On February 28, 2022 Genialis, a computational precision medicine company unraveling complex biology to find new ways to address disease, reported it will work with Inhibrx in an effort to develop a predictive biomarker for INBRX-109 in solid tumors (Press release, Inhibrx, FEB 28, 2022, View Source [SID1234609170]). Genialis will utilize its AI/ML clinical biomarker discovery platform, ResponderID, to help Inhibrx identify features for potential patient stratification and model the underlying biologies that predict response to the drug candidate.

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INBRX-109 is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to exploit the tumor-biased cell death induced by DR5 activation. In January 2021, the FDA granted Fast Track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma. In collaboration with clinical researchers and data scientists at Inhibrx, Genialis is using ResponderID to derive representative gene sets and model the complex biologies that govern response to DR5 agonism. This work incorporates numerous data sets from Inhibrx’s preclinical studies and clinical programs, the public domain, and Genialis’ proprietary ML-ready database. The goal is to improve resolution of patient stratification to accurately identify potential responders and understand patient outcomes.

"Genialis’ ResponderID platform has enabled the capture of specific, sophisticated signal related to INBRX-109 sensitivity in both preclinical and clinical samples," said Brendan Eckelman, Ph.D., CSO of Inhibrx. "As we move forward in the clinic and generate more data, we anticipate the Genialis’ platform will allow us to better understand the relevant biology, and leverage that understanding into a predictive biomarker."

ResponderID defines, models, and validates new biomarkers for drug development and discovery programs. The platform is a technology suite for clinical and translational research, built from years of experience working with partners across the industry and advanced internal R&D. ResponderID incorporates technologies and proprietary tools for feature selection, data harmonization, and machine learning modeling. While ResponderID can complement virtually any data analysis environment, it is typically powered by data from Genialis Expressions, the FAIR-inspired data management, and bioinformatics processing software suite. The collaboration with Inhibrx marks the first publicly disclosed collaboration of the Genialis ResponderID platform since the commercial launch in November 2021 and represents a new stage of partnership between the companies in developing biomarkers for potential clinical guidance in the application of the therapeutic.

"Genialis’ focus has always been to harness the power of advanced data analytics to benefit human health," said Rafael Rosengarten, Ph.D., CEO of Genialis. "With Inhibrx, we have found a partner that shares this commitment and has a pipeline of exciting potential new medicines to achieve the goal. We are excited to continue our precision medicine journey together as we help advance their lead drug candidate to reach the patients most in need."

Genialis, a founding member of the Alliance for AI in Healthcare (AAIH), also released a new podcast from its popular series, "Talking Precision Medicine." The first episode of 2022 features well-known executive, investor, author, and entrepreneur Harry Glorikian to discuss his new book, "The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer." The podcast is available through Spotify and Apple. For more information, please visit www.genialis.com.

On February 28, 2022 Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (Nasdaq:SGEN) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has confirmed its previously adopted positive opinion, recommending approval of PADCEV (enfortumab vedotin) as monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received platinum-containing chemotherapy and a PD-1/L1 inhibitor (Press release, Seagen, FEB 28, 2022, View Source [SID1234609093]).

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The CHMP initially adopted a positive opinion of enfortumab vedotin on December 16, 2021, providing its recommendation to the European Commission (EC) for a final decision. During the EC’s decision-making process, further safety information was brought to the attention of the CHMP. Following a request from the EC and taking into account the latest information, the CHMP re-adopted its positive opinion.1 If approved by the EC, enfortumab vedotin will be the first antibody-drug conjugate authorized in the European Union for people living with advanced urothelial cancer.

The positive opinion from the CHMP will now be reviewed by the EC. EC decisions are valid in the European Union Member States, as well as Iceland, Norway and Liechtenstein.2

About Urothelial Cancer

Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.3 Globally, approximately 573,000 new cases of bladder cancer and 212,000 deaths are reported annually.4

About Enfortumab Vedotin

Enfortumab vedotin is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5,6 Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).6

PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information

BOXED WARNING: SERIOUS SKIN REACTIONS

PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
Closely monitor patients for skin reactions.
Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.
U.S. Indication

PADCEV is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.5
Important Safety Information

Warnings and Precautions

Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN, occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. Withhold PADCEV and refer for specialized care for suspected SJS or TEN or for severe (Grade 3) skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN, or for Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials, 14% of the 680 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20.3). Hyperglycemia led to discontinuation of PADCEV in 0.6% of patients. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Pneumonitis Severe, life-threatening or fatal pneumonitis occurred in patients treated with PADCEV. In clinical trials, 3.1% of the 680 patients treated with PADCEV had pneumonitis of any grade and 0.7% had Grade 3-4. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6). Monitor patients for signs and symptoms indicative of pneumonitis, such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis.

