Tetanus

With nonprofit MassBiologics discontinuing production of tetanus vaccines, the Centers for Disease Control and Prevention anticipates a shortage of the shots in the U.S. later this year. Sanofi becomes the lone supplier of tetanus vaccines for the U.S. It’s time to add another vaccine to the shortage list in the U.S. as the Centers for Disease Control and Prevention (CDC) has urged healthcare providers to conserve their supply of tetanus shots. The warning from the national public health agency comes after one of the two providers of tetanus shots in the U.S., nonprofit MassBiologics, discontinued production of its tetanus and diphtheria (Td) vaccine. MassBiologics’ exclusive distributor, Grifols USA, told the CDC that supply of the product, which is called TdVax, will last until June of this year. Meanwhile, the other manufacturer of tetanus shots for the U.S., Sanofi, “is taking steps to augment their available supply,” the CDC said. Sanofi’s product is Tenivac, which also defends against tetanus and diphtheria. The CDC has installed temporary controls on the “public and private sectors” on ordering the vaccines, it said, “to help manage the gap in supply.” Another option, without any supply issues, are combination vaccines for tetanus, diphtheria and acellular pertussis (Tdap). The CDC has asked providers to transition to use of Tdap vaccines “whenever possible.” Tdap vaccines available in the U.S. are Sanofi’s Adacel and GSK’s Boostrix. The shots are more expensive than Td vaccines but have increased in popularity, while sales of Td shots have declined. Td vaccines should only be provided to those who can’t receive pertussis-containing shots, the agency added. The shots present a small risk of encephalopathy (brain damage). Pertussis is more commonly known as whooping cough. Tetanus is a virus caused by bacteria Clostridium, which is often found in soil. The bacteria can cause muscle contractions, especially in the neck and mouth, also referred to a “lockjaw.” In recent months, the CDC also has dealt with a shortage of a new immunization to combat respiratory syncytial virus (RSV). Called Beyfortus, the antibody from partners Sanofi and AstraZeneca is the lone RSV immunization in the U.S. for infants.

HEPLISAV-B® 2023 net product revenue grew 69% year-over-year to $213 million Achieved market leader status in key segments retail pharmacy and IDNs in 2023 2024 HEPLISAV-B net product revenue expected to be $265 - $280 million Cash position increased to $742 million at year end and expect to be cash flow positive for full year 2024 Conference call today at 4:30 p.m. ET/1:30 p.m. PT EMERYVILLE, Calif., Feb. 22, 2024 /PRNewswire/ -- Dynavax Technologies Corporation (Nasdaq: DVAX), a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines, today reported financial results for the fourth quarter and full year ended December 31, 2023. "2023 was characterized by record revenue growth for HEPLISAV-B, and the achievement of becoming the market share leader in the two largest growth segments, demonstrating important progress toward our goal of establishing HEPLISAV-B as the leading vaccine in the U.S. adult hepatitis B vaccine market," said Ryan Spencer, Chief Executive Officer of Dynavax. "We expect 2024 to be an important year in building a vaccine portfolio of best-in-class products, including further growing the HEPLISAV-B brand as well as advancing our pipeline programs into clinical trial initiations and data readouts. Importantly, our strong financial position provides us with the optionality to continue to build value across our business, including through investing to drive the HEPLISAV-B market opportunity, advancing and expanding our R&D efforts, and pursuing strategic opportunities to accelerate our growth." BUSINESS UPDATES HEPLISAV-B® [Hepatitis B Vaccine (Recombinant), Adjuvanted] HEPLISAV-B vaccine is the first and only adult hepatitis B vaccine approved in the U.S., the European Union and Great Britain that enables series completion with only two doses in one month. Hepatitis B vaccination is universally recommended for adults aged 19-59 in the U.S. HEPLISAV-B vaccine net product revenue for the fourth quarter and full year 2023 were approximately $51.1 million and $213.3 million, respectively, representing year-over-year growth of approximately 46% and 69% compared to the fourth quarter and full year 2022. HEPLISAV-B total market share in the U.S. increased to approximately 42% at the end of 2023, compared to approximately 35% at the end of 2022. HEPLISAV-B market share in the retail pharmacy segment increased to