Cure rate for L braziliensis bolivian CL has been 70%-80% for standard systemic and local monotherapies. It would benefit patients if cure rates could be consistently >90%, so testing a combination of two treatments is proposed. The most attractive systemic therapy is the only oral agent, miltefosine during 28 days, and the most attractive local therapy is application of Paromomycin cream for 28 days.

Start Date01 Feb 2019

Sponsor / Collaborator-

NCT03759886

/ Unknown statusNot Applicable

Mechanical Bowel Preparation and Oral Antibiotic Prophylaxis vs. Mechanical Bowel Preparation in Colorectal Surgery With i.v. Antibiotic Prophylaxis

The investigators perform a case-control study to compare preparation before elective colorectal surgery. The first group is a prospective patient - registry in all patients with mechanical bowel preparation (MBP) and oral antibiotic prophylaxis the day before colorectal surgery. The second group is a historic collective of patients with MBP only and colorectal surgery. The cases were matches in American Society of Anesthesiologists (ASA) physical status classification system, BMI, operative procedure and risk factors.

Start Date17 Dec 2018

Sponsor / Collaborator

Universität Leipzig

NCT03399955

/ Unknown statusPhase 2IIT

An Open Label, Randomized, Parallel Arm Clinical Trial of Two Regimens to Assess the Safety and Efficacy for Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) Patients in Sudan

This is an open label, randomized non comparative phase II clinical trial conducted on parallel groups, to assess the safety and efficacy of the combination of Paromomycin (20 mg/kg/d) IM for 14 days and Miltefosine (allometric dosing) oral for 42 days, and a combination of AmBisome® (20 mg/kg total dose) IV over 7 days and Miltefosine oral for 28 days (allometric dosing) for the treatment of PKDL patients in Sudan.

Start Date09 May 2018

Sponsor / Collaborator

Drugs for Neglected Diseases initiative

100 Clinical Results associated with Paromomycin Sulfate

100 Translational Medicine associated with Paromomycin Sulfate

100 Patents (Medical) associated with Paromomycin Sulfate

3,312

Literatures (Medical) associated with Paromomycin Sulfate

01 Feb 2025·CHEMOSPHERE

A biomarkers study of human skin fibroblasts exposition to glyphosate-based herbicide using an untargeted and targeted metabolomics approach

Article

Author: Gomes, Dawidson A ; Rodrigues, Michele A ; Menezes, Helvécio C ; Cardeal, Zenilda L ; Batista, Josimar M ; Armijos, María J G

Metabolomics is a valuable tool to assess glyphosate exposure and its potential impact on human health. However, few studies have used metabolomics to evaluate human exposure to glyphosate or glyphosate-based herbicides (GBHs). In this study, an untargeted and targeted metabolomics approach was applied to human skin fibroblasts exposed to the GBH Roundup (GLYP-R). Cytotoxicity, cell death, and oxidative stress assays were performed to evaluate potential damage caused by GLYP-R in fibroblasts. The herbicide showed a cytotoxic effect at concentrations above 100.0 mg L^-1, with IC₅₀ = 164.2 ± 8.7 mg L^-1, inducing significant reactive oxygen species (ROS) production and necrosis. A GC×GC/Q-TOFMS method using derivatization with propyl chloroformate/propanol was developed for untargeted analysis, allowing the identification of 400 metabolites of different classes in the samples. The most significant compounds in the discrimination and classification of the samples were fatty acids and amino acids (AA). Based on the relevance of AA in untargeted analysis, a targeted analysis of 21 AA was performed using the same validated GC×GC method. Metabolomic analyses allowed the construction of two biomarker models with performance evaluated by receiver operating characteristic (ROC) curves: an untargeted model formed by four metabolites (methylcysteine, N-acetyl-l-methionine, methyl stearate, and linoleic acid) and a targeted model formed by three AA (l-glutamic acid, l-cysteine, and γ-aminobutyric acid). This study is the first to report the use of metabolomics to evaluate human skin cells exposed to GLYP-R, contributing to the toxicological research on glyphosate.

