On November 4, 2021 DYNAVAX TECHNOLOGIES CORPORATION (Nasdaq: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, reported financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, Dynavax Technologies, NOV 4, 2021, View Source [SID1234594417]).

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"This quarter we continued to make strong progress with both our lead commercial vaccine, HEPLISAV-B, and our CpG 1018 vaccine adjuvant platform," commented Ryan Spencer, Chief Executive Officer of Dynavax. "Our belief in the significant value of both assets is reinforced by the continued growth in market share and revenue for HEPLISAV-B along with multiple positive data readouts for adjuvanted COVID-19 vaccine candidates demonstrating the capabilities of CpG 1018 to help drive efficacy and high levels of antibodies while maintaining a favorable tolerability profile. Strong execution on a thoughtful, timely strategy has resulted in $244 million in year-to-date total revenue and $215 million in cash flow from operations, generating approximately $414 million in cash and equivalents at the end of this quarter which further enables our ability to continue to make investments which we believe will drive long-term value."

THIRD QUARTER AND RECENT BUSINESS UPDATE

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

HEPLISAV-B achieved another quarterly high with $22.7 million in revenue during the third quarter of 2021, compared to $11.6 million for the third quarter 2020. This increase was primarily driven by continued success in the field targeted accounts. Market share in the accounts targeted by the field sales team increased to 33.5%, up from 23% in the third quarter of 2020. With a consistent seroprotection rate of over 90% across all patients and the only FDA-approved two-dose hepatitis B vaccine for adults that is completed in one month, in a market where three-dose compliance is known to be a significant challenge, the Company believes HEPLISAV-B can protect more adults against hepatitis B than all other competitor vaccines.

The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) at its November 2021 meeting voted unanimously to recommend that all adults 19 to 59 years of age should receive hepatitis B vaccination. This recommendation greatly simplifies the identification of patients who need a hepatitis B vaccine compared to the current risk-based recommendation, and significantly expands the number of adults in the United States who should be vaccinated against hepatitis B.

CpG 1018 (Vaccine Adjuvant)

The Company’s strategy to expand the use of its CpG 1018 adjuvant platform and proven technology in multiple modalities of vaccine development continued to generate positive results in the third quarter. Through global partnerships, multiple data read outs for late-stage clinical trials of COVID-19 vaccine candidates adjuvanted with CpG 1018 generated impressive efficacy, immunogenicity and tolerability results. These clinical results enhance the data supporting CpG 1018’s ability to help enable new and improved vaccines that are effective and well-tolerated.

Net product revenue for CpG 1018 adjuvant during the third quarter of 2021 was $84.3 million, compared to $1.7 million for the third quarter 2020. The increase was associated with commercial supply agreements for COVID-19 collaborations. With the meaningful progress made across our COVID-19 partnership portfolio, the Company now expects 2021 full-year CpG 1018 revenue to be approximately $375- $425 million.

