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1、Landscape Overview Q1 2022Cancer Vaccine IndustryPseudo-colored scanning electron micrograph of a cancer cell being attacked by two immune cells.www.deep-pharma.techinfodeep-pharma.techvisualsonline.cancer.govIntroduction and Mindmaps3Level of Cancer Vaccine Innovation of 30 Leading Companies in Dru
2、g Discovery Sector8Neoantigen Platform13Key Players18SWOT Analysis22Tumor-Associated Antigens Platform23Key Players27SWOT Analysis30Cellular Platform31Key Players36SWOT Analysis39Table of ContentsAntigenic Essence Platform40Key Players45SWOT Analysis46Oncolytic Viruses Platform47Key Players51SWOT An
3、alysis55Cancer Vaccines Delivery Systems56Key Players60Key Takeaways and General Conclusions 66Appendix:List of Entities70Overview of Proprietary Analytics by Deep Pharma Intelligence84Disclaimer903Deep Pharma IntelligenceThe most powerful weapon against malignancies can be hidden inside the host hu
4、man body and it is called immune system.Cancer mechanisms usually trick our immune system but a proper therapy can turn our immunity back against the tumor.Thats the very aim of cancer vaccination to activate host immunity cells to destroy the tumour cells.There are multiple platforms developed to o
5、btain cancer vaccines,in this report we are going to discuss 5 of such platforms,which serve as a basement for vaccines creation.Some of these cancer vaccine platforms overlap and evolve out of each other while still have some unique distinguishable features which was a reason for suggested classifi
6、cation.Tumor-Associated AntigensCellularOncolytic VirusesCancer Vaccine PlatformsNeoantigensAntigenic EssenceIntro:What is a Cancer Vaccine?4Deep Pharma IntelligenceAt first,cancer vaccines didnt succeed:the enthusiasm and interest towards this technology dropped after seeing the high level of adver
7、se effects versus low efficacy.However,with the development of sequencing technologies,innovative delivery systems,bioinformatic data treatment strategies and vaccine adjuvants cancer vaccines have more and more prominent chances to become deeply integrated into the market.In 2021 the market size of
8、 cancer vaccines was estimated as 4.72 billion US$and it is expected to reach 10.07billion US$in 2022.Considering this tendency,it is reasonable to say that cancer vaccines start forming a separate branch of industry.Cancer Vaccine Industry$4.72billion$10.07billionSequencing technologies Cancer vacc
9、ines market size growth 2021-2022Bioinformatic data treatmentAdvanced delivery systems Novel adjuvant technologyFaster,cheaper&more optimized Biologically advanced technologiescytotoxic CD8+T-cells 5Deep Pharma IntelligenceWe targeted cytotoxic CD8+T-cells to kill the cancer cellsWe need to engage b
10、oth CD8+and memory CD4+T-cells to prolongate the effect We found out that the tumour lysates can activate the immune response to cancerOff-tumor effects became a severe reason for the damage so scientists are working to decrease themWe learnt how to target tumors through their unique mutations-neoan
11、tigensTo prevent tumour escape we need to target multiple antigens on the tumour cellIntro:Where is Cancer Vaccination Right Now?Viral VectorsDendritic CellsDNACancer Vaccines and Cell Immunotherapies by Delivery Form Companies-130 Investors-360RNAPeptides and ProteinsInvestorsCompaniesCAR-TArtifici
12、al Vectors and Immune Cells Cancer Vaccine Companies Landscape InvestorsCompaniesWhole-cell antigensCancer Vaccines by Antigen TypeTumor-associated antigensTumor-specific antigensCompanies-115 Investors-250Cancer Vaccine Companies Landscape 8Deep Pharma IntelligenceLevel of Cancer Vaccine Innovation
13、 of 30 Leading Companies in Drug Discovery Sector8 8Methodology:database creation followed by the detailed analysis of every individual use case by the quantitative and qualitative features such as:cancer vaccine category;complexity and development possibilities of the technology;number of similar p
14、roducts on the market/development pipelines;novelty of the product;addressment of the unmet needs etc.Innovative ApproachBiobohemia1AiVita Biomedical2Gradalis3Editas Medicine4Genocea Biosciences(NASDAQ:GNCA)5Gritstone Oncology(NASDAQ:GRTS)6Heat Biologics(NASDAQ:HTBX)7NexImmune(NASDAQ:NEXI)8Oxford Va
15、cmedix9IO Biotech10Scancell Holdings(LSE:SCLP)11Sorrento Therapeutics(NASDAQ:SRNE)12Ionis Pharma(NASDAQ:IONS)13Rubius Therapeutics(NASDAQ:RUBY)14Arrowhead Pharmaceuticals(NASDAQ:ARWR)15Classic ApproachAgenus Inc.(NASDAQ:AGEN)1AstraZeneca(NSE:ASTRAZEN)2BioNTech(NASDAQ:BNTX)3CureVac(NASDAQ:CVAC)4Vacci
16、tech5Enochian Biosciences(NASDAQ:ENOB)6Immunomic Therapeutics7Inovio Pharmaceuticals(NASDAQ:INO)8GlaxoSmithKline(NYSE:GSK)9Moderna Therapeutics(NASDAQ:MRNA)10Northwest Biotherapeutics(OTC:NWBO)11OncoPep12Gilead Sciences 13PsiOxus Therapeutics14Nykode Therapeutics15Cancer vaccines development shifted
17、 into the direction of more specific tumor targeting due to neoantigen platform.Still,the tremendous majority of such neoantigen vaccines dont overcome the problem of tumor escape mutations and the heterogeneity of cancer cells.Only restricted number of innovative platforms try to face and solve bot
18、h issues of highly specific tumor targeting and escape mutations prevention.They apply new approaches on already developed platforms(such as whole-cell,neoantigen,TAA)or initialize new platform(antigenic essence).9Deep Pharma IntelligenceComparison of Top-30 Leading Drug Discovery Companies Expertis
19、e in Cancer Vaccines R&D Expertise in Drug Discovery10Deep Pharma IntelligenceClinical pipeline(phase 3)Clinical pipeline(phase 1-2)Validated R&D Use casesand preclinical pipeline Mildly specific but can address tumor heterogeneity Highly specific but no or limited heterogeneity addressedHighly spec
20、ific and addresses tumor heterogeneityTumor targeting efficiency Comparison of Top-30 Leading Drug Discovery Companies Expertise in Cancer Vaccines R&D11Deep Pharma IntelligenceComparison of Top-30 Leading Drug Discovery Companies Expertise in Cancer Vaccines R&DCancer vaccine leaders belong both to
21、 big pharma companies with multiple directions and to fast-growing start-ups which are more oriented on cancer vaccine development only.Such big pharma companies mostly keep up with mainstream approaches like neoantigens in the form of mRNA vaccines(Moderna Therapeutics and BioNTech)and raise fundin
22、g from various sources.At the same time there is a drastic growth experienced by companies who apply more innovative approaches.According to the study of TOP-15 cancer vaccine companies with innovative approach at the moment of Q2 2021 they already raised roughly twice as much as during the whole 20
23、20($850 million and$484 million correspondingly).12Deep Pharma IntelligenceAbove$250M$50M-$250M$1M-$50M Mildly specific but can address tumor heterogeneity Highly specific but no or limited heterogeneity addressedHighly specific and addresses tumor heterogeneityLevel of Capital RaisedTumor targeting
24、 efficiency Comparison of Top-25 Leading Drug Discovery Companies Expertise in Cancer Vaccines R&DNeoantigen PlatformDEEP PHARMA INTELLIGENCEDNA sequencing-first stage for neoantigens identificationNeoantigens represent a large platform in cancer vaccines fied and generally in tumor immunotherapy.Ne
25、oantigens include antigens produced by tumor viruses integrated into the genome and antigens originated by mutant proteins,which are abundantly expressed specifically in cancer cells and have strong immunogenicity and tumor heterogeneity.Currently a considerable number of neoantigens have been disco
26、vered,which are unique to tumor cells and are not affected by immune tolerance mechanism.14Deep Pharma IntelligenceNeoantigensPrivateSharedCommon across different cancer patients and not present in the normal genomeShared neoantigens that are highly immunogenic have the potential to be screened for
27、use as broad-spectrum therapeutic cancer vaccines for patients with the same mutated gene.Unique to most neoantigens and completely different from patient to patientPersonalized neoantigen preparation drug can only be specifically targeted to each patient,that is,personalized therapyZhang et al.,Fro
28、ntiers in Immunology(2021)Viral infectionProtein coding sequence mutationGene rearrangementAlternative splicingNeoantigen Platform:Overview20004115Deep Pharma IntelligenceFirstly applied next-generation sequencing technology to identify immunogenic neoantigens in mouse tumor mo
29、delsPersonalized neoantigen peptide and RNA vaccines could induce specific T-cell populations that recognize autologous tumorFirst mass spectrometry identification of neoantigens in human tumor tissueComplete regression in a melanoma patient after infusion of a cell product with a high proportion of
30、 neoantigen-reactive T-cellsNeoantigen-directed immune escape in lung cancer evolutionJiang et al.,Journal of Hematology&Oncology(2019)Neoantigen Platform:Development MilestonesStudy reported that antitumor T-cells could recognize aberrant peptides derived from tumor-specific mutationsOutburst of in
31、terest to mRNA vaccines development due to Covid-19 pandemic16Deep Pharma IntelligenceCollection of tumor and normal tissueGenome sequencingTranscriptome sequencingBioinformatic candidate idMass spectrometry Evaluationof immuno-genicitySynthetic vaccine(DNA/mRNA/peptides/DC)There are no yet approved
32、 neoantigen vaccines,but according to ClinicalTrials.gov search there are 190 cases of neoantigen studies and none of them entered yet the third clinical phase(not considering HPV-vaccines).It is 30 more cases compared to the search results in Q3 2021,which demonstrates a tremendous growth of intere
33、sts in this cancer vaccines platform.Many of these studies have shown the good application value of neoantigen(Search term is“neoantigen”).However,the study of neoantigen therapy starts relatively late and still in the laboratory stage.The first stages of neoantigen vaccines development are complex
34、and time consuming.Even though genome and transcriptome sequencing technologies are actively developing,they remain a milestone together with bioinformatic treatment of data.As the result,the complications of neoantigen platform overlap with the well-known issues of sequencing cost,speed,data storag
35、e and analysis.However,with the rapid digitalisation and a broad introduction of artificial intelligence,smart robotics and data storage technologies these issues are expected to be at least reduced if not almost fully eliminated.Neoantigen Platform:Cancer Vaccines in DevelopmentStep-by-step scheme
36、of neoantigen cancer vaccine development17Deep Pharma IntelligenceGenocea Biosciences GEN-009 vaccine trial(NCT03633110)is now on the Phase 1/2a clinical trials and have shown the best efficacy among the current neoantigen personalization therapies with an estimated completion date of December 2022.
