Oculodigitoesophagoduodenal Syndrome

ENGLEWOOD, Colo., April 18, 2023 /PRNewswire/ -- Ampio Pharmaceuticals, Inc. (NYSE American: AMPE) (the "Company") today released the following letter to stockholders from its Chairman, Kevin Buchi and Chief Executive Officer, Mike Martino. Dear Ampio Stockholders: On March 28, 2023, we filed our 2022 Annual Report on Form 10-K. In this letter we would like to elaborate on two key operational points which were included in that Annual Report. Firstly, we want to elaborate on progress with the development of what we have previously called, "AR-300." We gained a considerable amount of knowledge about osteoarthritis (OA) from the company's previous clinical and in vitro studies with Ampion. In January 2022, we began work on "AR-300," a series of synthetic formulations of what we believed to be the three active pharmaceutical ingredients (APIs) that were present at low levels in Ampion. Our development efforts in the first quarter 2023 have focused on rigorously testing different formulations of these APIs at an independent, well-respected research organization, using two validated, well-published rodent models of OA, which we will highlight here. The first model, called the medial meniscal tear (MMT) model, results in pathology that highly resembles the pathology that occurs with OA in humans, and is the most common preclinical model used by industry to identify potential therapies that may inhibit cartilage degeneration associated with OA. The second model, the mono-iodoacetate (MIA) model, measures the effects of potential therapies on the pain associated with progressive stages of OA, and is also the most common preclinical model used by industry to identify potential therapies to treat the pain associated with OA. To-date, we have shown cartilage protection in the MMT model with multiple combinations of the prospective APIs, with one formulation generating especially encouraging results. Additionally, in the MIA model, several alternative formulations have demonstrated immediate and early pain reduction in the inflammatory pain phase of the model. The combination of pain reduction and prevention of cartilage degeneration provides optimism that we have a drug candidate to treat OA of the knee (OAK). Of course, we will have to demonstrate these benefits in clinical trials acceptable to regulators and payers, but we are encouraged by these results. Additionally, we want to emphasize that these are results that were never observed with Ampion, nor with the original formulations of AR-300. These results show that we are now in possession of new and unique formulations, separate and distinct from both Ampion and AR-300, that demonstrate their own therapeutic potential. Because of that, we have already taken steps to protect this new intellectual property, worldwide. Based on this progress, we have focused our ongoing efforts toward optimizing two potential formulations to take forward into development. In the third quarter of 2023, we intend to select one of these optimized formulations to move towards clinical development. Given that these formulations are unique, proprietary, and are neither Ampion nor AR-300 (or derivatives thereof), we will now refer to development of these new formulations as OA-20X program. With the data from these additional studies, we will be in position later this year to seek scientific advice meetings with the FDA, UK, and EU regulatory authorities. Secondly, we want to elaborate on our progress in implementing a hybrid, virtual organizational model. From the outset, our intent was (and remains) to retain the organizational capabilities to govern a publicly traded company, comply with related reporting requirements, lead strategy development and program selection, and identify, retain, and manage third-party contractors with specific and proven expertise in the different, related activities required to develop a drug (e.g., drug candidate selection, formulation development, GMP manufacturing, preclinical development, clinical development, regulatory, etc.) on a just-in-time, as needed basis. We believe this model positions us to drive strategic development in the most expeditious and cost-effective way. We communicated, and began implementing, this organizational strategy at the end of 2022 with a planned reduction in force, which continued into the first quarter 2023. In addition, we entered into a sublease agreement effective March 1, 2023, whereby we have subleased the entire Ampio facility in Colorado. As a result of implementing this organizational strategy, Ampio now has five full-time employees, numerous engaged consultants with industry leading expertise in osteoarthritis (OA) drug development (as outlined above) and independent labs and contract manufacturing partners, all collaborating to further the development of the OA-20x program. We expect to remain a Colorado-based company for the foreseeable future and for the time being have retained our current mailing address. We estimate that this strategy will result in annualized cost savings of approximately $4.6 million, allowing us to focus our cash investment on OA-20x development for 2023 in addition to our ongoing governance and reporting obligations as a publicly traded company and other necessary expenses. Again, this update elaborates on just two points from our recently filed Annual Report, and we encourage you to read the full Annual Report in its entirety because it contains important information. We look forward to updating you following conclusion of the third quarter 2023. Best regards, J. Kevin Buchi, Chair of the Board of Directors Michael A. Martino, Chief Executive Officer Caution Regarding Forward-Looking Statements All statements other than statements of historical facts contained in this letter, including statements regarding our anticipated future clinical developments, future financial position, and plans and objectives of management for future operations, are forward-looking statements. Words such as "may", "will", "should", "forecast", "could", "expect", "suggest", "believe", "estimate", "continue", "anticipate", "intend", "ongoing", "opportunity", "potential", "predicts", "seek", "plan," or similar words, or the negatives of such terms or other variations on such terms or comparable terminology, typically identify forward-looking statements. Forward-looking statements are based on certain assumptions and expectations of future events and trends that are subject to risks and uncertainties including: we are dependent on the success of our OA-20X program and we cannot be certain that any preclinical data will support its further development; there can be no assurance that we will be successful in identifying or completing any strategic alternative or that any such strategic alternative will yield value for our stockholders; we may not be able to manage third parties to provide timely, high quality, and cost-effective services to us; our history of losses and our cash resources available to execute our business plan over the next twelve months raise substantial doubt about our ability to continue as a going concern; we are involved in legal proceedings that likely will adversely affect our financial position and our pursuit of strategic alternatives; we may need additional capital to fund our future operations, the development of the OA-20X program and any strategic transaction; we are dependent on adequate protection of our patent and proprietary rights; the price of our stock has been and may continue to be extremely volatile; if we cannot continue to satisfy the NYSE American continued listing requirements and rules, our securities may be delisted, which could negatively impact the price of our securities; and other risks described in "Risk Factors" and elsewhere in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022 and subsequent periodic reports filed with the SEC. We undertake no obligation to update or revise publicly any forward-looking statements to reflect events or circumstances after the date of such statements for any reason, except as otherwise required by law. For more information, contact: Ampio Pharmaceuticals, Inc. Michael Martino Chief Executive Officer [email protected] SOURCE Ampio Pharmaceuticals, Inc.

