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1、 Precigen.All rights reserved.Precigen,Inc.January 11,2023January 11,2023Helen Sabzevari,PhDPresident&Chief Executive Officer41stAnnual J.P.Morgan Healthcare Conference Precigen.All rights reserved.Forward-looking Statements2Some of the statements made in this presentation are forward-looking statem
2、ents.These forward-looking statements are based uponthe Companys current expectations and projections about future events and generally relate to plans,objectives,and expectations for the development of the Companys business,including the timing and progress of preclinical studies,clinical trials,di
3、scovery programs and related milestones,the promise of the Companys portfolio of therapies,and in particular its CAR-T and AdenoVerse therapies.Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable,all forward-looking
4、statements involve risks and uncertainties,including the possibility that the timeline for the Companys clinical trials might be impacted by the COVID-19 pandemic,and actual future results may be materially different from the plans,objectives and expectations expressed in this presentation.The Compa
5、ny has no obligation to provide any updates to these forward-looking statements even if its expectations change.All forward-looking statements are expressly qualified in their entirety by this cautionary statement.For further information on potential risks and uncertainties,and other important facto
6、rs,any of which could cause the Companys actual results to differ from those contained in the forward-looking statements,see the section entitled Risk Factors in the Companys most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.This presenta
7、tion contains market data and industry statistics and forecasts based on studies and clinical trials sponsored by third parties,independent industry publications and other publicly available information.Although Precigen believes these sources are reliable,it does not guarantee the accuracy or compl
8、eteness of this information and has not verified this data.All of the pharmaceutical products described in this presentation are investigational new drugs,which are currently undergoing pre-clinical and/or human clinical trial testing.As a result,none of them have had their safety or efficacy establ
9、ished or are approved by the U.S.Food and Drug Administration or any other regulatory agency.All information in this presentation is as of the date of its cover page,and Precigen undertakes no duty to update this information unless required by law.Precigen.All rights reserved.Precigen is Deploying N
10、ovel Gene&Cell Therapeutic Approaches to Address High Unmet Healthcare Needs3AdenoVerse ImmunotherapyUltraCAR-TNon-viral multi-gene deliveryNon-exhausted,stem-like T cell phenotypeHigher antigen-specific expansionEnhanced in vivo persistenceAbility to deplete with kill switchOvernight manufacturing
11、processLarge payload capacityLow seroprevalence in humansAbility for repeat administrationDurable antigen-specific immune responseHighly productive manufacturing process Precigen.All rights reserved.Precigen Clinical Pipeline4ADENOVERSEIMMUNOTHERAPYPRODUCTPRODUCTPLATFORMPLATFORMINDICATIONINDICATIOND
12、ISCOVERYDISCOVERYPRECLINICALPRECLINICALPHASE 1PHASE 1PHASE 1BPHASE 1BPHASE 2PHASE 2PHASE 3PHASE 3PRGNPRGN-20092009AdenoVerseHPV+Solid TumorsPRGNPRGN-20122012AdenoVerseRecurrent Respiratory Papillomatosis(RRP)PRODUCTPRODUCTPLATFORMPLATFORMINDICATIONINDICATIONDISCOVERYDISCOVERYPRECLINICALPRECLINICALPH
13、ASE 1PHASE 1PHASE 1BPHASE 1BPHASE 2PHASE 2PHASE 3PHASE 3PRGNPRGN-30053005UltraCAR-TOvarian CancerPRGNPRGN-30063006UltraCAR-TAML,MDSPRGNPRGN-30073007UltraCAR-TROR1+Hematological&Solid TumorsULTRACAR-TPRODUCTPRODUCTPLATFORMPLATFORMINDICATIONINDICATIONDISCOVERYDISCOVERYPRECLINICALPRECLINICALPHASE 1PHAS
