Ampion (aspartyl-alanyl diketopiperazine) / Ampio - LARVOL DELTA

The Efficacy and Safety of Intra-articular Low Molecular Weight Fraction of Human Serum Albumin for the Management of Moderate to Moderately Severe Knee Osteoarthritis: A Systematic Review and Meta-Analysis. (PubMed, Cureus) - "On the other hand, LMWF-5A did not demonstrate superiority over saline in terms of efficacy. Therefore, it is not an effective drug for managing knee osteoarthritis."

Journal • Retrospective data • Review • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

AMPIO PHARMACEUTICALS ISSUES LETTER TO STOCKHOLDERS (Yahoo News) - "We have also informed the FDA that we have discontinued development of Ampion and have withdrawn the 3 Investigational New Drug (INDs) applications we held: intra-articular injection for Osteoarthritis, intravenous and nebulized COVID. These actions conclude all development efforts on Ampion."

Discontinued • CNS Disorders • Immunology • Osteoarthritis • Pain

Study of Ampion for the Treatment of Pain and Function in Patients With Severe Osteoarthritis of the Knee. (clinicaltrials.gov) - P3 | N=1043 | Terminated | Sponsor: Ampio Pharmaceuticals. Inc. | Completed ➔ Terminated; The AP-013 study was prematurely terminated by the sponsor after Data Safety Monitoring Board (DSMB) guidance.

Trial termination • Immunology • Osteoarthritis • Pain • Rheumatology

An Efficacy and Safety Study of Two Doses of Intra-Articular Ampion Injection for Pain of Osteoarthritis of the Knee (clinicaltrials.gov) - P2 | N=329 | Completed | Sponsor: Ampio Pharmaceuticals. Inc. | Phase classification: P3 ➔ P2

Phase classification • Immunology • Osteoarthritis • Pain • Rheumatology

Ampio Pharmaceuticals, Inc. to Hold Conference Call (PRNewswire) - "Ampio Pharmaceuticals, Inc...announced that the Company will be hosting a conference call on April 28, 2022 at 8am EDT regarding the update from the Food and Drug Administration with respect to its AP-013 study."

FDA event • CNS Disorders • Osteoarthritis • Pain

AMPIO PROVIDES REGULATORY UPDATE (PRNewswire) - "Ampio Pharmaceuticals, Inc...today announced the receipt of written responses from the United States Food and Drug Administration (FDA) pursuant to a Type C meeting request submitted by the Company earlier in the year regarding the AP-013 trial results....FDA responded that it did not agree with the Company's proposed change from the ITT population to the mITT population for the primary endpoint analysis, that mITT is a substantive and material change to the Protocol and Statistical Analysis Plan that is not in accordance with the Special Protocol Assessment agreement....FDA further stated that it did not agree that AP-013 could serve as a second pivotal trial for Ampion based on both the change in the analysis population and the analysis of pain only instead of the original prespecified co-primary endpoints."

FDA event • CNS Disorders • Osteoarthritis • Pain

Ampio Pharmaceuticals Reports Fourth-Quarter and Full-Year 2021 Financial Results and Operational Highlights (PRNewswire) - P3 | N=1,043 | AP-013 (NCT03988023) | Sponsor: Ampio Pharmaceuticals. Inc. | "Ampio Pharmaceuticals, Inc...today reported financial results and operational highlights for the fourth quarter and year ended December 31, 2021. In the mITT population, Ampion demonstrated a statistically significant reduction in pain (p=0.042) and trended toward improvement in function versus saline control. In the Per Protocol population of AP-013, Ampion demonstrated statistically significant reduction in pain (p = 0.020) and a statistically significant improvement in function (p = 0.027) versus saline control. The Intent to Treat population was impacted by a large amount of missing data and mandated imputation due to COVID-19 and did not demonstrate statistically significant reduction in pain or statistically significant improvement in function."

P3 data • CNS Disorders • Immunology • Osteoarthritis • Pain

Ampio Pharmaceuticals Reports Fourth-Quarter and Full-Year 2021 Financial Results and Operational Highlights (PRNewswire) - "Cash and Cash Equivalents of $34 Million Expected to Fund Current Operations into 2H 2023....Type C Meeting with FDA: The FDA has agreed to a written response to our Type C Meeting request regarding the AP-013 study. By the end of the first half of this year, the Company expects to have FDA clarity on whether the AP-013 trial together with AP-003-A will support an Ampio BLA for the treatment of pain associated with severe OAK."