37、The purpose of this study was to evaluate the safety,tolerability,immunogenicity,and antitumor activity of the personalized vaccine GEN-009 for the treatment of patients with solid tumors,which is targeted at a broad range of cancers.The results so far show that 40 doses of the vaccine have been adm
38、inistered and no dose limiting toxicity(DLT)occurred and so far,no patients who have received the vaccine have relapsed.BioNTech and Moderna are big pharma leaders in development of cancer vaccines of various forms based of neoantigens.BioNTech has 6 cancer vaccines in development with shared neoant
39、igens(FixVac platform)and 2 cancer vaccines owned together with Genentech based on individualized approach(iNeST platform).DiscoveryPre-INDPhase 1/2Phase 3CommercializationGEN-009 Neoantigen vaccine by GenoceaBNT111 Shared neoantigen vaccine by BioNTechPCV mRNA-4157 Neoantigen vaccine by ModernaBNT1
40、22 Individualized neoantigen vaccine by BioNTech and GenentechNeoantigen Platform:Cancer Vaccines in DevelopmentNeoantigen cancer vaccines development pipeline18Deep Pharma IntelligenceBioNTech big pharma company that mostly specializes on various cancer immunotherapies.They own technologies with de
41、veloped mRNA platform cell therapies antibodies small molecule immunomodulatorsBioNTech is oriented on individualized immunotherapy with patient-specific approach.It requires a complex bioinformatic data treatment,that is why the company gathered expertise in bioinformatics of mutation detection,can
42、cer genomics and immunotherapySource BioNTech ApproachNeoantigen Platform:Key PlayersBioNTechs validated patient-centric bioinformatic processUnique patientSequencing patients tumorMapping of mutationsBioinformatic algorithms Selection of neoepitopes19Deep Pharma IntelligenceFixVac cancer vaccine wi
43、th shared neoantigensContains selected combinations of unmodified,pharmacologically optimized mRNA,encoding known cancer-specific shared antigens;mRNA is delivered using lipoplex technology.iNeST Individualized Neoantigen Specific Immunotherapy cancer vaccine with private neoantigensContains unmodif
44、ied,pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens,delivered by RNA-LPX formulation.BNT 111 Advanced MelanomaBNT 112 Prostate CancerBNT 113 HPV16+Head and Neck CancerBNT 114 Triple Negative Breast CancerBNT 115 Ovarian CancerBNT 116 NSCLCAll of them currently are on
45、phase 1 of clinical trialsBNT 122 Metastatic Melanoma(currently on the phase 2 of clinical trials)And for locally advanced or metastatic solid tumors(currently on the phase 1 of clinical trials)Rights are equally shared with GenentechSources BioNTech Pipeline,BioNTech PlatformsNeoantigen Platform:Ke
46、y PlayersCancer vaccine can be used for the treatment of group of people and shouldnt be tailored individuallyNeoantigen Platform:Key PlayersGenocea Biosciences owns an innovative approach for neoantigen vaccines development-ATLAS platform.It is a unique bioassay that enables a superior,patient biol
47、ogy-driven approach to identify targets of protective T cell responses.ATLAS zeroes in on only those surface-presented antigens that trigger anti-tumor T cell responses.ATLAS is unique in the way that it can identify pro-tumor inhibitory antigens(Inhibigens),which subvert anti-tumor immune responses
48、.Vaccination with such Inhibigens is proved to drive tumor hyperprogression in mice.Comprehensive identification of patient-and tumor-relevant T-cell responsesTumor biopsyNGSAnalysisBacterial vectors expressing each condidateUnique plasmids for every candidate neoantigenBlood sampleAutologous dendri
49、tic cellAutologous T-cell20Deep Pharma IntelligenceMultiplexed cytokine readoutCD4+and CD8+T-cell responsesIdentify inhibigensSources Genocea ScienceHow does the Genoceas ATLAS approach work?Neoantigen Platform:Key Players 21Deep Pharma IntelligenceGenocea Biosciences greatly focuses in the antigen
50、selection for the best tumor targeting and destruction,which lies at the very basement of the ATLAS platform.GEN-009 is a neoantigen vaccine candidate in a Phase 1/2a clinical trial to treat a variety of solid tumors.ATLAS identifies neoantigens optimized both to patients T cell responses and their
51、tumors,underscoring the advantages of the technology for neoantigen selection.Other vaccine candidate GEN-011 belong to the class of adoptive T cell therapy.GEN-011 Neoantigen-activated Peripheral T cells(NPTs)are peripheral blood T cells activated by the ATLAS-identified patient-specific neoantigen
52、s and expanded to create a customized therapeutic.Sources Genocea PipelineCollect available fixed tumor and blood sample,send for sequencingPatient sees oncologist,begins SoC ICINeoantigens(up to 20 peptides)synthesized as peptides and formulated with Poly-ICLCPatient receives 5 SC doses over 6 mont
53、hsInhibigens and neoantigens identified by ATLASHow does the Genoceas ATLAS approach work?22Deep Pharma IntelligenceNeoantigen Platform:SWOT Analysis Weaknesses The development cycle of neoantigen vaccine is too long Preparation and delivery of vaccines remains a challenge The heterogeneity of the t
54、umor is difficult to resolve with neoantigen platform Limited number of antigens meet the neoantigen criteria Expensive Opportunities Vaccines possibly can enter the clinical trials phase 3 Neoantigen cancer vaccines might be the best personalized solution for cancer treatment Great financial suppor
55、t which moves the platforms faster to clinical research Absolute specificity to the tumor cells Already have products in clinical phase of development Cancer vaccine can be delivered in various forms StrengthsThreats Platform has a limited number of directions to develop further in case of failure I
56、t might be substituted with novel platforms which are more cost-effective and highly specific for cancer cells at the same timeOTSWTumor-Associated Antigens PlatformDEEP PHARMA INTELLIGENCEMacrophages attacking cancer cellsTumor-Associated Antigens(TAA)are self-proteins that are abnormally expressed
57、 by cancer cells.It means they are present both in healthy and cancer cells and differ just by the level of exposure or presentation by cell.This makes TAA slightly easier to discover compared to neoantigens,but at the same time TAA might cause peripheral tolerability issues in patients,lack of T-ce
58、ll activation and collateral damage.Even though TAA are used for the currently well-developed CAR-T technology,they still remain to be challengeable for cancer vaccines development.24Deep Pharma IntelligenceTumor-Associated AntigensCancer testis antigensOverexpressed proteinsDifferentiation antigens
59、Detected both on healthy and cancer cells of human body but due to the higher amount at malignant cells their detection will be preferableDifferentiation factors are meant to be present at cells only during the early development and are saved only in small subset of cells in developed bodyAre not su
60、pposed to be present in healthy adult somatic tissues but are expressed in testicles in male germ cellsTumor-Associated Antigens Platform:Overview25Deep Pharma IntelligenceCancer immunotherapy field experienced at least two significant breakthroughs connected with tumor-associated antigens platform:
61、Promising approval of Provenge cancer vaccine(sipuleucel-T)by FDA for the treatment of prostatic cancer,which used tumor-associated antigen as a target Development and approval of multiple CAR-T therapies which are based on targeting of TAAAntigensDay 1Day 2 3Day 3 4Patient leukapheresisSipuleucel-T
62、 is manufacturedPatient is infusedPROVENGECART-CellCAR-T CellA key fighter in the immune systemA specific receptor is added to the T cell T cells with the CAR find and fight cancer cells2010-first FDA approved cancer vaccine 2017-first FDA approved CAR-T Tumor-Associated Antigens Platform:Developmen
63、t MilestonesDiscoveryPre-INDPhase 1/2Phase 3CommercializationNEXI-002 Cellular vaccine for Multiple Myeloma by NeximmuneTumor-associated antigens is one of the most well-developed platforms,thats why there is plenty of clinical candidates even not considering CAR-T and counting only cancer vaccines.
