EveryCat Health Foundation Report of FIP Funded Projects 2019 to 2021

2020-2021

W21-006: “Determining the in vitro intrinsic clearance (feline microsomes) and in vivo pharmacokinetic profile of remdesivir in cats with naturally occurring feline infectious peritonitis (FIP). Principal Investigator(s): Dr. Sally Coggins, BVSc (hons I) MANZCVS (Feline Medicine); Associate Professor Merran Govendir; Dr. Benjamin Kimble; Sydney School of Veterinary Science, The University of Sydney, Australia. (New Investigator Award) (Bria Fund)

Remdesivir was recently approved for treatment of the coronavirus infection, COVID-19, in people in Australia, but has not been widely used due to few cases in that country. Preliminary studies show this drug is also effective against the coronaviral infection, feline infectious peritonitis. This study will examine how the drug is metabolized to determine the effective dose of Remdesivir in cats.

W21-017: “Use of a liposome-toll-like receptor complex (LTC) immune stimulant in the treatment of effusive FIP – A clinical trial.” Principal Investigator(s): Petra Cerna, Michael Lappin, Steven Dow, Colorado State University (Bria Fund)

Feline Infectious peritonitis is a fatal coronaviral infection of cats with no approved treatment. This study investigates a new immune therapy to determine its effectiveness in treating this devastating disease.

MT20-008 - Development of improved cell culture systems for feline coronavirus and FIP vaccine development, Aim 2. Principal Investigators: Gary Whittaker, Cornell University; Susan Baker, Loyola University. Feline infectious peritonitis is a common, fatal disease of cats caused by a coronavirus, similar to the one that causes COVID-19 in humans. This study will identify and characterize the specific receptor on susceptible cells that allows the virus to infect cats, leading to potential treatments and preventions such as vaccines.

2019-2020

W20-002 - Mechanism of action of doxycycline in inhibiting feline infectious peritonitis virus. Principal Investigator: Gary R. Whittaker, PhD, Cornell University; $25,000 (Bria Fund)

This study evaluates the anti-viral effects of doxycycline, a common antibiotic on feline infectious peritonitis (FIP), a fatal coronavirus infection of cats. Doxycycline is highly cost- effective, licensed and approved for use in cats. The study’s results may provide strong evidence to support the use of doxycycline in future clinical trials for treating FIP as part of a possible combination therapy, which will be ultimately necessary to combat FIP.

W20-003 - Developing a safe and effective anticoronaviral therapy for client-owned cats with FIP (continuation study). Principal Investigators: Dr. Brian Murphy, Niels C. Pedersen, University of California, Davis; $21,500 (Bria Fund)

Recently, effective treatments for feline infectious peritonitis (FIP), a fatal coronaviral infection of cats, were discovered. This study looks at several new antiviral compounds to

evaluate their efficacy and determine possible combinations (combined anticoronaviral therapy (CACT)) that may be more effective than a single drug.

W20-005 - Determining the clinical efficacy of mefloquine for treatment of naturally occurring feline infectious peritonitis, stage 1. Principal Investigators: Jacqueline Norris, Merran Govendir, Dr. Benjamin Kimble, University of Sydney; $20,500 (Bria Fund)

Mefloquine, a common and available anti-malarial drug, inhibits replication of feline infectious peritonitis (FIP) virus, a fatal coronavirus infection of cats, in laboratory tests. An earlier study found mefloquine to be well absorbed and safe to use. This study will evaluate the effectiveness of this drug in cats with naturally occurring FIP.

2018-2019

W19-024 – Identification of Diagnosis Biomarkers of Feline Infectious Peritonitis

PIs: Dr. Gregg Dean and Dr. Kelly Santangelo, Colorado State University; $25,000 (Bria Fund) Feline infectious peritonitis (FIP) is perhaps the most devastating infectious disease of cats and there remains a desperate need for a fast and reliable diagnostic test. FIP is caused by the Feline Infectious Peritonitis Virus (FIPV), which has undergone subtle mutations from its normal gastrointestinal counterpart, Feline Enteric Coronavirus (FECV). Clinical signs in the cat are vague and nonspecific, and can include inappetence, lethargy, disorientation, vomiting and diarrhea. Unfortunately, a definitive diagnosis of FIP is often challenging and is typically a diagnosis of exclusion, which is frustrating for owners and veterinarians, alike. While several assays capable of confirming FIP have been developed, these tests can require invasive methods and lengthy wait times for results. We have employed a powerful new technology to simultaneously measure more that 1300 proteins in the blood of cats with FIPV. We compared these results to normal cats and cats infected with other viruses to identify unique proteins that might allow diagnosis of FIPV. We then evaluated a total of 56 cats and utilized statistical modelling to reduce the number of candidate proteins from >1300 to 18. Our current plan is to further evaluate these 18 proteins for accuracy with feline samples prior to ultimately validating a diagnostic test for FIPV.