approximately 58% at the end of 2023, compared to approximately 42% at the end of 2022. HEPLISAV-B market share in the Integrated Delivery Networks (IDNs) and Large Clinics segment increased to approximately 56% at the end of 2023, compared to approximately 47% at the end of 2022. A supplemental Biologic License Application (sBLA) for HEPLISAV-B vaccination of adults on hemodialysis is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) action date planned for May 13, 2024. Driven by the Centers for Disease Control and Prevention's Advisory Committee of Immunization Practices (ACIP) universal recommendation for adult hepatitis B vaccination, the hepatitis B vaccine market continues to expand in the U.S. and Dynavax believes the U.S. market has the potential to grow to approximately $800 million by 2027, with HEPLISAV-B well-positioned to achieve a majority market share. Clinical Pipeline Dynavax is advancing a pipeline of differentiated product candidates that leverage its CpG 1018® adjuvant, which has demonstrated its ability to enhance the immune response with a favorable tolerability profile in a wide range of clinical trials and real-world commercial use. Shingles vaccine program: Z-1018 is an investigational vaccine candidate being developed for the prevention of shingles in adults aged 50 and older. Dynavax recently submitted an Investigational New Drug Application (IND) to the U.S. FDA to support initiation of a Phase 1/2 trial of Z-1018 in the first half of 2024. Tdap vaccine program: Tdap-1018 is an investigational vaccine candidate intended for active booster immunization against tetanus, diphtheria, and pertussis (Tdap). Dynavax plans to submit an IND to the U.S. 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 conducted by the Canadian Center for Vaccinology to establish the human challenge dose. Plague vaccine program: Dynavax is developing a plague (rF1V) vaccine candidate adjuvanted with CpG 1018® currently in a Phase 2 clinical trial in collaboration with, and fully funded by, the U.S. Department of Defense. Dynavax anticipates top line data for the randomized, active-controlled Phase 2 clinical trial evaluating immunogenicity, safety, and tolerability of the plague vaccine candidate in 2024. FOURTH QUARTER AND FULL YEAR 2023 FINANCIAL HIGHLIGHTS Total Revenues and Net Product Revenue. HEPLISAV-B vaccine net product revenue was $51.1 million for the fourth quarter of 2023, compared to $34.9 million for the fourth quarter of 2022, and $213.3 million for the full year 2023, compared to $125.9 million for the full year 2022. Other revenue was $4.5 million for the fourth quarter of 2023, compared to $2.3 million for the fourth quarter of 2022, and $19.0 million for the full year 2023, compared to $9.0 million for the full year 2022. Other revenue primarily includes revenue from the plague vaccine agreement with the U.S. Department of Defense. The increase was primarily driven by the advancement into a nonhuman primate challenge study. No CpG 1018 adjuvant product revenue was recorded in the fourth quarter and full year 2023, compared to $147.2 million and $587.7 million in the same periods of 2022, respectively, due to completion of all obligations and product delivery under the Company's CpG 1018 adjuvant COVID-19 collaboration agreements as of the end of 2022. Total revenues for the fourth quarter of 2023 were $55.6 million, compared to $184.5 million for the fourth quarter of 2022, and $232.3 million for the full year 2023, compared to $722.7 million for the full year 2022. Cost of Sales - Product. Cost of sales - product for HEPLISAV-B the fourth quarter of 2023 decreased to $8.7 million, compared to $12.4 million for the fourth quarter of 2022, and $50.2 million for the full year 2023, compared to $40.1 million for the full year 2022. Research and Development Expenses (R&D). R&D expenses for the fourth quarter of 2023 increased to $14.1 million, compared to $12.9 million for the fourth quarter of 2022, and $54.9 million for the full year 2023, compared to $46.6 million for the full year 2022. The increase was primarily driven by continued investments in advancing our clinical and preclinical development programs and collaborations. Selling, General, and Administrative Expenses (SG&A). SG&A expenses for the fourth quarter of 2023 increased to $41.3 million, compared to $31.0 million for the fourth quarter of 2022, and $152.9 million for the full year 2023, compared to $131.4 million for the full year 2022. The increase was primarily driven by higher compensation and related personnel costs and an overall increase in targeted