On May 5, 2022 AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) reported that it has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy (Press release, AstraZeneca, MAY 5, 2022, View Source [SID1234613608]).

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Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The approval by the Food and Drug Administration (FDA) was based on positive results from the DESTINY-Breast03 Phase III trial that showed Enhertu reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.0001) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The approval was granted under the FDA’s Real-Time Oncology Review (RTOR) programme and converts the accelerated approval of Enhertu in later line HER2-positive metastatic breast cancer to standard approval, broadening Enhertu’s breast cancer indication in the US to earlier lines of use in patients with HER2-positive metastatic breast cancer.

Erika Hamilton, MD, Director of the Breast Cancer and Gynecological Cancer Research Program for Sarah Cannon Research Institute, Nashville, Tennessee, US, said: "Enhertu has demonstrated significant progression-free survival in the earlier metastatic setting, potentially establishing it as a new standard of care in previously treated patients with HER2-positive metastatic breast cancer. Today’s approval is an important milestone for the clinical community as we will now be able to offer Enhertu to these patients earlier in their treatment."

Catherine Ormerod, Executive Vice President, Strategy and Mission, Living Beyond Breast Cancer, said: "This is an important day for the breast cancer community. With this approval, Enhertu now provides a new treatment option for patients with HER2-positive metastatic breast cancer which can be used earlier in treatment to potentially delay progression of disease."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Enhertu is already established in the later-line treatment of patients with HER2-positive metastatic breast cancer, and we are thrilled that with this approval, patients in the US will now be able to access the transformative potential of Enhertu earlier in their treatment. We look forward to bringing this important, potentially paradigm-shifting medicine to even more patients across the globe in an earlier setting as quickly as possible."

Ken Keller, Global Head, Oncology Business and President and CEO, Daiichi Sankyo, Inc, said: "Today’s FDA approval, which converts the accelerated approval of Enhertu to regular approval, highlights the importance of the FDA’s accelerated pathway that allows for earlier approval of medicines to treat serious medical conditions such as breast cancer. Data from DESTINY-Breast03 not only confirmed the results of DESTINY-Breast01, but also demonstrated the superiority of Enhertu in prolonging progression-free survival compared to T-DM1 in an earlier setting of HER2-positive metastatic breast cancer."

The DESTINY-Breast03 Phase III trial results were recently published online in The New England Journal of Medicine.1 In the trial, the safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.

Based on the DESTINY-Breast03 data, fam-trastuzumab deruxtecan-nxki (Enhertu) recently was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines) as the Category 1 preferred regimen as second-line therapy for recurrent unresectable (local or regional) or Stage IV HER2-positive disease.2

The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. Five national health authorities collaborated with the FDA on this review, including the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration and Switzerland’s Swissmedic.

This approval follows the recent Priority Review and Breakthrough Therapy Designation of Enhertu in the US in this earlier setting.

Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

Notes

Financial considerations
Following this approval for Enhertu in the US, an amount of $100m is due from AstraZeneca to Daiichi Sankyo as a 2nd-line milestone payment in HER2-positive metastatic breast cancer. In AstraZeneca, the milestones paid will be capitalised as an addition to the upfront payment made in 2019 and subsequent capitalised milestones and amortised through the profit and loss.

Sales of Enhertu in the US are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in the US as collaboration revenue in the Company’s financial statements. For further details on the financial arrangements, please consult the collaboration agreement from March 2019.

HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide and in the US.3,4 More than two million patients with breast cancer were diagnosed in 2020, with nearly 685,000 deaths globally.3 More than 290,000 new cases are expected in the US in 2022, with more than 43,000 deaths.5 Approximately one in five cases of breast cancer are considered HER2-positive.6

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers.7 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.8

Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.9 More treatment options are needed to further delay progression and extend survival.9-11

DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate (ORR), duration of response, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy, based on results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is also approved in approximately 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2 based regimen based on the results from the DESTINY-Breast03 trial.

Enhertu was granted Breakthrough Therapy Designation in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results of the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.

Enhertu is also currently under review in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2 (ERBB2) mutation and who have received a prior systemic therapy, based on the DESTINY-Lung01 trial, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE:4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in HER2-negative early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On May 5, 2022 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported financial results for the first quarter ended March 31, 2022, as well as recent business highlights (Press release, C4 Therapeutics, MAY 5, 2022, View Source [SID1234613637]).

