Downing v. Anavex Life Sciences Corporation — Entry #23: DECLARATION of Theodore L
Case: Downing v. Anavex Life Sciences Corporation nysd · 1:24-cv-03529
filed May 08, 2024
What this document is
Docket entry #23 · filed August 23, 2024
DECLARATION of Theodore L. Kornobis in Support re: 22 MOTION to Dismiss .. Document filed by Anavex Life Sciences Corporation, Christopher U. Missling. (Attachments: # 1 Exhibit Form 10-K, # 2 Exhibit Form 10-K, # 3 Exhibit Press Release, # 4 Exhibit Transcript, # 5 Exhibit Presentation, # 6 Exhibit Report, # 7 Exhibit Earnings Call, # 8 Exhibit Transcript, # 9 Exhibit Press Release, # 10 Exhibit Press Release, # 11 Exhibit Press Release).(Kornobis, Theodore) (Entered: 08/23/2024)
Who is involved
- Anavex Life Sciences Corporation
- Christopher U. Missling
- Kenneth Downing
Why we have it
We follow this case because it names a company we track, although that company is not a party:
- CleanSpark: its name “CleanSpark, Inc.” appears in a filing in this case.
…Page(s) Bishins v. CleanSpark, Inc., No. 21-cv-511 (LAP), 2021 WL 5741574 n…
A free copy from the RECAP archive of federal court filings (mirrored at the Internet Archive), retrieved October 25, 2026. Federal court filings are public records.
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Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 1 of 13
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 2 of 13
EXHIBIT 99.1
Forward Looking Statement
This presentation contains forward-looking statements made within the meaning of the Private Securities Litigation
Reform Act of 1995 by Anave x® Life Sciences Corp. and its representatives. These statements can be identified by
introductory words such as "expects," "plans," "intends," "believes," "will," "estimates, " "forecasts ," "projects," or words of
similar meaning, and by the fact that they do not relate strictly to historical or current facts. Forward-looking statements
frequently are used in discussing potential product applications, potential collaborations, product development activities,
clinical studies, regulatory submissions and approvals, and similar operating matters. Many factors may cause actual
resu lts to differ from forward-looking statements, including inaccurate assumptions and a broad variety of risks and
uncertainties, some of which are known and others of which are not. Known risks and uncertainties include those
identified from time to time in reports filed by Anavex Life Sciences Corp. with the Securities and Exchange
Commission, which should be considered together with any forward-looking statement. No forward-looking statement is
a guarantee of future results or events, and one should avoid placing undue reliance on such statements. Anavex Life
Sciences Corp. undertakes no obligation to update publicly any forward-looking statements, whether as a result of new
information, future events or otherwise . Anavex Life Sciences Corp. cannot be sure when or if it will be permitted by
regulatory agencies to undertake clinical trials or to commence any particular phase of any clinical trials. Because of
this, statements regarding the expected timing of clinical trials cannot be regarded as actual predictions of when Anavex
Life Sciences Corp. will obtain regulatory approval for any "phase" of clinical trials. We also cannot be sure of the clinical
outcome for efficacy or safety of our compounds. Potential investors should refer to the risk factors in our reports filed
on Edgar.
anavex 2
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 3 of 13
What is Rett Syndrome?
Devastating Neuro-developmental Disease in Girls with both Movement Impairment and Cogn t ve
Impairment
Rett Syndrome (RTT)
• Non-Inherited genetic postnatal disorder caused by mutations
In the MECP2 gene
Occurs almost exclusively in girls
Leads to severe impairments, affecting nearly every aspect of the child's life
Impairment includes ability to speak, walk, eat and even breathe easily
Hallmark of RTT is near constant repetitive hand movements while awake
Occurs worldwide in approximately one in every 10,000 to 15,000 live female
births
The population of patients with Rett syndrome is estimated to be -11,000
patients in the U.S.