01 Feb 2025·SOUTH AFRICAN JOURNAL OF BOTANY

Unlocking nature's pharmacy: Euphorbia hirta (L.) as a potent defense against Escherichia coli and Klebsiella pneumoniae infections in Tanzania

Author: Kisula, Lydia ; Giliba, Richard A. ; Mbwale, Issaya ; Kemboi, Douglas

Urinary tract infections (UTIs) are among the most common bacterial infections, primarily caused by Escherichia coli and Klebsiella pneumoniae, both of which have mostly developed resistance to various antibiotics.The Maasai and Meru communities in Tanzania have traditionally used Euphorbia hirta to combat resistant pathogens, particularly those causing UTIs.This study aimed to evaluate the antimicrobial compounds of aqueous extracts and the antibacterial compounds in methanolic extracts of E. hirta.We specifically focused on the antibacterial activity of aqueous and methanolic extracts against E. coli and K. pneumoniae strains, which are significant contributors to UTIs.In March 2024, we randomly collected E. hirta plant parts from the Kikwe and Kisongo wards in the Arusha region of Tanzania.The samples were washed with distilled water and shade-dried for three weeks to prevent the degradation of bioactive compoundsAfter drying, the samples were powd. using a laboratory grinder and stored in sterile nylon bags.We conducted qual. and quant. analyses to assess the presence of various phytochems., including alkaloids, saponins, coumarins, terpenoids, quinones, flavonoids, and glycosides, in the aqueous and methanolic extracts of E. hirta.To identify specific phytochem. compounds in these extracts, we used gas chromatog.-mass spectrometry (GC-MS) and disk diffusion assays to test their antibacterial activity against E. coli and K. pneumoniae.The GC-MS anal. identified sixteen potential bioactive compounds with antibiotic properties, including dodecanal, trans-Farnesol, phytol, 13-tetradecynoic acid, Me ester, cis-5,8,11,14,17-Eicosapentaenoic acid, 2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro-4,4,7a-trimethyl-, (R)-, paromomycin, decanoic acid, Me ester, azelaic acid, undecanoic acid, 10-methyl-, Me ester, palmitoleic acid, 9,12,15-Octadecatrienoic acid (Z,Z,Z), 7-Hydroxy-3-(1,1-dimethylprop-2-enyl) coumarins, linoleyl Me ketone, and 8,11,14-Eicosatrienoic acid, Me ester (Z,Z,Z).When tested at a concentration of 1 g/mL, all extracts demonstrated significant antibacterial activity.The methanolic extract exhibited the highest performance, with a min. inhibition zone of 12.0 ± 2.35 mm, followed by the aqueous cold extract at 9.25 ± 1.75 mm, and the aqueous boiled extract at 8.0 ± 1.35 mm.The traditional methods employed by the Maasai and Meru communities for preparing herbal medicine from E. hirta, such as boiling and soaking in cold water, seemed to be effective in treating UTIs.Organic solvent extraction using methanol generally showed superior antibacterial activity compared to aqueous extractionHowever, soaking in cold water produced extracts with higher inhibitory activity against E. coli, while boiling was more effective against K. pneumoniae.This study validates the local practices of E. hirta preparation, suggesting that water-based extracts could be both effective and safe for treating certain bacterial strains responsible for UTIs in the Arusha region.

01 Feb 2025·JOURNAL OF INFECTION AND CHEMOTHERAPY

Escherichia coli with increased aminoglycoside resistance due to an amino acid substitution at position 85 of HemC

Article

Author: Kirikae, Teruo ; Tada, Tatsuya ; Komeda, Tomoki ; Hishinuma, Tomomi

OBJECTIVE:

The mechanism of aminoglycoside resistance due to abnormal hemin synthesis remains unclear. We investigate an Escherichia coli strain with a single amino acid substitution at position 85 of HemC.

METHODS:

An aminoglycoside-resistant Escherichia coli DH5α was selected by passaging in Lysogeny Broth (LB) medium containing amikacin. Whole genome sequencing was performed to determine the genetic profile of the strain. An isogenic strain of E. coli DH5α was created. Growth rates, drug susceptibilities and expressions of the heme synthetic genes were compared between the original strain and the isogenic strain.

RESULTS:

Whole genome sequencing revealed a nucleotide substitution at position 254 of hemC from adenine (A) to thymine (T), resulting in an amino acid substitution at position 85 of HemC from histidine (H) to leucine (L). There were no mutations in other heme synthetic genes, including hemA, hemB, hemC, hemD, hemE, hemF, hemG, hemH, hemL, hemN, hemX and hemY. The isogenic strain of E. coli DH5α with H85L in HemC was less susceptible to aminoglycosides, and its growth was slower than that of E. coli DH5α before passage. Quantitative real-time PCR showed that the expression of hemA was higher and the expressions of hemL, hemG and hemX lower in the isogenic strain than before passage.

CONCLUSION:

This is the first report of aminoglycoside resistance due to an amino acid substitution in HemC. These findings suggested that mutations in the heme synthetic genes may indirectly affect the growth rates of E. coli strains and their susceptibilities to aminoglycosides.

