Ensysce Biosciences, Inc. · NASDAQ:ENSC
Ensysce Biosciences — Investor Presentation (May 2022)
53 slides from Ensysce Biosciences's investor presentation, May 5, 2022
Slide 1: The next generation of opioids?
The next generation of opioids? , NASOMG: ENS Lynn Kirkpatrick, PhO - Ensysce" ary 2022
Slide 2: Disclaimer
Disclaimer Ensysce's PF614 and nafamostat are currently in clinical and pre-clinical trials, Involving both the TAAP platform and MPAR platform. Accordingly, PF614 and nafamostat have the risks and uncertainties inherent in any drug in trial-phase, which include, but are not limited to, a failure to
Slide 3: Analgesic care in 2022 - the next generation
Analgesic care in 2022 -
Slide 4: Analgesic care in 2022 - the next generation
Analgesic care in 2022 - the next generation. * Chronic and severe pain W ° The opioid crisis J - 2 potential new classes of agents: TAAP™ and MPAR™ * PF614 data: the first TAAP opioid
Slide 5: Chronic and severe pain
Analgesic core in 2022 - the next generation. * Chronic and severe pain
Slide 6: How are we doing?!
how are we doing?! No Mild Moderate Severe Very Severe Worst Pain Pain Pain Pain Pain Pain Possible
Slide 7: Analgesia 2022 - More pain, more abuse, more deaths
Slide 8: In the USA
IN THE USA: Chronic Pain — 50 million Opioid Rx — 191 million Cost — $560 billion Deaths per day - 222
Slide 9: In perspective
- IN PERSPECTIVE
Slide 10: Pain is Up, Painkillers are Down
Pain is Up Painkillers are Down Ref: IQVIA 2021. 388 Sales $ Volume s ¢ s s Integrated View All Opioid brands and generics s 220 20 200m 800 800 ‘TRx Volume ao 60m fmm 02200 ANALG NARCOTIC (Sales $ Volume) =°=02200 ANALG NARCOTIC (TRx Volume) 10
Slide 11: Opioid use/abuse
OPIOID USE/ ABUSE
Slide 12: The Opioid Receptor as an Analgesic Target
Pare lroet The Opioid Receptor as an Analgesic Target Immune cell peptide Phospholipase C, Inositol triphosphate ‘Acid-sensing ion channels, Hyperpolarization-activated cyclic nucleotide-gated Front. Pharmacol., 29 November 2018 G protein-coupled inwardly-rectying potassium channels (GIRKs) https://
Slide 13: Chronification
“CHRONIFICATION” Surgery or injury . causes Sustained inflammation currents Transient Activation Sensitization Sustained Activation Ref: P Fine. CNS = Central Nervous System ‘Structural Remodeling CHRONIC PAIN B
Slide 14: Pain impacts
PAIN IMPACTS Substance Misuse, ‘Abuse Secondary Anxiety medical problems XN Functional uncti Depression Disabilities ~~ =. Sleep > / Persistent Pain y € Cognitive Distortions disturbance: Ref: M Cheatle.
Slide 15: Interplay
Ref: L Webster INTERPLAY Pain Disorders Addiction Combined Psychiatric Disorders Effects. Disorders Drugs - Rx drugs and illicit 15
Slide 16: How bad is it!
- how bad is it! How Treatment for Chronic Pain Can Help Reduce Suicide Risk Reports show that 50 percent of chronic pain patients consider suicide to escape their physical pain. Treatments can help people chooselife, von Chronic Pain and Suicide: Signs You or a Loved One Needs Help, and How to Get
Slide 17: Outlawing is not the answer
Outlowing is not PRESCRIPTION BLANK Ref: Ballotpedia v
Slide 18: Pain impact - worried about Rx drug addiction
PAIN IMPACT - worried about Rx drug addiction! Which of the following would you describe as a major health problem in the U.S.? (multiple responses allowed) Cancer 59% Heart disease 52% Diabetes 52% Depression 42% Alcoholism 37% Alzheimer’s disease 34% Parkinson’s disease 15% Not sure 15% 18
Slide 19: The Opioid Crisis
Analgesic core in 2022 - the next generation. * The Opioid Crisis 19
Slide 20: Addiction
Addiction Ref: NIDA/ N Volkow. 20
Slide 21: Stress
stress Drug-Abusing Behavior Low Moderate High Patient Stress Level Ref: L Webster
Slide 22: When liking becomes wanting
Whenlikingbecomes =
Slide 23: Individual
individual Tek do a ~~ T
Slide 24: Individual receptor variation
individual Receptor Variation for Same Patient With Different Drug Level of Activation Drug 4 Sn Drug 2 MOR-1 MOR-1 MOR-1 MOR-1 MOR-1 Variant5 Variant2 Variant3.--Variant4—- Variant 5 Receptor
Slide 25: Spot the 1?