ENGLEWOOD, Colo., April 18, 2023 /PRNewswire/ -- Ampio Pharmaceuticals, Inc. (NYSE American: AMPE) (the "Company") today released the following letter to stockholders from its Chairman, Kevin Buchi and Chief Executive Officer, Mike Martino. Dear Ampio Stockholders: On March 28, 2023, we filed our 2022 Annual Report on Form 10-K. In this letter we would like to elaborate on two key operational points which were included in that Annual Report. Firstly, we want to elaborate on progress with the development of what we have previously called, "AR-300." We gained a considerable amount of knowledge about osteoarthritis (OA) from the company's previous clinical and in vitro studies with Ampion. In January 2022, we began work on "AR-300," a series of synthetic formulations of what we believed to be the three active pharmaceutical ingredients (APIs) that were present at low levels in Ampion. Our development efforts in the first quarter 2023 have focused on rigorously testing different formulations of these APIs at an independent, well-respected research organization, using two validated, well-published rodent models of OA, which we will highlight here. The first model, called the medial meniscal tear (MMT) model, results in pathology that highly resembles the pathology that occurs with OA in humans, and is the most common preclinical model used by industry to identify potential therapies that may inhibit cartilage degeneration associated with OA. The second model, the mono-iodoacetate (MIA) model, measures the effects of potential therapies on the pain associated with progressive stages of OA, and is also the most common preclinical model used by industry to identify potential therapies to treat the pain associated with OA. To-date, we have shown cartilage protection in the MMT model with multiple combinations of the prospective APIs, with one formulation generating especially encouraging results. Additionally, in the MIA model, several alternative formulations have demonstrated immediate and early pain reduction in the inflammatory pain phase of the model. The combination of pain reduction and prevention of cartilage degeneration provides optimism that we have a drug candidate to treat OA of the knee (OAK). Of course, we will have to demonstrate these benefits in clinical trials acceptable to regulators and payers, but we are encouraged by these results. Additionally, we want to emphasize that these are results that were never observed with Ampion, nor with the original formulations of AR-300. These results show that we are now in possession of new and unique formulations, separate and distinct from both Ampion and AR-300, that demonstrate their own therapeutic potential. Because of that, we have already taken steps to protect this new intellectual property, worldwide. Based on this progress, we have focused our ongoing efforts toward optimizing two potential formulations to take forward into development. In the third quarter of 2023, we intend to select one of these optimized formulations to move towards clinical development. Given that these formulations are unique, proprietary, and are neither Ampion nor AR-300 (or derivatives thereof), we will now refer to development of these new formulations as OA-20X program. With the data from these additional studies, we will be in position later this year to seek scientific advice meetings with the FDA, UK, and EU regulatory authorities. Secondly, we want to elaborate on our progress in implementing a hybrid, virtual organizational model. From the outset, our intent was (and remains) to retain the organizational capabilities to govern a publicly traded company, comply with related reporting requirements, lead strategy development and program selection, and identify, retain, and manage third-party contractors with specific and proven expertise in the different, related activities required to develop a drug (e.g., drug candidate selection, formulation development, GMP manufacturing, preclinical development, clinical development, regulatory, etc.) on a just-in-time, as needed basis. We believe this model positions us to drive strategic development in the most expeditious and cost-effective way. We communicated, and began implementing, this organizational strategy at the end of 2022 with a planned reduction in force, which continued into the first quarter 2023. In addition, we entered into a sublease agreement effective March 1, 2023, whereby we have subleased the entire Ampio facility in Colorado. As a result of implementing this organizational strategy, Ampio now has five full-time employees, numerous engaged consultants with industry leading expertise in osteoarthritis (OA) drug development (as outlined above) and independent labs and contract manufacturing partners, all collaborating to further the development of the OA-20x program. We expect to remain a Colorado-based company for the foreseeable future and for the time being have retained our current mailing address. We estimate that this strategy will result in annualized cost savings of approximately $4.6 million, allowing us to focus our cash investment on OA-20x development for 2023 in addition to our ongoing governance and reporting obligations as a publicly traded company and other necessary expenses. Again, this update elaborates on just two points from our recently filed Annual Report, and we encourage you to read the full Annual Report in its entirety because it contains important information. We look forward to updating you following conclusion of the third quarter 2023. Best regards, J. Kevin Buchi, Chair of the Board of Directors Michael A. Martino, Chief Executive Officer Caution Regarding Forward-Looking Statements All statements other than statements of historical