There is currently no cure for Rett syndrome
Source: https:llwww.rettsy11<Jrome.org/about-ret1-syndrome anavex
ANAVEX®2-73 MoA: SIGMAR1 Activation Prevents Cellular Stress Before and After Gene Transcription
Chromatin Chromatin
•
Remodeling Remodeling
Proteins
Cytoplasm
SIGMAR1 protects healthy SIGMAR1 prevents toxic RNA
gene expression through from translating into proteins
Chromatin Remodeling (post-transcription)
(pre-transcription)
Sourcs: Couly et al., Knocking our s;gma.1 Recsf)lors Reveals Diverse~
Problems. Cell Moi Neuroboi (2020); Lee el al .. Sigm;,-1 receptor chaperones Healthy RNA _ _ __.,
rescue nucleccytoplasmlc transport deficit seen in ce/ltJ/ar all<! Drosop/1//a ALS/FTD
mo<Je/s. Nat Commun. 2020Nov4;11(1):5580 :vex
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 4 of 13
ANAVEX® Rett Syndrome Program
Completed and ongoing late-stage clinica l studies fo r Rett Syndrome in 2022 :
• U.S. Phase 2 Adult Rett Syndrome Trial (ClinicalTrials.gov Identifier: NCT03758924) - completed
• AVATAR Phase 3 Adult Rett Syndrome Trial (ClinicalTrials.gov Identifier: NCT03941444) - completed
• EXCELLENCE Phase 2/3 Pediatric Rett Syndrome Trial (ClinicalTrials.gov Identifier: NCT04304482)
- ongoing
• ANAVEX®2-73 Rett Syndrome Program Received Fast Track Designation, Orphan Drug Designation
and Rare Pediatric Disease Designation
Pivotal Efficacy Supportive Efficacy Safety Database
• Positive Phase 3 • Positive Phase 2 U.S. • Safety and Tolerability
AVATAR Study Rett Syndrome Study Data from
Completed & Ongoing
Studies
anavex 5
Phase 3 AVATAR ANAVEX®2-73-RS-002 Trial in Adult Patients
with Rett Syndrome - Design Overview
Randomized, Double-blind, Placebo-controlled Multi-center Clinical Trial
Arm Number of participants
48-
ANAVEX2 -73 n=20 week
(once dBf/ up 10 31Jmg lkjuilJ 00:e,,e)
OLE
Placebo n=13 study
oroe ai'y J>ti-0 HQ d dcee ongoing
Week 0 Week 4 Week 7
(Base line) (End of Trial [E OT] )
Assessments:
Primary: Assessment of RSBQ AUC response and safety
• Secondary: Emotional behavior (ADAMS) response and CGl-1 (Clinical Global Impression of Improvement) response
• Exploratory: Sleep (CSHQ), VAS (top caregiver concerns), Child Health Questionnaire PFSO (CHQ-PFSO), Rett syndrome
Caregiver Inventory Assessment (RTT-CIA), Seizure diary
• Biomarkers of response and/or surrogate endpoints: DNA & mRNA profiles and metabolomics biomarkers
SIGMAR1 variants: Prespecified analyses of population with wi ld type (WT) variant
CfinfcBITriBls.gov: NCT0394 1444
Separate paUenl co/Jori (n=3) underwent " 3-weeh inlensi"" ph1Jm>acok1netic (PK) assessment wlfh s1Jfely, toiembiMy. phann,,col<ine/1c Bnd efficacy eva/uaf,on of A NA Vi=)('lt2-73
Open-/abei-<,xtension (OL£) after £nd of Trial for al leas/ 48 """ks 6
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 5 of 13
Baseline Characteristics
ANAVEX®2-73 (n=20) PLACEBO (n=13) TOTAL (n=33)
24 .8 236 243
Range - Min, Max 18.20, 38.35 19.53, 40.78 18.20, 40.78
Weight (kg) - Median 41 .6 54.8 46 .8
Range - Min, Max 33. 0, 76.0 29.0, 84.0 29.0, 84 .0
Baseline AED medications, %
Baseline CGl-5 Category, n (%)
4-Moderately Ill
5-Markedly Ill 11 (55%)
6-Severely Ill 4 (20% ) 3 (23%) 7(21 % )
7-Extremnely Ill 0 (0%) 0 (0%) 0 (0%)
anavex 1
Appropriate Primary Endpoint for Rett Syndrome
Background for Pivo '11 Trial Endpoint
• Statistical significance alone not sufficient for determining whether an individual patient
has experienced a meaningful clinical benefit
• As a stand-alone caregiver reported primary outcome assessment, the RSBQ does not
appear optimally suited , on its own , for the determination of a clinical trial outcome
(e .g. , could lead to either type 1 or type 2 error) 1
• FDA:
• Anchor-based responder method 2 - linking of scores from one clinical outcome
assessment (e.g., RSBQ) 3 with scores from a simple reference "anchor" cl inical
outcome assessment with a clinically meaningful threshold (e.g ., CG l- 1)4 to
facilitate interpretation of what constitutes a meaningful within and between patient
change in clinical outcome assessment scores (e.g., RSBQ AUC) 5
1/ Hou W. BoottachBl}'a U, Pradana WA, Ta,qumio DC. Assessment of a Ciirocal Tna/ Met,., for Rell Syndrome; Cntkal AnalySIS of the Rett Syndrome Behavio<,ral Questronnairo Pedialr
N,,uro/. 2020 .Ju11;107:4/J-51i. doi: 10. 101 l;i{j.padiarmeurot. 2020.01 .009. Ef)<Jb 2020 Foo 4. PMID. 32165033
