On March 1, 2022 Epizyme (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering transformative therapies for cancer against novel epigenetic targets, reported fourth quarter and full year 2021 financial results and provided business and portfolio updates (Press release, Epizyme, MAR 1, 2022, View Source [SID1234609288]).

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"Epizyme entered 2022 demonstrating continued progress on our commercial efforts to drive prescription growth for TAZVERIK as a monotherapy, as well as advancing our key combination clinical studies, which we believe have the potential to significantly expand the value and reach of TAZVERIK among physicians and patients as the data mature," said Grant Bogle, President and Chief Executive Officer. "In support of our commercialization and development efforts, we continue to make operational changes to reduce our expenses and extend our cash runway, while strategically deploying our resources to the areas we believe may be of highest impact for the company and its stakeholders."

Recent Highlights and 2022 Projected Milestones

TAZVERIK (tazemetostat) commercial progress:
TAZVERIK generated net product revenue of $11.6 million for the fourth quarter and $30.9 million for the full year 2021, including $4.2 million and $7.4 million, respectively, related to the sale of TAZVERIK commercial product for third-party pharmaceutical company use in clinical trials. TAZVERIK commercial net sales in the fourth quarter of 2021 were $7.4 million, representing an increase of approximately 42% when compared to $5.2 million in the third quarter of 2021.
The amount of free goods supplied to patients through Epizyme’s patient assistance program represented approximately 29% of total end user demand for the fourth quarter of 2021 and approximately 24% for the full-year 2021.
Total end user demand in the fourth quarter of 2021 represented a 14% increase over third quarter 2021 levels. This increase was driven primarily by sales for follicular lymphoma (FL).
Global start-up of Phase 3 portion of SYMPHONY-1 study underway; updated safety run-in data from Phase 1b portion expected in 2022: After completing the 30-day waiting period for its protocol amendment submitted to the U.S. Food and Drug Administration (FDA) in December 2021 with 800 mg twice-daily as the recommended Phase 3 dose, Epizyme accelerated global start-up activities, including sites in greater China with our collaboration partner HUTCHMED, for the Phase 3 portion of the SYMPHONY-1 (EZH-302) study, a confirmatory study assessing tazemetostat in combination with rituximab + lenalidomide (R2) compared with R2 plus placebo in patients with relapsed or refractory (R/R) FL previously treated with at least one systemic therapy, including those who are rituximab-refractory and/or have progression of disease within two years. The Company is currently screening patients in the Phase 3 portion and expects to enroll the first patient in the first quarter of 2022. Follow-up data from the Phase 1b safety run-in portion of the study are expected to be presented at a medical conference later this year.
LYSA Phase 2 study enrollment nearly complete; interim results expected in second half of 2022: Enrollment for the Phase 2 portion of the Lymphoma Study Association (LYSA) study, a Phase 1b/2 combination study of tazemetostat with R-CHOP in high-risk, front-line FL and diffuse large B-cell lymphoma (DLBCL) patients, is nearly complete with 111 patients out of a target of approximately 122 patients in DLBCL and 61 patients out of a target of approximately 62 patients in FL enrolled as of February 23, 2022. Epizyme, in collaboration with LYSA, anticipates presenting interim results from the Phase 2 portion of the study in the second half of 2022.
CELLO-1 Phase 2 study ~75% enrolled; updated safety run-in data and interim data expected in second half of 2022: The Phase 2 efficacy portion of the CELLO-1 study (EZH-1101), which is evaluating tazemetostat plus enzalutamide compared to enzalutamide monotherapy in metastatic castration-resistant prostate cancer patients (mCRPC), is approximately 75% enrolled toward a target of 80 patients. Epizyme expects to complete enrollment in the randomized Phase 2 portion of the study in 2022 and anticipates presenting updated data from the safety run-in portion as well as interim data from the Phase 2 portion of the study in the second half of 2022.
Initiated Phase 1b/2 tazemetostat hematological basket study (EZH-1501): During the fourth quarter of 2021, Epizyme initiated EZH-1501, its Phase 1b/2 signal finding basket study evaluating tazemetostat combinations in patients with hematological malignancies. Epizyme has entered into a clinical supply agreement with Roche for the bispecific cohort of the Company’s Phase 1b/2 basket study. This cohort will evaluate the investigational use of TAZVERIK (tazemetostat), in combination with mosunetuzumab, Roche’s investigational CD20xCD3 T-cell engaging bispecific antibody, for patients with R/R FL who have received two or more prior lines of therapy. Epizyme plans to provide updates as EZH-1501 reaches key enrollment milestones and plans to provide preliminary data from EZH-1501 in the second half of 2022.
Initiated first-in-human study of EZM0414 (SET-101): During the fourth quarter of 2021, Epizyme initiated the SET-101 study, a first-in-human Phase 1/1b study of EZM0414, Epizyme’s novel, first-in-class, oral SETD2 inhibitor, in adult patients with R/R multiple myeloma (MM) and R/R DLBCL. The Company expects to enroll between 30-36 patients in the Phase 1 dose escalation portion of the study. In October 2021, the FDA granted Fast Track designation for EZM0414 in adult patients with R/R DLBCL, and in January 2022, the FDA granted Orphan Drug designation for EZM0414 for MM. Epizyme plans to provide updates as the study reaches key enrollment milestones, along with preliminary data from SET-101 in 2022.
2022 Operating Plan Updates and Revised Financial Guidance

As part of Epizyme’s ongoing efforts to execute more effectively and advance its long-term growth strategy, the Company announced the following:

External Spending and Workforce Reductions: On March 1, 2022, the Company announced a further reduction of operating expenses, including a reduction in force of approximately 12% of its current employees. Estimated severance and termination costs of approximately $2.8-3.2 million are expected to be recorded in the first quarter of 2022.
Pipeline Reprioritization: Given the breadth of Epizyme’s current tazemetostat clinical development program, the Company has discontinued enrollment in its Phase 2 study of tazemetostat in combination with rituximab (SYMPHONY-2, EZH-1401), as well as its Phase 1/1b basket study evaluating tazemetostat combinations in patients with solid tumors (EZH-1301). The decision to discontinue enrollment in these studies was based on evolving market dynamics and a continued focus on optimizing the Company’s investments and eliminating potentially overlapping studies. The Company continues to study tazemetostat in combination with other therapies for both hematologic and solid tumor malignancies, both in ongoing Company-sponsored studies as well as investigator-initiated studies.
Revised 2022 Financial Guidance: 2022 total non-GAAP adjusted operating expenses are now expected to be between $160-180 million, compared to the prior guidance of $170-190 million. Based on the current operating plan, the Company expects that its existing cash, cash equivalents and marketable securities as of December 31, 2021, together with the $79.5 million in net proceeds raised from the common stock offering in January 2022, and expected cash generated from product sales, will be sufficient to fund planned operating expenses and capital expenditure requirements and pay debt service obligations as they become due, into the third quarter of 2023, without incorporating potential milestone payments, expense reimbursements from existing collaboration agreements or any future business development activities.
Fourth Quarter and Full Year 2021 Financial Results:

Cash Position: Cash, cash equivalents and marketable securities were $176.8 million as of December 31, 2021.
Revenue: Total revenue for the fourth quarter of 2021 was $11.6 million, compared to $4.5 million for the fourth quarter of 2020. Total revenue for the full year ended December 31, 2021 was $37.4 million, comprised of $30.9 million in net product revenue of TAZVERIK in the U.S. and $6.5 million in collaboration and other revenue.
Operating Expenses: Total GAAP operating expenses were $62.9 million for the fourth quarter of 2021 and $275.4 million for the full year ended December 31, 2021, compared to $70.5 million for the fourth quarter of 2020 and $241.2 million for the full year ended December 31, 2020. Total non-GAAP adjusted operating expenses were $54.7 million for the fourth quarter of 2021 and $243.4 million for the full year ended December 31, 2021, compared to $62.8 million for the fourth quarter of 2020 and $209.6 million for the full year ended December 31, 2020.
R&D expenses: GAAP R&D expenses were $28.9 million for the fourth quarter of 2021 and $131.0 million for the full year ended December 31, 2021, compared to $33.7 million for the fourth quarter of 2020 and $110.9 million for the full year ended December 31, 2020. Non-GAAP adjusted R&D expenses were $26.6 million for the fourth quarter of 2021 and $122.0 million for the full year ended December 31, 2021, compared to $31.5 million for the fourth quarter of 2020 and $101.3 million for the full year ended December 31, 2020.
SG&A expenses: GAAP SG&A expenses were $30.9 million for the fourth quarter of 2021 and $134.0 million for the full year ended December 31, 2021, compared to $35.0 million for the fourth quarter of 2020 and $125.2 million for the full year ended December 31, 2020. Non-GAAP adjusted SG&A expenses were $25.9 million for the fourth quarter of 2021 and $115.1 million for the full year ended December 31, 2021, compared to $30.5 million for the fourth quarter of 2020 and $106.2 million for the full year ended December 31, 2020.
Net Loss (GAAP): Net loss attributable to common stockholders was $50.7 million, or $0.49 per share, for the fourth quarter of 2021 and $251.1 million, or $2.45 per share, for the full year ended December 31, 2021, compared to $66.2 million, or $0.65 per share, for the fourth quarter of 2020 and $231.7 million, or $2.29 per share, for the full year ended December 31, 2020.
A reconciliation of non-GAAP adjusted financial measures directly comparable to GAAP financial measures is presented in the table attached to this press release.

Conference Call Information
Epizyme will host a conference call today, March 1, at 8:30 a.m. ET. To participate, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 4082815. A webcast, as well as supplemental slides to support the webcast, will be available in the investor section of the Company’s website at www.epizyme.com, and will be archived for 60 days following the call.

About Non-GAAP Financial Measures
In addition to financial information prepared in accordance with the U.S. generally accepted accounting principles (GAAP), this press release includes the following non-GAAP financial measures: total non-GAAP adjusted operating expenses on a historical and projected basis, non-GAAP adjusted cost of product revenue, non-GAAP adjusted R&D expenses on a historical basis and non-GAAP adjusted SG&A expenses on a historical basis. Epizyme derives these non-GAAP financial measures by excluding certain expenses and other items from the respective GAAP financial measure, that is most directly comparable to each non-GAAP financial measure. Specifically, the non-GAAP financial measures exclude stock-based compensation expense and depreciation and amortization of intangibles. The Company’s management believes that these non-GAAP financial measures are useful to both management and investors in analyzing its ongoing business and operating performance. Management does not intend the presentation of these non-GAAP financial measures to be considered in isolation or as a substitute for results prepared in accordance with GAAP, but as a complement to provide greater transparency. In addition, these non-GAAP financial measures may differ from similarly named measures used by other companies. A quantitative reconciliation of projected total non-GAAP adjusted operating expenses to total GAAP operating expenses is not available without unreasonable effort primarily due to the Company’s inability to predict with reasonable certainty the amount of future stock-based compensation expense.

About TAZVERIK (tazemetostat)
TAZVERIK is a methyltransferase inhibitor indicated for the treatment of:

Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications is contingent upon verification and description of clinical benefit in confirmatory studies.

