Attached files
| file | filename |
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| EX-99.1 - EXHIBIT 99.1 - Salarius Pharmaceuticals, Inc. | pressrelease991.htm |
| 8-K - 8-K - Salarius Pharmaceuticals, Inc. | a8-kms.htm |
FLEX-201: Exploratory Study of FLX-787 in
Multiple Sclerosis Patients
NASDAQ: FLKS
March 2018
2
Any statements in this presentation and the oral commentary about future expectations, plans and prospects for the company, including statements
about the company’s strategy, future operations, ongoing clinical trials, development of its consumer and drug product candidates, plans for potential
future product candidates and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,”
“project,” “suggest,” “target,” “potential,” “will,” “approximately,” “development plans,” “would,” “could,” “should,” “continue,” and similar expressions,
constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially
from those indicated by such forward-looking statements as a result of various important factors, including: the status, timing, design, costs, results
and interpretation of the company’s clinical studies; the uncertainties inherent in conducting clinical studies; results from our ongoing and planned
preclinical development; expectations of our ability to make regulatory filings and obtain and maintain regulatory approvals, our ability to commercialize
our consumer products; positioning and product attributes of our consumer products; results of early clinical studies as indicative of the results of
future trials; availability of funding sufficient for the company’s foreseeable and unforeseeable operating expenses and capital expenditure
requirements; other matters that could affect the availability or commercial potential of the company’s consumer or drug product candidates; the
inherent uncertainties associated with intellectual property; and other factors discussed in the Risk Factors set forth in the company’s Annual Report
on Form 10-K filed with the Securities and Exchange Commission (SEC) and in other filings the company makes with the SEC from time to time. We
may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on
our forward-looking statements. The forward-looking statements in this presentation represent our views as of the date of this presentation. We
anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking
statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore,
not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation.
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Forward-Looking Statements
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Electrically-induced
cramp model for:
Origins of FLX-787: A Single Molecule, Dual
TRPV1/A1 Activator
2014 2015 2016 2017 2018
Compositional Analysis
Numerous TRP activators
Isolation of single-agent dual
TRPA1/V1 activator, FLX-787
Synthetic pharmaceutical
grade FLX-787
Formulation of FLX-787
as an orally disintegrating
tablet
US IND open
Well-controlled
studies in severe,
neurodegenerative
diseases
Original
Proprietary
Extract
Formulation
Flex
R&D
Optimized
Consumer Beverage
4
MOA for Topical Modulation of the CNS by FLX-787:
Stimulation-Processing-Motor Output
Sensation
Alpha-motor neurons
connecting to muscle
Spinal cord
Descending
Inhibitory
Pathway
Nerves
Central processing in
brainstem leads to
inhibition through
descending fibers in spinal
cord
Sensory neurons with
TRPA1/V1 channels
stimulated by FLX-787
Descending inhibition
reduces: 1) alpha-motor
neuron hyperexcitability
halting muscle cramps and
2) reflex hyperexcitability
attenuating spasticity
1
2
3
5
Objectives and Design:
• Explore the potential of chemical neurostimulation with FLX-787 to improve
spasticity and decrease cramps/spasms in patients with MS
• Determine the patient characteristics and study design most sensitive to observed
clinical improvements by FLX-787 for incorporation into future regulatory trials
Study Design:
• A multi-center trial studying MS patients suffering from spasticity and
cramps/spasms
• A randomized, double-blind, placebo-controlled, 14-day per period crossover study
• Evaluated the effects of FLX-787 across multiple MS-associated endpoints
including muscle cramp/spasm frequency and spasticity
• Assessed the efficacy of FLX-787 when self-administered BID as an oral solution
containing 19 mg
Exploratory MS Study: Proof of Concept
FLX-787
FLX-787Inactive Control
Inactive
Control
Run-in
Placebo
Washout
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Multiple Signals of Biological Activity:
In pre-specified analyses of the parallel portion of the study, anti-
cramp/spasm and anti-spasticity activity was observed:
• 27.3% decrease in Cramp/Spasm Frequency (p=0.001)
• 1.4 day increase in Cramp-free Days (p=0.0457)
• Treating physicians reported that 7 of 28 FLX-787 patients had
“Much Improved” or “Very Much Improved” spasticity versus 0 of 26
on Control (Clinical Global Impression of Change in Spasticity)
Successful Exploratory MS Study Showing FLX-787
Activity Across Multiple MS-Associated Endpoints
7
• In a pre-specified analysis that included both cross-over periods, a
significant anti-spasticity effect was observed with FLX-787, when
compared to Control, as measured by CGI-C for spasticity (p=0.0427)
