On February 24, 2021 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported fourth quarter and full year 2020 financial results and recent business highlights (Press release, Sangamo Therapeutics, FEB 24, 2021, View Source [SID1234575539]).

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"We are very pleased with our execution and the progress we made in the challenging year of 2020 during the pandemic, where we advanced our hemophilia A product candidate into a Phase 3 clinical trial with Pfizer, dosed patients in our Phase 1/2 clinical study evaluating our wholly owned product candidate treating Fabry disease, entered into transformational neuroscience collaborations with Biogen and Novartis, brought in-house AAV manufacturing online in our Brisbane headquarters, and built a strong cash position," said Sandy Macrae, Chief Executive Officer of Sangamo. "In 2021, we will continue to build on our momentum with a focus on clinical execution and bringing our in-house cell therapy manufacturing facilities online."

Fourth Quarter Updates and Recent Business Highlights

Presented with collaborator Pfizer updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, a gene therapy product candidate to treat hemophilia A, which was generally well-tolerated and demonstrated sustained Factor VIII activity levels in the therapeutic range through one year for the five patients in the highest dose cohort. The data were presented at the 62nd American Society for Hematology Annual Meeting.
Announced with Pfizer that the first participant has been dosed in the registrational Phase 3 AFFINE trial of giroctocogene fitelparvovec.
Completed dosing in February 2021 of the third patient in the Phase 1/2 STAAR study evaluating ST-920 gene therapy for Fabry disease. This is the first patient in the second dose cohort.
Brought in-house AAV manufacturing capabilities online in Sangamo’s Brisbane, California headquarters at the end of 2020.
Announced global collaboration with Novartis to develop and commercialize gene regulation therapies to treat three neurodevelopmental targets, including genes linked to autism spectrum disorder and intellectual disability.
Announced global collaboration with Biogen to develop and commercialize gene regulation therapies for Alzheimer’s, Parkinson’s, neuromuscular and other neurological diseases.
Fourth Quarter and Full Year 2020 Financial Results

Consolidated net loss for the fourth quarter ended December 31, 2020 was $40.7 million, or $0.29 per share, compared to net income of $4.5 million, or $0.04 per share, for the same period in 2019. For the year ended December 31, 2020, consolidated net loss was $121.1 million, or $0.90 per share, compared to consolidated net loss of $95.4 million, or $0.85 per share, for the year ended December 31, 2019.

Revenues

Revenues for the fourth quarter ended December 31, 2020 were $25.8 million, compared to $54.9 million for the same period in 2019. The decrease in revenue was due primarily to milestones achieved under our collaboration agreements in the fourth quarter of 2019, which included $25.0 million from Pfizer for the completion of the investigational new drug, or IND, transfer for giroctocogene fitelparvovec and $7.5 million from Sanofi for dosing of the first patient in our Phase 1/2 clinical study evaluating our BIVV003 product candidate to treat sickle cell disease.

Revenues were $118.2 million in 2020, compared to $102.4 million in 2019. The increase in revenues was primarily due to recognition of upfront license fees under the Biogen and Novartis collaboration agreements entered into in 2020. This increase was partially offset by a decrease in revenues from our giroctocogene fitelparvovec collaboration agreement with Pfizer following the IND transfer in December 2019.

Operating expenses

Three Months Ended December 31,

Year Ended December 31,

(In millions)
2020

2019

2020

2019

Research and development
$

52.4

$

38.3

$

180.6

$

145.9

General and administrative

16.8

15.1

67.1

61.7

Total operating expenses

69.2

53.4

247.7

207.6

Stock-based compensation expense

(6.6

)

(5.2

)

(25.7

)

(19.3

)

Non-GAAP operating expenses
$

62.6

$

48.2

$

222.0

$

188.3

Total operating expenses for the fourth quarter ended December 31, 2020 were $69.2 million compared to $53.4 million for the same period in 2019. Stock-based compensation expense for the fourth quarter ended December 31, 2020 was $6.6 million, compared to $5.2 million for the same period in 2019. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the fourth quarter ended December 31, 2020 were $62.6 million, compared to $48.2 million for the same period in 2019.

Total operating expenses in 2020 were $247.7 million, compared to $207.6 million in 2019. Stock-based compensation expense in 2020 was $25.7 million, compared to $19.3 million in 2019. Non-GAAP total operating expenses, which exclude excluding stock-based compensation expense, were $222.0 million and $188.3 million in 2020 and 2019, respectively.

