Corporate Presentation - Bringing hope to people living with Alzheimer's Disease - Alpha Cognition
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Corporate
Presentation
Bringing hope to people living with Alzheimer's Disease
COPYRIGHT 2021 ALPHA COGNITION, INC.
Forward-Looking Statements
This presentation has been prepared by Alpha Cognition Inc. (“ACI” or the “Company”). This presentation includes forward-looking statements within the meaning of applicable securities laws. Except for
statements of historical fact, any information contained in this presentation may be a forward-looking statement that reflects the Company’s current views about future events and are subject to known and
unknown risks, uncertainties, assumptions and other factors that may cause the actual results, levels of activity, performance or achievements to be materially different from the information expressed or
implied by these forward-looking statements. In some cases, you can identify forward-looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,”
“objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “target,” “seek,” “contemplate,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology
intended to identify statements about the future. Forward-looking statements include statements regarding the Company’s business strategy, future plans, market size, potential growth opportunities, capital
requirements, clinical development activities, the timing and results of clinical trials, regulatory submissions, potential regulatory approval and commercialization of the technology. Although the Company
believes that we have a reasonable basis for each forward-looking statement, we caution you that these statements are based on a combination of facts and factors currently known by us and our expectations
of the future, about which we cannot be certain. The Company cannot assure that the actual results will be consistent with these forward-looking statements as a result of known and unknown risks,
uncertainties, assumptions and other factors. These risks include those associated with clinical studies and manufacturing; risks around development and commercialization of the Company’s products; the
need for additional financing to maintain operations; risks posed by the economic and political environments in which the Company operates and intends to operate; market instability due to the COVID-19
pandemic; the potential for losses arising from the expansion of operations into new markets; increased competition; assumptions regarding market trends and the expected demand and desires for the
Company’s products and proposed products; reliance on industry manufacturers, suppliers and key personnel; the failure to adequately protect intellectual property; a failure to adequately manage future
growth; adverse market conditions; and failure to satisfy ongoing regulatory requirements or obtain regulatory approvals. These forward-looking statements speak only as of the date of this presentation and,
other than as required by applicable securities laws, the Company undertakes no obligation to revise or update any forward-looking statements, even if new information becomes available in the future.
This presentation also contains estimates and other statistical, market and industry data from independent parties or made by us relating to our industry. This data involves a number of assumptions and
limitations, and you are cautioned not to give undue weight to such estimates. We cannot guarantee the accuracy and completeness of information from third party sources.
ALL CURRENCIES DENOTED ARE IN UNITED STATES DOLLARS UNLESS OTHERWISE INDICATED
COPYRIGHT 2021 ALPHA COGNITION, INC. 2
Late-Stage Biopharmaceutical Company Focused On
Neurodegenerative Diseases
ALPHA-1062: patented potential New Chemical Entity for the treatment of mild-to-moderate Alzheimer’s
Dementia
• Potential best-in-class treatment designed to optimize efficacious dose, minimize treatment-limiting side-effects and
improve long-term outcomes
• Large 11M RX market characterized by high (30%) turnover of patients
• Initiating Pivotal Study with Approval Targeted in 1H 2023
• De-risked 505(b)(2) new drug application with a high probability of success
