Slowing the Progression of Chronic Kidney Disease - Tricida Investor Presentation September 2021
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Slowing the Progression of Chronic Kidney Disease Tricida Investor Presentation September 2021
Forward Looking Statements
Any statements contained in this presentation or made during the accompanying oral presentation that are not statements of historical facts are
forward-looking statements as defined under the Federal securities laws. Examples of such statements include our plans, beliefs, intentions,
expectations and projections regarding, among other things: our expectations regarding event accrual rates for the VALOR-CKD renal outcomes
trial, our plans for interactions and communications with the FDA, our plans and expectations as to the pathway to approval of veverimer by the
FDA, if at all, our plans for future clinical development pathways for veverimer, our assessment of the future market potential for veverimer, and
our expectations regarding financial runway. Any such forward-looking statements are based on our current expectations and assumptions, but
are subject to a number of risks and uncertainties that could cause our actual future results to differ materially from our current expectations or
those implied by the forward-looking statements. In addition, this presentation contains industry and market data prepared by third parties or by
us. We have not independently verified this third-party data, and our data is based on our estimates and assumptions, which are subject to
uncertainty and risk. As a result, you should not place undue reliance on this industry and market data. The risks and uncertainties that could
adversely affect our forward-looking statements and the industry and market data include, but are not limited to: the timing of the FDA’s approval
of veverimer, if at all; the potential availability of the Accelerated Approval Program and the approvability of veverimer under that program; the
Company’s plans and expectations with regard to its interactions with the FDA, including the potential resubmission of an NDA for veverimer; the
Company’s plans and expectations for future clinical and product development milestones; the Company’s contractual and financial obligations to
its key suppliers and vendors; the Company’s financial projections and cost estimates; risks associated with the COVID-19 pandemic; risks
associated with the Company’s business prospects, financial results and business operations; risks related to the Company’s ability to retain its
key employees and executives; and risks related to the Company’s capital requirements and ability to raise sufficient funds for its operations.
These and other factors that may affect our future results and operations are identified and described in more detail in our filings with the
Securities and Exchange Commission (the “SEC”), including the Company’s most recent Annual Report filed on Form 10-K and our subsequently
filed Quarterly Report(s) on Form 10-Q. You should not place undue reliance on these forward-looking statements, which speak only as of the
date of this presentation. Except as required by applicable law, the Company does not intend to update any of the forward-looking statements to
conform these statements to actual results, later events or circumstances or to reflect the occurrence of unanticipated events.
2
Our Goals for Veverimer*
An Investigational Drug Candidate for Slowing CKD Progression in Patients with Metabolic Acidosis and CKD
First and ONLY Disease Improve How Patients
FDA-Approved Therapy Modifying Feel and Function
Significant unmet medical Slow CKD progression through Enhance physical
need to treat chronic the treatment of chronic functioning and physical
metabolic acidosis metabolic acidosis which functioning-related
affects ~3 M patients with quality of life
Stage 3 – 5 CKD in the US
*Veverimer is not yet approved by the FDA 3
Metabolic Acidosis is Commonly Caused by Kidney Disease
Diseased Kidneys Lose Capacity to Excrete Acid Serum Bicarbonate Levels Fall
Acid is generated Diseased kidneys An increase in retained acid leads to a
from dietary sources lose capacity to decrease in serum bicarbonate and a
and daily metabolism excrete excess acid vicious cycle leading to worsening CKD
Normal Range 22 – 29 mEq/L
Metabolic
12 –
Metabolic Acidosis Is a Serious Condition
~3,000,000
Patients with Stage
Common 3-5 CKD afflicted with
Metabolic Acidosis
Harmful
Accelerates Impacts
CKD Progression Bone and Muscle Health
100% Oral Alkali Treatment Rates
The Majority of
Needs to
% of Patients Receiving
No FDA Approved
80%
Oral Alkali Therapy
Patients with 60%
Be Treated Metabolic
Acidosis are
40% Treatments
20% 15.3%
NOT treated 2.7%
8.7% 8.8%
0%
Dobre 2013 Tangri Tricida Tangri 2019
TRCA-301 source is Wesson 2019 (Data on File) 301/301E
5
Veverimer: Designed to Bind and Remove HCl with High
Capacity and Selectivity
High Binding Capacity High Binding Selectivity
Oral Ingestion
NH2 NH2
veverimer
Non-absorbed
polymer GI Anions
NH2 NH2 Ranked by Size
H+ Bile Acids
NH3+ NH3+ Binds protons (H+) Fatty Acids
and then selectively
veverimer
Acid Binding in GI Tract
veverimer Citrate
binds chloride (Cl–)
NH3+ NH3+ in the GI tract
Phosphate
Cl-
Cl- Cl-
Chloride
NH3 + NH3 +
Excreted, resulting in The high degree of crosslinking in veverimer provides a
veverimer
removal of HCl*
NH3+ NH3+
size exclusion mechanism that leads to high selectivity
Cl- Cl- for binding chloride (the smallest anion) over larger anions
Excretion in Feces
GI: Gastrointestinal. HCl: Hydrochloric acid. *Veverimer’s maximum theoretical HCl binding capacity is approximately 10 mEq/gram. 6
Veverimer: Ease of Administration*
Once-a-day dosing
Orally administered as a suspension in
water
3 g, 6 g or 9 g dose sizes
2 oz.
