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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 Drug Discovery Sector8Neoantigen Platform13Key Players18SWOT Analysis22Tumor-Associated Antigens Platform23Key Players27SWOT Analysis30Cellular Platform31Key Players36SWOT Analysis39Table of ContentsAntigenic Essence Platform40Key Players45SWOT Analysis46Oncolytic Viruses Platform47Key Players51SWOT Analysis55Cancer 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 human 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 obtain 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 classification.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 adverse 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 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 vaccines 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 both 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-neoantigensTo 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-TArtificial 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 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 products 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 Vacmedix9IO 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)4Vaccitech5Enochian 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 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 both 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 Expertise 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 specific 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 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 funding 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 2020($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 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.Neoantigens 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 discovered,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 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.,Frontiers in Immunology(2021)Viral infectionProtein coding sequence mutationGene rearrangementAlternative splicingNeoantigen Platform:Overview201720162012200419882019202115Deep Pharma IntelligenceFirstly applied next-generation sequencing technology to identify immunogenic neoantigens in mouse tumor modelsPersonalized 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 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 interest 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 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 interests 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 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 storage 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 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.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 administered 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 neoantigens(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 ModernaBNT122 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 developed 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,cancer 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 with 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 unmodified,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 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:Key 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 biology-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.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 dendritic 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 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 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 neoantigens 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 monthsInhibigens 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 tumor 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 support 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 It 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 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-cell 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 antigensDetected 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 supposed 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: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 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:Development 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.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 enough 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 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 approach 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 antigen 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 mechanism 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 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 TechnologyInjectable 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 natural 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 trials29Deep 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 tumor-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 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)Tumor-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 enter 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 investigation 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 platform 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-cell 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.,Vaccines 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 al.,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 lysatesWhole 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 injected 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 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 immunotherapy Trying to increase the concentration of target antigens200820041991195318932010-2022DiscoveryPre-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 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-adjuvant 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 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 vaccines 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 mass 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 AiVita 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 cells 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 tumor 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 human 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 with 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 Platform: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 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 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 cancer 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 Pharma 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 be 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 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 revitalisation.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 number 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 previously 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 limitationsTargetingTumor 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 essence 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 IntelligenceHamid et al.,Cancer Immunology and Immunotherapy(2017)Antigenic Essence Platform:Development Milestones20052006-20082009-2010201420122017-20182015-20162020-2021Development of a“cell proteomic footprint”technology,antigenic essence initial stages of developmentFirst patent application and Eurasian patents 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 vaccination(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 FDACollaboration 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 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 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-loaded 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 surface antigens obtained with an antigenic essence approachIntracellular antigens which create noise in whole-cell vaccines99%1ll 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 obtained 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 platform 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 knowledge 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 Essence 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 solid 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 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 Pharma 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 vaccines 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 cellular 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 tumor 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 IntelligenceFirst 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 sarcomaMumps virus for solid tumorsFDA approval of T-VEC oncolytic virus cancer vaccineHamid et al.,Cancer Immunology and Immunotherapy(2017)Oncolytic Viruses Platform:Development Milestones19041955-197519972005200320212015DiscoveryPre-INDPhase 1/2Phase 3CommercializationCAN-2409 Adenovirus for prostate 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 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 DevelopmentOncolytic 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 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 Players 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 delivery 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 induces 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.Viral 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 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 better 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 immunotherapy.