On February 24, 2021 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported financial results for the year ended December 31, 2020 and provided a summary of recent business and clinical highlights (Press release, Zymeworks, FEB 24, 2021, View Source [SID1234575542]).

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"Throughout 2020, we initiated and advanced several clinical trials and achieved important regulatory milestones for zanidatamab and ZW49," said Ali Tehrani, Ph.D., Zymeworks’ President & CEO. "This has set up 2021 to be a data-rich year for both of our lead clinical assets as well as new preclinical candidates and therapeutic platforms, and we are well resourced to deliver on our priorities."

2020 Business Highlights and Recent Developments

Clinical Data Continues to Support Goal of Establishing Zanidatamab as the Foundational HER2 Targeted Therapy Across Multiple HER2-Positive Cancers
Updated clinical data was recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium for zanidatamab, in both HER2-expressing biliary tract cancer (BTC) and gastroesophageal adenocarcinoma (GEA). Overall zanidatamab was well tolerated with the majority of treatment-related adverse events being mild or moderate in severity. With respect to antitumor activity, both refractory BTC and GEA compare favorably to current standard of care and emerging treatments. These data support zanidatamab’s broad therapeutic potential as a foundational therapy across multiple HER2-expressing cancers.
Zanidatamab Advances in Accelerated Pivotal Trial Paving the Way for Commercialization
The U.S. Food and Drug Administration granted Breakthrough Therapy designation to zanidatamab for BTC, enabling an Accelerated Approval pathway for the global pivotal trial (HERIZON-BTC-01) for zanidatamab monotherapy in patients with previously treated HER2 gene-amplified BTC and submission of a Biologics License Application (BLA) as early as 2022. A second pivotal trial evaluating zanidatamab as first-line treatment for advanced HER2-positive GEA is on track to launch mid-2021. Zanidatamab received additional drug review special designations in the U.S. and the European Union that are expected to help to expedite clinical development of both trials.
ZW49 Demonstrates Antitumor Activity and Differentiated Safety Profile; Expansion Cohorts Enrolling while Dose Escalation Continues
ZW49, a bispecific antibody-drug conjugate targeting HER2, has begun enrolling patients into the expansion cohort portion of the ongoing Phase 1 clinical trial. Interim data were recently presented and showed no dose limiting toxicities or treatment-related hematologic, pulmonary, or liver toxicity. The majority of treatment-related adverse events were mild or moderate in severity with the most common being keratitis, fatigue, and diarrhea. ZW49 demonstrated antitumor activity at all dose levels evaluated in the once every three week regimen, including confirmed partial responses and stable disease per RECIST 1.1., and dose escalation is continuing at 3 mg/kg once every three weeks. Three indication-specific expansion cohorts (HER2-positive breast cancer, HER2-positive GEA, and a basket cohort of other HER2-positive cancers) utilizing the 2.5 mg/kg once every three week regimen have also been initiated to better ascertain antitumor activity in more homogeneous patient populations.
Milestone Payments Received and Deal Values Increase for Partnership Deals
Throughout 2020, partnerships continued to expand and additional milestones were achieved upon BeiGene initiating multiple clinical studies with zanidatamab, Merck and BMS expanding Azymetric and EFECT collaborations, and Iconic/Exelixis entering into a licensing deal for a ZymeLink ADC. Zymeworks has nine active collaborations that could result in up to $8.6 billion in potential milestone payments in addition to royalties on potential product sales.
Strengthened Balance Sheet
In January 2020, Zymeworks completed an upsized $320.8 million public financing to accelerate and expand global development of its lead clinical candidates, zanidatamab and ZW49, and support further advancement of its novel preclinical programs.
Financial Results for the Year Ended December 31, 2020

Revenue was $39.0 million in 2020 compared to $29.5 million in 2019. For both years, revenue related to non-recurring upfront fees, milestone payments, option fees, research support and other payments under our licensing and collaboration agreements. Revenue for 2020 included $15.0 million from BeiGene for development milestones, $12.0 million from BMS for an expansion fee and $12.0 million from other partners for research support, partner revenue, drug supply and other payments. Revenue for 2019 included $8.0 million from Lilly for achievement of a development milestone, $7.5 million and $3.5 million from BMS and Daiichi Sankyo, respectively, for exercise of commercial license options, $3.5 million for recognition of deferred revenue relating to our licensing and collaboration agreement with BeiGene, and $7.0 million from our partners for other development milestones, research support and other payments.