Peripheral neuropathy (PN) occurred in 52% of the 680 patients treated with PADCEV in clinical trials, including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without preexisting PN. The median time to onset of Grade ≥2 PN was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN.

Ocular disorders were reported in 40% of the 384 patients treated with PADCEV in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions

Most Common Adverse Reactions, Including Laboratory Abnormalities (≥20%)

Rash, aspartate aminotransferase (AST) increased, glucose increased, creatinine increased, fatigue, PN, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase (ALT) increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.

EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy.

Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite and fatigue (3% each). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST increased (12%), hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%).

EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for platinum-based chemotherapy.

Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥3%) were pneumonia, sepsis and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), AST increased and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%) and fatigue (7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST increased (12%), lipase increased (11%), ALT increased (10%), pneumonitis (4%) and infusion site extravasation (1%).

Drug Interactions

Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)

Concomitant use with a dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

On February 28, 2022 Dynavax Technologies Corporation (Nasdaq: DVAX), a commercial stage biopharmaceutical company developing and commercializing innovative vaccines, reported record 2021 total revenue of $439.4 million for the full year of 2021, marking a significant increase compared to $46.6 million for 2020 (Press release, Dynavax Technologies, FEB 28, 2022, View Source [SID1234609119]).

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"The Company’s strong performance throughout 2021 is a testament to the strategy, hard work and dedication of the Dynavax team. This past year we made tremendous progress across our three strategic focus areas – HEPLISAV-B commercialization, execution of CpG 1018 adjuvant supply for COVID-19 vaccines, and advancement of our clinical pipeline – driving 72% year-over-year growth in HEPLISAV-B sales and $375 million in CpG 1018 adjuvant supply revenue," commented Ryan Spencer, Chief Executive Officer of Dynavax. "With approximately $546 million in cash and investments at year-end, we are able to make thoughtful investments into our pipeline leveraging our proven adjuvant. In 2022, we expect continued growth with HEPLISAV-B and our CpG 1018 adjuvant supply business, generating another profitable year with record total revenue, as well as initial clinical data that we anticipate will support meaningful differentiation to establish our high value pipeline designed to produce best-in-class products targeting large markets."

2021 CORPORATE AND FINANCIAL HIGHLIGHTS

HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted]

•HEPLISAV-B achieved record annual revenue of $61.9 million for 2021, compared to $36.0 million for 2020, despite the disruptions to the healthcare system from the COVID-19 pandemic.
•Market share in the accounts targeted by the field sales team grew to approximately 34%, up from approximately 26% at the end of 2020.
•With a proven clinical profile and strong commercial execution, the Company expects further market share gains and revenue growth in 2022.
•Recent recommendations from the CDC’s Advisory Committee on Immunization Practices (ACIP) advise that all adults aged 19-59 should be vaccinated against Hepatitis-B, creating a significantly expanded market opportunity, which the company estimates to be $800 million in the U.S. by 2027. The Company believes that HEPLISAV-B is well-positioned to secure majority market share.

CpG 1018 Adjuvant Supply for COVID-19 Vaccines

•Dynavax has established a portfolio of global CpG 1018 adjuvant commercial supply agreements leveraging its adjuvant in the development of COVID-19 vaccines across a variety of vaccine platforms.
•CpG 1018 adjuvant revenue for 2021 of $375.2 million, compared to $3.3 million 2020.
•The Company expects 2022 full-year CpG 1018 adjuvant COVID-19 supply revenue to be at least $550 million, based on committed adjuvant orders, with gross margin of approximately 50%.
•CpG 1018 adjuvant supply partner status:
oBiological E (Bio E) received Emergency Use Authorization (EUA) from the Drugs Controller General of India (DCGI) for their subunit COVID-19 vaccine candidate, CORBEVAX adjuvanted with CpG 1018, for adults in

