, pharmacokinetic and pharmacodynamic readouts, and identify a dose of ORB-011 for use in future studies. It is being conducted at this time at the M.D. Anderson Cancer Center in Houston, Texas and at Honor Health Research Institute in Scottsdale, Arizona. About the A-Kine® Platform Orionis’s A-Kine® platform is designed to harness the intrinsic function and therapeutic potential of cytokines as key immune system regulators and natural defenders against cancer and infections. A-Kines® are designed to be highly selective for intended cell targets, such as immune cells, and to avoid broad systemic activity and associated toxicities observed with traditional cytokine therapies. The platform covers multiple cytokine classes, including interferons, interleukins, and tumor necrosis factors, to generate a diversified pipeline of targeted immunotherapy candidates. These redesigned cytokines are leveraged to restart a stalled Cancer Immunity Cycle at multiple different positions to elicit natural mechanisms of immune attack against a variety of cancers. About Orionis Biosciences Orionis Biosciences is a life sciences company pioneering the discovery of conditionally active drug modalities for life threatening diseases. These operate by leveraging induced molecular proximity and cooperativity mechanisms in unique fashion to gain novel target access, drug potency and precision. The company applies its design concepts and technological innovations to the discovery of small molecules, with a focus on monovalent molecular glues with its Allo-Glue™ platform, and to the design and engineering of novel classes of precision biologics and cytokine-based immunotherapies with its A-Kine® platform. The company is advancing a deep and diversified pipeline of drug modalities, including agents that engage components of the adaptive and innate immune systems, creating new avenues for the development of single agent-effective therapies for patients with cancer or other diseases. To learn more, please visit .

The research article entitled “Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming” was published today in Science Immunology. The study was led by Asgard’s co-founder Filipe Pereira in collaboration with Asgard Therapeutics and other international partners. The research demonstrates the ability of Asgard’s technology to reprogram cancer cells into professional antigen-presenting cells, suppressing tumorigenesis and inducing in-vivo anti-tumor immunity in models resistant to checkpoint inhibitors. These findings support Asgard’s lead cancer immunotherapy program AT-108 which is progressing to advanced pre-clinical development, with an IND planned for 2026. Lund, Sweden – July 7, 2023 – Asgard Therapeutics (“Asgard”), a private biotech company pioneering in-vivo direct reprogramming approaches for cancer immunotherapy, is proud to announce the publication in Science Immunology demonstrating reprogramming of over 60 mouse and human tumors cells across a broad spectrum of tumor types into functional antigen-presenting cells. This study[1] represents a significant milestone for Asgard’s reprogramming technologies, providing the foundation for the ongoing development of its in-vivo engineering programs. To access the publication: DOI: 10.1126/sciimmunol.add4817 Fabio Rosa, PhD, Co-Founder and Head of Research at Asgard Therapeutics, said: “This study represents a major output of our long-lasting collaboration with the Pereira Lab at Lund University focusing on the unique anti-tumor properties of conventional type 1 dendritic cells (cDC1s). We showed for the first time that reprogrammed cDC1s kick start in-vivo anti-tumor immunity, leading to complete regression of tumors! In addition, reprogramming induced loss of tumorigenic properties in cancer cells, supporting the feasibility of moving towards an in-vivo engineering approach. At Asgard, we have recently selected our lead candidate AT-108, an off-the-shelf gene delivery vector encoding our proprietary combination of reprogramming factors. AT-108 is delivered directly in-vivo to recreate cDC1s’ functional properties in tumor cells and kick-start personalized anti-tumor immunity, bypassing limitations of ex-vivo cell therapies and complex tumor neoantigen identification. AT-108 is now moving into advanced pre-clinical development with IND