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.Their 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 identified 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 outburst 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 advanced 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 extensive 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 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 body 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 System57Deep 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 vaccines 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 microenvironment,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 deeper 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-degradable 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 while 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 medicinal 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 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 released 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 efficacy 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 Systems59Deep 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 activation.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-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 scaffold 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 geometric 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 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 project 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 Delivery 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 adaptive 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 types 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 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 include 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 pharmaceutical 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 Vaccines 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 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 solubility 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 medicines,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 Alnylam 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 protect 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 to 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 nervous 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 acidic 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 tissues.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 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 Platform,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 and 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 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 safety.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 IntelligenceThe 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 vaccination 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 pharmaceutical 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 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 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 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 conducted 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 companies,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 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 specificity,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 Therapeutics7Anixa Biosciences8910Antion BiosciencesApeiron BiologicsArrowhead Pharmaceuticals1112Arcellx1314AstraZeneca15Boehringer IngelheimAvrobioBavarian NordicBrightPath BiotherapeuticsAutolus16AVAX Technologies171819BioMedicure20BioNTech21BioVaxys22BriaCell Therapeutics232425CalviriCaroGenCeldara Medical2627CARsgen Therapeutics2829Celgene30DendreonCelyadCodiak BiosciencesEditas MedicineCellectis31Celularity323334Corixa Corporation35CureVac36Defence Therapeutics37Dynavax Technologies Corporation383940Elicio TherapeuticsElios TherapeuticsEnochian Biosciences4142Enara Bio4344EpiThany45Deep Pharma Intelligence72150 Cancer Vaccine ompaniesFrame TherapeuticseTheRNAEvaxion BiotechGemVax&KaelEpitopoietic Research Corporation46EpiVax Oncology474849ExploRNA Therapeutics50EXUMA Biotech51Flow Pharma52Galena Biopharma535455Geneos TherapeuticsGenerex BiotechnologyGeovax5657Genocea Biosciences5859GlaxoSmithKline60ImmunicumGritstone OncologyHeat BiologicsImmunoRestorationGracell Biotechnologies61Gradalis626364Hookipa Pharma65Hubro Therapeutics66Immunetune67Immunomic Therapeutics686970ImvaxInovio PharmaceuticalsIO Biotech7172InProTher ApS7374Ionis Pharmaceuticals75Lytix BiopharmaJuno TherapeuticsKhloris BiosciencesMaxiVAXISA Pharmaceuticals76Janssen Pharmaceuticals777879Kite Pharma80Lava Therapeutics81Legend Biotech82Magenta838485MedigeneMidatech PharmaMustang Bio8687Moderna Therapeutics8889Neuvogen90Deep Pharma Intelligence73150 Cancer Vaccine ompaniesOnco Therapy ScienceNoile-Immune BiotechNorthwest BiotherapeuticsONYvaxNewLink Genetics Corporation91NexImmune929394Nouscom95NovaRx96Nykode Therapeutics97OncoPep9899100Oryx Translational MedicineOsivaxOxVax101102Oxford Vacmedix103104PDC*line Pharma105Providence TherapeuticspHLIPPhoreus BiotechRegen BioPharmaPepscan106Personalis107108109Polynoma110Precision BioSciences111ProMab Biotechnologies112PsiOxus Therapeutics113114115Rhovac ApSRNAimmuneRubius Therapeutics116117Roche118119SapVax120Deep Pharma Intelligence74150 Cancer Vaccine ompaniesOnco Therapy ScienceNoile-Immune BiotechNorthwest BiotherapeuticsONYvaxNewLink Genetics Corporation136NexImmune137138139Nouscom140NovaRx141Nykode Therapeutics142OncoPep143144145Oryx Translational MedicineOsivaxOxVax146147Oxford Vacmedix148149PDC*line Pharma150Southwest Oncology GroupSensei BiotherapeuticsSilvacxStrike PharmaScancell Holdings121SELLAS Life Sciences122123124Socium Therapeutics125Sonoma126Sorrento Therapeutics127SpyBiotech128129130Sumitomo Pharma OncologyTakeda PharmaceuticalsTargovax131132Takis Biotech133134Tmunity Therapeutics135Deep Pharma Intelligence75390 Cancer Vaccine InvestorsAdage Capital Management5AM VenturesAbingworthAlaska Permanent Fund3B Future Health Fund14BIO Capital234Accelerate New York Seed Fund5Access BridgeGap Ventures6Access Industries7Aisling Capital8910Alexandria Venture InvestmentsAlgot InvestAlly Bridge Group1112Alliance of Angels1314AFLA15ArrowMark PartnersAndera PartnersAndreessen HorowitzAtlas VentureAmgen Ventures16Anaxago171819Apeiron Investment Group20ARCH Venture Partners21Arix Bioscience22Asymmetry Ventures232425Auriga PartnersBWVBaker Brothers Advisors LLC2627Baillie Gifford2829BankInvest Biomedical Venture30BARDABe The Match BioTherapiesBezos ExpeditionsBioNTechBarer&Son Capital31BB Biotech Ventures323334Bill&Melinda Gates Foundation35Binex36BioAtla37BioMedPartners383940Biox BiosciencesBirk VentureBlackstone Life Sciences4142Blackstone Group4344BNP Paribas Private Equity45Deep Pharma Intelligence76390 Cancer Vaccine InvestorsBrightEdge FundBpifranceBraavos Investment AdvisersBusiness FinlandBIVF46Boxer Capital474849Brace Pharma50Brain Asset Management51Brainchild Holdings52Bristol Myers Squibb535455BXR Partners LLPCaaS Capital ManagementCIRM5657Calculus Capital5859California Technology Ventures60CelgeneCancer RopCARB-XCMMTCAM Capital61Cambrian Biopharma626364Care Capital65Casdin Capital66Catalio Capital Management67Chartwave686970Cherwell CapitalCGPHHClarus Ventures7172Clal Biotechnology Industries7374CEPI75Deep Track CapitalCrimson PeakCrystal BioscienceDTRAConnecticut Innovations76Cormorant Asset Management777879Dai-ichi Life80DARPA81DBJ Capital82Deerfield Capital Management838485DPCM LPDragasac LimitedEDBI8687EcoR1 Capital8889EFung Capital90Deep Pharma Intelligence77390 Cancer Vaccine InvestorsF1 BioVenturesEuropean Innovation CouncilEuropean Investment BankFlagship PioneeringEIR Ventures91European Commission929394Eventide95Evotec96F-Prime Capital97FMRC9899100Flerie InvestFortress Investment GroupFrazier Healthcare Partners101102Franklin Templeton Investments103104Fund 105GlaxoSmithKlineGeneMatrixGenzymeGreat Point PartnersFuture Planet Capital106Future Ventures107108109German Federal Ministry of ER110Gilde Healthcare111Gilead Sciences112Global Bio Fund113114115GrifolsGVHansongneotech116117Hambro Perks Ltd.118119HBM Healthcare Investments AG120Hunza VenturesHoratio Ventures NYCHorizon 2020Idinvest PartnersHigh-Tech Grunderfonds121Hillhouse Capital Group122123124Horizon Technology Finance125Hudson Bay Capital Management126Human Longevity127Hygea VCT128129130Imperial Innovationsinfinitas capital groupInnovation Fund Denmark131132Innovation Engine133134Innovation Norway135Deep Pharma Intelligence78390 Cancer Vaccine InvestorsJennison AssociatesInvusIppon CapitalJM Family EnterprisesInovio Pharmaceuticals136Invesco137138139Irving Investors140Janus Henderson Investors141Jebsen Capital142JIC 143144145Johnson&Johnson InnovationJolly Innovation VenturesKeiretsu Capital146147Kaitai Capital148149Keiretsu Forum150Korify Capital AGKhosla VenturesKing Star CapitalKSPKeiretsu Forum Northwest151KfW152153154Kinled Holding155Kleiner Perkins156Korea Investment Partners157Kreftforeningen158159160KTB VenturesKukje PharmaLandeskreditbank BW161162Kurma Partners163164LBBW Asset Management165Lifeforce CapitalLeukemia&Lymphoma SocietyLife Science AngelsLilly Asia VenturesLead Compass Investment166Leerink Partners167168169Life Sciences Pennsylvania170Life Sciences Partners171Life Sciences Research Partners.172Lightspeed Venture Partners173174175Livzon Pharmaceutical GroupLoyal Valley CapitalLSP BioVentures176177LSP178179Luminous Ventures180Deep Pharma Intelligence79390 Cancer Vaccine InvestorsMeusinvest(Noshaq)Lupus VenturesM&G InvestmentsMinority Angel Investor NetworkLundbeckfonden Emerge181Lundbeckfonden Ventures182183184MBLVC185Mercia Asset Management PLC186Merck187Mid Atlantic Bio Angels188189190Mirae Asset Global InvestmentsMiraeAsset Financial GroupMohr Davidow Ventures191192MKB&Technofonds Flevoland193194MCRF195Nextech InvestMRL Ventures FundMSD PartnersNippon Venture CapitalMoore Strategic Ventures196Morningside Venture Partners197198199National Cancer Institute200National Institutes of Health201New Enterprise Associates202NextWaveBio203204205Norinnova ForvaltningNorinnova InvestNorwegian Research Council206207Northleaf Capital Partners208209Novalis LifeSciences210Oxford Capital PartnersODYSSEE VENTUREOmega FundsOxford Sciences InnovationNovartis211Novo Ventures212213214OrbiMed215Osage University Partners216Outsized Ventures217Oxford Investment Consultants 218219220Oxford