Leishmaniasis, Cutaneous

FDA approved LIKMEZ™ (ATI-1501) for Metronidazole Oral Suspension 500mg/5mL Additional USAFA funding commitment from the U.S. Air Force Academy, intended to advance the ATI-1701 program toward an IND submission to the FDA Engaging regulatory authorities to align on ATI-1801 development plans HALIFAX, Nova Scotia, Feb. 13, 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 biodefense products, today announced its financial and operational results for the third quarter of its fiscal year 2024, which ended on December 31, 2023. All figures are stated in Canadian dollars unless otherwise stated. In recent months, we've achieved significant milestones by solidifying ATI-1701 government partnerships, engaging regulatory authorities for ATI-1801, and bringing our most advanced innovative asset, LIKMEZ™ (ATI-1501) to market through our partner. Beginning 2024, Appili’s skilled team stands with a clear vision, and committed funding enabling us to execute on our infectious disease program priorities, said Don Cilla, Pharm.D., M.B.A., President and Chief Executive Officer of Appili. “Additionally, the issuance of the patent claims for ATI-1701, shortly after receiving an additional funding commitment from USAFA, strengthens the programs position in biodefense and the new methods are expected to allow Appili to further develop a valuable vaccine that is urgently needed on the market”. Operational Highlights LIKMEZ™ ATI-1501: FDA Approved Product, In September 2023, Appili announced the FDA approval of LIKMEZ™ (ATI-1501), our proprietary taste-masked liquid suspension reformulation of metronidazole, through our U.S. partner, Saptalis Pharmaceuticals LLC. LIKMEZ is the first and only FDA approved ready-made suspension of metronidazole for the treatment of antimicrobial infections that addresses the unmet need in patients with dysphagia to avoid risks associated with drug compounding, and discontinuation related anti-microbial resistance. Saptalis launched LIKMEZ in November 2023 and commercial sales in the United States are ongoing. The FDA approval of LIKMEZ, shortly after securing patent coverage through 2039, is an important milestone that demonstrates Appili’s ability to identify promising opportunities and develop and monetize them for the benefit of both patients and shareholders. Collaborating with Saptalis, Appili earned US$600,000 in milestone payments in fiscal 2024. Appili expects to receive sales-based milestone payments and royalties from Saptalis based on sale of the product. ATI-1701, our Biodefense Vaccine Candidate with Strong Government Support ATI-1701 is a novel, live-attenuated vaccine for the prevention of F. Tularensis, has received awards totaling US$14 million from the U.S. Air Force Academy (“USAFA”). Under the terms of the USAFA Cooperative Agreement, Appili oversees a comprehensive development program for ATI-1701, which includes nonclinical studies, CMC/manufacturing, clinical preparatory, and regulatory activities to support an IND submission in 2025. Appili was granted a pre-IND meeting with the FDA to discuss ATI-1701’s regulatory, CMC, toxicology, and Phase 1 strategies and expects to receive feedback in early 2024. ATI-1801, our Licensed Topical Antiparasitic Product ATI-1801 is a novel topical formulation of paromomycin (15% w/w) under advanced clinical development for the treatment of cutaneous leishmaniasis, a disfiguring infection of the skin that affects hundreds of thousands of people around the world annually. In January 2024, Appili requested a meeting with the FDA to discuss the previously generated Phase 3 data and agree on the necessary registration package to support a New Drug Application submission, which the Company expects will include available nonclinical, manufacturing, and clinical data generated to date. Annual Financial Results The Company prepares its financial statements in accordance with IFRS 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 $0.2 million or $0.00 loss per share for the three months ended December 31, 2023, was $2.4 million lower than the net loss and comprehensive loss of $2.6 million or $0.02 loss per share during the three months ended December 31, 2022. This relates mainly to an increase in milestone revenue of $0.5 million, an increase in government assistance of $2.0 million and a decrease in general and administrative expenses of $0.9 million. These decreases were offset by an increase in research and development expenses of $0.9 million and an increase in financing costs of $0.2 million. As of December 31, 2023, the Company had cash of $0.6 million, compared to $2.5 million on March 31, 2023. As of February 13, 2024, the Company had 121,266,120 issued and outstanding Common Shares, 7,957,000 stock options, and 44,856,874 warrants outstanding. This press release should be read in conjunction with the Company’s unaudited interim condensed financial statements for the third quarter of the 2024 fiscal year and the related MD&A, copies of which are available under the Company’s pro SEDAR+ at . About Appili Therapeutics Appili Therapeutics is a biopharmaceutical company that is purposefully built, portfolio-driven, and people-focused to fulfill its mission of solving life-threatening infectious diseases. 