UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
September 25, 2017
Date of Report (Date of earliest event reported)
Flex Pharma, Inc.
(Exact name of registrant as specified in its charter)
Delaware | 001-36812 | 46-5087339 | ||
(State or other jurisdiction | (Commission File Number) | (IRS Employer Identification No.) | ||
of incorporation) | ||||
800 Boylston Street, 24th Floor Boston, MA | 02199 | |
(Address of principal executive offices) | (Zip Code) | |
Registrant’s telephone number, including area code: (617) 874-1821
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligations of the registrant under any of the following provisions:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x
Item 7.01. Regulation FD Disclosure.
A copy of the slide presentation that will be used by representatives of Flex Pharma, Inc. (the "Company") in connection with investor meetings or presentations from time to time (the "Corporate Presentation") is attached to this Current Report on Form 8-K as Exhibit 99.1. The Corporate Presentation is current as of September 25, 2017, and the Company disclaims any obligation to correct or update this material in the future.
The information in this Form 8-K (including Exhibit 99.1) shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
The following exhibit relating to Item 7.01 shall be deemed to be furnished, and not filed:
Exhibit No. | Description | ||
99.1 | Corporate Presentation current as of September 25, 2017 | ||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Flex Pharma, Inc. | ||
Dated: September 25, 2017 | ||
By: | /s/ Robert Hadfield | |
Robert Hadfield | ||
General Counsel and Secretary | ||
INDEX TO EXHIBITS
Exhibit No. | Description | ||
99.1 | |||
Novel Treatments for Severe Neurological Diseases
NASDAQ: FLKS
September 2017
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, 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.
This presentation also contains estimates and other statistical data made by independent parties and by the company relating to market size and
growth and other data about the company’s industry. This data involves a number of assumptions and limitations, and you are cautioned not to give
undue weight to such estimates. In addition, projections, assumptions and estimates of the company’s future performance and the future performance
of the markets in which the company operates are necessarily subject to a high degree of uncertainty and risk.
This presentation contains references to our trademarks and to trademarks belonging to other entities. Solely for convenience, trademarks and trade
names referred to in this presentation, including logos, artwork and other visual displays, may appear without the ® or TM symbols, but such
references are not intended to indicate, in any way, that their respective owners will not assert, to the fullest extent under applicable law, their rights
thereto. We do not intend our use or display of other companies' trade names or trademarks to imply a relationship with, or endorsement or
sponsorship of us by, any other companies.
Forward-Looking Statements
3
Chemical neurostimulation, a therapy based upon novel TRP ion channel biology
from our co-founders (MacKinnon Nobel Prize 2003).
Insights in neuromuscular physiology led to a potential treatment for severe and
debilitating muscle cramps and spasticity in neurodegenerative diseases
Focus on Severe Neurological diseases with FLX-787:
• Exploratory MS Spasticity (Australia)
• ALS Phase 2 (US Fast Track Designation)
- ≈ 20k patients in US1
• CMT Phase 2 (US) initiating Q3 2017
- ≈ 150k patients in US2
Human safety & efficacy assessed in electrically-induced cramps (EIC) and
spontaneous, nocturnal leg cramps (NLC) in human subjects:
• EIC model produced sigmoidal dose response curve (p<0.05)
• Efficacy signals in randomized, blinded, controlled, POC studies with FLX-787 in subjects with NLC
• Safety and tolerability assessed in 200+ subjects
1 ALS Association / 2 Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review. Neuroepidemiology 2016; 46:157-165. NIH National Library of Medicine /
Flex Pharma Overview
4
ANTICIPATED TIMELINE
FLX-787