News (Medical) associated with Paromomycin Sulfate

14 Nov 2024

·www.globenewswire.com

Appili Therapeutics Reports Financial and Operational Results for Second Quarter of Fiscal Year 2025

Overwhelming shareholder support in favour of take-private transaction with Aditxt Studies presented at IDWeek 2024™ demonstrate ATI-1701 provides full protection against lethal tularemia in animal models after one year Alignment with U.S. Food and Drug Administration on development requirements for ATI-1801 NDA Submission HALIFAX, Nova Scotia, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Appili Therapeutics Inc. (TSX:APLI; OTCPink: APLIF) (the “Company” or “Appili”), a biopharmaceutical company focused on drug development for infectious diseases and medical countermeasures, today announced its financial and operational results for the second quarter of its fiscal year 2025, which ended on September 30, 2024. All figures are stated in Canadian dollars unless otherwise stated. “During fiscal year 2025, Appili shareholders voted overwhelmingly in favor of the transaction with Aditxt, facilitating our access to capital and activating promising opportunities for Appili,” said Dr. Don Cilla, President and CEO of Appili. “The shareholder vote is an important milestone for Appili and brings us one step closer to ‘Making Promising Innovations Possible Together’ through Aditxt’s social incubator platform.” ATI-1701, Biodefense Vaccine Candidate with Strong U.S. Air Force Academy Funding Commitments ATI-1701, a novel live-attenuated vaccine for preventing F. tularensis, has previously secured US$14 million in awards from the United States Air Force Academy (“USAFA”). Under the cooperative agreement with USAFA, Appili manages a comprehensive development program, including nonclinical studies, CMC/manufacturing, clinical preparatory, and regulatory activities supporting an IND submission in 2025. Recent data presented by Appili's scientific team at the Military Health System Research Symposium and IDWeek 2024™ demonstrated strong efficacy results. Studies showed that a single dose of ATI-1701 provided full protection against lethal tularemia in animal models, with protection for one year after vaccination. Additional research highlighted the heightened risk of tularemia outbreaks in conflict zones and positioned ATI-1701 as a potentially valuable tool in protecting warfighters. Appili has recently had positive interactions with the United States Food and Drug Administration (“FDA”) in the form of a pre-IND meeting, confirming the development pathway for the majority of Appili’s proposed development plan. Appili is currently in the process of implementing suggested changes in its development effort. ATI-1801, Demonstrated safety and efficacy across multiple Phase 2 and Phase 3 studies ATI-1801, a novel topical formulation of paromomycin (15% w/w), is under advanced clinical development for treating cutaneous leishmaniasis, a disfiguring skin infection affecting hundreds of thousands globally. In a recent response to Appili’s Type B meeting request, the FDA agreed with the Company’s proposed strategy to establish a scientific bridge between previous clinical trial material and new drug product batches. The approach enables Appili to leverage key results from the clinical dossier for ATI-1801 licensed from U.S. Army Medical Materiel Development Activity, including the successful results of a Phase 3 study, and allows the completion of an New Drug Application much sooner than if additional clinical data were required. ATI-1801 has received Orphan Drug Designation from the FDA for certain forms of cutaneous leishmaniasis. The company is evaluating ATI-1801’s eligibility for a priority review voucher (“PRV”), which, if confirmed, would make it the second PRV-eligible program at Appili, alongside ATI-1701, which is potentially eligible for a PRV pending renewal of certain U.S. legislation. LIKMEZ™ (ATI-1501), FDA Approved Liquid Oral Reformulation of the Antibiotic Metronidazole In September 2023, Appili, together with its U.S. partner, Saptalis Pharmaceuticals LLC., announced the approval by the FDA of LIKMEZ™ (ATI-1501), LIKMEZ® is the first and only FDA-approved liquid formulation of metronidazole providing a novel prescribing option for patients with difficulty swallowing or experiencing taste-related hurdles. LIKMEZ, with patent coverage through 2039, addresses the unmet need in patients with dysphagia to avoid risks associated with drug compounding, and discontinuation related anti-microbial resistance. In November 2023, Saptalis, through a commercialization partner, launched LIKMEZ in the U.S. and the product is now available to patients and doctors. Appili earned milestone payments from Saptalis and is entitled to receive additional sales-based milestone payments and royalties from Saptalis based on sale of the product. Saptalis is currently in the process of identifying an alternative commercialization partner. Aditxt Arrangement On November 6, 2024, shareholders of the Company overwhelmingly voted in favour of a special resolution approving a plan of arrangement pursuant to which Aditxt Inc. (NASDAQ:ADTX) (“Aditxt”), through its wholly-owned subsidiary, Adivir, Inc. will acquire all of the issued and outstanding Class A common shares of the Company by way of a court-approved plan of arrangement under the Business Corporations Act (Ontario) (the “Transaction”). Approximately 29.50% of the outstanding Appili Shares were voted by shareholders and the Transaction was approved by 99.79% of the votes