On February 24, 2022 Kineta, Inc., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, reported that the company will participate in Cowen’s 42nd Annual Health Care Conference which is taking place virtually on March 7 – 9, 2022 (Press release, Kineta, FEB 24, 2022, View Source;utm_medium=rss&utm_campaign=kineta-invited-to-participate-in-the-cowen-42nd-annual-health-care-virtual-conference [SID1234608971]). Members of Kineta’s management team will be available for one-on-one meetings during the conference. The conference incorporates presentations, fireside chats and innovative panel discussions hosted by members of the Cowen research team that focus on various aspects of the health care industry.

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On February 24, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported fourth quarter and full year 2021 financial results and corporate updates (Press release, Iovance Biotherapeutics, FEB 24, 2022, View Source [SID1234608970]).

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Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "Throughout 2021, we continued to build upon the strength of clinical data for Iovance TIL therapy in multiple solid tumor types and treatment settings. Highlights included long-term clinical data for one-time treatment with lifileucel in metastatic melanoma, the potential to increase response rates for TIL therapy in combination with pembrolizumab as an earlier treatment for melanoma, cervical and head and neck cancers, as well as an important proof-of-concept for Iovance TIL therapy in non-small cell lung cancer. We also advanced our genetically modified TIL pipeline and expect to initiate our first clinical study of a gene-edited TIL product candidate later this year. Our top priority remains our ongoing work to address feedback from the U.S. Food and Drug Administration (FDA) regarding the potency assays for lifileucel to support our planned biologics license application (BLA) submission in the first half of this year. We remain increasingly confident in the broad potential for TIL as the next class of paradigm-shifting therapy for cancer patients with significant unmet need."

Full Year 2021 Highlights and Recent Corporate Updates

Regulatory

Potency assays for lifileucel: Following FDA feedback regarding the potency assays for lifileucel, Iovance has continued ongoing work developing and validating its potency assays and has engaged in discussions with the FDA during the second half of 2021. The anticipated BLA submission for lifileucel continues to be planned for the first half of 2022. Resolution of the potency assay for lifileucel in melanoma is also a key step towards regulatory plans in other indications.
U.S. FDA Fast Track Designation for lifileucel in combination with pembrolizumab in metastatic melanoma: The FDA granted fast track designation for lifileucel in combination with pembrolizumab for the treatment of immune checkpoint inhibitor (ICI) naïve (frontline) metastatic melanoma based on the unmet medical need and potential advantages for this combination over available care.
Clinical

Iovance TIL therapy (lifileucel) in metastatic melanoma:
Lifileucel in late line (post-anti-PD-1) melanoma: Follow up data as assessed by investigators from Cohort 2 (n=66) in the C-144-01 study of lifileucel in advanced melanoma were presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting. The overall response rate (ORR) was 36.4% (4.5% complete response rate and 31.8% partial response rate) and median duration of response (DOR) was not reached at 33.1 months of median study follow up. Iovance expects to report clinical data from the pivotal melanoma Cohort 4 as assessed by an independent review committee (IRC) in 2022 in connection with its BLA submission.
Lifileucel in combination with pembrolizumab in early line (anti-PD-1 naïve) melanoma (Cohort 1A in the IOV-COM-202 study): Initial clinical data were presented at ASCO (Free ASCO Whitepaper) 2021 and updated results were presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2021. The updated ORR was 60% and the complete response rate was 30% at a median follow up of 11.5 months in Cohort 1A (n=10). Based on these results, Iovance intends to expand Cohort 1A and define a development strategy in early line melanoma in 2022.

Iovance TIL therapy (LN-145) in non-small cell lung cancer (NSCLC):

LN-145 monotherapy in metastatic NSCLC (mNSCLC): Results from Cohort 3B in the IOV-COM-202 study were highlighted at SITC (Free SITC Whitepaper) 2021. LN-145 showed a 21.4% ORR in the full analysis set (n=28) and 25% in the efficacy-evaluable set (n=24). One complete response and one partial response were ongoing at 20.7 months and 3.0 months, respectively, at a median study follow up of 9.8 months. These results demonstrated activity for TIL therapy in heavily pretreated mNSCLC patients who received one or more prior systemic therapies, including anti-PD-1 therapy, and support the ongoing development strategy for LN-145 in second line mNSCLC patients in the IOV-LUN-202 study.
LN-145 in second-line mNSCLC: Enrollment is ongoing at more than 30 active clinical sites in the U.S., Canada and Europe for the IOV-LUN-202 study of LN-145 in patients with mNSCLC following a single line of approved systemic therapy. Iovance is engaged in discussions with the FDA about IOV-LUN-202 and intends to incorporate FDA feedback into the study design to support registration.