W19-025 – Generating an Attenuated Feline Infectious Peritonitis (FIP) Vaccine by Inactivating EndoU PIs: Dr. Gary R. Whittaker and Dr. Susan G. Baker, Cornell University and Loyola University, Chicago; $25,000 (Bria Fund)

Feline infectious peritonitis (FIP) is an important cause of death in cats and is caused by a coronavirus. There are currently no effective treatments or vaccines for FIP. Based on new information demonstrating that mutation of a specific viral gene allows for a robust immune response to coronavirus infection without causing disease, we propose to develop a new live-attenuated vaccine for FIP.

W19-026 – Developing a Safe and Effective Anticoronaviral Therapy for Cats with FIP (continuation) PIs: Dr. Brian Murphy and Dr. Niels C. Pedersen, University of California Davis; $23,779 (Bria Fund)

Feline infectious peritonitis (FIP), caused by mutant feline coronavirus known as FIPV, is a common and generally lethal disease of domestic cats. Over the past 3 years, and with the help of funds provided by Winn Feline Foundation, our research group at University California Davis has conclusively demonstrated that naturally acquired FIP is a curable disease using a nucleoside analog called GS-441524 (Gilead).

However, this drug is not yet available for use in cats. In its place, Gilead has provided 48 related nucleoside analogs and if any are found to be equivalent, they have agreed to provide the necessary animal rights. Preliminary data indicates
that 3 or more of these drugs will have potent anti-FIPV properties and be non-cytotoxic in feline cells. The most promising of these compounds will be synthesized in much larger amounts and ultimately tested in cats for safety and efficacy. Another collaborator, Mark Olsen (Midwestern University) is creating a set of drug compounds targeting a different viral protein. The results of our initial studies, although not immediately yielding a marketable drug for cats, lead us to conclude that that FIP is in fact a curable disease.

Winn Feline Foundation Report of FIP Funded Projects through June 26, 2019

Key: W- Winn MT- Miller Trust MTW- Special Cycle Bria Fund Financed The Bria Fund Projects to date:

Note: The Bria Fund was founded in November of 2005. Donations were sufficient to support its first study in 2008.

W19-024

Identification of diagnostic biomarkers of feline infectious peritonitis. Principle Investigators: Dr. Gregg Dean and Dr. Kelly Santangelo; Colorado State University. Grant Amount $25,000.

W19-025

Generating an attenuated Feline Infectious Peritonitis (FIP) vaccine by inactivating EndoU. Principle Investigators: Dr. Gary R. Whittaker and Dr. Susan G. Baker; Cornell University and Loyola University Chicago. Continuation of previous funded studies. Grant Amount $25,000.

W19-026

Developing a safe and effective anticoronaviral therapy for cats with FIP. Principle Investigators: Dr. Brian Murphy and Dr. Niels C. Pedersen, University of California, Davis. Continuation of previous funded projects. Grant amount $23,779.

W19-027

Determining the pharmacokinetic profile of mefloquine in clinically normal cats as a preliminary in-vivo study towards a potential treatment for Feline Infectious Peritonitis. Principle Investigators: Dr. Merran Govendir and Dr. Jaqueline Norris, University of Sydney. This project is a continuation of Project W16-023. Grant Amount $24, 624.

W18-010 (Bria Fund and New Feline Investigator Award) Understanding genetic differences in immunity to feline infectious peritonitis (FIP). Principal Investigator: Drs. Emi Barker and Christopher Helps; Langford Vets, University of Bristol, UK. Although feline infectious peritonitis (FIP) is caused by a coronavirus, only some infected cats get the disease. This study will examine how genetic differences in a cat's immune system play a role in this disease, and how common these differences are in the general cat population. Grant amount $6,400.

MTW 17-022 Generating an attenuated feline infectious peritonitis (FIP) vaccine by creating a protective immune response. Principal Investigator: Gary Whittaker, PhD; Cornell University, Susan Baker, PhD; Loyola University-Chicago. Feline infectious peritonitis (FIP) is a common and deadly disease of cats. Previous attempts at developing a vaccine were ineffective and

increased the likelihood of the disease. New information shows that mutation of a specific gene in the virus can protect against this infection without causing disease. This study attempts to develop a new live-attenuated vaccine for FIP. Grant amount $35,000.

MTW-17-020 Developing a Safe and Effective Combined Anticoronaviral Therapy (CACT) for Cats with FIP. Principal Investigators: Brian Murphy, DMV, PhD, Niels Pedersen PhD, University of California-Davis. Feline infectious peritonitis (FIP) is a common and deadly disease of cats with previously no effective treatment. This study uses compounds developed for antiviral therapy in humans to treat this disease, with promising early results. Combination

anticoronaviral therapy, used successfully in humans, will be evaluated for enhanced treatment of this otherwise fatal disease. Grant amount $20,500.

