On February 28, 2022 FibroGen, Inc. (NASDAQ: FGEN) reported financial results for the fourth quarter and full year 2021 and provided an update on the company’s recent developments (Press release, FibroGen, FEB 28, 2022, View Source [SID1234609124]).

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!

"We are excited to advance pamrevlumab in three high value indications – completing enrollment in our LAPIS and LELANTOS-1 Phase 3 studies, and expecting to complete enrollment of the ZEPHYRUS-1 Phase 3 study in idiopathic pulmonary fibrosis in the next few weeks," said Enrique Conterno, Chief Executive Officer, FibroGen. "In China, roxadustat had a strong 2021 performance and after inclusion in the updated NRDL, we are off to a good start in 2022."

Recent Developments and Key Events:

Following the European Commission approval of EVRENZO (roxadustat) for the treatment of adult patients with symptomatic anemia associated with chronic kidney disease (CKD), Astellas has launched EVRENZO in Germany, the United Kingdom, Netherlands, Austria, and the Nordic countries.
Completed enrollment of the LAPIS Phase 3 clinical trial of pamrevlumab in patients with locally advanced unresectable pancreatic cancer (LAPC).
Completed enrollment of the LELANTOS-1 Phase 3 clinical trial of pamrevlumab in patients with Duchenne muscular dystrophy (DMD).
Exercised option to exclusively license HiFiBiO’s CCR8 drug program to advance next-generation therapies for patients with solid tumors.
China:

Roxadustat net transfer price from sales to the distribution entity (JDE) jointly owned by FibroGen and AstraZeneca was $12.2 million for the fourth quarter. From the net transfer price, FibroGen defers a certain portion for revenue recognition purposes under U.S. GAAP. FibroGen reported $5.5 million in roxadustat net product revenue for the quarter.
In the fourth quarter of 2021, China’s National Healthcare Security Administration renewed the listing of roxadustat on the National Reimbursement Drug List (NRDL).
Due to the price reduction associated with the NRDL listing renewal, we have updated our estimates and reflected a cumulative adjustment in our revenue in the fourth quarter.
Fourth quarter total roxadustat net sales in China1 of $32.0 million2 by FibroGen and the JDE compared to $29.2 million in the fourth quarter of 2020.
Full year 2021 total roxadustat net sales in China1 of $186.1 million by FibroGen and the JDE compared to $72.5 million in the full year 2020.
Roxadustat continues to be the number one brand based on value share in the anemia of CKD market in China.
Upcoming Milestones:

Expect to complete enrollment in the ZEPHYRUS-1 Phase 3 study of pamrevlumab in idiopathic pulmonary fibrosis (IPF) in the next few weeks.
Interim analysis of event free survival of the LAPIS Phase 3 study of pamrevlumab in LAPC expected to be conducted in 2Q 2022.
Topline data from the LELANTOS-1 Phase 3 study of pamrevlumab in DMD expected 1H 2023.
Topline data from the ZEPHYRUS-1 Phase 3 study of pamrevlumab in IPF expected mid-2023.
Topline data from the MATTERHORN Phase 3 study of roxadustat in anemia of myelodysplastic syndromes (MDS) expected 2H 2022 / 1H 2023.
Corporate:

Implemented a plan to reduce our projected expenses by approximately $100 million per year, for each of the next 3 years, compared to our previous internal plans.
Financial:

Total revenue for the fourth quarter of 2021 was $16.5 million, as compared to $65.0 million for the fourth quarter of 2020.
Total revenue for 2021 was $235.3 million as compared to $176.3 million in 2020.
Net loss for the fourth quarter of 2021 was $134.1 million, or $1.45 net loss per basic and diluted share, compared to a net loss of $58.6 million, or $0.64 net loss per basic and diluted share one year ago.
Net loss for the year was $290.0 million, or $3.14 net loss per basic and diluted share, compared to a net loss of $189.3 million, or $2.11 net loss per basic and diluted share one year ago.
At December 31, 2021, FibroGen had $590.4 million in cash – defined as cash, cash equivalents, investments, and accounts receivable.
Based on our latest forecast, we estimate our 2022 ending cash to be in the range of $270 to $300 million.
1 Total roxadustat net sales in China includes sales made by the distribution entity as well as FibroGen China’s direct sales, each to its own distributors. The distribution entity jointly owned by AstraZeneca and FibroGen is not consolidated into FibroGen’s financial statements.
2 As a result of the price reduction associated with the NRDL listing renewal, the roxadustat net sales for the fourth quarter of 2021 reflected a one-time adjustment driven by a revaluation of channel inventory.

