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BERWYN, Pa., April 27, 2023 (GLOBE NEWSWIRE) -- (NYSE: ANVS) ("Annovis" or the "Company"), a clinical-stage drug platform company developing treatments for neurodegenerative diseases announced today that the United States Patent and Trademark Office (USPTO) has granted the Company a patent with claims covering the use of Annovis Bio’s lead drug candidate, buntanetap, for the prevention and treatment of diseases caused by the disruption in heavy metal homeostasis. U.S. Patent 11,596,621 B2 is titled, “Prevention or Treatment of Disease States Due to Metal Dis-homeostasis Via Administration of Posiphen [buntanetap] to Healthy or Sick Humans” and was issued on March 7, 2023. The patent is expected to confer protection for use of buntanetap and its related analogue molecules for the prevention and treatment of various neurodegenerative diseases associated with metal dis-homeostasis out to early 2040. The ‘621 patent covers the use of buntanetap for maintaining or restoring heavy metal homeostasis as a method of prevention in healthy humans or as a method of treatment in sick humans. Metal dis-homeostasis, particularly iron, is a hallmark of various conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and vital organ dysfunction (i.e., brain, heart, liver, lung, and/or kidney). Iron plays a crucial role in many biological processes including translational regulation of neurotoxic proteins. In neurodegenerative diseases, such proteins include amyloid precursor protein (APP), amyloid-β, tau, α-synuclein, TDP-43, TSE, superoxide dismutase, huntingtin, prion, and c9orf72. The translation of these proteins are regulated by the iron regulatory protein 1 (IRP1) which binds a preserved sequence of mRNA. When this preserved sequence is bound to IRP1, the mRNA is prevented from attaching to the ribosome and being translated. An overload of iron leads to the release of the mRNA from IRP1 and to the translation of the mRNA by the ribosome resulting in the high levels of neurotoxic proteins. Annovis Bio’s lead drug candidate, buntanetap, inhibits the production of these neurotoxic proteins and therefore has broad clinical utility across a wide spectrum of neuro-inflammatory diseases, including Alzheimer’s disease and Parkinson’s disease. “The basis for this newly issued U.S. patent is the ability of buntanetap to augment the binding of IRP1 to mRNA under high iron conditions preventing the translation of neurotoxic proteins and restoring homeostasis,” said Maria L. Maccecchini, Ph.D., Founder, President, and CEO of Annovis. “Expanding our intellectual property portfolio remains a key strategic focus of Annovis. By introducing buntanetap as a preventative and/or restorative agent for different diseases characterized by an imbalance in metal homeostasis, we seek to expand the IP protections surrounding the clinical utility of this unique and differentiated therapy across a broad range of diseases and conditions impacted by the disruption of heavy metal homeostasis.” The ‘621 patent provides coverage for several aspects of treatment with buntanetap, preventing disease through chronic prophylactic use of buntanetap in healthy humans to maintain iron homeostasis, and use of the drug to restore iron homeostasis in sick humans. Annovis Bio has patents that cover a wide range of chronic neurodegenerative as well as acute neurodegenerative diseases. It furthermore has patents covering neuropsychiatric disorders. About BuntanetapBuntanetap (previously known as ANVS401 or Posiphen) is an oral translational inhibitor of neurotoxic aggregating proteins (TINAPs) which play a role in axonal injury, inflammation, and cell death. By targeting these mechanisms, buntanetap was shown to improve cognitive functions in patients with different neurodegenerative disorders. In Phase 2a clinical trial in AD and PD patients, buntanetap was well-tolerated and safe, and resulted in statistically significant improvement in motor function in PD patients and cognition in AD patients. About Annovis Bio, Inc. Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. (Annovis) is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer's disease (AD), Parkinson's disease (PD), and other chronic neurodegenerative diseases. We believe that we are the only company developing a drug for AD and PD that is designed to inhibit more than one neurotoxic protein and has a mechanism of action designed to restore axonal and synaptic activity. By improving brain function, our goal is to treat memory loss and dementia associated with AD as well as body and brain function associated with PD. Annovis conducted two Phase 1/2 studies: one in AD patients and one in both AD and PD patients. In the AD/PD study buntanetap showed improvements in cognition in AD as well as body and function in PD patients. For more information on Annovis Bio, please visit the Company's website www.annovisbio.com and follow us on LinkedIn and Twitter. Forward-Looking StatementThis 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. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The Company advises caution in reliance on forward-looking statements. Forward-looking statements include, without limitation, the Company's plans related to clinical trials and projections regarding the use of and need for capital. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially from those implied by forward-looking statements, including regarding patient enrollment, the effectiveness of Buntanetap, the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety and tolerability of Buntanetap, and the timing of costs required to fund the Company's operations including such clinical trials. See also additional risk factors set forth in the Company's periodic filings with the SEC, including, but not limited to, those risks and uncertainties listed in the section entitled "Risk Factors," in the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the SEC. All forward-looking statements in this press release are based on information available to the Company as of the date of this filing. The Company expressly disclaims any obligation to update or alter its forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. Media ContactNic JohnsonRusso Partners, LLC (303) 482-6405nic.johnson@russopartnersllc.com Investors Contact: Chris Calabrese LifeSci Advisors, LLC+1 (917) 680-5608ccalabrese@lifesciadvisors.com Kevin Gardner+1 (617) 283-2856LifeSci Advisors, LLCkgardner@lifesciadvisors.com SOURCE Annovis Bio