Water
No observed drug-drug interactions
*Targeted profile if approved. Parsell 2021
7
Robust Patent Portfolio for Veverimer Provides Protection Until 2038
in the United States
Europe
United States
Orange Book eligible patents provide patent protection
until 2038
• Three issued EPO patents providing patent
protection until 2034 and two issued patents
providing protection until 2035
• Several pending EPO patent applications
Rest of World
• Several pending patent applications • Issued patents provide protection in numerous
countries/regions outside the US and Europe*
• Corresponding pending patent applications in
other commercially significant countries
Patent term does not include any extension related to Hatch-Waxman in the United States, or a Supplementary Protection Certificate in Europe. Veverimer is an in-house discovered, new chemical
entity. * Patents expected to provide protection for veverimer until at least 2035 in Hong Kong, Israel, Japan, Mexico and Russia and until at least 2034 in Australia, China and certain other markets. 8
Veverimer: TRCA-301 and TRCA-301E Trial Results
Published in The Lancet
TRCA-301 Results TRCA-301E Results
Wesson DE et al., Lancet 2019; 393: 1417-27 Wesson DE et al., Lancet 2019; 394: 396-406
9Summary Data from the TRCA-301/301E Clinical Trials
TRCA-301 Veverimer-Treated Subjects Experienced a Mean TRCA-301 / TRCA-301E
Increase from Baseline in Serum Bicarbonate of 4.5 mEq/L Prespecified Time-to-Event Analyses (52 Weeks)
21.7 65% Reduction in the Annualized Event Rate for Veverimer-Treated Subjects
22
21.6 22.0
21.6 21.7
4% DD50
21 incidence rate
20.8
4.5 mEq/L
20 20.2 (P< 0.0001) 12% DD50
0 0 incidence rate
19 19.0
18.6 18.6 18.9
18.4
18.5
18 18.1
17.3 17.3
17
BL Week 1 Week 2 Week 4 Week 6 Week 8 Week Week
Placebo Veverimer 10 12
TRCA-301 / TRCA-301E TRCA-301 / TRCA-301E
KDQOL Physical Function Domain Repeated Chair Stand Test
11.4
Improved physical function
-1.4
Improved physical function
0
-4.3
-0.7
0 12 Time since randomisation (weeks) 40 52
BL: Baseline. W: Week. Error bars: Standard error of the mean. DD50: Death, dialysis or ≥50% reduction in eGFR.