• 505(b)(2) supplemented with safety and tolerability differentiation data
• Patents extending to 2040
Pipeline provides multiple opportunities for value creation
• ALPHA-1062 + Memantine for moderate-to-severe Alzheimer’s dementia
• ALPHA-1062 intranasal delivery for mild Traumatic Brain Injury
• ALPHA-0602 for Amyotrophic Lateral Sclerosis (Orphan Drug Designation granted by US FDA)
Experienced Leadership Team
• Seasoned team with deep expertise with over 50 years of cumulative experience in Neurology and over 20 product
launches
• Track record of success in drug development with over 250 approvals in the USA and Europe
COPYRIGHT 2021 ALPHA COGNITION, INC. 1. Symphony METYS Retail 2019:Includes donepezil, galantamine, rivastigmine and Namzaric 3
Pipeline Programs
Phase 3 / Status /
Indication Preclinical Phase 1 Phase 2 Pivotal Upcoming Milestones
Alzheimer’s Dementia
Initiate Pivotal Study Q3/21
ALPHA-1062
Top-line Results Q1/22
Enteric-coated Tablet
NDA filing Q3/22
Formulation development
ALPHA-1062 +
ongoing for 505(b)(2) regulatory
Memantine
pathway
Mild Traumatic Brain Injury
Phase 1a/b studies completed
ALPHA-1062
Ongoing animal studies of TBI
Intranasal Formulation
Top-line Results Q1/22
Amyotrophic Lateral Sclerosis
Ongoing preclinical development
ALPHA-0602 to identify optimal construct
Top-line Results Q1/22
COPYRIGHT 2021 ALPHA COGNITION, INC. 4
Alzheimer’s Disease Overview
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease
for which there is no cure
AD is characterized by loss of cholinergic neurons in the brain
Decreased acetylcholine levels and loss of receptors negatively impacts learning, memory and function
AD Impacts an
estimated 6 million
people in the U.S.1 Estimated healthcare cost
for Alzheimer’s and 8 out of 10 Only 4.5 out of 10
other dementias AD patients start on remain on therapy
$355 Billion an ACHEI as standard at 12 months due to
1 person per year and expected to first-line therapy2 side-effects2
is diagnosed
increase to more than
every 65 seconds
$1.1 Trillion
annually by 20501
COPYRIGHT 2021 ALPHA COGNITION, INC. 1. Alzheimer’s Association 2021 https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf 5
2. Symphony Health
ALPHA-1062 Is A Pro-Drug of Galantamine With
Decreased Side-Effects And Increased Bioavailability
The formation of the benzoyl ester eliminates AChE inhibition; the gluconate salt
increases solubility
ALPHA-1062 is absorbed in the small intestine as an inactive compound with minimal
or no side effects
ALPHA-1062 is subject to 1st pass effect, cleaving the benzoyl ester, resulting in the
release of galantamine (active moiety)
Galantamine, the metabolite, is free to circulate with greater bioavailability
COPYRIGHT 2021 ALPHA COGNITION, INC. 6
ACHEIs Activity In The GI Nervous System Overstimulates Local
Neurons Resulting In Side-Effects
INTESTINAL LUMEN
AChEl absorbed
in small intestine
AChEl
AChEl
AChEl Binds to AChE,
AChEl increases ACh levels
and overstimulates
ALPHA-1062 is
local neurons
absorbed as an
AChEl
inert drug
No activity in
GI nervous system
AChEl
Nausea Bioavailability
Vomiting of ACHEI is
Diarrhea reduced
Nausea Bioavailability
Vomiting of galantamine
Diarrhea is enhanced
COPYRIGHT 2021 ALPHA COGNITION, INC.
COPYRIGHT 2021 ALPHA COGNITION, INC. 7
Galantamine Enhances Acetylcholine Levels And Nicotinic
Receptor Sensitivity
Decreased acetylcholine levels and loss of
nicotinic acetylcholine receptors (nAChR)
negatively impacts learning, memory, and
function
B
Current therapeutics1 increase acetylcholine
levels by inhibiting acetylcholinesterase
(AChE)
A
Enhancement of nAChR (a7/a4b2)2: B
• Stimulates the cholinergic pathway
• modulates inflammation C
• buffers the effects of amyloid
• enhances release of other transmitters:
Glu, DA, GABA, 5HT - resulting in enhanced: A Galantamine raises the concentration of Ach in the synaptic cleft by inhibiting AChE
B Galantamine modulates nAChRs, making them more sensitive to Ach
– Memory acquisition and retrieval
C Raised Ach and enhanced response of nAChRs to Ach lead to greater post-synaptic response
– Attention and activity
– Stabilization of behavior
– Inhibition of cell death and neuroprotection
COPYRIGHT 2021 ALPHA COGNITION, INC. 1. Excluding Memantine for moderate-to-severe Alzheimer’s disease. 8