In July, Medigen Vaccine Biologics Corporation received Emergency Authorization (EUA) from the Taiwan Food and Drug Administration for MVC-COV1901, their COVID-19 vaccine adjuvanted with CpG 1018, and began vaccinating Taiwan residents in late August.
In July, Dynavax and Biological E (Bio E) entered into a commercial supply agreement for the use of CpG 1018 adjuvant in the commercial production of Bio E’s subunit COVID-19 vaccine candidate, CORBEVAX. Upon completion of their Phase 2/3 clinical trial in India and subsequent EUA, Bio E stated India’s Union Ministry of Health has reserved 300 million doses of CORBEVAX.
In September, Clover Biopharmaceuticals reported positive data for their protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum) adjuvanted with Dynavax’s CpG 1018, which achieved the primary and secondary efficacy endpoints in SPECTRA, a global pivotal Phase 2/3 clinical trial that enrolled over 30,000 participants. Vaccine efficacy was successfully demonstrated in an environment where 100% of SARS-CoV-2 strains observed in the efficacy analysis were variants. SCB-2019 (CpG 1018/Alum) demonstrated a favorable safety and tolerability profile. Subject to receiving Emergency Use Listing (EUL) from the World Health Organization (WHO), Clover said it plans to supply up to 414 million doses of its COVID-19 vaccine candidate globally through the COVAX Facility.
In September, Dynavax and the U.S. Department of Defense (DOD) executed an agreement for approximately $22 million over two and a half years to develop a recombinant plague vaccine adjuvanted with CpG 1018. Enrollment for the Phase 2 clinical trial is expected to commence in 2022.
In October, Valneva SE reported positive topline data for their inactivated whole virus COVID-19 vaccine candidate, VLA2001, adjuvanted with Dynavax’s CpG 1018, in Cov-Compare, a comparative immunogenicity PHASE 3 trial in approximately 4,000 adults. The trial successfully met both co-primary endpoints of superior neutralizing antibody titer levels compared to the active comparator vaccine, AstraZeneca’s AZD1222 (ChAdOx1-S), and neutralizing antibody seroconversion rate above 95%. VLA2001 was well-tolerated, demonstrating a statistically significant better tolerability profile compared to AZD1222.
Corporate Updates

In October, Scott Myers was appointed to Board of Director and elected Chairman.
Upcoming Milestones

Multiple CpG 1018 COVID-19 collaboration partners’ regulatory submissions for emergency or conditional use authorization are expected by the end of 2021 and may provide additional revenue opportunity in 2022.
Data from Tdap-1018 in the ongoing Phase 1 clinical trial for an improved tetanus, diphtheria, and acellular pertussis booster vaccine candidate adjuvanted with CpG 1018 are expected in the first quarter of 2022.
FINANCIAL RESULTS FOR THE THIRD QUARTER

Product Revenue, Net.

Total revenue for the third quarter of 2021 was $108.3 million.

HEPLISAV-B product revenue, net was $22.7 million in the third quarter of 2021 compared to $11.6 million in the same period in 2020.
CpG 1018 product revenue, net was $84.3 million in the third quarter of 2021 compared to $1.7 million in the same period in 2020. As CpG 1018 revenues are generally recorded upon shipment to a customer, there may be fluctuations in revenues between quarters, as shipments often consist of large-sized batches.
Cost of Sales – Product. Cost of sales – product for the third quarter 2021 increased to $60.1 million, compared to $4.0 million for the third quarter of 2020. The increase was primarily due to manufacturing costs for increased volumes of CpG 1018 and HEPLISAV-B sold to customers.

Research and Development Expenses (R&D). R&D expenses for the third quarter of 2021 decreased to $6.2 million, compared to $8.5 million for the third quarter of 2020. The decrease is primarily associated with certain non-recurring expenses incurred in the third quarter of 2020 associated with the wind-down of the Company’s legacy immuno-oncology business.

Selling, General and Administrative Expenses (SG&A). SG&A expenses for the third quarter of 2021 increased to $26.9 million, compared to $21.5 million for the third quarter of 2020. This increase is primarily driven by compensation and related personnel costs, including non-cash stock-based compensation, associated with higher headcount.

Income (loss) from Operations and Net Income (loss). Income from operations for the third quarter of 2021 was $16.1 million compared to a loss from operations of $13.8 million in the third quarter of 2020. Net loss for the third quarter of 2021 was $28.4 million compared to net income of $4.4 million for the third quarter of 2020.

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 third quarter of 2021 resulted in a loss of $45.1 million, compared to a gain of $21.2 million in the third quarter of 2020.

Earnings per share. Basic and diluted net loss per share were ($0.24), for the third quarter of 2021, compared to basic net income per share of $0.04 and diluted net loss per share of ($0.15) in the third quarter of 2020.