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"We recently shared our first clinical data for single agent CFT7455 that demonstrated its unique properties, including differentiated pharmacokinetics and potency compared to approved and investigational IKZF1/3 degraders and we are now focused on optimizing dose and schedule to improve the therapeutic index and advance the program in multiple myeloma and non-Hodgkin’s lymphomas," said Andrew Hirsch, chief executive officer of C4 Therapeutics. "At AACR (Free AACR Whitepaper), we also presented data highlighting the capability of our TORPEDO platform to develop highly potent and selective degraders against three distinct oncology target classes that we are progressing to the clinic. Our strong balance sheet provides runway to enable us to execute our strategy of optimizing the dosing regimen for CFT7455 and advance CFT8634, CFT1946 and CFT8919."

FIRST QUARTER 2022 AND RECENT HIGHLIGHTS

CFT7455: CFT7455 is a novel degrader candidate targeting IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL), including peripheral T-cell lymphoma and mantle cell lymphoma.

Presented Clinical Data from Cohort A at AACR (Free AACR Whitepaper): In April 2022, C4T presented clinical data from Cohort A of its ongoing CFT7455 Phase 1/2 clinical trial. Data demonstrated that single agent CFT7455 resulted in deep and durable degradation of IKZF1/3, as quantified by mass spectrometry, and meaningful decreases in serum free light chain. Neutropenia, a known on-target toxicity associated with IKZF1/3 degraders, was dose-limiting at the 50 μg daily 21 day on/7 day off starting dose and schedule. No serious adverse events were reported.
Progressed Ongoing Phase 1/2 Clinical Trial: Enrollment is ongoing in Cohort B1, exploring CFT7455 as a monotherapy for relapsed or refractory MM, and Cohort C, exploring CFT7455 as a monotherapy for NHL.
Presented Pre-clinical Data at AACR (Free AACR Whitepaper): In April 2022, C4T characterized the chemical structure of CFT7455, the resulting improvements in potency and optimized pharmacokinetic properties. In vitro data suggested that CFT7455 resulted in a high cereblon binding affinity (KD = 0.9 nM) along with rapid, selective and deep degradation of IKZF1/3 that is associated with apoptosis, leading to broad and potent antiproliferative activity in a panel of MM cell lines. In vivo MM models treated with CFT7455 indicated regression in the treatment-naïve H929 MM tumor models at doses ≥10 µg/kg/day, as well as durable antitumor responses consistent with long-lived pharmacodynamic activity. Moreover, CFT7455 was observed to be efficacious in MM models resistant or insensitive to currently approved IMiD treatments.
CFT8634: CFT8634 is a degrader candidate targeting BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.

Activated Sites for Phase 1/2 Clinical Trial: With sites now active, C4T remains on track to dose the first patient in the Phase 1/2 clinical trial of CFT8634 in synovial sarcoma and SMARCB1-null solid tumors in 1H 2022. The Phase 1/2 trial will primarily investigate safety, tolerability and anti-tumor activity, with secondary and exploratory objectives to characterize the pharmacokinetic and pharmacodynamic profile of CFT8634. The Phase 1 portion of the study will evaluate CFT8634 as an oral, single agent therapy for patients with synovial sarcoma and SMARCB1-null solid tumors to identify a recommended Phase 2 dose.
Presented Pre-clinical Data at AACR (Free AACR Whitepaper): In April 2022, C4T presented pre-clinical data on the discovery and characterization of CFT8634, a BiDAC degrader of BRD9. The pre-clinical data demonstrated that CFT8634 selectively inhibits the growth of BAF-perturbed cell lines and demonstrates robust efficacy in clinically relevant patient-derived xenograft models of synovial sarcoma. This pre-clinical data suggests that CFT8634 is a potent and selective degrader of BRD9 in vitro.
Received Orphan Drug Designation: In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to CFT8634 for the treatment of soft tissue sarcoma.
CFT1946: CFT1946 is a mutant-selective degrader of BRAF V600X for the treatment of V600 mutant solid tumors.

