Corporate Presentation
Sept 2022
URICA Therapeutics, Inc.
Differentiated URAT1 Inhibitor with Established Long-term
Efficacy and Safety for the Treatment of Gout
1
Forward Looking Statements
URICA Therapeutics, Inc. is a subsidiary of Fortress Biotech, Inc.
Some statements in this presentation that are not descriptions of fact may be forward-looking statements, for which
we and our majority-owned parent company Fortress Biotech claim the protection of the safe harbor for forward-
looking statements contained in the Private Securities Litigation Reform Act of 1995. Such statements include, but
are not limited to, any statements relating to our growth strategy, products and product development programs.
Forward-looking statements are based on management’s current expectations and are subject to risks and
uncertainties that could negatively affect our business, operating results, and financial condition. Factors that could
cause actual results to differ materially from those currently anticipated include: risks related to our growth strategy;
risks relating to the results of research and development activities; our ability to obtain, perform under and maintain
financing and strategic agreements and relationships; uncertainties relating to preclinical and clinical testing; our
dependence on third party suppliers; our ability to attract, integrate, and retain key personnel; the early stage of
products under development; our need for and continued access to additional funds; government regulation; patent
and intellectual property matters; competition as well as other risks described in the Securities and Exchange
Commission filings of our parent, Fortress Biotech, Inc. We expressly disclaim any obligation or undertaking to
release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in
our expectations or any changes in events, conditions or circumstances on which any such statement is based,
except as may be required by law. The information contained herein is intended to be reviewed in its totality, and any
stipulations, conditions or provisos that apply to a given piece of information in one part of this presentation should
be read as applying mutatis mutandis to every other instance of such information appearing herein.
2
Executive Summary
• Potential to be a safe and effective oral therapy for lowering sUA
• Higher potency and selectivity for URAT1 versus other marketed uricosurics
4
• Approved in Japan (2020) with clinical data from 1000+ subjects across 17 clinical trials
5
3
• Unique product profile and positioning to potentially overcome US market barriers with improved commercial appeal
• $1B+ sales potential in the US alone for gout with multi-billion-dollar expansion opportunity in CKD and other indications
• Patent exclusivity through 2038 (plus potential patent term extension)
• URICA owns exclusive rights in the US, EU, Canada, and UK
Dotinurad products
6
have the potential to transform US gout practice
Dotinurad is a differentiated URAT1 inhibitor with substantial clinical data and experience
US gout patients still need effective, safe and convenient urate-lowering drugs
• Allopurinol’s modest efficacy and mandatory dose titration are significant drivers of non-adherence for patients and
contribute to inability to achieve serum uric acid (sUA) treatment goals
1
• Febuxostat’s black box warning and increased CV death risk contributed to a nearly 40% drop in Rx from 2016 to 2021
2
• Up to 2.5 million US patients have inadequately controlled sUA, which may lead to worsening of symptoms and QoL
3
1. Semin Arthritis Rheum. 2021 Sep 16;51(6):1162-1169 and company market research. 2. Uloric product label and Symphony Rx data as of June 2022. 3. Company market research.
4. J Pharmacol Exp Ther. 2019 Oct;371(1):162-170. 5. Urece
®
Japanese product label. 6. URICA’s proprietary investigational drug products based on Dotinurad and other components.
Dotinurad Products are investigational and not approved for use in the United States.