- CGI-C Responders (defined as “Much Improved” or “Very Much
Improved”) were more prevalent on FLX-787 (N=13/54) versus control
(N=2/52) (p=0.004, post-hoc analysis)
• No statistically significant improvement in cramp/spasm frequency, NRS or
clinical spasticity scales from data that included both cross-over periods
(ITT)
Successful Exploratory MS Study Showing FLX-787
Activity Across Multiple MS-Associated Endpoints
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• FLX-787 at doses up to 19 mg (BID) in an oral solution was generally well
tolerated
• No treatment-related SAEs occurred during the study
• The most-commonly reported AEs with FLX-787 were GI-related, mild to
moderate, and self-limiting
• 2 subjects (1 Control; 1 Placebo) and 3 FLX-787 subjects discontinued the
study due to an adverse event
• No clinically relevant laboratory, vital signs or ECG abnormalities were
noted
Summary of Safety
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• Cross-over design studies typically have more power to compare within
patients but can be subject to confounding factors
• Specifically, FDA has identified the following concerns that could impact the
interpretation of cross-over studies with FLX-787:
- Carryover effects
- Drop-outs, especially between periods
- Unblinding
- Sequence and period effects
- Learning effects which may be different in each period
- Interpretability of results from the second period
Parallel Period Analysis Simulates Blinded Parallel
Group Design Without Cross-over Limitations
FLX-787
FLX-787 Inactive Control
Inactive
Control
Run-in
Placebo
Washout
Parallel Period of Study
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• In pre-specified Parallel Period Analyses, FLX-787 decreased the number
of Cramps/Spasms and increased Cramp-free Days (changes from baseline
in cramp/spasm population, over a 14-day treatment period)
• The results from data that included both cross-over periods were not
statistically significant
FLX-787 Significantly Decreased Cramps/Spasms and
Increased Cramp-free Days
Efficacy Endpoint FLX-787 Control p-value
Change in Cramp/Spasm
Frequency -9.7 2.9 0.0017
%Change in Cramp/Spasm
Frequency -27.3% 14.2% 0.0010
Change in Cramp Free Days 1.4 0.0 0.0457
Table 14.2.1.29.2.c
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• 7/28 (25%) on FLX-787 vs 0/26 (0%) on Control were judged by the treating
physician as “Much Improved” or “Very Much Improved”
• Comparison of the proportions with Fisher’s exact test confirmed this difference to
be statistically significant (p=0.01)
FLX-787 Improved Spasticity by CGI-C
(Parallel Period Analysis)
Score Placebo
(Run-in, n=57)
FLX-787
(n=28)
Inactive Control
(n=26)
Very Much Improved (1) 0 (0%) 0 (0%) 0 (0%)
Much Improved (2) 0 (0%) 7 (25%) 0 (0%)
Minimally Improved (3) 6 (11%) 10 (36%) 6 (23%)
No Change (4) 35 (61%) 7 (25%) 10 (38%)
Minimally worse (5) 12 (21%) 3 (11%) 10 (38%)
Much Worse(6) 3 (5%) 1 (4%) 0 (0%)
Very Much Worse (7) 1 (2%) 0 (0%) 0 (0%)
p=0.01
Clinicians were asked to “rate total improvement of Spasticity and whether or not, in your clinical
judgement, it is due entirely to drug treatment”.
CGI-C
Responders
12
Score Placebo
(Run-in, n=57)
FLX-787
(n=54)
Inactive Control
(n=52)
Very Much Improved (1) 0 (0%) 1 (2%) 0 (0%)
Much Improved (2) 0 (0%) 12 (22%) 2 (4%)
Minimally Improved (3) 6 (11%) 14 (26%) 18 (35%)
No Change (4) 35 (61%) 19 (35%) 18 (35%)
Minimally worse (5) 12 (21%) 5 (9%) 12 (23%)
Much Worse(6) 3 (5%) 3 (6%) 1 (2%)
Very Much Worse (7) 1 (2%) 0 (0%) 1 (2%)
Source: Table 14.2.1.29.1.a, 14.2.1.23a, file 2018-03-18_ivrsnumtabCA17071_stat)
FLX-787 Improved Spasticity by CGI-C
(Both Crossover Periods)
Clinicians were asked to “rate total improvement of Spasticity and whether or not, in your clinical
judgement, it is due entirely to drug treatment”.
p=0.0427
CGI-C
Responders
13
FLX-787 Reduced Cramps/Spasms in First
Treatment Exposure Anaysis
Run-in 1st Crossover 2nd Crossover
35.1
Δ+2.9
Control
Δ-5.0
FLX-787
20.5
Δ-9.7
FLX-787
Δ-1.6
Control
M
ed
ia
n
C
ra
m
p/
S
pas
m
F
re
qu
en
cy
FLX-787
Effect
FLX-787
Effect
Tables 14.2.1.1.2.c
p= 0.0003
To correct for baseline imbalance and potential sequence and temporal effects,
post-hoc analyses evaluated first exposure to drug, and change from previous
treatment as baseline (serial period analysis)
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• Reduction in Cramp/Spasm Frequency
• Increase in Cramp-free Days
• Greater number of patients assessed with spasticity “Much Improved” or
“Very Much Improved”
• FLX-787 was generally well tolerated with minor GI side effects.
Based on this evidence of FLX-787-mediated biological activity in MS
patients, we are planning our Phase 2b program
Overall Summary: FLX-787 Improved
Cramps/Spasms and Spasticity in MS Patients
15
Longer run-in to account for disease variability
Longer treatment periods to allow greater time to achieve
maximal drug effect
Parallel treatment design
Increased dosing frequency (BIDTID)
Explore dose range (higher doses e.g.)
Use orally-disintegrating tablet with longer oral residence time
Optimized patient characteristics
Future Phase 2b MS Cramping and Spasticity Trial
Novel Treatments for Neuromuscular Conditions
NASDAQ: FLKS