Presented Pre-clinical Data at AACR (Free AACR Whitepaper): In April 2022, C4T presented its pre-clinical evaluation of CFT1946. Data demonstrated that CFT1946 induces on-mechanism BRAF-V600E degradation, potent inhibition of MAPK signaling and loss of viability in BRAF-V600E cells without impacting wild type-BRAF. In addition, CFT1946 is active in vitro and in vivo in models with BRAF-V600E-driven disease and in the escape mutant BRAF-V600E/NRAS-Q61K-driven model, which is a model of clinical resistance to BRAF inhibitors.
Corporate

Named Bruce Downey as Lead Independent Director: In January 2022, C4T named Bruce Downey as lead independent director. Mr. Downey chairs C4T’s Organization, Leadership and Compensation Committee and also serves on the Audit Committee and Nominating and Corporate Governance Committee. Mr. Downey previously served as chairman and chief executive officer of Barr Pharmaceuticals.
Appointed Utpal Koppikar to Board of Directors: In March 2022, C4T appointed Utpal Koppikar, MBA, to its board of directors, where Mr. Koppikar will also serve as chair of the Audit Committee and a member of the Organization, Leadership and Compensation Committee. Mr. Koppikar is currently the chief financial officer of Atara Biotherapeutics.
KEY UPCOMING MILESTONES

The company anticipates the following milestones:

CFT7455: Continued enrollment of the Phase 1/2 trial throughout 2022. These efforts will inform the identification of a recommended Phase 2 dose(s) and schedule(s) for MM and NHL.
CFT8634: Dose the first patient in CFT8634 Phase 1/2 clinical trial in 1H 2022 and continue to enroll the trial throughout 2022. These efforts will inform the identification of a recommended Phase 2 dose for synovial sarcoma and SMARCB1-null solid tumors.
CFT1946: Submit an IND application and initiate a Phase 1 trial of CFT1946 in BRAF V600X-driven cancers including melanoma, colorectal and non-small cell lung cancer in 2H 2022.
CFT8919: Complete IND-enabling activities for CFT8919 by year-end 2022.
FIRST QUARTER 2022 FINANCIAL RESULTS

Revenue: Total revenue for the first quarter of 2022 was $7.7 million, compared to $7.4 million for the first quarter of 2021. Total revenue reflects revenue recognized under collaboration agreements with Roche, Biogen and Calico.

Research and Development (R&D) Expense: R&D expense for the first quarter of 2022 was $26.2 million, compared to $20.5 million for the first quarter of 2021. The increase in R&D expense was primarily attributable to increased personnel expenses, including an increase in stock compensation expenses of $2.4 million.

General and Administrative (G&A) Expense: G&A expense for the first quarter of 2022 was $12.8 million, compared to $7.4 million for the first quarter of 2021. The increase in G&A expense was primarily attributable to increased personnel expenses, including an increase in stock compensation expense of $2.6 million, and higher facilities costs resulting from additional leased space.

Net Loss and Net Loss per Share: Net loss for the first quarter of 2022 was $31.6 million, compared to $21.0 million for the first quarter of 2021. Net loss per share for the first quarter of 2022 was $0.65, compared to $0.49 for the first quarter of 2021.

Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of March 31, 2022, were $421.7 million, compared to $451.5 million as of December 31, 2021. The decrease in cash was primarily driven by expenditures to fund operations. C4T expects that its cash, cash equivalents and marketable securities as of March 31, 2022, together with future payments expected to be received under existing collaboration agreements, will be sufficient to fund planned operating expenses and capital expenditures to the end of 2024.

On May 5, 2022 Dynavax Technologies Corporation (Nasdaq: DVAX), a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines, reported financial results and provided business updates for the three months ended March 31, 2022 (Press release, Dynavax Technologies, MAY 5, 2022, View Source [SID1234613653]).

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Ryan Spencer, Chief Executive Officer of Dynavax, commented: "Following a year of record revenue for both HEPLISAV-B vaccine and CpG 1018 adjuvant, 2022 is off to a great start and has the potential to be another pivotal year. In the first quarter, HEPLISAV-B grew 21% compared to the fourth quarter, exceeding the overall hepatitis B market growth of 14%. The first quarter also marked another quarter of significant revenue for CpG 1018 adjuvant supply for COVID-19 vaccines as we continue to demonstrate strong execution across our portfolio of commercial supply agreements. Looking ahead, we are on track to achieve our second consecutive profitable year with continued revenue growth fueled by HEPLISAV-B and our CpG 1018 adjuvant supply business. This year we also expect additional clinical data readouts from both of our Phase 1 pipeline programs for Tdap and shingles."

FIRST-QUARTER CORPORATE HIGHLIGHTS

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

HEPLISAV-B vaccine is the first and only U.S. FDA-approved adult hepatitis B vaccine that enables series completion with only two doses in one month.