The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

View the U.S. Full Prescribing Information here: Epizyme.com

About EZM0414
EZM0414 is a potent selective, oral, small molecule, investigational drug agent that inhibits the histone methyltransferase, SETD2, which plays a role in oncogenesis. SETD2 methylates histone as well as non-histone proteins, and this activity is involved in several key biological processes including transcriptional regulation, RNA splicing, and DNA damage repair. Based on the preclinical data on SETD2 inhibition by EZM0414 in multiple settings, including high risk t(4;14) multiple myeloma (MM) and in other B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL), the Company is conducting SET-101, a Phase 1/1b study of EZM0414, for the treatment of adult patients with relapsed or refractory MM and DLBCL.

On March 1, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the full year and fourth quarter of 2021 and provided financial guidance for 2022 (Press release, Jazz Pharmaceuticals, MAR 1, 2022, View Source [SID1234609306]).

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"2021 was a transformative year for Jazz, delivering over $3 billion in revenue for the first time. Our talented team achieved our goal of five key launches through 2020 and 2021, delivering innovative medicines to patients in critical need. We also acquired and integrated GW Pharmaceuticals, which expanded our commercial portfolio with Epidiolex, enhanced our R&D capabilities and talent, and added the industry-leading GW cannabinoid platform," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "These accomplishments underscore a significant advance in Jazz’s evolution to an innovative global biopharmaceutical company. We expect these achievements, coupled with our expanded capabilities and disciplined capital allocation, to drive sustainable growth and enhanced value as part of Vision 2025, which we announced in January. As we begin 2022, we remain focused on growing and diversifying our revenue, investing in our pipeline of novel therapies and delivering innovative therapies for patients."

"In 2021, our R&D organization advanced key programs across our portfolio, further broadening our pipeline into disease areas with significant unmet patient need and market potential. In the fourth quarter, we made important progress with key programs, including Phase 2 trial initiations in essential tremor and PTSD. Jazz and its partners also initiated multiple clinical trials to evaluate Zepzelca together with Tecentriq in first-line extensive stage small cell lung cancer (SCLC), and in its current indication in second-line SCLC. We were also pleased to have submitted a Supplemental Biologics License Application (sBLA) for Rylaze for Monday/Wednesday/Friday intramuscular dosing at the end of January, which will be reviewed under the Real-Time Oncology Review (RTOR) program," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Our R&D productivity, which has been strengthened by investment in our organization and the addition of GW programs and expertise, positions us well to deliver at least five additional novel product approvals by the end of the decade, a key component of Vision 2025."

Key Highlights

Commercial and R&D Excellence

Positive early feedback underpins November 2021 launch of Xywav for idiopathic hypersomnia
Drove exceptional Xywav adoption in narcolepsy in 2021
Epidiolex/Epidyolex year-over-year revenue growth1 of 29% underscores blockbuster potential
Rapidly established Zepzelca as the treatment of choice in second-line SCLC
Rylaze launch progressing well with strong early demand
Significant revenue diversification with 59% of net product sales in 4Q21 from products launched or acquired since 2019
Advanced value-driving pipeline programs with 5 key trials initiated in 2H21
Entering 2022 well-positioned to deliver on Vision 2025
Financial

Growing and durable commercial franchises drove 2021 total revenues of $3.1 billion; 31% increase compared to 2020
Significant deleveraging accomplished following GW acquisition:
Net leverage ratio at 4.1x as of December 31, 20212
0.8x improvement in 8 months following close of GW transaction
On-track for target of less than 3.5x by the end of 2022
Meaningful top- and bottom-line growth expected with 2022 total revenue guidance of $3.46 to $3.66 billion
________________________

1.

On a proforma basis

2.

On a non-GAAP adjusted basis. Non-GAAP net leverage ratio is a non-GAAP financial measure. For further information, see " Non-GAAP Financial Measures."

Business Updates

Key Commercial Products

Oxybate (Xywav and Xyrem):

Net product sales for the combined oxybate business increased 3% to $1,801.1 million in 2021 and increased 4% to $471.4 million in 4Q21 compared to the same periods in 2020.
Average active oxybate patients on therapy was approximately 16,200 in 4Q21, an increase of approximately 6% compared to the same period in 2020.
Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution:

Xywav net product sales were $535.3 million in 2021 and $182.7 million in 4Q21.
There were approximately 6,900 active Xywav patients exiting 4Q21.
Xywav has broad patent protection to 2033.
Xywav for Narcolepsy:

In 2021, the Company drove market-leading adoption of Xywav in narcolepsy.
There were approximately 6,650 active Xywav patients with narcolepsy exiting 4Q21.
In June 2021, FDA recognized seven years of Orphan Drug Exclusivity (ODE), through July 2027, for Xywav and published its summary of clinical superiority findings stating that "Xywav is clinically superior to Xyrem by means of greater safety because Xywav provides a greatly reduced chronic sodium burden compared to Xyrem." Further, FDA stated that "the differences in the sodium content of the two products at the recommended doses will be clinically meaningful in reducing cardiovascular morbidity in a substantial proportion of patients for whom the drug is indicated."
Xywav for Idiopathic Hypersomnia (IH):

The Company launched Xywav for IH on November 1, 2021, with initial launch efforts focused on the approximately 37,000 currently diagnosed patients in the U.S. who are actively seeking healthcare.
Positive early launch momentum with approximately 250 active Xywav patients with IH exiting 4Q21. Healthcare providers are excited to have a treatment option with positive and compelling clinical trial results that address IH and not just its symptoms.
FDA recognized ODE for IH in January 2022 extending to August 2028.
Xyrem (sodium oxybate) oral solution:

Xyrem net product sales decreased 27% to $1,265.8 million in 2021 and decreased 34% to $288.8 million in 4Q21 compared to the same periods in 2020, reflecting the continued strong adoption of Xywav.
Epidiolex/Epidyolex (cannabidiol):