Lifileucel in cervical cancer: The C-145-04 study is investigating lifileucel for the treatment of metastatic cervical cancer patients following chemotherapy (Cohort 1), after chemotherapy and anti-PD-1/PD-L1 therapy (Cohort 2), and in combination with pembrolizumab in patients who have not had therapy for advanced disease (Cohort 3).

Lifileucel monotherapy in advanced cervical cancer: Iovance is engaged in regulatory discussions about a potential BLA for lifileucel in cervical cancer and intends to execute an updated registrational strategy based on FDA dialogue and feedback.
Lifileucel in combination with pembrolizumab in early line cervical cancer: Initial results from Cohort 3 (n=14) in the C-145-04 study were presented at SITC (Free SITC Whitepaper) 2021 and demonstrated an ORR of 57.1% at a median follow up of 7.6 months.
Iovance TIL therapy combinations in additional solid tumor cancers: In Cohort 2A of the IOV-COM-202 study, Iovance is also investigating TIL therapy in combination with pembrolizumab in patients with head and neck squamous cell carcinoma (HNSCC) who are naïve to therapy with ICIs. Updated Cohort 2A data were presented at SITC (Free SITC Whitepaper) 2021 and demonstrated a 38.9% ORR (n=18) at a median study follow up of 7.8 months. The IOV-COM-202 study is also investigating TIL combinations in patients with NSCLC including TIL therapy plus pembrolizumab (Cohort 3A) and TIL plus ipilimumab/nivolumab (Cohort 3C).
Next-Generation Genetically Modified TIL Products and Research Programs

Iovance expects to initiate its first clinical study of a genetically modified TIL product candidate in 2022. The lead program, designated IOV-4001, leverages the TALEN technology licensed from Cellectis S.A. to inactivate PD-1 expression in the TIL product.
Additional targets for genetic modification using the TALEN technology, including double knock-out programs, are in preclinical development.
Approaches to increase TIL potency using CD39/69 double negative TILs and gene knock-in targets are also in preclinical development.
Accepted abstracts at the upcoming Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR Tandem Meetings, April 23-26, 2022, describe TIL products manufactured from cryopreserved tumor samples shipped from Australia and a potential approach to optimize TIL memory-like phenotype and increase functionality during the manufacturing process.
Iovance continues to advance additional research and preclinical studies of next generation TIL therapies and related technologies, including a novel IL-2 analog (IOV-3001).
Manufacturing

Iovance Cell Therapy Center (iCTC): Commissioning activities were completed and clinical manufacturing of TIL product commenced at the iCTC, Iovance’s 136,000 square foot cell therapy manufacturing facility, in the third quarter of 2021. Commercial manufacturing remains on track to commence with a potential BLA approval.
Generation 3 (Gen 3) manufacturing: TIL product manufactured using a shorter 16-day third generation process (Gen 3) is being investigated in cohorts of metastatic melanoma patients in the IOV-COM-202 study as well as NSCLC patients in the IOV-LUN-202 study.
Corporate

Cash position of $602.1 million at December 31, 2021 is expected to be sufficient into 2024.
A strong organization of approximately 350 employees with an average of more than four years of cell therapy experience is in place to advance research, development, manufacturing, and commercial launch preparations.
Iovance continues to expand its intellectual property portfolio and currently owns more than 35 granted or allowed U.S. and international patents for TIL compositions and methods of treatment and manufacturing in a broad range of cancers. Iovance’s Gen 2 patent rights are expected to provide exclusivity into 2038. Iovance’s portfolio also includes patent applications and granted patents directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic TIL modifications, tumor digest and fragment compositions and methods (including cryopreservation), and combinations of checkpoint inhibitors and TIL products.
Fourth Quarter and Full Year 2021 Financial Results

Iovance had $602.1 million in cash, cash equivalents, investments and restricted cash at December 31, 2021 compared to $635.0 million at December 31, 2020. The cash position is expected to be sufficient to fund current and planned operations into 2024.

Jean-Marc Bellemin, Chief Financial Officer, stated, "With late-stage clinical assets in our pipeline, as well as a strong balance sheet and investments focused on launch preparations, we are well positioned to execute our operating plan. We are confident in our prospects to deliver new treatment options to patients with great unmet need while enhancing shareholder value."