Commercial • FDA event • CNS Disorders • Osteoarthritis • Pain

Study of Ampion for the Treatment of Pain and Function in Patients With Severe Osteoarthritis of the Knee. (clinicaltrials.gov) - P3 | N=1043 | Completed | Sponsor: Ampio Pharmaceuticals. Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jul 2020 ➔ Sep 2021 | Trial primary completion date: Jul 2020 ➔ Jul 2021

Trial completion • Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology

Ampio Pharmaceuticals, Inc. Releases Positive Phase 3 Data Analysis for Ampion Targeting Severe Osteoarthritis of the Knee (OAK) (PRNewswire) - P3 | N=1,034 | NCT03988023 | Sponsor: Ampio Pharmaceuticals. Inc. | Ampio Pharmaceuticals...today announced positive data from the modified Intent-to-Treat (mITT) population in the Company's AP-013 study, a Phase 3 clinical trial of the company's lead candidate, Ampion™, in patients suffering from severe osteoarthritis of the knee (OAK)....In this mITT population (n = 618), which retained more than 85% power to evaluate improvements in pain, Ampion demonstrated a statistically significant reduction in pain (p=0.042) and trended favorably toward improvement in function versus saline control. Further, the results in the Per Protocol efficacy population (n = 580), included in the original AP-013 statistical analysis plan, support these observations with a statistically significant reduction in pain (p = 0.020) and a statistically significant improvement in function (p = 0.027) versus saline control."

P3 data • CNS Disorders • Osteoarthritis • Pain

Ampio Pharmaceuticals, Inc. Announces Third Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "Ampio Pharmaceuticals, Inc...today reported results for the three- and nine-month periods ended September 30, 2021 and provided a corporate overview and business update....We have locked the osteoarthritis Phase 3 pivotal trial database, and are currently analyzing the data, which may provide a significant treatment option for an unmet medical need in severely disabled patients."

P3 data • CNS Disorders • Immunology • Osteoarthritis • Pain

AMPIO PHARMACEUTICALS ANNOUNCES TOP-LINE RESULTS FROM AP-013 PHASE III STUDY OF AMPION IN ADULT PATIENTS SUFFERING FROM SEVERE OSTEOARTHRITIS OF THE KNEE (OAK) (Ampio Press Release) - P3, N=1,034; NCT03988023; Sponsor: Ampio Pharmaceuticals. Inc.; "The resulting data demonstrates a statistically significant impact from the pandemic (p<0.001). In addition, a separate statistical analysis of data from the 725 patients that the Company believed not to have been impacted by the pandemic demonstrated a statistically significant reduction in pain (p=0.0260) and improvement in function (p=0.0073), versus a critical p-value of 0.05, at 12 weeks with Ampion treatment compared to saline control. We plan to thoroughly analyze and consolidate all this study data with data from severe OAK patients in previous single-injection clinical studies performed by the Company and present it to the FDA in support of a BLA....'We will complete the analysis of the AP-013 study and present all data to the FDA with the goal of filing a BLA for Ampion.'"

P3 data: top line • CNS Disorders • Osteoarthritis • Pain

Ampio Pharmaceuticals to Present at the 14th International Congress on Systemic Lupus Erythematosus (LUPUS 2021) & 6th International Congress on Controversies in Rheumatology and Autoimmunity (CORA) (PRNewswire) - P=NA, N=NA; “Ampio Pharmaceuticals…today announced details on the Company's abstract presentation...being given virtually at the 14th International Congress on Systemic Lupus Erythematosus (LUPUS 2021) & 6th International Congress on Controversies in Rheumatology and Autoimmunity (CORA) on October 6-9, 2021.…The presentation will summarize evidence that treatment utilizing Ampion suppresses Toll Like Receptor 7/8 (TLR7/8) signaling in monocytic/macrophage lineages and suggests a role for Ampion in treating the dysregulation of these pathways observed in lupus nephritis as well as in COVID-19.”

Clinical data • Immunology • Lupus • Novel Coronavirus Disease • Systemic Lupus Erythematosus

Ampio Provides Update on Osteoarthritis of the Knee (OAK) Program, Reiterates Compelling Data in Earlier Phase III Trials of Ampion in Severe OAK (PRNewswire) - "Ampio Pharmaceuticals...reported newly integrated data from four of its earlier clinical trials with consistent inclusion, exclusion, and demographic populations utilizing Ampion for treating osteoarthritis of the knee (OAK). Data from these 585 patients categorized as severe (i.e., Kellgren-Lawrence grade 4, or KL 4) demonstrates Ampion's consistent and statistically significant clinical effect in the reduction of pain compared to saline at two, ten, and twelve-week intervals subsequent to intra-articular injection...The pooled data show an even greater statistical significance, with a reduction in pain of 34.3% at two weeks (compared to 28.6% for saline, p value 0.041), 38.1% at ten weeks (30.4% for saline, p value 0.006) and 36% at twelve weeks (25.7% for saline, p value <0.001)."

Retrospective data • CNS Disorders • Osteoarthritis • Pain

Ampio Pharmaceuticals to Present at the 2021 International Society for Pharmaceutical Engineers Annual Meeting and Expo (PRNewswire) - "Ampio Pharmaceuticals...announced details on the Company's poster presentation...being given at the 2021 International Society for Pharmaceutical Engineers (ISPE) Annual Meeting and Expo in Boston, Massachusetts from November 1st to 3rd, 2021....The presentation highlights Ampio's innovative work which has significantly and rapidly expanded the capabilities of its wholly owned, automated drug manufacturing facility that was initially focused on producing 4 cc vials of its platform immunomodulatory drug Ampion™ for intra-articular injections into patients with osteoarthritis of the knee. In less than 4 months, the manufacturing facility was reprogrammed to manufacture Ampion products packaged to be clinically administered in doses more than ten times larger, either intravenously (IV) to, or inhaled by, patients suffering from acute respiratory distress due to COVID-19."