Epidiolex/Epidyolex net product sales were $463.6 million in 2021, or $658.3 million on a proforma basis, and $193.8 million in 4Q21. On a proforma basis, these net product sales represent growth of 29% and 35% compared to 2020 and 4Q20 respectively.
Net product sales in 4Q21 were favorably impacted by approximately $18 million, compared to 3Q21, relating to a temporary increase in specialty pharmacy inventory levels.
Epidyolex is now commercially available and fully reimbursed in four of the five key European markets: United Kingdom, Germany, Italy and Spain, with an anticipated launch in France in 2022. The Company has made significant progress on its European rollout with launches in Spain, Italy and Switzerland in 3Q21 and Ireland in 1Q22.
The Company expects to initiate a Phase 3 pivotal trial of Epidiolex for Epilepsy with Myoclonic-Atonic Seizures (EMAS), the fourth target indication for Epidiolex, in 1H22.
The Company continues to strengthen the IP durability of Epidiolex. The U.S. FDA Orange Book Listed patent (US 11,207,292) was granted in December 2021, and extends through 2039. This patent covers the composition of the botanically derived cannabidiol (CBD) preparation used in Epidiolex and the treatment of indicated disorders using that CBD preparation.
Zepzelca (lurbinectedin):

Zepzelca net product sales were $246.8 million in 2021, the first full calendar year on the market following launch in July 2020, and increased 21% to $64.8 million in 4Q21 compared to 4Q20.
The Company is pleased to have established Zepzelca as the treatment of choice in the second-line SCLC setting after only eighteen months on the market.
Zepzelca development program updates:
The Company has initiated the Phase 2 basket trial evaluating Zepzelca as monotherapy in select relapsed/refractory solid tumors.
Jazz and collaborator F. Hoffmann-La Roche Ltd (Roche) have initiated a Phase 3 trial to evaluate first-line use of Zepzelca in combination with Tecentriq (atezolizumab), compared to Tecentriq alone, as maintenance therapy, in patients with extensive-stage SCLC after induction chemotherapy. The first patient was enrolled in November 2021.
The Company’s partner, PharmaMar, initiated a confirmatory trial, LAGOON, in second-line SCLC in December 2021. If positive, this trial would confirm the benefit of Zepzelca in the treatment of SCLC when patients progress following first-line treatment with a platinum-based regimen.
Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn):

Rylaze net product sales were $85.6 million in 2021 and $65.0 million in 4Q21, following commercial launch on July 15, 2021. 2021 revenues reflect the strong demand for Rylaze and include initial inventory build.
In January 2022, the Company completed the submission of an sBLA to FDA seeking approval for a Monday/Wednesday/Friday (M/W/F) intramuscular dosing schedule for Rylaze. The submission will be reviewed under the RTOR program.
The Company presented initial data, for the first time, from the Phase 2/3 study of Rylaze in patients with acute lymphoblastic leukemia and lymphoblastic lymphoma who developed hypersensitivity or silent inactivation to a long-acting E. coli–derived asparaginase, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021. This data showed that with the proposed M/W/F dosing schedule, patients maintain a clinically meaningful level of nadir serum asparaginase activity through the entire duration of treatment.
The Company anticipates that data from the current development program will support regulatory filings in Europe in mid-2022, including intravenous (IV) administration, with potential for approval in 2023, as well as a further submission to FDA to support IV administration later this year. The Company is also working with a partner to advance the program for potential submission, approval and launch in Japan.
Key Pipeline Highlights

Nabiximols:

The Company initiated the third Phase 3 nabiximols clinical trial, NCT04984278, in multiple sclerosis (MS)-related spasticity in 3Q21. This is a randomized, double-blind, placebo-controlled trial with a primary endpoint of muscle tone, expected to enroll approximately 190 patients.
The Company anticipates data from its first Phase 3 trial, NCT04657666, in 1H22; positive findings may enable a New Drug Application submission to FDA in 2022. Data from the two additional Phase 3 trials will follow in late 2022 and early 2023.
Suvecaltamide (JZP385):

Suvecaltamide, a highly selective modulator of T-type calcium channels, is in clinical development for the treatment of essential tremor.
The Company initiated a Phase 2b trial in 4Q21 and announced that the first patient was enrolled in December 2021. Top-line data read-out is anticipated in 1H24.
JZP150:

JZP150, a selective fatty acid amide hydrolase, or FAAH, inhibitor, is in clinical development for the potential treatment of post-traumatic stress disorder (PTSD).
The Company initiated a Phase 2 trial in 4Q21 and announced that the first patient was enrolled in December 2021. Top-line data read-out is anticipated in late 2023.
The Company received Fast Track Designation for JZP150 development in PTSD from FDA in 4Q21, underscoring the significant unmet medical needs of patients.
Other Products

Sunosi (solriamfetol):

Sunosi net product sales increased by 104% to $57.9 million in 2021 and increased 71% to $14.9 million in 4Q21 compared to the same periods in 2020.
In 4Q21, U.S. prescriptions increased by 4% compared to 3Q21.
Vyxeos (daunorubicin and cytarabine) liposome for injection:

Vyxeos net product sales increased 11% to $134.1 million in 2021 and increased 12% to $34.8 million in 4Q21 compared to the same periods in 2020.
Defitelio (defibrotide sodium) / defibrotide:

Defitelio/defibrotide net product sales increased 1% to $197.9 million in 2021 and decreased 23% to $42.5 million in 4Q21 compared to the same periods in 2020 due to the timing of distributor orders.
Financial Highlights

Commencing in 2020, following consultation with the staff of the Division of Corporation Finance of the U.S. Securities and Exchange Commission, the Company no longer excludes upfront and milestone payments from the Company’s non-GAAP adjusted net income, its line item components and non-GAAP adjusted EPS. See "Non-GAAP Financial Measures" below.

GAAP net income (loss) for 2021 was ($329.7 million), or ($5.52) per diluted share, compared to $238.6 million, or $4.22 per diluted share, for 2020. GAAP net income (loss) for 4Q21 was ($35.4 million), or ($0.57) per diluted share, compared to $133.4 million, or $2.33 per diluted share, for 4Q20.