Conference Call and Webcast Details
FibroGen will host a conference call and webcast today, Monday, February 28, 2022, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time) to discuss financial results and provide a business update. A live audio webcast of the call may be accessed in the investor section of the Company’s website, www.fibrogen.com. To participate in the conference call by telephone, please dial 1 (877) 658-9081 (U.S. and Canada) or 1 (602) 563-8732 (international), reference the FibroGen fourth quarter 2021 financial results conference call, and use confirmation number 1795663. A replay of the webcast will be available shortly after the call for a period of 7 days. To access the replay, please dial 1 (855) 859-2056 (domestic) or 1 (404) 537-3406 (international) and use passcode 1795663.

About Pamrevlumab
Pamrevlumab is a first-in-class antibody developed by FibroGen that inhibits the activity of connective tissue growth factor (CTGF), an important biological mediator in fibrotic and proliferative disorders. Pamrevlumab is in Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), locally advanced unresectable pancreatic cancer (LAPC), and Duchenne muscular dystrophy (DMD). For information about pamrevlumab studies currently recruiting patients, please visit www.clinicaltrials.gov.

About Roxadustat
Roxadustat, an oral medication, is the first in a new class of medicines comprising HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for anemia of chronic kidney disease (CKD) and anemia associated with myelodysplastic syndromes (MDS), and for chemotherapy-induced anemia (CIA).

Roxadustat is approved in European Union (EU) member states, including the European Economic Area (EEA) countries, as well as in Japan, China, Chile, and South Korea for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by partners, Astellas and AstraZeneca to regulatory authorities across the globe, and are currently under review.

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the U.S., China, other markets not licensed to Astellas.

On February 28, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported business highlights and financial results for the fourth quarter and full year ended December 31, 2021 (Press release, Fate Therapeutics, FEB 28, 2022, View Source [SID1234609123]).

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!

"We have begun 2022 with strong clinical and regulatory momentum driving our off-the-shelf, iPSC-derived NK cell programs in relapsed / refractory lymphoma, and look forward to working with the FDA under the Regenerative Medicine Advanced Therapy designation to accelerate therapeutic development in areas of significant unmet need, such as patients who have progressed following autologous CAR T-cell therapy, and to bringing transformative cell therapies to patients in the community setting including as part of early-line treatment," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We maintain a strong financial position and are poised in 2022 to achieve key clinical milestones and data read-outs across our wholly-owned disease franchises, to extend our leadership in the manufacture and CMC of iPSC-derived cell therapies with the launch of our second cGMP manufacturing facility, and to bring new multiplexed-engineered NK and T-cell product candidates to patients."