Net loss for the fourth quarter ended December 31, 2021, was $99.3 million, or $0.63 per share, compared to a net loss of $68.4 million, or $0.47 per share, for the fourth quarter ended December 31, 2020. Net loss for the full year period ended December 31, 2021, was $342.3 million, or $2.23 per share, compared to a net loss of $259.6 million, or $1.88 per share, for the full year period ended December 31, 2020.

Research and development expenses were $75.6 million for the fourth quarter ended December 31, 2021, an increase of $23.1 million compared to $52.5 million for the fourth quarter ended December 31, 2020. Research and development expenses were $259.0 million for the full year period ended December 31, 2021, an increase of $57.3 million compared to $201.7 million for the full year ended December 31, 2020.

The increase in research and development expenses in the fourth quarter 2021 over the prior year period was primarily attributable to an increase in costs associated with growth of the internal research and development team, including stock-based compensation expense, and increases in clinical trial costs and facility related costs associated with the iCTC. The increase in research and development expenses in the full year 2021 over the prior full year period was primarily attributable to growth of the internal research and development team and an increase in clinical trial costs and facility related costs associated with the iCTC.

General and administrative expenses were $23.8 million for the fourth quarter ended December 31, 2021, an increase of $7.7 million compared to $16.1 million for the fourth quarter ended December 31, 2020. General and administrative expenses were $83.7 million for the full year period ended December 31, 2021, an increase of $23.5 million compared to $60.2 million for the full year ended December 31, 2020.

The increases in general and administrative expenses in the fourth quarter and full year 2021 compared to the prior year periods were primarily attributable to an increase in costs associated with growth of the internal general and administrative team, including stock-based compensation expense, and an increase in intellectual property filing related costs.

Webcast and Conference Call

Iovance will host a conference call today at 4:30 p.m. ET to discuss the fourth quarter and full year 2021 financial results and corporate updates. The conference call dial-in numbers are 1-(844) 646-4465 (domestic) or 1-(615) 247-0257 (international) and the access code is 2877242. The live webcast can be accessed in the Investors section of the company’s website at View Source The archived webcast will be available for a year in the Investors section at www.iovance.com.

On February 24, 2022 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported financial results for the fourth quarter and full year ended December 31, 2021, and recent business achievements (Press release, Ionis Pharmaceuticals, FEB 24, 2022, View Source [SID1234608969]).

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"During 2021, we made significant progress towards achieving our vision of becoming a leading fully-integrated biotechnology company. We advanced our commercial strategy and go-to-market plans for our near-term commercial opportunities, eplontersen, olezarsen and donidalorsen. Our collaboration with AstraZeneca to jointly develop and commercialize eplontersen enables us to potentially maximize benefit for patients, bolster our commercial organization and accelerate preparations for our near-term product launches. Most recently, we initiated Phase 3 studies with olezarsen in patients with severely high triglycerides and donidalorsen in patients with hereditary angioedema. This expands our Phase 3 pipeline to six medicines addressing eight indications. We also advanced our technology, positioning us to build on our leadership in RNA-targeted therapeutics and add value for our future medicines," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We look forward to a steady cadence of catalysts throughout this year, highlighted by eplontersen Phase 3 data in patients with hATTR polyneuropathy planned for mid-year. We expect to file for regulatory approval for eplontersen before year end, assuming positive data. We also expect to make continued advancements to expand and diversify our technology. Based on our anticipated near- and mid-term catalysts, we believe we are well positioned to drive increasing value for patients and shareholders."

2021 Summary Financial Results

Exceeded 2021 financial guidance
$810 million in total revenues
$695 million of operating expenses on a non-GAAP basis(1) and $840 million on a GAAP basis
Net income of $116 million on a non-GAAP basis(1) and a net loss of $29 million on a GAAP basis
Well capitalized with cash and short-term investments of $2.1 billion at year-end, enabling accelerating investments in 2022 with the goal to drive substantial future growth
Recent Marketed Products Highlights