Cash Position and cash flow from operations. Cash, cash equivalents and marketable securities totaled $414.2 million on September 30, 2021. Cash flow from operations for the nine months ended September 30, 2021 was approximately $215.0 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 www.dynavax.com. Alternatively, participants may dial (866) 420-4066 or (409) 217-8237 and refer to conference ID 5994808. A replay of the webcast will be available for 30 days following the live event.

Please see Important Safety Information below.

For more information about HEPLISAV-B, visit View Source

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 20 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 has worldwide commercial rights to 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 immunisation 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 unrecognised HBV infection to be present at the time of immunisation. 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

CpG 1018 is the adjuvant used in HEPLISAV-B. Dynavax developed CpG 1018 adjuvant to provide an increased vaccine immune response, which has been demonstrated in HEPLISAV-B. 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 November 4, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported recent company highlights and financial results for the third quarter ended September 30, 2021 (Press release, Cardiff Oncology, NOV 4, 2021, View Source [SID1234594416]).

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"During the third quarter, the data we released from our Phase 1b/2 KRAS-mutated metastatic colorectal cancer trial showed meaningful improvements in treatment response and durability relative to historical controls," said Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology. "With radiographic responses achieved across multiple KRAS mutation variants, we believe these findings differentiate onvansertib from agents targeting individual KRAS mutations such as G12C."

Dr. Erlander added, "Beyond our KRAS-focused programs, we also continue to leverage onvansertib’s broadly applicable mechanism of action to advance its development as a platform molecule. By targeting PLK1, onvansertib inhibits DNA repair and processes that promote mitosis, positioning it to combine synergistically with a range of anti-cancer agents and potentially improve outcomes across a broad array of difficult-to-treat indications."

Program highlights for the quarter ended September 30, 2021, include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced new data from Phase 1b/2 trial evaluating onvansertib plus FOLFIRI/bevacizumab continuing to show robust objective response rate and progression-free survival

The data were presented as part of a key opinion leader webinar and showed that trial participants treated with onvansertib plus standard-of-care FOLFIRI/bevacizumab had an objective response rate (ORR) and median progression-free survival (mPFS) that substantially exceeded those previously achieved with FOLFIRI/bevacizumab alone. Highlights from the webinar include:

Efficacy data in patients evaluable for disease response as of data cutoff date (July 2, 2021):

Patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) across Phase 1b and Phase 2
7 of 19 (37%) achieved a confirmed partial response (PR; based on further follow-up of patients with an initial PR as of data cutoff date)
ORRs observed in historical control trials in similar patient populations treated with standard-of-care are 5-13%1-4
Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2) across Phase 1b and Phase 2
10 of 32 (31%) have achieved a confirmed PR (based on further follow-up of patients with an initial PR as of data cutoff date)
mPFS biomarker, and safety data as of cutoff date

mPFS across all response-evaluable patients (n = 32) is 9.4 months (95% confidence interval: 7.8 – not yet reached); which favorably compares to ~4.5-5.7 months reported in historical control trials in similar patient populations treated with standard-of-care1-4
PRs were observed across different KRAS mutation variants, including the 3 most common observed in colorectal cancer (G12D, G12V, G13D)
The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 10% (49/490) of reported treatment-emergent adverse events being G3/G4
A replay of the key opinion leader webinar, which featured the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP, USC Norris Comprehensive Cancer Center, key clinical advisor Afsaneh Barzi, M.D., Ph.D., City of Hope Comprehensive Cancer Center, and members of the Cardiff Oncology management team, can be viewed here.

Corporate Highlights:

Strengthened management team with the appointments of Katherine L. Ruffner, M.D., as chief medical officer and James E. Levine as chief financial officer

Dr. Ruffner is a US-trained hematologist/oncologist with over 25 years of clinical care, oncology, biotechnology and pharmaceutical drug development experience, most recently serving as vice president, clinical development for ALX Oncology. Mr. Levine was most recently the CFO of Cidara Therapeutics and has over two decades of corporate and investment banking experience in the biotechnology and pharmaceutical sectors.