University InnovationPenn Medicine Co-Investment Pfizer Venture Investments221222Perceptive Advisors223224PFM Health Sciences225Deep Pharma Intelligence80Deep Pharma Intelligence80390 Cancer Vaccine InvestorsPoint72Pictet Private Equity Investors.Piedmont Capital PartnersPPM Oost NVPhoton Fund226Picasso Kapital227228229Piper Sandler230Platinum Asset Management231PMV232Pontifax AgTech233234235Presight CapitalPura Vida InvestmentsQatar Investment Authority236237Pureos Bioventures238239RA Capital Management240Runway Growth CapitalRegeneronRidgeback CapitalSAIKYORadium Hospital Research Foundation241Redmile Group242243244Riverbank Capital Securities245Robin Hood Ventures2 46Rotating Boulder Fund247S.R.I.W.248249250Skorn Invest NordSambrinvestSand Hill Angels251252Samsara BioCapital253254Sanofi Ventures255SSSBSchroder AdveqSection 32Shinhan-Cognitive Start-up FundSansei Capital Investment256Sante Ventures257258259Sequoia Capital260Serrado Capital261SFPI-FPIM262Shibuya Kogyo263264265Shiyu CapitalSilence TherapeuticsSirnaomics266267Sinobioway Group268269Sirona Capital270Deep Pharma Intelligence81Deep Pharma Intelligence81390 Cancer Vaccine InvestorsSparebanken Nord-NorgeSofinnova PartnersSoftBankStanford UniversitySixty Degree Capital271Smooth River272273274Sorrento Therapeutics275Sosei CVC276South China Venture Capital277SR One278279280Summer CapitalSunstone Life Science VenturesSurveyor Capital281282SunTerra Capital283284SV Health Investors285TencentTakedaTakeda VenturesTeralys CapitalSyncona Partners LLP286T.Rowe Price287288289TCG Crossover290Technofund Flevoland291Temasek Holdings292Tera Science293294295The Future FundThe Longevity FundThird Rock Ventures296297The Watermill Group298299TPG300UTC Investment Co.Two RiverU.S.Department of DefenseVenrockTrend Investment Group301Trygve Schiorbeck302303304UCLB305United Therapeutics306University of Pennsylvania307venBio Select Advisor308309310Versant VenturesVienna Insurance GroupVivo Capital311312Viking Global Investors313314Wageningen Business Generator3158282390 Cancer Vaccine InvestorsYsios CapitalWoodford Investment Xfund4PPF GroupWellington Management316Westlake Village BioPartners317318319YTLO320Yijing Capital321York Capital Management322Yukon Partners323324325Alexandria VentureAlpha HoldingsArie Belldegrun326327Alta Partners328329BiGEN330DCI PartnersBoris NikolicCardinal PartnersHealthcare InnovationBill Maris331Blackstone Credit332333334Cdric Delorme335Citadel336David Castle337Duke Management Company338339340Heritage GroupHLB CoJacque J.Sokolov341342Ibis Capital Partners343344John Sigurd Svendsen345Quantum Technology PartnersMitzi KrockoverNovo HoldingsSFC CoMason Ng346Matthew Katz347348349Oxford Technology Management350Oystein Rekdal351Polaris Partners352SCALE AI353354355Starr Insurance CompaniesThynk Capital,LLC.VI Partners356357Tony Robbins358359Alice Ventures360Deep Pharma IntelligenceDeep Pharma Intelligence8383390 Cancer Vaccine InvestorsDroia VenturesAvidity PartnersBay City CapitalForward VenturesAlta Berkeley Venture Partners361Ames Seed Capital362363364Biotechnology Value Fund365Chicagoland 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 Management376Magnetar Capital377378379NLG Advisors380OVP Venture Partners381Quark Venture382Terra Magnum Capital Partners383384385Vida VenturesZiff Capital PartnersEnterprise Partners3863873i Group388389WILD Group Management390Deep Pharma IntelligenceDeep Pharma IntelligenceOverview of Proprietary Analytics 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 innovation 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 company 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 of 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 sector.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 growing 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.BiopharmaTrend 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 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 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 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more: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 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 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 mentioned herein.In addition,employees of DPI may have purchased or may purchase securities in one 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Q4 2022Cancer Vaccine Industrywww.deep-pharma.techinfodeep-pharma.techOverview Introduction and Mindmaps3Level of Cancer Vaccine Innovation of 30 Leading Companies in Drug Discovery Sector9Neoantigen Platform14Key Players21SWOT Analysis25Tumour-Associated Antigens Platform26Key Players31SWOT Analysis34Cellular Platform35Key Players41SWOT Analysis44Table of ContentsAntigenic Essence Platform45Key Players48SWOT Analysis51Oncolytic Viruses Platform52Key Players55SWOT Analysis60Cancer Vaccines Delivery Systems61Key Players65Key Takeaways and General Conclusions 71General Conclusions74Overview of Proprietary Analytics by Deep Pharma Intelligence75Disclaimer803Deep Pharma IntelligenceThe most powerful weapon against malignancies can be hidden inside the host human 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 tumour.This is the aim of cancer vaccination to activate host immunity cells to destroy the tumour cells.A number of FDA-approved vaccines are cancer prevention vaccines,proving that cancer vaccines are more than just a pipe dream.Researchers nowadays are developing vaccines with the goal of reliably and effectively inducing the immune system to target cancer cells.Additionally,they are looking into additional strategies to improve the immune systems response to malignant cells.Tumour-Associated AntigensCellularOncolytic VirusesCancer Vaccine PlatformsNeoantigensAntigenic EssenceIntro:What is a Cancer Vaccine?Neoantigen PlatformDeveloping vaccines based on specific class of antigens which include those created by tumour viruses that have integrated into the genome and those produced by mutant proteins.They are abundantly expressed only in cancer cells and have a high immunogenicity and tumour heterogeneity.Tumour-Associated Antigens PlatformDeveloping vaccines based on antigens that are inappropriately expressed by cancer cells.The antigens are present in both healthy and cancerous cells,with the only difference being the degree of exposure or presentation by the cell.Cellular PlatformDeveloping vaccines by considering all cellular antigens,including tumour-associated antigens(TAA)and neoantigens.Whole-cell platforms,as opposed to TAA or neoantigen platforms,contain both recognised and uncharacterised TAA and tumour-specific antigens TSA.Oncolytic viruses platformDeveloping vaccines through viruses modified to target cancer cells and enhance the immune response to completely destroy the tumour.Antigenic Essence PlatformDeveloping vaccines by using surface-presented antigens,recognised by human immune system.0501020304Cancer Vaccine Platforms ClassificationThere are multiple platforms developed to obtain cancer vaccines.In this report we are going to discuss five such platforms,which serve as a basement for vaccines creation.Some of these cancer vaccine platforms overlap and evolve out of each other while other still have some unique distinguishable features,which was a reason for suggested classification.4Deep Pharma Intelligence5 Cancer Vaccine Platformscytotoxic CD8 T-cells 5Deep Pharma IntelligenceWe targeted cytotoxic CD8 T-cells to kill the cancer cells.We need to engage both CD8 and memory CD4 T-cells to prolongate the effect.We found out that the tumour lysates can activate the immune response to cancer.Off-tumour effects became a severe reason for cellular damage,so scientists are working to decrease them.We learnt how to target tumours through their unique mutations neoantigens.To prevent tumour escape,we need to target multiple antigens on the tumour cell.Intro:Where is Cancer Vaccination Right Now?6Deep Pharma IntelligenceAt first,cancer vaccines did not succeed:the enthusiasm and interest towards this technology dropped after seeing the high level of adverse 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 cancer vaccines was estimated as US$10.72 billion,and it has reached$16.47billion in 2022.Considering this tendency,it is reasonable to say that cancer vaccines start forming a separate branch of industry.Cancer Vaccine Industry$10.72billion$16.47billionSequencing technologies Cancer vaccines market size growth 2021-2022Bioinformatic data treatmentAdvanced delivery systems Novel adjuvant technologyFaster,cheaper,and more optimised Biologically advanced technologiesInvestorsCompaniesWhole-cell antigensCancer Vaccines by Antigen TypeTumour-associated antigensTumour-specific antigensCompanies 150 Investors 350Cancer Vaccine Companies Landscape View More:www.deep-pharma.techViral VectorsDendritic CellsDNACancer Vaccines and Cell Immunotherapies by Delivery Form Companies 170 Investors 420RNAPeptides and ProteinsInvestorsCompaniesCAR-TArtificial Vectors and Immune Cells Cancer Vaccine Companies Landscape View More:www.deep-pharma.tech9Deep Pharma IntelligenceLevel of Cancer Vaccine Innovation of 40 Leading Companies in Drug Discovery Sector9 9Methodology: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 products on the market/development pipelines;novelty of the product;addressment of the unmet needs,etc.Innovative ApproachAiVita Biomedical1Arrowhead Pharmaceuticals(NASDAQ:ARWR)2Biobohemia3CimCure4Editas Medicine5Epitopea6Genocea Biosciences(NASDAQ:GNCA)7Gradalis8Gritstone Oncology(NASDAQ:GRTS)9Heat Biologics(NASDAQ:HTBX)10Hookipa Biotech(NASDAQ:HOOK)11ImCheck12IO Biotech13Ionis Pharma(NASDAQ:IONS)14Iovance Biotherapeutics(NASDAQ:IOVA)15Classic ApproachAdaptimmune(NASDAQ:ADAP)1ADC Therapeutics(NYSE:ADCT)2Affimed Therapeutics(NASDAQ:AFMD)3Agenus Inc.