facts contained in this letter, including statements regarding our anticipated future clinical developments, future financial position, and plans and objectives of management for future operations, are forward-looking statements. Words such as "may", "will", "should", "forecast", "could", "expect", "suggest", "believe", "estimate", "continue", "anticipate", "intend", "ongoing", "opportunity", "potential", "predicts", "seek", "plan," or similar words, or the negatives of such terms or other variations on such terms or comparable terminology, typically identify forward-looking statements. Forward-looking statements are based on certain assumptions and expectations of future events and trends that are subject to risks and uncertainties including: we are dependent on the success of our OA-20X program and we cannot be certain that any preclinical data will support its further development; there can be no assurance that we will be successful in identifying or completing any strategic alternative or that any such strategic alternative will yield value for our stockholders; we may not be able to manage third parties to provide timely, high quality, and cost-effective services to us; our history of losses and our cash resources available to execute our business plan over the next twelve months raise substantial doubt about our ability to continue as a going concern; we are involved in legal proceedings that likely will adversely affect our financial position and our pursuit of strategic alternatives; we may need additional capital to fund our future operations, the development of the OA-20X program and any strategic transaction; we are dependent on adequate protection of our patent and proprietary rights; the price of our stock has been and may continue to be extremely volatile; if we cannot continue to satisfy the NYSE American continued listing requirements and rules, our securities may be delisted, which could negatively impact the price of our securities; and other risks described in "Risk Factors" and elsewhere in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022 and subsequent periodic reports filed with the SEC. We undertake no obligation to update or revise publicly any forward-looking statements to reflect events or circumstances after the date of such statements for any reason, except as otherwise required by law. For more information, contact: Ampio Pharmaceuticals, Inc. Michael Martino Chief Executive Officer mmartino@ampiopharma.com View original content to download multimedia: SOURCE Ampio Pharmaceuticals, Inc. Company Codes: NYSE:AMPE, AMEX:AMPE

A decrease in protein synthesis in cells of the developing gut contributes to a rare genetic disorder, and an inexpensive nutritional supplement may help reverse that decrease, according to a new study. A decrease in protein synthesis in cells of the developing gut contributes to a rare genetic disorder, and an inexpensive nutritional supplement may help reverse that decrease, according to a new study publishing November 1 in the open access journal PLOS Biology by Yun-Fei Li of Zhejiang University School of Medicine in Hangzhou, China, and colleagues. The finding is an advance in understanding the pathogenesis of the disease, and may lead to new treatments. Feingold syndrome type 1 leads to multiple problems in development, including of the skeleton and nervous system, but the symptom with the greatest impact on patients' lives is intestinal atresia, or incomplete development of the gastrointestinal tract. The disorder is caused by loss-of-function mutations in the gene Mycn, which encodes a critical transcription factor that regulates the activity of many genes, but to date there has been no animal model to study the effects of that loss. The authors created that model by using CRISPR genome editing to delete a portion of the Mycn gene in zebrafish, whose gut development shares important similarities with that of humans. They found that the resulting loss of gene activity led to a dramatic reduction in the size of the intestine, both in length and in the folding that gives the intestine its enormous surface area for absorption. Within a particularly affected subgroup of cells in the developing intestine, they found a significant down-regulation of numerous ribosomal genes, leading to reduced gene translation and protein synthesis. Particularly affected were genes in the mTOR signaling pathway, a central regulator of protein synthesis; treatment of wild-type zebrafish with an mTOR inhibitor recapitulated the intestinal developmental defects seen in Mycn mutants. When the authors treated the mutant fish with leucine, an amino acid known to activate the mTOR pathway, the result was a partial normalization of the intestinal size in the mutants. "Our work shows that during embryonic development, intestinal cells, which are in a highly proliferative state, require high Mycn expression levels," the corresponding authors, Peng-Fei Xu and Xi Jin, say, "and that the proliferation arrest caused by reduced protein synthesis was the main reason for the developmental defects in the intestines of the Mycn mutant. This suggests a possible treatment strategy for the intestinal symptoms in patients with Feingold syndrome type 1, although confirmation in a human intestinal organoid system is essential." The first authors, Yun-Fei Li and Tao Cheng, add, "Feingold syndrome resulting from Mycn deficiency has been discovered for decades, however, the mechanism that leads to gastrointestinal atresia in Feingold syndrome type 1 is still unclear. We developed a Mycn mutant zebrafish model which recapitulates key phenotypes of Feingold syndrome type 1, and also provided a possible treatment strategy for Feingold syndrome type 1."