cast. For further details regarding the Transaction, please see Appili’s press release dated April 2, 2024 and Appili’s management information circular (the “Circular”) dated October 4, 2024, a copy of which is available under Appili’s profile on SEDAR+ (sedarplus.ca). Appili and Aditxt are in the process of satisfying the remaining closing conditions, which include: (1) the Company obtaining final court approval for the Transaction, and (2) Aditxt securing sufficient financing to complete the Transaction. Subject to satisfaction or waiver of the remaining closing conditions, Appili expects the Transaction to close in December 2024. Financial Results The Company prepares its financial statements in accordance with IFRS Accounting Standards as issued by the International Accounting Standard Board and Part I of Chartered Professional Accountants of Canada Handbook–Accounting. All figures are stated in Canadian dollars unless otherwise stated. The net loss and comprehensive loss of $0.8 million or $0.01 loss per share for the three months ended September 30, 2024, was $0.2 million lower than the net loss and comprehensive loss of $1 million or $0.01 loss per share during the three months ended September 30, 2023. This relates mainly to an increase in research and development expenses of $1 million, an increase in financing costs of $0.1 million and a decrease in revenue of $0.3 million. This increase was offset by a decrease in general and administrative expenses by $0.1 million, an increase in government assistance of $1.3 million, and an increase of $0.2 million in foreign exchange gain. As of September 30, 2024, the Company had cash of $0.7 million, compared to $0.1 million on March 31, 2024. As of November 13, 2024, the Company had 121,266,120 issued and outstanding Common Shares, 11,520,281 stock options, and 41,356,874 warrants outstanding. This press release should be read in conjunction with the Company’s unaudited interim condensed consolidated financial statements for the second quarter of the 2025 fiscal year and the related MD&A, copies of which are available under the Company’s profile on SEDAR+ at www.sedarplus.ca. About Appili TherapeuticsAppili Therapeutics is an infectious disease biopharmaceutical company that is purposefully built, portfolio-driven, and people-focused to fulfill its mission of solving life-threatening infections. By systematically identifying urgent infections with unmet needs, Appili’s goal is to strategically develop a pipeline of novel therapies to prevent deaths and improve lives. The Company is currently advancing a diverse range of anti-infectives, including an FDA approved ready-made suspension of metronidazole for the treatment of antimicrobial infections, a vaccine candidate to eliminate a serious biological weapon threat, and a topical antiparasitic for the treatment of a disfiguring disease. Led by a proven management team, Appili is at the epicenter of the global fight against infection. For more information, visit www.AppiliTherapeutics.com. Forward looking statementsThis news release contains “forward-looking statements”, including with respect to the funding commitment from USAFA and expected timing of invoice payment, advancing program towards IND, further anticipated milestones and the timing thereof, the Company’s development plans and timelines with respect to ATI-1501, ATI-1701 and ATI-1801, the timing of any milestone and/or royalty payments in respect of ATI-1501, consideration to be received by shareholders in connection with the proposed Transaction, the expected timing and process to complete the Transaction, and the Company’s expectations with respect to its ability to operate as a going concern and satisfy its ongoing working capital requirements. Wherever possible, words such as “may,” “would,” “could,” “should,” “will,” “anticipate,” “believe,” “plan,” “expect,” “intend,” “estimate,” “potential for” and similar expressions have been used to identify these forward-looking statements. These forward-looking statements reflect the current expectations of the Company’s management for future growth, results of operations, performance and business prospects and opportunities and involve significant known and unknown risks, uncertainties and assumptions, including, without limitation, those listed in (i) the annual information form of the Company dated June 25, 2024, (ii) the Cicular, and (iii) the other filings made by the Company with the Canadian securities regulatory authorities (which may be viewed at www.sedarplus.ca). Should one or more of these risks or uncertainties materialize or should assumptions underlying the forward-looking statements prove incorrect, actual results, performance or achievements may vary materially from those expressed or implied by the forward-looking statements contained in this news release. These factors should be considered carefully, and prospective investors should not place undue reliance on the forward-looking statements. The Company disclaims any intention or obligation to revise forward-looking statements whether as a result of new information, future developments or otherwise, except as required by law. All statements included in this press release relating to the Arrangement are qualified by reference to the “Forward Looking Statements” section included in the Arrangement Press Release. Media Contact:Jenna McNeil, Communications ManagerAppili Therapeutics E: JMcNeil@AppiliTherapeutics.com Investor Relations Contact:Don Cilla, President and CEOAppili TherapeuticsE: Info@AppiliTherapeutics.com

