About Dynavax Technologies

Dynavax Technologies Corporation operates as a commercial stage biopharmaceutical company. The company is developing and commercializing innovative vaccines in areas of significant unmet need, leveraging the company’s demonstrated expertise and capabilities in vaccines and its proven, proprietary vaccine adjuvant technology. The company is focused on its efforts to drive long-term shareholder value by maximizing utilization of the company’s HEPLISAV-B hepatitis B vaccine, expanding the company’s own portfolio of innovative vaccine candidates leveraging its proven adjuvant technology, and leveraging the company’s CpG 1018 adjuvant supply strategy through both commercial and research collaborations. HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted] The company’s first marketed product, HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted], is approved in the United States, the European Union and Great Britain for prevention of infection caused by all known subtypes of hepatitis B virus (‘HBV’) in adults aged 18 years and older. HEPLISAV-B is the only two-dose hepatitis B vaccine for adults approved in the United States, the European Union and Great Britain. In Phase 3 trials, HEPLISAV-B demonstrated faster and higher rates of protection with two doses in one month compared to other approved hepatitis B vaccines, which require three doses over six months, with similar safety profiles. The company received marketing authorization approval of HEPLISAV-B in February 2021 from the European Commission for prevention of infection caused by all known subtypes of HBV in adults aged 18 years and older. In May 2021, the company entered into a commercialization agreement with Bavarian Nordic for the marketing and distribution of HEPLISAV-B in Germany, and in May 2022, the company commenced commercial shipments of HEPLISAV-B in Germany. In March 2023, the company received marketing authorization in Great Britain for HEPLISAV-B for the active immunization against hepatitis B virus infection caused by all known subtypes of hepatitis B virus in adults aged 18 years and older. Pipeline Programs The company is advancing a pipeline of differentiated product candidates that leverage the company’s CpG 1018 adjuvant to develop improved vaccines in indications with unmet medical needs. These programs include vaccine candidates under development for shingles, Tdap and plague. Shingles vaccine program: Z-1018 is an investigational vaccine candidate being developed for the prevention of shingles in adults aged 50 and older. Tdap vaccine program: Tdap-1018 is an investigational vaccine candidate intended for active booster immunization against tetanus, diphtheria, and pertussis (‘Tdap’). Plague vaccine program: The company is developing a plague (rF1V) vaccine candidate adjuvanted with CpG 1018, in a Phase 2 clinical trial in collaboration with, and fully funded by, the U.S. Department of Defense (‘DoD’). Additionally, the company manufactures and has supplied in the past CpG 1018 adjuvant, the adjuvant used in HEPLISAV-B, through both commercial supply agreements and preclinical and clinical research collaborations with third-party organizations. Adjuvant Technology Overview: Toll-like Receptor Immune Modulation Platform Toll-like receptors (TLRs) are a family of transmembrane proteins that play a vital role in innate immunity and subsequent adaptive immunity. Signaling through these receptors is triggered by the binding of a variety of pathogen-associated molecules and is essential to generation of innate immunity. The innate immune response is the first line of defense against viruses, bacteria and other potential pathogens. Importantly, the innate response initiates and regulates the generation of an adaptive immune response composed of highly specific antibodies and T cells. Compounds used in vaccine products that stimulate enhanced immune responses are generally referred to as adjuvants. The company’s work in this area has been focused primarily on stimulation of a subset of TLRs that recognize bacterial and viral nucleic acids. This work resulted in the identification of proprietary unmethylated synthetic oligonucleotides (short segments of deoxyribonucleic acid (DNA)), that mimic the activity of microbial DNA, and selectively activate one of these important receptors, TLR9. These TLR9 agonists are called CpG oligonucleotides – or ‘CpGs’ for short – referring to the presence of specific nucleotide sequences containing the CG base pair. The company’s vaccine research to date has focused on the use of TLR9 agonists as novel vaccine adjuvants. B-Class TLR9 agonists, such as the company’s CpG 1018 adjuvant, stimulate release of cytokines necessary for T cell activation establishing long-term immunity. TLR9 stimulation particularly helps generate Th1 immune responses that are important to control pathogens such as viruses and bacteria. As a result, TLR9 adjuvanted vaccines induce a specific Th1 immune response and