“Hyperuricemia with gout” is a highly prevalent, poorly managed, progressive
inflammatory condition
4
Gout Flare Around Toe
Urate crystal
deposits
Intense pain
Gout flare, tissue damage and disabilities
• Concentrated sUA forms crystals in low pH environment, such as joints, which
may elicit inflammation and causes severe pain, known as gout flare
• As it progresses, flare may become more frequent and eventually persistent
• Inadequate control of sUA may lead to Tophi, palpable deposits of urate crystal,
which may erode bones, restrict movement and compromise QOL
High Purine
Food
HypoxanthinePurines Xanthine
Uric acid
Hyperuricemia
• In healthy subjects, sUA is cleared via renal and GI excretion
• Hyperuricemia occurs when the body over-produces or under-excretes urate,
which leads to high sUA levels and formation of urate crystals
Uric acid formation pathway
Excretion
Gout flares
Tophi
Three classes of urate-lowering therapies (ULTs) are approved in the US
5
Xanthine Oxidase Inhibitors Uricosuric Agents Uricases
URAT1
Reabsorbs
Secreted UA
Glomerulus
Input
UA
XO
UA
Allantoin
• Oral drugs that reduce UA
production by inhibiting liver
Xanthine Oxidase
Mechanism
• Oral drugs enhance UA renal
excretion by inhibiting renal UA
transporters, such as URAT1
• IV infused biologics that degrade
UA into allantoin
• U.S. standard of care despite
inadequate excretion being the
primary case in 90% pts; 33%
achieve treatment goals**
Use cases
• Minimally used in US due to
limited efficacy and frequent
dosing
• Used as last line of therapy for
severe Chronic Refractory Gout
• Allopurinol
• Febuxostat
Drugs
• Probenecid (approved 1951) • Krystexxa
®
(approved 2010)
**Arthritis Rheumatol. 2019 Jun; 71(6): 991–999
Currently Approved Urate-Lowering Therapies are Inadequate
Approved 1966
Oral, once or twice daily
Annual cost $104*
Approved 2009
Oral, once daily
Annual cost $4000* (branded)
Approved 1951
Oral, up to 2 grams/4 times daily
Annual cost $217*
Approved 2010
IV infusion every 2 weeks
Annual cost >$300,000**
Drug
Profile
Benefits
Risks
Utilization
Modest efficacy
1
Long history of use
Hypersensitivity reaction (HLA 58:1)
Dose limited in renal impaired, GI
Modest efficacy
1
Not limited by renal impairment
Higher CV death rate than Allo
1
Rash, GI, Hepatic adverse reactions
Drug-drug interactions
Rapid reduction of sUA
Tophi reduction
Anaphylaxis, infusion reactions,
G6PD deficiency associated
hemolysis and methemoglobinemia
Mild efficacy
3
1
st
line therapy despite limitations
and used unless contraindicated
Titrate burden & poor adherence
2
Mostly used in younger patients
without cardiovascular risk
Low utilization due to limited
efficacy, burdensome dosing and
drug interactions
~2000 pts/yr
6
Allopurinol Febuxostat Probenecid
Krystexxa
®
Mkt Share
Reduce Uric Acid Synthesis Increase Uric Acid Elimination
94.2% (2021) 7.1% (2016) à 4.5% (2021) 1.2% (2021)
<5% of chronic refractory market,
rapid growth
1. Febuxostat Compared with Allopurinol in Patients with Hyperuricemia and Gout. N Engl J Med 2005; 353:2450-2461
2. Allopurinol adherence, persistence and patterns of use in individuals with diabetes and gout. Semin Arthritis Rheum. 2021 Sep 16;51(6):1162-1169
3. Comparison of allopurinol and probenecid. Ann Rheum Dis . 1966 Nov;25(6 Suppl):623-6.
* Based on list price from MediSpan as of June 20, 2022
** Based on list price of $26K/vial and recommended dosage of 1 vial infused every 2 weeks, assumption of 6 months of therapy
“Benefit/Risk” statements are based on latest product labels respectively, KOL interviews and company market research
“Market share/utilization” statements are based on public company filings, databases and prescription data from Symphony Rx as of June 16, 2022
The Dynamics of US Gout Market
• Based on the American College of Rheumatology 2020 guideline for gout, allopurinol is the first drug of
choice for most patients initiating ULT
1
• Mandatory step titration starts from 100mg/day, with 100mg increment up to 800mg/day if tolerated
1
• Considerable time and multiple clinical visits are needed to up titrate, which contribute to low adherence
2
• Nearly 85% of Allopurinol prescriptions are from GPs
2,3
• Nearly 80% of GPs do not titrate Allopurinol beyond 300mg
4
• Only about 38% patients reach sUA target with Allopurinol 300mg
5
• Forced titration, long time-to-target, and modest efficacy are key reasons gout patients have poor adherence
2
to
Allopurinol and many of them have inadequately controlled sUA
6
• Febuxostat is now mostly used in younger patients without CV risk