Non-GAAP adjusted net income for 2021 was $992.8 million, or $16.23 per diluted share, compared to $704.0 million, or $12.46 per diluted share, for 2020. Non-GAAP adjusted net income for 4Q21 was $262.0 million, or $4.21 per diluted share, compared to $228.7 million, or $4.00 per diluted share, for 4Q20.

Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release.

Total Revenues

Net product sales for Epidiolex/Epidyolex and Sativex are included from the acquisition of GW Pharmaceuticals plc (GW Acquisition) on May 5, 2021.

Total revenues increased 31% in 2021 and 35% in 4Q21 compared to the same periods in 2020.

Products launched or acquired since 2019 comprised 59% of total net product sales in 4Q21.
Neuroscience net product sales in 2021 increased 31% to $2,335.4 million compared to 2020 primarily driven by Epidiolex/Epidyolex net product sales in 2021 of $463.6 million, following the GW Acquisition. In 2021, oxybate net product sales increased 3% to $1,801.1 million led by strong Xywav net product sales of $535.3 million partially offset by a decrease in Xyrem net product sales as a result of the strong adoption of Xywav by existing Xyrem patients. Neuroscience net product sales in 4Q21 increased 48% to $684.8 million compared to the same period in 2020 primarily driven by Epidiolex/Epidyolex net product sales in 4Q21 of $193.8 million. In 4Q21, oxybate net product sales increased 4% to $471.4 million.
Oncology net product sales in 2021 increased 32% to $733.8 million compared to 2020 primarily driven by an increase in Zepzelca net product sales of $156.4 million, following launch in the U.S. in July 2020. Oncology net product sales in 4Q21 increased 5% to $207.1 million compared to the same period in 2020 primarily driven by an increase in Zepzelca net product sales of $11.4 million.
Operating Expenses and Effective Tax Rate

Operating expenses changed over the prior year periods primarily due to the following:

Cost of product sales increased in 2021 and in 4Q21 compared to the same periods in 2020, on a GAAP and on a non-GAAP adjusted basis, due to increased net product sales as a result of the GW Acquisition. In addition, acquisition accounting inventory fair value step-up expense of $223.1 million in 2021 and $74.4 million in 4Q21 impacted GAAP cost of product sales.
Selling, general and administrative (SG&A) expenses increased in 2021 and in 4Q21 compared to the same periods in 2020, on a GAAP and on a non-GAAP adjusted basis, primarily due to an increase in compensation-related expenses driven by higher headcount as a result of the GW Acquisition and increased investment to support the Company’s recent product launches. SG&A expenses in 2021 and in 4Q21 on a GAAP basis also included transaction and integration related expenses of $229.0 million and $37.8 million related to the GW Acquisition.
Research and development (R&D) expenses increased in 2021 and in 4Q21 compared to the same periods in 2020, on a GAAP and on a non-GAAP adjusted basis, primarily due to the addition of costs related to clinical programs for nabiximols, Epidiolex and cannabinoids, an increase in costs related to suvecaltamide (JZP385) and JZP150, an increase in compensation-related expenses due to higher headcount primarily driven by the GW Acquisition and milestone expense of $10.0 million in 4Q21 relating to our asset purchase and collaboration agreements with Redx Pharma.
Acquired in-process research and development (IPR&D) expense in 2020 on a GAAP and on a non-GAAP adjusted basis primarily related to a $200.0 million upfront payment to PharmaMar for the exclusive U.S. commercialization and development rights to Zepzelca and a $35.0 million upfront payment to SpringWorks Therapeutics, Inc., in the fourth quarter, for a FAAH inhibitor program.
In 2020, the Company recorded an impairment charge of $136.1 million on a GAAP basis following the Company’s decision to stop enrollment in its Phase 3 clinical study of defibrotide for the prevention of veno-occlusive disease due to an Independent Data Monitoring Committee determination that it was highly unlikely that the study would reach its primary endpoint.
Cash Flow and Balance Sheet

As of December 31, 2021, cash and cash equivalents were $591.4 million, and the outstanding principal balance of the Company’s long-term debt was $6.4 billion compared to $6.6 billion as of September 30, 2021. In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $500.0 million. For the year ended December 31, 2021, the Company generated $778.5 million of cash from operations. In 4Q21 the Company made another voluntary payment of $251 million on its term loan B.

2022 Financial Guidance

Following the adoption of ASU 2020-06, diluted EPS must be calculated using the if-converted method which assumes full conversion of our Exchangeable Senior Notes. Diluted EPS calculations for 2022 include 9 million shares related to the assumed conversion of the Exchangeable Senior Notes and the associated interest expense add-back to net income of $29 million, on a GAAP basis, and $25 million on a non-GAAP basis, under the "if converted" method.

Non-GAAP adjusted EPS guidance for 2022 reflects dilution of approximately $2.00 post adoption of ASU 2020-06.

As illustrated below, had ASU 2020-06 been adopted in 2021, the impact on adjusted EPS for the year ended December 31, 2021 would have been a reduction of $1.73 to $14.47. There would have been no impact on GAAP net loss per diluted share as it was anti-dilutive.

Conference Call Details

Jazz Pharmaceuticals will host an investor conference call and live audio webcast today at 4:30 p.m. ET (9:30 p.m. GMT) to provide a business and financial update and discuss its 2021 full year and 4Q21 results and provide 2022 financial guidance. The live webcast may be accessed from the Investors section of the Company’s website at www.jazzpharma.com. Please connect to the website prior to the start of the conference call to ensure adequate time for any software downloads that may be necessary. Investors may participate in the conference call by dialing +1 855 353 7924 in the U.S., or +1 503 343 6056 outside the U.S., and entering passcode 6895455.