more durable levels of protective antibodies relative to non-adjuvanted vaccines. The company’s CpG 1018 adjuvant has an established tolerability profile demonstrated in a wide range of clinical trials and real-world, commercial use, and has consistently demonstrated its ability to enhance the immune response without excessive reactogenicity as shown in multiple clinical trials in the company’s HEPLISAV-B and COVID-19 vaccine collaboration programs. Strategy The company’s strategy is focused on its core priorities: drive growth in the company’s HEPLISAV-B commercial vaccine, advance a differentiated vaccine pipeline, and identify strategic opportunities to accelerate growth. Key elements of the company’s strategy include: Increase the company’s HEPLISAV-B vaccine market share to become the market leader in the future; Maximize total addressable HEPLISAV-B vaccine market based on the ACIP Universal Recommendation; Leverage HEPLISAV-B vaccine as a foundational commercial asset to support company growth and pipeline development; Deliver on the company’s innovative and diversified pipeline leveraging CpG 1018 adjuvant with proven antigens; Build an adult vaccine portfolio of best-in-class products; Advance innovative pre-clinical and discovery efforts leveraging collaborations; and Pursue external opportunities to further leverage the company’s U.S. commercial vaccine capabilities, prioritizing first or best-in-class assets. HEPLISAV-B [Hepatitis B Vaccine, (Recombinant), Adjuvanted] The company’s first commercial product, HEPLISAV-B [Hepatitis B Vaccine, (Recombinant), Adjuvanted], is approved by the FDA, the European Commission and the UK Medicines and Healthcare products Regulatory Agency for prevention of infection caused by all known subtypes of HBV in adults aged 18 years and older. HEPLISAV-B combines CpG 1018 adjuvant, the company’s proprietary TLR9 agonist adjuvant, and recombinant hepatitis B surface antigen (‘rHBsAg’ or ‘HBsAg’) that is manufactured by Dynavax GmbH, the company’s wholly owned subsidiary, in Düsseldorf, Germany. HEPLISAV-B and each of the vaccines it directly competes against use rHBsAg to elicit an immune response to the virus. Protection Against Hepatitis B by HEPLISAV-B The approval of HEPLISAV-B by the FDA was based on data from three Phase 3 non-inferiority trials involving nearly 10,000 adult participants who received HEPLISAV-B. These pivotal studies compared HEPLISAV-B administered in two doses over one month to Engerix-B administered in three doses over a six-month schedule. Results from HBV-23, the largest Phase 3 trial, which included 6,665 participants, showed that HEPLISAV-B demonstrated a statistically significantly higher rate of protection of 95% compared with 81% for Engerix-B. Across the three clinical trials, the most common local reaction was injection site pain (23% to 39%). The most common systemic reactions were fatigue (11% to 17%) and headache (8% to 17%). The company has worldwide commercial rights to HEPLISAV-B. In addition to HEPLISAV-B, there are four other vaccines approved for the prevention of hepatitis B in the U.S.: Engerix-B and Twinrix from GlaxoSmithKline plc (GSK), Recombivax-HB from Merck & Co. (‘Merck’) and PreHevbrio from VBI Vaccines Inc. HEPLISAV-B is approved in the U.S., the EU and Great Britain for the prevention of hepatitis B in adults. The company is also considering additional territories where it would be commercially feasible to market HEPLISAV-B. The largest segments of the market are concentrated in independent hospitals and clinics, integrated delivery networks, dialysis centers, public health clinics and prisons, the Departments of Defense and Veterans Affairs and retail pharmacies. The company’s promotional activity is focused on the largest accounts in each segment. The company’s field sales force of approximately 117 people are targeting customers that have the highest impact on adult hepatitis B vaccine utilization in the U.S. The company deploys its sales force to the physician or pharmacist level, as well as at the procurement level within respective healthcare segments where vaccines are utilized. The company continues to explore ways to enhance the clinical profile of HEPLISAV-B. The company completed an open-label, single-arm study of a 4-dose regimen of HEPLISAV-B in adults with end-stage renal disease who are initiating or undergoing hemodialysis. Final immunogenicity results included a seroprotection rate of 89.3% with high levels of anti-HBs antibodies. Safety data showed HEPLISAV-B was well tolerated and no safety concerns were observed. The safety and effectiveness of HEPLISAV-B in adults on hemodialysis have not yet been established. This study alone, regardless of results, may not be sufficient to support a label change to include dialysis patients. If the company does receive approval of this dosing schedule, the company expects to add dialysis centers to the company’s personal promotion efforts. An sBLA for HEPLISAV-B vaccination