POZ TM The Era of Once Weekly Continuous Drug Delivery in Parkinson’s Disease is Here

1. POZTM The Era of Once Weekly Continuous Drug Delivery in Parkinson’s Disease is Here

2. POZ™ - Next Generation in Polymer Technology • Proprietary drug delivery technology platform based on poly(2-oxazoline) (POZ™) • Dominant IP with over 30 issued patents, and 25+ pending • Global exclusive license to “click” chemistry from Scripps for POZ-therapeutics (unlimited right to sublicense) • Non-immunogenic • Does not accumulate in any tissues • Is not metabolized • Clears entirely by renal filtration • POZ™ provides continuous drug deliveryof small molecules when administered via subcutaneous administration • Clinically validated – safe, very well-tolerated • Optimizes safety / efficacy profile of known molecules • Extends interval of administration for improved half life and greater patient compliance • Creates new IP and extends market exclusivity • Serina pipeline utilizes POZ™ in low risk development strategy for improved versions of established drugs with known safety and efficacy profiles #PODD2019

3. How we prepare “polymer therapeutics” Immunotherapy • A polymer of POZ is illustrated above with • Rotigotine (a potent dopamine agonist) is attached to multiple pendent groups (SER-214) • Via a cleavable ester linker (a cleavable linker is one that will release the intact drug following cleavage by an enzyme in the blood - butyrylcholinesterase) • If the polymer shown has an extended profile of circulation in the body • The release of the attached drug from the polymer will also be extended = continuous drug delivery

4. Chemical Structures of Pipeline CompoundsAll have an accessible chemical handle Immunotherapy Buprenorphine Rotigotine Apomorphine Tetrahydrocannabinol THC Cannabidiol CBD • Candidate small molecules must have a “chemical handle” • Linkers are attached to the –OH (creates a stable ester), an azide moiety on the end of the linker allows for stable “click chemistry” attachment to the pendent alkyne of the polymer backbone • Search known structures (AdisInsight) = thousands of candidate molecules (phenolic hydroxyl, alcohols, carboxylates)

5. Serina Pipeline #PODD2019 HEAL Initiative – Helping to End Addiction Long-term

6. Why is continuous drug delivery so important ? Continuous drug delivery improves outcomes, avoids dyskinesia liability improves outcomes Naïve MPTP-monkeys were divided into two groups Apomorphine rod implant, vs Daily (x 3) apomorphine injections Apomorphine rod implanted monkeys remained ON without any dyskinesia for 6 months (!) Daily SC apomorphine monkeys were transiently ON – and all developed severe dyskinesia within the first day Immunotherapy #PODD2019 6 6

7. The challenge in Parkinson’s – Continuous drug deliveryThis is the typical day in the life of a Parkinson’s patient with advancing disease “ON” with dyskinesia Weekly SC Injection Good “ON” Time Therapeutic Dose Range This is where most patients with Parkinson’s disease spend their day Mostly unpredictable “ON-OFF” Wearing Off Dose Failure Partial “ON” Unpredictable “ON-OFF” Morning off 6 AM 7 8 12 PM 4 8 10 11 Dose • The green area illustrates the blood levels where patients are in the therapeutic range • “What if you could administer a single SC injection that provided continuous drug delivery in the therapeutic window – for an entire week ?”

8. A Weekly SC Injection of SER-214 Provides continuous drug delivery in monkeys – Data from 13-wk toxicology study (IND 126914) Cynomolgus macaque monkeys (~ 3 kg) received a single weekly SC injection of ~ 58 mg SER-214 (~ 7 mg equivalents rotigotine) / kg in a final volume of ~ 0.5 cc In weeks 1/5/9/12 daily plasma rotigotine levels were determined Following a slow rise to Tmax on Day 3-4 plasma levels of released rotigotine remained within a narrow range of 6-9 ng/ml without accumulation or accelerated clearance #PODD2019

9. A Weekly SC Injection of SER-214 Provides continuous drug delivery in stable, non-fluctuating Parkinson’s disease patients • Data from Cohort 3 in the multiple dose portion of the Phase Ia trial in Parkinson’s disease patients • Patients received: an initial subcutaneous dose of 50 mg SER-214; 100 mg dose in Week 2 (not shown) and 200 mg in Week 3 & Week 4 • Plasma levels of released rotigotine are shown for Week 3 and Week 4 and compared to the 3 mg Neupro patch #PODD2019

10. A Weekly SC Injection of SER-214 Dose-dependent decline in UPDRS (part III) • Data from Cohorts 1,2 and 3 in the multiple dose portion of the Phase Ia trial in Parkinson’s disease patients • Change from baseline in UPDRS (Part III) as a function of dose • The predicted change in UPDRS (Part III) at the 400 mg+ doses of SER-214 would approximate the change in • UPDRS (part III) of Neupro (8 mg patch) #PODD2019

11. Summary SER-214 Single weekly SC injection for early and advanced PD – Provides continuous drug delivery • A single weekly subcutaneous injection of SER-214 represents a significant advance for Parkinson’s disease • Parkinson’s disease • Improved compliance, markedly improved tolerability without skin reactions, improved QoL issues, in blinded product profile SER-214 chosen over Neupro • KOLs believe it would be used primarily in early PD • SER-214 is predicted to reduce “off” time (based upon data from the PREFER trial comparing 8 mg Neupro to placebo) • Treat or prevent dyskinesia in patients with early motor complications • 505(b)(2) – rely on the established safety/efficacy of Neupro • Potential for a single Phase 3 trial • Commercial launch in 2025 • Readily penetrable market in US of $100-200 M #PODD2019