2. Lilienfeld, S. (2002) CNS Drug Reviews, 8(2), 159-176.
Exploratory Studies Have De-risked Pivotal BA/BE Trial
Bioequivalence Study Demonstrating 15% Parameters Required to Establish
Superior Bioavailability Bioequivalence3,4
50
Razadyne IR 8mg Tablet2 ALPHA-1062
ALPHA-1062
11 mg RAZADYNE
ALPHA-1062 SL 11mg* Tablet1 Pharmacokinetic 11 mg
Parameter Enteric 8 mg IR
40 Sublingual
(n=10)
Coated (n=10)
(n=10)
Concentration (ng/ml)
30
AUC 523 519 451
20 Cmax (ng/mL) 52.7 52.9 46.3
Tmax (h) 1.50 2.49 1.1
10
90% Confidence Interval (CI) acceptance criteria is 80-125% for the test/reference ratio
0
0 10 20 30 40
Time (Hours)
COPYRIGHT 2021 ALPHA COGNITION, INC. 1. Alpha Cognition: Sublingual Tablet equivalent to 8 mg RAZADYNE, Data on file 3. Alpha Cognition: Sublingual and Enteric Coated Tablet equivalent to 8 mg RAZADYNE Data on file 9
2. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021615s000_ 4. FDA Guidance: https://www.fda.gov/files/drugs/published/Bioavailability-and-Bioequivalence-Studies-Submitted-in-NDAs-or-INDs
Razadyne_medr.pdfALPHA-1062 Pivotal Bioavailability/ Bioequivalence Study
Screening 1st Dose 2nd Dose Bioanalysis Topline Data Study Report
Food
Effect
Study 7-day Washout Data Analysis
2-months
Screening
Study Report 1st Dosing 2nd Dosing Bioanalysis Topline Data
Fasted
Study
7-day Washout Data Analysis
2-months
Study Design
• Single dose, crossover under Fasted Conditions
• Single dose, crossover under Fed Conditions
• 32 Healthy Adults Subjects per study
• Bioequivalence criteria: 90% CI – PK parameters for AUC and Cmax within 80% - 125%
COPYRIGHT 2021 ALPHA COGNITION, INC. 10
COPYRIGHT 2021 ALPHA COGNITION, INC.Exploratory Studies Have Demonstrated Improved
Gastrointestinal Side Effect Profile*
No reported GI side-effects with oral formulations of ALPHA-1062
(Enteric Coated and Sublingual Tablets, n=30)
Diarrhea Nausea & Vomiting
40 37.8
35
% of Subjects Reporting GI Episode
30
25
20.0
20
15
10 8 9
5
0 0
0
ALPHA-1062 11* mg RAZADYNE 8 mg/day RAZADYNE Pooled AE Data
Single Dose Single Dose (Doses ranging 8 to 32 mg / day)
(n=30)1 (n=120)2 (n=2,932)3
Gal. equiv. ~8mg Median duration of nausea was
5-7 days per episode
*Data from separate product monographs; comparative clinical significance has not been proven
COPYRIGHT 2021 ALPHA COGNITION, INC. 1. Alpha Cognition: Data on File 11
2. ISSO; Completed Phase 1 trials in healthy adults; J&J Reminyl NDA package submission
3. RAZADYNE Full Prescribing Information accessed: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RAZADYNE+ER-pi.pdfLong-Term Use Of Galantamine Is Associated With Delayed
Placement In Long-Term Care
80% of galantamine-treated patients % Patients Living Outside of Nursing Home1
were living independently versus 100%
30% of untreated patients at 36 months1 90%
80%
80%
With each year of treatment with 70%
galantamine, risk of nursing home 60%
60%
Galantamine –
admission reduced 31% Treated
50%
40%
30%
30% 25%
Placebo /
20%
No Treatment
10%
0%
0 6 12 18 24 30 36 42 48
Months of Therapy
COPYRIGHT 2021 ALPHA COGNITION, INC. 1. Feldman et al. International Journal of Geriatric Psychiatry 2009; 24: 479–488 12Long-term Effects Of Cholinesterase Inhibitors On Mortality and
Cognitive Decline