Single agent TRP activator
2017 2018 2019
Multiple Sclerosis (MS)
Amyotrophic Lateral
Sclerosis (ALS)
Charcot-Marie-Tooth
(CMT)
Flex Pharma Development Path
Phase 3
Exploratory Spasticity
Cross-over
Australia
Spasticity
IND
Phase 2
US
Cramp
IND
Phase 2
US
Fast Track Designation
Phase 3Phase 2US
Data
EOP2
EOP2
Data
Data
Data
MS
IND
Cramp
IN
Cramp
IND
THE PROBLEM:
Cramps & Spasticity
6
No FDA approved treatment
95% of ALS patients report cramps1
Cramps can be frequent: median of 4 cramps/day 2
55% of ALS patients with pain attributed that pain to muscle cramps 3
57% of ALS patients to seek treatments directed at limiting cramps.4
Cramping interferes with sleep and reduces QoL for patients suffering from
degenerative neurological diseases 5
1 Caress, JB, et al, Muscle Nerve. 2016 April;53(4): 513-517./ 2 Stephens HE 2016, Caress JB 2016, Weiss MD 2016, Weber M 2010,/ 3 Bedlack RS, 2009 Stephens, Joyce, Oskarsson. National Study of Muscle
Cramps in ALS in the USA, 2016a / 4 Ganzini et al, Correlates of suffering in amyotrophic lateral sclerosis. Neurology 1999 Apr 22;52(7):1434-40. / 5 Hanisch F, Skudlarek A, Berndt J, Kornhuber ME, Brain Behav. 2015
Mar;5(3)
FLX-787 granted Fast Track designation for the treatment of
severe muscle cramps associated with ALS (July 2017)
Severe and Debilitating Muscle Cramps: Significant
Morbidity and Medical Need in Neurological Diseases
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Baclofen
• Spasticity Tx, Limited cramp efficacy
• Sedating, ataxia (incoordination),
memory problems
Quinine • Malaria Tx, Not approved for NLC• Black Box warning
Mexilitine • Anti-arrhythmia• Black Box warning
Benzodiazepines • Sedating, ataxia• Addictive
Limitations of Current Cramp Treatments
Many patients seek and receive treatments that are ineffective or un-safe1
F
r
e
q
u
e
n
c
y
o
f
U
s
e
1 Stephens, Joyce, Oskarsson. National Study of Muscle Cramps in ALS in the USA, 2016a
Mexilitine BLACK BOX
Increased Mortality
excessive mortality or nonfatal
cardiac arrest rate (7.7%
encainide/flecainide vs. 3% placebo)
in asymptomatic non-life-threatening
ventricular arrhythmias w/ MI 6 days -
2 years prior; restrict use to life-
threatening ventricular arrhythmias,
no survival benefit in pts w/o life-
threatening arrhythmias
Quinine BLACK BOX
Hematologic Toxicity
serious and life-threatening toxicity
incl. thrombocytopenia and HUS/TTP
may occur w/ use for nocturnal leg
cramp tx or prevention; TTP-assoc.
chronic renal impairment reported;
risk assoc. w/ nocturnal leg cramp
use in absence of evidence of
efficacy does not outweigh any
potential benefit
The Science
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The Origin of Muscle Cramping:
Literature Review
Cramps are generally NOT caused by dehydration, lactic acid build-up
or electrolyte imbalances affecting the muscle 1,2
1. MillerK, Current Sports Medicine Reports, Review 1537-890X/1405/353-354, 2015. / 2. MinettoMA, HolobarA, BotterA, and Farina D. Exerc. Sport Sci. Rev.41(1): 3-10, 2013.
Muscle cramps are neurogenic in origin, and caused by the
hyperexcitability of alpha-motor neurons
Muscle cramping is caused by excessive
firing of hyperexcitable alpha-motor
neurons originating in the spinal cord,
resulting in painful muscle contractions
Neurodegenerative diseases induce this
hyperexcitability through diminished
inhibition, causing them to fire
excessively and trigger crampingAlpha-motor neuron
Satkuna L. Rehabilitation medicine: 3. Management of Adult Spasticity. CMAJ 169(11) 25 Nov 2003
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Hyperexcitable Motor Neurons from ALS Patients
Control-derived ALS-derived
Inducible pluripotent stem cell
lines from healthy normal and ALS
patients were differentiated to
motor neurons
Stimulated motor neurons from
ALS patients were hyperexcitable,
relative to controls
Wainger BJ, Kiskinis E, Mellin C, Wiskow O, Han SS, Sandoe J, Perez NP, Williams LA, Lee S, Boulting G, Berry JD, Brown RH Jr, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ.
Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 2014 7:1-11.
11
Vagal Nerve Stimulation:
A Proven Therapeutic Approach
Early anatomical drawing of the vagus nerve.