Research and development expense was $168.5 million in 2020 compared to $115.9 million in 2019. The $52.6 million increase related primarily to additional clinical trial activities and associated drug manufacturing costs for zanidatamab, as well as an increase in salaries and benefits expense resulting from a higher headcount. Expenses also increased in 2020 for higher development activity for ZW49 and an increase in-licensing and milestone payments for discovery and research activities. Research and development expense included non-cash stock-based compensation expense of $12.3 million in 2020 and $14.3 million in 2019.

General and administrative expense was $57.9 million in 2020 compared to $64.2 million in 2019. General and administrative expense included non-cash stock-based compensation expense of $16.1 million in 2020 and $34.2 million in 2019. Excluding stock-based compensation expense, general and administrative expense increased by $11.9 million year over year primarily due to an increase in salaries and benefits expense resulting from a higher headcount, as well as higher insurance and professional services expenses.

Net loss was $180.6 million in 2020 compared to $145.4 million in 2019. The increase in net loss was primarily due to the increases in research and development expenses referred to above partially offset by lower general and administrative expense and higher revenue and other income.

Zymeworks expects research and development expenditures to increase over time in line with the advancement and expansion of the Company’s clinical development of its product candidates, as well as its ongoing preclinical research activities. Additionally, Zymeworks anticipates continuing to receive revenue from its existing and future strategic partnerships, including technology access fees and milestone-based payments. However, Zymeworks’ ability to receive these payments is dependent upon either Zymeworks or its collaborators successfully completing specified research and development activities.

As of December 31, 2020, Zymeworks had $451.6 million in cash resources consisting of cash, cash equivalents, short-term investments and certain long-term investments.

On February 24, 2021 Arcus Biosciences, Inc. (NYSE:RCUS), an oncology-focused biopharmaceutical company working to create best-in-class cancer therapies reported financial results for the fourth quarter and year ended December 31, 2020 and provided operational highlights (Press release, Arcus Biosciences, FEB 24, 2021, View Source [SID1234575541]).

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"With $735 million in cash at the end of the year, plus $220 million from Gilead’s recent equity investment, we are extremely well-positioned to accelerate the advancement of our pipeline, initiate our first registrational trials for domvanalimab, and deliver multiple readouts from the randomized portions of our ongoing clinical studies," said Terry Rosen, Ph.D., CEO. "These readouts include the interim analysis for ARC-7, our Phase 2 randomized study evaluating domvanalimab and zimberelimab in first-line, PD-L1 high, non-small cell lung cancer, in the second quarter of 2021, as well as initial data from our randomized studies evaluating our A2a/A2b adenosine receptor antagonist, etrumadenant. In 2021, we also expect to continue to advance AB680, our CD73 inhibitor, in pancreatic cancer and to expand the clinical program for this first-in-class small molecule to other tumor types. We are also pleased to announce that we received IND clearance for AB308 in January, allowing us to achieve a new milestone with five molecules now in clinical development, and we expect to advance at least one new small molecule program into clinical development in the second half of 2021."