Clinical ResultDrug ApprovalVaccineOrphan DrugPhase 3

06 Nov 2024

·www.globenewswire.com

Appili Therapeutics Announces Results of Special Meeting of Shareholders

NOT FOR DISTRIBUTION TO UNITED STATES NEWSWIRE SERVICES OR FOR DISSEMINATION IN THE UNITED STATES HALIFAX, Nova Scotia, Nov. 06, 2024 (GLOBE NEWSWIRE) -- Appili Therapeutics Inc. (TSX: APLI; OTCPink: APLIF) (the “Company” or “Appili”), a biopharmaceutical company focused on drug development for infectious diseases and medical countermeasures, today announced the results from its special meeting of shareholders held earlier today (the “Meeting”). Shareholders of the Company (the “Shareholders”), overwhelmingly voted in favour of a special resolution approving a plan of arrangement pursuant to which Aditxt Inc. (NASDAQ:ADTX) (“Aditxt”), through its wholly-owned subsidiary, Adivir, Inc. will acquire all of the issued and outstanding Class A common shares of the Company (the “Appili Shares”) by way of a court-approved plan of arrangement under the Business Corporations Act (Ontario) (the “Transaction”). A total of 35,770,287 Appili Shares were voted at the Meeting, representing approximately 29.50% of the outstanding Appili Shares. The Transaction was approved by (i) 99.79% of the votes cast by Shareholders at the Meeting and (ii) 99.65% of the votes cast by Shareholders at the Meeting (excluding the votes cast by persons whose votes may not be included in determining minority approval of a “business combination” in accordance with Multilateral Instrument 61-101 – Protection of Minority Security Holders in Special Transactions). The successful close of this transaction is an important milestone for Appili as it focuses on advancing its pipeline of anti-infective therapies and delivering on its mission to protect patients from severe infectious diseases. “The alignment with Aditxt will facilitate our access to capital and activates promising opportunities for Appili across multiple fronts. Through Aditxt’s social incubator platform, we can amplify our impact and reach in the infectious diseases and medical countermeasure landscape.” said Dr. Don Cilla, President and CEO of Appili. “By leveraging Aditxt’s mission to "Make Promising Innovations Possible Together", we aim to prepare ATI-1701 for IND submission, implement FDA’s agreed upon strategy for ATI-1801, and enhance commercialization for LIKMEZ™ and capitalize on the strategic value of two potential PRV eligible programs.” The Transaction is conditional upon certain customary closing conditions and Aditxt raising at least US$20 million in financing. The Transaction is expected to close in Q4 2024. The Company has filed a report of the voting results on the resolution voted on the Meeting on the Company’s SEDAR+ profile at www.sedarplus.ca. About Appili Therapeutics Appili Therapeutics is an infectious disease biopharmaceutical company that is purposefully built, portfolio-driven, and people-focused to fulfill its mission of solving life-threatening infections. By systematically identifying urgent infections with unmet needs, Appili’s goal is to strategically develop a pipeline of novel therapies to prevent deaths and improve lives. The Company is currently advancing a diverse range of anti-infectives, including an FDA approved ready-made suspension of metronidazole for the treatment of antimicrobial infections, a vaccine candidate to eliminate a serious biological weapon threat, and a topical antiparasitic for the treatment of a disfiguring disease. Led by a proven management team, Appili is at the epicenter of the global fight against infection. For more information, visit www.AppiliTherapeutics.com. About Aditxt Aditxt, Inc.