Source: Wellcome Library/Public Domain
Electrical Stimulation
of the vagal nerve is FDA
approved for:
Treatment-resistant
epilepsy (1997)
Treatment-resistant
depression (2005)
Cluster headaches (2017)
Chemical Neurostimulation
from topical treatment of
nerves in the mouth and
throat:
Selective chemical
stimulation of TRPV1 and
TRPA1 ion channels on the
vagal, glossopharyngeal, and
facial nerves resets
descending inhibition via the
spinal cord
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MOA for Topical Modulation of CNS by FLX-787:
Stimulation-Processing-Motor Output
Spicy!
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
Firing of alpha-motor
neurons slows down halting
muscle cramp
1
2
3
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Muscle Cramping:
ALS, CMT, MS, Renal Dialysis,
Chemotherapy Induced Nausea,
Hereditary Spastic Paraplegia
Autonomic Control:
Migraine/Cluster Headache, Overactive
Bladder, Obstructive Sleep Apnea,
Raynaud’s, Gastroparesis, Emesis,
Menstrual Cramping
Non-autonomic Control
(complex motor):
Cervical Dystonia, Bruxism, Dysphagia
Neuro-Psychiatric:
Epilepsy, Depression, PTSD, Tinnitus,
Panic Attack
Potential Applications of Chemical Neurostimulation
1. Muscaritoli M, et al, Nutrition(2012) 28(10):959–66; 2. Onesti E, et al, Frontiers in Neurology. 2017;8:94; 3. Cook IJ, Kahrillas PJ. Gastroenterology 1999; 116: 455-78.; 4. K Tjaden, Top Geriatr Rehabil. 2008 ; 24(2):
115–126; 5. National Institute on Deafness and Other Communication Disorders [NIDCD], n.d.; Steele, Greenwood, Ens, Robertson, & Seidman-Carlson, 1997; 6. Kawashima, Motohashi, & Fujishima, 2004; 7. Serra-Prat
et al., 2011; 8. AHCPR, 1999; 9. Rofes, LJ Gastroenterol (2014) 49:1517–1523; 10.Hirata A, et al, Biol. Pharm. Bull. 39, 1107–1111 (2016)
Dysphagia (Difficult/Unsafe Swallowing):
• Dysphagia emerges in more than 80% of ALS patients
during the advanced phases of the disease1
• Over a ~2 year period, the % of ALS patients suffering
from dysphagia increased to 73% in patients with spinal
onset and 98% in those with bulbar onset.2
Aspiration pneumonia is a common cause of death in
ALS3
• 40% to 95% of persons with Parkinson Disease have
dysphagia4
• Up to 38% of the elderly (>65 YOA) living independently,
and up to 68% of those in long-term care have
dysphagia5,6,7
• 1/3 of patients with dysphagia develop pneumonia each
year, and 60k die from their pneumonia8
• TRP channel activators from pepper9 and ginger
extracts10 have been shown to improve swallowing in the
elderly.
Clinical Development
15
Electrically-induced
cramp model for:
1. POC
2. Optimization of
extract formulation
Evolution of Flex Pharma R&D
2014 2015 2016 2017 2018
Compositional Analysis
Numerous TRP activators
Isolation of single-agent dual
TRPA1/V1 activator, FLX-787
• Optimized Consumer
Beverage
• Natural & Organic,
non-GMO Extract Blend
Synthesis of pure,
pharmaceutical grade
FLX-787
Formulation of FLX-787
as orally disintegrating
tablet
US IND open
Well-controlled
studies in severe,
neurodegenerative
diseases
Original
Proprietary
Extract
Formulation R&D
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TRP Ion Channel Co-crystal Structures –