2/ Gwdance for Jndus/,y Patient-Reported Outcome Measures; Use ,n Medical Product Development to Suppo,I Labeling Claims hllps.'llwwwJda.qa,,/regulalory-in(ormationlsearch--fda-
qui<Jance--dqcumsnts,pati9nt-rs00t1ed-0utcomG--me.asurAA:VAA-n1GdiCcJl--producf-d9velppment-sµpporl-fabefin9:cJaims
3/ Reff Syndrome Behavioural Questionna;,e
4/ C/1nieaJ Global Impression of Improvement
5/ Area Undar tha Effactiva Curve to accotJ!lt fry drug axposure O'V6f the rou= of dr;rafi® ot the trial :VeX 6
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 6 of 13
Primary Endpoint for Phase 3 AVATAR Clinical Trial for Adult Patients with Rett
Syndrome
Capturing Clinically Meaningful Treatment Effect and Disease Progression
The RSBQ AUC (area under the effect curve) is a summary measure that combines both
treatment effect and disease progression into one composite score
• It captures not only the end of treatment effect, but also the progression of the disease over the
course of the study with better precision than only an end of treatment score 1
CGl-1 (Clinical Global Impression of Improvement) anchored RSBQ AUC score: Improvement
threshold of at least 1 full point in the 7-point scale from 'No Change' (i.e., 4) to at least
'Minimally Improved' (i.e., 3) or 'Much Improved' (i.e., 2) or 'Very Much Improved' (i.e., 1)
Responder is defined as a study participant who exceeds the clinically meaningful CGl-1
threshold with corresponding RSBQ AUC linked value indicating improvement
• CGl-I anchored RSBQ AUC has been previously successfully assessed as efficacy endpoint in
U.S. Rett Syndrome ANAVEX®2-73-RS-001 trial
' Pham B, Cro111Hly A, Boors M. Verhooven AC, Wells G, Tugw<>II P. Validity of area-under-the-curve analysis lo summarize effect in
rheumatoid arthritis c/10,ca/ lna/s. J Rheumalol. 1999;26(3):712-716. anavex
CG -1 Scale
crn·cal Glob I lmpress·on of l11provem t (CGl-1)
The Clinical Global Impression of Improvemen t Scale (CGl-I) is a measure developed for use in clinical trials to provide a brief. stand-alone assessment of
the clinician's view of the patient's global functioning prior to and after initiating a study medication. Each time the patient is seen after medication has been
initiated. the clinician compares the patient's overall clinical condition to the period just prior to the initiation of medication use (the so-called baseline visit).'
Mimics what a physician would do in practice if an intervention is helping
Measure both global and individual domain ratings like CGI-S (Clinical Global Impression of Severity)
CGl-I measures clinical change in a "Very Much Worse" (7 score) to "Very Much Improved" (1 score) range
The CGI-S score obtained at the baseline (initiation) visit serves as a good basis for making this assessment The following question is rated on a
seven-point scale: ·compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much
improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally
worse; 6= much worse: l=very much worse since the initiation of treatment.··
Only scores of 1 or 2 or 3 are defined as treatment "responders"
Score of 3 or less represent clearly observable clinically meaningful manifestation of drug effect
This implies that the minimal important difference is a change of 1 unit from a CGl-1 of 4 (no change) to a CGl-I of 3 (minimal improvement)
iltillllll=El1ll1l·II
Il
X
7
X
6
X
5
X
4 " 3 "2
T
"1
Very Much Much Mi nimally Minima lly Much Very M uch
No Change
Worse Wors e Wor:se Im p roved lmp,oved Im proved
' Busner J, T8fgtim SD. The cliroca/ global impressions scale.· applying a research loo/ in cl,mca/ practice. Psychiatry (Edgroonl), 2007;4(7):28-37, 10
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 7 of 13
ADAMS Scale
Anxiety, Depression, and Mood Scale (ADAMS)
The Anxiety, Depression, and Mood Scale (ADAMS) is a measure of anxiety and mood symptoms in
individuals with intellectual disability. 1 It has been clinically validated for use in Rett syndrome 2 and in
Fragile X syndrome 3
The ADAMS generates a total score and 5 subscale scores:
Manic/hyperactive behavior
Depressed mood
Social avoidance
General anxiety
Obsessive compulsive behavior
1) Esbensen AJ, Roja Im J, Amen MG, Ruedlicll S. Reliability and validity of an assessme/l/ 1ns/romen/ tor anxiety, depression, and mood among individuals with ment,,t retardatioo. J Autism
Dev D,sord. 2003;33:617-29 K!u""'r Academ,c Publishers-Plenum Publishers.