Wesson DE et al., Lancet 2019; 393:1417-27. Wesson DE et al., Lancet 2019; 394: 396-406. 10Veverimer: TRCA-301/301E Safety Summary
TRCA-301 TRCA-301E
Veverimer Placebo Veverimer Placebo
(n=124) (n=93) (n=112) (n=81)
Serious adverse events
(none assessed to be related to 2.4% 2.2% 1.8% 4.9%
study drug)*
Discontinued study 4.0% 4.3% 2.6% 9.8%
Discontinued study due to an
0.8% 2.2% 0 1.2%
adverse event*
Treatment-emergent adverse
54.0% 46.2% 81.3% 80.2%
events*
Gastrointestinal adverse events 16.9% 8.6% 21.4% 25.9%
* These were prespecificed safety endpoints for the TRCA-301E trial. Wesson 2019; Wesson 2019; data on file. 11Summary of FDA Interactions for the Veverimer NDA*
• Submitted NDA for August 2019
Based on the analysis and rationale provided in the CRL and
ADL, we believe FDA:
Key Goals to Address
review through the
• Seeks data beyond the TRCA-301/TRCA-301E trial
the FDA Issues in the
Accelerated Approval
Program
regarding the magnitude and durability of the
treatment effect of veverimer on the surrogate marker
CRL and ADL
of serum bicarbonate and expressed concern
• Received CRL August 2020 regarding whether the demonstrated effect size would
be reasonably likely to predict clinical benefit (e.g., 1. Generate outcome
sufficient powering for the VALOR-CKD confirmatory
• Held End-of-Review
Type A meeting with
October 2020
renal outcomes trial) data showing the
FDA Division of • Questions the applicability of the treatment effect in impact of veverimer
Cardiology and the TRCA-301/TRCA-301E trial to the U.S. population
Nephrology and the practice of medicine in the United States on CKD progression
• Expressed concern about reliability given that the
• Submitted FDRR to the December 2020 findings of our single registrational trial, TRCA- 2. Show that the data
OND 301/TRCA-301E, were driven by a single, high-
enrolling trial site located in Eastern Europe. (Note: are applicable to the
FDA did not raise any concerns related to FDA’s
• Received ADL from the February 2021 completed inspection of this site and there was no US population
FDA Form 483 issued)
OND
• Did not identify any safety, clinical
pharmacology/biopharmaceutics, CMC, or non-clinical
issues in the CRL
* For a more complete description of Tricida’s interactions with the FDA, please review its SEC filings as well as the associated risk factors contained therein.
ADL = Appeal Denied Letter CRL. = Complete Response Letter. FDRR = Formal Dispute Resolution Request. NDA = New Drug Application. OND = Office of New Drugs. 122021 Focus: Execution of the VALOR-CKD Renal Outcomes Trial
• Time-to-event, randomized, double-blind, placebo-controlled trial
‒ 1,600 subjects (1:1 randomization)
‒ Trial scheduled to end after 511 primary endpoint events
‒ A prespecified interim analysis for early stopping for efficacy
Interim analysis will occur after 250 events
• Primary endpoint: time to first occurrence of renal death, ESRD or a confirmed ≥ 40%
reduction in eGFR (DD40)
Screening
1,600 subjects with Veverimer QD (n~800) End of study:
Treatment
~ 4 Years
serum bicarbonate 511 primary
of 12 – 20 mEq/L, endpoint
eGFR of 20 – 40 events
ml/min/1.73m2 Placebo QD (n~800)
VALOR-CKD has 87% power to detect a 24% reduction in primary endpoint
events in the veverimer group versus placebo
13Making Good Progress in Conducting our VALOR-CKD Renal
Outcomes Trial
As of August 6, 2021, the VALOR-CKD trial has randomized 1,455 of 1,600
subjects with an average treatment duration of ~17 months and has
accrued 127 of the 511 required subjects with positively adjudicated
primary endpoint events (renal death, ESRD, and/or ≥ 40% reduction in
eGFR)
• Due in part to the change in geographic focus, as well as the impact of
COVID-19 on patient recruitment and enrollment, we now expect to
complete enrollment in the first half of 2022
14VALOR-CKD Primary Endpoint Events Continue to Accrue on Track
127 subjects with primary endpoint events as of August 6, 2021
32 additional events since the May 6, 2021, first quarter financial results call
Interim analysis at 250
events:
Anticipated mid-2022
Final analysis:
Anticipated 2024
*127 Subjects with Primary Endpoint Events
Source: Inker et al. JASN 30:1735-1745, 2019, Data on event rates among 2197 control group patients in 29 CKD trials. Required baseline eGFR of 20 to 40 mL/min/1.73m2 15Historical Perspective on Hazard Ratios from Previous Analyses
• Epidemiological studies
– Models show a consistent linear relationship between change in serum bicarbonate and
slowing of CKD progression (7 – 9% lower risk per each 1 mEq/L higher serum
bicarbonate)
• 3.15 mEq/L difference in serum bicarbonate associated with ~24% lower risk of CKD
progression: HR = 0.76
• Prospective treatment studies
– Trials published by de Brito-Ashurst et al, Garneata et al and Dubey et al demonstrated
80%, 69% and 51% lower risk of CKD progression, respectively, with correction of
metabolic acidosis: HR = 0.20, 0.31 and 0.49, respectively
Tangri 2018;Tangri 2021; de Brito-Ashurst 2009; Garneata 2016; Dubey 2020. 16Probability of Stopping for Efficacy at the Interim* or Final Analysis
Probability of Probability of Cumulative
Stopping at the Success at the Probability of
True Hazard Ratio
250-Event Interim Final Analysis Success at the
Analysis (%) 511 Events (%) Final Analysis (%)
0.76 22 65 87
0.70 47 51 98
0.60 88 12 99.99
0.50 99.6 0.4 99.99
• Interim alpha spending approach: O'Brien-Fleming alpha spending function
– Nominal one-sided alpha required for significance at
• Interim analysis: 0. 00153**; observed HR will need to be < 0.67
• Final analysis: 0.0245; observed HR will need to be < 0.83
* If the independent unblinded Interim Analysis Committee does not recommend stopping the trial early for efficacy, we will receive no information from the interim
analysis. ** This represents a change from 0.00151 that was presented when the protocol included both the 150- and 250-event interim analyses. 17Powering Assumptions and Observed Hazard Ratios for Stopping
the VALOR-CKD Trial for Administrative Reasons, if Necessary*
Administrative Stop at:
True Hazard Ratio
150 Events 250 Events
The examples
0.76 39% Power 58% Power provided are for
illustrative purposes.