planned for 2026.” Filipe Pereira, PhD, Co-founder and Head of Innovation at Asgard Therapeutics, Professor and Group leader at Lund University said: “Cancer cells downregulate antigen presentation to evade immune surveillance. Reversal of this mechanism has been attempted with definite mediators and downstream pathways, but we wanted to take it a step forward. By applying our knowledge of cell fate reprogramming, we have now demonstrated that the minimal transcription factor network of cDC1s[2] can be applied to engineer cancer cells’ identity. We observed that a common cDC1 and antigen presenting signature (of more than 600 genes) was commonly upregulated across mouse and human cancer cells, including patient-derived samples from 7 indications, broadly activating downstream pathways critical for efficient anti-tumor immunity (i.e. class I and II MHC molecules, co-stimulatory signaling, IL-12, CXCL10, among others). Our findings support the platform potential of our reprogramming approach which armed cancer cells with the ability to present their own endogenous tumor antigens and activate in-vivo cytotoxic CD8+ T cell responses, leading to increased survival of tumor-bearing mice”. The study was led by Filipe Pereira in a collaborative effort between his team in the Cell Reprogramming in Hematopoiesis and Immunity Group at Lund University Stem Cell Center (LSCC), Asgard Therapeutics, a member of SmiLe Incubator, and its collaborators, Inge Marie Svane from the National Center of Cancer Immune Therapy in Denmark, Lennart Greiff and Malin Lindstedt from Lund University, among many others. The research at Asgard has been carried out with support from the Eurostars-2 Joint Program with co-funding from the European Union’s Horizon 2020 research and innovation program, and Sweden’s Innovation Agency, E!115376 REPRINT Grant 2021-03371, and the Strategic innovation programs Swelife and Medtech4Health, a joint venture by Vinnova, Formas and the Swedish Energy Agency, Grant 2020-04744. The illustration depicts a novel Trojan horse approach to cancer immunotherapy by reprogramming cancer cells to become traitors to their kind. Using the minimal regulatory network of type 1 conventional dendritic cells (connections and cells inside the horse), Zimmermannova & Ferreira et al. reprogrammed human and mouse cancer cells into dendritic cells. This strategy bypassed tumor evasion mechanisms and endowed tumor cells with professional antigen presentation leading to activation of specific CD8+ T cells (soldiers), and anti-tumor immunity in vivo. This study paves the way for a new class of cancer immunotherapies based on cell fate reprogramming. Credit: Sandeep Menon. For investor relations:  Asgard Therapeutics  Cristiana Pires, Co-founder, and CEO  +46 (0) 731 566 072  cristiana.pires@asgardthx.com  For scientific inquiries:  Asgard Therapeutics  Fábio Rosa, Co-founder, and Head of Research +46 (0) 763 059 937 fabio.rosa@asgardthx.com Lund University Filipe Pereira, Professor and Group leader at Lund University +46 (0) 72 243 00 14 filipe.pereira@med.lu.se About Asgard Therapeutics®  Asgard Therapeutics is a private biotech company exploring the application of direct cell reprogramming technologies for cancer immunotherapies. Formed as a spin-off from Lund University, the Company is pioneering a gene therapy approach based on its proprietary reprogramming technology, designed to set in motion immune responses based on the biological properties of professional antigen-presenting cells. Backed by Novo Holdings, Boehringer Ingelheim Venture Fund, and Industrifonden, Asgard Therapeutics aims to build a pipeline of personalized cancer immunotherapies optimized for each unique patient. For more information, please visit: www.asgardthx.com.   About the Pereira Lab at Lund University Professor Filipe Pereira is head of the Cell Reprogramming in Hematopoiesis and Immunity Group at the Lund University Stem Cell Center (LSCC). LSCC is one of six Swedish strategic centers of excellence in life sciences. Filipe Pereira is considered an influential researcher in the cell reprogramming field with >45 publications, >3,300 citations. Find more at https://pereiralab.com/ and https://www.stemcellcenter.lu.se/. [1] DOI: 10.1126/sciimmunol.add4817 [2] DOI: 10.1126/sciimmunol.aau4292; DOI: 10.1126/sciimmunol.abg5539