Corporate and Partnership Updates

Announced that Gilead increased its ownership in Arcus from approximately 13.0% to 19.5%. The $220 million received from this investment will enable Arcus to accelerate the development plans for Arcus’s five clinical-stage molecules.
Continued to advance our clinical collaboration with AstraZeneca for the conduct of PACIFIC-8, a registrational trial designed to evaluate domvanalimab and durvalumab in Stage 3 non-small cell lung cancer (NSCLC). We expect this trial to start in the second half of 2021.
Expanded our relationship with Wuxi Biologics and Arcus’s portfolio of molecules targeting the ATP-adenosine axis through a licensing and collaboration agreement with WuXi for anti-CD39 antibodies. We expect to file an IND for an antibody from this program in 2022 and to develop it in combination with our first-in-class small molecules targeting other points of intervention in this pathway.
As part of our option agreement with Taiho for their development and commercialization of Arcus’s molecules in Japan and other territories in Asia (excluding China), Taiho is planning to initiate clinical development of zimberelimab, our anti-PD-1 antibody, to advance assets in their portfolio. To date, Taiho has exercised its option rights to zimberelimab and etrumadenant.
Domvanalimab (FcR-silent TIGIT antibody)

Recent Highlights:

Initiated ARC-10, Arcus’s first registrational trial, evaluating domvanalimab + zimberelimab vs. zimberelimab vs. chemotherapy in first-line PD-L1≥50%, locally advanced or metastatic NSCLC. This "two-in-one" study involves a single trial to support the potential approvals of both zimberelimab monotherapy and domvanalimab + zimberelimab, and the timing of the study initiation aligns well with the planned interim analysis for ARC-7 in the second quarter. We expect to initiate other registrational trials for domvanalimab later in the year.
Upcoming Milestones:

Interim analysis from ARC-7, our randomized, three-arm Phase 2 trial ongoing in the U.S. and Asia, evaluating zimberelimab + domvanalimab vs. zimberelimab vs. zimberelimab + domvanalimab + etrumadenant in first-line PD-L1≥50% locally advanced or metastatic NSCLC, is expected in the second quarter of 2021, and we plan to provide a directional update on the data at that time. We expect to present data from this analysis at a medical conference in the second half of 2021.
AB680 (CD73 inhibitor)

Recent Highlights:

Presented promising preliminary data from the dose-escalation portion of ARC-8, our Phase 1/1b study evaluating AB680 in combination with zimberelimab and gemcitabine/nab-paclitaxel (G/NP) in first-line metastatic pancreatic cancer at the ASCO (Free ASCO Whitepaper) GI Conference in January.
As of the efficacy data cut-off date (DCO) of 12/9/20, 17 patients across the four dose-escalation cohorts (25mg, 50mg, 75mg and 100mg) were evaluable for response. In these patients, the objective response rate (ORR) was 41% (three confirmed partial responses (PRs), four PRs pending a second confirmatory scan). One of the confirmed PRs converted to a complete response after the DCO.
The confirmed ORR for Abraxane (nab-paclitaxel), as stated in its FDA approved label for use in combination with gemcitabine, is 23%. To date, PD-1 antibodies have not shown any benefit when added to G/NP in this setting.1,2,3,4
Initiated enrollment of the dose-expansion portion of ARC-8 using a dosing regimen of 100mg of AB680 administered intravenously every two weeks. Due to ARC-8’s rapid enrollment, we expect to open a control arm of AB680 plus G/NP by the end of this quarter, which will inform the design of a potential registrational trial. We and our investigators continue to be encouraged by the number of responses seen in ARC-8, and if data continue to look promising, we anticipate discussing these data with health authorities later in the year.
Nearing completion of a study with the oral formulation of AB680 in healthy volunteers. Having both oral and intravenous formulations of AB680 will give us flexibility to customize AB680’s dosing regimens based upon the combination partner.
Initiated enrollment of our first cohort evaluating the combination of AB680 and etrumadenant. This cohort is part of our ongoing ARC-6 metastatic castrate-resistant prostate cancer (mCRPC) platform study. We also intend to evaluate AB680 + etrumadenant combinations in our ARC-9 metastatic colorectal cancer (mCRC) platform study and to evaluate other AB680 combinations in other settings and tumor types.
Upcoming Milestones:

More mature data from ARC-8, including data from the dose-escalation and dose-expansion cohorts, are expected to be presented at a medical conference in the second half of 2021.
Etrumadenant (A2a/A2b adenosine receptor antagonist)

Recent Highlights:

Initiated the Stage 2 randomized portion of the etrumadenant + zimberelimab + docetaxel cohort in ARC-6, our ongoing Phase 1b/2 platform study evaluating etrumadenant-based combinations in mCRPC. Stage 2 was initiated after passing the Stage 1 futility assessment and is evaluating etrumadenant + zimberelimab + docetaxel vs. a docetaxel control arm.
Initiated ARC-9, a randomized Phase 1b/2 platform study to evaluate etrumadenant in combination with other agents in 2L+ mCRC based on intriguing durability and response data, particularly those in late-line mCRC patients, from the ARC-3 study.
Upcoming Milestones:

Updated data from ARC-3, including overall survival and progression-free survival data for the 3L+ mCRC cohort, will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting being held April 10-15, 2021 (week 1) and May 17-21, 2021 (week 2).
Initial data from Stage 1 of ARC-6 are expected to be presented in the second quarter of 2021. These data will be from the etrumadenant + zimberelimab + docetaxel cohort in 2L mCRPC in patients that failed androgen deprivation therapy. Initial data from the Stage 2 randomized portion, which compares this etrumadenant combination to docetaxel, are expected to be presented in the second half of 2021.
Initial randomized data from ARC-4, our ongoing study evaluating etrumadenant + zimberelimab + chemotherapy vs. zimberelimab + chemotherapy in EGFRmut tyrosine kinase inhibitor (TKI)-relapsed and refractory NSCLC, are expected to be presented at a medical conference in the second half of 2021.
Other Programs

Received IND clearance for AB308, Arcus’s FcR-enabled anti-TIGIT antibody, in January. We plan to evaluate AB308 in settings where the depletion of TIGIT-bearing cancer cells could be beneficial, such as certain hematological malignancies.
Our Phase 1/1b dose-escalation study for AB308, which will leverage Arcus’s anti-TIGIT antibody development experience, is designed to quickly establish the safety, pharmacokinetics and pharmacodynamics of AB308 in combination with zimberelimab and could enable the advancement of AB308 into a registrational trial by year-end 2021.
Initiation of clinical development for our HIF-2a inhibitor is anticipated in the second half of 2021.
Financial Results for the Fourth Quarter and Full Year Ended December 31, 2020

Cash, cash equivalents and investments were $735.1 million as of December 31, 2020, compared to $188.3 million at December 31, 2019. After December 31, 2020, Arcus received an additional $220.4 million in proceeds from the sale of equity to Gilead. The increase from December 31, 2019 to December 31, 2020 was primarily due to net proceeds of $326.2 million from the May 2020 public equity offering and $375 million received upon closing of the Gilead agreements, partially offset by cash utilized for our operations. We expect cash, cash equivalents and investments on-hand to be sufficient to fund operations at least through 2023.
Revenues: Collaboration and license revenues were $9.5 million for the three months ended December 31, 2020, compared to $9.8 million for the same period in 2019. The revenues in 2020 were comprised of $7.7 million from our Gilead collaboration and $1.8 million from our Taiho agreement for both partners’ ongoing rights to access our research and development pipeline. The revenues in 2019 were solely from our Taiho agreement and related to $8.0 million for Taiho’s exercise of its option for rights to zimberelimab as well as $1.8 million for Taiho’s ongoing rights to access our research and development pipeline. Collaboration and license revenues were $77.5 million for the full year ended December 31, 2020, compared to $15.0 million for the same period in 2019.
R&D Expenses: Research and development expenses were $48.7 million for the three months ended December 31, 2020, compared to $20.7 million for the same period in 2019. The increase was primarily due to increases in manufacturing and clinical costs required to supply and conduct our ongoing clinical studies, as well as increases in employee compensation costs driven by an increase in our headcount, approximately $2.6 million of which consists of non-cash stock-based compensation. Research and development expenses were $159.3 million for the full year ended December 31, 2020, compared to $78.5 million for the same period in 2019.
G&A Expenses: General and administrative expenses were $12.8 million for the three months ended December 31, 2020, compared to $6.6 million for the same period in 2019. The increase in expense was due to increases in employee compensation driven by an increase in headcount, approximately $2.9 million of which consists of non-cash stock-based compensation costs. Additional increases in legal and accounting expenses resulted from ongoing public company compliance obligations. General and administrative expenses were $42.4 million for the full year ended December 31, 2020, compared to $25.2 million for the same period in 2019.
Net Loss: Net loss was $51.9 million for the three months ended December 31, 2020, compared to a net loss of $16.6 million for the same period in the prior year. The increase in net loss was primarily attributable to an increase in operating expenses as noted above. Net loss for the full year ended December 31, 2020 was $122.9 million, compared to $84.7 million for the same period in 2019.