•HEPLISAV-B vaccine achieved net product revenue of $20.8 million for the first quarter of 2022, up 151% compared to $8.3 million for the first quarter of 2021.
•Market share in the accounts targeted by the Dynavax field sales team was approximately 33%, with a total market share of approximately 26% in the first quarter of 2022, up from approximately 27% and 14%, respectively, in the first quarter of 2021.
•The CDC’s Advisory Committee on Immunization Practices (ACIP) recommendation for hepatitis B vaccination in adults has been published (link), advising that all adults aged 19-59 should be vaccinated against hepatitis B. Dynavax believes this will enable a significantly expanded total market opportunity of up to $800 million in the U.S. by 2027, with HEPLISAV-B well positioned to secure a majority market share over time.

CpG 1018 Adjuvant Supply for COVID-19 Vaccines

Dynavax has established a global portfolio of CpG 1018 adjuvant commercial supply agreements currently focused on the development of COVID-19 vaccines across a variety of vaccine platforms.

•CpG 1018 adjuvant revenue for the first quarter of 2022 was $91.5 million, up 23% compared to $74.6 million for the first quarter of 2021.
•The Company continues to expect 2022 full-year CpG 1018 adjuvant COVID-19 supply revenue to be at least $550 million, based on committed adjuvant orders, with full-year gross margin anticipated to be approximately 50%. Revenue and margins are expected to fluctuate quarter to quarter based on customer mix and timing of product delivery.

•CpG 1018 adjuvant supply partner selected recent regulatory updates:
oBiological E (Bio E) has received Emergency Use Authorization (EUA) from the Drugs Controller General of India (DCGI) for its subunit COVID-19 vaccine candidate, CORBEVAX utilizing CpG 1018 adjuvant, for adults (December 2021), for adolescents aged 12 to less than 18 years of age (February 2022) and for use in children ages 5-12 (April 2022).
oClover Biopharmaceuticals has 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 CpG 1018 adjuvant. Clover anticipates that its submissions are to be completed in mid-2022 for the China NMPA and by the third quarter of 2022 for the WHO and EMA.
oMedigen Vaccine Biologics Corporation received EUA for MVC-COV1901, its COVID-19 vaccine candidate utilizing 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 recently announced that the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom has granted Conditional Marketing Authorization (CMA) for its COVID-19 vaccine candidate, VLA2001 utilizing CpG 1018 adjuvant. Valneva also reported that it now expects a decision from CHMP on its recommendation for potential conditional approval by the European Medicines Agency (EMA) in the second quarter of 2022.

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.

•Tdap vaccine program: Interim adult data from the ongoing Phase 1 study evaluating a new Tdap vaccine candidate utilizing CpG 1018 adjuvant demonstrated it was safe and well tolerated with immunogenicity data supporting continued advancement. Adolescent data from the same trial is expected in the second half of 2022.
•Shingles vaccine program: Topline data from an ongoing Phase 1 study evaluating the safety, tolerability, and immunogenicity in adults compared to Shingrix, the leading marketed shingles vaccine in the U.S., is anticipated by the end of 2022.
•Plague vaccine Phase 2 study: In collaboration with, and funded by, the U.S. Department of Defense, the Company plans to initiate a Phase 2 clinical trial in the second half of 2022.

FIRST-QUARTER FINANCIAL HIGHLIGHTS

Total Revenues and Product Revenue, Net.

Total revenues for the first quarter of 2022 were $114.0 million, compared to $83.3 million for the first quarter of 2021.

•HEPLISAV-B vaccine product revenue, net was $20.8 million for the first quarter of 2022, compared to $8.3 million for the first quarter of 2021.
•CpG 1018 adjuvant product revenue, net was $91.5 million in the first quarter of 2022 compared to $74.6 million in the first quarter of 2021.
Cost of Sales – Product. Cost of sales – product for the first quarter of 2022 increased to $40.0 million, compared to $24.6 million for the first quarter of 2021. The increase was primarily due to manufacturing costs for increased volumes of CpG 1018 adjuvant sold to COVID-19 supply partners and increased HEPLISAV-B vaccine sales volume.

Research and Development Expenses (R&D). R&D expenses for the first quarter of 2022 increased to $11.1 million, compared to $7.8 million for the first quarter of 2021. The increase was primarily driven by higher compensation and personnel costs, including non-cash stock-based compensation, associated with higher headcount and higher external costs as the Company continued to invest in 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 first quarter of 2022 increased to $32.2 million, compared to $22.4 million for the first quarter of 2021. The increase was primarily driven by compensation and related personnel costs, including non-cash stock-based compensation, primarily associated with increased headcount as the Company expanded its field sales team to support HEPLISAV-B vaccine commercialization in mid-2021.