The increase in operating expenses in the full year and fourth quarter was due primarily to headcount growth and facilities expansion to support the advancement of our clinical trials and manufacturing capabilities. The full year and fourth quarter increase was partially offset by a decrease in travel and corporate costs arising from the COVID-19 pandemic.

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of December 31, 2020 were $692.0 million, compared to $384.3 million as of December 31, 2019. The balance as of December 31, 2020 includes a $30.0 million milestone from Pfizer for the initiation of the AFFINE trial for giroctocogene fitelparvovec and a $5.0 million milestone from Pfizer for our C9ORF72 collaboration with Pfizer.

In August 2020, we entered into an Open Market Sale Agreement with Jefferies LLC providing for the sale of up to $150.0 million of our common stock from time to time in ‘at-the-market’ offerings under our shelf registration statement. Through February 19, 2021, we sold 1,034,762 shares of our common stock pursuant to this agreement for net proceeds of approximately $15.7 million.

Initial Financial Guidance for 2021

On a GAAP basis, we expect total operating expenses in the range of approximately $285 million to $305 million in 2021, which includes non-cash stock-based compensation expense.

We expect non-GAAP total operating expenses, excluding estimated non-cash stock-based compensation expense of approximately $30 million, in the range of approximately $255 million to $275 million.

Conference Call

Sangamo will host a conference call today, February 24, 2021, at 5:00 p.m. Eastern Time, which will be open to the public. The call will also be webcast with live Q&A and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 1795427. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 1795427.

On February 24, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported a corporate and financial update for the fourth quarter and full-year ended December 31, 2020 (Press release, G1 Therapeutics, FEB 24, 2021, View Source [SID1234575538]).

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"With the recent approval of COSELA, we have a tremendous opportunity to introduce an effective and innovative therapy to proactively address chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer," said Jack Bailey, Chief Executive Officer of G1 Therapeutics. "The launch is underway with our partners at Boehringer Ingelheim, and the initial interest among medical oncologists and oncology nurses is extremely promising. COSELA has a broad mechanism of action, and as such, we are taking a tumor-agnostic approach to the development of COSELA as we advance it into and through multiple Phase 2 and registrational studies. We are confident in the potential for COSELA and look forward to delivering on our goal of improving the lives of as many people living with cancer as possible."

Fourth Quarter 2020 and Recent Highlights

Commercial

COSELA Approved by U.S. Food and Drug Administration (FDA): On February 12, 2021, the FDA approved COSELA for injection to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive stage small cell lung cancer (ES-SCLC). It is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to the start of chemotherapy. COSELA is expected to be commercially available through G1’s specialty distributor partner network in early March. (Press release here)
Clinical