December 2021. In February 2022, Bio E received EUA for adolescents aged 12 to less than 18 years of age by the DCGI.
oClover Biopharmaceuticals reported it is in the process of submitting conditional regulatory approval applications for its protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum) utilizing our CpG 1018 adjuvant, to China’s National Medical Products Administration, the European Medicines Agency (EMA) and the World Health Organization (WHO).
oMedigen Vaccine Biologics Corporation received EUA for MVC-COV1901, its COVID-19 vaccine utilizing our CpG 1018 adjuvant, from the Taiwan Food and Drug Administration in 2021 and from Paraguay’s National Directorate of Health Surveillance (DINAVISA) in February 2022.
oValneva SE reported it is continuing to provide data to the European Medicines Agency (EMA), the UK Medicines and Healthcare products Regulatory Agency, and the National Health Regulatory Authority in Bahrain (NHRA) as part of the rolling submissions process for initial approval of VLA2001.
oCpG 1018 adjuvant supply partners have ongoing clinical trials evaluating the immunogenicity or efficacy of their vaccine candidates for global use, homologous and heterologous boosters, as well as additional indications including pediatrics.

Clinical Pipeline

•The Company is advancing its clinical pipeline leveraging its CpG 1018 adjuvant to develop improved vaccines in indications with unmet medical need.
•CpG 1018 adjuvant has demonstrated its ability to enhance immune responses with a favorable tolerability profile established through a wide range of clinical trials and real-world commercial use.
•The Company is currently advancing three clinical-stage programs with important milestones in 2022:
oTopline data is expected in the first half of 2022 from the Company’s ongoing Tdap Phase 1 clinical trial evaluating the safety, tolerability, and immunogenicity in adults, with adolescent data expected in the second half of 2022.
oIn January 2022, the first patient was dosed in a Phase 1 clinical trial evaluating the safety, tolerability, and immunogenicity in the Company’s investigational shingles vaccine program utilizing CpG 1018 adjuvant. Topline data from the trial is expected by the end of 2022.
oIn collaboration with, and funded by, the U.S. Department of Defense, the Company will conduct a Phase 2 clinical trial for a plague vaccine utilizing CpG 1018 adjuvant with trial initiation anticipated in the second half of 2022.

Board of Directors Additions

•In October, Scott Myers was appointed to the Board of Directors and elected Chairman.
•In December, Elaine Sun was appointed to the Board of Directors.

FOURTH QUARTER AND FULL YEAR 2021 FINANCIAL HIGHLIGHTS

Total Revenues and Product Revenue, Net.

Total revenues for the fourth quarter of 2021 were $195.1 million, compared to $19.6 million for 2020.

•HEPLISAV-B product revenue, net was $17.2 million for the fourth quarter of 2021 compared to $11.5 million for the fourth quarter of 2020.
•CpG 1018 product revenue, net was $177.4 million in the fourth quarter of 2021 compared to $1.6 million in the fourth quarter of 2020.

Total revenues for the full year 2021 were $439.4 million, compared to $46.6 million for the full year 2020.

•HEPLISAV-B product revenue, net increased 72% to $61.9 million for 2021 compared to $36.0 million for the full year 2020.
•CpG 1018 product revenue, net was $375.2 million for 2021 compared to $3.3 million for the full year 2020.
Cost of Sales – Product. Cost of sales – product for the fourth quarter of 2021 increased to $74.0 million, compared to $4.1 million for the fourth quarter of 2020. Full year 2021 cost of sales – product was $173.6 million compared to $11.4 million for the full year of 2020. The increase was primarily due to manufacturing costs for increased volumes of CpG 1018 sold to COVID-19 supply partners, and HEPLISAV-B sales, coupled with approximately $4.8 million in excess capacity charges in connection with an expansion project at the Company’s manufacturing facility in Dusseldorf and $2.6 million write-off of HEPLISAV-B inventory that had been manufactured prior to the beginning of the COVID-19 pandemic and not expected to be sold due to the prolonged impact of the pandemic.

Research and Development Expenses (R&D). R&D expenses for the fourth quarter of 2021 increased to $11.1 million, compared to $9.5 million for the fourth quarter of 2020. Full year 2021 R&D expenses were $32.2 million compared to $28.6 million for the full year 2020. The increase in both periods was primarily driven by higher compensation and personnel costs, including non-cash stock-based compensation, associated with higher headcount and external costs as the Company advances its product candidates with CpG 1018 adjuvant through pre-clinical and clinical collaborations and additional discovery efforts.

Selling, General and Administrative Expenses (SG&A). SG&A expenses for the fourth quarter of 2021 increased to $29.2 million, compared to $17.8 million for the fourth quarter of 2020. Full year 2021 SG&A expenses were $100.2 million compared to $79.3 million for the full year 2020. The increase in both periods was primarily driven by compensation and related personnel costs, including non-cash stock-based compensation, associated with higher headcount as the Company expanded its field sales team to increase HEPLISAV-B market share.