Third Quarter 2021 Financial Results:

As of September 30, 2021, Cardiff Oncology had approximately $134 million in cash, cash equivalents, and short-term investments.

Total operating expenses were approximately $7.1 million for the three months ended September 30, 2021, an increase of $2.6 million from $4.5 million for the same period in 2020. The increase in operating expenses is attributed to advancing ongoing and new onvansertib clinical development programs and preclinical activities, additional outside services for legal fees mainly related to the expansion of our patent portfolio, recruiting fees and stock compensation expense.

Research and development expenses increased by approximately $1.3 million to $4.2 million for the three months ended September 30, 2021, from $2.9 million for the same period in 2020. The increase in research and development expenses was primarily due to advancing the onvansertib clinical and preclinical programs and recruitment fees to fill critical medical and clinical operations positions.

Selling, general and administrative expenses increased by approximately $1.3 million to $2.9 million for the three months ended September 30, 2021, from $1.6 million for the same period in 2020. The increase is attributed to increased outside services for legal fees related to the expansion of our patent portfolio, recruitment fees, and stock compensation expense.

Net cash used in operating activities for the third quarter of 2021 was approximately $5.5 million, an increase of approximately $2.0 million from $3.5 million for the same period in 2020.

References

Giessen et al., Acta Oncologica 2015, 54: 187-193
Cremolini et al., Lancet Oncol 2020, 21: 497–507
Antoniotti et al., Correspondence Lancet Oncol June 2020
Bennouna et al., Lancet Oncol 2013; 14: 29–37

On November 4, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported publication of two abstracts featuring preclinical data from its expanding pipeline in advance of the 63rd ASH (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, Adagene, NOV 4, 2021, View Source [SID1234594415]).

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The preclinical results show compelling differentiation of ADG153, an anti-CD47 SAFEbody and ADG152, a CD20xCD3 POWERbody integrating the company’s proprietary bispecific T-cell engager (TCE) platform with SAFEbody masking technology. The full abstracts will be available on the ASH (Free ASH Whitepaper) Annual Meeting and Exposition website in anticipation of poster presentations at the hybrid meeting being held virtually and in Atlanta, Georgia from December 11-14, 2021.

Details for the poster presentations during ASH (Free ASH Whitepaper) 2021 include:

Title: ADG153, an Anti-CD47 Monoclonal Antibody Prodrug, Has Strong In Vivo Anti-Tumor Activity, Minimal RBC-Related and Antigen Sink Liabilities, and Extended Half Life in Comparison with Benchmark Clinical Antibodies of the Same IgG Subclass
Publication Number: 3342
Date: Monday, December 13, 2021
Poster Session III: 9:00 a.m. – 8:00 p.m. ET
Location & Time (for in-person participants): Hall B5 from 6:00 p.m. – 8:00 p.m. ET

Title: ADG152, a Novel CD20xCD3 T Cell Engager Prodrug with Enhanced Therapeutic Index, Demonstrates Strong Anti-Tumor Activity with Improved Safety
Publication Number: 1204
Date: Saturday, December 11, 2021
Poster Session I: 9:00 a.m. – 7:30 p.m. ET
Location & Time (for in-person participants): Hall B5 from 5:30 p.m. – 7:30 p.m. ET
"We are excited to share the first preclinical results from our ongoing evaluation of ADG152 and ADG153, which are two novel programs emerging from our deep, broad, and differentiated pipeline," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "The known challenges of targeting CD47 — specifically, the need for a Fc dependent efficacious antibody without triggering on-target off tumor liabilities, including binding to red blood cells or showing significant antigen sink in healthy cells — and those of bispecific CD3 TCEs — a clinically validated, powerful modality with cytokine release syndrome limiting their utility — are the ideal problems for our AI-powered platform and antibody engineering teams to overcome in a tailor-made manner."