64、At the moment of our research there were roughly 200 cases of tumor-associated antigens studies according to ClinicalTrials.gov search.After approval of Provenge in 2010 no other cancer vaccine entered the global market.Provenge passed clinical trials stage with a low efficiency level,but just enoug
65、h to pass it,so now it is not as frequently used as we could wish it were and toxic chemotherapy remains to be more effective way to treat prostate cancer.Provenge Cellular vaccine with PAP for prostate cancer by Dendreon PVX-410 TAA vaccine by OncoPep 26Deep Pharma IntelligenceINO-5401 TAA vaccine
66、by Inovio Pharmaceuticals Tumor-Associated Antigens Platform:Cancer Vaccines in DevelopmentTumor-associated antigens cancer vaccines development pipelineTumor-Associated Antigens Platform:Key Players 27Deep Pharma IntelligenceNexImmune biopharmaceutical company which implements an innovative approac
67、h to improve and develop tumor-associated antigens cancer vaccines.They own a nanotechnological Artificial Immune Modulation(AIM)platform.NexImmune constructs“synthetic dendritic cells”in the form of AIM nanoparticles,which are capable of directing a specific T cell-mediated immune response.During a
68、ntigen presentation T cells can recognize multiple antigens in the form of peptides.This produces T-cells with multiple immune targets for a robust antitumor activity.AIM Nanoparticles induce the production of both memory cells and cytotoxic effector cells.Effector cells will be the main direct mech
69、anism to destroy tumor cells through the release of cytotoxic granules,while memory cells will store in the bloodstream.Sources NexImmune Technology60 nano-metersAIM ACT NanoparticleT-Cell5-7 micronTumor-Associated Antigens Platform:Key Players 28Deep Pharma IntelligenceNexImmune is oriented on few
70、principles in developing cancer vaccines with TAA:The ability to expand T cell populations that recognize and attack multiple antigen-specific targets Consistency in containing T cell subtypes that support anti-tumor potency,self-renewal,proliferation,and long-term T cell survivalSources NexImmune T
71、echnologyInjectable modality is presented by injectable AIM nanoparticles for solid tumorsAdoptive cell therapy modality includes cancer vaccines in the form of donor-or patient-derived T cells for AML,multiple myeloma and solid tumorsAIM nanoparticles are designed to mimic the immune functions of n
72、atural antigen presenting cells,such as dendritic cells,by delivering two key immune-directing T cell signalsPatientAIM ACT nanoparticles CREATE the productAIM INJ nanoparticles ARE the productINJECTABLE THERAPEUTICSCELL THERAPYCurrently in preclinical developmentCurrently in phase III clinical tria
73、ls29Deep Pharma IntelligenceInovio Pharmaceuticals is a biotech company which is oriented on DNA medicines development.One of the main focuses of the company is HPV-vaccines with candidates on the third phase of clinical trials.At the same time there are promising cancer vaccine candidates with tumo
74、r-associated antigens in the second phase of clinical trials.SynCon uses a proprietary computer algorithm that has been designed to identify and optimize the DNA sequence of the target antigen.INOVIOs DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using
75、 one of INOVIOs proprietary hand-held CELLECTRA smart devices.Sources Inovio DNA Medicines TechnologyINO-5401 cancer vaccineWT1,PSMA,hTERT antigens for glioblastoma multiforme(with PD-1 inhibitor)INO-5151 cancer vaccinePSA,PSMA antigens for prostate cancer(with PD-1 inhibitor and immune modulator)Tu
76、mor-Associated Antigens Platform:Key Players 30Deep Pharma IntelligenceTumor-Associated Antigens Platform:SWOT Analysis Weaknesses Cancer vaccines with TAA are not highly specific to tumor cells High number of adverse effects Peripheral tolerability riskOpportunities Cancer vaccine candidates can en
77、ter phase 3 of clinical trials Using the experience of FDA approved immunotherapies cam improve the developing products faster There are already examples of FDA approved immunotherapies using TAA Applicable to almost any tumor Lots of accumulated knowledge due to the long time of platform investigat
78、ion StrengthsThreats his platform is likely to be pushed out of the cancer vaccines field by platforms with higher specificity Provenge cancer vaccine is seldomly used due to the low activity and high cost even though it was FDA approvedOTSWCellular PlatformDEEP PHARMA INTELLIGENCEWhole-cell platfor
79、m for cancer vaccines is the earliest platform developed with the principle“vaccinate with something you want to fight against”.Whole-cell vaccines consist of the all cellular antigens,which means there are tumor-associated antigens and neoantigens included.Unlike TAA or neoantigen platform-whole-ce
80、ll platform contains both characterized and uncharacterized TAA and TSA.This approach is suitable,in theory,for any solid tumor regardless its mutation burden and the general process of its development takes less steps compared to TAA or neoantigen platforms.32Deep Pharma IntelligenceRazi et al.,Vac
81、cines for Cancer Immunotherapy(2019)Irradiated gene-modified tumor cellsIrradiated gene-modified autologous or allogeneic tumor cells,which were engineered to encode immunostimulatory agents including cytokines and costimulatory molecules.Cellular Platform:Overview33Deep Pharma IntelligenceRazi et a
82、l.,Vaccines for Cancer Immunotherapy(2019)Tumor-derived exosomesTumor cell derived exosomes could be obtained from ascites,pleural effusion,and plasma samples of patients;such exosomes comprise various tumor antigens,one of the leading antigens investigated is heat shock proteinTumor cell lysatesWho
83、le tumor cell lysates contain all tumor cell antigens.Autologous or allogeneic lysates could be prepared in different ways leading to cell death:cells can be frozen and thawed repeatedly or irradiated with ultraviolet B(UVB)Cellular Platform:Overview34Deep Pharma IntelligenceFirst cancer patient inj
84、ected with Coleys toxinFirst report of a human tumor antigen recognized by T-cells,reported by Pierre van der Bruggen,C.Traversari,P.Chomez,et alGVAX failed the clinical trials due to the lack of efficiencyGVAX(whole-cell cancer vaccine)entered the clinical trials phase IIIMitchison et al.discovers
85、passive transport of antitumor immunity in transplant mice Cellular Platform:Development MilestonesThe research in the field moved to the increasing efforts to improve previously developed products by Adding new adjuvants Using different delivery strategies Combining with other forms of immunotherap
86、y Trying to increase the concentration of target antigens2008200432010-2022DiscoveryPre-INDPhase 1/2Phase 3CommercializationDCVax-L for solid tumors(brain and ovarian cancer)by Northwest Biopharmaceuticals Despite the large number of developed products none of them has entered the cancer
87、vaccine market yet.Whole-cell platform for cancer vaccines is an attractive field for various ways of improvement to eliminate its considerable cons such as low efficiency and high toxicity.Heat Biologics is developing its two products:HS-110 and HS-130 by implementing the pan-antigenic self-adjuvan
88、t technology.On the other hand Northwest Biopharmaceuticals has a classic approach for cancer vaccines development but focuses more on clinical application optimization for clinicians and patients.Still,history of whole-cell cancer vaccines shows some failures such as one of the most advanced cancer
89、 vaccine candidates GVAX which resulted into higher mortality level in clinical trial phase 3 patients.HS-110 vaccine for NSCLC by Heat Biologics35Deep Pharma IntelligenceTAA enriched vaccine for glioblastoma by Aivita(NCT03400917)Cellular Platform:Cancer Vaccines in DevelopmentCellular cancer vacci
90、nes development pipelineCellular Platform:Key Players36Deep Pharma IntelligenceAiVita Biomedical is a medicine company which develops personalized cancer vaccines with a set of TAA-enriched whole-cell antigens.Their therapies are oriented to kill tumor-initiating cells(a small portion of the tumor m
91、ass which is the most prolific in the ability to generate additional cancer cells)while implementing pan-antigenic approach.They developed AV-GBM-1-cancer vaccine in the form of autologous dendritic cells loaded with tumor antigens from a short-term cell culture of autologous tumor cellsSources AiVi
92、ta Cancer ImmunotherapyOn the first steps the sample of the patients tumor undergoes cell culture.The aim of this step is enrichments with tumor-initiating cells and their amplification.It is the most critical stage since it reduces the non-specific signals from cells.Selected in such way tumor cell
93、s are used to load antigen-presenting(dendritic)cells,which are delivered to the patient back in the form of subcutaneous injections.Tumor cells isolationImmune cells isolationMonocytes isolationTumor cell cultureEnhancement of TAADendritic cells deriveryDendritic cells are loaded with patients tumo
94、r antigensTreatment is administered through the injectionCellular Platform:Key Players37Deep Pharma IntelligenceHeat Biologics is a biotechnology clinical-stage company focused on developing its proprietary“ImPACT”(Immune Pan-Antigen Cytotoxic Therapy)adjuvant technology.It is first-in-class fully h
95、uman adjuvant system that functions as an immune stimulator and an antigen-delivery system at the same time.Leading product HS-110(viagenpumatucel-L)Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-IgClinical phase II stage,in combination wit
96、h checkpoint inhibitornivolumab(Opdivo)or pembrolizumab(Keytruda)HS-130 Vaccine derived from irradiated human lung cancer cells expressing the co-stimulatory fusion protein OX40L-IgClinical phase I stage for a wide range of solid tumorsSources Heat Biologics Technology,clinicaltrials.govCellular Pla