A replay of the conference call will be available through March 8, 2022 by dialing +1 855 859 2056 in the U.S., or +1 404 537 3406 outside the U.S., and entering passcode 6895455. An archived version of the webcast will be available for at least one week in the Investors section of the Company’s website at www.jazzpharma.com.

On March 1, 2022 NanoString Technologies, Inc. (NASDAQ:NSTG), a leading provider of life science tools for discovery and translational research, reported financial results for the fourth quarter and year ended December 31, 2021 (Press release, NanoString Technologies, MAR 1, 2022, View Source [SID1234609335]).

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Fourth Quarter Financial Highlights
•Product and service revenue of $42.0 million, 18% year-over-year growth
•GeoMx Digital Spatial Profiler (DSP) revenue of $18.0 million, 48% year-over-year growth. GeoMx DSP revenue includes:
◦Instrument revenue of $11.9 million, 27% year-over-year growth
◦Consumables revenue of $6.1 million, 117% year-over-year growth, annualized pull-through of approximately $109,000 per installed system
•nCounter revenue, inclusive of all service revenue, of $24.0 million, 2% year-over-year growth. nCounter revenue includes:
◦Instrument revenue of $5.7 million, 5% year-over-year decline
◦Consumables revenue of $13.8 million, flat year-over-year, annualized pull-through of approximately $53,000 per installed system
◦Service revenue of $4.6 million, 20% year-over-year growth
Full Year 2021 Financial Highlights
•Product and service revenue of $144.0 million, 29% year-over-year growth
•GeoMx DSP revenue of $51.9 million, 49% year-over-year growth. GeoMx DSP revenue includes:
◦Instrument revenue of $34.8 million, 17% year-over-year growth
◦Consumables revenue of $17.1 million, 226% year-over-year growth, average annualized pull-through of approximately $97,000 per installed system
•nCounter revenue, inclusive of all service revenue, of $92.1 million, 20% year-over-year growth. nCounter revenue includes:
◦Instrument revenue of $20.8 million, 14% year-over-year growth
◦Consumables revenue of $54.8 million, 22% year-over-year growth, average annualized pull-through of approximately $55,000 per installed system
◦Service revenue of $16.5 million, 22% year-over-year growth
•Cash, cash equivalents and short-term investments balance of $348.9 million
"We delivered a strong finish to 2021, generating more than 70 Q4 instrument orders across GeoMx and CosMx. This demonstrates the appeal of our unique spatial biology portfolio, which addresses scientific questions at any scale," said Brad Gray, President and CEO of NanoString. "During 2022, we plan to extend our leadership in spatial biology by driving GeoMx into mainstream research, launching CosMx as the market-leading spatial molecular imager, and integrating both with a cloud-based informatics portal, all while sustaining the growth of our nCounter platform."
Operational Highlights
Spatial Biology
•Spatial Genomics Summit: Held fourth annual Spatial Genomics Summit on February 28th, focused on scientific advancements and new technology in the spatial genomics market. Panelists included leading researchers from Mayo Clinic, Massachusetts General Hospital, New York University, Weill Cornell Medical Center, Boston University School of Medicine, Oregon Health and Science University and Illumina
GeoMx DSP
•GeoMx Orders: Generated record orders for more than 50 GeoMx DSP systems in the fourth quarter, representing approximately 80% growth as compared to the fourth quarter of 2020
•GeoMx Installed Base: Grew installed base to approximately 255 GeoMx DSP Systems at December 31, 2021, representing 96% growth over the prior year
•Workflow Automation: Partnered with Leica, a division of Danaher, to provide a fully automated workflow for using the Leica Bond RX system to prepare slides for GeoMx DSP
•Publications: Continued growth of peer-reviewed publications utilizing GeoMx DSP technology, with approximately 20 new publications in the fourth quarter, bringing the cumulative total to approximately 90 peer-reviewed publications as of December 31, 2021
CosMx SMI
•CosMx Orders: Secured customer orders for 20 CosMx Spatial Molecular Imager (SMI) systems through a limited program open to existing and new GeoMx customers
•Commercial Unveiling: Announced the initiation of a formal pre-order program for CosMx SMI with first shipments expected in late 2022
nCounter
•nCounter Installed Base: Grew installed base to approximately 1,050 nCounter Analysis Systems at December 31, 2021, representing 11% growth over the prior year
•Publications: Surpassed 5,200 cumulative peer-reviewed publications utilizing nCounter technology, representing an increase of more than one thousand publications over the last year, demonstrating continued research momentum for the nCounter platform
2022 Outlook
The company, based on its plans and initiatives for 2022, expects to record results approximately as follows:
•Total product and service revenue of $170 to $180 million, representing growth of 18% to 25% as compared to 2021
◦GeoMx DSP revenue of $73 to $78 million, representing growth of 41% to 50% as compared to 2021
◦nCounter revenue, inclusive of all service revenue, of $97 to $102 million, representing growth of 5% to 11% as compared to 2021
•Adjusted gross margin on product and service revenue of 56% to 58%
•Adjusted operating expenses of $155 to $165 million
•Adjusted EBITDA loss of $55 to $65 million
Financial Results
We have elected to present selected non-GAAP, or adjusted, financial measures, including Adjusted EBITDA. These adjusted financial measures are calculated excluding certain items that may make it more challenging to compare our GAAP operating results across periods. Such items may include collaboration revenue, stock-based compensation, depreciation and amortization, or one-time charges such as transaction related fees and expenses or restructuring charges and severance costs. A reconciliation of adjusted financial measures to the nearest comparable GAAP financial measure can be found in the notes and table at the end of this press release.
Supplemental Information
As a supplement to the table above, we have posted to the investor relations section of our website, at www.nanostring.com, supplemental financial data that include our adjusted financial measures as compared to the nearest comparable GAAP financial measures, for the fourth quarter and the full year of 2021 and for each quarter and the full year of 2020.
Conference Call
Management will host a conference call today beginning at 1:30 pm PT / 4:30 pm ET to discuss these results and answer questions. Investors and other interested parties can register for the call in advance by visiting View Source After registering, an email confirmation will be sent including dial-in details and unique conference call codes for entry. Registration is open throughout the call, but to ensure connection for the full call, registration in advance is recommended. The link to the webcast and audio replay will be made available at the Investor Relations website: www.nanostring.com. A replay of the call will be available beginning March 1, 2022 at 7:30pm ET through midnight ET on March 10, 2022. To access the replay, dial (866) 813-9403 or (929) 458-6194 and reference Conference ID: 709416. The webcast will also be available on our website for one year following the completion of the call.
Non-GAAP, or Adjusted, Financial Information
We believe that the presentation of non-GAAP, or adjusted, financial information provides important supplemental information to management and investors regarding financial and business trends relating to our financial condition and results of operations. Reconciliation of adjusted financial measures to the most directly comparable financial result as determined in accordance with GAAP are included at the end of this press release following the accompanying financial data. A reconciliation of adjusted guidance measures to corresponding GAAP measures is not available on a forward-looking basis without unreasonable effort due to the uncertainty regarding certain expenses that may be incurred in the future. For further information regarding why we believe that these adjusted measures provide useful information to investors, the specific manner in which management uses these measures and some of the limitations associated with the use of these measures, please refer to "Notes Regarding Non-GAAP Financial Information" at the end of this press release.