® is an innovation platform dedicated to accelerating promising health innovations. Aditxt’s ecosystem of research institutions, industry partners, and shareholders collaboratively drives their mission to "Make Promising Innovations Possible Together." The innovation platform is the cornerstone of Aditxt’s strategy, where multiple disciplines drive disruptive growth and address significant societal challenges. Aditxt operates a unique model that democratizes innovation, ensures every stakeholder’s voice is heard and valued and empowers collective progress. Aditxt currently operates two programs focused on immune health and precision health. The Company plans to introduce two additional programs dedicated to public health and women’s health. For these, Aditxt has entered into an Arrangement Agreement with Appili Therapeutics, Inc. (“Appili”) (TSX: APLI; OTCPink: APLIF), which focuses on infectious diseases, and a Merger Agreement with Evofem Biosciences, Inc. Each program will be designed to function autonomously while collectively advancing Aditxt’s mission of discovering, developing, and deploying innovative health solutions to tackle some of the most urgent health challenges. The closing of each of the transactions with Appili and Evofem is subject to several conditions, including but not limited to approval of the transactions by the respective target shareholders and Aditxt raising sufficient capital to fund its obligations at closing. No assurance can be provided that all of the conditions to closing will be obtained or satisfied or that either of the transactions will ultimately close. For more information, www.aditxt.com. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This news release contains “forward-looking information” within the meaning of applicable securities laws. Forward-looking information contained in this press release may be identified by the use of words such as, “may”, “would”, “could”, “will”, “likely”, “expect”, “anticipate”, “believe, “intend”, “plan”, “forecast”, “project”, “estimate”, “outlook” and other similar expressions. Forward-looking information is not a guarantee of future performance and is based upon a number of estimates and assumptions of management in light of management’s experience and perception of trends, current conditions and expected developments, as well as other factors relevant in the circumstances, including assumptions in respect of current and future market conditions, the current and future regulatory environment, and the availability of licenses, approvals and permits. Forward-looking statements in this news release include, but are not limited to closing of the Transaction and the timing thereof. Actual results and developments may differ materially from those contemplated by these statements. Such forward-looking statements are based on certain assumptions regarding Aditxt and Appili, including the successful completion of the conditions precedent of the Transaction. While Appili considers these assumptions to be reasonable, based on information currently available, they may prove to be incorrect. Among other things, there can be no assurance that the Transaction will be completed. Forward-looking information is subject to a variety of risks and uncertainties that could cause actual events or results to differ materially from those projected in the forward-looking information. Consequently, readers are cautioned not to place undue reliance on the forward-looking statements and information contained in this press release. The statements in this press release are made as of the date of this release. Appili disclaims any intent or obligation to update any forward-looking information, whether as a result of new information, future events or results or otherwise, other than as required by applicable securities laws. No securities regulatory authority has either approved or disapproved of the contents of this press release. This press release is for information purposes only and shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Neither CIRO nor any stock exchange or other securities regulatory authority accepts responsibility for the adequacy or accuracy of this release. Media Contact:Jenna McNeil, Corporate Affairs and Communications ManagerAppili TherapeuticsE: JMcNeil@AppiliTherapeutics.com Investor Relations Contact:Don Cilla, Pharm.D. M.B.A.Appili TherapeuticsE: Info@AppiliTherapeutics.com