SPINRAZA: the global market leader for the treatment of spinal muscular atrophy (SMA) patients of all ages
$1.9 billion in worldwide SPINRAZA sales in 2021
More than 11,000 patients worldwide on therapy at the end of 2021 across commercial, expanded access and clinical trial settings
Biogen continued to expand upon SPINRAZA’s competitive profile through the ongoing ASCEND, RESPOND and DEVOTE studies
TEGSEDI and WAYLIVRA: important medicines approved for the treatment of patients with hereditary TTR amyloidosis with polyneuropathy and familial chylomicronemia syndrome, respectively
TEGSEDI and WAYLIVRA achieved innovative drug pricing in Brazil
WAYLIVRA is under review in Brazil for the treatment of familial partial lipodystrophy (FPL). If approved, WAYLIVRA will be the first approved treatment for patients with FPL in Brazil
Fourth Quarter 2021 and Recent Events

Advancing Ionis’ near-term commercial opportunities toward the market
Eplontersen: potential to change the standard-of-care for patients with TTR amyloidosis (ATTR)
Initiated a collaboration with AstraZeneca to jointly develop and commercialize eplontersen valued at up to $3.6 billion in an upfront and potential milestone payments, plus cost-sharing and royalties
The U.S. FDA granted orphan drug designation to eplontersen for the treatment of patients with ATTR
Olezarsen: potential first-in-class treatment for patients with elevated triglycerides
Initiated the Phase 3 CORE study of olezarsen in patients with severe hypertriglyceridemia (SHTG) with data expected in 2024
Reported positive data from the Phase 2 study of olezarsen in patients with moderate hypertriglyceridemia and at high risk for or with established cardiovascular disease in the European Heart Journal
Donidalorsen: potential best-in-class prophylactic treatment for patients with hereditary angioedema (HAE)
Initiated the Phase 3 OASIS-HAE study of donidalorsen in patients with HAE with data expected in 2024
Presented positive data from the Phase 2 study of donidalorsen in patients with HAE at the ACAAI annual scientific meeting
Advancing Ionis’ leading cardiovascular disease franchise
AstraZeneca presented new data from the Phase 1 multiple ascending dose study of ION449 (AZD8233) targeting PCSK9 in statin treated subjects with dyslipidemia at the AHA scientific sessions
Addressing substantial unmet medical needs with Ionis’ broad neurological disease franchise
Biogen licensed ION306 (BIIB115) for the treatment of SMA with the potential for extended dosing intervals, resulting in a $60 million payment from Biogen
Biogen reported that while the Phase 3 VALOR study of tofersen in patients with SOD1-ALS did not meet the primary endpoint, signs of reduced disease progression across multiple secondary and exploratory endpoints were observed. Biogen continues to engage with regulators to discuss a path forward for tofersen
Roche announced plans to initiate a new Phase 2 study of tominersen in patients with Huntington’s disease based on new findings from a post-hoc analysis of the Phase 3 GENERATION-HD1 study
Initiated the Phase 1/2 HALOS study of ION582 (BIIB121) in patients with Angelman syndrome, resulting in a $10 million payment from Biogen
Advanced three neurological disease programs, resulting in $23 million in payments from Biogen
Dynacure advanced IONIS-DNM2-2.5Rx, resulting in $7.5 million in payments from Dynacure
Advancing additional programs in Ionis’ clinical pipeline for diseases with unmet medical need
Initiated a Phase 2 study of sapablursen (formerly known as IONIS-TMPRSS6-LRx) in patients with polycythemia vera, the second indication for sapablursen
Reported topline results from the Phase 2 study of cimdelirsen (formerly known as IONIS-GHR-LRx) in patients with uncontrolled acromegaly, achieving proof of mechanism with a strong indication of proof of concept
Advanced two metabolic disease programs, resulting in $40 million in payments from AstraZeneca
2022 Pipeline Milestones(2)

2021 Financial Results and 2022 Financial Guidance

"Over the last year, we achieved numerous pipeline and technology milestones, advanced multiple medicines towards the market and accelerated preparations for our near-term commercial launches. We also exceeded our 2021 financial guidance, driven by revenue from advancing multiple partnered programs and by strengthening and streamlining our business," said Elizabeth L. Hougen, chief financial officer of Ionis. "We have a long history of financial responsibility that provides us with a strong financial foundation. With more than $2 billion of cash and a substantial and sustainable base of commercial and R&D revenues, we are well positioned to accelerate our investments in 2022 to drive substantial future growth."

2022 Financial Guidance

Ionis’ full year 2022 financial guidance consists of the following components (on a non-GAAP basis)(1):

(1)All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards. In 2021 and 2020 all non-GAAP amounts also excluded expenses related to the Akcea Merger and restructured commercial operations and the related tax effects. Please refer to the section below titled "Financial Impacts of Akcea Merger and Restructured Commercial Operations" for a summary of the costs specific to these transactions. Additionally, please refer to the detailed reconciliation of non-GAAP and GAAP measures, which is provided later in this press release.