2) Bames KV; Coughlin FR, O'Lea,y HM, Bruck N, Baz,n GA, &in<>cke EB, Walco AC, Cantwell NG, Kaufmann WE. Anri<>ty-llke l)ehavK)I" in Reff syndrome: characterislics and assessment t,y
anxiety scales, J Neurodev Disord, 2015;7(1):30, do,; 10, 11Ws11689-0115-9127-4 Epub 2015 Sep 15.
3) Corr:leiro L. Ballinger E, Hi!!J6rman R. Hess/ D. Clinical assessment of DSM-IV anxo,ty disorders in fra,}ila >< syndrome: prevalanca and charar;terizali-On. J Neurodev Disord. 2011;3.57-oT.
do/: 10.1007/s11689.()10•~7-y. Epub 2010 Dec 3.
anav _ 11
Primary Endpoint
Primary Efficacy Endpoint
80
72.2
70
p = 0037
38.S
10
ANAVEX2-73 Placebo
ANAVEX®2-73 induces a clinical meaningful improvement of RSBQ AUC* in 72.2% of
patients as compared to 38.5% on placebo; (p = 0.037)
Cohen's d effect size 1.91 (very large)
"Improvement tl,reshold of al leas/ 1 full point in the CGl-1 scale from 'No Change ' (I.e .. 4) to at least 'Minimally Improved' (I.e., 3) or 'Much Improved' (I.e.. 2) or
'Ve,y Much Improved · (i.e .. 1) :vex 12
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 8 of 13
Secondary Endpoints
Secondary Efficacy Endpoints ADAMS and CGl-1
. 80
72.l
"' 70
"'
.
'7
Lo
;::- 60
p = 0.010 p = 0.037
,. 40
38.5
,. §. 30
20
a
u
IO
10
0
ANil.'a'flQ -73 pi.c.,t,(> A.NA\IE:Q•73
Clinically meaningful and statistically significant reduction of Significantly more patients achieve clinically meaningful CGl-I
emotional behavioral symptoms (ADAMS) response• for response'* over the treatment duration in ANAVEX®2-73-treated
ANAVEX®2-73 treated adult patients with Rett syndrome (52 .9%) group (72.2%) as compared with placebo (38.5%); (p = 0.037)
vs placebo (8.3%); (p = 0.010)
Cohen 's d effect size 1.91 (very large)
Cohen's d effect size 0.609 (large)
• /mprow,meol I/iresllold o/ al /eaS/ -20% c/Jar,ge (lmprovemenl) o/ ADAMS Iota/ •• Improve men/ lhreshold of al least 1 full point in /he CGl-1 scale from 'No Change·
scorn from baseline
(i.e., 4) lo al leas/ 'Minimally Improved· (1.e., 3) or "Much Improved' (i.e., 2) or 'Ve,y
a
Much Improved' /i.e., 1)
13
Other Endpoints
Quality of Life (QoL) Assessment and Distribution of Seizure Count by Treatment Arm
ANAVEX2-73 Placebo
Child Health Questionnaire-Parent
Form 50 (CHQ-PF50)
The CHQ-PF50 is an internationally
recognized general health-related 60-
global measure of Quality of Life (Qol)
encompassing physical and
Treatment
psychosocial concepts (physical ANAVEX2-73
function , psychosocial, behavior, bodily Plocebo
pain, emotional impact, family
activities, family cohesion, and general 20-
health perception)
ANAVEX®2-73 demonstrated dose-
related significant improvement in o- • • •
0 2'5 5'0 75 I) 2'5 50 75
.