• In an April 2021 Neurology publication, 39,196 Alzheimer/Mixed Dementia patients (Swedish
Dementia Registry) were evaluated between 2007-2017 with a 5yrs follow-up
• Galantamine was associated with lower risk of death (P-valueALPHA-1062 Offers Potential Best-In-Class Profile Versus
Approved ACHEIs
ALPHA-1062 Donepezil Galantamine Rivastigmine*
Time to
Faster onset of improvement when
Symptomatic
started at therapeutic dose
Improvement
Time to Initiate therapy at most efficacious dose
Therapeutic Dose with low/no titration
Reduced GI side-effects,
Safety Profile
low incidence of dizziness and insomnia
Dual mechanism of action that
Mechanism of
Action potentiates acetylcholine transmission
and enhances nAChR (a7/a4b2)2
Significant risk reduction in progression to
Long Term Outcome
severe dementia
Reduction in Nursing Significant risk reduction nursing home
Home Admission admission
*Rivastigmine is also available as a transdermal patch
COPYRIGHT 2021 ALPHA COGNITION, INC. ARICEPT is a registered trademark of Eisai Co., Ltd. 14
RAZADYNE is a registered trademark of Johnson & Johnson
EXELON is a registered trademark of Novartis Pharmaceuticals Corp.Multiple AD Launches Have Achieved Blockbuster Status
AD Launches
COPYRIGHT 2021 ALPHA COGNITION, INC. Source – IQVIA National Sales Perspectives – 1993 through 2020. 15ACHEIs Market Large but Dissatisfied Creating Opportunity For
Improved Treatment Option
Prescriptions by Specialty Total Prescriptions
11.6
11.4
2019 TRx Count (Millions)
11.2
Neuro/
Psych 11
LTC Rivastigmine
10.8
27% 36% 10.6
Galantamine
10.4
10.2 Donepezil
Other PCP 10
9% 28% 9.8
9.6
• ACHEI Market • 85% of newly diagnosed patients are treated
– 11M prescriptions dispensed per year with an ACHEI
– $5B in branded sales • High discontinuation rates of current
• Neurologists and LTC account for 63% of total therapies due to side-effects
market Rx’s – 30% discontinue treatment by month 4
– 45% discontinue treatment by end of 1 year
• Branded medications used more commonly in
LTC market
COPYRIGHT 2021 ALPHA COGNITION, INC. + Symphony METYS Retail 2019 16Commercialization Strategy Will Leverage Technology And
Focused Sales Effort At Launch
Commercial leadership intends to build
a best-in-class Neurology and LTC
sales force with the following focus: Success to be further enabled by:
Highly targeted and efficient multi-channel
Potential key points of differentiation
marketing campaign
Exploit key issues with existing ACHEI
Caregivers motivated to request ALPHA-1062
treatments
Franchise with potential additional indications
Limited payor barriers
and new products
Strategic partnerships will be used to expand
ACI’s promotional efforts
COPYRIGHT 2021 ALPHA COGNITION, INC. 17ALPHA-1062 Opportunity
De-risked
Large but ALPHA-1062 Clinical Development Near-term
Dissatisfied Market Potential Program Milestones
$5B in sales Reduced GI Side- Single Pivotal Trial
at brand price Effects Bioequivalence Initiation Q3 2021
and Study Tolerability Trial
Low/No Titration required for NDA
schedule required Initiates
30% Discontinue
Preliminary 1H 2022
treatment at Delayed
4 months Placement into Pilot Studies
support profile NDA Submission
Long Term Care
Q3 2022
COPYRIGHT 2021 ALPHA COGNITION, INC. 18ALPHA-1062 + Memantine Will Expand Usage Into Severe