B-cell Malignancy Disease Franchise

FT596+R Multi-dose, Multi-cycle Escalation Cohort Enrolling at 900 Million Cells per Dose. The first patients have been treated with a multi-dose, multi-cycle treatment schedule of FT596 in combination with rituximab (FT596+R) for relapsed / refractory (r/r) B-cell lymphoma (BCL) in the dose-escalation stage of the Company’s multi-center Phase 1 study. FT596 is being administered on Day 1 and Day 15 at 900 million cells per dose in each cycle, with the potential to dose escalate to 1.8 billion cells per dose. The Company plans to initiate multiple disease-specific, dose-expansion cohorts in the first quarter of 2022.
Positive Interim Phase 1 Clinical Data Reported for FT596+R Single-dose Escalation Cohorts. At the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December, the Company presented positive interim Phase 1 clinical data from the single-dose escalation cohorts of its FT596 Phase 1 study. In the second (90 million cells; n=4), third (300 million cells; n=6), and fourth (900 million cells; n=6) single-dose escalation cohorts of FT596+R, 11 of 16 patients (69%) achieved an objective response (ORR), including nine patients (56%) who achieved a complete response (CR), on Day 29 as assessed by PET-CT scan per Lugano 2014 criteria. As of the data cutoff date of October 11, 2021, of the 10 patients in the second and third single-dose escalation cohorts, six patients responded and were evaluable for duration of response assessment. Five patients, all of whom were treated with a second FT596+R single-dose cycle, continued in ongoing response at a median follow-up of 4.6 months, including two patients in ongoing CR at 6.0 and 10.8 months; and one patient, who was treated with a second FT596+R single-dose cycle, reached six months in CR and subsequently had disease progression at 6.7 months. Treatment with FT596+R was well tolerated, with two low-grade adverse events (one Grade 1, one Grade 2) of cytokine release syndrome (CRS) and no adverse events of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD).
RMAT Designation Granted by FDA for FT516 in R/R DLBCL. In December, the Company announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to FT516 for the treatment of r/r diffuse large B-cell lymphoma (DLBCL). RMAT designation is designed to expedite the development and review of regenerative medicine therapies that have demonstrated the potential to address an unmet medical need based on preliminary clinical evidence, and allows for early interactions with the FDA, including to discuss efficient drug development and pathways for accelerated approval. The Company plans to discuss its manufacturing, CMC, and pivotal study design with the FDA during the first half of 2022. In its ongoing FT516 Phase 1 clinical trial, the Company is currently enrolling patients in three disease-specific expansion cohorts at 900 million cells per dose, each of which uses cyclophosphamide (Cy) and fludarabine (Flu) as conditioning chemotherapy: patients with r/r aggressive lymphomas who have previously been treated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy; patients with r/r aggressive lymphomas who are naïve to treatment with CD19-targeted CAR T-cell therapy; and patients with r/r follicular lymphoma. In addition, the Company is also enrolling patients in a fourth expansion cohort, without Cy/Flu conditioning chemotherapy, adding FT516 to rituximab plus bendamustine (R-Benda), a standard-of-care treatment regimen for BCL.
Positive FT516 Interim Phase 1 Clinical Data Reported in Multi-dose, Multi-cycle Escalation Cohorts. At the ASH (Free ASH Whitepaper) Annual Meeting in December, the Company highlighted positive interim Phase 1 clinical data of FT516 in combination with rituximab from the multi-dose, multi-cycle escalation cohorts for the treatment of r/r BCL. Of the 18 patients treated at ≥90 million cells, 10 patients were naïve to treatment with autologous CD19-targeted CAR T-cell therapy, eight of whom achieved an ORR (80%), including five patients who achieved a CR (50%); and eight patients were previously treated with autologous CD19-targeted CAR T-cell therapy, three of whom achieved a CR (38%). All 11 responding patients continued in ongoing response at three months following initiation of treatment (61%), and eight patients continued in ongoing response (44%) at a median follow-up of 8.3 months. The multi-dose, multi-cycle treatment regimen was well tolerated, with no adverse events of CRS, ICANS, or GVHD.
Initial FT819 Dose-Escalation Cohort Cleared with No DLTs for R/R BCL in Landmark Phase 1 Study of Off-the-shelf, iPSC-derived CAR T-cell Therapy. FT819 is the first-ever T-cell therapy manufactured from a clonal master induced pluripotent stem cell (iPSC) line to undergo clinical investigation. The product candidate’s clonal master iPSC line is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct (1XX-CAR19) integrated into the T-cell receptor alpha constant (TRAC) locus, ensuring complete bi-allelic disruption of T-cell receptor expression and promoting uniform CAR expression. In the first FT819 single-dose escalation cohort (90 million cells) for r/r BCL in the Company’s Phase 1 study of FT819, there were no dose-limiting toxicities (DLTs) and no FT819-related Grade ≥3 adverse events. Enrollment is now ongoing in three treatment regimens for r/r BCL: single-dose cohort at 180 million cells; single-dose cohort at 90 million cells administered with low-dose IL-2 cytokine support; and three-dose cohort at 30 million cells per dose. In addition, enrollment is ongoing in the first single-dose escalation cohorts (90 million cells) for r/r chronic lymphocytic leukemia (CLL) and for r/r acute lymphoblastic leukemia (ALL).
AML Disease Franchise