2
, due to its boxed warning on CV death
7
• Febuxostat market share has stably declined by 40% since 2016
3
• Krystexxa (IV) is reserved for the severe patients who must step through oral therapies at maximally
tolerated dose
8
• Strong market demand exists for an effective oral drug as alternative to the IV product
2
• Horizon is actively increasing awareness of gout to both the medical community and general public
9
7
1. https://pubmed.ncbi.nlm.nih.gov/32391934/; 2. KOL interviews and company market research; 3. Symphony Rx as of 2021; 4. https://pubmed.ncbi.nlm.nih.gov/26190562/; 5. Febuxostat,
Zurampic NDAs. 6. Semin Arthritis Rheum. 2021 Sep 16;51(6):1162-1169; 7. Febuxostat product label as of 2022; 8. Krystexxa product label as of 2022; 9. Endpoint News, May 13, 2022
Dotinurad has significant clinical experience in Japan, which extensively validated
safety and efficacy profiles in humans
• Dotinurad is approved in Japan for hyperuricemia with or without gout
1,2
• Japanese approval based on 1000+ subjects treated in 17 clinical trials
o 500+ patients received Dotinurad in 3 Phase 3 trials up to 58 weeks in duration
4-6
o 4mg dotinurad achieved 100% patient sUA <6mg/dL at 58 weeks
3
o Well-tolerated with excellent adverse event profile
o No significant cardiovascular, hepatic or renal adverse events
4-6
o Label allows use in gout patients with mild-to-moderate CKD
• Dotinurad has been widely licensed:
o Eisai – China & Southeast Asia
o Standard Chem & Pharm Co. Ltd – Tai wa n
o URICA – US, EU, UK, and Canada
1. https://pubmed.ncbi.nlm.nih.gov/31754883/
2. https://www.fujiyakuhin.co.jp/medicine/m-fujiyakuhin/
3. 2mg Dotinurad resulted in 89.1% and 91.3% sUA under target Week 34 and 58
4. https://pubmed.ncbi.nlm.nih.gov/31980978/
5. https://pubmed.ncbi.nlm.nih.gov/31970593/
6. https://pubmed.ncbi.nlm.nih.gov/31875931/
8
Dotinurad Products are investigational and not approved for use in the United States.
Nonclinical data suggest Dotinurad is more URAT1-selective than other tested
uricosurics
Non-specific inhibition of OAT1/3 and ABCG2 may increase risk of renal toxicity***
9
Pharmacological Evaluation of Dotinurad, a Selective Urate Reabsorption Inhibitor, J Pharmacol Exp Ther . 2019 Oct;371(1):162-170
***Hypouricemic agents reduce indoxyl sulfate excretion by inhibiting the renal transporters OAT1/3 and ABCG2, Sci Rep . 2021 Mar 31;11(1):7232.
URAT1 Selectivity
Dotinurad
≥36 times more selective to URAT1 than other urate transporters
Lesinurad
25 times
less selective to URAT1 than other urate transporters
Benzbromarone
≥5 times more selective to URAT1 than other urate transporters
Probenecid
100 times
less selective to URAT1 than other urate transporters
Dotinurad Products are investigational and not approved for use in the United States.
Dotinurad demonstrated safety in Japanese clinical development
10
Adapted from Dotinurad Japanese product label, n>1000
≥ 5% 1% to 5% < 1%
Gastrointestinal
Diarrhea
Hepatobiliary
Increase
g-GTP
Musculoskeletal
Gouty arthritis**
Arthritis**
Limb discomfort**
Arthralgia
Renal and urinary
Nephrolithiasis
Nephrocalcinosis
Increased urine
b-2-macroglobulin
Increased blood creatinine
Increased blood urea nitrogen to creatinine ratio
Albuminuria
**Gout flares often occur during the initiation phase of ULT. JP practice does not use prophylaxis. US practice recommends prophylaxis.
Dotinurad Products are investigational and not approved for use in the United States.
Dotinurad has the potential to capture significant share of US market
Approved 1966
Oral, once or twice daily
Annual cost $500
Approved 2010
IV infusion every 2 weeks
Annual cost >$300,000
Drug
Profile
Benefits
Risks
Utilization
Modest efficacy
Long history of use
Hypersensitivity reaction (HLA 58:1)
Dose limited in renal impaired pts
Rapid reduction of sUA
Tophi reduction
Anaphylaxis, infusion reactions,
G6PD deficiency associated
hemolysis and methemoglobinemia
Workhorse drug despite limitations
1
st
line use unless contraindicated
Titrate burden***
~2000 pts/yr
** Febuxostat Compared with Allopurinol in Patients with Hyperuricemia and Gout. N Engl J Med 2005; 353:2450-2461
***Allopurinol adherence, persistence and patterns of use in individuals with diabetes and gout. Semin Arthritis Rheum. 2021 Sep 16;51(6):1162-1169
11
Allopurinol
Krystexxa
®
Proprietary Product Positioning
To be discussed under a confidentiality agreement
≥ 2.5 Million Target Patients
Dotinurad Products
Dotinurad Products are investigational and not approved for use in the United States.