Interest Expense. Interest expense was $1.7 million in the fourth quarter of 2021 and $11.2 million for the full year 2021, primarily in connection with the convertible senior notes due 2026.

Other income (expense). Other income (expense) includes the change in fair value of warrant liability which is a non-cash adjustment to fair value each reporting period. The change in fair value of warrant liability for the fourth quarter of 2021 resulted in a gain of $19.2 million, compared to a loss of $0.1 million in the fourth quarter of 2020.

Income Tax Expense. Income tax expense was $0.8 million for the full year 2021 and the Company’s effective tax rate was 1.03%. No income tax expense was recorded for the full year 2020. The increase in income tax expense and the effective tax rate are both due to achieving the Company’s first profitable year with GAAP net income of $76.7 million.

Net Income (Loss). GAAP net income was $99.8 million, or $0.80 per share (basic) and 0.55 per share (diluted) in the fourth quarter of 2021, compared to GAAP net loss in the fourth quarter of $15.5 million, or $0.14 per share (basic) and $0.14 per share (diluted) in the fourth quarter of 2020. GAAP net income was $76.7 million, or $0.62 per share (basic) and $0.57 per share (diluted) for the full year 2021, compared to GAAP net loss of $75.2 million, or $0.75 per share (basic) and $0.78 per share (diluted) for the full year 2020.

Cash Flow Statement and Balance Sheet Highlights

•Dynavax ended 2021 with $546 million in cash, cash equivalents and marketable securities, compared to $165 million at the end of 2020.
•Dynavax generated $120.5 million in cash from operations in the fourth quarter of 2021, compared to cash used in operations of $15.7 million in the fourth quarter of 2020. The Company generated $335.5 million in cash from operations for the full year 2021, compared to cash used in operations of $92.3 million for the full year 2020.

2022 Financial Guidance

In 2022, Dynavax anticipates:

•Full year CpG 1018 adjuvant net product revenues of at least $550 million, with associated gross margin of approximately 50%
•Selling, general and administrative expenses to be between approximately $120 – $140 million
•Research and development expenses to be between approximately $55 – $70 million
•Interest expense of approximately $7 million

Conference Call and Webcast Information

Dynavax will hold a conference call today 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 View Source Alternatively, participants may dial (866) 420-4066 or (409) 217-8237 and refer to conference ID 4678925. A replay of the webcast will be available for 30 days following the live event.

About Hepatitis B

Hepatitis B is a viral disease of the liver that can become chronic and lead to cirrhosis, liver cancer and death. The hepatitis B virus is 50 to 100 times more infectious than HIV,i and transmission is on the rise. There is no cure for hepatitis B, but effective vaccination can prevent the disease.

In adults, hepatitis B is spread through contact with infected blood and through unprotected sex with an infected person. The U.S. Centers for Disease Control (CDC) recommends vaccination for those at high risk for infection due to their jobs, lifestyle, living situations and travel to certain areas.ii Because people with diabetes are particularly vulnerable to infection, the CDC recommends vaccination for adults age 19 to 59 with diabetes as soon as possible after their diagnosis, and for people age 60 and older with diabetes at their physician’s discretion.iii Approximately 26 million U.S. adults have diabetes, and 1.5 million new cases of diabetes are diagnosed each year.iv

About HEPLISAV-B

HEPLISAV-B is an adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax’s proprietary Toll-like Receptor (TLR) 9 agonist CpG 1018 to enhance the immune response. Dynavax wholly owns HEPLISAV-B.

Important U.S. Product Information

HEPLISAV-B is indicated for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older.

Safety and effectiveness of HEPLISAV-B have not been established in adults on hemodialysis.

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 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%).

Important EU/EEA Product Information

HEPLISAV B is indicated for active immunization against hepatitis B virus infection (HBV) caused by all known subtypes of hepatitis B virus in adults 18 years of age and older.

The use of HEPLISAV B should be in accordance with official recommendations.

It can be expected that hepatitis D will also be prevented by immunization with HEPLISAV B as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.

For full EU/EEA. Prescribing Information for HEPLISAV-B, click here.

Important EU/EEA Safety information

Do not receive HEPLISAV B if you have had a sudden life-threatening, allergic reaction after receiving HEPLISAV B in the past, or if you are allergic to any of components of this vaccine, including yeast. Signs of an allergic reaction may include itchy skin, rash, shortness of breath and swelling of the face or tongue.