W17-021 Analysis of Plasma to Identify Biomarkers for the Diagnosis and Prognosis of FIP. Principal Investigators: Gregg Dean, DVM, PhD, DACVP, Kelly Santangelo, DVM, PhD, DACVP; Colorado State University. Feline infectious peritonitis (FIP) is
a fatal disease of cats that causes vague symptoms and currently defies diagnosis. This study uses a novel approach to develop a simple test using plasma biomarkers for this devastating disease, Grant Amount $25,000.

W16-024 Exploring Humoral Responses to Non-Structural Proteins of Feline Coronaviruses, Principal Investigator: Magdalena Dunowska, BVsc, PhD; Massey University, New Zealand, Grant Amount $25,000.

W16-023 Mefloquine’s Potential To Inhibit FIPV Infection In The Cat, Principal Investigator:

Merran Govendir, BVSc, PhD, Jacqueline Norris, BVSc, PhD; The University of Sydney, Australia, Grant Amount $11,750.

W16-022: Evaluating New Drug Compounds For Treating Feline Coronavirus, A Continuation Study, Principal Investigator: Brian Murphy, DVM, PhD, ACVP; Niels Pedersen, DVM, PhD; University of California, Davis, Grant Amount $12,175.

W15-030: Using Small Interfering RNA For Treatment of Feline Infectious Peritonitis, Principal Investigator: Emin Anis, PhD; Rebecca Wilkes, DVM, PhD; The University of Tennessee, Grant Amount $16,500.

W15-026: Systemic Feline Coronavirus and Its Relationship to FIP, Principal Investigator: Gary R. Whittaker, PhD; Cornell University, Grant Amount $24,967.

W15-013 A Feline Tumor Necrosis Factor Inhibitor for FIP. Principal Investigator: Yunjeong Kim, DVM, PhD, ACVIM; Kansas State University, Grant Amount $23,758.

W15-010: Evaluating New Drug Compounds For Treating Feline Coronavirus, Principal Investigator: Brian Murphy, DVM, PhD, ACVP; Niels Pedersen, DVM, PhD; University of California, Davis, Grant Amount, $14, 970.

W14-018: Characterizing how FIP Virus Binds and Enters Cells. Principal Investigator: Gary Whittaker; Cornell University, Grant Amount $24,851.

W13-020: In Vivo Efficacy Study of Virus Protease Inhibitors Against Feline Coronaviruses in a Mouse Model, Principal Investigator: Yunjeong Kim; Kansas State University, Grant Amount $19,920.

W13-019: Host Immune Response of Feline Kidney Cells to Pathogenic and Non-Pathogenic

Feline Coronavirus Strains: Developing Biomarkers for FIP, Principal Investigator: Yvonne Drechsler, PhD and Pedro Diniz, DVM, PhD; Western University of Health Sciences, Grant Amount $25,000.

W12-026: Anti-Immune Evasive Therapy in the Treatment of FIP - Randomized, Controlled Clinical Trial, Hans Nauwynck & Sabine Gleich; Ghent University, Grant Amount $24,962.

W11-008: Evolution of Feline Infectious Peritonitis Virus Within FIP Cats and Tissue-specific Adaptation of the Virus to Activating Proteases, Gary R. Whittaker, Professor, Cornell University, Grant amount $23,986.

W10-039: Development of a Novel Treatment Strategy to Inhibit the Immune Evasion Mechanism of Feline Infectious Peritonitis Virus (FIPV), Sabine Gleich, DVM; Hannah Dewerchin, DVM; Hans Nauwynck, DVM; Ghent University, Grant amount $12,700.

W10-038: Polyprenyl Immunostimulant for the Treatment of the Dry Form of Feline Infectious Peritonitis, Alfred Legendre, DVM, MS, DACVIM; University of Tennessee, Grant Amount $14,825.

W10-037: Development of Feline Infectious Peritonitis Therapeutics in a Mouse Model, Gary R. Whittaker, BSc (Hon), PhD; Cornell University, Grant amount $15,000.

W10-036: Molecular Prevalence and Viral Load of Replicating Feline Coronavirus in the Bloodstream of Healthy Shelter Cats in Southern California, Pedro Paulo Diniz, DVM, PhD; Yvonne Drechsler, PhD; Linda Kidd, DVM, PhD, DACVIM; Frank Bossong, DVM; Ellen

Collisson, MS, PhD; Western University of Health Sciences, Grant Amount $10,000.

W09-027: Determining Genetic Correlates of FIP Susceptibility, Jacqueline Norris, BVSc, MVS, MASM, PhD; Steven A. Holloway BVSc, MVS, MACVSc, DACVIM, PhD; Craig McLure, BSc, PhD; The University of Sydney, Australia, Grant Amount $12,240.

