fighting a war on two fronts: immunitybio targets cancer ......fighting a war on two fronts:...

A D V E R T I S E M E N T F E A T U R E

A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T

ImmunityBio, LLCwww.immunitybio.com

Fighting a war on two fronts: ImmunityBiotargets cancer and COVID-19ImmunityBio is applying its second-generation human adenovirus 5 vaccine platform, used as part ofits orchestrated multi-modal treatment approach to advanced cancer, to prevent COVID-19.

The SARS-CoV-2 pandemic crisis and COVID-19disease has brought into sharp focus a critical obser-vation about viral diseases and cancer: both displayhigh infectivity—metastasis in cancer—and an abil-ity to subvert the host immune response to create amicroenvironment favorable to their own survival.

ImmunityBio, Inc. is a privately held immuno-therapy company dedicated to effectively activatingthe immune system to seek out, attack and destroycancer cells or viral particles and has one of thebroadest portfolios of biological molecules spanningalbumin-linked chemotherapeutics, peptides, fusionproteins, cytokines, monoclonal antibodies and bothadenovirus and yeast vaccine therapies. ImmunityBio,a part of the NANT ecosystem of companies, hasadvanced a comprehensive immunological approachto cancer that centers on the use of vaccines and isnow extending this expertise to COVID-19.

ImmunityBio’s vaccine approach is distinguishedby its use of a human second-generation adeno-virus 5 (hAd5) [E1−, E2b−, E3−] platform. Currentfirst-generation Ad5 platforms have a number ofdisadvantages: they are ineffective if the individualreceiving the vaccine has pre-existing immunityto Ad5; if they do not, they can readily developimmunity to the vaccine vector (Ad), whichnegates their utility for future vaccination. Non-human adenoviruses have been used as vectorsto avoid pre-existing immunity, but may still elicita vector-directed immune response, which againmakes them ineffective for repeated use.

The hAd5 platform overcomes these limitationsby deletion of the genes encoding the E1, E2b andE3 Ad5 proteins, which enables the generation ofvaccines that are effective even in the presence ofpre-existing Ad5 immunity. The deletions have thefurther benefit of leaving additional ‘cargo space’which, in the case of the ImmunityBio hAd5-S-Fusion+ N-ETSD vaccine, can be used to allow expressionof two antigens to increase vaccine efficacy.

Applications in cancerImmunityBio has already used the hAd5 [E1−, E2b−,E3−] platform to produce anti-cancer vaccines tar-geted at a number of antigens, including carcinoem-bryonic antigen, brachyury, HER2 and MUC1. Thesevaccines are currently undergoing clinical evalua-tion by NantKwest, a clinical-stage immunotherapycompany harnessing the power of innate immu-nity to fight cancer and viral infections that is alsopart of the NANT family. In phase 1 and 2 studies,ImmunityBio’s vaccines have demonstrated safetyin immunocompromised patients as components oforchestrated combination therapies for advanced

cancer that include biologics such as high-affinitynatural killer cells, chemotherapy including nanopar-ticle albumin-bound paclitaxel and/or aldoxorubicin,checkpoint inhibitors such as anti-PD-1 and PD-L1and N-803, an immune-activating interleukin-15superagonist also developed by ImmunityBio.

The therapeutic promise of this vaccine approachis now being leveraged by ImmunityBio to advance a‘personalized’ approach to cancer therapy that usesneoantigens unique to the individual patient’s tumoras the basis for the vaccine. In recent pre-clinicalstudies performed by ImmunityBio and partnersat the National Cancer Institute, administration ofhAd5 neoantigens resulted in total tumor remissionin models bearing tumors expressing the neoantigen.

ImmunityBio has extensive experience with vac-cines against infectious diseases and has publishedseveral peer-reviewed articles of studies showingthat the second-generation hAd5 platform canachieve both humoral and cell-mediated immu-nity against H1N1 influenza, HIV, SIV, Lassa fever,Chikungunya and Zika virus. With the outbreakof the COVID-19 pandemic, ImmunityBio rapidlydirected its energy to creating a vaccine againstthis novel coronavirus and has now generated twohAd5–SARS-CoV-2 vaccine constructs.

Targeting COVID-19ImmunityBio’s first vaccine construct, hAd5-S-Fusion, comprises the spike (S) viral surface proteinthat the virus uses to gain entry to host cells viathe membrane-spanning angiotensin converting

enzyme 2 (ACE2) with a fusion linker. S is highlyantigenic, and will likely result in an effective immuneresponse. The second construct, hAd5-S-Fusion +N-ETSD, contains both S and the viral nucleocapsid(N) protein, which is also highly conserved and anti-genic (Fig. 1). ImmunityBio has added a proprietarysignal sequence to the N protein that directs it to theappropriate subcellular compartment so that it elicitsa vigorous immune response. These vaccines areexpected to induce both humoral antibody-based andcell-mediated including innate antiviral responsesthat are both safe and durable. ImmunityBio hasmanufactured finished dosage forms of both vac-cines at small scale in its current good manufactur-ing practice (cGMP) facilities, and has submitted aninvestigational new drug (IND) application to theUS Food and Drug Administration to test them in aphase 1 trial anticipated to begin in June 2020.

ImmunityBio is seeking partnerships with clini-cal investigators, clinical trial sites and investors toaccelerate development of the hAd5–SARS-CoV-2vaccines and to build large-scale cGMP facili-ties to manufacture potentially billions of doses.ImmunityBio is also open to collaborations with otherpharma companies around its therapeutic molecules.

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Fig. 1 | ImmunityBio’s hAd5-S-Fusion + N-ETSD vaccine. This is comprised of both the viral spike (S)protein and the nucleocapsid (N) protein with an enhanced T cell stimulation domain (ETSD).

Phillip Yang, VP Strategic InitiativesImmunityBio, LLCEl Segundo, California, USAEmail: info@immunitybio.comCO

NTA

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