14、E 1PHASE 1BPHASE 1BPHASE 2PHASE 2PHASE 3PHASE 3AG019AG019ActoBioticsType 1 DiabetesACTOBIOTICS Precigen.All rights reserved.Precigen in 2022:Significant Clinical and Fiscal Accomplishments5 PRGN-3006UltraCAR-TPresented positive safety and efficacy Phase 1 data at ASH;Activated Mayo Clinic(MN)as expa
15、nsion site for the Phase 1b trial enhancing the decentralized manufacturing model;FDA clearance received for redosing;FDA granted Fast Track designation PRGN-3005UltraCAR-TCompleted enrollment in Phase 1 clinical trial;Initiated Phase 1b expansion trial;FDA clearance received for redosing;Tech trans
16、fer underway for expansion to major US cancer centers PRGN-3007 Next Gen UltraCAR-TTech transfer complete for initiation of the Phase 1 umbrella trial in ROR1+hematological(CLL,MCL,ALL,DLBCL)and solid tumors(TNBC);Phase 1 trial open for enrollment PRGN-2012 AdenoVerse Immunotherapy Completed enrollm
17、ent(N=15)in Phase 1 trial in recurrent respiratory papillomatosis;Phase 2 trial initiated and rapidly enrolling patients(N=20 enrolled to date);Announced upcoming presentation of complete Phase 1 safety and efficacy data(January 24th)PRGN-2009 AdenoVerse Immunotherapy Enrollment and dosing complete
18、in the Phase 1 mono(N=6)and combo therapy(N=11)in HPV-associated cancers;Enrollment ongoing in Phase 2 mono arm in newly diagnosed oropharyngeal squamous cell carcinoma(OPSCC)with 19 of 20 enrolled as of end of 2022 CorporateMaximized value of Trans Ova Genetics leading to sale of non-health subsidi
19、ary for$170M upfront and a potential$10M earn-out CorporateRetired$157M of the outstanding convertible notes due in July 2023 in a non-dilutive manner,resulting in$5.7M in interest and discount savings as of the end of 2022LEGEND:goal met;goal expected Q1 23UltraCAR-T PlatformOverview&Differentiatio
20、n Precigen.All rights reserved.December 11,2022Ash 2022 fast production fails to cure Car-Ts problem1Novartis and Gracells two-day manufactured Cars do not solve cell therapys biggest bottleneck yet.Data presented at Ash by Novartis and Gracell suggested that manufacturing time can be cut drasticall
21、y,from a few weeks to two days,but the elephant in the room remains:patients still have to wait weeks or months before they receive therapy.Current CAR-T Therapies Have Not Solved One of Cell Therapys Biggest Bottlenecks Long Vein-to-Vein Times Leading to Delayed Patient Treatment7Jacob PliethHow lo
22、ng?This shortcoming was laid bare at Sundays Ash session when the presenter,Dr Pere Barba of Vall dHebron University Hospital,repeatedly dodged questions about what the vein-to-vein time was in a phase 1 lymphoma study of the T-Charge-manufactured YTB323(rapcabtagene autoleucel).After insisting that
23、 a clinical trial setting was suboptimal to assess this,Dr Barba eventually admitted that vein-to-vein time the time taken from apheresis to cell reinfusion was“similar”to the industry norm for autologous Car-T therapies,implying two to six weeks.This is only part of the problem.Current capacity con
24、straints mean that,once a patient is deemed a candidate for Car-T therapy,it then takes weeks before a slot can be booked for their cells to be manufactured.Dr Barba said some patients were kept waiting for so long that they had to be bridged with chemo,and indeed some went into remission as a resul
25、t.Dr Barba presented a swimmers plot of responses that pointedly omitted patients time between enrolment and dosing.this was shown to be between two and three months,with one patient waiting as long as six months.Against this backdrop shaving a week or two off manufacturing time seems paltry.Precige
26、n.All rights reserved.UltraCAR-TAutologous CAR-TAllogeneic CAR-T/NK#Manufacturing1 DayUp to 4 Weeks*4+Weeks*Quality Control Release AssaysSame Day(80%of ovarian tumors1Limited expression found on healthy tissuesInitial target is advanced stage platinum resistant ovarian cancerPRGN-3005 Binding SiteT