(NASDAQ:AGEN)4AstraZeneca(NSE:ASTRAZEN)5BioNTech(NASDAQ:BNTX)6Brenus Pharma7CureVac(NASDAQ:CVAC)8Enochian Biosciences(NASDAQ:ENOB)9Gilead10GlaxoSmithKline(NYSE:GSK)11Immunomic Therapeutics12Inovio Pharmaceuticals(NASDAQ:INO)13Moderna Therapeutics(NASDAQ:MRNA)14Northwest Biotherapeutics(OTC:NWBO)15NexImmune(NASDAQ:NEXI)16Oxford Vacmedix17Rubius Therapeutics(NASDAQ:RUBY)18Scancell Holdings(LSE:SCLP)19Sorrento Therapeutics(NASDAQ:SRNE)20Nykode Therapeutics16OncoPep17PsiOxus Therapeutics18Transgene(EPA:TNG)19Vaccitech20Cancer vaccines development shifted into the direction of more specific tumour targeting due to neoantigen platform.Still,the tremendous majority of such neoantigen vaccines dont overcome the problem of tumour escape mutations and the heterogeneity of cancer cells.Only restricted number of innovative platforms try to face and solve both issues of highly specific tumour targeting and escape mutations prevention.They apply new approaches on already developed platforms(such as whole-cell,neoantigen,TAA)or initialise new platform(antigenic essence).10Deep Pharma IntelligenceComparison of Top-40 Leading Drug Discovery Companies Expertise in Cancer Vaccines R&D Expertise in Drug Discovery11Deep Pharma IntelligenceClinical pipeline(Phase III)Clinical pipeline(Phase I-2)Validated R&D Use casesand preclinical pipeline Mildly specific but can address tumour heterogeneity Highly specific but no or limited heterogeneity addressedHighly specific and addresses tumour heterogeneityTumour targeting efficiency Comparison of Top-40 Leading Drug Discovery Companies Expertise in Cancer Vaccines R&D12Deep Pharma IntelligenceComparison of Top-40 Leading Drug Discovery Companies Expertise in Cancer Vaccines R&DCancer vaccine leaders belong both to Big Pharma companies with multiple directions and to fast-growing start-ups that are 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 funding 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,as of Q2 2021,they already raised roughly twice as much as during the whole 2020($850 million and$484 million,correspondingly).13Deep Pharma IntelligenceAbove$250M$50M-$250M$1M-$50M Mildly specific but can address tumour heterogeneity Highly specific but no or limited heterogeneity addressedHighly specific and addresses tumour heterogeneityLevel of Capital RaisedTumour targeting efficiency Comparison of Top-35 Leading Drug Discovery Companies Expertise in Cancer Vaccines R&DNeoantigen PlatformDEEP PHARMA INTELLIGENCEDNA sequencing first stage for neoantigens identificationNeoantigens represent a large platform in the field of cancer vaccines and generally in tumour immunotherapy.Neoantigens include antigens produced by tumour viruses integrated into the genome and antigens originated by mutant proteins,which are abundantly expressed specifically in cancer cells and have strong immunogenicity and tumour heterogeneity.Currently,a considerable number of neoantigens have been discovered that are unique to tumour cells and are not affected by immune tolerance mechanism.15Deep 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 use as broad-spectrum therapeutic cancer vaccines for patients with the same mutated gene.Unique to most neoantigens and completely different from patient to patientPersonalised neoantigen preparation drug can only be specifically targeted to each patient,that is,personalised therapyZhang et al.,Frontiers in Immunology(2021)Viral infectionProtein coding sequence mutationGene rearrangementAlternative splicingNeoantigen Platform:OverviewNeoantigen Platform:Development MilestonesDeep Pharma IntelligenceJiang et al.,Journal of Hematology&Oncology(2019)161988Study reported that anti-tumour T-cells could recognise aberrant peptides derived from tumour-specific mutations2004Complete regression in a melanoma patient after infusion of a cell product with a high proportion of neoantigen-reactive T-cells2012Firstly applied next-generation sequencing technology to identify immunogenic neoantigens in mouse tumour models2016First mass spectrometry identification of neoantigens in human tumour tissue2017Personalised neoantigen peptide and RNA vaccines could induce specific T-cell populations that recognise autologous tumour2019Neoantigen-directed immune escape in lung cancer evolution2021Outburst of interest to mRNA vaccines development due to the COVID-19 pandemic2022Increased number of precision cancer therapies targeting mutations expressed by tumour cells(neoantigens)17Deep Pharma IntelligenceCollection of tumour and normal tissueGenome sequencingTranscriptome sequencingBioinformatic candidate IDMass spectrometry Evaluationof immuno-genicitySynthetic vaccine(DNA/mRNA/peptides/DC)There are no yet approved neoantigen vaccines.However,according to ClinicalTrials.gov search,there are 190 cases of neoantigen studies,and none of them has yet entered 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 interests in this cancer-vaccines platform.Many of these studies have shown a good application value of neoantigen(Search term neoantigen).However,the study of neoantigen therapy starts relatively late and is still in the laboratory stage.The first stages of neoantigen vaccines development are complex and time consuming.Even though genome and transcriptome sequencing technologies are actively developing,they remain a milestone,together with bioinformatic treatment of data.As a result,the complications of neoantigen platform overlap with the well-known issues of sequencing cost,speed,data storage,and analysis.However,with the rapid digitalisation and a broad introduction of Artificial Intelligence(AI),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 of Neoantigen Cancer Vaccine DevelopmentLandscape of Selected Neoantigen CompaniesDeep Pharma IntelligenceNucleotide/Protein-BasedVaccinesOncolytic Viruses-Based VaccinesNeoantigen-specific Cell TherapyPriming ApproachUndisclosedPrivate Neoantigens Public Neoantigens 19Deep Pharma IntelligenceGenocea Biosciences GEN-009 vaccine trial(NCT03633110)is now on the Phase I/IIa clinical trials and has shown the best efficacy among the current neoantigen personalisation therapies,with an estimated completion date of December 2022.The purpose of this study was to evaluate the safety,tolerability,immunogenicity,and anti-tumour activity of the personalised vaccine GEN-009 for the treatment of patients with solid tumours,which is targeted at a broad range of cancers.The results so far show that 40 doses of the vaccine have been administered 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 six cancer vaccines in development with shared neoantigens(FixVac platform)and two cancer vaccines owned together with Genentech based on individualised approach(iNeST platform).DiscoveryPre-INDPhase I/IIPhase IIIGEN-009 Neoantigen vaccine by GenoceaBNT111 Shared neoantigen vaccine by BioNTechPCV mRNA-4157 Neoantigen vaccine by ModernaBNT122 Individualised neoantigen vaccine by BioNTech and GenentechNeoantigen Platform:Cancer Vaccines in DevelopmentNeoantigen Cancer Vaccines Development Pipeline20Deep Pharma IntelligenceAchilles Therapeutics is a biopharmaceutical company developing precision T-cell therapies that target clonal neoantigens.Currently,they have two vaccine trials that are at the Phase I/IIa clinical trials:Chiron for therapy of advanced nonsmall cell lung cancer and Thetis for therapy of melanoma.The purpose of this study was to evaluate the safety and clinical activity of neoantigen reactive T-cells.Transgene finished Phase I clinical trial studies of personalised neoantigen vaccine TG4050 in ovarian carcinoma and head and neck carcinoma.This cancer vaccine is based on Transgenes myvac platform and powered by NECs cutting-edge AI capabilities.Granite and Slate are two cancer vaccines developed by Gritstone Oncology.Both of them are now at Phase I/IIa clinical trials for the treatment of different types of solid tumours.DiscoveryPre-INDPhase I/IIPhase IIICHIRON and THETIS Shared neoantigen vaccines by Achilles TherapeuticsVXM01 Neoantigen vaccine by VAXIMMNeoantigen Platform:Cancer Vaccines in DevelopmentNeoantigen Cancer Vaccines Development PipelineTG4050 Individualised neoantigen vaccine by TransgeneGRANITE and SLATE Neoantigen vaccines by Gritstone Oncology21Deep Pharma IntelligenceBioNTech Big Pharma company that mostly specialises on various cancer immunotherapies.They own technologies with developed mRNA platform;cell therapies;antibodies;small molecule immunomodulators.BioNTech is oriented on individualised immunotherapy with patient-specific approach.It requires a complex bioinformatic data treatment.That is why the company gathered expertise in bioinformatics of mutation detection,cancer genomics,and immunotherapy.Source BioNTech ApproachNeoantigen Platform:Key PlayersBioNTechs Validated Patient-Centric Bioinformatic ProcessUnique patientSequencing patients tumourMapping of mutationsBioinformatic algorithms Selection of neoepitopes22Deep Pharma IntelligenceFixVac cancer vaccine with shared neoantigens.Contains selected combinations of unmodified,pharmacologically optimised mRNA,encoding known for cancer-specific shared antigens.mRNA is delivered using lipoplex technology.iNeST Individualised Neoantigen Specific Immunotherapy cancer vaccine with private neoantigens.Contains unmodified,pharmacologically optimised 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 at Phase I of clinical trialsBNT 122 Metastatic Melanoma(currently on the Phase II of clinical trials)And for locally advanced or metastatic solid tumours(currently on the Phase I of clinical trials)Rights are equally shared with GenentechSources BioNTech Pipeline,BioNTech PlatformsNeoantigen Platform:Key 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 biology-driven approach to identify targets of protective T-cell responses.ATLAS zeroes in on only those surface-presented antigens that trigger anti-tumour T-cell responses.ATLAS is unique in the way that it can identify protumour inhibitory antigens(Inhibigens),which subvert anti-tumour immune responses.Vaccination with such inhibigens is proved to drive tumour hyperprogression in mice.Comprehensive identification of patient and tumour-relevant T-cell responsesTumour biopsyNGSAnalysisBacterial vectors expressing each condidateUnique plasmids for every candidate neoantigenBlood