97、tform:Key Players38Deep Pharma IntelligenceNorthwest Biopharmaceuticals biotechnology company focused on discovering,developing and commercializing immunotherapy products that generate and enhance immune responses to treat cancer.This company is fully focused of the development of whole-cell cancer
98、vaccines based on DCVax technology(the technology which implements dendritic cells for a cancer treatment)or simply the direct usage of DC for cancer treatment.Sources Northwest Biopharmaceuticals Product Candidates Dendritic cell cancer vaccine loaded with cancer antigens from tumor lysate from the
99、 patients own tumor tissue.DCVax-L is expected to be used for any solid tumor cancers.DCVax-DirectDCVax LThe partially matured dendritic cells are injected directly into the patients tumor(s)it is suitable for the situations in which the tumors are inoperable Besides focusing on the development of c
100、ancer vaccine candidates,one of the Northwest Biotherapeutics priorities is a user-friendly approach for both patients and physicians.Simplicity in the vaccine preparation,storage and delivery is one of the top values,which creates a multi-directional approach with a broad coverage of needs.39Deep P
101、harma IntelligenceCellular Platform:SWOT Analysis WeaknessesCellular noise Low concentration of immunogenic antigensHigher toxicity due to non-specific targeting of healthy cells Low immunogenicityOpportunitiesThe vaccines developed earlier in whole-cell platform which failed clinical trials might b
102、e upgraded with innovative platform Targeting of all cellular antigens Natural antigens compositionCost-effective StrengthsThreatsIt might not reach the needed level of efficiency on clinical trials even using adjuvants,checkpoint inhibitors and immune stimulators etc.It is likely to be substituted
103、by more innovative platformGVAX(an advanced product in whole-cell cancer vaccine platform)failed clinical phase 3 with a high mortality rateOTSWAntigenic Essence PlatformDEEP PHARMA INTELLIGENCEAntigenic essence platform is an innovative platform which can be considered as a cellular vaccines revita
104、lisation.It implemented the lessons from other platforms and created a novel product.Unlike whole-cell vaccines antigenic essence includes only surface-presented antigens,recognised by immune system.At the same time,unlike neoantigens or tumor-associated antigens antigenic essence targets a wide num
105、ber of antigens and doesnt require a complex data treatment and only limited application of one proteomics method.41Deep Pharma Intelligence Antiangiogenic SANTAVAC Targeted for tumor cells Preventive cancer vaccinesTherapeutic cancer vaccinesNovel platform-based cancer vaccines Upgrade of previousl
106、y established vaccinesAntigenic essenceAntigenic Essence Platform:Overview2 Key AdvantagesAntigenic EssenceCost and Time Efficiencypersonalized or group;peptides or dendritic cells;manufacturing friendlyWhole CellApproachRevitalizationmore effectiveand more specific,while eliminatingall limitationsT
107、argetingTumor Micro-environmentkilling any solidtumor bydestroying itsvascular systemAntigenic essence includes only visible for immune system antigensThe size of antigens is optimal to be presented by MHC to immune systemAntigenic essence is a specific footprint of cellular antigensAntigenic essenc
108、e can target not only cancer cells,but endothelial cells tooAntigenic essence can be a platform for the universal medicine for solid tumorsTargets the whole antigens spectrum-revolutionary antiangiogenic approachAntigenic Essence Platform:Overview42Deep Pharma Intelligence43Deep Pharma IntelligenceH
109、amid et al.,Cancer Immunology and Immunotherapy(2017)Antigenic Essence Platform:Development Milestones20-2010201420-20162020-2021Development of a“cell proteomic footprint”technology,antigenic essence initial stages of developmentFirst patent application and Eurasian pat
110、ents were granted.The trademark SANTAVAC was registered.USA patent was granted.Cell proteomic footprint technology was published(Biobohemia together with Bruker),antigenic essence vaccine preparation method was publishedPublication of the cancer response escape study as a result of anti-cancer vacci
111、nation(Biobohemia with Bruker and Institute of Biomedical Chemistry)The research for antigenic essence was extended to the antiangiogenic cancer vaccine conceptPublication of SANTAVAC concept.European,Korean,etc.patents were granted.Design of final SANTAVAC productsIND packages registration in FDACo
112、llaboration net expansion and a growing interest in the platform44Deep Pharma IntelligenceAntigenic essence platform may be considered as a significant upgrade of whole-cell platform.It means that antigenic essence is Cost and time-effective Applicable for all solid tumors regardless their mutation
113、burden status Applicable both for personalized or group medicine Can be used to direct tumor cells or vessels This platform can be a a solution for previously failed whole-cell cancer vaccines or a good collaborator for developing ideas.Right now antigenic essence platform is at preclinical stage of
114、 development but according to analysed data it should come to final phases of clinical trials(for example GVAX and CanVaxin)and pass it due to significant revitalization of the technology.Cell line or primary cell cultureAntigenic essence preparationMass spectrometry Natural peptides or peptide-load
115、ed DC vaccineComplex Omics approaches and bioinformatic data treatment are not neededOnly for quality control of antigenic essence products Antigenic Essence Platform:Cancer Vaccines in DevelopmentStep-by-step scheme of antigenic essence cancer vaccine development45Deep Pharma IntelligenceSpecific s
116、urface antigens obtained with an antigenic essence approachIntracellular antigens which create noise in whole-cell vaccines99%1%Cell antigensNaturally produced antigens by the tumor cells tend to induce the most accurate targeting of these cancer cells.Even though such native-cell antigens are obtai
117、ned by the appliance of cellular vaccines platform,whole-cell vaccines also have a tremendous majority of ballast intracellular proteins.This cellular noise dillutes target antigens results into the undesired immune response reduces the cancer vaccine specificityThat is why antigenic essence platfor
118、m met the need to develop a novel cell-based cancer vaccine free from intracellular immunogenic molecules.Antigenic Essence Platform:Key PlayersBiobohemia,Inc.biotechnology company focused on the development of cancer vaccines.They fully own an antigenic essence platform which is based on a deep kno
119、wledge in proteomics and provides the tool for a revitalization of cellular vaccines.The antigenic essence technology allows to control the composition,as well as an efficient purification from ballast substances(cellular noise),and evasion of MHC restrictions.46Deep Pharma IntelligenceAntigenic Ess
120、ence Platform:SWOT Analysis Weaknesses Not directed to target non-solid tumors(20%of cancer cases)Low public awareness about the new technologyOpportunities Can be used to upgrade cellular vaccines developed earlier Can become a new emergent star of cancer vaccines market Potentially can cure any so
121、lid tumor Can become a leader in preventive cancer vaccines field Innovative platform which eliminates all the cons of previously developed platforms Targeting of only surface antigens visible for immune system High concentration of antigens Controllable set of antigens in dosesStrengthsThreats The
122、platform is not validated in preclinical study,although preliminary validation is strong Operational capacity,structuring business processesOTSWOncolytic Viruses PlatformDEEP PHARMA INTELLIGENCEEngineered oncolytic poliovirus for cancer treatmentCredit:Duke Cancer Institute and cancer.gov48Deep Phar
123、ma IntelligenceOncolytic virotherapy is based on the property of some viruses to infect the cells and induce the cell lysis.In case of cancer vaccination these viruses are modified to target cancer cells and enhance the immune response to completely destroy the tumor.Oncolytic viruses cancer vaccine
124、s platform is greatly based on the neoantigens and tumor-associated antigens platforms,since the viruses and“taught”to target such antigens on the cancer cells.But due to the drastic uniqueness of the mechanism of action of such vaccines it is fair enough to separate them from other molecular and ce
125、llular cancer vaccines.(+)INSERTImmune-stimulating genes(-)REMOVEDisease-causing genes(selective targeting of tumors)Oncolytic VirusInfection of tumor cell and virus replicationTumor cell lysisand release of tumor antigens and cytokinesCytokinesVirus attacks other tumor cellsT-cell attacks other tum
126、or cellsActivation of T-cellsLocal inflammation-destruction of tumor microenvironmentOncolytic Viruses Platform:OverviewH1O1 variant approved in China Herpes simplex virus type I(HSV I)+granulocyte-macrophage colony-stimulating factor(GM-CSF)under the name of T-VEC is developed49Deep Pharma Intellig
127、enceFirst viral infection-induced leukemia regressionFirst clinical trials with engineered virusActive development of oncolytic viruses delivery technologies to reduce side effects for the intravenous injection Use of Adenovirus for cervical cancerNDV and measles virus for leukemiaParvovirus for sar
128、comaMumps virus for solid tumorsFDA approval of T-VEC oncolytic virus cancer vaccineHamid et al.,Cancer Immunology and Immunotherapy(2017)Oncolytic Viruses Platform:Development Milestones12015DiscoveryPre-INDPhase 1/2Phase 3CommercializationCAN-2409 Adenovirus for prostat
129、e cancer by Candel TherapeuticsFor today there is one FDA approved oncolytic virus immunotherapy-Talimogene laherpavepvec(T-VEC)owned by Amgen.Stil there is active development of oncolytic viruses which would target a wider spectrum of tumors and wont induce the formation of undesired antibodies by