27、MCytoplasmic TailCOOHSEA ModulesPutativeCleavage SiteTandemRepeatsDomainN-TerminalDomainNH2MUC16 shed portionPRGNPRGN-3005 EXPANSION&PERSISTENCE IN PERIPHERAL BLOOD3005 EXPANSION&PERSISTENCE IN PERIPHERAL BLOODINTRAPERITONEAL(IP)ARM02040608103104105DayCAR-T Copies/g of DNADose Level
28、 1Dose Level 3Dose Level 2 Precigen.All rights reserved.PRGN-3005 Phase 1/1b Clinical Trial:Interim Data in the IP Arm Demonstrate Favorable Safety and Positive Clinical Activity in Ovarian Cancer Patients15INTRAPERITONEAL(IP)ARMINTRAPERITONEAL(IP)ARMCHANGE IN SUM OF DIAMETERS OF TARGET LESIONSPatie
29、nt administered low dose(19 x 106Total UltraCAR-T cells)PRGN-3005 via IP administration without lymphodepletionExample of observed decrease in size of target lesions,including solid lesions such as the bladder(above)CASE STUDY 1CASE STUDY 1CAR-T Cell Toxicity(N=10)CRS(ASTCT guidelines)Neurotoxicity(
30、CARTOX-10)CRS,any grade:0%0%(0/10)Use of tocilizumab:0%0%(0/10)Neurotoxicity,any grade:0%0%(0/10)Favorable safety profile across the Dose Levels tested in IP ArmNo incidences of CRSNo neurotoxicitySAFETY SUMMARYSAFETY SUMMARYCASE STUDY 2CASE STUDY 2Patient administered low dose(7.5 x 106Total UltraC
31、AR-T cells)PRGN-3005 via IP administration without lymphodepletionComplete response in axillary lymph node target lesion after 3 months BaselinePost-infusionBaselinePost-infusionAdenoVerse Immunotherapy PlatformOverview&Differentiation Precigen.All rights reserved.AdenoVerse Platform:Potential for B
32、road Applications in Gene Therapy17 Precigen.All rights reserved.AdenoVerse:Industry-leading Adenovector PlatformINTERNAL&CONFIDENTIAL18PRECIGENS GORILLA ADENOVECTORS SHOW PRECIGENS GORILLA ADENOVECTORS SHOW SUPERIOR PERFORMANCE CHARACTERISTICSSUPERIOR PERFORMANCE CHARACTERISTICS Large genetic paylo
33、ad capacity Off-the-shelf availability Ability for repeat administration Durable antigen-specific immune response Non-replicating adenoviruses Highly productive manufacturing processLIMITATIONS OF COMPETING APPROACHESLIMITATIONS OF COMPETING APPROACHESVACCINES Limited antigen coverage DNA vaccines m
34、ay have relatively poor immunogenicity Pre-existing immunity to human Ad5 may limit efficacy1TCR-T CELLS Applicable in only a small subset of patients due to HLA polymorphism Target only a single antigen epitope Long and expensive manufacturing process Potential for the mispairing of endogenous and
35、exogenous TCR chains18 Precigen.All rights reserved.AdenoVerse Immunotherapy Explained19PRGN-2012 AdenoVerse Immunotherapy for Recurrent Respiratory Papillomatosis Precigen.All rights reserved.21R&D DAY PARTICIPANTSHelen Sabzevari,PhDPresident and CEOPrecigenClint T.Allen,MDSenior Investigator,Surgi
36、cal Oncology ProgramCenter for Cancer Research National Cancer Institute(NCI)Lead associate investigator for the PRGN-2012 clinical trialPrecigen Virtual R&D Day Tuesday,January 24,20234:30 PM ET Precigen.All rights reserved.Recurrent Respiratory Papillomatosis(RRP):Need for Safe and Effective Treat
37、mentRRP IS CAUSED BY HPV6 OR HPV11 INFECTIONRRP IS CAUSED BY HPV6 OR HPV11 INFECTION1 1-2 2A rare disease in which benign tumors called papillomas grow in the respiratory tractSymptoms include hoarse voice,difficulty sleeping and swallowing,chronic coughing,or breathing problemsAffects both children
38、 and adultsTracheal involvement and airway obstruction occurs in 25%of casesNormal tracheaRRP PatientCURRENT TREATMENT PARADIGMCURRENT TREATMENT PARADIGMRepeat surgery is the only standard-of-care treatment for RRPPatients can require hundreds of lifetime surgeries22RATIONALE FOR HPV6/11 THERAPEUTIC
39、 VACCINE FOR RRPRATIONALE FOR HPV6/11 THERAPEUTIC VACCINE FOR RRPImmune-mediated clearance of HPV is the only way to potentially cure RRPT cells are the only immune cell that can specifically detect and kill HPV infected cellsLack of HPV-specific T cells in RRP patientsProphylactic vaccines cannot g