commercial and marketing efforts designed to increase HEPLISAV-B market share and maximize the opportunities presented by the ACIP's universal recommendation. Net Income. GAAP net income was $0.2 million, or less than $0.01 per share (basic and diluted) in the fourth quarter of 2023, compared to GAAP net income of $67.7 million, or $0.53 per share (basic) and $0.45 per share (diluted) in the fourth quarter of 2022. GAAP net loss was $6.4 million, or $0.05 per share (basic and diluted) for the full year 2023, compared to GAAP net income of $293.2 million, or $2.32 per share (basic) and $1.97 per share (diluted) for the full year 2022. Cash and Marketable Securities. Cash, cash equivalents and marketable securities were $742.3 million as of December 31, 2023. 2024 FINANCIAL GUIDANCE Dynavax is providing the following full year 2024 financial guidance, based on the Company's current operating plan: HEPLISAV-B net product revenue between approximately $265 - $280 million, including approximately $3 million in ex-U.S. sales through commercialization agreement with Bavarian Nordic in Germany HEPLISAV-B gross margin of approximately 80% for full year 2024 Research and development expenses between approximately $60 - $75 million Selling, general and administrative expenses between approximately $160 - $180 million Expect to be cash flow positive for full year ended December 31, 2024 Conference Call and Webcast Information Dynavax will host a conference call and live audio webcast on Thursday, February 22, 2024, at 4:30 p.m. ET/1:30 p.m. PT. The live audio webcast may be accessed through the "Events & Presentations" page on the "Investors" section of the Company's website at . A replay of the webcast will be available for 30 days following the live event. To dial into the call, participants will need to register for the call using the caller registration link. It is recommended that participants dial into the conference call or log into the webcast approximately 10 minutes prior to the call. Important U.S. Product Information HEPLISAV-B is indicated for the prevention of infection caused by all known subtypes of hepatitis B virus in adults aged 18 years and older. For full U.S. Prescribing Information for HEPLISAV-B, click here. Important U.S. Safety Information (ISI) Do not administer HEPLISAV-B to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B. Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B. Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration. The most common patient-reported adverse reactions reported within 7 days of vaccination were injection site pain (23% to 39%), fatigue (11% to 17%), and headache (8% to 17%). About Dynavax Dynavax is a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines to help protect the world against infectious diseases. The Company has two commercial products, HEPLISAV-B® vaccine [Hepatitis B Vaccine (Recombinant), Adjuvanted], which is approved in the U.S., the European Union and Great Britain for the prevention of infection caused by all known subtypes of hepatitis B virus in adults 18 years of age and older, and CpG 1018® adjuvant, currently used in HEPLISAV-B and multiple adjuvanted COVID-19 vaccines. Dynavax is advancing CpG 1018 adjuvant as a premier vaccine adjuvant with adjuvanted vaccine clinical programs for shingles and Tdap, and through global collaborations, currently focused on adjuvanted vaccines for COVID-19, plague, seasonal influenza and universal influenza. For more information about our marketed products and development pipeline, visit . Forward-Looking Statements This press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to a number of risks and uncertainties. All statements that are not historical facts are forward-looking statements. Forward-looking statements can generally be identified by the use of words such as "anticipate," "believe," "continue," "could," "estimate," "expect," "forecast," "intend," "will," "may," "plan," "project," "potential," "seek," "should," "think," "toward," "will," "would" and similar expressions, or the negatives thereof, or they may use future dates. Forward-looking statements made in this document include statements regarding our expected financial results and market share as of and for the year and quarter ended December 31, 2024, expectations regarding future growth and market share, and the timing of IND filings, initiation and completion of clinical studies, the publication of results, and interaction with regulators. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in our business, including, the risk that actual demand for our products may differ from our expectations, risks relating to our ability to commercialize and supply HEPLISAV-B, risks related to the timing of completion and results of current clinical studies, risks related to the development and pre-clinical and clinical testing of vaccines containing CpG 1018 adjuvant, as well as other risks detailed in the "Risk Factors" section of our Annual Report on Form 10-K for the year ended December 31, 2023 and periodic filings made thereafter, as well as discussions of potential risks, uncertainties and other important factors in our other filings with the U.S. Securities and Exchange Commission. These forward-looking statements are made as of the date hereof, are qualified in their entirety by this cautionary statement and we undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. Information on Dynavax's website at is not incorporated by reference in our current periodic reports with the SEC. For Investors/Media: Paul Cox [email protected] 510-665-0499 Nicole Arndt [email protected] 510-665-7264 SOURCE Dynavax Technologies

After stealing the show at December’s American Society of Hematology (ASH) meeting with promising early data of lupus patients treated with CAR-T cell therapy, a team of German scientists has now published updated results in the NEJM that suggest the one-time treatment can lead to sustained remission for patients with several autoimmune diseases.At 29 months of follow-up, all eight patients with systemic lupus erythematosus (SLE) had no signs of disease activity. “Even though it is premature to judge whether these patients are indeed cured from their autoimmune disease, CD19 CAR T cells at least appear to be able to achieve sustained disease- and drug-free remission,” the authors wrote.While four CD19-directed CAR-T therapies have been approved for various haematological malignancies, Thursday’s study adds to a growing body of evidence that the modality could also be an effective tool to treat autoimmune diseases because they target the same underlying culprit: B-cells. But while the approved treatments attack malignant B-cells in patients with cancer, for those with an autoimmune disease, the goal is a deep depletion of autoreactive B-cells.The study authors note that antibody treatments targeting B-cells have had modest efficacy in autoimmune diseases, but they’ve yet to achieve long-lasting drug-free remission. The goal with CAR-T therapy is to unleash one powerful treatment that reduces B-cells to a level so low that it can essentially result in a reboot of the immune system. Resetting autoimmunityThe study enrolled 15 patients who had an inadequate response to at least two previous immune-suppressive treatments, including eight with SLE, three with idiopathic inflammatory myositis, and four with systemic sclerosis. Each received a single treatment with MB-CART19.1, an experimental CD19-directed CAR-T therapy from Miltenyi Biomedicine. No authors on the paper are affiliated with the German biotech.At ASH, the researchers announced that all 15 patients had discontinued immunosuppressive drugs at the 15-month follow-up. In Thursday’s paper, the authors revealed more details they say supports the long-term benefit of CAR-T to treat autoimmune diseases, including autoantibody depletion, B-cell reconstitution, and vaccination response.  All but one of the lupus patients were evaluable for a one-year post-infusion autoantibody test, which found that all of them exhibited a sustained absence of SLE-specific autoantibodies. Additionally, all eight patients showed normal levels of complement factor C3, and seven experienced complete resolution of proteinuria.Moreover, all patients experienced full B-cell reconstitution for as long as two years without relapse, suggesting a one-time CAR-T treatment can “reset” pathologic autoimmunity. The cell therapy’s potential to be an immune on/off switch was also supported by the appearance of a naive non–class-switched B-cell system, the disappearance of circulating plasmablasts, and the down-regulation of specific disease-associated heavy and light chains.“Although CAR T-cell therapy is directed to both pathogenic and nonpathogenic B cells, the rebooting of the B-cell system after the disappearance of CAR T cells obviously occurs in the absence of the pathogenic B cells that trigger autoantibody production,” the authors wrote.Finally, the researchers administered standard vaccines to each lupus patient, including tetanus, measles, mumps, rubella, varicella–zoster virus, and Epstein–Barr virus, and their protective IgG antibody responses remained stable.