Flex Drug Targets in Nature Papers1
1 TRPV1: E. Cao, M. Liao, Y. Cheng and D. Julius, Nature, 5 Dec 2013 / TRPA1: C.E. Paulsen, J. Armache, Y.
Gao, Y. Cheng and D. Julius, Nature, 8 April 2015
TRPA1TRPV1
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Synergistic Effects of TRPA1 & TRPV1 Activation
Co-activation of TRPV1 and TRPA1 channels is synergistic, resulting in
strong, sustained firing of sensory nerves
Potentiation of [Ca2+]i by TRPV1 and TRPA1 activators in isolated
human dorsal root ganglion (DRG) neurons
0 100 200 300
-0.1
0.0
0.1
0.2
0.3
0.4
Time (sec)
F
/
F
100 uM TRPA1 agonist
50 nM TRPV1 agonist
TRPA1+TRPV1 combo
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FLX-787: Dose Dependent Inhibition of EIC in HNV
Presented at Society for Neuroscience Nov. 15, 2016; Presentation Number: 537.15
• HNV = Healthy Normal Volunteers
• AUC = Area under the Curve (intensity & duration) of electromyogram of the cramping muscle (flexor hallucis brevis)
• 6 doses of FLX-787 (n=5, p<0.05)
30 mg Phase 2 dose
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FLX-787: Efficacy in Human Cramp Subjects
Spontaneous Cramps (NLC)*
(BV-003; N=26/63)
Induced Cramps (EIC)
(Flex-015; N=9)
* 26 of 63 questionnaire respondents, of 72 subjects enrolled, were independently adjudicated as having possible or probable NLC.
Presented at ACTRIMS, Feb 2017. Poster “ Flex-201: A Multicenter, Randomized, Blinded Study to Evaluate the Efficacy and Tolerability of FLX-787 in MS.”
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Screening
Period 1
Run‐In
Placebo capsules
Period 2
Cross‐
Over
FLX‐787
Period 2
Cross‐Over
Control
7 day follow
up call
14 days
14 days
14 days
Period 3
Cross‐
Over
Control
14 days
Period 3
Cross‐
Over
FLX‐787
14 days
MS – Spasticity
• n<60, Cross-Over design
• 19mg BID FLX-787 liquid vs. placebo
• Spasticity, cramps/spasms, pain, sleep, QoL, safety
• Trends/Signals in Q1 2018
ALS – Cramping
• N=11, Cross-Over design
• Expected only to inform conduct of COMMEND trial
• Data Q4 2017
7‐14 day
washout
Ongoing Exploratory Spasticity Study in MS
Under Australian CTN
Randomization
Randomization Criteria
• Mean NRS spasticity scores >6
• >6 spasms/cramps
• Score of 3‐7 on the CGI‐spasticity scale
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Ongoing Phase 2 Studies in ALS & CMT
Randomized, Blinded Phase 2 Trials under US IND
• ALS: Cramps, spasticity, ALS-FRS, pain (PGIC), sleep, QoL, safety
• CMT: Cramps, pain (PGIC), sleep, QoL, safety
• 30mg FLX-787 ODT three times daily vs. Control
• Parallel design, N~100
• Data 3Q 2018
FLX‐787‐ODT
28 days
ODT Control
28 days
Subjects excluded if:
<5 cramps/wk
OR ≥50% drop in cramp frequency wk 1 vs wk4)
OR not dosing/diary compliant
Screening
(Estimated ≥ 3
cramps week prior.
≥ 12 cramps last
month)
R
a
n
d
o
m
i
z
a
t
i
o
n
Run‐in
Control‐ODT
28 days
7‐day safety
follow‐up call
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Safety
Over 200 subjects tested with
extract and/or FLX-787 for
safety and anti-cramp efficacy
Initial PK data (n=5) detected1
no drug in plasma; effect is
“topical” in mouth, tongue, and
throat
Robust human data set
No drug-related SAEs
Mostly GI-related AEs
(“hot”/“spicy” taste,
nausea, diarrhea)
Vast majority are mild
to moderate, transient,
and self-limiting
Adverse events
Human Safety Experience
1. LLOQ = 0.1 ng/mL (PK study, NESCA-015, n=5 subjects)
CFR 21 Part 182 – Natural
product extracts Generally
Regarded as Safe (GRAS)
23
FDA Written Guidance
FDA written guidance informs FLX-787 development for ALS and CMT*
Fast Track designation for ALS Cramps facilitates FDA interaction and
allows rolling NDA
Regulatory Guidance
• Endpoint: change in cramp frequency “could be an acceptable primary efficacy