40、enerate HPV-specific T cell responsePRGNPRGN-20122012TARGETS HPV6/11 INFECTED CELLSTARGETS HPV6/11 INFECTED CELLSGorilla adenoviral vector,with the ability for repeat injectionsDesigned to elicit T-cell mediated immune responses against papilloma cells infected with HPV6 or HPV11PRGNPRGN-20122012 Pr
41、ecigen.All rights reserved.Recurrent Respiratory Papillomatosis(RRP):Need for Safe and Effective Treatment23RRP DISEASE PREVALENCERRP DISEASE PREVALENCEESTIMATED MARKET OPPORTUNITYESTIMATED MARKET OPPORTUNITY$1BPeak annual market opportunity in US4$2BPeak annual market opportunity including ex-US5Ac
42、tive Cases in USActive Cases in US1:10,000 Adult Cases6,000 Juvenile Cases Active Cases ExActive Cases Ex-USUS2:60,000 Adult CasesANNUAL DIRECT COSTS3$100,000+INDIRECT COSTS=$MILLIONSUS ECONOMIC BURDEN ON RRP PATIENTSUS ECONOMIC BURDEN ON RRP PATIENTSOther HPV6 and HPV11 US disease burden6 350,000 c
43、ases of genital warts in sexually active adultsE.G.,LOSS OF INCOME/WORKPOTENTIAL FUTURE OPPORTUNITYPOTENTIAL FUTURE OPPORTUNITYIMPLIED LIFETIME COSTS Precigen.All rights reserved.Preliminary Data Showed Encouraging Activity of PRGN-2012 in Severe,Aggressive RRPCASE STUDYCASE STUDYPatient required su
44、rgery once every 6 weeks for 2.5 years prior to enrollment8 surgeries in 12 months prior to PRGN-2012 treatment startPatient received 4 vaccinations of PRGN-2012 at 5x1011vp/dose(Dose Level 2)Patient did not require surgery at 6 weeks follow up after treatment completion CASE STUDY:PRGNCASE STUDY:PR
45、GN-2012 TREATMENT RESULTS IN 2012 TREATMENT RESULTS IN INCREASE IN TINCREASE IN T-CELL INFILTRATION OF PAPILLOMACELL INFILTRATION OF PAPILLOMABaseline6 weeks post treatment completionLow levels of T cells at baseline consistent with lack of HPV-specific T cells in RRP patientsSignificant(10X)increas
46、e in T cells infiltrating papilloma post PRGN-2012 treatment Post-treatmentPhotomicrographs of multispectral immunofluorescence identifying T cells in papilloma sections from a patient24PRGN-2009 AdenoVerse Immunotherapy for HPV-associated cancers Precigen.All rights reserved.PRGN-2009:First-in-clas
47、s Investigational Therapy for HPV-associated CancersDISEASE SNAPSHOTDISEASE SNAPSHOTPRGNPRGN-2009:MULTI2009:MULTI-EPITOPE ANTIGEN DESIGN EPITOPE ANTIGEN DESIGN TO TARGET HPV16/18TO TARGET HPV16/18 Gorilla adenoviral vector with ability for repeat injections Multi-epitope antigen design to induce a r
48、obust immune response against HPV16/18 MultiMulti-epitope antigen designepitope antigen design2626690,000New cancer cases in key markets attributable to HPV infections per year2HPV infections account for 5%of all cancers10200,000400,000600,00042,000 cervical cancer570,000 oropharyngeal cancerGlobal
49、Addressable New Cases Per Year Significant unmet need with 15%ORR with Keytruda6ESTIMATED MARKET OPPORTUNITYESTIMATED MARKET OPPORTUNITY26$1BPeak Annual Market Opportunity3 3Cervical Cancer+Head&Neck Cancer$10BGlobal Market for Cervical Cancer+Head&Neck Cancer4,5therapies to grow from$6.7B in 2021 t
50、o$10B in 2030 Precigen.All rights reserved.PRGN-2009 Phase I Study:Summary of Responses to PRGN-2009+M7824PRGN-2009+M7824All(n=10)Cervical(n=2)Head and Neck(n=7)Disease Control Rate(DCR)at first restaging40%(4/10)2/2(100%)2/7(28%)Objective Response Rate(ORR)30%(3/10)2/2(100%)1/7(14%)SUMMARY OF RESPO
51、NSESSUMMARY OF RESPONSESBEST OVERALL RESPONSE BEST OVERALL RESPONSE CR:Complete ResponsePR:Partial ResponseSD:Stable DiseasePD:Progressive Disease0500300350400450500550600Duration Since First Dose(days)SDPRCRPD2PRGN-2009 MonotherapyPRGN-2009 +M782427CASE STUDYCASE ST
52、UDYCervical cancer patient PRGN-2009 at 5x1011vp/dose in combination with M7824CR from approx.6 monthsCR from approx.6 monthsSummaryPrecigen in 2023:Major Anticipated Clinical Milestones29Continue enrollment and add additional clinical sites to the Phase 1b expansion trial of PRGN-3006 in AMLPhase 1