Dotinurad U.S. Product Positioning
• We are designing proprietary Dotinurad products to overcome barriers in the US gout market
• Core unmet needs for US gout patients:
• Reduced burden of titration to improve patient adherence
• Speed in reaching sUA target
• Effective therapy to significantly reduce sUA below target
• Benign safety and tolerability profile
• Oral therapy that is easy to administer
• Therapy applicable to variable disease severity, from mild to severe
• Ability to reduce flares and tophi
• We will be delighted to discuss our product positioning and development strategy under a
confidentiality agreement
12
Dotinurad Products are investigational and not approved for use in the United States.
Executive Summary
• Potential to be a safe and effective oral therapy for lowering sUA
• Higher potency and selectivity for URAT1 versus other marketed uricosurics
4
• Approved in Japan (2020) with clinical data from 1000+ subjects across 17 clinical trials
5
13
• Unique product profile and positioning to potentially overcome US market barriers with improved commercial appeal
• $1B+ sales potential in the US alone for gout with multi-billion-dollar expansion opportunity in CKD and other indications
• Patent exclusivity through 2038 (plus potential patent term extension)
• URICA owns exclusive rights in the US, EU, Canada, and UK
Dotinurad products
6
have the potential to transform US gout practice
Dotinurad is a differentiated URAT1 inhibitor with substantial clinical data and experience
US gout patients still need effective, safe and convenient urate-lowering drugs
• Allopurinol’s modest efficacy and mandatory dose titration are significant drivers of non-adherence for patients and
contribute to inability to achieve serum uric acid (sUA) treatment goals
1
• Febuxostat’s black box warning and increased CV death risk contributed to a nearly 40% drop in Rx from 2016 to 2021
2
• Up to 2.5 million US patients have inadequately controlled sUA, which may lead to worsening of symptoms and QoL
3
1. Semin Arthritis Rheum. 2021 Sep 16;51(6):1162-1169 and company market research. 2. Uloric product label and Symphony Rx data as of June 2022. 3. Company market research.
4. J Pharmacol Exp Ther. 2019 Oct;371(1):162-170. 5. Urece
®
Japanese product label. 6. URICA’s proprietary investigational drug products based on Dotinurad and other components.
Dotinurad Products are investigational and not approved for use in the United States.
Management and Advisory Board
14
Paul Brooke
Executive Chairman
• Chairman Emeritus of the Board of Caelum Biosciences, acquired by AstraZeneca in Oct 2021
• Founder and former Managing Partner of venBio, a pharmaceutical investment company
• Former global head of healthcare research and strategy at Morgan Stanley
Lindsay Rosenwald, MD
Director
• Chairman, President, and CEO at Fortress Biotech (NASDAQ: FBIO)
• Previously, Founder/Board Member of multiple biotech companies: Cougar Biotechnology (acquired by JNJ), Chelsea Therapeutics
(acquired by Lundbeck), Indevus Pharma (acquired by Endo), Biocryst, Keryx, CorMedix, and Ziopharm
Raymond Zheng, PhD
Interim President and Chief Scientific
Officer
• Experienced Biotech Entrepreneur with combined 20+ years of experience in drug discovery and development
• Previously held multiple business development roles at Fortress Biotech, Agenus, and Harvard Medical School
• PhD from University of California, Riverside, with research fellowship at Harvard Medical School
Scott Baumgartner, MD
Interim Chief Medical Officer
• Experienced clinical development and medical affair expert
• Previously VP of Medical Affairs at AstraZeneca/Ardea Biosciences and Amgen
• Experienced in the clinical development and post-launch activities of Lesinurad and Verinurad
• MD from University of Washington with 20 years of clinical rheumatology experience
Dr. Robert Terkeltaub, MD
University of California, San Diego
Chief of Rheumatology
• Professor of Medicine, UCSD, and Section Chief of Rheumatology at the VA Medical Center in San Diego
• Associate Editor of Arthritis and Rheumatism, and serves on numerous NIH Study Sections in arthritis
• Graduate of McGill University, where completed his medicine residency and rheumatology fellowship
Dr. Michael Pillinger, MD
New York University
Chief of Rheumatology
• Chief of Rheumatology at VA NY Harbor Healthcare System
• Professor of Medicine at NYC Grossman School of Medicine
• Received medical degree from NYU School of Medicine; has practiced rheumatology for more than 20 years
Dr. Lee Simon, MD
Consultant
• FDA's Division Director of Analgesic, Anti-inflammatory and Ophthalmologic Drug Products (2001-2003)
• Worked, for 12 years, as a NIH funded investigator and he has served two terms on the Board of Directors of the American College of
Rheumatology (ACR)
• Served as Chair of Education for the ACR and the National Arthritis Foundation
Executive Management
Scientific Advisory Board