(2)Partnered program milestones are based on partners’ most recent publicly available disclosures.

Revenue

Ionis’ revenue was comprised of the following (amounts in millions):

The Company’s revenue increased by more than 10 percent compared to 2020 driven in large part by significant partner payments across multiple partnered programs. In 2021, the Company earned $200 million from its new collaboration with AstraZeneca to jointly develop and commercialize eplontersen. The Company also earned more than $160 million from Biogen for advancing several neurology disease programs.

The Company successfully completed the transition of its TEGSEDI and WAYLIVRA operations in the EU and North America to Sobi in the first and second quarters of 2021, respectively. The decrease in TEGSEDI and WAYLIVRA revenue in 2021 compared to 2020 was due to the shift from product sales to distribution fees based on net sales generated by Sobi. As part of the transition, Ionis restructured its commercial operations resulting in substantial cost savings.

Operating Expenses

Ionis is advancing a large late-stage pipeline and as a result, its non-GAAP operating expenses increased in 2021 compared to 2020. Higher R&D expenses were driven by the expanded number of Phase 3 studies the Company was conducting, which doubled over the course of 2021 from 3 to 6 studies. Additionally, the Company recognized $35 million in R&D expense in the third quarter of 2021 for licensing Bicycle Therapeutic’s technology. Lower SG&A expenses primarily reflected operating efficiencies achieved from integrating Akcea and restructuring the Company’s commercial operations.

Net Loss Attributable to Ionis Common Stockholders

Net loss attributable to Ionis’ common stockholders in 2021 decreased compared to 2020 for the reasons discussed above. Also contributing to the decrease in Ionis’ net loss in 2021 compared to 2020 was the non-cash adjustment of the valuation allowance Ionis recorded against its federal net deferred tax assets in 2020.

Balance Sheet

As of December 31, 2021, Ionis had cash, cash equivalents and short-term investments of $2.1 billion, compared with $1.9 billion as of December 31, 2020.

The Company revised its 2020 amounts to reflect the simplified convertible instruments guidance the Company adopted retrospectively on January 1, 2021.

Webcast

Ionis will conduct a webcast today at 11:30 a.m. Eastern time to discuss this announcement and related activities. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address.

On February 24, 2022 Invitae (NYSE: NVTA), a leading medical genetics company, reported financial and operating results for the fourth quarter and year ended December 31, 2021 (Press release, Invitae, FEB 24, 2022, View Source [SID1234608968]).

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

"2021 was another year of industry leading growth and the addition of almost 1 million patients onto the Invitae platform, providing further evidence that the Invitae vision and one-of-a-kind testing, digital health and data network are ushering in the era of genomic health management," said Sean George, Ph.D., co-founder and CEO of Invitae. "Looking into 2022, we intend to maintain our focus on driving that shift to a healthcare ecosystem underscored by genomic information and management, while demonstrating operational excellence and charting a clear path towards operating cash flows."

Full Year and Fourth Quarter 2021 Financial Results

Generated revenue of $460.4 million in 2021, including $126.1 million in the fourth quarter.
Reported billable volume of 1.17 million in 2021, including 327,000 in the fourth quarter.
Total active healthcare provider accounts in 2021 totaled 18,458, more than 50 percent growth since the beginning of 2020.
Active pharma and commercial partnerships grew to 178, an increase of approximately 170 percent since the beginning of 2020 driving continued revenue growth from Invitae’s data and data services platform to pharma, health system and software and services partners.
Total patient population is more than 2.5 million with over 62 percent available for data sharing.
Achieved gross profit of $111.8 million in 2021, including $30.0 million in the fourth quarter. Non-GAAP gross profit was $168.4 million in 2021, and $46.0 million in the fourth quarter.
Total operating expense, which excludes cost of revenue, for the full year 2021 was $503.4 million. Operating expense for the fourth quarter of 2021 was $244.6 million. Non-GAAP operating expense was $771.1 million for the full year 2021, and $215.7 million in the fourth quarter.

Net loss for the full year 2021 was $379.0 million, or a $1.80 net loss per share. For the fourth quarter of 2021, Invitae reported a net loss of $205.1 million, or a $0.90 net loss per share. Non-GAAP net loss was $654.3 million, or a $3.10 non-GAAP net loss per share in 2021. For the fourth quarter of 2021, Invitae reported a non-GAAP net loss of $184.7 million, or a $0.81 non-GAAP net loss per share.