overall Quality of Life (Qol) measured Seizure counts
with CHQ-PF50 Total Score (p = 0.030)
ANAVEX®2-73 is associated with a 50.7%
reduction in weekly seizure risk
:vex 14
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 9 of 13
Biomarkers Increase Probability of Success
Precision Medicine
76%
Patient
selection
biomarkers
55%
46% Higher
therapeutic
response
28%
Lower
variability in
the target
population
Phase 11to Phase Il l Phase Ill to NDNBLA
• Without Bi oma rkers Wi lh Patient Selecti on Biomarkers
Thomas DWel 81. CJ,nicaJ Development Sucoess RB/es 2006-2015. BIO Industry Analysis anavex 15
ANAVEX®2-73 Mechanism of Action for Rett Syndrome
SIG AR1 Activation is e efcial i Restoring Neuronal Homeostasis
MECP2 mutation alters S/GMAR1 act1vatlon closes ANAVEX®2-73 reverses
synaptic development and chromatin to counteract ch ron,c behaviora l, motor, and
drives ch ronic cellu lar stress cell ular stress, restoring synaptic imbalances by
by open ing chromatin 1,2 mitochondria and synapses 3.4 activating StGMAR1s. 6 7.a,
!
l;',:.~:;'i:;::.:~
MECP2
Aberrant Expression
Synaptic Balance
V
Mitochondrial Function
f Inflammation
Synaptogenesis
M,tochondnal Function
l
l
1nflammat1on
GABA
Neurotrophic Factors
l
(BONF)
Seizures
Neurodegeneration Markers
(L-AAA)
1/ U et o/.. 2020; 2) Wang eta/ 2020; 3/ Crouzieret o/., 2020: 4/ Lee el al, 2020; 5) Kaufmann et a/, 2019;
ij/ Kaolmann el al , 201!11;,; 7) Lahmy el al, 2015; ~) Lioak el al., 2020; 9) ANAVfaX2-7J-R$-002 Dalo :vex 16
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 10 of 13
GABA a Potential Biomarker, Predicting Clinical Outcome in
ANAVEX®2-73 Rett Syndrome Study
In patients with RTT. MECP2 • AVATAR efficacy endpoints
deficiency disrupts the demonstrated statistically significant
and clinically meaningful reductions
GABAergic cycle 1, resulting in
in Rett syndrome symptoms with
decreased GABA, and impaired related changes in potential
synaptic and mitochondrial biomarkers of disease pathology:
fu net ion 1.2,3,4.5,s
• GABA7was significantly increased
(p = 0.0205)
GAIAP;athw;rys
Otli1t1illll!llo - Onli-mfl
• Gliotoxin L-Alpha-aminoadipic acid
(L-AAA) 8 was significantly decreased
(p = 0.0392)
1) Jin et Bl., 2015: 2) Chao et Bl., 2020: 3) HBmbergeret Bl. , 1992: 4) l..appB/Binen et Bl., 1996; 5) Neu/ et al., 2020 6) KBufmBnn et Bl., 2005
7} U,e K, Lu H, Wang W, el Bl. RestornlHJn of Meq,2 express,oo m GABAe,gic neurons ,s sufficient to rescue mu/~ple disease featu,es m a mouse model of Rett syndrome. Elite
2016 Jun 21;5:e 14198; 8) Wu HQ, Ungerste<ll U, Schwarci R L-;i/pha~noadipic acl<J as a regulator of kynurenic ar;1rJ proor;c/ion in the hlppocampus· a microdialysis stucly in
freely iooving rats. Eur J PhBrmacol. 1995 Jul 25;2B1(1):55~1 ef\/eX 17
Safety and Adverse Events During Treatment Period
ANAVEX®2-73 was well tolerated with
very good medication compliance of Adverse Events During the Treatment Period
95%
Similar TEAE rates observed in ANAVEX®2-73 (n=20) Placebo (n=13)
ANAVEX®2-73 and placebo arms num ber(%) nu mber(%)
Patients w th any TEAE 15 (75.0%) 8 (61.5%)
AEs ~10% were predominantly mild
or moderate Patients w th a serious TEAE 3(15.0%) 2(154%)
Patients w th a TEAE leading to
No clinically significant changes in 2(10.0%) 1 (7 7~.)