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 . Forward looking statements This news release contains “forward-looking statements”, including with respect to the funding commitment from USAFA and expected timing of invoice payment, 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, 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 the annual information form of the Company dated June 22, 2023, and the other filings made by the Company with the Canadian securities regulatory authorities (which may be viewed at ). 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, Communications Manager Appili Therapeutics E: JMcNeil@AppiliTherapeutics.com Investor Relations Contact: Don Cilla, President and CEO Appili Therapeutics E: Info@AppiliTherapeutics.com

For the first time, scientists have begun to figure out why the disfiguring skin lesions caused by cutaneous leishmaniasis don't hurt. For the first time, scientists have begun to figure out why the disfiguring skin lesions caused by cutaneous leishmaniasis don't hurt. Researchers analyzed leishmaniasis lesions on mouse skin to detect metabolic signaling pathways that differed from uninfected mice. Results suggested the parasites that cause the disease change pain perception -- presumably as a way to delay treatment and promote their own survival. "No one knows why these lesions are painless -- but it has been thought that the parasite somehow manipulates the host physiological system," said Abhay Satoskar, senior author of the study and professor of pathology in The Ohio State University College of Medicine. "Based on our data, something the parasites do triggers pathways that suppress pain. How they do that, we're still investigating." Beyond increasing understanding of this parasitic disease afflicting 1 million new patients each year, the research could lead to development of new non-narcotic pain medications. "We hypothesize that any molecules the parasite's presence is producing could be potential painkillers for other health problems," Satoskar said. The study was published recently in the journal iScience. The lack of pain in leishmaniasis lesions has puzzled scientists for years, especially when similar blisters caused by conditions like chicken pox, staphylococcus infections or the herpes virus are itchy, oozy and sore. After giving mice chronic infections with Leishmania mexicana, the species that causes cutaneous leishmaniasis in South, Central and North America, researchers used an unbiased mass spectrometry analysis of the lesions to identify molecules known to be associated with pain suppression. They found numerous metabolites -- products of bio-chemical reactions that break down food to produce energy and perform other essential functions -- that have been linked in previous research to blockage of pain perception. They also found pathways with pain-relief properties tied to the brain's endocannabinoid system, which is involved in a host of physiological processes, including the pain response. Cell-culture experiments in infected macrophages, the immune cells in which Leishmania parasites live, showed an increase in most, but not all, of the same changes as in the lesions. The parasites use these metabolites as nutrition to help them replicate. But finding that certain pain-suppression pathways aren't increased in infected macrophages leaves some questions unanswered, said Satoskar, also a professor of microbiology at Ohio State. "The infection does something in the cell that could be a direct or indirect effect -- we don't know. But the environment that the infection creates leads to production of these metabolites," he said. "The exciting thing is that this is the first time we've begun to understand the cellular basis of why there is no pain in these lesions. "The next key question is, if we know these pathways are responsible, then how are they triggered? By the parasite, or something the parasite is doing to the host cell, or a combination of both? There could be a lot of things happening." Skin test for immunity to Leishmania-caused diseases Satoskar has also co-led an initiative to develop a standardized skin test to check for immunity to Leishmania donovani, the parasite that causes visceral leishmaniasis -- a potentially lethal form of the disease that affects the organs and is fatal if untreated. He and colleagues recently reported in Nature Communications on this work, which is critical for disease surveillance in the most affected regions of the world