Vaccine

31 Oct 2024

·www.globenewswire.com

Appili Therapeutics Announces Alignment with FDA on Development Requirements for ATI-1801 Topical Antiparasitic Product NDA Submission

Demonstrated safety and efficacy across multiple Phase 2 and Phase 3 studies Appili provides update on Aditxt transaction and encourages shareholders to vote their shares as soon as possible for the November 6, 2024 shareholders meeting HALIFAX, Nova Scotia, Oct. 31, 2024 (GLOBE NEWSWIRE) -- Appili Therapeutics Inc. (TSX: APLI; OTCPink: APLIF) (the “Company” or “Appili”), a biopharmaceutical company focused on drug development for infectious diseases and medical countermeasures, today announced that the U.S. Food and Drug Administration (“FDA”) has provided positive feedback regarding the development strategy for ATI-1801, and agreed on the necessary registration package to support a New Drug Application (“NDA”). ATI-1801, a novel topical formulation of paromomycin (15% w/w), is under advanced clinical development for treating cutaneous leishmaniasis, a disfiguring skin infection affecting hundreds of thousands globally. “This positive response from the FDA simplifies and de-risks our development program for ATI-1801,” said Don Cilla, President and CEO of Appili Therapeutics. “The agency's agreement with our proposed strategy enables Appili to leverage key results from the clinical dossier for ATI-1801 licensed from U.S. Army Medical Materiel Development Activity (“USAMMDA”), including the successful results of a Phase 3 study, and provides a clear path towards an NDA submission.” In a recent response to Appili's Type B meeting request, the FDA agreed with the Company's proposed strategy to establish a scientific bridge between previous clinical trial material and new drug product batches. This approach includes developing an appropriately validated in-vitro release test (“IVRT”) method and manufacturing a new reference standard to use in IVRT studies to support the scientific bridge to products used in prior studies. This will allow completion and submission of an NDA much sooner than if additional clinical data were required. Subject to securing the requisite funding Appili expects to implement the agreed-upon strategy and continue to advance ATI-1801 topical paromomycin cream (15% w/w) program to NDA submission. ATI-1801 has received Orphan Drug Designation from the FDA for certain forms of cutaneous leishmaniasis. The company is evaluating ATI-1801’s eligibility for a priority review voucher (“PRV”), which, if confirmed, would make it the second PRV-eligible program at Appili, alongside ATI-1701, which is potentially eligible for a PRV pending renewal of certain U.S. legislation. Aditxt Arrangement On April 2, 2024, the Company announced that it had entered into a definitive arrangement agreement (the “Arrangement Agreement”) pursuant to which Aditxt Inc. (NASDAQ: ADTX) (“Aditxt”), through its wholly-owned subsidiary, Adivir, Inc., agreed to acquire all of the issued and outstanding Class A common shares of the Company. Under the terms of the Arrangement Agreement, shareholders of the Company will receive (i) US$ 0.0467 in cash and (ii) 0.0000686251 of a share of Adixt common stock (the “Transaction”). This Transaction represents a premium to Appili’s recent trading price, and assuming the completion of the transaction, provides shareholders with immediate value. On October 1, 2024, the Company obtained an interim order from the Ontario Superior Court of Justice in connection with the Transaction. The order permits the mailing of all requisite meeting materials in connection with the special meeting of Appili shareholders (the “Meeting”) scheduled to be held virtually on November 6, 2024 at 11:00 am ET. Shareholders are encouraged to vote their shares as soon as possible. The notice of the special meeting of shareholders and management information circular containing all relevant details with respect to the Meeting (including voting instructions) and the Transaction are available on the Company’s website at: www.appilitherapeutics.com/proxy-info/ as well as under Appili’s profile on SEDAR+ www.sedarplus.ca. About ATI-1801Licensed from the U.S. Department of Defense through the U.S. Army Medical Materiel Development Activity, Appili’s ATI-1801 is a novel topical product with demonstrated safety and efficacy across multiple Phase 2 and Phase 3 studies. As current treatments are often invasive and require hospitalization, ATI-1801 has the potential to significantly reduce suffering from cutaneous leishmaniasis by providing patients in need with a safe and effective topical therapy that can be used in the outpatient setting. About Appili TherapeuticsAppili Therapeutics is an infectious disease biopharmaceutical company that is purposefully built, portfolio-driven, and people-focused to fulfill its mission of solving life-threatening infections. By systematically identifying urgent infections with unmet needs, Appili’s goal is to strategically develop a pipeline of novel therapies to prevent deaths and improve lives. The Company is currently advancing a diverse range of anti-infectives, including an FDA approved ready-made suspension of metronidazole for the treatment of antimicrobial infections, a vaccine candidate to eliminate a serious biological weapon threat, and a topical antiparasitic for the treatment of a disfiguring disease. Led by a proven management team, Appili is at the epicenter of the global fight against infection. For more information, visit www.AppiliTherapeutics.com. Forward Looking StatementsThis news release contains “forward-looking statements”, including with respect to (i) the potential for ATI-1801 as a treatment for leishmaniasis and the proposed development plan for ATI-1801(including the NDA submission and the expected timing thereof) and (ii) the potential that certain of Appili’s programs may be PRV-eligible. Wherever possible, words such as “may,” “would,” “could,” “should,” “will,” “anticipate,” “believe,” “plan,” “expect,” “intend,” “estimate,” “potential for” and similar expressions have been used to identify these forward-looking statements. These forward-looking statements reflect the current expectations of the Company’s management for future growth, results of operations, performance and business prospects and opportunities and involve significant known and unknown risks, uncertainties and assumptions, including, without limitation, those listed in the annual information form of the Company dated June 25, 2024, and the other filings made by the Company with the Canadian securities regulatory authorities (which may be viewed at www.sedarplus.ca). Should one or more of these risks or uncertainties materialize or should assumptions underlying the forward-looking statements prove incorrect, actual results, performance or achievements may vary materially from those expressed or implied by the forward-looking statements contained in this news release. These factors should be considered carefully, and prospective investors should not place undue reliance on the forward-looking statements. The Company disclaims any intention or obligation to revise forward-looking statements whether as a result of new information, future developments or otherwise, except as required by law. Media Contact:Jenna McNeil, Corporate Affairs and Communications ManagerAppili TherapeuticsE: JMcNeil@AppiliTherapeutics.com Investor Relations Contact:Don Cilla, Pharm.D. M.B.A.Appili TherapeuticsE: Info@AppiliTherapeutics.com