Initiated Pivotal Trial of COSELA in Patients with First Line Colorectal Cancer in the Fourth Quarter of 2020: Patient enrollment has begun in a ~300 patient randomized, double-blind placebo-controlled pivotal registrational trial of COSELA in colorectal cancer. The primary endpoint is myelosuppression; secondary endpoints include progression free survival, overall survival, and patient reported outcomes. The data readout is expected in the first half of 2023.
Announced New Upcoming Registrational Trial of COSELA in First-line / Second Line Metastatic Triple-Negative Breast Cancer (mTNBC); Initiation Expected in First Half of 2021: The Company expects to initiate a randomized, double-blind placebo-controlled registrational trial of COSELA in mTNBC in the first half of 2021. The trial is expected to enroll approximately 250 participants, with approximately 170 in the first line cohort. The trial will enroll patients who are both PD-L1-positive and PD-L1-negative in the first-line cohort. The primary endpoint is overall survival; secondary endpoints include patient-reported outcomes measures, safety/tolerability, myeloprotective measures, and progression-free survival. (Press release here)
Announced Two Upcoming Phase 2 Trials of COSELA in First-Line Metastatic Bladder Cancer (mUC) and Second Line / Third Line Non-Small Cell Lung Cancer (NSCLC); Initiation Expected in the First Half of 2021: The Company expects to initiate Phase 2 trials of COSELA in first-line treatment of locally advanced or metastatic bladder cancer (locally advanced or metastatic urothelial carcinoma, or mUC) and second- and third-line treatment of NSCLC, both of which are known immunogenic tumors, in the first half of 2021. Both trials are designed to evaluate the anti-tumor efficacy of COSELA.
Entered into Clinical Trial Collaboration for Upcoming First-Line Locally Advanced or Metastatic Bladder Cancer (mUC) Trial: G1 has entered into a clinical trial collaboration with the alliance between Merck KGaA, Darmstadt, Germany and Pfizer whereby the alliance will contribute clinical supply of the checkpoint inhibitor avelumab to the G1-sponsored and funded first-line mUC trial.
Presented Final Data from the Randomized Phase 2 Trial of COSELA in mTNBC at the 2020 San Antonio Breast Cancer Symposium (SABCS): New data presented at the SABCS meeting showed that COSELA significantly improved overall survival (OS) in patients with mTNBC treated with COSELA prior to administration of a chemotherapy regimen of gemcitabine/carboplatin (GC) compared with GC alone, and that COSELA enhanced immune system function. Compared to GC alone (Group 1), statistically significant improvements in OS were achieved in both COSELA arms (Group 2: HR=0.31, p=0.0016; Group 3: HR=0.40, p=0.0004). As of the data cutoff of July 17, 2020, the median OS was 12.6 months in patients receiving GC alone, not yet reached for Group 2, and 17.8 months in Group 3. The median OS for Groups 2 and 3 combined was 19.8 months (HR=0.37, p<0.0001). Patients with both PD-L1-positive and PD-L1-negative tumors treated with COSELA and GC demonstrated improvement in OS compared to patients receiving GC alone, with the PD-L1-positive subset achieving statistically significant improvement. Data from T-cell clonality analysis suggest that administering COSELA prior to chemotherapy enhanced immune system function. (Poster here)
Presented Updated Results from Phase 1b Monotherapy Trial of Rintodestrant in ER+, HER2- Breast Cancer at the 2020 SABCS: In a heavily pre-treated patient population, G1’s oral selective estrogen receptor degrader (SERD) rintodestrant showed evidence of clinical activity as monotherapy, including a clinical benefit rate of 30%. Safety and tolerability findings across all doses, including the 600 mg and 1,000 mg expansion cohorts, were consistent with previously reported data. These findings supported the Company’s decision to move the 800mg dose into the ongoing 40-patient Phase 2 combination trial with CDK4/6 inhibitor palbociclib. The data readout is expected in the second quarter of 2021. (Poster here)
Corporate

On February 23, 2021, the Board of Directors adopted the G1 Therapeutics, Inc. 2021 Inducement Equity Incentive Plan (the "Plan"). There are 500,000 shares of our common stock reserved under the Plan to be used exclusively for grants of awards to individuals that were not previously employees or directors of G1, as an inducement material to the individual’s entry into employment with G1 within the meaning of Rule 5635(c)(4) of the Nasdaq Listing Rules. The Plan was approved by Board of Directors without stockholder approval pursuant to Rule 5635(c)(4), and the terms and conditions of the Plan are substantially similar to G1’s stockholder-approved 2017 Equity Incentive Plan, as amended.
Fourth Quarter and Full Year 2020 Financial Results

As of December 31, 2020, cash and cash equivalents totaled $207.3 million, compared to $269.2 million as of December 31, 2019.

Subsequent to December 31, 2020, between January 14th, 2021 and February 9th, 2021, we sold 3,513,027 shares of common stock pursuant to our 2018 sales agreement for "at the market offerings" with Cowen and Company, LLC, resulting in $86.4 million in net proceeds. This ATM offering is now closed. In addition, the Company now has access to $30 million of the remaining $80M of our debt financing facility with Hercules Capital upon achievement of the FDA approval of COSELA milestone.

License revenue for the fourth quarter of 2020 was $16.5 million, primarily related to an upfront payment for our license agreement with Simcere recognized following the transfer of the related technology and know-how which occurred during the period. In addition, we recognized revenue for existing inventory transfers related to our license agreements with Genor and EQRx, as well as revenue for reimbursable clinical trial costs due from EQRx. License revenue for the full-year 2020 was $45.3 million.

Operating expenses for the fourth quarter of 2020 were $40.6 million, compared to $36.6 million for the fourth quarter of 2019. GAAP operating expenses include stock-based compensation expense of $4.8 million for the fourth quarter of 2020, compared to $4.5 million for the fourth quarter of 2019. Operating expenses for the full-year 2020 were $141.8 million, compared to $129.0 million for the prior year. Stock-based compensation expense for the full-year 2020 was $18.8 million, compared to $16.4 million for the prior year.