Study D scontinuat on
vital signs, lab values and ECG AEs~10%
parameters in ANAVEX®2-73 and Somnolence 4 (20.0%) 2 (15.4%)
placebo groups Loth argy' 4 (20.0%) 0 (0.0%)
Sedation 2 (10.0%) 0 (0.0%)
No incidence of diarrhea or vomiting Constipation 2(10,0%) 1 (7.7%)
Urinary tract infection 2(10.0%) 1 (7.7%)
Safety findings are consistent with the
Hypophagia 2(10,0%) 0 (0.0%)
known safety profile of ANAVEX®2-73
Sk n rash 2(10.0%) 1 (7.7%)
1 Medical history of Somnolence in 3 patients; 1 severe, all oHlers mild
' All mold
:vex 18
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 11 of 13
Overall Summary
Phas 3 AVATAR Clin·cal Tr"al for tlul Paf nt with Rett Syndrome
Primary (RSBQ AUC ; p = 0.037) and secondary (ADAMS; p = 0.D1 0); (CGl -I; p = 0.037) efficacy and safety endpoints met
Efficacy endpoints demonstrated statistically significant and clinically meaningful reductions in Rett syndrome symptoms
with related changes in potential biomarkers of disease pathology:
• GABA was significantly increased (p = 0.0205)
• L-Alpha-aminoadipic acid (L-AAA) was significantly decreased (p = 0.0392)
Convenient once daily oral liquid doses of up to 30mg ANAVEX®2-73 were well tolerated without safety concerns identified
Confirmed dose-response:
• RS-001 study 5mg ANAVEX®2-73 dose RSBQ AUC Cohen's d (effect size) of 0.517
• RS-002 study 30mg ANAVEX®2-73 dose RSBQ AUC Cohen's d (effect size) of 1.91
Analysis of weekly seizure counts indicated that relative to placebo, ANAVEX®2-73 is associated with a 50.7% reduction in weekly
seizure risk
ANAVEX®2-73 demonstrated dose-related significant improvement in overall Quality of Life (QoL) measured with CHQ-PF50
(p = 0.030)
Key milestone met to advance regulatory approval pathway for adult patients with Rell syndrome
Discussing with FDA a pathway for potential approval of ANAVEX®2-73 for adult patients with Rett syndrome
-.vex 19
Acknowledgments
We thank all the patients and their family members
participating in the Rett syndrome ANAVEX®2-73-RS-002 study, as well as the
investigators and their staff conducting these studies and the global Rett Syndrome Associations.
dn~vex .o
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 12 of 13
Broad Pipeline Platform Targeting Neurodegenerative and Neurodevelopmental Autism Spectrum
Disorders with Significant Unmet Medical Need
CAttOIDATI:'. PRE,CLINICAL PHASE 1 PHASE2
ALZHEIMER'S DISEASE AD ANAVEX 0 2-73-AD-004
ANAVEX 0 2-73
-- -------- ------ ------ ----- ------ ----- ---
(Blorcameslne)
-- -------- -- ---------- ------------- ----- --
PARKINSON'S DISEASE DEMENTIA ANAVEX 0 2-73~DD--001
•RITT SYNDROME EXCELLENCE ANAVEX 0 2-73-RS-003
Fast Tra ck1 Rare Pediatric.
•RITT SYNDROME U S ANAVEX 0 2-73-RS-001
Orphan Drug (U. S./EU)
., AVATAR ANAVEX 0 2-73-RS-002
•INFANTILE SPASMS
-·- ...... ··-
FRAGILEX
............
ANGELMAN'S (ml
UNDISCLOSED RARE DISEASE
•FRONTOTEMPORAL DEMENTIA (FTD) ANAVEX 0 3-71--001
ANAVEX 0 3-71 )Ill
...