and will be needed for phase 3 clinical trials of leishmaniasis vaccines the team has developed. The test, using an antigen called leishmanin, is similar to a skin test for tuberculosis -- a positive response means a person has been exposed to the parasite and has cellular immunity that prevents further clinical symptoms. No tests or reagents are available to detect sporadic cases of leishmaniasis reported in the southern United States, so the skin test being developed will facilitate surveillance studies to assess exposure throughout the endemic regions for leishmaniasis -- which include the U.S. "This is a very important test in the field to understand who is exposed to this disease or not," Satoskar said. "For many stakeholders going into a community to conduct surveillance, knowing who is immune and who is not immune is essential so they can deploy their limited resources appropriately for disease control." Leishmanin skin tests have existed and been in use in past years but are no longer available. This research team developed the antigen following Good Laboratory Practice guidelines and tested it in hamsters, a model for human visceral leishmaniasis, to ensure the skin test triggers the expected immune response to both infection and vaccination. "This kind of data can be used for fast-track approval for Leishmania vaccines which are under development. We anticipate fulfilling the need of the entire global community," Satoskar said. Co-lead authors of the Nature Communications paper were Sanjay Singh of Gennova Biopharmaceuticals, Shinjiro Hamano of Nagasaki University, Sreenivas Gannavaram and Hira Nakhasi of the Food and Drug Administration, Greg Matlashewski of McGill University, and Shaden Kamhawi and Jesus Valenzuela of the National Institute of Allergy and Infectious Diseases (NIAID). The Nature Communications work was supported by the Global Health Innovative Technology Fund, the Canadian Institutes of Health Research, the FDA, the National Institutes of Health, NAIAD and the Fonds de recherche du Quebec-Sante. Nakhasi, Gannavaram and Nazli Azodi of the FDA also co-authored the iScience paper along with co-authors Greta Volpedo, Blake Cox, Yulian Mercado, Candice Askwith, and Matthew Bernier of Ohio State and Timur Oljuskin of the U.S. Department of Agriculture. The iScience study was supported by the Metabolomics Workbench/National Metabolomics Data Repository, Common Fund Data Ecosystem and Metabolomics Consortium Coordinating Center.

FDA approves ATI-1501 for Metronidazole Oral Suspension 500mg/5mL and its brand name LIKMEZ™ Appili received an additional funding commitment from the U.S. Air Force Academy for ATI-1701, bringing the total program funding awarded to US$14 million Appili Therapeutics Appoints Seasoned Biopharma Executive Mr. Prakash Gowd to its Board of Directors HALIFAX, Nova Scotia--(BUSINESS WIRE)-- Appili Therapeutics Inc. (TSX:APLI; OTCQB: APLIF) (the “Company” or “Appili”), a biopharmaceutical company focused on drug development for infectious diseases and biodefense products, today announced its financial and operational results for the second quarter of its fiscal year 2024, which ended on September 30, 2023. All figures are stated in Canadian dollars unless otherwise stated. "Notably, the Company’s most advanced asset ATI-1501, received U.S. Food and Drug Administration (“FDA”) approval on September 22, 2023, along with its brand name LIKMEZ. The approval of LIKMEZ, shortly after securing patent coverage through 2039, is an important milestone that demonstrates Appili’s ability to identify promising opportunities, accelerate their development, and unlock value for the benefit of both patients and shareholders, ” said Don Cilla, Pharm.D., M.B.A., President and Chief Executive Officer of Appili Therapeutics, "Importantly, ATI-1701 recently received an additional funding commitment from USAFA, bringing the total program funding awarded to US$14 million. At Appili, we are proud of our strong government partnerships which enable us to advance this biodefense program towards an Investigational New Drug (“IND”).” Operational Highlights The Company has made significant operational progress during this quarter. The Company received FDA approval for LIKMEZ (ATI-1501) for the treatment of anaerobic bacterial infections on September 22, 2023. Appili expects to receive additional milestone payments and royalties from its partner, Saptalis Pharmaceuticals (“Saptalis”) based on this FDA approval and Saptalis’ commercialization. Saptalis is preparing for commercial launch in late 2023. On October 13, 2023, the Company’s recently issued U.S. patent related to LIKMEZ with coverage through 2039, U.S. Application No. 18/072,154 was listed in the FDA publication, “Approved Drug Products with Therapeutic Equivalence Evaluations”, commonly known as the “Orange Book”. Appili’s development program ATI-1701, for