Phase 3NDAOrphan Drug

100 Deals associated with Paromomycin Sulfate

External Link

KEGG	Wiki	ATC	Drug Bank
-	Paromomycin Sulfate	A07AA06	DB01421

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Amebiasis	-	-	01 Jan 1959
Cryptosporidiosis	-	-	01 Jan 1959
Giardiasis	-	-	01 Jan 1959

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Leishmaniasis, Cutaneous	Phase 3	US	Appili Therapeutics, Inc.	13 Apr 2022

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03399955 (not available, Pubmed \| PLoS Negl Trop Dis)	Phase 2	Post-Kala-azar dermal leishmanioid	110	Paromomycin/Miltefosine	jmtebtksmk(kjsttnkkzy) = dxwujvcldy wkeksgxmlm (ypbeotiiru, 90.3 - 100)	Positive	21 Nov 2023
				Liposomal Amphotericin B/Miltefosine	jmtebtksmk(kjsttnkkzy) = pvlneizqsi wkeksgxmlm (ypbeotiiru, 70.2 - 91.9)
NCT03129646 (Pubmed)	Phase 3	Leishmaniasis, Visceral	439	Paromomycin plus Miltefosine	zqsslwfzbq(wavmzisoen) = ayccouzxco rgxpgpopzp (ibptgmupmu, -6.2 to 7.4)	Positive	27 Sep 2022
				Sodium Stibogluconate plus Paromomycin	zqsslwfzbq(wavmzisoen) = xugiixeahm rgxpgpopzp (ibptgmupmu, -6.2 to 7.4)
NCT03759886 (Pubmed \| Int J Colorectal Dis)	Not Applicable	-	120	Intervention group (oral paromomycin and metronidazole)	rsdbvvvvqy(glunyowyeq) = showed a tendency towards decreased frequencies in the intervention group pzvzkkxonj (xjqotiumxk )	-	25 Apr 2021
				paromomycine (Control group (no intervention))
NCT01790659 (CTgov)	Phase 3	Leishmaniasis, Cutaneous	399	WR 279,396 (WR 279,396)	grftxmzgux(cwzutqltqa) = rcgbgyxtlw rscziobbbb (xtqvnuunkk, oybmbaemiq - xemgwempze) View more	-	23 Aug 2017
				Paromomycin (Paromomycin)	grftxmzgux(cwzutqltqa) = pyveipyteq rscziobbbb (xtqvnuunkk, zstpqggwpi - ojkqnyplzo) View more
NCT00606580 (CTgov)	Phase 3	Leishmaniasis, Cutaneous	375	WR 279,396 topical cream (WR 279,396 Topical Treament)	ehdihcwung(ohbowzxcax) = mkeryvnlvh hzywzupmlu (uqfqosucow, wupsbqvfqt - zuhtwqgmrc) View more	-	14 Jul 2014
				Paromomycin Alone topical cream (Paromomycin Alone Topical Treatment)	ehdihcwung(ohbowzxcax) = gguxttpler hzywzupmlu (uqfqosucow, huywtpgywt - tpclpqpmtm) View more
NCT00255567 (Pubmed \| PLoS Negl Trop Dis)	Phase 2	Leishmaniasis, Visceral	42	Paromomycin 20 mg/kg/day for 21 days	rvtalvbajm(mmxghrteby) = jrrajbkggh qdfonnzifj (rutjctjaig, 63.7% - 97.0%)	-	26 Oct 2010
				Paromomycin 15 mg/kg/day for 28 days	rvtalvbajm(mmxghrteby) = gndyxlvilw qdfonnzifj (rutjctjaig, 69.6% - 98.8%)
NCT00629031 (Pubmed \| Clin Infect Dis)	Phase 3	Leishmaniasis, Visceral	329	paromomycin (Group A)	idvknxdwmi(frunqaflmr) = Mild grade injection site pain was the most common adverse event ofccvbfcee (mjuibcybuw ) View more	-	15 Sep 2009
				paromomycin (Group B)
NCT00216346 (Pubmed \| N Engl J Med)	Phase 3	Leishmaniasis, Visceral	667	Paromomycin	mjoqwqpjiz(poufetvpww) = fevers djouuldkqn (saoposjtqa ) View more	Positive	21 Jun 2007
				Amphotericin B

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