SCHIZOPHRENIAS lo
(AF710B)
ALZHEIMER'S DISEASE
ANAVEX 0 1-41 STROKE
• Differentiated clin ical-stage CNS assets
NEURODEGENERATIVE DISEASES
targeting significant and growing markets
VISCERAL PAIN • Patent protection to 2030-2039 , worldwide rights
ACUTE & NEUROPATHIC PAIN for all product candidates
• o,pt,an Onlg Dasignation by FDA; Dashed lines indicate planned clinical s/udies onove 21
Anavex is the only Company
PRECISION MEDICINE PLATFORM IMPROVES CHANCE
pursuing by OF CLINICAL SUCCESS
Applying to
Develop Treatments for both V Testing for biomarkers demonstrated improved clinical
response to ANAVEX®2-73 in Rett syndrome ,
Parkinson's and Alzheimer 's patients correlated with
CNS diseases mRNA SIGMAR1 gene expression
(Alzheimer's, Parkinson's), as
well as STRONG IP POS ITION AROUND NOVEL MECHANISM
diseases, /A OF A~;:~~X®2 -73 , is an ora ll y available Sigma-1
Rett Syndrome with High Unmet " receptor agonist that has been shown to restore
homeostasis (composition of matter patent protection
Needs to 2037)
•
COMPELLING HUMAN DATA PLATFORM
2018 Alzheimer'sAssoeialion
ANAVEX®2 -73 Phase 3 and Phase 2 in Rett
OVERARC~IINGMESSAGE syndrome , Phase 2 Parkinson 's disease dementia
A to add ress the (POD) and Phase 2a trial in Alzheime r's disease with
favorable safety and exp loratory efficacy resu lts
tota lity of CNS diseases through 148 weeks
:vex 22
Case 1:24-cv-03529-CM Document 23-5 Filed 08/23/24 Page 13 of 13
Contact Us
References
C,Oia,i,, L eo-.iI:, S Roque-a C, l""elElr C BElllcMe, R, Ar,guel JB<:quemln ""· BooettoA.. D~reit B, Mauno&T. Sigma-, (a1jf8Cep,11Y .acii~ ly iii 11'8CElbl>.3'}' kll'Phre!Dklglcal llra,11 plaebcty In m,oe Ellf
~europ,;yd,oph;mn.,CDI 2(120 Od:39 29-45 l1ol 10 1016,lj i:tJrnn~uro 2020 08 010
tt.,r.tshi T Su TP" Si.ginit-1 r~~pklr d1.:1pero11es.itl 1t11~ ERr11irocho11drion inl.t!rfit0e regul.:!!e Ca(2•)s~n!!tmy 1111d ot!ll surviv~ Cell. 2007 No~ 2 131(3).596-610. doi. 10.1D16.•j ~1.2007.08.03.EI
l(eufmM'ln WE S~IJlie J. Retl0'""9 N. Haner,111 T Klami;ir D. Mlsslil'l!J CU ANA'VEX©2-f3.(tllercarn9illl4!/. a Sl!lma-1 r909Ptor 9gonl&t Bn1ellQJate& n0vrok)glc1mp miB'f!tEi In a mou:e,,e m:idl;ll Flelti;~mtome
Ph1nm:2col Biochcr11 Beh;:i-.,_ 2019 187.17279113 dai. 10.1D1EI~ pbb.2019. 172796
l(aufmann WE. Pett:-/ A¥. Lane JB. OD8fl'Tl1111 LM Touta,n S. F«iroch JA, ~IS611ng CU Treelrn~of Aet1 &:;ndrome ..,.,th the :sigma-1 recep1orblareame&lne prel1n,r1111")' effcacyanaty.&es lnadul15 NORD R11re
Di~.:12!1 zmd Orpho,m Producl.!i 6r~k1!1rough Surrir11il (1:1bslntct/, Oe1olit!1 2t-22 20Hfu W1t!ihlr1glon.. 0 C
Lahmy V, Loog Fl. Mc,rin D Vd~ V, "'1aur,ce T. toctlondrl&I prol&etlon by lhe mlJ:edmo&CllftOO'o1 Ilg.and A.NAVEX2-73, a 1e-trah)'iittll'uren <IE!rfo'atr.-&, In ~25-J5 p~t.::10-tflle<::le<I me&, a 00fllran!19er11c
AILJ-11Smt!r'11, di=i:tsl!; modt!I. frcnl Ct!II Nl!;urc5ci. 2015 Ja11 20,8.463 dui 10 3J891rnce1 2(] 14.00463
Lee r,r, L~B JC, Warig 5M Clluang JY. KflalM B. Wu HE Chaing WC "'6urk:e T, 5U TP 51ii,"lll-1 r~tor Chap,erooes f89CW NdeocylOplaemle 1ranepCft de1d &eefl.11(1 Ol!Qulaf aNI Dro&apll•la ALS1'FTO