Enrollment Ongoing in Two FT538 Phase 1 Clinical Trials. The Company’s Phase 1 study of FT538 as monotherapy and an investigator-initiated study of FT538 in combination with the CD38-targeted monoclonal antibody daratumumab are each currently enrolling patients in the second multi-dose escalation cohort (300 million cells per dose) for r/r acute myeloid leukemia (AML). The combination of FT538 with daratumumab is designed to exploit the product candidate’s proprietary high-affinity, non-cleavable (hnCD16) receptor and CD38 knock-out (CD38KO) to recognize, bind, and kill CD38+ leukemic blasts through antibody-dependent cellular cytotoxicity (ADCC).
Multiple Myeloma Franchise

First Patients Treated in FT576 Phase 1 Study. FT576 is derived from a clonal master iPSC line engineered with four functional components (CAR-BCMA + hnCD16 + IL-15RF + CD38KO) designed to enable multi-antigen targeting of myeloma cells, augment ADCC, promote NK cell activation without exogenous cytokine support, enhance NK cell persistence and prevent anti-CD38 monoclonal antibody-induced fratricide. The Company has treated the first patients in its multi-center Phase 1 clinical trial to assess single-dose and multi-dose treatment regimens of FT576 as monotherapy and in combination with daratumumab for the treatment of r/r multiple myeloma (MM).
Phase 1 Study of FT538+D Cleared Initial Dose-Escalation Cohort with No DLTs. The Phase 1 clinical trial is designed to assess three once-weekly doses of FT538 in combination with daratumumab (FT538+D) for r/r MM. There were no DLTs observed in the first multi-dose escalation cohort (100 million cells per dose), and enrollment is now ongoing in the second multi-dose escalation cohort (300 million cells per dose) at eight U.S. sites.
Solid Tumor Franchise

First Patients Treated in Phase 1 Study of FT538 in Combination with Monoclonal Antibody Therapy. The Company has treated the first patients in its multi-center Phase 1 clinical trial to assess the safety and activity of three once-weekly doses of FT538 in combination with monoclonal antibody therapy for advanced solid tumors. The clinical protocol includes combination with each of four monoclonal antibodies: EGFR-targeted cetuximab; HER2-targeted trastuzumab; PD1-targeted pembrolizumab; and PDL1-targeted avelumab. Each patient is eligible to receive up to two FT538 treatment cycles, and additional FT538 treatment cycles may be administered to patients that achieve initial clinical response. These off-the-shelf treatment cycles are designed to be administered in the outpatient setting.
IND Allowed for FT536 CAR MICA/B-targeted NK Cell Product Candidate. In December 2021, the FDA cleared an Investigational New Drug (IND) application for FT536, the Company’s off-the-shelf, multiplexed-engineered, iPSC-derived NK cell product candidate, which incorporates a novel CAR targeting the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB). High expression of MICA and MICB proteins (MICA/B), which is induced by cellular stress, damage or transformation, has been reported on many solid tumors, although the proteolytic shedding of the α1 and α2 domains of MICA/B is recognized as a common tumor escape mechanism. The clonal master iPSC bank for FT536 was created from a single iPSC engineered with four functional elements, including the novel CAR which uniquely targets the α3 domain of MICA/B and is designed to overcome tumor escape mechanisms mediated by loss of MHC Class I expression and proteolytic shedding. The Company is preparing to initiate a multi-center Phase 1 clinical trial to assess a multi-dose, multi-cycle treatment schedule of FT536 as monotherapy and in combination with monoclonal antibody therapy for advanced solid tumors.
Other Corporate Highlights