Review • Immunology • Infectious Disease • Novel Coronavirus Disease

AMPIO PHARMACEUTICALS PROVIDES UPDATES ON CLINICAL PROGRAMS FOR AMPION IN OSTEOARTHRITIS AND COVID-19 (Ampio Press Release) - "Ampio Pharmaceuticals...announced that it had received a positive response from the U.S. Food and Drug Administration (FDA) on its plans for its AP-013 Phase III trial for the intra-articular injection of Ampion™, its novel anti-inflammatory, for patients suffering from severe osteoarthritis of the knee (OAK)...'We will provide additional details on our upcoming earnings call on May 5th.'...'We have IRB approvals for both trials will commence enrolling patients in the U.S.'"

Trial status • CNS Disorders • Osteoarthritis • Pain

Ampio Receives feedback from the FDA on Ampio's Proposed Modifications to the special protocol assessment for Ampion treatment of severe Osteoarthritis of the knee (PRNewswire) - "Ampio Pharmaceuticals, Inc....announced today it has received guidance from the U.S Food & Drug Administration ('FDA') regarding the impact of COVID-19 on its Phase III clinical trial for osteoarthritis of the knee ('OAK')....The AP-013 study is being conducted under a Special Protocol Assessment ('SPA') which provides a documented framework for communication and gaining agreement with the FDA to support a commercial Biologics Licensing Application ('BLA')....The FDA provided practical guidance for the AP-013 study to navigate the pandemic, and to complete the study without re-running the trial."

FDA event • CNS Disorders • Immunology • Osteoarthritis • Pain

"$AMPE Ampio Receives feedback from the FDA on Ampio's Proposed Modifications to the special protocol assessment for Ampion treatment of severe Osteoarthritis of the knee https://t.co/qI3WaQ2puS" (@stock_titan)

Clinical • Immunology • Osteoarthritis • Pain • Rheumatology

Ampio Enters into Collaborative Research Agreements to Explore Additional Clinical Indications for its Immunomodulatory Drug, Ampion (PRNewswire) - "Ampio Pharmaceuticals, Inc....announced today that it has entered into two collaborative research agreements to explore new clinical indications for its immunomodulatory drug, Ampion™....Both parties will work together and conduct exploratory research to determine whether the anti-inflammatory and signaling pathways of Ampion could play a role in the treatment of certain rare Inflammatory Pediatric Diseases."

Licensing / partnership • Immunology

LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC. (PubMed, J Transl Med) - "In this report, we provide evidence that LMWF5A reduces pro-inflammatory cytokine release by activating the immunoregulatory transcription factors PPARγ and AhR. In addition, our data indicate that LMWF5A suppresses NF-κB and STAT1α pro-inflammatory pathways. This suggests that LMWF5A acts through these mechanisms to decrease pro-inflammatory transcription factor activity and subsequent inflammatory cytokine production."

Journal • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Osteoarthritis • Pain • Rheumatology

Molecular basis of regio- and stereo-specificity in biosynthesis of bacterial heterodimeric diketopiperazines. (PubMed, Nat Commun) - "Determining the crystal structures (1.70-1.47 Å) of Nas (ligand-free and substrate-bound Nas and its Q65I-A86G and S284A-V288A mutants) and molecular dynamics simulation finally elucidate the specificity-conferring mechanism of these residues. Our results provide a clear molecular and mechanistic basis into this family of HTDKP-forming P450s, laying a solid foundation for rapid access to the molecular diversity of HTDKP frameworks through rational engineering of the P450s."

Journal

Study of Nebulized Ampion for the Treatment of Adult COVID-19 Patients With Respiratory Distress (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Ampio Pharmaceuticals. Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease

Fractionation platform for target identification using off-line directed two-dimensional chromatography, mass spectrometry and nuclear magnetic resonance. (PubMed, Anal Chim Acta) - "Five proline-based 2,5-diketopiperazines were successfully identified in soy sauce. These cyclic dipeptides might contribute to taste by giving a bitter flavour or indirectly enhancing umami flavour."

Journal

Ampio Updates Regulatory and Clinical Trial Events (PRNewswire) - "Patients with severe osteoarthritis of the knee (OAK): The amendment to the OAK Phase III clinical trial (AP-013), that harmonizes the FDA agreement on the Special Protocol Assessment (SPA) with FDA guidance for clinical trials on hold due to COVID-19, has been received by the FDA. The FDA notified the Company that a formal response will be provided by the end of this year."

Special Protocol Assessment • CNS Disorders • Osteoarthritis • Pain

New Thiodiketopiperazine and 3,4-Dihydroisocoumarin Derivatives from the Marine-Derived Fungus Aspergillus terreus. (PubMed, Mar Drugs) - "Compound 3 displayed antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 32 μg/mL) and antifungal activity against Candida albicans (MIC = 32 μg/mL). In addition, compound 3 exhibited an inhibitory effect on protein tyrosine phosphatase 1 B (PTP1B), an important hypoglycemic target, with an inhibitory concentration (IC) value of 12.25 μM."

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