Dr. Luo continued, "We look forward to presenting more detailed results during the ASH (Free ASH Whitepaper) sessions, including new data from our ADG153 program, with one of the first ever anti-CD47 antibodies of the IgG1 isotype on track for clinical development. Additionally, ADG152 is the first novel bispecific TCE that incorporates our SAFEbody anti-CD3 antibody which has a low binding affinity and demonstrates strong anti-tumor activity while maintaining an impressive control of cytokine release in vivo, an outstanding issue facing many TCEs in clinical development. We are extremely encouraged by the data supporting differentiation of these candidates, which collectively showcase how we are on the forefront of antibody discovery and development to address patient needs."

The preclinical findings also reflect the advantages of the company’s AI-driven antibody discovery and development platform, which integrates the dynamic properties of antibody-based therapeutics into structure and design. Specifically, by targeting novel epitopes and introducing conditionally-activated masking technology, Adagene develops antibody candidates with tailor-made safety and efficacy profiles. When applied to powerful antibody-based modalities such as bispecific TCEs and antibody-drug conjugates, these therapeutic candidates are designed to reach beyond the therapeutic potency of traditional monospecific antibodies, while maintaining patient safety. These transformative technologies are known as NEObody, SAFEbody and POWERbody.

Both ADG152 and ADG153 are potential Investigational New Drug candidates from Adagene’s growing portfolio of preclinical discovery programs, five of which are in IND-enabling studies.

On November 4, 2021 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 third quarter ended September 30, 2021 (Press release, Fate Therapeutics, NOV 4, 2021, View Source [SID1234594414]).

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"The interim Phase 1 data from our FT516 and FT596 programs in relapsed / refractory lymphoma demonstrate that our off-the-shelf, iPSC-derived NK cell product candidates have the potential to deliver substantial therapeutic benefit for patients along with a differentiated safety profile that supports outpatient treatment. We look forward to sharing additional clinical data from both of these programs at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We also continue to be pleased with the clinical advancement of our multiplexed-engineered, iPSC-derived NK cell pipeline, where we have now successfully treated the first patients with FT516 in disease-specific expansion cohorts for lymphoma and with FT538 in combination with daratumumab for multiple myeloma. Additionally, we have successfully completed GMP manufacture and release of FT576, our multi-antigen targeted, CAR BCMA product candidate for multiple myeloma, and have initiated enrollment in our Phase 1 study."