On February 24, 2021 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company focused on helping conquer cancer globally through use of its proprietary blood tests, vast data sets and advanced analytics, reported financial results for the quarter and full year ended December 31, 2020 (Press release, Guardant Health, FEB 24, 2021, View Source [SID1234575540]).

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Recent Highlights

Revenue of $78.3 million for the fourth quarter and $286.7 million for the full year of 2020, representing 25% and 34% increases, respectively, over the corresponding periods of 2019
Launched Guardant Reveal, the first blood-only test with a 7-day turnaround time, for residual disease and recurring monitoring in patients with early-stage colorectal cancer
Announced development of tissue-based Comprehensive Genomic Profiling assay to provide a comprehensive product offering to oncologists, and its launch later in 2021
Announced partnership with a premier cancer center in Spain, Vall d’Hebron Institute of Oncology, to build a liquid biopsy laboratory and submitted application for regulatory approval of Guardant360 in Japan
Strengthened balance sheet with $1 billion capital raise and ended 2020 with approximately $2 billion in cash, cash equivalents and marketable securities
"I am proud of the Guardant team for the progress made across our business amidst a uniquely challenging year," said Helmy Eltoukhy, PhD, co-founder and CEO. "Looking ahead in 2021, we will continue to invest aggressively across our business to build the foundations for complete cancer testing to significantly improve outcomes across the continuum of cancer care."

Fourth Quarter 2020 Financial Results

Revenue was $78.3 million for the three months ended December 31, 2020, a 25% increase from $62.9 million for the three months ended December 31, 2019. Precision oncology revenue grew 13% driven predominantly by an increase in clinical testing revenue which grew 47% over the prior year period. There were 17,353 clinical tests and 4,841 biopharmaceutical tests performed during the fourth quarter of 2020. Development services and other revenue increased 148% primarily related to the timing of project related milestones for companion diagnostic development programs.

Gross profit, or total revenue less cost of precision oncology testing and cost of development services and other, was $49.9 million for the fourth quarter of 2020, an increase of $8.9 million from $41.1 million for the corresponding prior year period. Gross margin, or gross profit divided by total revenue, was 64%, as compared to 65% for the corresponding prior year period.

Operating expenses were $141.1 million for the fourth quarter of 2020, as compared to $67.0 million for the corresponding prior year period, an increase of 110%.

Stock-based compensation expense was $56.8 million for the fourth quarter of 2020, as compared to $5.1 million for the fourth quarter of 2019.

Net loss attributable to Guardant Health, Inc. common stockholders was $93.7 million for the fourth quarter of 2020, as compared to $25.2 million for the corresponding prior year period. Net loss per share attributable to Guardant Health, Inc. common stockholders was $0.94 for the fourth quarter of 2020, as compared to $0.27 for the corresponding prior year period.

Non-GAAP adjusted EBITDA loss was $29.8 million for the fourth quarter of 2020, as compared to a $17.1 million loss for the corresponding prior year period.