Research and development (R&D) expenses for the fourth quarter of 2020 were $16.4 million, compared to $24.5 million for the fourth quarter of 2019. The decrease in R&D expenses was primarily due to decreases in clinical program costs, external costs related to discovery and preclinical development, and costs for manufacturing pharmaceutical active ingredients. R&D expenses for the full-year 2020 were $73.3 million, compared to $89.0 million for the prior year.

General and administrative (G&A) expenses for the fourth quarter of 2020 were $24.3 million, compared to $12.1 million for the fourth quarter of 2019. The increase in G&A expenses was largely due to an increase in compensation due to increases in headcount, pre-commercialization activities, medical affairs costs, and professional fees and other administrative costs necessary to support our operations. G&A expenses for the full-year 2020 were $68.5 million, compared to $40.0 million for the prior year.

The net loss for the fourth quarter of 2020 was $25.3 million, compared to $35.4 million for the fourth quarter of 2019. Net loss for the full-year 2020 was $99.3 million, compared to a net loss of $122.4 million for the prior year. The basic and diluted net loss per share for the fourth quarter of 2020 was $(0.67) compared to $(0.94) for the fourth quarter of 2019. The basic and diluted net loss per share for the full-year 2020 was $(2.62) compared to $(3.27) for the full-year 2019.

Financial Guidance

The Company expects its current financial position to be sufficient to fund its operations and capital expenditures into 2023.

Webcast and Conference Call

G1 will host a webcast and conference call at 4:30 p.m. ET today to provide a corporate and financial update for the fourth quarter and full-year 2020 ended December 31, 2020. The live call may be accessed by dialing (866) 763-6020 (domestic) or (210) 874-7713 (international) and entering the conference code: 5267698. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.
WARNINGS AND PRECAUTIONS

Injection-Site Reactions, Including Phlebitis and Thrombophlebitis

COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis, which occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. Monitor patients for signs and symptoms of injection-site reactions, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA. Injection-site reactions led to discontinuation of treatment in 3 (1%) of the 272 patients.
Acute Drug Hypersensitivity Reactions

COSELA administration can cause acute drug hypersensitivity reactions, which occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). Monitor patients for signs and symptoms of acute drug hypersensitivity reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA.
Interstitial Lung Disease/Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, including COSELA, with which it occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. Monitor patients for pulmonary symptoms of ILD/pneumonitis. For recurrent moderate (Grade 2) ILD/pneumonitis, and severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue COSELA.
Embryo-Fetal Toxicity

Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose.
ADVERSE REACTIONS

Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis.

Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%).

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each).

Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA.

The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.
DRUG INTERACTIONS

COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin).

On February 24, 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 fourth quarter ended December 31, 2020 (Press release, Fate Therapeutics, FEB 24, 2021, View Source [SID1234575537]).

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"2020 was a pivotal year for Fate Therapeutics. We demonstrated the clinical safety and therapeutic activity of engineered iPSC-derived NK cell therapy as patients with relapsed / refractory lymphoma achieved objective responses across our FT516 and FT596 Phase 1 studies. We successfully worked with the FDA to enable clinical investigation of FT538, the first-ever CRISPR-edited, iPSC-derived cell therapy, and FT576, the first-ever cell therapy engineered with four functional anti-tumor modalities, in patients with multiple myeloma. We also made strong progress with our strategic partners, Ono Pharmaceutical and Janssen, in leveraging the unique advantages of our iPSC product platform to advance multiplexed-engineered CAR NK and CAR T-cell product candidates toward clinical development for solid tumors," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We look forward to a promising 2021 where we expect to have clinical read-outs across our programs, treat patients with the first-ever iPSC-derived CAR T-cell therapy, submit IND applications for two iPSC-derived CAR NK cell programs targeting novel antigens in solid tumors, and open our second cGMP manufacturing facility for an additional 40,000 square feet of capacity."