sampleAutologous dendritic cellAutologous T-cell23Deep Pharma IntelligenceMultiplexed cytokine readoutCD4 and CD8 T-cell responsesIdentify inhibigensSources Genocea ScienceHow does the Genoceas ATLAS approach work?Neoantigen Platform:Key Players 24Deep Pharma IntelligenceGenocea Biosciences greatly focuses in the antigen selection for the best tumour targeting and destruction,which lies at the very basement of the ATLAS platform.GEN-009 is a neoantigen vaccine candidate in a Phase I/IIa clinical trial to treat a variety of solid tumours.ATLAS identifies neoantigens optimised both to patients T-cell responses and their tumours,underscoring the advantages of the technology for neoantigen selection.Other vaccine candidate GEN-011 belongs 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 neoantigens and expanded to create a customised therapy.Sources Genocea PipelineCollect available fixed tumour and blood sample and send for sequencingPatient sees oncologist,begins SoC ICINeoantigens(up to 20 peptides)synthesised as peptides and formulated with Poly-ICLCPatient receives five SC doses over 6 monthsInhibigens and neoantigens identified by ATLASHow does the Genoceas ATLAS approach work?25Deep 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 tumour 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 III;Neoantigen cancer vaccines might be the best personalised solution for cancer treatment.Great financial support,which moves the platforms faster to clinical research;Complete specificity to the tumour cells;Already has 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;It might be substituted with novel platforms,which are more cost-effective and highly specific for cancer cells at the same time.OTSWTumour-Associated Antigens PlatformDEEP PHARMA INTELLIGENCEMacrophages attacking cancer cellsTumour-Associated Antigens(TAA)are self-proteins that are abnormally expressed by cancer cells.It means they are present both in healthy and cancer cells and differ only 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-cell 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.27Deep Pharma IntelligenceTumour-Associated AntigensCancer testis antigensOverexpressed proteinsDifferentiation antigensDetected 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 supposed to be present in healthy adult somatic tissues but are expressed in testicles in male germ cellsTumour-Associated Antigens Platform:Overview28Deep Pharma IntelligenceCancer immunotherapy field experienced at least two significant breakthroughs connected with tumour-associated antigens platform:Promising approval of Provenge cancer vaccine(sipuleucel-T)by FDA for the treatment of prostatic cancer,which used tumour-associated antigen as a target;Development and approval of multiple CAR-T therapies based on targeting of TAA.AntigensDay 1Day 2 3Day 3 4Patient leukapheresisSipuleucel-T 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 Tumour-Associated Antigens Platform:Development MilestonesDiscoveryPre-INDPhase I/IIPhase IIICommercialisationNEXI-002 cellular vaccine for multiple myeloma by NeximmuneTumour-associated antigens platform is one of the most well-developed platforms.That is why there is plenty of clinical candidates even not considering CAR-T and counting only cancer vaccines.At the moment of our research,there were roughly 200 cases of tumour-associated antigens studies,according to ClinicalTrials.gov search.After approval of Provenge in 2010,no other cancer vaccine entered the global market.Provenge passed the clinical trials stage with a low efficiency level,but just enough to pass it,so now it is not as frequently used as we wish it to be.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 29Deep Pharma IntelligenceINO-5401 TAA vaccine by Inovio Pharmaceuticals Tumour-Associated Antigens Platform:Cancer Vaccines in DevelopmentTumour-Associated Antigens Cancer Vaccines Development PipelineDiscoveryPre-INDPhase I/IIPhase IIITAEK-VAC TAA vaccine developed by Bavarian NordicITI-1000 is a dendritic cell therapy comprised of autologous dendritic cells,which is now at a Phase II clinical trial and was developed by Immunomic Therapeutics.ITI-1000 is being tested in a randomised,blinded,and placebo-controlled Phase-II study in patients with newly-diagnosed glioblastoma(GBM),which is anticipated to close in 2022.TAEK-VAC is an innovative immuno-oncology candidate developed by Bavarian Nordic using MVA-BN technology.In 2021,a Phase I/II open label trial of the vaccine administered intravenously to individuals with advanced HER2 and brachyury-expressing tumours was started.Vigil is a fully personalised,patient-specific cancer immunotherapy that can be applied to virtually any cancer developed by Gradalis.The most advanced study is continuing now in patient with recurrent/refractory Ewings sarcoma.Vigil TAA vaccine that can be applied to virtually any type of cancer developed by Gradali 30Deep Pharma IntelligenceTumour-Associated Antigens Platform:Cancer Vaccines in DevelopmentTumour-Associated Antigens Cancer Vaccines Development PipelineITI-1000 cellular vaccine for glioblastoma developed by Immunomic TherapeuticsTumour-Associated Antigens Platform:Key Players 31Deep Pharma IntelligenceNexImmune biopharmaceutical company which implements an innovative approach to improve and develop tumour-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 antigen presentation,T-cells can recognise multiple antigens in the form of peptides.This produces T-cells with multiple immune targets for a robust anti-tumour activity.AIM Nanoparticles induce the production of both memory cells and cytotoxic effector cells.Effector cells will be the main direct mechanism to destroy tumour cells through the release of cytotoxic granules while memory cells will store in the bloodstream.Sources NexImmune Technology60 nano-metersAIM ACT NanoparticleT-Cell5-7 micronTumour-Associated Antigens Platform:Key Players 32Deep Pharma IntelligenceNexImmune is based on few principles in developing cancer vaccines with TAA:The ability to expand T-cell populations that recognise and attack multiple antigen-specific targets;Consistency in containing T-cell subtypes that support anti-tumour potency,self-renewal,proliferation,and long-term T-cell survival.Sources NexImmune TechnologyInjectable modality is presented by injectable AIM nanoparticles for solid tumours.Adoptive cell therapy modality includes cancer vaccines in the form of donor-or patient-derived T-cells for AML,multiple myeloma,and solid tumours.Artificial Immune Modulation(AIM)nanoparticles are designed to mimic the immune functions of natural antigen presenting cells,such as dendritic cells,by delivering two key immune-directing T-cell signals.PatientAIM ACT nanoparticles CREATE the productAIM INJ nanoparticles ARE the productINJECTABLE THERAPEUTICSCELL THERAPYCurrently in preclinical developmentCurrently in phase III clinical trials33Deep 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 tumour-associated antigens in the second phase of clinical trials.SynCon uses a proprietary computer algorithm that has been designed to identify and optimise the DNA sequence of the target antigen.INOVIOs DNA medicines deliver optimised plasmids directly into cells,intramuscularly or intradermally using 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)Tumour-Associated Antigens Platform:Key Players 34Deep Pharma IntelligenceTumour-Associated Antigens Platform:SWOT Analysis Weaknesses Cancer vaccines with TAA are not highly specific to tumour cells;High number of adverse effects;Peripheral tolerability risk.Opportunities Cancer vaccine candidates can enter Phase III of clinical trials;Using the experience of FDA-approved immunotherapies can improve the developing products faster.There are already examples of FDA approved immunotherapies using TAA;Applicable to almost any tumour;Lots of accumulated knowledge due to the long-time platform investigation.StrengthsThreats This 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 approved by FDA.OTSWCellular PlatformDEEP PHARMA INTELLIGENCEWhole-cell platform 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 tumour-associated antigens and neoantigens included.Unlike TAA or neoantigen platform,whole-cell platform contains both characterised and uncharacterised TAA and TSA.This approach is suitable,in theory,for any solid tumour regardless its mutation burden,and the general process of its development takes fewer steps,compared to TAA or neoantigen platforms.36Deep Pharma IntelligenceRazi et al.,Vaccines for Cancer Immunotherapy(2019)Irradiated Gene-Modified Tumour CellsIrradiated gene-modified autologous or allogeneic tumour cells,which were engineered to encode immunostimulatory agents,including cytokines and costimulatory molecules.Cellular Platform:OverviewCell culturePart of the tumourRadiation mutagenesisGene modificationProteasesLysed tumourPatient37Deep Pharma IntelligenceRazi et al.,Vaccines for Cancer Immunotherapy(2019)Tumour-Derived ExosomesTumour cell derived exosomes could be obtained from ascites,pleural effusion,and plasma samples of patients;such exosomes comprise various tumour antigens,one of the leading antigens investigated is heat shock protein.Tumour cell lysatesWhole tumour cell lysates contain all tumour 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:OverviewPatientPart of the tumourProteasesLysed tumourPatientPatientPart of the tumourProteasesAdding new adjuvants;Using different delivery strategies;Combining with other forms of immunotherapy;Trying to increase the concentration of target antigens.Tumour Associated Antigens Platform:Development Milestones19532008Deep Pharma IntelligenceJiang et al.,Journal of Hematology&Oncology(2019)19913818932004GVAX(whole-cell cancer vaccine)entered the clinical trials Phase IIIMitchison et al.discover passive transport of anti-tumour immunity in transplant mice The research in the field moved to the increasing effortsto improve previously developed products byFirst cancer patient injected with Coleys toxinFirst report of a human