Appropriate medical treatment and supervision should be readily available in case of rare anaphylactic reactions following the administration of the vaccine.

The administration of HEPLISAV B should be postponed in subjects suffering from acute severe febrile illness.

Immunocompromised persons may have a diminished immune response to HEPLISAV B.

Because of the long incubation period of hepatitis B, it is possible for unrecognized HBV infection to be present at the time of immunization. HEPLISAV B may not prevent HBV infection in such cases.

There are very limited data on the immune response to HEPLISAV B in individuals who did not mount a protective immune response to another hepatitis B vaccine.

As a precautionary measure, it is preferable to avoid the use of HEPLISAV B during pregnancy. Vaccination during pregnancy should only be performed if the risk-benefit ratio at the individual level outweighs possible risks for the fetus.

The most common patient-reported side effects reported within 7 days of vaccination were pain, swelling or redness at the injection site, feeling tired, headache, muscle aches, feeling unwell and fever.

About CpG 1018 Adjuvant

Dynavax developed CpG 1018 adjuvant to provide an increased vaccine immune response with improved tolerability profile, which has been demonstrated in HEPLISAV-B and two COVID-19 vaccines that have received Emergency Use Authorization. CpG 1018 adjuvant provides a well- developed technology and a significant safety database, potentially accelerating the development and large-scale manufacturing of novel or improved vaccines.

On February 28, 2022 MaaT Pharma (EURONEXT: MAAT – the "Company"), a French clinical-stage biotech and a pioneer in the development of microbiome-based ecosystem therapies dedicated to improving survival outcomes for patients with cancer reported its cash position as of December 31, 2021, and its full-year 2021 revenues (Press release, MaaT Pharma, FEB 28, 2022, View Source [SID1234609135]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"2021 has been an eventful year for MaaT Pharma. Promising results from our Phase 2 and from the Early Access Program for MaaT013, our lead candidate ready to enter a Phase 3 study, marked our clinical development. We also reached a new milestone in our history in 2021 with the success of our IPO on the Euronext, which allowed us to raise EUR 35.7 million. We are in a solid financial position and are moving forward in our development with value-creating clinical milestones expected in the upcoming months for MaaT013 and our second drug candidate, MaaT033, as well as scaling up our manufacturing capacities," stated Hervé Affagard, CEO and co-founder of MaaT Pharma.

Cash position1
As of December 31, 2021, total cash and cash equivalents were EUR 43.3 million, as compared to EUR 19.9 million as of December 31, 2020. The increase in cash flow is due to the capital raise of EUR 35.7 million following the Company’s IPO on Euronext on November 8, 2021. The Company believes it has sufficient cash to cover needs of the development programs presented during the IPO up until the end of the third quarter of 2023.

Revenues in 20211
MaaT Pharma reported revenues of EUR 1.0 million for the year ended December 31, 2021, which includes compensation from the Temporary Authorization for Use program (ATUn), known as compassionate access program since July 1, 2021, and approved by the French National Drug Safety Agency (Agence Nationale de Sécurité du Médicament or ANSM). In 2021, new patients, mostly suffering from graft-versus-host disease, were granted early access treatment with MaaT013. To date in 2022, requests for the early access program are following as similar trend to that observed in 2021.

Upcoming financial communication and investor conference participation
March 3, 2022 (10:00am CET) – Ordinary and Extraordinary Shareholders’ General Meeting (regarding resolutions relative to the implementation of a Liquidity Contract, the Annual General meeting will take place at a later date).
April 15, 2022 – Annual results 2021
April 20 and 21, 2022 – 14th Kempen Life Sciences Conference, Amsterdam
June 29 and 30, 2022 – 9th Portzamparc Annual conference, Paris

On February 28, 2022 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that its Chief Executive Officer, Nancy Simonian, M.D., will participate in a panel discussion and present a corporate overview at two upcoming virtual investor conferences in March (Press release, Syros Pharmaceuticals, FEB 28, 2022, View Source [SID1234609152]). Management will also be available for one-on-one meetings. Details are as follows:

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Cowen 42nd Annual Healthcare Conference
Date: Monday, March 7
Panel Title: Novel Oncology Targets
Panel Time: 12:50 p.m. ET

Oppenheimer 32nd Annual Healthcare Conference
Date: Wednesday, March 16
Presentation Time: 3:20 p.m. ET

To access the webcasts and subsequent archived recording of each event, please visit the Investors & Media section of the Syros website at www.syros.com. An archived replay of each webcast will be available for approximately 30 days following each presentation.