Spot the 1?
Slide 26: Over-consuming
Over-consuming Crushing and drinking/ chewing Crushing and snorting Crushing and injecting Combining with other drugs
Slide 27: Abuse Quotient
QUOTIENT - The attractiveness of a drug for abuse, the “abuse potential” Extended release formulations (Abuse Deterrent of a drug increases as the value of the AQ increases Formulations; ADF) were developed to reduce AQ. Form Route PK PD 3 oral a AQ = Crnax/Tmax ed 3 2 Tine 8 «= 3 — 8 3 oral / 5 2 g
Slide 28: ADFs
ADFs: OxyContin: Intact vs manipulated 28
Slide 29: Words are important: deterrent vs protectant
Words are Deterrent vs protectant Deterrent: a thing that discourages or is intended to discourage someone from doing something. "cameras are a major deterrent to crime”. Protectant: a substance that provides protection, e.g. against disease or ultraviolet radiation. 29
Slide 30: Potential new classes: TAAP and MPAR
Analgesic core in 2022 - the next generation. * 2 potential new classes: TAAP™ and MPAR™ 30
Slide 31: Stepladder
Stepladder ‘Song’ opioid + nonoplld -tadjuvant therapy ‘Weak’ opioid: nenopioid + adjuvant therapy Nonopoid + adjuvant therapy Figure 1. modern rendton ofthe orginal 1986 WHO pain ladder wit 3 steps. Patents begin athe frst rung and then based on pan Intent progress, ung by rung, up the ladder oy as
Slide 32: Ideal opioid
IDEALOPIOID = Reinforcing Efficacy Comes Before Therapeutic Efficacy Comes Before Therapeutic Efficacy Reinforcing Efficacy Therapeutic” Efficacy / / Reintorcing Efficacy Reinforcing Efficacy ‘Therapeutic / efficacy / Toxicity Toxicity / / Response Response Drug Dose Drug Dose 323 REF: THOMPSON 1977
Slide 33: Opioid
OPIOID Therapeutic Efficacy Low Reward Low Toxicity Must Relieve Pain Not “reinforcing” in the therapeutic dose range: does not drive drug seeking behavior Side effects separated from beneficial (analgesic) effects
Slide 34: Imagine an opioid...
IMAGINE AN OPIOID... > Impossible to alter PK profile > Disliked by, unattractive to, abusers > Yet highly effective in relieving severe pain
Slide 35: TAAP - 2-step verification mechanism
TAAP - 2-step verification mechanism to improve oral delivery, with release of active ingredient only in the small intestine with exposure to trypsin IMPROVED TAAP chemical modification VI TAAP is only activated by trypsin, f y TAAP not altered by manipulation.,
Slide 36: TAAP two-step release process
TAAP Two-Step Release Process Step 1: Swallow drug + Following ingestion, the drug is activated only after exposure to trypsin, a digestive enzyme that is active only in the small intestine Step 2: Timing chemically controlled + Asecond step is required for full release of the active drug. The chemi
Slide 37: MPAR anti-overdose platform
T™T™ MULTI PILL ABUSE _ : ; RESISTANT MPAR™ is a smart anti-overdose platform that is designed to protect patients from overdosing when it is combined with TAAP opioids. ANTI-OVERDOSE e PLATFORM MPAR" is only triggered n overdose. e MPAR™ inhibits trypsin activation step e Using a prescribed dose gi
Slide 38: MPAR Mechanism of Action
MPAR™ Mechanism of Action ae Combination Product With Dose-Triggered Trypsin Inhibition C_ mm PRESCRIBED DOSE No Interference when normal dose taken; Low dose of trypsin inhibitor (nafamostat) does not affect release of the opioid Trypsin activation releases free and active drug product SUB-THRESHOL
Slide 39: PF614-MPAR preclinical data
PF614-MPAR™ Without MPAR™ With MPAR™ TAAP + MPAR™: PRECLINICAL DATA PF614 without TI nafamostat PF614 with TI nafamostat + Combination product of PF614 with an ultrapotent = trypsin inhibitor, nafamostat 2 j + Taken at prescribed doses there is no change in i? | i oxycodone release from PF614 i /\ B
Slide 40: PF614 Data
Analgesic care in 2022 - the next generation. -PF614 Data 40