Interest Expense. Interest expense was $1.7 million in the first quarter of 2022, a decrease of $3.0 million from $4.7 million in the first quarter of 2021, reflecting a decreased interest rate associated with the Company’s 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 first quarter of 2022 resulted in a gain of $1.8 million, compared to a loss of $25.6 million in the first quarter of 2021 due to the final mark-to-market adjustment from January 1, 2022, through the expiration date of the warrants on February 12, 2022. There were no warrants outstanding as of March 31, 2022.

Net Income. GAAP net income was $32.9 million, or $0.26 per share (basic) and 0.22 per share (diluted) in the first quarter of 2022, compared to GAAP net income of $0.9 million, or $0.01 per share (basic and diluted) in the first quarter of 2021.

2022 Financial Guidance

Dynavax anticipates 2022 revenues, operating expenses, and other costs to be in the ranges shown below, unchanged from the Company’s previous financial guidance provided on February 28, 2022:

•Full-year CpG 1018 adjuvant net product revenues of at least $550 million, with an associated gross margin of approximately 50%
•Research and development expenses to be between approximately $55 – $70 million
•Selling, general and administrative expenses to be between approximately $120 – $140 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 4282730. 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 are 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’s (CDC) Advisory Committee on Immunization Practices (ACIP) recommends that adults aged 19–59 years and adults aged ≥60 years with risk factors for hepatitis B should receive HepB vaccines, and that adults aged ≥60 years without known risk factors for hepatitis B may receive HepB vaccines.iii Because people with diabetes are particularly vulnerable to infection, the CDC recommends vaccination for adults aged 19 to 59 with diabetes as soon as possible after their diagnosis, and for people aged 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 Vaccine [Hepatitis B Vaccine (Recombinant), Adjuvanted]

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

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 CpG 1018 Adjuvant

Dynavax developed CpG 1018 adjuvant to provide an increased vaccine immune response with an improved tolerability profile, which has been demonstrated in HEPLISAV-B vaccine and multiple COVID-19 vaccines that have received Emergency Use Authorization outside of the U.S. 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 May 5, 2022 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company developing medicines for metabolic and immunological diseases through its proprietary approach to synthetic biology, reported the Company will release its first quarter 2022 financial results before the market opens on Thursday, May 12, 2022 (Press release, Synlogic, MAY 5, 2022, View Source [SID1234613668]). The press release will be followed by a conference call at 8:30 am ET, which will be open to the public via telephone and webcast. During the conference call, the Company will review its financial results and provide a business update.

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The conference call dial-in numbers are (844) 815-2882 for domestic callers and (213) 660-0926 for international callers. The conference ID number for the call is 5149412. Participants may access the live webcast in the "Events Calendar" of the Investors & Media section

On May 5, 2022 Keros Therapeutics, Inc. ("Keros" or the "Company") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, reported financial results for the quarter ended March 31, 2022 (Press release, Keros Therapeutics, MAY 5, 2022, View Source [SID1234613684]).

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

"The first quarter of fiscal 2022 saw positive momentum across all of our programs," said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer. "We remain on track to report additional data from our ongoing Phase 2 clinical trial of KER-050 in patients with myelodysplastic syndromes ("MDS") in mid-2022, as well as to report initial data from Part 1 of our ongoing Phase 1 clinical trial of KER-012 in healthy volunteers in the second quarter of 2022."

First Quarter 2022 Financial Results

Keros reported a net loss of $24.2 million in the first quarter of 2022 as compared to a net loss of $15.9 million in the first quarter of 2021. The increase in net loss for the first quarter was largely due to increased research and development efforts as well as additional infrastructure expenses to support the achievement of Keros’ corporate goals.

Research and development expenses were $18.1 million for the first quarter of 2022 as compared to $11.5 million for the same period in 2021. The increase of $6.6 million was primarily due to additional research and development efforts, manufacturing activities, and personnel expenses to support the advancement of Keros’ pipeline.

General and administrative expenses were $6.0 million for the first quarter of 2022 as compared to $4.3 million for the same period in 2021. The increase of $1.8 million was primarily due to increase in personnel expenses and other external expenses to support Keros’ organizational growth.

Keros’ cash and cash equivalents as of March 31, 2022 was $228.6 million compared to $230.0 million as of December 31, 2021. Keros expects that the cash and cash equivalents it had on hand at March 31, 2022 will fund its operating expenses and capital expenditure requirements into the first quarter of 2024.