130、the immune system.ONCR-177 HSV for intratumoral injections by OncorusOLVI-VEC for ovarian cancer by Genelux50Deep Pharma IntelligenceParxOryx for GBM by OryxTumor destruction and immune responseT-VEC T-VEC injection into tumorHerpes virus modificationOncolytic Viruses Platform:Cancer Vaccines in Dev
131、elopmentOncolytic viruses cancer vaccines development pipeline51Deep Pharma IntelligenceSources Oncorus TechnologyThey state that their approach not only activates antitumoral immunity but also stimulates the release and presentation of a greater number and variety of neoantigens.One more important
132、mechanism is a synthesis of transgenes which influence tumor microenvironment.Oncorus biotechnology company which develops next-generation viral immunotherapies for oncology.Their technology enables immune system to target cold tumors converting them into hot tumors.Oncolytic Viruses Platform:Key Pl
133、ayers Oncolytic Virus(Herpes Simplex-1 Virus or Synthetic VirusResponding Tumor TUMOR CELL T CELL CDCONCOLYTIC VIRUS NK CELL TUMOR CELL LYSISOncorus is moving into two directions in virotherapy field:Herpes Simplex Virus platform and viral RNA platform.The products of such platforms have different d
134、elivery approaches:directly intratumoral through the injection and intravenous respectively.52Deep Pharma IntelligenceSources Oncorus TechnologyoHSVONCR-177 is a leading product of this platform which is an oncolytic virus which should be administered directly into the tumor site;consequently this i
135、nduces immunogenic cancer cell death and drives llasting and systemic anti-tumor responseOncolytic virus brings 5 immunostimulatory agents:IL-12,CCL4,FLT3LG,anti-PD-1 and anti-CTLA-4vRNAThis technology is supposed to be less immunogenic which should result into a lower non-specific immune response.V
136、iral RNA is delivered in lipid nanoparticles.Leading programs ONCR-021 and ONCR-788 are based on coxsackievirus A21(CVA21)and Seneca Valley Virus(SVV)respectivelyOncolytic Viruses Platform:Key Players 53Deep Pharma IntelligenceAdenovirus PlatformCAN-2409 is an engineered gene construct encoding the
137、thymidine kinase gene,which should be transported into infected tumour cells.Administered in the form of intratumoral injection.HSV PlatformCAN-3110 is engineered to express the gene responsible for viral replication only when it is activated by a tumor-specific Nestin promoter.This provides a bette
138、r regulation of immune response and precise targeting.multifactorial approach which enables virus-based vectors to activate cancer-killing mechanismsOncolytic Viruses Platform:Key Players Candel Therapeutics focuses on preventing the recurrence and progression of cancer by applying viral immunothera
139、py.They are aimed to reach a low toxicity level which is well suited for the treatment of less aggressive or slower growing cancers.54Deep Pharma IntelligenceGenelux is an innovative biopharmaceutical company which develops oncolytic virotherapy and combines it with other cancer vaccine approaches.T
140、heir leading product is Olvi-Vec is currently on the stage 2 of clinical trials and it is stated that it can effectively fight multiple cancers(including both solid tumors and blood malignancies).Genelux owns a Choice Discovery Platform to develop an extensive library oncolytic viruses strains ident
141、ified from multiple in vitro and in vivo selection criteria.Sources Genelux TechnologyV2ACT(Virus and Vaccine(Neoantigen)-Enhanced Adoptive Cell Therapy)is a unique combinational approach for immunotherapy developed by Genelux.This immunotherapy is aimed to produce a strong immune response and an ou
142、tburst of primed cancer neoantigen-specific effector T cell precursors Oncolytic Viruses Platform:Key Players Olvi-Vec Immuno-Therapy Chemotherapy(platinum)refractory and/or resistant cancersGeneration Oncolytic VirusRegional(Advantages)Intravenous(Advantages)Local(Advantages)Ability to target advan
143、ced and metastatic diseasesAbility to target cancers without prolonged treatment burdenAbility to target and treat tumors of varying sizesRobust immune activation profile55Deep Pharma IntelligenceOncolytic Viruses Platform:SWOT Analysis Weaknesses Usually causes undesirable immune response with exte
144、nsive antibodies production which neutralise the virus Limited number of the antigens which can be targeted Mostly needs to be administered through the injectionOpportunities Can be efficiently improved through combinational therapies Can become the main mechanism of the tumor immunization if it is
145、not reachable for other therapies Can reach cold tumors and turn them into hot tumors Targets both tumor and its microenvironment Creates a strong immune responseStrengthsThreats Severe side effects resulted by the viral activity regarding healthy cells Gene modified viruses injected into a human bo
146、dy might cause some ethical concernsOTSWCancer Vaccines Delivery Systems DEEP PHARMA INTELLIGENCEEngineered nanoparticles for drug deliveryLiposomes and other lipid-based strategiesPLA and PLGA nanoparticlesExosomesInjectable mesoporous silica nanoparticles(MPS)The Need of Effective Delivery System5
147、7Deep Pharma IntelligenceOne of the main challenges in modern immunotherapy is targeting cold tumors(tumors surrounded by immunosuppressive cells)-the subclass of solid tumors.Implementing the appropriate delivery system is the primary way to overcome this challenge.Many clinical trials of cancer va
148、ccines fail because of ineffective delivery methods.For example,vaccination using unmodified peptides generated an overall response rate of only 3%due to difficulty activating antigen-presenting cells.Biopolymers-based delivery systems could enable spatiotemporal presentation to cells and the microe
149、nvironment,thus enhancing efficacy and reducing potential adverse effects.Nowadays,the science of biopolymers is rapidly developing,which allows the usage of different biopolymers to overcome various delivery challenges specific to each type of vaccine.Combining advances in biomaterials with a deepe
150、r understanding of cancer immunology is critical for developing a clinically effective cancer vaccine platform.Biopolymers-based Delivery SystemsParticulate-based Delivery SystemsScaffold-based Delivery SystemsPLGA scaffolds Hydrogel-based scaffolds Injectable mesoporous silica-based scaffolds Non-d
151、egradable DC homing devices Sources Emerging biomaterial-based strategies for personalized therapeutic in situ cancer vaccinesParticulate-based Delivery Systems58Deep Pharma IntelligenceParticulate-based approaches have long been utilized to improve therapeutic delivery to particular tissue areas wh
152、ile minimizing off-target and systemic side effects.Sources Emerging biomaterial-based strategies for personalized therapeutic in situ cancer vaccinesLiposomesLiposomes have a hydrophobic outer layer and a hydrophilic inner core,making them ideal for encapsulating both hydrophobic and hydrophilic me
153、dicinal cargo.Stable Long depot action at the injection site Limited loading capacity Once released,vaccines become impossible to retrieve-uncontrollable responsesMPS NanoparticlesExosomesNanoparticlesNanoparticles are used for oncotherapeutics delivery because they display target specificity to the
154、 tissue of interest,based on size,charge,surface properties and dissemination strategy.Limited off-target accumulation Limited delivery efficiency Limited loading capacity Limited to a cargo of peptides Exosomes,microvesicles,and apoptotic bodies,which are membrane-bound extracellular vesicles relea
155、sed from the endosomal compartment of most eukaryotic cells,can be used as drug delivery vehicles.Many manufacturing challenges New technology which requires more research before trials in humanMesoporous silica-based(MPS)approaches aim to address the challenge in high variability in delivery effica
156、cy dependent on cellular interactions by leveraging their well-established drug carrier properties and high versatility in conjunction with other materials.Silica is non-toxic material Large loading capacity New technology which requires more research before trials in humanScaffold-based Delivery Sy
157、stems59Deep Pharma IntelligenceScaffold-based vaccines are structures intended to initiate antitumor immunity locally at the implantation or injection site.For in situ cancer vaccines,most deliver stimulatory adjuvants and antigens to induce in situ DC homing and subsequent antigen-specific immune a
158、ctivation.In general,in situ cancer vaccines utilizing scaffolds must be designed to address three key criteria.They should be macroporous,clinically translatable,and should release immune potentiating adjuvants.PLGA Scaffolds Hydrogel-based Scaffolds Injectable Mesoporous Silica-based Scaffolds Non
159、-degradable DC Homing Devices PLGA scaffold is a biocompatible synthetic linear copolymer characterized by the modified surface for intracellular interactions.Sources Emerging biomaterial-based strategies for personalized therapeutic in situ cancer vaccinesScaffold-based SystemsHydrogel-based scaffo
160、ld is crosslinked hydrophilic polymer insoluble in water that can be loaded with bioactive molecules forming an enriched microenvironment for cellular interaction.Injectable mesoporous silica-based scaffold is system composed of nano-sized spheres or rods of silica in a predetermined non-specific ge
161、ometric arrangement for loading with drug.It can be improved by addition of functional groups and capping treatment.Non-degradable DC homing device is an implantable stable medical device for sustained and constant release of therapeutic cargo for different medical applications.SilVacx is a spin-off