Clinical Programs

FT516 (hnCD16) NK Cell Product Candidate

Reported Positive Interim Clinical Data for B-cell Lymphoma. In December 2020, the Company reported positive interim data from its Phase 1 study of FT516 in combination with rituximab for patients with relapsed / refractory B-cell lymphoma (BCL) who have previously failed or progressed on CD20-targeted monoclonal antibody therapy. As of a November 16, 2020 cutoff date, three patients in the second dose cohort (90 million cells per dose) and one patient in the third dose cohort (300 million cells per dose) had each received two FT516 treatment cycles, each cycle consisting of three days of outpatient lympho-conditioning, one dose of rituximab, and three once-weekly infusions of FT516 with IL-2 cytokine support. Three of four relapsed / refractory patients achieved an objective response, including two complete responses, following the second FT516 treatment cycle. The two-cycle treatment regimen was well-tolerated, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting. No dose-limiting toxicities (DLTs), no FT516-related serious adverse events (AEs), no FT516-related grade 3 or greater AEs, and no events of any grade of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) were reported by investigators. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected.
Phase 1 Dose Escalation Ongoing at 900 Million Cells. The Phase 1 clinical trial is designed to assess the safety and determine the maximum dose of FT516 as a monotherapy for the treatment of relapsed / refractory acute myeloid leukemia (AML) and in combination with CD20-targeted monoclonal antibody therapy for the treatment of relapsed / refractory BCL (NCT04023071). Dose escalation is ongoing at 900 million cells per dose in both disease regimens.
FT596 (CAR19 + hnCD16 + IL-15RF) NK Cell Product Candidate

Presented Patient Case Study Demonstrating Clinical Activity in Refractory DLBCL. The case study, which was presented at the 62nd Annual Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2020, described a heavily pre-treated patient with diffuse large B-cell lymphoma (DLBCL) who was enrolled in the first dose cohort (30 million cells) and achieved a partial response following administration of a single dose of FT596 as monotherapy. The patient subsequently received a second, single dose of FT596, which resulted in a deepening response as evidenced by further decreases in both tumor size and metabolic activity. No DLTs, no FT596-related serious AEs, and no events of any grade of CRS, ICANS, or GvHD were reported by the investigator. The patient had previously received seven prior treatment regimens, including five rituximab-containing regimens as well as autologous stem cell transplantation, and was most recently refractory to an experimental natural killer (NK) cell therapy regimen comprised of fludarabine and cyclophosphamide lympho-conditioning followed by ex vivo expanded, donor-derived NK cells, IL-2, and rituximab.
First CLL Patient Treated. The Phase 1 clinical trial is designed to assess the safety and determine the maximum dose of FT596 as a monotherapy and in combination with CD20-targeted monoclonal antibody therapies for the treatment of relapsed / refractory BCL and chronic lymphocytic leukemia (CLL) (NCT04245722). Dose escalation for the treatment of BCL is ongoing in the second dose cohorts of 90 million cells as monotherapy and in combination with rituximab. The first patient with CLL has been treated in the first dose cohort of 30 million cells as monotherapy, and the Company plans to begin enrollment in combination with obinutuzumab upon clearance of the first monotherapy dose cohort.
First Patients Treated in Investigator-initiated Study for Relapse Prevention following HSCT. Investigators from the Masonic Cancer Center, University of Minnesota, are conducting a Phase 1 study of FT596 in combination with rituximab for the prevention of relapse in patients with BCL who have undergone autologous hematopoietic stem cell transplant (HSCT) and are considered high risk for early relapse (NCT04555811). The first patients have been treated in the first dose cohort of 90 million cells.
FT538 (hnCD16 + IL-15RF + CD38KO) NK Cell Product Candidate

First AML Patients Treated. FT538 is the first-ever CRISPR-edited cell therapy derived from a clonal master engineered induced pluripotent stem cell (iPSC) line, and is modified with three functional components to enhance innate immunity. The Phase 1 clinical trial is designed to assess three once-weekly doses of FT538 as a monotherapy for patients with relapsed / refractory AML and in combination with the CD38-targeted monoclonal antibody daratumumab for patients with relapsed / refractory multiple myeloma (NCT04614636). The first patients with AML have been treated in the first dose cohort of 100 million cells per dose.
Second IND Allowed by FDA for AML in Combination with CD38-targeted Monoclonal Antibody. In December 2020, the FDA allowed a second Investigational New Drug (IND) application for the clinical investigation of three once-weekly doses of FT538 in combination with daratumumab for the treatment of relapsed / refractory AML. The Phase 1 clinical trial is sponsored and managed by investigators from the Masonic Cancer Center, University of Minnesota. CD38 expression on leukemic blasts has been observed in a significant number of AML patients, indicating the potential of CD38 as a therapeutic target for AML.
FT576 (CAR-BCMA + hnCD16 + IL-15RF + CD38KO) NK Cell Product Candidate