the prevention of F. Tularensis, has received awards totalling US$14 million from the U.S. Air Force Academy (“USAFA”). Under the terms of the recently modified agreement with USAFA governing such awards, Appili will be reimbursed for subcontractor and vendor costs necessary to carry out the technical tasks. Additionally, Appili will be reimbursed for direct labour costs associated with budgeted program activities, including a portion of its overhead costs. During our second fiscal quarter, Appili progressed early-stage development activities and regulatory activities. In addition, Appili successfully completed a knowledge transfer and executed a technology transfer for the ATI-1701 drug substance manufacturing process to the Phase 1 Contract Manufacturing Organization (“CMO”). With respect to Appili’s ATI-1801 program, for the treatment of cutaneous leishmaniasis, the Company plans to request a meeting with the FDA later this year to discuss the previously generated Phase 3 data and agree on the registration package necessary to support a New Drug Application (“NDA”) submission, which the Company expects will include available nonclinical, manufacturing, and clinical data generated to date. Appili expects to pursue non-dilutive funding and partnership opportunities with NGOs and government agencies which share the Company’s focus on tropical diseases to help complete remaining development work. Upcoming Milestones Appili anticipates receiving royalty and milestone payments from its partner Saptalis, based on LIKMEZ NDA approval and commercialization. Appili plans to hold a pre-IND meeting with the FDA to discuss ATI-1701’s regulatory, CMC, toxicology, and Phase 1 strategies. Appili expects the ATI-1701 CMO to successfully produce engineering batches. Appili plans to request a meeting with the FDA later this year to discuss the previously generated ATI-1801 Phase 3 data and agree on the necessary registration package to support an NDA submission. Corporate Update Today the company announced that it has appointed Prakash Gowd, MBA, BSc. Pharm, C.Dir., to its Board of Directors. Mr. Gowd’s career covers a broad range of commercial successes involving corporate development, fundraising, and marketing across multiple business models and therapeutic areas. “We are very pleased to welcome Prakash to Appili’s Board. His background in corporate finance, product development and strategic planning will be very valuable as we advance our programs through multiple milestones, from ATI-1701’s IND submission, to the FDA interactions for our ATI-1801 asset,” said Dr. Armand Balboni, Chair of the Appili Board. “We are thrilled to have Prakash as a Board member and look forward to his leadership experience as we progress our candidates through these next crucial stages.” Annual Financial Results The Company prepares its financial statements in accordance with IFRS 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 $1.0 million or $0.01 loss per share for the three months ended September 30, 2023, was $0.6 million lower than the net loss and comprehensive loss of $1.6 million or $0.02 loss per share during the three months ended September 30, 2022. This relates mainly to an increase in milestone revenue of $0.3 million, an increase in government assistance of $1.0 million, a decrease in foreign exchange losses of $0.2 million and a decrease in general and administrative expenses of $0.1 million. These decreases were offset by an increase in research and development expenses of $0.8 million and an increase in financing costs of $0.2 million. As of September 30, 2023, the Company had cash of $0.4 million, compared to $2.5 million on March 31, 2023. As of November 13, 2023, the Company had 121,266,120 issued and outstanding Common Shares, 7,842,000 stock options, and 44,856,874 warrants outstanding. This press release should be read in conjunction with the Company’s unaudited interim condensed financial statements for the second quarter of the 2024 fiscal year and the related MD&A, copies of which are available under the Company’s pro SEDAR+ at . About Appili Therapeutics Appili Therapeutics is a biopharmaceutical company that is purposefully built, portfolio-driven, and people-focused to fulfill its mission of solving life-threatening infectious diseases. 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 . Forward looking statements This news release contains “forward-looking statements”, including with respect to the funding commitment from USAFA and expected timing of invoice payment, 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, 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 the annual information form of the Company dated June 22, 2023, and the other filings made by the Company with the Canadian securities regulatory authorities (which may be viewed at ). 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.