endpoint”; must also show that reduction in cramp frequency “is clinically
meaningful to patients”
• Design: Recommend using parallel-designed trials
• Regulatory Path: “a 4-week study and a 3-month study may be sufficient to provide
substantial evidence of efficacy”
Following the completion of its Phase 2 studies, Flex will seek further
regulatory guidance for each indication
* Based upon NLC pre-IND written guidance and ALS IND comments
24
Management Team
• William McVicar, PhD, President & CEO; Sandoz/Novartis, Rhone Poulenc Rorer, Sepracor, Inotek
• David Golod, PhD, VP Clinical Operations; Vertex
• Rob Hadfield, General Counsel; Cooley LLP, Kiva Systems, SG Cowen
• John McCabe, CFO; Ariad, Charles River Associates, Biogen, Arthur Andersen
• Glenn Short, PhD, VP, Non-Clinical and Translational Research; CombinatoRx, Zalicus
• Angelene Simonello, VP Corporate and Program Development; Viacell, Biogen
• Thomas Wessel, MD PhD, CMO; J&J (Razadyne®), Sepracor (Lunesta®), Acorda (Ampyra®)
• Elizabeth Woo, SVP, Investor Relations; Biogen, Ironwood, Cubist
Board of Directors
• Christoph Westphal, MD PhD, Chairman; Cofounder/Lead investor ALNY MNTA XLRN SIRT Alnara CNCE
VSTM OVAS
• Jeff Capello, CFO Beacon Health; BOD OVAS, former Boston Scientific CFO, PKI, PWC
• Peter Barton Hutt, former Chief Counsel FDA; Sirtris, Momenta, Concert, Covington and Burling
• Marc Kozin, LEK Consulting, former President of North American practice; BOD OVAS, ECYT, DYAX, UFPT
• Rod MacKinnon, MD, Co-founder, Chair, SAB; Nobel Prize 2003, ion channels; Professor, Rockefeller; NAS
• Rob Perez, former CEO Cubist; former Biogen, BOD AMAG, CDTX
• Stuart Randle, Ivenix CEO, former CEO GI Dynamics, former CEO ACT Medical, Baxter
• Michelle Stacy, former Keurig President, Gillette/P&G, BOD iRobot
Management Team and Board of Directors
25
Scientific Advisory Board
Scientific Advisory Board
• Rod MacKinnon, MD, Cofounder, Chair, SAB; Nobel Prize 2003, ion channels; Professor,
Rockefeller; National Academy of Science (NAS)
• Bruce Bean, PhD, Cofounder, Chair, SAB; Winthrop Professor, Harvard Med;
Neurophysiology; NAS
• W. Larry Kenney, PhD; Penn State Univ Professor Physiology
• Alfred Sandrock, MD, PhD; Neurologist, Chief Medical Officer of Biogen
• Roger Tung, PhD; Medicinal chemist, Vertex, Merck (inventor multiple drugs); CEO, Concert
• Chris Walsh, PhD; Professor Emeritus, Harvard Med; Genzyme, Verastem, Sirtris; NAS
• John Winkelman, MD, PhD; Chief Sleep Disorders, MGH; BWH, RLS clinical development
26
Financial Profile
NASDAQ: FLKS
~$47 M Cash balance as of 6/30/17
Cash into early 2019 based on
current operating plan
~17.9 million shares outstanding
No debt
27
Phase 2a (POC) Phase 2b
ALS (US IND; N = 100)
ALS (2nd Endpoint; US IND; N = 100)
FLX-787 for Cramps
FLX-787 for Spasticity
MS (Australian CTN; N ≈ 45-50)
Charcot Marie Tooth (US IND; N = 100)*
FLX-787 for Dysphagia
ALS – dysphagia/tongue fasciculations
(US IND; N ≈ 10-15)*
Renal Dialysis (US IND; N ≈ 10-20)
Natural history*
Intervention†
Clinical Program of FLX-787: Therapies for
Neurologic Diseases and their Symptoms
* Initiation planned 3/4Q2017; † Initiation 2018
28
Anticipated Upcoming Milestones
H1 2017: File IND (Effective April)
July 2017: Fast Track Designation for ALS
Q3 2017: Initiate ALS/MND Phase 2 parallel-design study (US)
Q3 2017: Initiate CMT Phase 2 parallel-design study (US)
2018: Clinical Readouts
• Exploratory MS Spasticity Phase 2 study (Australia)
• Phase 2 ALS trial (US)
• Phase 2 CMT trial (US)
• Phase 1/2a Renal Dialysis cramping studies
• Phase 1/2a Dysphagia (swallowing)/tongue fasciculations studies in ALS
Novel Treatments for Neuromuscular Conditions
NASDAQ: FLKS