of adults on hemodialysis is currently under priority review by the FDA with a Prescription Drug User Fee Act action date planned for May 13, 2024. CpG 1018 Vaccine Adjuvant The favorable immunogenicity and safety results achieved with HEPLISAV-B utilizing the company’s CpG 1018 adjuvant support its efforts to develop it as a broadly useful vaccine adjuvant platform. CpG 1018 adjuvant has an established profile for the potential development of safe and effective vaccines. It has a well-defined mechanism of action, targeting select immune system cells, with well-characterized effects on the immune response that mimic the immune response to naturally occurring TLR9 agonists in pathogens. This results in potent adjuvant activity for antibody responses. In HEPLISAV-B, the company’s CpG 1018 adjuvant is believed to drive faster and consistently higher rates of seroprotection than Engerix-B, even in the elderly and populations known to be less responsive to other vaccines. CpG 1018 adjuvant differentially elicits a preferred T Helper 1 (Th1) cell polarized response and drives protective antibody production. CpG 1018 adjuvant has a large safety database that indicates a favorable reactogenicity profile with lower reactogenicity compared to other adjuvants. The company has established several clinical and preclinical collaborations with vaccine developers to evaluate CpG 1018 adjuvanted vaccine product candidates against influenza, other infectious diseases, and particularly COVID-19 across a variety of vaccine platforms. Data from studies in non-human primates demonstrate the company’s CpG 1018 adjuvant can elicit a robust immune response to COVID-19 and protect animals from disease in challenge studies. Results from Phase 2 and 3 human clinical studies demonstrated vaccines utilizing CpG 1018 adjuvant had a favorable safety and tolerability profile, induced strong immune responses, including neutralizing antibodies and Th1-biased cell-mediated immunity, and resulted in a high efficacy against COVID-19 disease. Vaccine Research and Development Pipeline The company is building a pipeline of investigational vaccine product candidates, leveraging the company’s proven, proprietary vaccine adjuvant technology. A summary of the company’s pipeline programs follows: Shingles Vaccine Program Shingles is an extremely painful consequence of the reactivation of a latent varicella-zoster virus (‘VZV’) infection, with attacks leading to potential complications, including chronic pain. The company’s CpG 1018 adjuvant has demonstrated its ability to enhance the immune response without excessive reactogenicity in both HEPLISAV-B and multiple COVID-19 clinical trials. Importantly, CpG 1018 adjuvant has shown the ability to generate high levels of CD4+-cells, which have been demonstrated to be key cell types in controlling latent VZV infection to avoid reactivation leading to shingles, with potentially lower reactogenicity compared to the current standard of care. In January 2022, the company initiated a Phase 1 clinical trial of its shingles vaccine candidate, utilizing the company’s CpG 1018 adjuvant. The global Phase 1 study was designed to evaluate safety, tolerability and immunogenicity of the vaccine candidate which is consisted of glycoprotein E (gE) plus CpG 1018 adjuvant. In January 2023, the company announced the completion of a randomized Phase 1 clinical trial of the company’s shingles vaccine program evaluating the safety, tolerability, and immunogenicity in adults. At four weeks following the 2-dose regimen, the investigational shingles vaccine Z-1018 demonstrated high antibody and CD4 positive T-cell vaccine response rates in all arms, which were similar to the licensed comparator. Robust increases in CD4 positive T-cells were observed in all Z-1018 arms, although lower than the comparator. Total frequency of solicited systemic adverse events and local post-injection reactions and moderate and severe reactions were similar across the Z-1018 arms and lower than the comparator. In June 2023, the company presented results from a Phase 1 randomized, active-controlled, dose escalation, multicenter trial to evaluate the safety, tolerability, and immunogenicity of Z-1018, at the National Foundation for Infectious Diseases’ 2023 Annual Conference on Vaccinology Research. These results demonstrate the opportunity to develop a shingles vaccine with improved vaccine tolerability and comparable efficacy to Shingrix and support the continued development of the company’s shingles vaccine candidate. The company received Type B meeting feedback from the FDA on the Z-1018 clinical development plan and submitted an IND to the FDA to support the initiation of a Phase 1/2 trial of Z-1018, upon IND clearance, in the first half of 2024. Tdap Vaccine Program The company’s Tdap booster vaccine candidate adjuvanted with CpG 1018 is anticipated to improve the durability of protection against pertussis by redirecting T cell responses and enhancing protective antibody