W08-036: Blood Parameters Potentially Associated with Susceptibility to Feline Coronavirus in Birman cats: Saverio Paltrinieri, DVM, PhD, DECVCP; University of Milan, Grant amount $14,780.

W08-006: Identification of the Cellular Receptor for Feline Coronaviruses: H.F. Egberink, DVM, PhD and P.J.M. Rottier, PhD; Utrecht University, Grant Amount $15,000.

W08-004: Molecular Basis of Feline Coronavirus Pathogenesis and Development of FIP in Cats, Phase One, Principal Investigator: Gary R. Whittaker, PhD; Cornell University, Grant Amount: $15,000.

Miller Trust Awards: Reviewed and Selected by Winn’s Grant Review Committee and Board of Directors

MT16-014: Structure-based design of a novel subunit immunogen for development as a feline infectious peritonitis (FIP) vaccine, Principal Investigator: Gary Whittaker, PhD; Cornell University, Grant Amount $30,273.

MT11-007: Effectiveness of Small Interfering RNA (siRNA) to Inhibit Feline Coronavirus Replication Principle Investigators Rebecca P. Wilkes, DVM, PhD, Assistant Professor; Eman Anis, BS, MS; Alfred Legendre, MS, DVM, Professor; Stephen Kania, BS, MS, PhD; The University of Tennessee College of Veterinary Medicine, Grant Amount $23,600.

MT13-006: Pharmacokinetic and toxicity testing of novel feline coronavirus protease inhibitors

in laboratory cats. Principal Investigator: Neils Pedersen, DVM University of California – Davis, Grant Amount $22,464.00.

MT13-008: Transduction of hematopoietic stem cells to stimulate RNA interference for treatment of feline infectious peritonitis. Principal Investigator: Rebecca P. Wilkes, DVM, PhD, University of Tennessee, College of Veterinary Medicine, Grant Amount $19,453.04.

MT08-004: Molecular basis of feline coronavirus pathogenesis and development of FIP in cats, phase two, Principal Investigator: Gary R. Whittaker; Cornell University, Grant Amount: $35,514.

MT06-015: Screening for FCoV to the 7b protein of Feline Coronavirus in cats for detection of persistent infection, Principal Investigator: Melissa Kennedy, DVM, PhD, University of Tennessee, Grant Amount: $14,750.

MT05-005: Phase II studies on the heritability resistance/susceptibility to FECV infection in randomly-bred, colony-reared, domestic cats, Principal Investigator: Niels Pedersen, Leslie Lyons; University of California-Davis, Grant Amount: $15,000.

MT04-015: Phase II studies on the heritability resistance/susceptibility to FECV infection in randomly-bred, colony-reared, domestic cats, Principal Investigator: Niels Pedersen, Leslie

Lyons; University of California-Davis, Grant Amount: $15, 000.

Note: The following FIP research projects were funded by the Winn Feline Foundation before Susan E. Gingrich founded the Bria Fund for FIP Research:

W04-005: Post transcriptional changes of Alpha-1-Acid Glycoprotein during Feline Coronavirus infections, Principal Investigator: Saverio Paltrinieri, DVM, PHD, DECVCP; Fabrizio Ceciliani, DVM, PhD; Alessia Giordano, DVM and Vanessa Pocacqua; University of Milan, Italy, Grant Amount: $14, 489.

W02-025: Screening for FCoV 7b antibodies for diagnosis of FIP, Principal Investigator: Melissa Kennedy, Stephen Kania, University of Tennessee, Grant Amount: $15, 000.

W02-023: Immunopathogenesis of systemic FIP and prospects of intervention, Principal Investigator: Janet Foley, University of California-Davis, Grant Amount: $15,000.

W01-015: Immunopathogenesis and medical intervention in neurological FIP, Principal Investigator: Janet Foley, University of California-Davis, Grant Amount: $14, 500.

W03-024: Healthy carriers of feline coronavirus, Principal Investigator: Diane D. Addie, Department of Veterinary Pathology, University of Glasgow, Grant Amount: $15, 000.

W97-FOLEY: The influence of age and passive systemic immunity on the severity and duration of Feline Enteric Coronavirus infection, Principal Investigator: J.E. Foley, DVM, MS, PhD; N.C. Pedersen, DVM, PhD; University of California, Davis, Grant Amount: $10, 000.

W98-ADDIE: Virus excretion in Feline Coronavirus excretion, Principal Investigator: Diane D. Addie, PhD; Oswald Jarrett, BVMS, PhD; University of Glasgow, Scotland, Grant Amount: $15, 000.

W97-ADDIE: Feline Coronavirus excretion, Principal Investigator: Diane D. Addie, BVMS, RCVS, PhD; Oswald Jarrett, BVMS, RCVS, PhD; University of Glasgow, Scotland, Grant Amount: $15, 000.