At December 31, 2021, cash, cash equivalents, restricted cash and marketable securities totaled $1.06 billion as compared with $1.25 billion as of September 30, 2021. Net increase in cash, cash equivalents, restricted cash, and marketable securities was $695 million in 2021, and a net decrease of $196.7 million for the fourth quarter. Cash burn was $195.6 million in the fourth quarter of 2021. Cash burn for the quarter would have been $186.1 million excluding the cash paid for acquisitions.

Guidance
The company has issued 2022 annual revenue guidance of year-over-year revenue growth of 40 percent, or approximately $640 million. New guidance categories for 2022 include gross margin and cash burn measures. Gross margin for 2022 is expected to be between 42-45 percent with cash burn, including cash used for acquisition-related activities, expected to be in the range of $600-$650 million in 2022, a more than $200 million year-over-year reduction.

Webcast and Conference Call Details
Management will host a conference call and webcast today at 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time to discuss financial results and recent developments. To access the conference call, please register at the link below:

View Source

Upon registering, each participant will be provided with call details and a conference ID.

The live webcast of the call and slide deck may be accessed here or by visiting the investors section of the company’s website at ir.invitae.com. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the company’s website.

On February 24, 2022 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing potentially curative therapies leveraging CRISPR-based technologies, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2021 (Press release, Intellia Therapeutics, FEB 24, 2022, View Source [SID1234608967]).

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"We began 2022 with strong momentum, executing against our strategic priorities for the advancement of our CRISPR-based pipeline and platform. We continued to make steady progress across our multiple clinical programs. In addition, we nominated two new development candidates – NTLA-2003 and NTLA-6001. Notably, we are looking forward to sharing additional data from the landmark study of NTLA-2001 next week," said Intellia President and Chief Executive Officer John Leonard, M.D. "In parallel, we continue to propel our own scientific innovation, as well as leverage external capabilities from across the industry to generate the next wave of clinical candidates. As part of this strategy, we completed several important transactions to further bolster our industry-leading genome editing toolbox and pipeline. Intellia is well-positioned to extend its leadership position as we aim to harness the full potential of genomic medicines."

Fourth Quarter 2021 and Recent Operational Highlights

In Vivo Program Updates

NTLA-2001 for ATTR amyloidosis: NTLA-2001 is the first investigational CRISPR-based therapy to be systemically delivered to edit genes inside the human body and has the potential to be the first single-dose treatment for transthyretin (ATTR) amyloidosis. Delivered with the Company’s in vivo lipid nanoparticle (LNP) technology, NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, potentially lifelong reduction in transthyretin (TTR) protein after a single dose. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc. (Regeneron).
Intellia will be hosting a virtual investor event on February 28, 2022, at 4:30 p.m. ET to present additional interim clinical data from the ongoing Phase 1 study of NTLA-2001 in patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). Data to be presented will come from all four ATTRv-PN dose cohorts in Part 1, the single-ascending dose portion, and include safety and serum TTR reduction for Cohorts 3 and 4, as well as an early look at durability across all cohorts. The Company remains on track to initiate Part 2, a single-cohort expansion, in the polyneuropathy arm in the first quarter of 2022.
Intellia continues to dose patients in the cardiomyopathy arm of the Phase 1 study with NTLA-2001. In December 2021, Intellia initiated dosing in new dose-escalation cohorts in patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM) as part of the expanded Phase 1 study. Enrollment across both ATTRv-PN and ATTR-CM patient populations is expected to complete in 2022.
NTLA-2002 for HAE: NTLA-2002 leverages Intellia’s proprietary in vivo LNP delivery technology to knock out the KLKB1 gene in the liver with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of hereditary angioedema (HAE). This investigational approach aims to prevent attacks for people living with HAE by providing continuous suppression of plasma kallikrein activity following a single dose and to eliminate the significant treatment burden associated with currently available HAE therapies.
In December 2021, Intellia announced the first patient was dosed with NTLA-2002. The first-in-human study is expected to evaluate the safety, tolerability and activity of NTLA-2002 in adults with Type I or Type II HAE.
The Company anticipates presenting interim data from the Phase 1/2 study in the second half of 2022. The data are expected to characterize the emerging safety and activity profile of NTLA-2002, and to potentially demonstrate preliminary proof of concept.