162、 from Merck AG,which specializes on developing novel delivery systems for cancer immunotherapy,including cancer vaccines.SilVacx technology is based on silicon dioxide nanoparticles,which can help to make cancer vaccines material delivery in the human body efficient and cost-effective.SilVacx projec
163、t is supported by Life Science Inkubator GmbH(LSI),which is the first time LSI supported a research project originating from a pharma company.The platform is mainly oriented for therapeutic cancer vaccines,but can be used for preventive vaccines as well.Companies Applying Advanced Cancer Vaccines De
164、livery Systems60Deep Pharma IntelligenceSources SilVacXCurrently the platform is designed for neoepitope-based personalized antitumor vaccines and extremely powerful for HPV(human papillomavirus)induced cancers.SilVacxs technology provides stimulation of the innate immune system stimulation of the a
165、daptive immune systemVirus-sized particles with a virus-like morphology provide an efficient uptake and processing of antigens by dendritic cells.Osivax is a clinical stage biotechnology company,which owns a novel proprietary nanoparticle technology.This technology-oligoDOM-can be applied for many t
166、ypes of vaccines,including cancer vaccines.It is specifically designed to trigger superior T-cell responses,in addition to strong and sustained B-cell responses.In other words,it engages both cytotoxic and memory immune cells.Companies Applying Advanced Cancer Vaccines Delivery Systems61Deep Pharma
167、IntelligenceSources Osivax TechnologyOligoDOM technology was tested with different antigens,as well as within different vaccine forms.It can be combined with recombinant proteins,or mRNA technology,leading to multiple value generation opportunities.Currently Osivax is expanding their portfolio to in
168、clude cancer targets,such as HPV antigen.Single geneProtein monomeroligoDOM vaccineExpressedAuto-assembleFull length target antigenRecombinant protein from a single gene with three synergistic domainsA large,positively charged,highly immunogenic version of the antigenMidatech Pharma is a pharmaceuti
169、cal company focused on drug delivery technology and its application for various diseases,including cancer.Midatech owns three drug delivery platforms which enable comprehensive improvement of biodelivery and biodistribution of on-market and pre-approval drugs.Companies Applying Advanced Cancer Vacci
170、nes Delivery Systems62Deep Pharma IntelligenceSources Midatech Pharma Technology proprietary 3D printing technology that encapsulates medicines into bioresorbable polymer microspheres with precision characteristicsMicro-encapsulation PLGA polymer depot systemAdvanced piezo printing technologySeveral
171、 million microspheres produced per secondultra-small gold nanoparticle(GNP)drug conjugatesThe small size and multi-functional arrangement of molecules around a gold core underpin MidaCores ability to improve biodistribution and targeted drug deliverysolubilises potent molecules that have minimal sol
172、ubility at biological pH extending available routes of administrationUsed for direct-to-tumor deliveryQ-SpheraMidaCoreMidaSolveAlnylam Pharmaceuticals is a biopharmaceutical company that develops therapy with an RNA interference(RNAi)approach.The companys therapeutic focus areas are genetic medicine
173、s,cardio-metabolic diseases,infectious diseases,central nervous system(CNS)and ocular diseases.For delivery of their therapy,Alnylam utilizes two delivery platforms-lipid nanoparticles(LPNs)and conjugates.Companies Applying Advanced Cancer Vaccines Delivery Systems63Deep Pharma IntelligenceSources A
174、lnylam Pharmaceuticals Lipid Nanoparticles ConjugatesAlnylam has an approved iRNA therapy that utilizes LNP-based delivery-ONPATTRO(patisiran).LNPs are chemically synthesized multicomponent lipid formulations(100 nm in size)that encapsulate siRNAs and deliver the medicine to the target tissue.LNPs p
175、rotect the drug from degradation by ubiquitous nucleases.LNPs in ONPATTRO have an affinity for apolipoprotein E which is expressed on the surface of hepatocytes,that allows the accurate delivery of siRNA to the liver.Conjugates are single chemical entities that have siRNA coupled to target ligands t
176、o aid them in finding their way to a particular cell or tissue in the body.The ligand attached to the siRNA has an affinity to the receptor on the target cell,which creates a“lock and key”system.Alnylam has developed two conjugate approaches to enable targeted delivery to the liver and the central n
177、ervous system(CNS).The company utilises GalNAc conjugates that bind to the asialoglycoprotein receptor for targeting the liver,which is abundantly expressed on liver cells(hepatocytes).pHLIP is a company that develops peptide-based targeted delivery platforms to cure cancer,inflammation and other ac
178、idic tissue diseases.Their innovative platform pHLIPs(pH-Low Insertion Peptides)is a platform technology of pH-sensitive peptides that exploit pH differences between healthy and diseased cells as a biomarker for targeting and delivering therapeutic and imaging agents to cells in acidic diseased tiss
179、ues.Companies Applying Advanced Cancer Vaccines Delivery Systems64Deep Pharma IntelligenceSources Philip Inc.Molecular Mechanism:pHLIP peptides sense and target pH at cell surfaces,where the pH is the lowest,thus providing high sensitivity.pHLIP peptides exploit folding and insertion across the cell
180、 membrane,a cooperative process that gives high specificity.pHLIP peptides do not target or accumulate in cells with normal surface pH in healthy tissue.Codiak Biosciences is a biopharmaceutical company focused on pioneering the development of exosome-based therapeutics.Codiak created the engEx Plat
181、form,which allows us to build and engineer exosomes with unique features,load them with a variety of therapeutic compounds,and guide their tropism to particular target cells.The platform uses exosome-associated proteins-PTGFRN and BASP1 as scaffolds to direct proteins of interest(targeting ligands a
182、nd therapeutic molecules)to the surface or the lumen of exosomes.Companies Applying Advanced Cancer Vaccines Delivery Systems65Deep Pharma IntelligenceSources Exosomes have the potential to be a beneficial therapeutic method due to their capacity to selectively transport a wide range of therapeutic
183、payloads to cells,opening the door to a wide range of possible applications in illnesses that have eluded other treatments.Targeted DeliveryImmune SilentMulti-FunctionalExosome tropism can be designed so they reach specific cell types in the body.The targeted delivery enhances drug efficacy and safe
184、ty.Exosomes are composed of natural human proteins and lipids,making them inherently non-immunogenic.Exosomes can be loaded with multiple different types of molecules and can influence their targets in multiple ways.Key Takeaways and General Conclusions DEEP PHARMA INTELLIGENCE67Deep Pharma Intellig
185、enceThe graph demonstrates the growing number of publications mentioning cancer vaccines by year.Over a decade the annual publishing grew more than 2.5 fold and is expected to continue increasing.Sources PubMed Databasepredicted number by the end of 2022Key Takeaways The interest in cancer vaccinati
186、on is continually growing and is currently experiencing an outburst in 2021.This mature field of immunotherapy requires novel approaches and revitalization solutions.The most actively developing platform right now is neoantigens platform,which we observe from analysing the lead products of big pharm
187、aceutical companies.The most prominent research vectors in the field of cancer vaccines are aimed at enhancement of immunogenicity while reducing a non-targeted damage of healthy cells,targeting multiple antigens and developing an universal vaccine for a broad spectrum of malignancies.68Deep Pharma
188、IntelligenceBesides the common tendency of having the highest number of product candidates on the first phases of clinical trials,there is an even distribution of numbers depending on the delivery form of cancer vaccine.Peptide/protein form was represented by over 115 candidates on different stages
189、of clinical trials being the leading platform for vaccine delivery to the target cells.Dendritic cells appear to be the second leader with already approved Sipuleucel-T.Fewer number of cancer vaccines are delivered in the form of DNA and RNA,which can be due to higher cost of development and younger
190、 age of the platform.The information is given according to the clinicaltrials.gov investigation by Cuzzubbo et al.Key Takeaways69Deep Pharma IntelligenceWe have reviewed the 5 cancer vaccine platforms which are actively developing their products to enter the market of immunotherapy.As a result we co
191、nducted assessment of more than 150 companies and R&D centers,and detailed analysis of more than 30 of them.Identified cancer vaccine platforms have distinguishable features and development timelines,as well as representative companies with the products pipelines.All the reviewed key player companie
192、s,in our opinion,possess strong R&D bases,have well-developed level of technology and intellectual property and large total addressable markets for their products.We believe that cancer vaccine development is moving into the direction of more specific tumour targeting while reducing side effects by
193、the novel delivery methods,antigen identification applications or vaccine preparation process itself.Currently,the major attention is paid to neoantigen platform,but it will probably be pushed out with such growing cancer vaccine platform as antigenic essence,which is likely to combine a high specif