B-cell Malignancy Disease Franchise

Positive FT596 Interim Phase 1 Clinical Data Observed in Single-dose Treatment Regimens. In August, the Company highlighted interim clinical data from its dose-escalating Phase 1 study of FT596 as monotherapy and in combination with rituximab for the treatment of relapsed / refractory (r/r) B-cell lymphoma (BCL). As of the data cutoff date of June 25, 2021, in the second (90 million cells) and third (300 million cells) dose cohorts of the single-dose monotherapy and combination regimens, 10 of 14 patients (71%) achieved an objective response (ORR), including seven patients (50%) that achieved a complete response (CR), on Day 29 as assessed by PET-CT scan per Lugano 2014 criteria. Treatment with FT596 was well tolerated, with two reported low-grade adverse events (one Grade 1, one Grade 2) of cytokine release syndrome (CRS) and no reported adverse events of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD). Dose escalation is ongoing with enrollment in the fourth (900 million cells) single-dose cohorts. In addition, the Company has initiated enrollment of a two-dose treatment schedule in both regimens, with FT596 administered on Day 1 and Day 15 at 300 million cells per dose with the potential to dose escalate to 900 million cells per dose.
Encouraging Safety Profile with Second FT596 Cycle Supports Re-treatment. The FT596 Phase 1 clinical protocol allows for the re-treatment of eligible patients with a second FT596 cycle. As of the June 25, 2021 data cutoff date, in the second (90 million cells) and third (300 million cells) dose cohorts, eight of 10 patients responding after the first single-dose cycle were re-treated with a second single-dose cycle. Of these eight re-treated patients, four patients with CR at the end of the first cycle remained in CR following disease assessment at the end of the second cycle, and the other four patients had not yet been assessed for response following the end of the second cycle. The second cycle was well tolerated, and no adverse events of CRS, ICANS, or GVHD were observed.
Positive FT516 Interim Phase 1 Clinical Data Reported in Multi-dose, Multi-cycle Treatment Regimen. In August, the Company updated interim clinical data from its dose-escalating Phase 1 study of FT516 in combination with rituximab for the treatment of r/r BCL. As of the data cutoff date of July 7, 2021, in the second and third multi-dose cohorts (90 million cells per dose and 300 million cells per dose, respectively), eight of 11 patients (73%) achieved an objective response, including six patients (55%) that achieved CR, on Day 29 of the second FT516 treatment cycle as assessed by PET-CT scan per Lugano 2014 criteria. Five of the 11 patients (45%) maintained their response without further therapeutic intervention, including four patients that remained in CR (4.6-9.5 months) and one patient that remained in partial response (6.1 months). The multi-dose, multi-cycle treatment regimen was well tolerated, and no adverse events of CRS, ICANS, or GVHD were reported.
Dose-expansion Stage of FT516 Phase 1 Study Initiated. The Company has completed enrollment in the dose-escalation stage of its Phase 1 study of FT516 in combination with rituximab for the treatment of r/r BCL, and has initiated enrollment in the study’s dose-expansion stage at 900 million cells per dose. The Company plans to enroll patients in three disease-specific expansion cohorts using cyclophosphamide (Cy) and fludarabine (Flu) as conditioning chemotherapy: patients with r/r aggressive lymphomas who have previously been treated with CD19-targeted 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 plans to enroll an expansion cohort without Cy / Flu conditioning chemotherapy, combining FT516 with rituximab and bendamustine, a standard-of-care treatment regimen for lymphoma.
Landmark Phase 1 Study of Off-the-shelf, iPSC-derived CAR T-cell Therapy Ongoing at Multiple Sites. In July, the first patient was treated in the Company’s landmark Phase 1 clinical trial of FT819, 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. The first patients have been treated with a single FT819 dose of 90 million cells for r/r acute lymphoblastic leukemia (ALL) and for r/r BCL, and the study is open to patient recruitment at three U.S. sites.
AML Disease Franchise

FT538 Phase 1 Study Enrolling in Dose Cohort 2. The Company is currently enrolling patients in the second multi-dose cohort (300 million cells per dose) in its dose-escalating Phase 1 study of FT538 as monotherapy for the treatment of r/r acute myeloid leukemia (AML). In addition, enrollment has commenced in an investigator-initiated Phase 1 clinical trial of FT538 in combination with the CD38-targeted monoclonal antibody daratumumab in patients with r/r AML, a therapeutic strategy 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).
Dose-escalation Stage of FT516 Phase 1 Clinical Trial Completed. The Company completed enrollment in the dose-escalation stage of its Phase 1 study of FT516 as monotherapy for the treatment of r/r AML, having enrolled seven patients in the third multi-dose cohort (900 million cells per dose). The maximum tolerated dose was not established with the third multi-dose cohort, and treatment with FT516 was well-tolerated.
Multiple Myeloma Franchise

First Patient Treated in Phase 1 Study of FT538 in Combination with Daratumumab. The Phase 1 clinical trial is designed to assess three once-weekly doses of FT538 in combination with daratumumab for patients with r/r multiple myeloma (MM). The first patient has been treated in the first multi-dose cohort (100 million cells per dose), and the study is open to patient recruitment at seven U.S. sites.
Initiated Enrollment 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 initiated enrollment of a 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 MM.
Solid Tumor Franchise