tumour antigen recognised by T-cells GVAX failed the clinical trials due to the lack of efficiencyDiscoveryPre-INDPhase I/IIPhase IIIDCVax-L for solid tumours(brain and ovarian cancer)by Northwest Biopharmaceuticals Despite the large number of developed products,none of them has entered the cancer 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 two products:HS-110 and HS-130 by implementing the pan-antigenic self-adjuvant technology.On the other hand,Northwest Biopharmaceuticals has a classic approach for cancer vaccines development but focuses more on clinical application optimisation for clinicians and patients.Still,history of whole-cell cancer vaccines shows some failures such as one of the most advanced cancer-vaccine candidates,GVAX,which resulted into higher mortality level in clinical trial Phase III patients.HS-110 vaccine for NSCLC by Heat Biologics39Deep Pharma IntelligenceTAA enriched vaccine for glioblastoma by Aivita(NCT03400917)Cellular Platform:Cancer Vaccines in DevelopmentCellular cancer vaccines development pipelineDiscoveryPre-INDPhase I/IIPhase IIITLPO autologous vaccine for melanoma by Elios TherapeuticsThe Tumour Lysate,Particle Only(TLPO)vaccine,developed by Elios Therapeutics,is an autologous therapeutic cancer vaccine intended to arouse the immune system to recognize tumour cells and combat a patients particular cancer.TLPO vaccine research for adjuvant melanoma treatment is currently underway.PDC*line Pharma developed PDC*vac cancer vaccine based on a cell line of Plasmacytoid Dendritic Cells(PDC*line),their top candidate for nonsmall-cell lung cancer is PDC*lung.This vaccine targets common antigens that are widely expressed.In 2019,a Phase Ib/II trial assessing its security and biological activity was started.Bria-IMT is a targeted immunotherapy being developed by BriaCell for the treatment of advanced breast cancer.This cancer vaccine is currently enrolling in Phase I/II combination study with Incytes checkpoint inhibitor retifanlimab in patients with advanced breast cancer.40Deep Pharma IntelligencePCD*lung cancer vaccine for nonsmall-cell lung cancer by PDC*line PharmaCellular Platform:Cancer Vaccines in DevelopmentCellular Cancer Vaccines Development PipelineBria-IMT in combination with immune checkpoint inhibitors by BriaCellCellular Platform:Key Players41Deep Pharma IntelligenceAiVita Biomedical is a medicine company that develops personalised cancer vaccines with a set of TAA-enriched whole-cell antigens.Their therapies are oriented to kill tumour-initiating cells(a small portion of the tumour mass that 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 tumour antigens from a short-term cell culture of autologous tumour cells.Sources AiVita Cancer ImmunotherapyOn the first steps the sample of the patients tumour undergoes cell culture.The aim of this step is enrichments with tumour-initiating cells and their amplification.It is the most critical stage since it reduces the nonspecific signals from cells.Selected in such a way,tumour cells are used to load antigen-presenting(dendritic)cells,which are delivered to the patient back in the form of subcutaneous injections.Tumour cells isolationImmune cells isolationMonocytes isolationTumour cell cultureEnhancement of TAADendritic cells deriveryDendritic cells are loaded with patients tumour antigensTreatment is administered through the injectionCellular Platform:Key Players42Deep Pharma IntelligenceHeat Biologics is a BioTech clinical-stage company focused on developing its proprietary ImPACT(Immune Pan-Antigen Cytotoxic Therapy)adjuvant technology.It is first-in-class fully human adjuvant system that functions as both an immune stimulator and an antigen-delivery system.Leading product HS-110(viagenpumatucel-L)Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig.Clinical Phase II stage,in combination with checkpoint inhibitornivolumab(Opdivo)or pembrolizumab(Keytruda)HS-130 Vaccine derived from irradiated human lung cancer cells expressing the costimulatory fusion protein OX40L-IgClinical Phase I stage for a wide range of solid tumoursSources Heat Biologics Technology,clinicaltrials.govCellular Platform:Key Players43Deep Pharma IntelligenceNorthwest Biopharmaceuticals BioTech company focused on discovering,developing,and commercialising immunotherapy products that generate and enhance immune responses to treat cancer.This company is fully focused of the development of whole-cell cancer vaccines based on DCVax technology(the technology that implements dendritic cells for a cancer treatment)or the direct usage of DC for cancer treatment.Sources Northwest Biopharmaceuticals Product Candidates Dendritic cell cancer vaccine loaded with cancer antigens from tumour lysate from the patients own tumour tissue.DCVax-L is expected to be used for any solid tumour cancers.DCVax-DirectDCVax LThe partially matured dendritic cells are injected directly into the patients tumour(s)it is suitable for the situations in which the tumours are inoperable.Besides focusing on the development of cancer 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 multidirectional approach with a broad coverage of needs.44Deep Pharma IntelligenceCellular Platform:SWOT Analysis Weaknesses Cellular noise;Low concentration of immunogenic antigens;Higher toxicity due to nonspecific targeting of healthy cells;Low immunogenicity.OpportunitiesThe vaccines developed earlier in whole-cell platform which failed clinical trials might be upgraded with innovative platform.Targeting of all cellular antigens;Natural antigens composition;Cost-effective.StrengthsThreats It might not reach the needed level of efficiency on clinical trials even using adjuvants,checkpoint inhibitors,immune stimulators,etc.GVAX(an advanced product in whole-cell cancer vaccine platform)failed clinical Phase III with a high mortality rate.OTSWAntigenic Essence PlatformDEEP PHARMA INTELLIGENCEAntigenic essence platform is an innovative platform that can be considered as a cellular vaccines revitalisation.In it,scientists 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 tumour-associated antigens,antigenic essence targets a wide number of antigens and doesnt require a complex data treatment.46Deep Pharma Intelligence Antiangiogenic SANTAVAC Targeted for tumour cells Preventive cancer vaccinesTherapeutic cancer vaccinesNovel platform-based cancer vaccines Upgrade of previously established vaccinesAntigenic EssenceAntigenic Essence Platform:Overview2 Key AdvantagesAntigenic EssenceCost and Time Efficiencypersonalised or group;peptides or dendritic cells;manufacturing friendlyWhole-CellApproachRevitalisationmore effectiveand more specific,while eliminatingall limitationsTargetingTumour Micro-environmentkilling any solidtumour 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 essence can target not only cancer cells,but endothelial cells tooAntigenic essence can be a platform for the universal medicine for solid tumoursTargets the whole antigens spectrum revolutionary antiangiogenic approachAntigenic Essence Platform:Overview47Deep Pharma IntelligenceOverall,it is important to mention that the whole complement of native antigens is inherited via antigenic essence,which is free of any substantial drawbacks.For instance,it solves MHC restriction,allows precise control of antigen composition,lacks cellular ballast(nontarget antigens),and does much more.It makes logical to improve the current cellular cancer vaccines by switching out entire cells with their antigenic components.Antigenic Essence Platform:Development Milestones2009-2010Cell proteomic footprint technology was published(Biobohemia together with Bruker),antigenic essence vaccine preparation method was published2014The research for antigenic essence was extended to the antiangiogenic cancer vaccine concept2015-2016Publication of SANTAVAC concept.European,Korean,and other patents were granted.Design of final SANTAVAC products2017-2018The trademark SANTAVAC was registered.The US patent was granted.2012Publication of the cancer response escape study as a result of anti-cancer vaccination(Biobohemia with Bruker and Institute of Biomedical Chemistry)IIND packages registration in FDA Collaboration net expansion and a growing interest in the platformDeep Pharma IntelligenceHamid et al.,Cancer Immunology and Immunotherapy(2017)2020-20212005482006-2008First patent application and Eurasian patents were grantedDevelopment of a cell proteomic footprint technology,antigenic essence initial stages of development49Deep 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 tumours regardless their mutation burden status Applicable both for personalised or group medicine Can be used to direct tumour cells or vessels This platform can be a a solution for previously failed whole-cell cancer vaccines or a good collaborator for developing ideas.Currently,antigenic essence platform is at the preclinical stage of development,but according to analysed data,it should come to final phases of clinical trials(e.g.GVAX and CanVaxin)and pass it due to significant revitalisation of the technology.Cell line or primary cell cultureAntigenic essence preparationMass spectrometry Natural peptides or peptide-loaded 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 development50Deep Pharma IntelligenceSpecific surface antigens obtained with an antigenic essence approachIntracellular antigens which create noise in whole-cell vaccines99%1ll antigensNaturally produced antigens by the tumour cells tend to induce the most accurate targeting of these cancer cells.Even though such native-cell antigens are obtained 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,and reduces the cancer vaccine specificity.That is why antigenic essence platform met the need to develop a novel cell-based cancer vaccine free from intracellular immunogenic molecules.Antigenic Essence Platform:Key PlayersBiobohemia,Inc.a BioTech company focused on the development of cancer vaccines.They fully own an antigenic essence platform which is based on a deep knowledge in proteomics and provides the tool for a revitalisation 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.51Deep Pharma IntelligenceAntigenic Essence Platform:SWOT Analysis Weaknesses Not directed to target nonsolid tumours(20%of cancer cases);Low public awareness about the new technology.Opportunities Can be used to upgrade cellular vaccines developed earlier;Can become a new emergent star of cancer vaccines market;Potentially can cure any solid tumour;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 doses.StrengthsThreats The platform is not validated in preclinical study although preliminary validation is strong;Operational capacity,structuring business processes.OTSWOncolytic Viruses PlatformDEEP PHARMA INTELLIGENCEEngineered oncolytic poliovirus for cancer treatmentCredit:Duke Cancer Institute and cancer.gov53Deep Pharma 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 tumour.Oncolytic viruses cancer vaccines platform is greatly based on the neoantigens and tumour-associated antigens platforms since the viruses are 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 cellular cancer vaccines.