0.70 59% Power 81% Power An administrative
stop would occur if
we are unable to
0.60 88% Power 98% Power ensure that we have
adequate resources
to complete the trial
0.50 99% Power >99% Power in accordance with
the protocol.
Observed hazard ratio needed for
0.72 Hazard Ratio 0.78 Hazard Ratio
significance
* Assumes no interim analyses have been conducted prior to stopping the trial for administrative reasons. No decision has
been made with respect to an administrative stop at this time. 18Veverimer Market Assessment as a Potential Treatment for Slowing CKD Progression in Patients with Metabolic Acidosis and CKD
We Updated Our Market Assessment to Evaluate the Opportunity for
Veverimer Based Upon a Slowing CKD Progression Target Product Profile
2019 Survey 2021 Survey
Target Product Profile with Serum Bicarbonate Data* Target Product Profile with Outcomes Data*
Treatment with Product X significantly reduced progression
Product X demonstrated a sustained increase in serum
Primary Primary of chronic kidney disease as demonstrated by the reduced
bicarbonate over 1-year. The proportion of Product X treated
Efficacy Efficacy risk of occurrence of the primary composite endpoint (DD40)
patients achieving at least a 4mEq/L increase or
Endpoint Endpoint based on a time-to-event analysis. The projected treatment
normalization of serum bicarbonate
effect yielded a hazard ratio of 0.73
Product X treatment improved both patient-reported and
objective measures of physical function. After 1 year of
treatment, Product X patients demonstrated:
Secondary • 11-point improvement in self-reported ability to perform tasks of daily Secondary
Efficacy living, such as walking multiple blocks and climbing a flight of stairs, Efficacy Same as 2019 survey
Endpoints exceeding the accepted minimal clinically important difference of a 3 to 5 Endpoints
point improvement
• 4.3 second improvement in ability to stand up from a chair 5-times,
exceeding the accepted minimal clinically important difference of 1.7
seconds
Product X was well tolerated with high adherence to
Safety treatment, a safety profile similar to placebo, and no drug- Safety Same as 2019 survey
drug interaction
* These target product profiles are not intended to represent the potential approved label. 20Utilizing a Target Product Profile with Outcomes Data, We Expanded our
Physician Survey
2021 Survey Participants Included Nephrologists,
Cardiologists, Endocrinologists and PCPs
100
90 Nephrologist
Cardiologist
44% 38%
80 (n=71)
70
60
50 Endocrinologist
33%
40 Non-nephrologist
56%
30 (n=91)
20 PCP
29%
10
0
Total Non-nephrologists
PCP = Primary Care Physician. Tricida 2021 survey conducted May-June 2021. 21Approval of Veverimer for Slowing of CKD Progression Could
Expand the Addressable Patient Population
Prevalence of Metabolic Acidosis in Patients with CKD and
Estimated Number of Patients Treated by Physician Type
Increased awareness drives higher metabolic 3,000,000
acidosis diagnosis and treatment Patients with CKD
and metabolic Expanded Market Opportunity
acidosis
Outcome data related to slowing CKD progression
could expand the market opportunity for veverimer
Expansion to non-nephrologist-treated 1,100,000
patients provides additional opportunity Diagnosed
for veverimer patients
Focus on nephrologist-treated patients ~600,000 Focused Market Opportunity
provides initial opportunity for veverimer High-prescribing nephrologists believe there is a link between
Nephrologist-
treated metabolic acidosis and kidney, bone and muscle health
patients
Data on file. 2019 US Census data. USRDS ADR 2017. Inker LA et al., JASN 2011.