IND Application Allowed by FDA for Multiple Myeloma. FT576 is an investigational, off-the-shelf, chimeric antigen receptor (CAR) NK cell cancer immunotherapy targeting B-cell maturation antigen (BCMA). FT576 is derived from a clonal master iPSC line engineered with four functional components designed to enable multi-antigen targeting of myeloma cells, augment antibody-dependent cellular cytotoxicity (ADCC), enhance cell persistence and prevent anti-CD38 monoclonal antibody-induced fratricide. In December 2020, the U.S. Food & Drug Administration (FDA) allowed the Company’s IND application for clinical investigation of FT576 in patients with relapsed / refractory multiple myeloma who have failed at least two lines of therapy. The Company is preparing to initiate a Phase 1 clinical trial to assess single-dose and multi-dose treatment regimens of FT576 as monotherapy and in combination with CD38-targeted monoclonal antibody therapy.
Preclinical Programs for Solid Tumors

CAR MICA/B Program Featured in Oral Presentation at ASH (Free ASH Whitepaper). Dr. Kai W. Wucherpfennig, Chair of Cancer Immunology and Virology and Director of the Center for Cancer Immunotherapy Research at Dana-Farber Cancer Institute (DFCI), presented preclinical data highlighting the Company’s development of FT536, a novel CAR NK cell product candidate targeting the alpha-3 domain of the pan-tumor associated stress antigens MICA and MICB. While MICA/B are selectively expressed at high levels on many solid tumors, proteolytic shedding of MICA/B is a prominent mechanism of tumor escape from NK cell-mediated destruction. Several recent publications have shown that targeting the alpha-3 domain strongly inhibits MICA/B shedding, resulting in a substantial increase in the cell surface density of MICA/B and restoration of NK cell-mediated tumor immunity. The Company plans to submit an IND application in the second half of 2021 to initiate a Phase 1 clinical trial of FT536 for the treatment of solid tumors.
CAR B7H3 Program Featured in Oral Presentation at SITC (Free SITC Whitepaper). During an oral session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November 2020, preclinical data from the Company’s collaboration with Dr. Jeffrey S. Miller, Professor of Medicine and Deputy Director of the Masonic Comprehensive Cancer Center, University of University of Minnesota, was presented that highlighted the specificity and activity of CAR T cells incorporating a proprietary camelid single-domain antibody fragment targeting B7H3, a pan-tumor associated antigen expressed on a wide range of cancers. The Company is currently incorporating novel CAR constructs targeting B7H3 into multiplexed engineered master iPSC lines for selection of a preclinical development candidate.
Other Corporate Highlights

Preclinical Milestone Reached under iPSC-derived CAR T-Cell Collaboration with Ono Pharmaceutical. In December 2020, the Company and Ono reviewed a preclinical data package for an iPSC-derived CAR T-cell product candidate incorporating Ono’s proprietary antigen binding domain targeting a cancer-specific antigen expressed on certain solid tumors. The Company and Ono elected to continue preclinical development of the iPSC-derived CAR T-cell product candidate under the collaboration, and the Company received a $10 million milestone fee from Ono. Ono maintains an option to develop and commercialize the iPSC-derived CAR T-cell product candidate in all territories of the world, with the Company retaining the option to co-develop and co-commercialize the product candidate in the United States and Europe under a joint arrangement with Ono whereby Fate is eligible to share at least 50% of the profits and losses.
Completed $460 Million Public Offering. In January 2021, the Company completed an underwritten public offering of 5.1 million shares of its common stock priced at $85.50 per share and, in lieu of common stock to certain investors, pre-funded warrants to purchase 0.3 million shares of its common stock priced at $85.499 per pre-funded warrant. Net proceeds to the Company were approximately $432 million.
Fourth Quarter 2020 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of December 31, 2020 were $482.9 million. This amount does not include net proceeds to the Company of approximately $432 million from the January 2021 underwritten public offering.
Total Revenue: Revenue was $15.9 million for the fourth quarter of 2020, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $39.0 million for the fourth quarter of 2020, which includes $5.3 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $10.3 million for the fourth quarter of 2020, which includes $3.4 million of non-cash stock-based compensation expense.
Other Expenses: Other expenses, net were $19.7 million, which includes a $20.1 million non-cash charge equal to the fair value change of certain contingent milestone payments that will be owed to Memorial Sloan Kettering Cancer Center upon the Company’s achievement of a specified clinical milestone with an iPSC-derived CAR T-cell product candidate and the subsequent appreciation of the Company’s common stock price per share.
Shares Outstanding: Common shares outstanding were 87.7 million, and preferred shares outstanding were 2.8 million, as of December 31, 2020. Each preferred share is convertible into five common shares. Common shares outstanding does not include 5.4 million common shares, including 0.3 million common shares issuable upon exercise of pre-funded warrants, that were issued in the January 2021 underwritten public offering.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Wednesday, February 24, 2021 at 5:00 p.m. ET to review financial and operating results for the quarter ended December 31, 2020. In order to participate in the conference call, please dial 877-303-6235 (domestic) or 631-291-4837 (international) and refer to conference ID 6368962. The live webcast can be accessed under "Events & Presentations" in the Investors & Media 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 an open-label, 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 an open-label, multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor 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 an open-label, 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 an open-label, 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).