Two proteins ensure that cells can take up iron when needed. If both control proteins are switched off in mice, the animals develop severe anemia, as expected. Surprisingly, at the same time a cell type of the innate immune defense, the neutrophils, also dramatically decreases. Iron deficiency, a known defense mechanism against infectious pathogens, is a double edged sword, as it simultaneously curbs the defensive power of an important arm of the innate immune system. Two proteins ensure that cells can take up iron when needed. If both control proteins are switched off in mice, the animals develop severe anemia, as expected. Supprisingly, at the same time a cell type of the innate immune defense, the neutrophils, also dramatically decreases, as scientists from the German Cancer Research Center now have shown for the first time. Iron deficiency, a known defense mechanism against infectious pathogens, is a double edged sword, as it simultaneously curbs the defensive power of an important arm of the innate immune system. A balanced iron metabolism is an essential prerequisite for our health. Drugs that target iron deficiency or iron excess are among the most widely prescribed therapies worldwide. The fact that iron is an indispensable component of the blood is almost common knowledge: The metal is an important component of the blood pigment hemoglobin, which is responsible for transporting oxygen in the red blood cells. The iron supply to the cells is controlled by the two proteins IRP-1 and IRP-2. If the cell lacks iron, IRP-1 and IRP-2 crank up the production of the various iron transporter proteins that take iron into the cell. IRP-1 and IRP-2 also ensure that an equally dangerous excess of iron does not occur. IRP-1 and IRP-2 are essential for survival: mice lacking both control proteins during embryonic development die while still in the womb. But what happens when IRP-1 and IRP-2 fail in adult mice? A team led by Bruno Galy at DKFZ has now investigated this in mice whose IRP production can be shut down by injecting a drug. As the researchers had expected, the most striking change after IRPs were switched off was a pronounced decrease in red blood cells. Due to the lack of hemoglobin, these erythrocytes reached only a minimal size. However, the researchers were surprised to see that white blood cells also decreased extremely. Closer examination revealed that this decline was mainly due to a deficiency of neutrophils. These immune cells account for up to two-thirds of white blood cells in humans and are an important component of the innate immune system. This decline is not a caused by a mass death of neutrophils, but a developmental blockade in the hematopoietic system: the precursor cells in the bone marrow no longer develop into mature neutrophils, as this differentiation process is apparently iron-dependent. Other types of white blood cells, such as monocytes, were not affected by the IRP-dependent developmental blockade. Iron limitation is a double-edged sword "This strong iron dependence of neutrophils was previously unknown. It possibly affects the immune defense against bacterial pathogens," says Bruno Galy. Interestingly, on the other hand, iron deficiency is one of the body's defense strategies in bacterial infections: many pathogens are dependent on iron. To slow down their multiplication, the body hoards the metal in certain cells that serve as a storage chamber to make it more difficult for pathogens to access this valuable resource. Another publication in the same issue of the journal Science Advances, in which Galy is also involved, demonstrates that iron deficiency in blood serum, as typically occurs with infections, leads to a decrease in neutrophils in mice and limits the ability of these immune cells to fight bacteria. "Iron deficiency apparently modulates the innate immune system. It suppresses the maturation of neutrophils and also throttles their defensive power," says Bruno Galy, adding: "The limitation of available iron is apparently a double-edged sword: On the one hand, the body thereby prevents bacteria from spreading. On the other hand, the function of an important arm of the innate immune system suffers." Not only infections but also inflammations often lead to iron deficiency and thus to anemia. Cancer patients whose disease is accompanied by chronic inflammatory conditions are therefore often affected by anemia, which can severely limit their quality of life. "Next, we want to investigate whether iron deficiency in chronic inflammation also impairs immune function," Galy says. Michael Bonadonna, Sandro Altamura Elisabeth Tybl, Gael Palais, Maria Qatato, Maria Polycarpou-Schwarz, Martin Schneider, Christina Kalk, Wibke Rüdiger, Alina Ertl, Natasha Anstee, Ruzhica Bogeska, Dominic Helm, Michael D. Milsom, Bruno Galy: Iron regulatory protein (IRP-)mediated iron homeostasis is critical for neutrophil development and differentiation in the bone marrow.