12. POZ-apomorphineApomorphine has ideal properties for POZny of the characteristics ideal for POZ • The first dopamine agonist used in the treatment of Parkinson’s disease (1884) • Most potent dopamine agonist known (our experts call it the “holy grail” of dopamine Rx) • Reverse akinesia within minutes • Limited bioavailability makes it unsuitable as an oral, transdermal, inhaled or suppository drug • Present formulations limited by significant skin irritation through transcutaneous approaches that require daily administration and a continuous infusion device (APO-go) • Hypothesis - Attachment to POZ should keep the molecule on the polymer until it reaches the blood (no BChE in the SC compartment ) • Upon entry into the vascular compartment the apomorphine is immediately cleaved, provides continuous drug release as long as the polymer circulates #PODD2019

13. Apomorphine (APO-go1)Significantly reduces OFF time in advanced patients, but has severe skin reactions in 40-60% of patients advanced PD … current formulation has significant adverse reactions Patients with advanced PD have > 6 hours a day of OFF periods - they are unable to perform even routine daily tasks Patients use an infusion device to provide continuous delivery of apomorphine ~ 12-16 hours a day Removed at bedtime Severe skin reactions Nodules 1 APO-go is approved in the EU, not yet approved in the US

14. POZ-apomorphine (SER-240 and SER-241 - differ by linker)Human plasma hydrolysis demonstrates programmable drug release via linker chemistry and drug load hydrolysis demonstrates programmable drug release SER-240 The ability to program the release rates of attached molecules in vitro allows for the selection of linkers that will lead to a predictable range of plasma release rates in vivo SER-241 #PODD2019

15. APO-go vs POZ-apomorphineWill POZ-apomorphine provide continuous drug delivery and avoid skin issues ? POZ-conjugates avoid the development of skin issues ? • Single dose study in monkey of infusion of APO-go versus SER-240 versus SER-241 • Group I : 12 hour infusion of 1% APO-go solution (dose equivalent to human equivalent dose of ~ 1.5 mg / kg) • End of infusion • Daily cage-side observations • Biopsy of infusion site • Group II (SER-240) and Group III (SER-241) : SC injection of ~ 0.6 mL of 1.5 mg POZ-apomorphine / kg • Daily cage-side observations • Biopsy of injection site APO-go #PODD2019

16. Apomorphine (APO-go)At end of infusion a slight degree of redness at sitein advanced PD … current formulation has significant adverse reactions • At 12 hours there were no skin reactions other than slight redness at site on infusion #PODD2019

17. Apomorphine (APO-go)By 72-96 hours all monkeys in Group I had draining abscessesn advanced PD … current formulation has significant adverse reactions • At 72-96 hours there were draining abscesses at site of infusion in all monkeys in the APO-go group #PODD2019

18. Group III – SER-241 MonkeyNone of the monkeys in Group II or Group III had evidence of abscess, nor histologic evidence of inflammation PD … current formulation has significant adverse reactions • At 72-96 hours there were draining abscesses at site of infusion in all monkeys in the APO-go group #PODD2019

19. PK Profiles of APO-go versus SER-240 and SER-241 (single dose)POZ-conjugates provide continuous drug release of apomorphine without skin reactions PD … current form APO-go was administered by continuous infusion over 12 hours – typical peak:trough PK profile SER-240 or SER-241 when administered as a single SC injection provide continuous delivery of released apomorphine #PODD2019

20. Predicted PK Profile of SER-241 in HumansSER-241 predicted to provide plasma levels of apomorphine that may prevent OFF periodsd PD … current formulation has significant adverse reactions PK of SER-241 was modeled using a 1- compartment fit to predict human PK A weekly dose of ~ 0.5 mg eq/kg SER-241 is predicted to yield plasma levels ~ 5-10 ng/mL free apomorphine This would require a device to deliver between 5-7 mL over ~15 minutes once each week #PODD2019

21. Needleless Transfer SystemAvoids needle and syringe Attach WFI vial to needleless transfer system (West) Attach to vial of lyophilized SER-214 (under slight vacuum) Water is drawn into vial instantaneously, goes into solution within 3-5 minutes Avoids exposure to needle injury #PODD2019

22. Enable InjectionsInjection systems designed for ease of use, compliance, and avoidance of needle injury Attach resuspended SER-214 to port on vial transfer system Nitrogen is pumped into vial, which filters and loads the enFuse device automatically Does not need a healthcare provider to administer Avoids exposure to needle injury Vial transfer system is in late stage development at Enable Injections #PODD2019

23. Enable InjectionsInjection systems designed for ease of use, compliance, and avoidance of needle injury Remove device from filling system, adhesive is exposed automatically Press onto clean skin area Press button, infusion begins automatically Device retracts needle when infusion is complete, button pops up Remove device, no exposure to needle #PODD2019

24. SUMMARY • The era of once weekly continuous drug delivery in Parkinson’s disease is here • A patient-friendly and convenient approach that does not require a health care provider, and can be administered in the home once a week • Improved compliance, convenience, QoL and optimizes outcomes • SER-214 (POZ-rotigotine) • Parkinson’s disease – poised to enter Phase Ib/II in 2020 • Indication - early PD as initial therapy (but could be used in advanced PD) • Addresses a penetrable market in the US of between $100-200 M • Commercial launch in 2025 • SER-241 (POZ-apomorphine) • Parkinson’s disease – poised to enter Phase Ia in 2020 • Indication – advanced PD, potential to prevent OFF periods • Addresses a market between $600-1,600 M • Commercial launch in 2027-2028 #PODD2019