On March 1, 2022 TG Therapeutics, Inc. (NASDAQ: TGTX) reported its financial results for the fourth quarter and year ended December 31, 2021, and recent company developments, along with a business outlook for 2022 (Press release, TG Therapeutics, MAR 1, 2022, View Source [SID1234609214]).

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Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, stated, "While we’ve faced numerous challenges over the last several months, we continued to progress our programs forward toward commercialization. With both MS and CLL BLA/sNDA submissions pending at the FDA, we continue to see 2022 as potentially the most transformative year in the Company’s history." Mr. Weiss continued, "We are looking forward to the upcoming ODAC meeting where we can showcase the clinical profile of UKONIQ monotherapy in its approved indications and in combination with ublituximab in CLL. We are also very excited about the evolving profile of ublituximab and its potential role in the treatment of RMS. We continue to receive positive feedback from the MS community about the safety, efficacy and one hour infusion offered by ublituximab."

2021 Highlights & Recent Developments

Ublituximab in Multiple Sclerosis

U.S. Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) for ublituximab, as a treatment for patients with relapsing forms of multiple sclerosis (RMS) and set a Prescription Drug User Fee Act (PDUFA) goal date of September 28, 2022.
Presented positive results, including new analyses, from the ULTIMATE I and II Phase 3 trials at the 2021 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and at the 2022 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) annual forum. As previously reported, both trials met their primary endpoint with ublituximab treatment demonstrating a statistically significant reduction in annualized relapse rate (ARR) over a 96-week period compared to teriflunomide in patients with RMS. Additional secondary, tertiary and post-hoc sensitivity analyses were also presented, including T1 and T2 lesions, no evidence of disease activity (NEDA), brain volume, multiple sclerosis functional composite (MSFC) score, neutralizing antibodies and antidrug antibodies, and pharmacodynamics of B-cell depletion.
Ublituximab plus UKONIQ (umbralisib) (U2) in Chronic Lymphocytic Leukemia

FDA accepted a BLA for ublituximab and a supplemental New Drug Application (sNDA) for UKONIQ, both submissions requesting approval of U2 as a treatment for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). These applications were based on results from the UNITY-CLL Phase 3 trial, which included both treatment-naïve and relapsed or refractory (R/R) CLL patients. FDA notified the Company that it plans to host a meeting of the Oncologic Drugs Advisory Committee (ODAC), in connection with its review of the pending BLA/sNDA for U2, in the March/April 2022 timeframe. Due to the pending ODAC meeting, the Company does not expect a decision on the BLA/sNDA by the current PDUFA goal date of March 25, 2022.
Related to the concerns giving rise to the ODAC, FDA imposed a partial clinical hold on studies of U2 and its components in CLL and NHL.
UKONIQ in Relapsed or Refractory Marginal Zone Lymphoma & Follicular Lymphoma

Launched UKONIQ in the U.S. for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 based regimen and adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.
Generated $6.5 million in total net UKONIQ revenue from launch through the end of Q4 2021, approximately ten months.
Achieved broad U.S. payor coverage for more than 95% of Medicare and commercial lives and inclusion in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for MZL and FL.
TG-1701 in B-cell Malignancies

Presented updated data on TG-1701, our investigational bruton tyrosine kinase (BTK) inhibitor, as a monotherapy and in combination with U2 in patients with B-cell malignancies at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.
Strengthened Cash Position

Ended the year with more than $350 million in cash, cash equivalents and investment securities.
Key Objectives for 2022

Obtain a favorable outcome at the upcoming ODAC meeting.
Obtain FDA approval of U2 in CLL and SLL.
Obtain FDA approval of ublituximab in RMS.
Continue to advance our early pipeline candidates including TG-1501 (cosibelimab), our PDL1 inhibitor, TG-1701, our BTK inhibitor and TG-1801 our CD47/CD19 bispecific antibody.
Financial Results for the Fourth Quarter and Full Year 2021

Product Revenue, net: Product revenue, net was approximately $2.3 million and $6.5 million for the three and twelve months ended December 31, 2021. Net product revenues represent U.S. sales from our sole commercial product, UKONIQ, which received accelerated approval from the FDA on February 5, 2021.