Alzheimer’s Dementia
Mild
• Memantine indicated for moderate-to-severe
Alzheimer’s dementia
• Often used in combination with an ACHEI
– 7.7 million Rx written for memantine-
containing product1
• 505(b)2 regulatory path for approval of
combination product
– Precedent with NAMZARIC
Severe
COPYRIGHT 2021 ALPHA COGNITION, INC. ARICEPT is a registered trademark of Eisai Co., Ltd. EXELON is a registered trademark of Novartis Pharmaceuticals Corp. 19
RAZADYNE is a registered trademark of Johnson & Johnson NAMENDA and NAMZARIC are registered trademarks of Merz Pharma GmbH & Co., KGaAEarly Stage Pipeline Provides Additional Opportunities For Value
Creation
ALPHA-1062 in Mild Traumatic Brain Injury ALPHA-0602 in ALS
• Acetylcholine transmission is impaired in TBI • Progranulin deficiency results in exaggerated
neuroinflammation and neurodegeneration
• Galantamine efficacious in animal models
of concussion1 • Pre-clinical efficacy of progranulin in models of ALS
– Other ACHEIs have not shown consistent results2 has been published
• Unique dual mechanism of action believed • ALPHA-0602 is the full length progranulin molecule
to contribute to differential response1 delivered as a gene therapy in preclinical
development
– Inhibition of acetylcholinesterase
– α-7 nicotinic receptor modulation • Orphan Drug Designation granted in 2020
• ALPHA-1062 Pre-clinical study ongoing
– Phase 1a and 1b intranasal studies complete
COPYRIGHT 2021 ALPHA COGNITION, INC. 1. Zhao, J et al. 2018. JOURNAL OF NEUROTRAUMA 35:362–374 20
2. Bondi, C et. al. 2018. RESTOR NEUROL NEUROSCI 36;45-57Key Investor Considerations
De-risked clinical program with accelerated path to FDA approval:
targeted approval in 1H 2023
Large established market; significant patient and physician dissatisfaction with
current treatments
Differentiated product that addresses areas of high unmet medical need
Efficient use of capital with near-term value building inflection points
Strong patent estate with protection extending to 2040
COPYRIGHT 2021 ALPHA COGNITION, INC. 21Executive Team Has Over 250 Drug Approvals And
20 Commercial Launches
$4.1M
Michael Mcfadden Fred Sancilio Colleen Johns
CEO President, Product Development SVP, Product Development
$25.0M
Lauren D’Angelo Jeremy Wright Denis Kay
Chief Commercial Officer Chief Financial Officer Chief Scientific Officer
COPYRIGHT 2021 ALPHA COGNITION, INC.
COPYRIGHT 2021 ALPHA COGNITION, INC. 22Potential Catalysts & Upcoming Event
2021
Begin enrollment of the ALPHA-1062 pivotal trial in AD
Complete enrollment in ALPHA-1062 pivotal trial in AD
ALPHA-1062 pre-clinical study initiation in mTBI
ALPHA-0602 pre-clinical study initiation
2022
Top-line results of the ALPHA-1062 study in mTBI (Q1)
Top-line results of the ALPHA-1062 pivotal trial in AD (Q1)
Top-line results of ALPHA-0602 pre-clinical study results (Q1)
Begin enrollment of ALPHA-1062 label enabling study in AD (Q2)
Submit NDA for ALPHA-1062 in AD (Q3)
2023
Potential ALPHA-1062 FDA approval for mild-to-moderate AD (Q2)
Top-line data results of ALPHA-1062 label enabling study in AD (Q2)
Potential ALPHA-1062 label change (Q4)
COPYRIGHT 2021 ALPHA COGNITION, INC.
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