Note: The market potential is based on the target product profile and could change based on actual label approved by FDA 22New Physician Survey Shows Strong Interest in Veverimer Based
Upon Slowing CKD Progression
2019 TPP with Serum Bicarbonate Data 2021 TPP with Outcomes Data
100% 100% 93%
Definitely 80%
79%
or
80%
71%
Probably
60% 60%
Would 40% 40%
Prescribe 20% 20%
0%
Not Tested
0%
Nephrologist Non-Nephrologist Nephrologist Non-Nephrologist
100% 100%
80% 80% 74%
Peak
58%
Patient 60% 52% 60%
Penetration 40% 40%
20% 20%
Not Tested
0% 0%
Nephrologist Non-Nephrologist Nephrologist Non-Nephrologist
23
TPP = Target Product Profile. Peak patient penetration survey results are unadjusted and assume price is not an issue and there is insurance coverage.Managed Markets Research Update
Objectives Key Findings
• Disease-modifying mechanism of
Conducted new payer survey action and correlation to risk reduction
incorporating the Target remains a headline
Product Profile based upon • Outcomes-based endpoint / indication
is a net positive
outcomes data (DD40) with
• Ability to deliver cost offsets rounds
11 payers: 3 Pharmacy out the strong value story
Benefit Managers, 3 National
Plans, 5 Regional Plans ~$36,000 per year is considered by
survey respondents to be a
“reasonable” price and is in the same
range as previous survey results.
DD40 = Renal death, ESRD or ≥ 40% decline in eGFR. 24Positive VALOR-CKD Data Has the Potential to Support an Expanded Veverimer Development Program
In Patients with CKD, Acid (H+) Retention is Mitigated by Multiple Biological Strategies:
Serum Bicarbonate Levels Are a Lagging Indicator of Acid Retention
Interaction between Acid Mitigation Strategies
Wesson DE, CJASN, 2021. HCO3- = bicarbonate, H+ = Proton or hydrogen ion, NH4+ = ammonium, NH3 = ammonia, CO32- = carbonate, PO43- = phosphate, CO2 =
carbon dioxide, H2O = water 26Veverimer Was Designed to Supplement Acid Excretion in
Patients with Metabolic Acidosis and CKD
Normal Acid Excretion Kidney Unable to Fully Excrete Acid Load Veverimer Binds and Removes Acid
Endogenous acid production Endogenous acid production Endogenous acid production
Acid load is quantitatively titrated by Acid load exceeds available Smaller acid load is
HCO3- derived from: HCO3-. Additional quantitatively titrated by
HCl bound to veverimer
eliminated via GI tract
Acid retention
mechanisms are recruited HCO3- derived from:
• Net acid excretion from kidney to increase HCO3-.
• Net acid excretion from
• Upregulation of hormones
• Organic acid metabolism kidney
by the kidney
• Base absorption from GI tract • Muscle protein catabolism • Organic acid metabolism
to release glutamine
• Base absorption from GI
• Bone dissolution to
tract
release carbonate and
phosphate
H+ excreted Excess H+ excreted H+
H+ excreted H+ excreted as NH4+ H+ excreted H+ excreted
as NH4+ and Acid is NOT as NH4 and excreted
+
as CO2 gas and titratable acid as CO2 gas as CO2 gas
titratable acid Excreted titratable acid as HCl
Wesson DE, CJASN, 2021. Alpern RJ and Sakhaee K, AJKD, 1997. Klaerner G et al, J Pharmacol Exp Ther. 2020. Wesson DE et al, Lancet, 2019 27Potential for Future Veverimer Trials Could Parallel the Expanded
Opportunity Seen with SGLT2 Inhibitors
CREDENCE DAPA-CKD EMPA-
VALOR-CKD VICTORY-CKD TRIUMPH-CKD CKD indication for
Ongoing trial Future trial Future trial
CKD indication for KIDNEY
canagliflozin approved dapagliflozin
Results expected for
Study inclusion: Study inclusion: Study inclusion: in 2019 approved in 2021
empagliflozin in
eGFR 20 to 40 and eGFR 20 to 60 and eGFRFinancial Position
• ~ $175.8 million cash, cash equivalents
and investments as of June 30, 2021
• Debt includes:
‒ $200 million of 3.50% Convertible Senior
Notes due 2027
• ~ 50 million total shares outstanding as of
June 30, 2021
29THANK YOU
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