NTLA-3001 for AATD-associated lung disease: NTLA-3001 is a wholly owned, first-in-class, CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of alpha-1 antitrypsin deficiency (AATD)-associated lung disease. It is designed with the aim to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to eliminate the need for sub-optimal weekly IV infusions of A1AT augmentation therapy or lung transplant in severe cases.
Intellia continues to conduct Investigational New Drug (IND)-enabling activities for NTLA-3001, with plans to file an IND or IND-equivalent in 2023.
NTLA-2003 for AATD-associated liver disease: NTLA-2003 is a wholly owned in vivo knockout development candidate for the treatment of AATD-associated liver disease. It is designed to inactivate the SERPINA1 gene responsible for the production of abnormal A1AT protein in the liver. This approach aims to halt the progression of liver disease and eliminate the need for liver transplant in severe cases.
Today, Intellia announced the nomination of a new development candidate, NTLA-2003, for treatment of AATD-associated liver disease. The Company is advancing towards IND-enabling activities for this program.
Ex Vivo Program Updates

NTLA-5001 for AML: NTLA-5001 is an autologous T cell receptor (TCR)-T cell therapy engineered to target the Wilms’ Tumor 1 (WT1) antigen for the treatment of all genetic subtypes of acute myeloid leukemia (AML).
In the fourth quarter of 2021, Intellia initiated screening of patients in the Phase 1/2a study of NTLA-5001 for patients with AML. The Company has begun enrolling patients and expects to dose its first patient in the coming weeks. Later this year, the Company plans to provide guidance around timing of the first expected data readout, with the goal of demonstrating clinical proof of concept for its TCR-based platform.
NTLA-6001 for CD30+ Lymphomas: NTLA-6001 is Intellia’s wholly owned allogeneic CAR-T development candidate targeting CD30 for the treatment of CD30-expressing hematologic cancers, including relapsed or refractory classical Hodgkin’s Lymphoma (cHL).
Today, Intellia announced the nomination of its first ex vivo allogeneic development candidate, NTLA-6001, for CD30-expressing hematologic cancers, including cHL. NTLA-6001 is developed using Intellia’s proprietary allogeneic cell engineering platform, which leverages a novel combination of sequential gene edits. Preclinical data presented on its differentiated allogeneic engineering platform showed allogeneic T cells were shielded from immune rejection, both host T and natural killer (NK) cell attack.
Intellia is advancing towards IND-enabling activities and plans to present preclinical data leading to the development of NTLA-6001 at an upcoming scientific conference in 2022.
Research and Corporate Updates

Modular Platform and Pipeline Expansion: Intellia is expanding its industry-leading genome editing platform and scientific leadership through editing, delivery and cell engineering innovations that may enable broader in vivo and ex vivo applications.
Following the nomination of NTLA-2003, Intellia plans to advance at least one new in vivo development candidate by the end of 2022.
The Company plans to highlight additional advances to its proprietary technology capabilities, including both genome editing and delivery tools, at upcoming scientific conferences in 2022.
Collaboration Updates
In February, the Company executed a licensing and collaboration agreement with ONK Therapeutics Ltd. (ONK) for the development of allogeneic CRISPR-edited NK cell therapies for the treatment of cancer. The agreement grants ONK a non-exclusive license to Intellia’s proprietary ex vivo CRISPR/Cas9-based genome editing platform and its LNP-based delivery technologies and exclusive rights to certain guide RNAs for development of up to five NK cell therapies. ONK will be responsible for preclinical and clinical development for the engineered NK cell therapies covered under the agreement. In addition, the agreement grants Intellia options to co-develop and co-commercialize up to two products worldwide with rights to lead commercialization in the U.S.
In December 2021, the Company executed a licensing and collaboration agreement with Kyverna Therapeutics (Kyverna) for the development of KYV-201, an allogeneic CD19 CAR-T cell investigational candidate for the treatment of select autoimmune diseases. This is a novel approach aimed at targeting CD19 for inflammatory diseases as compared to traditional oncology indications. Kyverna will lead and fund preclinical and clinical development for KYV-201 and, as part of the agreement, Intellia granted Kyverna rights to use its proprietary ex vivo CRISPR/Cas9-based allogeneic platform in exchange for an equity stake in Kyverna. Intellia will be eligible to receive certain development and commercial milestone payments, as well as low- to mid-single-digit royalties on potential future sales and may choose to exercise an option to lead U.S. commercialization for KYV-201 under a co-development and co-commercialization agreement.
In October 2021, the Company executed a strategic collaboration with SparingVision to develop novel genomic medicines utilizing Intellia’s proprietary CRISPR/Cas9 technology for the treatment of ocular diseases. In addition, Intellia received an equity stake in SparingVision. As part of the collaboration, Intellia will receive an option for exclusive U.S. commercialization rights for product candidates arising from two of three collaboration targets, eligibility for development and commercial milestone payments, as well as royalties on potential future sales of products arising from the collaboration. The companies will additionally research and develop novel self-inactivating AAV vectors and LNP-based approaches to address delivery of CRISPR/Cas9 genome reagents to the retina.
Corporate Updates
In February, Intellia completed the acquisition of Rewrite Therapeutics, Inc. (Rewrite), a private biotechnology company focused on advancing novel DNA writing technologies. Rewrite’s DNA writing technology may enable a range of precise editing strategies. These include targeted corrections, insertions, deletions and the full range of single-nucleotide changes, which could provide new ways to edit disease-causing genes and broaden the therapeutic potential for genomic medicines.
In February, the Company announced a lease agreement to develop a 140,000-square-foot manufacturing facility in Waltham, Massachusetts, to support the manufacturing of key components for its CRISPR-based investigational therapies. The new manufacturing facility will be Good Manufacturing Practice (GMP) compliant and support both the preclinical through commercial supply for key components of Intellia’s CRISPR-based therapies. Additionally, this facility, in combination with existing capabilities and partnerships, will provide capacity and capabilities in support of Intellia’s expanding pipeline and commercial readiness.
Upcoming Events