Full Year 2020 Financial Results

Revenue for the year ended December 31, 2020 was $286.7 million, a 34% increase from $214.4 million for the year ended December 31, 2019. Precision oncology revenue increased 31% driven predominantly by an increase in clinical testing revenue which grew 70% over the prior year. There were 63,254 clinical tests and 15,983 biopharmaceutical tests performed during 2020. Development services revenue increased 49% primarily due to new collaboration agreements entered in the year ended December 31, 2020 as well as progression of existing collaboration projects from biopharmaceutical customers for companion diagnostic development and regulatory approval services completed during the year ended December 31, 2020.

Gross profit was $194.2 million for the year ended December 31, 2020, an increase of $50.5 million from $143.7 million for the year ended December 31, 2019. Gross margin was 68% for the year ended December 31, 2020, as compared to 67% for the year ended December 31, 2019.

Operating expenses were $449.1 million for the year ended December 31, 2020, as compared to $226.0 million for the year ended December 31, 2019, an increase of 99%.

Stock-based compensation expense was $144.1 million for the year ended December 31, 2020, as compared to $17.0 million for the year ended December 31, 2019.

Net loss attributable to Guardant Health, Inc. common stockholders was $253.8 million for the year ended December 31, 2020, as compared to $75.7 million for the year ended December 31, 2019. Net loss per share attributable to Guardant Health, Inc. common stockholders was $2.60 for the year ended December 31, 2020, as compared to $0.84 for the year ended December 31, 2019.

Non-GAAP adjusted EBITDA loss was $85.2 million for the full year of 2020, as compared to a $53.3 million loss for the corresponding prior year period.

Cash, cash equivalents and marketable securities were $2.0 billion as of December 31, 2020.

2021 Guidance

Guardant Health expects full year 2021 revenue to be in the range of $360 million to $370 million, representing 26% to 29% growth over full year 2020. Clinical volumes for 2021 are expected to be greater than 90,000 tests, growing at least 42% over 2020.

Webcast Information

Guardant Health will host a conference call to discuss the fourth quarter 2020 financial results after market close on Thursday, February 24, 2021 at 2:00 pm Pacific Time / 5:00 pm Eastern Time. A webcast of the conference call can be accessed at View Source The webcast will be archived and available for replay for at least 90 days after the event.

Non-GAAP Measure

We believe that the exclusion of certain income and expenses in calculating non-GAAP Adjusted EBITDA can provide a useful measure for investors when comparing our period-to-period core operating results, and when comparing those same results to that published by our peers. To derive Adjusted EBITDA, we remove from GAAP results the impact of income (expenses) attributable to material non-cash items, specifically stock-based compensation and fair value remeasurements due to the subjectivity, management judgment, and market fluctuations involved around these amounts. We exclude certain other items because we believe that these income (expenses) do not reflect expected future operating expenses. Additionally, certain items are inconsistent in amounts and frequency, making it difficult to perform a meaningful evaluation of our current or past operating performance.

This non-GAAP financial measure is not intended to be considered in isolation from, as substitute for, or as superior to, the corresponding financial measure prepared in accordance with GAAP. There are limitations inherent in non-GAAP financial measures because they exclude charges and credits that are required to be included in a GAAP presentation, and do not present the full measure of our recorded costs against its revenue. In addition, our definition of the non-GAAP financial measures may differ from non-GAAP measures used by other companies.

Definition of Non-GAAP Adjusted EBITDA

Non-GAAP "Adjusted EBITDA" is defined as net loss attributable to Guardant Health, Inc. common stockholders before: (i) interest income,(ii) interest expense (iii) provision for (benefit from) income taxes, (iv) depreciation and amortization expense, (v) other (income) expense, net, (vi) stock-based compensation expense, (vii) adjustments relating to non-controlling interest and contingent consideration and, if applicable in a reporting period, and (viii) acquisition-related expenses, and other non-recurring items.

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).