( )INSERTImmune-stimulating genes(-)REMOVEDisease-causing genes(selective targeting of tumours)Oncolytic VirusInfection of tumour cell and virus replicationTumour cell lysisand release of tumour antigens and cytokinesCytokinesVirus attacks other tumour cellsT-cell attacks other tumour cellsActivation of T-cellsLocal inflammation-destruction of tumour microenvironmentOncolytic Viruses Platform:OverviewOncolytic Viruses Platform:Development MilestonesDeep Pharma Intelligence54Hamid et al.,Cancer Immunology and Immunotherapy(2017)1904First viral infection-induced leukemia regression1955-1975Use of Adenovirus for cervical cancerNDV and measles virus for leukemiaParvovirus for sarcomaMumps virus for solid tumours1997First clinical trials with engineered virus2003Herpes simplex virus type I(HSV I) granulocyte-macrophage colony-stimulating factor(GM-CSF)under the name of T-VEC is developed2005H1O1 variant approved in China2015FDA approval of T-VEC oncolytic virus cancer vaccine2021Active development of oncolytic viruses delivery technologies to reduce side effects for the intravenous injection DiscoveryPre-INDPhase I/IIPhase IIICAN-2409 Adenovirus for prostate cancer by Candel TherapeuticsCurrently,there is one FDA-approved oncolytic virus immunotherapy Talimogene laherpavepvec(T-VEC)owned by Amgen.Still,there is active development of oncolytic viruses that would target a wider spectrum of tumours and wont induce the formation of undesired antibodies by the immune system.ONCR-177 HSV for intratumoural injections by OncorusOLVI-VEC for ovarian cancer by Genelux55Deep Pharma IntelligenceParxOryx for GBM by OryxTumour destruction and immune responseT-VEC T-VEC injection into tumourHerpes virus modificationOncolytic Viruses Platform:Cancer Vaccines in DevelopmentOncolytic Viruses Cancer Vaccines Development Pipeline56Deep Pharma IntelligenceSources Oncorus TechnologyThey state that their approach not only activates anti-tumoural immunity but also stimulates the release and presentation of a greater number and variety of neoantigens.One more important mechanism is a synthesis of transgenes,which influence tumour microenvironment.Oncorus BioTech company which develops next-generation viral immunotherapies for oncology.Their technology enables immune system to target cold tumours(tumours surrounded by immunosuppressive cells),converting them into hot tumours.Oncolytic Viruses Platform:Key Players Oncolytic Virus(Herpes Simplex-1 Virus or Synthetic VirusResponding Tumour 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 these platforms have different delivery approaches:directly intratumoural through the injection and intravenous,respectively.57Deep Pharma IntelligenceSources Oncorus TechnologyoHSVONCR-177 is a leading product of this platform,which is an oncolytic virus that should be administered directly into the tumour site;consequently,this induces immunogenic cancer cell death and drives lasting and systemic anti-tumour response.Oncolytic virus brings five 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 nonspecific immune response.Viral RNA is delivered in lipid nanoparticles.Leading programmes ONCR-021 and ONCR-788 are based on coxsackievirus A21(CVA21)and Seneca Valley Virus(SVV),respectively.Oncolytic Viruses Platform:Key Players 58Deep Pharma IntelligenceAdenovirus PlatformCAN-2409 is an engineered gene construct encoding the thymidine kinase gene that should be transported into infected tumour cells.Administered in the form of intratumoural injection.HSV PlatformCAN-3110 is engineered to express the gene responsible for viral replication only when it is activated by a tumour-specific Nestin promoter.This provides a better regulation of immune response and precise targeting.Multifactorial approach that 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 immunotherapy.They aim to reach a low toxicity level,which is well suited for the treatment of less aggressive or slower growing cancers.59Deep Pharma IntelligenceGenelux is an innovative biopharmaceutical company which develops oncolytic virotherapy and combines it with other cancer vaccine approaches.Their leading product,Olvi-Vec,is currently on the Phase II of clinical trials and is stated to be able to effectively fight multiple cancers(including both solid tumours and blood malignancies).Genelux owns a Choice Discovery Platform to develop an extensive library oncolytic viruses strains identified 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 outburst of primed cancer neoantigen-specific effector T-cell precursors.Oncolytic Viruses Platform:Key Players Olvi-Vec Immunotherapy Chemotherapy(platinum)refractory and/or resistant cancersGeneration Oncolytic VirusRegional(Advantages)Intravenous(Advantages)Local(Advantages)Ability to target advanced and metastatic diseasesAbility to target cancers without prolonged treatment burdenAbility to target and treat tumours of different sizesRobust immune activation profile60Deep Pharma IntelligenceOncolytic Viruses Platform:SWOT Analysis Weaknesses Usually causes undesirable immune response with extensive antibodies production,which neutralises the virus;Limited number of the antigens that can be targeted;Mostly needs to be administered through an injection.Opportunities Can be efficiently improved through combinational therapies;Can become the main mechanism of the tumour immunisation if it is not reachable for other therapies.Can reach cold tumours and turn them into hot tumours;Targets both tumour and its microenvironment;Creates a strong immune response.StrengthsThreats Severe side effects resulted by the viral activity regarding healthy cells;Gene-modified viruses injected into a human body might cause some ethical concerns.OTSWCancer Vaccines Delivery Systems DEEP PHARMA INTELLIGENCEEngineered nanoparticles for drug deliveryLiposomes and other lipid-based strategiesPoly(lactic acid)(PLA)and poly(lactic-co-glycolic acid)(PLGA)nanoparticlesExosomesInjectable mesoporous silica(MPS)nanoparticles The Need of Effective Delivery System62Deep Pharma IntelligenceOne of the main challenges in modern immunotherapy is targeting cold tumours,the subclass of solid tumours.Implementing the appropriate delivery system is the primary way to overcome this challenge.Many clinical trials of cancer vaccines 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 microenvironment,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 deeper 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 Nondegradable DC homing devices Sources Emerging biomaterial-based strategies for personalized therapeutic in situ cancer vaccinesParticulate-based Delivery Systems63Deep Pharma IntelligenceParticulate-based approaches have long been utilised to improve therapeutic delivery to particular tissue areas,while minimising 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 medicinal 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 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 released 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 humansMesoporous silica-based approaches aim to address the challenge in high variability in delivery efficacy dependent on cellular interactions by leveraging their well-established drug carrier properties and high versatility in conjunction with other materials.Silica is nontoxic material Large loading capacity New technology that requires more research before trials in humansScaffold-based Delivery Systems64Deep Pharma IntelligenceScaffold-based vaccines are structures intended to initiate anti-tumour 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 activation.In general,in situ cancer vaccines utilising 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 Nondegradable DC Homing Devices PLGA scaffold is a biocompatible synthetic linear copolymer characterised by the modified surface for intracellular interactions.Sources Emerging biomaterial-based strategies for personalized therapeutic in situ cancer vaccinesScaffold-based SystemsHydrogel-based scaffold 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 a system composed of nano-sized spheres or rods of silica in a predetermined nonspecific geometric arrangement for loading with drug.It can be improved by addition of functional groups and capping treatment.Nondegradable 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 from Merck AG that specialises 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 project 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 it can also be used for preventive vaccines.Companies Applying Advanced Cancer Vaccines Delivery Systems65Deep Pharma IntelligenceSources SilVacXCurrently,the platform is designed for neoepitope-based personalised anti-tumour vaccines and extremely powerful for HPV(human papillomavirus)induced cancers.SilVacxs technology provides stimulation of the innate immune system stimulation of the adaptive 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 BioTech company that owns a novel proprietary nanoparticle technology