Slide 41: Cannot be altered
connot be altered * Unlike OxyContin, Ensysce’s opioid PF614, even when crushed, has no altered release kinetics: AQ * In Phase | studies have been able to dose match PF614 to marketed OxyContin dose units. & é Pre-clinical Blood Concentration of Opioid Vs. Time (dog) 20 CRUSHED Oxycodone 20mg UNTAM
Slide 42: PF614 TAAP chemical modification
PF614 TAAP chemical modification Cannot snort for joy — no trypsin in the nasal passage Cannot inject for joy — no trypsin in the blood stream Cannot crush to make work faster Added protection for OD (MPAR) 42
Slide 43: PF614-101: Softer, more efficient
PF614-101 Sofer, More Efficient : Oxycodone Concentration in Blood vs. Time following PF614 administered as oral solution xjloen nti cancemnantrg Slow Onset ‘max blood levels reached @ 4-h across all cohorts Dosen Naltrexone / meal s5ma/21/ ota Sint /22/ yes /tstes ‘TAAD: HUMAN CLINICAL DATA, PF614-
Slide 44: Compared to OxyContin
COMPARED TO OXYCONTIN Oxycodone halflife TARP: CLINICAL DATA ose (514 / OxyContin) ome wooo PF614-101Phase 1 Ensysce’s opioid PF614’s half-life is 12.7 hours, versus OxyContin’s 7.6 hours As a result, Ensysce’s PF614 is more convenient for the patient, since PF614 needs to be taken only twice- day,
Slide 45: PF614-102 MAD/BE
PF614-102 MAD/BE A Phase 1b, Randomized, 2-Part Single-Center Study to Evaluate the Pharmacokinetics and Safety of Multiple-Ascending Oral Doses of PF614 and the Food Effect and Bioavailability/Bioequivalence of Single Oral Doses of PF614 Relative to OxyContin in Healthy Adult Subjects The primary o
Slide 46: PF614-102 MAD Table of Adverse Events
PF614-102 MAD Table of Adverse Events PF614 OxyContin PF614 OxyContin OxyContin 50 mg 20 mg 100 mg 40 mg 200 mg n=6 n=2 n=6 n=2 n (%) n(%) n(%) n(%) Total subjects with at least 1 2 (33.3) 1 (50.0) 1 (16.7) 1 (50.0) 2 (100.0) TEAE* * Treatment Emergent Adverse Events: Vertigo, Photophobia, Nausea, C
Slide 47: PF614-102 MAD oxycodone concentrations
Oxycodone (ng/ml) PF614-102 MAD Oxycodone from 50, 100 and 200 mg PF614 n= 6 first 12 hours F614 50mg Solution F614 100 mg Solution —PF614 200 mg (2x 100mg capsules) Hours ‘Oxycodone (ng/ml) Oxycodone from 20, 40 and 80 mg OxyContin n=2 first 12 hours (OxyCantin 20 mg —onyContin 40 me —onyContin 80
Slide 48: PF614-102 MAD Cmax
PF614-102 MAD or PFBI4 Day 1 Cmax 20 40 20 Oxycodone mg equivalent dose +-PF614 -»-OxyContin max Day 5 Cmax 20 40 a0 Oxycodone mg equivalent dose +-PF614-*-OxyContin 43
Slide 49: PF614-102 MAD AUC
2500 ‘ngimL) Oxycodone (hr PF614-102 MAD orPFBI4 AUC, Day 1 AUC), ——— ae 20 0 80 Oxycodone mg equivalent dose *-PF614-*-OxyContin ‘ngimL) Oxycodone (h Day 5 AUC), Oxycodone mg equivalent dose *-PF614 ~e-OxyContin 49
Slide 50: PF614-102 MAD Day 1 and Day 5 AUC
2500 ‘Oxycodone (hingimL) PF614-102 MAD or PFE14 Day 1 and Day 5 AUC, OxyContin = 20 40 80 Oxycodone mg equivalent dose OxyContin D1 -~ OxyContin D5 Day 1 and Day 5 AUC,, PF614 6 20 40 a0 ‘Oxycodone mg equivalent dose PF614D1 -ePF614D5 50
Slide 51: PF614-MPAR-101
PF614-MPAR-101 PF614 (25 mag) with ond without nofamostat (10 ma) Average Systemic Oxycodone after A Systemic PF614 aft 25 mg Oral PF614 with/without 10 mg Nafamostat samara ane 25 mg Oral PF614 with/without 10 mg Nafamostat Oxycodone (ng/ml) F614 (ng/mL) hours hours —*-With Nafamostat ‘Without Nafa
Slide 52: The next generation of opioids?
The next generation of opioids? BASIS TO BELIEVE WE COULD BE THE NEXT GENERATION OF OPIOIDS. TAAP and MPAR EMPLOY SOPHISTICATED CHEMISTRY. DATA STRONG FOR TAAP AND MPAR AS PF614 ENTERS PHASE 3. MPAR OVERDOSE PROTECTION DEMONSTRATED IN HUMANS. WIDESPREAD SUPPORT WITH FAST TRACK AND NIH/NIDA. TAAP AND
Slide 53: Thank you
Thank you Lynn Kirkpatrick, PhD WWW.ensysce.com 53
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