194、icity,efficiency and time-and cost-effectiveness.General ConclusionsAppendix:List of EntitiesDEEP PHARMA INTELLIGENCEDeep Pharma Intelligence71150 Cancer Vaccine ompaniesAmgenAgenus Inc.AiVita BiomedicalAntigen ExpressAdaptVac1Aeon Therapeutics234Allogene Therapeutics5Alnylam Pharmaceuticals6Amal Th
195、erapeutics7Anixa Biosciences8910Antion BiosciencesApeiron BiologicsArrowhead Pharmaceuticals1112Arcellx1314AstraZeneca15Boehringer IngelheimAvrobioBavarian NordicBrightPath BiotherapeuticsAutolus16AVAX Technologies171819BioMedicure20BioNTech21BioVaxys22BriaCell Therapeutics232425CalviriCaroGenCeldar
196、a Medical2627CARsgen Therapeutics2829Celgene30DendreonCelyadCodiak BiosciencesEditas MedicineCellectis31Celularity323334Corixa Corporation35CureVac36Defence Therapeutics37Dynavax Technologies Corporation383940Elicio TherapeuticsElios TherapeuticsEnochian Biosciences4142Enara Bio4344EpiThany45Deep Ph
197、arma Intelligence72150 Cancer Vaccine ompaniesFrame TherapeuticseTheRNAEvaxion BiotechGemVax&KaelEpitopoietic Research Corporation46EpiVax Oncology474849ExploRNA Therapeutics50EXUMA Biotech51Flow Pharma52Galena Biopharma535455Geneos TherapeuticsGenerex BiotechnologyGeovax5657Genocea Biosciences5859G
198、laxoSmithKline60ImmunicumGritstone OncologyHeat BiologicsImmunoRestorationGracell Biotechnologies61Gradalis626364Hookipa Pharma65Hubro Therapeutics66Immunetune67Immunomic Therapeutics686970ImvaxInovio PharmaceuticalsIO Biotech7172InProTher ApS7374Ionis Pharmaceuticals75Lytix BiopharmaJuno Therapeuti
199、csKhloris BiosciencesMaxiVAXISA Pharmaceuticals76Janssen Pharmaceuticals777879Kite Pharma80Lava Therapeutics81Legend Biotech82Magenta838485MedigeneMidatech PharmaMustang Bio8687Moderna Therapeutics8889Neuvogen90Deep Pharma Intelligence73150 Cancer Vaccine ompaniesOnco Therapy ScienceNoile-Immune Bio
200、techNorthwest BiotherapeuticsONYvaxNewLink Genetics Corporation91NexImmune929394Nouscom95NovaRx96Nykode Therapeutics97OncoPep9899100Oryx Translational MedicineOsivaxOxVax101102Oxford Vacmedix103104PDC*line Pharma105Providence TherapeuticspHLIPPhoreus BiotechRegen BioPharmaPepscan106Personalis1071081
201、09Polynoma110Precision BioSciences111ProMab Biotechnologies112PsiOxus Therapeutics113114115Rhovac ApSRNAimmuneRubius Therapeutics116117Roche118119SapVax120Deep Pharma Intelligence74150 Cancer Vaccine ompaniesOnco Therapy ScienceNoile-Immune BiotechNorthwest BiotherapeuticsONYvaxNewLink Genetics Corp
202、oration136NexImmune137138139Nouscom140NovaRx141Nykode Therapeutics142OncoPep143144145Oryx Translational MedicineOsivaxOxVax146147Oxford Vacmedix148149PDC*line Pharma150Southwest Oncology GroupSensei BiotherapeuticsSilvacxStrike PharmaScancell Holdings121SELLAS Life Sciences122123124Socium Therapeuti
203、cs125Sonoma126Sorrento Therapeutics127SpyBiotech128129130Sumitomo Pharma OncologyTakeda PharmaceuticalsTargovax131132Takis Biotech133134Tmunity Therapeutics135Deep Pharma Intelligence75390 Cancer Vaccine InvestorsAdage Capital Management5AM VenturesAbingworthAlaska Permanent Fund3B Future Health Fun
204、d14BIO Capital234Accelerate New York Seed Fund5Access BridgeGap Ventures6Access Industries7Aisling Capital8910Alexandria Venture InvestmentsAlgot InvestAlly Bridge Group1112Alliance of Angels1314AFLA15ArrowMark PartnersAndera PartnersAndreessen HorowitzAtlas VentureAmgen Ventures16Anaxago171819Apeir
205、on Investment Group20ARCH Venture Partners21Arix Bioscience22Asymmetry Ventures232425Auriga PartnersBWVBaker Brothers Advisors LLC2627Baillie Gifford2829BankInvest Biomedical Venture30BARDABe The Match BioTherapiesBezos ExpeditionsBioNTechBarer&Son Capital31BB Biotech Ventures323334Bill&Melinda Gate
206、s Foundation35Binex36BioAtla37BioMedPartners383940Biox BiosciencesBirk VentureBlackstone Life Sciences4142Blackstone Group4344BNP Paribas Private Equity45Deep Pharma Intelligence76390 Cancer Vaccine InvestorsBrightEdge FundBpifranceBraavos Investment AdvisersBusiness FinlandBIVF46Boxer Capital474849
207、Brace Pharma50Brain Asset Management51Brainchild Holdings52Bristol Myers Squibb535455BXR Partners LLPCaaS Capital ManagementCIRM5657Calculus Capital5859California Technology Ventures60CelgeneCancer RopCARB-XCMMTCAM Capital61Cambrian Biopharma626364Care Capital65Casdin Capital66Catalio Capital Manage
208、ment67Chartwave686970Cherwell CapitalCGPHHClarus Ventures7172Clal Biotechnology Industries7374CEPI75Deep Track CapitalCrimson PeakCrystal BioscienceDTRAConnecticut Innovations76Cormorant Asset Management777879Dai-ichi Life80DARPA81DBJ Capital82Deerfield Capital Management838485DPCM LPDragasac Limite
209、dEDBI8687EcoR1 Capital8889EFung Capital90Deep Pharma Intelligence77390 Cancer Vaccine InvestorsF1 BioVenturesEuropean Innovation CouncilEuropean Investment BankFlagship PioneeringEIR Ventures91European Commission929394Eventide95Evotec96F-Prime Capital97FMRC9899100Flerie InvestFortress Investment Gro
210、upFrazier Healthcare Partners101102Franklin Templeton Investments103104Fund+105GlaxoSmithKlineGeneMatrixGenzymeGreat Point PartnersFuture Planet Capital106Future Ventures107108109German Federal Ministry of ER110Gilde Healthcare111Gilead Sciences112Global Bio Fund113114115GrifolsGVHansongneotech11611
211、7Hambro Perks Ltd.118119HBM Healthcare Investments AG120Hunza VenturesHoratio Ventures NYCHorizon 2020Idinvest PartnersHigh-Tech Grunderfonds121Hillhouse Capital Group122123124Horizon Technology Finance125Hudson Bay Capital Management126Human Longevity127Hygea VCT128129130Imperial Innovationsinfinit
212、as capital groupInnovation Fund Denmark131132Innovation Engine133134Innovation Norway135Deep Pharma Intelligence78390 Cancer Vaccine InvestorsJennison AssociatesInvusIppon CapitalJM Family EnterprisesInovio Pharmaceuticals136Invesco137138139Irving Investors140Janus Henderson Investors141Jebsen Capit
213、al142JIC 143144145Johnson&Johnson InnovationJolly Innovation VenturesKeiretsu Capital146147Kaitai Capital148149Keiretsu Forum150Korify Capital AGKhosla VenturesKing Star CapitalKSPKeiretsu Forum Northwest151KfW152153154Kinled Holding155Kleiner Perkins156Korea Investment Partners157Kreftforeningen158
214、159160KTB VenturesKukje PharmaLandeskreditbank BW161162Kurma Partners163164LBBW Asset Management165Lifeforce CapitalLeukemia&Lymphoma SocietyLife Science AngelsLilly Asia VenturesLead Compass Investment166Leerink Partners167168169Life Sciences Pennsylvania170Life Sciences Partners171Life Sciences Re
215、search Partners.172Lightspeed Venture Partners173174175Livzon Pharmaceutical GroupLoyal Valley CapitalLSP BioVentures176177LSP178179Luminous Ventures180Deep Pharma Intelligence79390 Cancer Vaccine InvestorsMeusinvest(Noshaq)Lupus VenturesM&G InvestmentsMinority Angel Investor NetworkLundbeckfonden E
216、merge181Lundbeckfonden Ventures182183184MBLVC185Mercia Asset Management PLC186Merck187Mid Atlantic Bio Angels188189190Mirae Asset Global InvestmentsMiraeAsset Financial GroupMohr Davidow Ventures191192MKB&Technofonds Flevoland193194MCRF195Nextech InvestMRL Ventures FundMSD PartnersNippon Venture Cap
217、italMoore Strategic Ventures196Morningside Venture Partners197198199National Cancer Institute200National Institutes of Health201New Enterprise Associates202NextWaveBio203204205Norinnova ForvaltningNorinnova InvestNorwegian Research Council206207Northleaf Capital Partners208209Novalis LifeSciences210
218、Oxford Capital PartnersODYSSEE VENTUREOmega FundsOxford Sciences InnovationNovartis211Novo Ventures212213214OrbiMed215Osage University Partners216Outsized Ventures217Oxford Investment Consultants 218219220Oxford University InnovationPenn Medicine Co-Investment Pfizer Venture Investments221222Percept
219、ive Advisors223224PFM Health Sciences225Deep Pharma Intelligence80Deep Pharma Intelligence80390 Cancer Vaccine InvestorsPoint72Pictet Private Equity Investors.Piedmont Capital PartnersPPM Oost NVPhoton Fund226Picasso Kapital227228229Piper Sandler230Platinum Asset Management231PMV232Pontifax AgTech23
220、3234235Presight CapitalPura Vida InvestmentsQatar Investment Authority236237Pureos Bioventures238239RA Capital Management240Runway Growth CapitalRegeneronRidgeback CapitalSAIKYORadium Hospital Research Foundation241Redmile Group242243244Riverbank Capital Securities245Robin Hood Ventures2 46Rotating
221、Boulder Fund247S.R.I.W.248249250Skorn Invest NordSambrinvestSand Hill Angels251252Samsara BioCapital253254Sanofi Ventures255SSSBSchroder AdveqSection 32Shinhan-Cognitive Start-up FundSansei Capital Investment256Sante Ventures257258259Sequoia Capital260Serrado Capital261SFPI-FPIM262Shibuya Kogyo26326
222、4265Shiyu CapitalSilence TherapeuticsSirnaomics266267Sinobioway Group268269Sirona Capital270Deep Pharma Intelligence81Deep Pharma Intelligence81390 Cancer Vaccine InvestorsSparebanken Nord-NorgeSofinnova PartnersSoftBankStanford UniversitySixty Degree Capital271Smooth River272273274Sorrento Therapeu
223、tics275Sosei CVC276South China Venture Capital277SR One278279280Summer CapitalSunstone Life Science VenturesSurveyor Capital281282SunTerra Capital283284SV Health Investors285TencentTakedaTakeda VenturesTeralys CapitalSyncona Partners LLP286T.Rowe Price287288289TCG Crossover290Technofund Flevoland291
224、Temasek Holdings292Tera Science293294295The Future FundThe Longevity FundThird Rock Ventures296297The Watermill Group298299TPG300UTC Investment Co.Two RiverU.S.Department of DefenseVenrockTrend Investment Group301Trygve Schiorbeck302303304UCLB305United Therapeutics306University of Pennsylvania307ven
225、Bio Select Advisor308309310Versant VenturesVienna Insurance GroupVivo Capital311312Viking Global Investors313314Wageningen Business Generator3158282390 Cancer Vaccine InvestorsYsios CapitalWoodford Investment Xfund4PPF GroupWellington Management316Westlake Village BioPartners317318319YTLO320Yijing C
226、apital321York Capital Management322Yukon Partners323324325Alexandria VentureAlpha HoldingsArie Belldegrun326327Alta Partners328329BiGEN330DCI PartnersBoris NikolicCardinal PartnersHealthcare InnovationBill Maris331Blackstone Credit332333334Cdric Delorme335Citadel336David Castle337Duke Management Com