Preclinical Milestone Reached for Second Product Candidate under Janssen Collaboration. In January 2022, Janssen elected to initiate IND-enabling activities for a second iPSC-derived CAR NK cell product candidate incorporating a Janssen proprietary antigen binding domain, triggering the payment of a milestone fee to the Company under the collaboration.
Key Executive Promotions. The Company promoted Yu-Waye (Wayne) Chu, M.D. to Chief Medical Officer and Jerome Bressi, Ph.D. to Senior Vice President, Regulatory Affairs and Quality Assurance. Dr. Chu joined the Company in 2019 from Genentech, where he led early clinical development of cancer agents spanning multiple therapeutic platforms, including polatuzumab vedotin (anti-CD79b antibody drug conjugate), mosunetuzumab (CD20/CD3 bispecific antibody), and tiragolumab (anti-TIGIT monoclonal antibody). Dr. Bressi joined the Company in 2018 and has played an integral role in pioneering the clinical investigation of iPSC-derived cell therapy in the United States, and leads the Company’s regulatory strategies and interactions with the FDA for its iPSC product platform.
Fourth Quarter 2021 Financial Results & 2022 Guidance

Cash & Investment Position: Cash, cash equivalents and investments as of December 31, 2021 were $716.6 million. Cash use in the fourth quarter included a $20 million milestone payment to Memorial Sloan Kettering Cancer Center associated with the treatment of the first patient with FT819.
Total Revenue: Revenue was $17.1 million for the fourth quarter of 2021, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $69.5 million for the fourth quarter of 2021, which includes $9.4 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $16.9 million for the fourth quarter of 2021, which includes $5.2 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 95.7 million, and preferred shares outstanding were 2.8 million, as of December 31, 2021. Each preferred share is convertible into five common shares.
2022 Guidance: For the full year ending December 31, 2022, the Company expects its GAAP Loss from Operations to be between $335 million to $365 million, which loss includes stock-based compensation expense, and its cash use to be between $290 million to $315 million, which use excludes any amounts that may be received under its collaborations with Janssen and Ono in connection with the achievement of development milestones. The Company expects its cash, cash equivalents, and investments to exceed $400 million at year-end 2022.
Today’s Conference Call and Webcast

The Company will conduct a conference call today, Monday, February 28, 2022 at 5:00 p.m. ET to review financial and operating results for the quarter and full year ended December 31, 2021. In order to participate in the conference call, please dial (877) 303-6235 (domestic) or (631) 291-4837 (international) and refer to conference ID 1888465. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of therapeutic antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of relapsed / refractory acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of relapsed / refractory B-cell lymphoma (NCT04023071).

About FT596
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity and prevents antigen escape, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About FT538
FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636). FT538 is also being investigated in a multi-dose Phase 1 clinical trial in combination with one of an array of tumor-targeting monoclonal antibodies for the treatment of advanced solid tumors (NCT05069935).

About FT576
FT576 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell maturation antigen (BCMA); a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. In preclinical studies, FT576 has demonstrated that the high-avidity binding of the BCMA-targeted CAR construct enables sustained tumor control in against various multiple myeloma cell lines, including in long-term in vivo xenograft mouse models. Additionally, in combination with daratumumab, FT576 has shown complete tumor clearance and improved survival compared to primary BCMA-targeted CAR T cells in a disseminated xenograft model of multiple myeloma. FT576 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).

On February 28, 2022 Exact Sciences Corp. (Nasdaq: EXAS), a leader in advanced cancer diagnostics, reported that company management will participate in the following conferences and invited investors to participate by webcast (Press release, Exact Sciences, FEB 28, 2022, View Source [SID1234609122]).

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!

Cowen Health Care Conference, virtual
Fireside Chat on Monday, March 7, 2022 at 9:50 a.m. ET

Raymond James Institutional Investors Conference, Orlando
Fireside Chat on Tuesday, March 8, 2022 at 4:00 p.m. ET
The webcasts can be accessed in the investor relations section of Exact Sciences’ website at www.exactsciences.com.

On February 28, 2022 Eli Lilly and Company (NYSE: LLY) reported that it will participate in the Cowen Health Care Conference on Tuesday, March. 8, 2022 (Press release, Eli Lilly, FEB 28, 2022, View Source [SID1234609121]). Anat Ashkenazi, Lilly senior vice president and chief financial officer, will participate in a virtual fireside chat at 10:30 a.m., Eastern time.

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!

A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s Investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.

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]).

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 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.