responses in a booster vaccine. In June 2017, the company entered into an agreement with Serum Institute of India Pvt. Ltd. (‘SIIPL’) to collaborate on development and commercialization of certain potential vaccines including Tdap booster adjuvated with CpG 1018. Under the collaboration, the company has exclusive worldwide rights to commercialize the vaccine, except that SIIPL has exclusive rights to distribute in India and to fulfill WHO/United Nations Children's Fund (UNICEF) tender contracts. Each party is responsible for clinical development cost in their respective territories. In October 2022, the company presented adult and adolescent safety data from the Phase 1 clinical trial of Tdap-1018, which was well tolerated with no safety concerns observed. Additionally, immunogenicity levels in adults met the company’s expectations and support the company’s plan to continue advancement of this clinical program. In December 2023, the company completed a pertussis challenge study in nonhuman primates demonstrating protection from disease upon challenge and robust Type 1 T helper (Th1) cell responses in nonhuman primates vaccinated with Tdap-1018. The company recently received Type B meeting feedback from the FDA on the Tdap-1018 clinical development plan. The company plans to submit an IND to the FDA to support the initiation of a Phase 2 human challenge study of Tdap-1018 in the second half of 2024, upon completion of the independent study being conducted by the Canadian Center for Vaccinology to establish the human challenge dose, which the company plans to utilize in its Phase 2 study. The U.S. Department of Defense (Plague Vaccine) Phase 2 Study In September 2021, the company entered into an agreement with the U.S. Department of Defense (‘DoD’) for the development of a recombinant plague vaccine adjuvanted with CpG 1018 for approximately $22.0 million over two and a half years. Under the agreement, the company agreed to conduct a Phase 2 clinical trial combining the company’s CpG 1018 adjuvant with the DoD's rF1V vaccine designed to show that two doses of CpG 1018 adjuvanted vaccine administrated within a period of one month is similar to three doses of the aluminum-adjuvanted vaccine administered over a period of six months. In August 2022, the company commenced the Phase 2 clinical trial with the first participant dosed, evaluating the immunogenicity, safety and tolerability of the DoD’s rF1V vaccine combined with the company’s CpG 1018 adjuvant, in adults 18 to 55 years of age. In January 2023, Part 1 of the Phase 2 clinical trial evaluating the immunogenicity, safety, and tolerability in adults of a plague (rF1V) vaccine candidate adjuvanted with CpG 1018 was successfully completed. Both CpG 1018 adjuvanted arms met the Part 1 primary endpoint and demonstrated a greater than two-fold increase in antibodies over the alum adjuvanted control arm after two doses. In 2023, the company completed enrollment and dosing in Part 2 of the Phase 2 clinical trial evaluating immunogenicity, safety, and tolerability. Preliminary results are expected in 2024. In July 2023, the company executed a contract modification with the DoD to support advancement of the plague vaccine candidate into a nonhuman primate challenge study, which was initiated in August 2023. CpG 1018 Adjuvant Supply Partnerships for COVID-19 Vaccine Development To support the fight against COVID-19, the company collaborated with five other organizations on their development of COVID-19 vaccines, by supplying them with CpG 1018 adjuvant under commercial supply agreements supported by two contract manufacturing organizations, with whom the company developed and implemented plans to help scale-up activities to support pandemic-level production of the company’s CpG 1018 adjuvant as necessary to support these and any future collaborations. As of December 31, 2023, all five of the company’s collaborators have received emergency use authorization and/or full approval for their COVID-19 vaccines, and the company’s delivery obligations under the company’s related supply agreements have been fully satisfied. The company continues to work to identify other programs where CpG 1018 adjuvant can be utilized to enhance the immune response to a coronavirus vaccine or other vaccines. Intellectual Property As of December 31, 2023, the company’s intellectual property portfolio included over 25 issued U.S. patents, over 65 granted foreign patents and over 115 additional Dynavax-solely owned or co-owned pending U.S. non-provisional and foreign patent applications claiming compositions containing TLR agonists or antagonists, methods of use, and/or methods of manufacture thereof. Specifically, the company’s portfolio includes: (i) three issued U.S. patents related to certain uses of HEPLISAV-B that expire in 2032; (ii) 23 pending U.S. and foreign patent applications related to an investigational tetanus, diphtheria, pertussis (Tdap) booster vaccine, which are co-owned with SIIPL; (iii) 17 