53、b expansion clinical trial data presentation expected in 2024Continue enrollment and add additional clinical sites to the Phase 1b expansion trial of PRGN-3005 in Ovarian CancerPhase 1b expansion trial clinical data presentation expected in 2024Initiate dosing in Phase 1 dose escalation study of PRG
54、N-3007 in ROR1+hematological and solid cancersPhase 1 clinical data presentation expected in 2024Complete Phase 1 safety and efficacy data presentation of PRGN-2012 in RRP scheduled for January 24,2023Outline regulatory strategy in RRP based on ongoing FDA discussionsPhase 1 monotherapy and combinat
55、ion therapy safety and efficacy data presentation of PRGN-2009 expected in 1H 23Interim Phase 2 monotherapy data of PRGN-2009 in newly diagnosed OPSCC expected in 2H 23UltraCAR-TAdenoVerseTM Precigen.All rights reserved.ReferencesSLIDE:Current CAR-T Therapies Have Not Solved One of Cell Therapys Big
56、gest Bottlenecks Long Vein-to-Vein Times Leading to Delayed Patient Treatment1-Plieth,J.,Ash 2022 fast production fails to cure Car-Ts problem.Evaluate Vantage(2022).https:/ Single Infusion of PRGN-3006 Leads to Objective Responses in AML Patients1-Sallman,D.,et al.,64th Annual Meeting and Expositio
57、n of the American Society of Hematology(ASH).Abstract 4633.Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes(2022).https:/ UltraCAR-T:First-in-class Investigational Therapy in Ovarian
58、 Cancer1-Modified from Pich,A.et al.,World J Obstet Gynecol.(2016)SLIDE:AdenoVerse:Industry-leading Adenovector Platform1-Geisbert.T.W.,J Virol.(2011)SLIDE:Recurrent Respiratory Papillomatosis(RRP):Need for Safe and Effective Treatment1-What is RRP?Recurrent Respiratory Papillomatosis Foundation,Acc
59、essed 2023.https:/rrpf.org/what-is-rrp/2-Venkatesan,N.N.,et al.,Recurrent Respiratory Papillomatosis.Otolaryngologic Clinics of North America,Volume 45,Issue 3,June 2012,Pages 671-694.https:/doi.org/10.1016/j.otc.2012.03.006SLIDE:Recurrent Respiratory Papillomatosis(RRP):Need for Safe and Effective
60、Treatment1-Derkay,C.S.,Task force on recurrent respiratory papillomas:a preliminary report.Archives of OtolaryngologyHead&Neck Surgery(1995).121(12),1386-1391;About RRP RRPF NIH Publication No.10-4307(2017)2-Donne,A.J.,et al.,Prevalence and management of recurrent respiratory papillomatosis(RRP)in t
61、he UK:cross-sectional study.(2016).DOI:10.1111/coa.126833-Derkay,C.S.,et al.,Update on Recurrent Respiratory Papillomatosis.(2019).DOI:10.1016/j.otc.2019.03.0114-Commissioned internal Precigen research;RRPF;OrphaNet;NORD;CDC;ScienceDirect;Wangu,Z.,et al.,(2016);Evaluate Pharma;GlobalData;FDA;Capital
62、IQ;OECD;WorldBank;FiercePharma;Gordon et al.(2018)5-Commissioned internal Precigen research on ex-US case numbers and discounted US penetration and pricing numbers6-Genital HPV Infection Basic Fact Sheet(2022).Division of STD Prevention,National Center for HIV,Viral Hepatitis,STD,and TB Prevention,C
63、enters for Disease Control and Prevention https:/www.cdc.gov/std/hpv/stdfact-hpv.htm#:text=Genital%20warts%3A%20Prior%20to%20HPV,U.S.%20will%20have%20cervical%20cancerSLIDE:PRGN-2009:First-in-class Investigational Therapy for HPV-associated Cancers1-Miles et al.,Gynecologic Oncology Research and Pra
64、ctice(2017)4:102-de Martel C,et al.,Volume 8,ISSUE 2,e180-e190,February 01,2020.Key markets include US,EU5 and Japan3-Commissioned Internal Precigen Research4-Arizton Advisory and Intelligence,Cervical Cancer Therapeutics Market Report Scope(2022)5-Grandview Research,Head And Neck Cancer Therapeutic
65、s Market Size,Share&Trends Analysis Report By Therapy Type(Chemotherapy,Immunotherapy,Targeted Therapy),By Route Of Administration,By Distribution Channel,By Region,And Segment Forecasts,2022 20306-FDA approves pembrolizumab for advanced cervical cancer with disease progression during or after chemotherapy(2018).https:/www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer-disease-progression-during-or-after-chemotherapy30