The Company will participate in the following events during the first quarter of 2022:

AAAAI Annual Meeting, February 25-28, Phoenix
Cowen Healthcare Conference, March 7, Virtual
Barclays Capital Global Healthcare Conference, March 15, Miami
Guggenheim Healthcare Talks Genomic Medicines and Rare Disease Day, March 31, Virtual
Upcoming Milestones

The Company has set forth the following for pipeline progression:

NTLA-2001 for ATTR amyloidosis:
Report additional interim data from Phase 1 study on February 28
Initiate Part 2, a single-dose expansion cohort, of the Phase 1 study of NTLA-2001 in Q1 2022
Complete enrollment of Phase 1 study for both ATTRv-PN and ATTR-CM subjects in 2022
NTLA-2002 for HAE: Present interim data from Phase 1/2 study in 2H 2022
NTLA-3001 for AATD: Plan to file an IND or IND-equivalent in 2023
NTLA-5001 for AML: Continue to enroll patients in Phase 1/2a study in 2022
NTLA-6001 for CD30+ Lymphomas: Plan to present preclinical data at an upcoming scientific conference in 2022
Pipeline Expansion:
Advance at least one new in vivo development candidate by the end of 2022
Advance additional novel platform capabilities in 2022

Fourth Quarter and Full-Year 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1,086.0 million as of December 31, 2021, compared to $597.4 million as of December 31, 2020. The increase was driven by net proceeds of $648.3 million from a follow-on offering in the third quarter of 2021, $45.3 million of net proceeds from the Company’s "At the Market" (ATM) agreement, $43.1 million in proceeds from employee-based stock plans, and $6.3 million of funding for cost-sharing agreements received from Regeneron. These increases were offset in part by cash used to fund operations of approximately $254.7 million.
Collaboration Revenue: Collaboration revenue increased by $6.3 million to $12.9 million during the fourth quarter of 2021, compared to $6.6 million during the fourth quarter of 2020. This increase was primarily driven by $5.8 million in revenue recorded in 2021 from our joint venture with AvenCell.
R&D Expenses: Research and development expenses increased by $32.9 million to $71.2 million during the fourth quarter of 2021, compared to $38.2 million during the fourth quarter of 2020. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs and expansion of the development organization.
G&A Expenses: General and administrative expenses increased by $11.3 million to $22.1 million during the fourth quarter of 2021, compared to $10.8 million during the fourth quarter of 2020. This increase was primarily related to employee related expenses, including stock-based compensation of $3.8 million.
Net Loss: The Company’s net loss was $81.2 million for the fourth quarter of 2021, compared to $42.2 million during the fourth quarter of 2020.

Conference Call to Discuss Fourth Quarter and Full-Year 2021 Results

The Company will discuss these results on a conference call today, Thursday, February 24, at 8:00 a.m. ET.

To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
Please visit this link for a simultaneous live webcast of the call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at intelliatx.com, beginning on February 24, at 12:00 p.m. ET.