pending U.S. and foreign patent applications related to an investigational shingles vaccine; (iv) over 55 pending U.S. non-provisional and foreign patent applications related to COVID-19 vaccines, which include patent families that are either solely-owned or co-owned with Valneva Austria GmbH, Medigen Vaccine Biologics Corporation, or Colorado State University Research Foundation; and (v) one pending U.S. patent application related to an investigational plague vaccine, which is co-owned with The Government of the United States, as Represented by the Secretary of the Army. Lastly, some of the patents and patent applications in the company’s portfolio relate to the company’s discontinued immuno-oncology programs. The company’s patent estate, based on patents existing now and expected by the company to issue based on pending applications, is projected to expire on dates ranging from 2024 to 2043. Competition HEPLISAV-B, a two-dose in one month adult hepatitis B vaccine, competes directly with three-dose over six months marketed vaccines Engerix-B from GSK, as well as Recombivax-HB marketed by Merck. In addition, HEPLISAV-B competes against Twinrix, a bivalent vaccine marketed by GSK for protection against hepatitis B and hepatitis A. Competition for the company’s adjuvant supply supporting COVID-19 and the company’s development pipeline including shingles, Tdap, plague and other potential pipeline indications The company is also in competition with companies developing vaccines, and vaccine adjuvants, generally including among others, GSK, Pfizer, Inc., Sanofi S.A., Merck, Bavarian Nordic A/S, Emergent BioSolutions, Inc., Novavax, Inc., Medicago Inc., Valneva, AstraZeneca plc, Moderna, Inc., Johnson & Johnson, and VBI. Government Regulation Manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMPs, which impose certain procedural and documentation requirements upon the company and its third-party manufacturers. The company is subject to diverse laws and regulations relating to data privacy and security, including HIPAA in the United States, the European Union's General Data Protection Regulation (‘EU GDPR’) in the European Economic Area (‘EEA’), and the United Kingdom's General Data Protection Regulation (‘UK GDPR’). For example, the EU GDPR which went into effect in May 2018 introduced strict requirements regarding the processing of personal data, which apply to non-EU entities that process, or control the processing of, the personal information of EU subjects, including clinical trial data. The EU GDPR implements more stringent operational requirements than its predecessor legislation. The company is required to discount such products to authorized users of the Federal Supply Schedule of the General Services Administration, under which additional laws and requirements apply. These programs require submission of pricing data and calculation of discounts pursuant to complex statutory formulas, as well as the entry into government procurement contracts governed by the Federal Acquisition Regulations, and the guidance governing such calculations is not always clear. In the United States and other potentially significant foreign markets for the company’s products, federal and state authorities, as well as third-party payors are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative products and therapies, which has resulted in lower average net selling prices. Manufacturing The company relies on its facility in Düsseldorf, Germany and third parties to perform the multiple processes involved in manufacturing HBsAg for use in HEPLISAV-B, the combination of the oligonucleotide and the antigens, and formulation, fill and finish. As is common in the company’s industry, in light of FDA inspection and licensing requirements for manufacturing sites, the company has relied on a limited number of suppliers to produce oligonucleotides for clinical trials and conduct fill and finish operations. Historically, the company relied on a single supplier to produce the company’s CpG 1018 adjuvant for HEPLISAV-B and for its collaborators. The company also has a second qualified supplier to produce CpG 1018 adjuvant for its collaboration partners, to the extent needed. Switching suppliers, or bringing on additional suppliers, could be complicated and time consuming, but the company generally seeks to maintain inventory to help bridge any unexpected gap in supply. In order to help the company successfully manufacture and commercialize HEPLISAV-B, the company has secured long-term supply agreements with the key third-party suppliers and vendors for commercial supply of its component products and finished goods. The company manufactures the HBsAg for HEPLISAV-B at its Dynavax GmbH facility. History The company was founded in 1996. It was incorporated in California in 1996. The company was formerly known as Double Helix Corporation and changed its name to Dynavax Technologies Corporation in September 1996. The company was reincorporated in Delaware in 2000.