BERWYN, Pa., Sept. 8, 2022 /PRNewswire/ -- Annovis Bio, Inc. (NYSE: ANVS) ("Annovis" or the "Company"), a late-stage clinical drug platform company addressing neurodegenerative diseases, today released the following letter to stockholders from its Chief Executive Officer Dr. Maria Maccecchini. Dear Fellow Stockholder, Over the years we have been talking about the potential of buntanetap to treat more than Alzheimer's disease. In cell models, animal models and human clinical studies, we have seen that buntanetap works in numerous acute and chronic neurodegenerative conditions. I would like to take this opportunity to explain how one drug can be so broadly applicable. Buntenatap works by inhibiting specific neurotoxic proteins such as amyloid precursor protein (APP), Tau, alpha-synuclein (αSYN), TAR DNA binding protein 43 (TDP-43), huntingtin (HTT) and prion protein. These proteins have normal functions but in their neurotoxic aggregating form, they impair axonal transport, slow synaptic transmission, cause inflammation, and ultimately, kill nerve cells, resulting in the loss of affected function in various neurodegenerative conditions. The overexpression and aggregation of these proteins is caused by elevated levels of iron in the nerve cell. The mRNAs of neurotoxic aggregating proteins contain an iron response element (IRE) which binds to an iron regulatory protein called IRP1. At normal iron levels, translation occurs at appropriate physiological levels. When iron flows into the cell, the mRNAs are released and translated at higher rates by the ribosome. When massive iron flows in, the mRNAs remain unbound for as long as the iron is high and the proteins for these neurotoxic aggregating proteins are overexpressed. In this high iron situation, buntanetap binds to the atypical IRE-IRP1 complex and prevents the mRNA from being released and, therefore, from being translated and overexpressed. Buntanetap is able to inhibit the translation of multiple neurotoxic proteins through this mechanism of action, and as a result has the potential to treat numerous acute and chronic neurodegenerative conditions that share this pathway. In mouse or rat models of Alzheimer's, Parkinson's, stroke, frontotemporal dementia, traumatic brain injury, glaucoma, and Down Syndrome, buntanetap has been shown to normalize the levels of these neurotoxic proteins and to restore function. Most importantly, this has been demonstrated in human clinical trials. In our recent Phase 2 clinical trial in Alzheimer's disease and Parkinson's disease, treatment with buntanetap resulted in reduction of aggregating proteins and statistically significant improvement in motor function in Parkinson's disease patients and cognition in Alzheimer's disease patients. We look forward to unlocking the full potential of buntanetap and addressing unmet needs across a range of acute and chronic neurological conditions. Maria L. Maccecchini, Ph.D., Founder, President, CEO and Executive Board Member About Buntanetap Buntanetap (previously known as ANVS401 or Posiphen) is an oral translational inhibitor of neurotoxic aggregating proteins (TINAPs), which mode of action leads to lower levels of neurotoxic proteins and consequently less toxicity in the brain. In a Phase 2a clinical trial in AD and PD patients, treatment with buntanetap resulted in statistically significant improvement in motor function in PD patients and cognition in AD patients. Additionally, the drug was well-tolerated and safe, and its pharmacokinetics were found to be in line with levels measured earlier in humans, meeting both the primary and secondary endpoints. About Annovis Bio, Inc. Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. is a late-stage clinical drug platform company developing transformative therapies that treat neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and other chronic and acute neurodegenerative diseases. The Company believes that it is the only company developing a drug that inhibits more than one neurotoxic protein, improves the information highway of the nerve cell, known as axonal transport, reduces inflammation and protects nerve cells from dying in chronic and acute neurodegeneration. Annovis conducted two Phase 2 studies: one in AD patients and one in both AD and PD patients. In the AD/PD study, buntanetap showed improvements in cognition and memory in AD as well as body and brain function in PD patients. For more information on Annovis Bio, please visit the Company's website and follow us on LinkedIn and Twitter. Forward-Looking Statements Statements in this press release contain "forward-looking statements" that are subject to substantial risks and uncertainties. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "expect," "believe," "will," "may," "should," "estimate," "project," "outlook," "forecast" or other similar words, and include, without limitation, statements regarding the timing, effectiveness, and anticipated results of buntanetap clinical trials. Forward-looking statements are based on Annovis Bio, Inc.'s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled "Risk Factors" in the Annual Report on Form 10-K for the year ended December 31, 2021, filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Annovis Bio, Inc. undertakes no duty to update such information except as required under applicable law. Media and Investor Contact: Nic Johnson Russo Partners, LLC (303) 482-6405 nic.johnson@russopartnersllc.com View original content to download multimedia: SOURCE Annovis Bio Company Codes: NYSE:ANVS