On February 24, 2021 Coherus BioSciences, Inc. ("Coherus" or the "Company", Nasdaq: CHRS), reviewed recent corporate events and reported financial results for the quarter and full year ended December 31, 2020 (Press release, Coherus Biosciences, FEB 24, 2021, View Source [SID1234575536]).

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UDENYCA (pegfilgrastim-cbqv) delivered strong results in 2020:

$476 million in net sales for the full year; $110 million for the fourth quarter.
With excellent commercial execution in the face of COVID-19 headwinds, maintained position as leading pegfilgrastim biosimilar in the United States with 21% share of the overall pegfilgrastim market and nearly 50% share of the pre-filled syringe segment.
Financial strength to execute on our immuno-oncology and biosimilar pipeline and commercial plans:

Cash flow from operating activities was $154 million for 2020 and $33 million for the fourth quarter of 2020.
Coherus had cash and cash equivalents of $541 million at December 31, 2020.
Net income was $132 million for 2020, or $1.62 per share on a diluted basis, and for the fourth quarter of 2020 was $10 million, or $0.12 per share on a diluted basis.
"We are very pleased with the strong performance of UDENYCA in the face of challenging COVID-19 conditions in 2020 and with the recent progress of our biosimilar pipeline candidates," said Denny Lanfear, Chief Executive Officer of Coherus. "With our recently announced collaboration with Junshi Biosciences, we are building a focused immuno-oncology franchise atop the strong foundation of UDENYCA and our late-stage Lucentis, Avastin and Humira biosimilar candidates. As our commercial biosimilar portfolio expands, we expect to generate strong cash flows to leverage into commercialization of toripalimab, if approved, as well as development of PD-1 combination therapies to drive longer-term growth."

Pipeline Progress and Recent Corporate Highlights

Immuno-oncology collaboration with Junshi Biosciences: In February, Coherus announced a collaboration with Junshi Biosciences for the development and commercialization of Junshi Biosciences’ anti-PD-1 antibody, toripalimab, in the United States and Canada. Upon satisfaction of closing conditions, which is expected to occur in the first quarter 2021, Coherus and Junshi Biosciences will co-develop toripalimab, and Coherus will be responsible for all commercial activities in the United States and Canada.
The U.S. Food and Drug Administration ("FDA") has granted breakthrough therapy designation to toripalimab for third-line nasopharyngeal carcinoma ("NPC"), and Coherus expects the first toripalimab biologics license application ("BLA") to be filed with the FDA for this indication in 2021. On February 20, 2021, Junshi Biosciences announced the approval in China of toripalimab for the treatment of patients with recurrent or metastatic NPC after failure of at least two lines of prior systemic therapy.
Coherus and Junshi Biosciences plan to file additional toripalimab BLA supplements with the FDA over the next three years for multiple rare and highly prevalent tumor types, including non-small cell lung cancer ("NSCLC").

FYB201, a biosimilar Lucentis (ranibizumab) product candidate in collaboration with Bioeq AG: Bioeq expects to file the FYB201 BLA mid-year 2021 following a supportive pre-BLA meeting with the FDA earlier in the first quarter of 2021. Bioeq reviewed new manufacturing data with the FDA which the agency requested last year, as well as other elements of the BLA filing.

CHS-1420, a wholly owned biosimilar Humira (adalimumab) product candidate: The FDA accepted for review the BLA for CHS-1420 and assigned a target action date in December 2021. Coherus plans to launch CHS-1420 on or after July 1, 2023, if approved.

