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A Novel, Broad Spectrum, Clinical Stage Antifungal to Address Severe and Difficult-to-Treat Invasive Fungal Infections

ATI-2307 is Appili’s novel clinical stage antifungal candidate. It has a highly differentiated mechanism of action and has demonstrated antifungal activity against multiple high priority and clinically important fungi, including Cryptococcus and multi-drug resistant Candida. ATI-2307 is undergoing rigorous preclinical evaluations to inform clinical development strategy and support initiation of Phase 2 development in 2022. Potential target indications include cryptococcal meningitis and invasive candidiasis.

Cryptococcal Meningitis

Cryptococcus is a fungus that primarily infects immunosuppressed individuals, often resulting in severe and invasive infections of the brain. Cryptococcal meningitis imposes a major burden and high mortality on vulnerable patient populations around the world. Although the problem is most acute in sub-Saharan Africa as well as South and Southeast Asia, the burden of cryptococcal meningitis in the United States is also unacceptably high and likely growing with increasing numbers of immunosuppressed transplant and cancer patients.  At least 5,000 patients are treated for Cryptococcus infections each year in the United States, with mortality rates of ~10-15% in hospital.  Longer-term, mortality rates are even higher in this underserved and growing orphan segment.


The current standard of care for cryptococcal meningitis, which is amphotericin B in combination with flucytosine, is associated with alarming toxicity that includes high rates of kidney failure.  We seek to offer ATI-2307 as a safer and more effective alternative. ATI-2307 has demonstrated potent fungicidal activity against Cryptococcus superior to standard of care agents and was well tolerated with an acceptable safety profile up to the highest dose level tested in Phase 1 studies. 

ATI-2307 is eligible for a Neglected Tropical Disease Priority Review Voucher if first approved by the U.S. Food and Drug Administration (FDA) for the treatment of cryptococcal meningitis




“Cryptococcal meningitis is a serious infection with considerable unmet need for novel therapies. ATI-2307 is highly active against Cryptococcus and has the potential to substantially improve the outcome in patients with these invasive Cryptococcal and other fungal infections.”

– Dr. Yoav Golan, CMO Appili Therapeutics, infectious disease specialist Tufts Medical Center

Invasive Candidiasis

Candida species are the most common cause of invasive fungal infections. A growing number of patients are underserved by currently available antifungals either due to resistance, lack of effectiveness, or drug intolerance. 


Resistance is threatening the current antifungal arsenal. Already, the U.S. Centers for Disease Control and Prevention (CDC) list fluconazole resistant Candida as a serious health threat, noting that resistant Candida may add millions of dollars in excess health costs every year.  Equally worrying are the species of Candida that are more often antifungal resistant – such as C. glabrata, C. kruzei and the newly emerged C. auris – and are increasingly common in the clinic. The CDC has identified C. auris in particular as a serious global health threat, in large part due to high levels of multidrug resistance, and difficulty eradicating the fungus from the hospital setting once introduced. 


The problem of Candida infections is not limited to resistance. With few classes of anti-fungal drugs available in the first place, physicians can quickly run out of treatment options if an infection is in a difficult-to-access part of the body or if a patient has drug intolerance. An especially urgent challenge is the treatment of Candida urinary tract infections due to the small number of drugs that can access the site of infection. Based on preliminary analyses, Appili estimates a significant proportion of Candida patients are treated with last resort and highly toxic amphotericin B in the US each year. The number of cases could grow if rates of immunosuppression and antifungal resistance continue to rise.


If approved by regulatory agencies, ATI-2307 may provide physicians with an urgently needed alternative for difficult-to-treat Candida infections. It has shown to be highly active against Candida species with in vivo proof of concept in multiple models including top priority C. auris and C. glabrata


Appili acquired the ATI-2307 program from FUJIFILM Toyama Chemical Co. Ltd. (FFTC) and holds worldwide development and commercialization rights outside of Japan. 


The National Institutes of Allergy and Infectious Disease (NIAID), part of the National Institutes of Health, has provided funding and support for ATI-2307. Appili is also working closely with leading antifungal clinical trial experts at the Mycoses Study Group to advance ATI-2307 in clinical development.


As a broad-spectrum agent with a differentiated mechanism of action, ATI-2307 has the potential to address multiple urgent unmet needs around the world. Appili intends to pursue regional and global partnerships to maximize value and access to ATI-2307 to help support unmet patient needs.



(1) Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, Denning DW, Loyse A, Boulware DR. Lancet Infect Dis. 2017 Aug;17(8):873-881. doi: 10.1016/S1473-3099(17)30243-8. Epub 2017 May 5


(2)  Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. AIDS. 2009 Feb 20;23(4):525-30


(3)  Epidemiology of cryptococcal meningitis in the US: 1997-2009. Pyrgos V, Seitz AE, Steiner CA, Prevots DR, Williamson PR. PLoS One. 2013;8(2):e56269


(4)  Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. Clin Infect Dis. 2010 Feb 1;50(3):291-322


(5)  Renal impairment and amphotericin B formulations in patients with invasive fungal infections. Saliba F, Dupont B. Med Mycol. 2008 Mar;46(2):97-112



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