mcJd~ Ni:itCcmmu11 2020 Ne"' 4, 11f1).5580. deli. I0.1038,'s.41467-020-19396-l
LI CH COIT,ey EL, Dall'AQ(lea.8 A, Htlnl'l&tl NIV Tang X, l·tt,,m,nge, JE. Platt~ a.,91J2 0, zamudio Al/. AIEl~llfl U:, Sct11.lyllrs J, Liu XS, ""'3rk0Ulakl S, Lur,g1ang\'!a T, LeRoy G S.-.oboda OS, Wogram E LEie Tl,
J.1cm ,;r.h R. Yeung RA Mr.CP:1' lr,ks hr.tcm:ir.lwmilliri <:ondr.,ns..,brls :md nr.urodcimlopmr.,nt,1.1 di~case N;ilum 2020 Oct:5~7829)·440-444 doi· 10 1038,'s.41 Sl!B..o:20.2574-4
Usak RP, NedeU.o::.-.S L Befljam ns JA S."ilma-1 racep'lof agoolat::1 as po1.&ntial proh,,c\i~e ller.eplee In mulcile ederol>l8. J NeurCNmmWl<ll. 2020 Fell 21,3~2 57718B. <10, 10.1016JJ.lneuro.m 2020 517188
Mori T Ha)'a91I T. H;n'Btih E Su TP S.sim1t--1 recep1or Chaperone at the ER-fTlltochondron lnler1ece lll9dli:tles t,e mltocilofldnon-ER-nuele~ sl!J{lallnsi 1c,- oeUular 61.lr'IIYal PloS On,e 2013 Ocl 1B:BI10) er6941
dol.10.1371~oumlll pooe0076941
'Villard V. EspaJte111ues J Keller E et al Anti..amn~lc al'd ~ellf'Oprolle~ 1)(1'8ntiH- of~,e m :red muscannlc f'8<:81lli0ri:sigma 1 (01) lgand AN.r..VEX2-/J 111 ~ I amlno'8lrah~rofuran clenvab"8 J
Psyc:haplwnl\aOUI 2011 Al.Jg 2D11,25(8).1101-17
War,g L Hu M Zuo ,-,,,o_ Zhao J Wu D. 1-klar"".il L Wil'l Y LI Y Chen F', Bao X Dor,g MC:!, LI G UP Rett syl'l(Jt'OO'l9-GSU&tfl!;I mutatloos compromM Mec.F'2-med\a'9d llr:,Jh1-• ci1.11d pha:se 581JSr.ition of chroma_,
Cell Rt!5. 2020 P.\.:sy,30(5) 3.93-407 dorr 1D.100B.i541422-<120-02!18-7
Ct,.;io HT Ctie,, H Samaco RC X1Je M Ctiahrour M, Yoo J ~ I JI. 64 al D)'-&fun<:lkirl lfl GA.BA &l!JflallFig mectate& autii;rn-1 &tereotyples al'l(J Re11 :!io~rom8 pherlotyp81i Nature 2010 No..-11 .1116$!f32:1)·263-9
doi 10 103&'ni:tlure095.a2
Hairtierver A, G I ~ C, PBlnl A 1-ldgbe,g B. Ele~a1e<I C.SF v1utama1tt In Rett O)'fldromB Ne,m:flelilatrlca 1992 Aug 23(-41.212:-3. <IOI. 10.1oss,·e.-2008-10713'1ll
Jin 1.W. Honuchi M WulH H. l,Ju XB Cor11JJ1.1!u;i Gill. Endu1r1 JO. M.,r,.i;aw,;i I Dy,;~uL,ton cf glul;wrnnn ••m,;jlClrtcr SN.A.Tl ,n Rctt ,;yndramr., mir.mgl~, ;a mr.d!.,ni~m For mitachaidn.,1 dyslunclKln ;and
rieurolc>Ad~. J Neoroscl. 2015 Feb 11,J5161.2516-29 001. 10.1523/JNEUROSCl.277B-14.2D15
K.,ufrn.1Tifl WE. Jotin,;ton Ml/, Blut1 r,.i E Mr.CP2 r-xprr-.,;~il)lt .ind frJnr.tion d.1ring br.a'1 dcvr.Jopmr.nt implc.1bon~ ftir Rr.tt ,;:,nliromr."s p,,ittiogr.nr.:-.,~ ;md cinir~ r.,v,oiuhOfl Br.iin Or.y 2005 t,,lcw 27 SuFJ!I 1·S77-S87
1101 10 1016,'j 1>ra1n<1e~.2~.1D.008
Lappalain,en Fl R kon&n RS Hl;ih leYel& of oeretro&p nal lluh:t ~tamale In Rett &"~l'l(JtOIJ'le Pedl~r Neurol 1996 Oct H,{3}21~ dol· 10 1016ts08Bt-8994({)6)0021S-4
N~ul JL SJw,n~ SA. Armet1e f Lane J. Ht!yder11i:iru1 P' Jare11, M, Kl!Ufn'll!lnn WE Gl.:!Lt! P ~ AK M~labolil: Siyna!ure11, Difft!~nlii:ill!I Rt!l! Syndron,e frcrn UrllLffl!ld.t!d Slilir,g11, Frcr1I lnlft!Jf ~rD:M:i. 2020 Ft!b
2~14·/ dol· 1033,8.9,'tn,nt2:02000001
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