IBI-305, a biosimilar Avastin (bevacizumab) product candidate in collaboration with Innovent Biologics (Suzhou) Co. Ltd: Earlier in the first quarter of 2021, Coherus initiated the three-way pharmacokinetic study required prior to potential BLA submission later this year.
Fourth Quarter and Full Year 2020 Financial Results

Net product revenue, consisting of net sales of UDENYCA, was $110.4 million for the fourth quarter of 2020 compared to $123.9 million for the same period in 2019. The decline was primarily due to an increase in discounts and allowances incurred, which was partially offset by an increase in the number of units of UDENYCA sold. Net product revenue for 2020 was $475.8 million compared to $356.1 million for 2019, an increase of $119.7 million. The increase was primarily due to an increase in the number of units of UDENYCA sold, which was partially offset by an increase in discounts and allowances incurred during the year ended December 31, 2020.

Research and development (R&D) expenses for the fourth quarter of 2020 were $44.6 million, compared to $34.9 million for the same period in 2019. The increase was mainly due to increased clinical development activities as well as payments for certain negotiation rights for pipeline development. R&D expense for 2020 was $142.8 million compared to $94.2 million for 2019, an increase of $48.6 million. The increase was primarily due to costs incurred in support of the BLA submission for CHS-1420 and for development activities related to other biosimilar product candidates.

Selling, general and administrative (SG&A) expenses were relatively unchanged quarter-over-quarter and year-over-year. SG&A expenses for the fourth quarter of 2020 were $37.7 million, compared to $36.1 million for the same period in 2019. SG&A expenses for 2020 were $139.1 million, compared to $137.0 million for 2019.

Cash and cash equivalents were $541.2 million as of December 31, 2020, compared to $177.7 million as of December 31, 2019. During 2020, Coherus generated $154.1 million in operating cash flow, used $14.4 million in investing activities, including $7.5 million in upfront and milestone payments to collaborators, and received net cash proceeds of $223.9 million from financing activities related to the issuance of convertible notes due in 2026, less issuance costs and the purchase of related capped call options, as well as proceeds from the exercise of stock options and from purchases under the stock purchase plan.

Net income for the fourth quarter of 2020 was $9.7 million, or $0.12 per share on a diluted basis, compared to a net income of $39.2 million, or $0.53 per share on a diluted basis for the same period in 2019. Net income for 2020 was $132.2 million, or $1.62 per share on a diluted basis, compared to a net income of $89.8 million, or $1.23 per share on a diluted basis for 2019.

Non-GAAP net income for the fourth quarter of 2020 was $18.6 million, or $0.23 per share on a diluted basis, compared to non-GAAP income of $56.7 million, or $0.75 per share on a diluted basis for the same period in 2019. Non-GAAP net income for 2020 was $176.7 million, or $2.16 per share on a diluted basis, compared to non-GAAP income of $133.1 million, or $1.82 per share on a diluted basis for 2019. See "Non-GAAP Financial Measures" below for a discussion on how Coherus calculates non-GAAP net income and a reconciliation to the most directly comparable GAAP measures.

2021 Guidance

Coherus projects lower UDENYCA net sales revenue in 2021 compared to 2020. Starting from a seasonally low first quarter impacted by customer buying patterns and COVID-19, Coherus expects UDENYCA revenue and market share to rise over the remainder of the year, assuming treatment patterns normalize as the general population is vaccinated against COVID-19.

Excluding upfront, milestone and development expenses related to the recently announced collaboration with Junshi Biosciences, which is expected to close in the first quarter of 2021, Coherus projects R&D and SG&A expenses combined will increase in 2021 to a range of $310 million to $350 million, with external R&D spending focused on manufacturing-related activities in preparation for the potential launch of CHS-1420, if approved, and development activities for IBI-305 and for additional presentations of UDENYCA.

This financial guidance excludes the effects of any potential future strategic acquisitions, collaborations or investments, the exercise of rights or options related to collaboration programs, and any other transactions or items not yet identified or quantified. This guidance is subject to a number of risks and uncertainties. See Forward-Looking Statements described in the section below.

On February 24, 2021 Amgen (NASDAQ:AMGN) reported that it will present at the Cowen 41st Annual Virtual Healthcare Conference at 12:50 p.m. ET on Thursday, March 4, 2021 (Press release, Amgen, FEB 24, 2021, https://investors.amgen.com/news-releases/news-release-details/amgen-present-cowen-41st-annual-healthcare-conference [SID1234575535]). Murdo Gordon, executive vice president of Global Commercial Operations and Peter H. Griffith, executive vice president and chief financial officer at Amgen will present at the conference. Live audio of the presentation can be accessed from the Events Calendar on Amgen’s website, www.amgen.com, under Investors. A replay of the webcast will also be available on Amgen’s website for at least 90 days following the event.

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

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