Initiated Enrollment in Phase 1 Study of FT538 in Combination with Monoclonal Antibody Therapy. The Phase 1 clinical trial is designed to assess the safety and activity of three once-weekly doses of FT538 in combination with monoclonal antibody therapy for the treatment of a broad array of solid tumors. The clinical protocol includes combination with each of three monoclonal antibodies: EGFR-targeted cetuximab; HER2-targeted trastuzumab; and PDL1-targeted avelumab. Each patient is eligible to receive up to two FT538 treatment cycles, with each cycle consisting of three days of outpatient lympho-conditioning, three once-weekly infusions of FT538, and monoclonal antibody therapy.
FT536 Preclinical Data to be Featured at SITC (Free SITC Whitepaper) in Oral Presentation. At the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), the Company plans to present IND-enabling preclinical data for FT536, its off-the-shelf, multiplexed-engineered, iPSC-derived NK cell product candidate that incorporates a novel CAR targeting the alpha-3 domain of the pan-tumor associated stress antigens MICA and MICB. The clonal master iPSC bank for FT536 was created from a single iPSC engineered with four functional elements, including the CAR which has a novel binding domain designed to overcome common tumor escape mechanisms mediated by loss of MHC Class I expression and by shedding of MICA and MICB. The Company expects to submit an Investigational New Drug (IND) application for FT536 in the fourth quarter of 2021 for the treatment of advanced solid tumors, including in combination with monoclonal antibody therapy to promote multi-antigen targeting.
Other Corporate Highlights

Peer-Reviewed Cell Stem Cell Publication Highlights Adaptive Phenotype and Functionality of FT538. The peer-reviewed article entitled "Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy" describes preclinical studies showing that FT538 shares metabolic, transcriptional, and functional features with adaptive NK cells, a rare subset of NK cells with memory-like properties that have a genome-wide epigenetic profile and recall response that parallel cytotoxic effector CD8+ T cells. The published data demonstrate that FT538 exhibits significantly enhanced serial killing and functional persistence compared to peripheral blood NK cells. The superior anti-tumor activity of FT538 was attributable to its novel engineered components, including the knockout of CD38 and the expression of IL-15/IL-15R fusion protein, which were shown to improve metabolic fitness, increase resistance to oxidative stress, and induce transcription of proteins that control NK cell activation and effector function. The studies in the Cell Stem Cell publication were conducted as part of a collaboration between scientists at Fate Therapeutics and the laboratory of Jeffrey S. Miller, M.D., University of Minnesota, and were led by Frank Cichocki, Ph.D., University of Minnesota.
Third Quarter 2021 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of September 30, 2021 were $803.6 million.
Total Revenue: Revenue was $14.2 million for the third quarter of 2021, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $53.1 million for the third quarter of 2021, which includes $8.6 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $15.7 million for the third quarter of 2021, which includes $5.0 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 95.4 million, and preferred shares outstanding were 2.8 million, as of September 30, 2021. Each preferred share is convertible into five common shares.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Thursday, November 4, 2021 at 5:00 p.m. ET to review financial and operating results for the quarter ended September 30, 2021. In order to participate in the conference call, please dial 877-303-6235 (toll free) or 631-291-4837 (toll) and refer to conference ID 9459084. 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 can 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 capable of overcoming 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 IgG1 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 acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumors resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

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, 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 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 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 (Valamehr et al. 2020). 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).

On November 4, 2021 Bio-Techne Corporation (NASDAQ: TECH) reported that Jim Hippel, Executive Vice President and Chief Financial Officer, will present virtually at the Credit Suisse 30th Annual Healthcare Conference on Tuesday, November 9, 2021 at 11:20 a.m. EST (Press release, Bio-Techne, NOV 4, 2021, View Source [SID1234594413]). A live webcast of the presentation can be accessed via the IR Calendar page of Bio-Techne’s Investor Relations website at View Source

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