R&D Expenses: Total research and development (R&D) expense was $62.6 million and $222.6 million for the three and twelve months ended December 31, 2021, compared to $43.0 million and $165.9 million for the three and twelve months ended December 31, 2020. The increase was due primarily to an increase in manufacturing expenses, as well as an increase in non-cash compensation R&D expense during the twelve months ended December 31, 2021 over the comparable period in 2020.
SG&A Expenses: Total selling, general and administrative (SG&A) expense was $32.4 million and $128.1 million for the three and twelve months ended December 31, 2021, and $43.9 million and $107.9 million for the three and twelve months ended December 31, 2020. The increase during the twelve months ended December 31, 2021 was primarily attributable to increased personnel and other selling, general and administrative costs associated with execution of the launch of UKONIQ and planning for the potential launches of U2 in CLL/SLL and ublituximab in RMS. The decrease during the three months ended December 31, 2021 was primarily related to non-cash compensation expense related to milestone-based vesting of restricted stock grants during the comparable period in 2020.
Net Loss: Net loss was $93.3 million and $348.1 million for the three and twelve months ended December 31, 2021, compared to $88.2 million and $279.4 million for the three and twelve months ended December 31, 2020. Excluding non-cash compensation, the net loss for the three and twelve months ended December 31, 2021 was approximately $79.0 million and $286.8 million, compared to a net loss of $54.7 million and $199.1 million for the three and twelve months ended December 31, 2020.
Cash Position and Financial Guidance: Cash, cash equivalents and investment securities were $350.3 million as of December 31, 2021, which the Company believes will be sufficient to fund the Company’s planned operations into 2023.
CONFERENCE CALL INFORMATION
The Company will host a conference call today, March 1, 2022, at 8:30 AM ET, to discuss the Company’s fourth quarter and year-end 2021 financial results and provide a business outlook for 2022.

In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live audio webcast will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source An audio recording of the conference call will also be available for replay at www.tgtherapeutics.com, for a period of 30 days after the call.

On March 1, 2022 Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology company developing tumor-selective immuno-oncology therapies for people living with cancer, reported pipeline and business progress and reported financial results for the fourth quarter and full year ended December 31, 2021 (Press release, Xilio Therapeutics, MAR 1, 2022, View Source [SID1234609247]).

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"Xilio made significant pipeline and business progress in 2021, becoming a clinical-stage organization and transitioning to a publicly traded company through the successful completion of our IPO," said René Russo, Pharm.D., president and chief executive officer of Xilio. "As we look to 2022, I am excited about the many opportunities ahead of us, including anticipated initial clinical data readouts for XTX101, our tumor-selective anti-CTLA-4 monoclonal antibody, and XTX202, our tumor-selective IL-2. In addition, we plan to submit an IND for XTX301, our tumor-selective IL-12, in the second half of the year and continue to generate new research programs by leveraging our robust platform. With our exceptional team and strong financial position, we believe we have the resources in place to advance our vision of bringing transformative immuno-oncology therapies to people living with cancer."

Pipeline and Business Progress

Cytokine Programs

●Xilio continues to advance enrollment in the Phase 1 portion of its Phase 1/2 clinical trial evaluating XTX202 for the treatment of patients with solid tumors. XTX202, a modified form of interleukin-2 (IL-2), is designed to localize activity in the tumor microenvironment, with the goal of overcoming the known tolerability challenges of existing IL-2 therapies while achieving enhanced anti-tumor activity. Xilio expects to report preliminary data from the Phase 1 portion of the trial in the second half of 2022.

●Xilio continues to progress preclinical studies for XTX301, a tumor-selective IL-12. The company plans to submit an investigational new drug application (IND) for XTX301 as a potential treatment for patients with solid tumors in the second half of 2022.

Checkpoint Inhibitor Program

●Xilio continues to advance enrollment in the Phase 1 portion of its Phase 1/2 clinical trial evaluating XTX101, a tumor-selective anti-CTLA-4 monoclonal antibody, as a monotherapy and in combination with pembrolizumab, an anti-PD-1, for the treatment of patients with advanced solid tumors. Xilio expects to report preliminary data from the monotherapy cohort of the Phase 1 portion of the trial in the middle of 2022 and preliminary data from the combination cohort of the Phase 1 portion of the trial in the second half of 2022.

Recent Business Highlights

●In January 2022, Xilio appointed Yuan Xu, Ph.D., to its board of directors.

Fourth Quarter and Full Year 2021 Financial Results

●Cash Position: Cash and cash equivalents were $198.1 million as of December 31, 2021, compared to $19.2 million as of December 31, 2020. The increase was primarily related to $144.9 million in net proceeds received from convertible preferred stock financings in the first quarter of 2021 and $116.4 million in net proceeds received from Xilio’s initial public offering in the fourth quarter of 2021. Net cash proceeds from financings were partially offset by operating uses of cash for the year ended December 31, 2021.

●Research & Development (R&D) Expenses: R&D expenses were $11.4 million for the quarter ended December 31, 2021, compared to $17.7 million for the quarter ended December 31, 2020. R&D expenses were $51.2 million for the year ended December 31, 2021, compared to $43.9 million for the year ended December 31, 2020. The year-over-year increase was primarily driven by higher personnel-related costs due to increased headcount and expenses associated with R&D programs.

●General & Administrative (G&A) Expenses: G&A expenses were $8.2 million for the quarter ended December 31, 2021, compared to $2.9 million for the quarter ended December 30, 2020. G&A expenses were $23.9 million for the year ended December 31, 2021, compared to $10.7 million for the year ended December 31, 2020. The year-over-year increase was primarily driven by higher personnel-related costs due to increased headcount and professional and consulting fees related to transitioning to and operating as a publicly traded company.

●Net Loss: Net loss was $19.7 million for the quarter ended December 31, 2021 and $75.8 million for the year ended December 31, 2021.

Financial Guidance

Xilio continues to believe that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into 2024.