oligoDOM.This technology can be applied for many types 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 Systems66Deep Pharma 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 include 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 pharmaceutical 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 Vaccines Delivery Systems67Deep Pharma IntelligenceSources Midatech Pharma Technology proprietary 3D-printing technology that encapsulates medicines into bioresorbable polymer microspheres with precision characteristics:Micro-encapsulation PLGA polymer depot system;Advanced piezo printing technology;Several million microspheres produced per second.ultra-small gold nanoparticle(GNP)drug conjugates.The small size and multi-functional arrangement of molecules around a gold core underpin MidaCores ability to improve biodistribution and targeted drug delivery.solubilises potent molecules that have minimal solubility at biological pH,extending available routes of administration.Used for direct-to-tumour delivery.Q-SpheraMidaCoreMidaSolveAlnylam Pharmaceuticals is a biopharmaceutical company that develops therapy with an RNA interference(RNAi)approach.The companys therapeutic focus areas are genetic medicines,cardio-metabolic,infectious,central nervous system(CNS),and ocular diseases.For delivery of their therapy,Alnylam utilises two delivery platforms lipid nanoparticles(LPNs)and conjugates.Companies Applying Advanced Cancer Vaccines Delivery Systems68Deep Pharma IntelligenceSources Alnylam Pharmaceuticals Lipid Nanoparticles ConjugatesAlnylam has an approved iRNA therapy that utilises LNP-based delivery ONPATTRO(patisiran).LNPs are chemically synthesised multicomponent lipid formulations(100 nm in size)that encapsulate siRNAs and deliver the medicine to the target tissue.LNPs protect 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 to 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 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 acidic 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 tissues.Companies Applying Advanced Cancer Vaccines Delivery Systems69Deep 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 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 Platform that 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 and therapeutic molecules)to the surface or the lumen of exosomes.Companies Applying Advanced Cancer Vaccines Delivery Systems70Deep Pharma IntelligenceSources Exosomes have the potential to be a beneficial therapeutic method due to their capacity to selectively transport a wide range of therapeutic 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 safety.Exosomes are composed of natural human proteins and lipids,making them inherently nonimmunogenic.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 INTELLIGENCE72Deep Pharma IntelligenceSources PubMed DatabaseKey Takeaways The interest in cancer vaccination is continually growing,experiencing an outburst in 2021.This mature field of immunotherapy requires novel approaches and revitalisation solutions.The most actively developing platform right now is neoantigens platform,which we observe from analysing the lead products of big pharmaceutical companies.The most prominent research vectors in the field of cancer vaccines are aimed at enhancement of immunogenicity,while reducing a nontargeted damage of healthy cells,targeting multiple antigens and developing an universal vaccine for a broad spectrum of malignancies.The 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.Here,we included all available article types on PubMed.predicted number by the end of 2022421973Deep Pharma 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 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 age of the platform.The information is given according to the clinicaltrials.gov investigation by Cuzzubbo et al.Key TakeawaysThis graph uses the information from clinicaltrials.gov and data provided by Cuzzubo et al.(2021).You can see data that summarise open cancer vaccine trials by trial phase and vaccine type.74Deep Pharma IntelligenceWe have reviewed five cancer vaccine platforms that are actively developing their products to enter the market of immunotherapy.As a result,we conducted an assessment of more than 200 companies and R&D centres and detailed analysis of more than 40 of them.Besides,we analyzed investments into those companies and found more that 350 investors.Identified cancer vaccine platforms have distinguishable features and development timelines,as well as representative companies with the products pipelines.All the reviewed key player companies,in our opinion,possess strong R&D bases,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 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 by such growing cancer vaccine platform as antigenic essence,which is likely to combine a high specificity,efficiency,and time-and cost-effectiveness.General ConclusionsLatest AchievementsNotable Case StudiesOver 350 investors5 Cancer Vaccine PlatformsDetailed analysis of 40 companies200 companies and R&D centresOverview of Proprietary Analytics by Deep Pharma IntelligenceDEEP PHARMA INTELLIGENCE76Deep Pharma IntelligenceDeep Pharma Intelligence New Era in Pharma Analytics Deep Pharma Intelligence(DPI),an analytical subsidiary of Deep Knowledge Group,is a highly specialised think tank in the area of BioTech innovation profiling,market intelligence,and BioTech development advisory.The company is dedicated to producing powerful data mining and visualisation systems,interactive analytics tools,and industry reports,offering deep technical insights,market intelligence,and strategic guidance in the high growth and significant opportunity areas.DPI is Focusing on Three Key Activities:Conducting Market IntelligenceCreating Big Data Analytical DashboardsProducing Scientific ContentProducing regular open-access and proprietary reports on the emerging topics and trends in the pharmaceutical and healthcare industries.All reports are supported by our back-end analytics systems and tools that allow to receive fresh insights and updates about opportunities and risks.Building a comprehensive Big Data Analytical Dashboard(SaaS)as a one-stop-platform for all market and business intelligence operations our customers may need,including profiling thousands of companies,market signals and trends based on tens of millions of constantly updated data points.DPI provides a full-cycle development of articles,scientific journals,and books.We are ready to develop a detailed Requirement Specifications document,including layout of the journal,fully designed brand book,with example templates for each chapter.77Deep Pharma IntelligenceAI in Drug Discovery Analytical DashboardMarket Intelligence Focus AI in Drug Discovery Analytical Dashboard is a fundamental tool for strategic insights,opportunity evaluation,competitor profiling,and other purposes relevant to Pharma and BioTech decision-makers,life science investors,consulting companies,and regulatory agencies.600Companies120Clinical Trials1,100Investors290R&D CollaborationsAutomated SWOT AnalysisStock Price ForecastingInteractive Chart BuilderAutomized Competitive AnalysisFinancial Portfolio ConstructorMatching Tool for Investors170Parameters of Automated SWOT Analysis78Deep Pharma IntelligenceComprehensive Market IntelligenceDeep Pharma Intelligences proprietary services include custom consulting projects based on the specific customer needs,as well as a collection of preproduced ready-to-use proprietary reports,developed by our research team and covering general trends and specific action ideas and strategy insights related to the most promising business prospects(e.g.new technologies,BioTech start-ups),M&A prospects(e.g.pipeline development targets),and strategic growth ideas(trends profiling,industry overviews,etc.).Selected Open Access ReportsArtificial Intelligence for Drug Discovery Landscape Overview,Q3 2022 is an analytical report that aims to provide a comprehensive overview of the AI in drug discovery industry,clinical research,and other aspects of pharmaceutical R&D.Epigenetic Drugs Q2 2022 report aims to provide a comprehensive overview of the current state of the epigenetic drugs market and research.The aim of this report is to provide insights into the diversity of possible epigenetic targets,mechanisms of their action in treating cancer and other diseases.Landscape of Advanced Technology Companies in Pharmaceutical Industry Q4 2021 is an analytical report providing insights into the expansion of technology developers and vendors in the pharmaceutical space,as well as their increasing role in the pharmaceutical business.79Deep Pharma IntelligenceBusiness Consulting ServicesDeep Pharma Intelligence offers a comprehensive range of consulting services,including market and competitor research,technology scouting and due diligence,investment landscape profiling,and comprehensive analytics support for investment decision-making.Investment Landscape ProfilingIdentifying investment trends in the pharma,BioTech,medicine,healthcare,drug development technological space,investments risk profiling based on risk tolerance,risk capacity,and risk requirements.Market ResearchThorough market assessment within a specific industry in the field of pharma,BioTech,medicine,healthcare,drug development,AI,and others.Technology Scouting and Due DiligenceIdentifying,locating,and evaluating existing or developing technologies,products,services,and emerging trends.The service includes business,science and technology,intellectual property(IP)profiling,and potential assessment.Competitor ResearchCompetitive analysis of companies,technologies,technological sectors,etc.Competitive analysis includes SWOT analysis and competitive profiling.Deep 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 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 mentioned 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 opinions 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 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