227、pany338339340Heritage GroupHLB CoJacque J.Sokolov341342Ibis Capital Partners343344John Sigurd Svendsen345Quantum Technology PartnersMitzi KrockoverNovo HoldingsSFC CoMason Ng346Matthew Katz347348349Oxford Technology Management350Oystein Rekdal351Polaris Partners352SCALE AI353354355Starr Insurance Co
228、mpaniesThynk Capital,LLC.VI Partners356357Tony Robbins358359Alice Ventures360Deep Pharma IntelligenceDeep Pharma Intelligence8383390 Cancer Vaccine InvestorsDroia VenturesAvidity PartnersBay City CapitalForward VenturesAlta Berkeley Venture Partners361Ames Seed Capital362363364Biotechnology Value Fu
229、nd365Chicagoland Investors366CRG367Excalibur Fund Managers368369370GF SecuritiesGlobal health sciences venture fundHP WILD HOLDING AG371372Hercules Capital373374InterWest Partners375Square 1 BankMidwest OilseedsNational Institute of Allergy and Infectious DiseasesTLP Investment PartnersIowa Capital
230、Management376Magnetar Capital377378379NLG Advisors380OVP Venture Partners381Quark Venture382Terra Magnum Capital Partners383384385Vida VenturesZiff Capital PartnersEnterprise Partners3863873i Group388389WILD Group Management390Deep Pharma IntelligenceDeep Pharma IntelligenceOverview of Proprietary A
231、nalytics by Deep Pharma IntelligenceDEEP PHARMA INTELLIGENCE85Deep Pharma IntelligenceDeep Pharma Intelligence is producing regular analytical reports on major areas of high-potential in the pharmaceutical and healthcare industries,maintaining ratings of companies and governments based on their inno
232、vation potential and business activity in the BioTech space,and providing strategic consulting and investment intelligence services to top-tier clients,including major investment funds and banks,family offices,insurance companies,government organizations,and big pharma companies among others.The com
233、pany is a joint venture between the two highly specialized UK-based market intelligence hubs in Pharma/BioTech space:Pharma Division of Deep Knowledge Analytics(PD-DKA),a specialized subsidiary of Deep Knowledge Analytics(DKA),the leading analytical entity specifically focused on deep intelligence o
234、f the high-potential areas in the pharma industry,including artificial intelligence(AI)for drug discovery sector.Deep Knowledge Analytics Pharma Division serves as the main source of investment intelligence and analytics for AI-Pharma,a specialized index hedge fund for the AI in the drug discovery s
235、ector.PD-DKAs insights are frequently covered by top media such as Forbes and the Financial Times,and are acknowledged by top pharma executives.Recently,MIT named this division a top technology think-tank,acknowledging the AI ranking framework it developed.BPT Analytics(BiopharmaTrend)-a rapidly gro
236、wing analytical portal and media resource,dedicated to tracking emerging companies(startups/scaleups),innovations,investments,and trends in the pharma and biotech space.BiopharmaTrends reports and articles were referenced by Deloitte,Forbes,and other high profile media and consulting companies.Bioph
237、armaTrend is a media partner to a number of top-tier conferences and symposia in preclinical and clinical research,and healthcare research.About Deep Pharma Intelligence86Deep Pharma IntelligenceServices:Investment landscape profiling,identifying investment ideas in the biotech/healthcare tech space
238、 Preliminary due-diligence(business,science and technology,intellectual property(IP)profiling,freedom of operation assessment,legal assessment etc)Comprehensive due-diligence(deep business,science and technology assessment,IP and legal assessment,growth potential assessment etc)Infringement analysis
239、 of technology(i.g.If you plan to partner or invest in a data-analytics biotechs,or AI-development vendors,it is essential to understand their technological assets,both in terms of innovation potential and in terms of legal protection and non-infringement risk management)SWOT analysis of companies a
240、nd technological sectors,competitive profiling Industry profiling and growth strategy development for top-tier companies and governments.Deep Pharma Intelligence(DPI)is a strategic partner to the leading Life Science organizations,investment institutions(VC funds,investment banks),and governments ac
241、ross the globe in matters related to investments,strategic positioning,and policy development in the areas of pharmaceutical and biotech research,and healthcare tech.While Deep Pharma Intelligence is regularly producing open industry reports covering high-growth sectors in the Life Sciences,includin
242、g artificial intelligence(AI),digital health,and new therapies,some of the more in-depth research is only available to our clients and strategic partners under the“Proprietary Analytics”category.Our range of proprietary services includes custom consulting projects,based on the specific customer need
243、s,as well as a collection of pre-produced“ready-to-use”proprietary reports,produced by our research team,covering general trends and specific action ideas and strategy insights related to the most promising investment prospects(e.g.new technologies,biotech startups),M&A prospects(e.g.pipeline develo
244、pment targets),and strategic growth ideas(trends profiling,industry overviews etc).Overview of Proprietary Analytics by Deep Pharma Intelligence87Deep Pharma IntelligenceThe value our reports can deliver:Deep analysis of the deal-making prospects in the biotech and healthcare tech space,identificati
245、on of top mini-trends and larger tendencies in innovations and technology adoption(e.g.AI,blockchain,eHealth tech,longevity biomarkers,new therapeutics and therapies etc.)Tangible forecasts on the 3-5 years horizon,providing an overview of future scenarios of the development of various technologies
246、in the pharma industry Practical guides for adopting various technological solutions and best practises,vendor profiling and contract research strategy building Analysis of key market players in the emerging and high-growth areas of the pharmaceutical and biotech industries.The parties who gain earl
247、y access to these reports will have deep expertise on how their strategic agendas can be optimized in order to leverage novel research,new technologies,and emerging market opportunities,and stay competitive in a rapidly-changing technological environment,and taking into account shifting global prior
248、ities and trends.Proprietary ReportsThere are a few 40+page reports delivering practical answers to these specific questions in order to optimize the short and long-term strategies of biopharma corporations and other institutions related to the industry,with a newly updated edition being released ea
249、ch quarter,incrementally increasing the precision,practicality and actionability of its technological and financial analysis.Our reports are supported by our rapidly developing data mining engine,data visualization platform and analytics dashboards.Overview of Proprietary Analytics by Deep Pharma In
250、telligence88Deep Pharma IntelligenceDeep Pharma Intelligence:Analytical DashboardOur company is building a sophisticated cloud-based engine for advanced market and business intelligence in the pharmaceutical and healthcare industries.It includes data mining engine,infrastructure for expert data cura
251、tion,and advanced visualization dashboards,including mindmaps,knowledge graphs,and 3-dimensional visualizations.Visit our dashboard to learn more:www.platform.dkv.global/dashboards/ai-for-drug-discoveryDeep Pharma Intelligence:Analytical Reports89Deep Pharma IntelligenceArtificial Intelligence for D
252、rug Discovery Landscape Overview,Q1 2022 is an analytical report created by Deep Pharma Intelligence company that aims to provide a comprehensive overview of the industry landscape in what pertains adoption of AI in drug discovery,clinical research and other aspects of pharmaceutical R&D.Learn more:
253、www.deep-pharma.tech/ai-in-drug-discovery-2022-q1Landscape of Advanced Technology Companies in Pharmaceutical Industry Q4 2021 is an analytical report that provides insights about the expansion of technology developers and vendors into the pharmaceutical space,and their increasing role and influence
254、 on the overall success of drug discovery and pharmaceutical business.Learn more:www.deep-pharma.tech/technology-report-q4-2021Deep Pharma Intelligence(DPI)Disclaimer.The information and opinions in this report were prepared by Deep Pharma Intelligence.The information herein is believed by DPI to be
255、 reliable but DPI makes no representation as to the accuracy or completeness of such information.There is no guarantee that the views and opinions expressed in this communication will come to pass.DPI may provide,may have provided or may seek to provide advisory services to one or more companies men
256、tioned herein.In addition,employees of DPI may have purchased or may purchase securities in one or more companies mentioned in this report.Opinions,estimates and analyses in this report constitute the current judgment of the author as of the date of this report.They do not necessarily reflect the op
257、inions of DPI and are subject to change without notice.DPI has no obligation to update,modify or amend this report or to otherwise notify a reader thereof in the event that any matter stated herein,or any opinion,estimate,forecast or analysis set forth herein,changes or subsequently becomes inaccura
258、te.This report is provided for informational purposes only.It is not to be construed as an offer to buy or sell or a solicitation of an offer to buy or sell any financial instruments or to participate in any particular trading strategy in any jurisdiction.E-mail:infodeep-pharma.techWebsite:www.deep-pharma.techLink to the Report:www.deep-pharma.tech/landscape-of-cancer-vaccines