On March 1, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the full year and fourth quarter of 2022 and provided financial guidance for 2023 (Press release, Jazz Pharmaceuticals, MAR 1, 2023, View Source [SID1234627985]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"2022 was a year of significant execution across our business that exemplified our purpose to innovate to transform the lives of patients and their families and advanced Jazz towards achieving Vision 2025. Our substantial top-line growth was led by the strength of our commercial franchises, including the continued adoption of Xywav across both narcolepsy and idiopathic hypersomnia (IH), meaningful Epidiolex growth, and robust demand for Rylaze, driven by critical unmet patient need," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "In addition to achieving considerable revenue growth in 2022, we generated $1.3 billion in cash from operations and significantly improved our operational efficiency in line with our objectives for Vision 2025. Our strong financial performance, alongside a more disciplined approach to capital allocation, allowed us to delever our balance sheet six months ahead of our stated target, while investing in multiple strategic transactions that have the potential to create meaningful long-term value for patients and shareholders. We are proud of our 2022 accomplishments, which position us in 2023 to grow our top-line revenues through continued commercial execution, enhance our pipeline investments in innovation, and demonstrate continued progress towards achieving Vision 2025."

"Building on several transformative years for R&D at Jazz, we have enhanced the breadth and depth of our pipeline, as well as our capabilities. In 2022, we added three promising candidates to our pipeline: zanidatamab, a late-stage novel HER2-targeted bispecific antibody with biparatopic binding, JZP441, an orexin-2 receptor agonist, and JZP898, a differentiated, conditionally-activated interferon alpha (IFNα) INDUKINE molecule. We’re very encouraged by the positive top-line results from the pivotal trial of zanidatamab in biliary tract cancers (BTC) and the first overall survival data for zanidatamab from the Phase 2 first-line (1L) metastatic gastroesophageal adenocarcinoma (GEA) trial that was announced at ASCO (Free ASCO Whitepaper) GI," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "With the initiation of multiple clinical trials in 2022, we continue to expand our pipeline into disease areas with significant unmet patient need and market potential, including difficult-to-treat cancers and Parkinson’s disease tremor, and we’ve rapidly progressed JZP441 since bringing it in-house to enable initial proof-of-concept in healthy volunteers in 2023. We enter 2023 with meaningfully increased investment in R&D, which coupled with our upcoming catalysts and expanded capabilities, gives us confidence in delivering sustainable long-term value."

Key Highlights

Business and Execution
•Xywav became the Company’s largest product by net sales in 4Q22, annualizing at more than $1 billion as a result of continued adoption in both narcolepsy and IH.
•Achieved a significant milestone exiting October 2022, with more narcolepsy patients taking Xywav than Xyrem. Expect Xywav to remain the oxybate of choice in 2023.
•Epidyolex delivered compelling growth in 4Q22 and is now launched and reimbursed in all five key European markets: United Kingdom, Germany, Italy, Spain and France.

•Received U.S. Food and Drug Administration (FDA) approval of Rylaze supplemental Biologics Licensing Application (sBLA) for Monday/Wednesday/Friday (MWF) intramuscular (IM) dosing.
•Strategic corporate development further expanded R&D pipeline with the addition of zanidatamab, a novel late-stage oncology asset.
•Positive top-line results from the pivotal trial of zanidatamab in BTC in December 2022 and the first overall survival data for zanidatamab from a Phase 2 trial in 1L HER2-expressing metastatic GEA in January 2023.
•Enrolled the first patient in a Phase 2 trial for suvecaltamide (JZP385) in Parkinson’s disease tremor in 4Q22.

Financial
•Growing and durable commercial franchises drove 2022 total revenues of $3.7 billion; 18% increase compared to 2021.
•Successfully delevered balance sheet in 2022; exiting the year at 2.9x adjusted net leverage ratio1.
•Focus on disciplined capital allocation and operational excellence drove:
◦Significantly increased cash from operations of $1.3 billion for the year ended December 31, 2022 compared to $779 million in 2021.
◦Improved leverage of selling, general and administrative (SG&A) expenses, which as a percentage of sales decreased significantly in 4Q22 and FY22 relative to the same periods in 2021.
◦Ability to invest nearly $450 million in strategic transactions in 2022, while still achieving net leverage target.
•2023 total revenue guidance of $3,675 to $3,875 million, 3% growth at the mid-point.
◦Total revenue guidance is underpinned by expectations of continued growth in net sales of Xywav, Epidiolex/Epidyolex and the oncology portfolio, a continued decline in net sales of Xyrem and royalties on net sales of Authorized Generics of Xyrem.
_______________________
1.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 10% to $1,978.9 million in 2022 and increased 12% to $528.9 million in 4Q22 compared to the same periods in 2021.
•Average active oxybate patients on therapy was approximately 18,000 in 4Q22, an increase of 11% compared to the same period in 2021.

Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution:
•Xywav net product sales increased 79% to $958.4 million in 2022 and increased 54% to $281.4 million in 4Q22 compared to the same periods in 2021.
•Xywav became the Company’s largest product by net product sales in 4Q22, annualizing at more than $1 billion as a result of continued adoption in both narcolepsy and IH.
•There were approximately 10,300 active Xywav patients exiting 4Q22.

Xywav for Narcolepsy:
•There were approximately 8,550 narcolepsy patients taking Xywav exiting 4Q22.
•Achieved another significant milestone exiting October 2022, with more narcolepsy patients taking Xywav than Xyrem.

•The benefits of lowering sodium intake continue to resonate with patients and prescribers. 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.

Xywav for Idiopathic Hypersomnia (IH):
•There were approximately 1,750 IH patients taking Xywav exiting 4Q22.
•The Company has achieved its goal of obtaining similar payer coverage to narcolepsy, with coverage now at approximately 90% of commercial lives for IH.
•The Company launched Xywav, the first and only treatment approved by FDA for IH, in November 2021. Initial launch efforts have focused on the approximately 37,000 currently diagnosed patients in the U.S. who are actively seeking healthcare. Healthcare providers are excited to have a treatment option with positive and compelling clinical trial results that addresses IH and not just its symptoms.
•FDA recognized ODE for IH in January 2022, extending regulatory exclusivity to August 2028.

Xyrem (sodium oxybate) oral solution:
•Xyrem net product sales decreased 19% to $1,020.5 million in 2022 and decreased 14% to $247.5 million in 4Q22 compared to the same periods in 2021, reflecting the continued adoption of Xywav by patients with narcolepsy.

Epidiolex/Epidyolex (cannabidiol):
•Epidiolex/Epidyolex net product sales increased 12%, on a proforma basis, to $736.4 million in 2022 and increased 7% to $207.0 million in 4Q22 compared to the same periods in 2021.
•The Company successfully completed the pricing and reimbursement process and the commercial launch of Epidyolex in France in 4Q22. Epidyolex is now launched in all five key European markets: United Kingdom, Germany, Italy, Spain and France.
•In 4Q22, the Company enrolled the first patient in a pivotal Phase 3 trial of Epidyolex for Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis in Japan.

Zepzelca (lurbinectedin):
•Zepzelca net product sales increased 9% to $269.9 million in 2022 and increased 11% to $72.0 million in 4Q22 compared to the same periods in 2021.
•The Company is pleased Zepzelca continues to be the treatment of choice in the second-line (2L) small cell lung cancer (SCLC) setting.
•Zepzelca development program highlights:
◦The EMERGE-201 Phase 2 basket trial evaluating Zepzelca as monotherapy in select relapsed/refractory solid tumors is ongoing.
◦Phase 3 trial in partnership with F. Hoffmann-La Roche Ltd (Roche) to evaluate 1L use of Zepzelca in combination with Tecentriq (atezolizumab), compared to Tecentriq alone, as maintenance therapy in patients with extensive-stage SCLC after induction chemotherapy is ongoing. The Company expects complete enrollment in the trial by the end of 2023.
◦The Company’s partner, PharmaMar, is conducting the Phase 3 confirmatory trial, LAGOON, in 2L SCLC. If positive, this trial could confirm the benefit of Zepzelca in the treatment of SCLC when patients progress following 1L treatment with a platinum-based regimen.

Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn):
•Rylaze net product sales were $281.7 million in 2022 compared to $85.6 million in 2021, following commercial launch in July 2021, and increased 25% to $81.0 million in 4Q22 compared to the same period in 2021.
•Strong demand for Rylaze in the first year of launch reflects the significant unmet patient need for a high-quality, reliable supply of Erwinia asparaginase for patients with acute lymphoblastic leukemia.

•In November 2022, the Company received FDA approval for a MWF IM dosing schedule for Rylaze.
•In May 2022, the Company completed the Marketing Authorization Application submission to European Medicines Agency for a MWF dosing schedule and IM and intravenous (IV) administration for JZP458 (approved as Rylaze in the U.S.) with potential for approval in 2023. The Company is also advancing the program for potential submission, approval and launch in Japan.
•In April 2022, the Company submitted an sBLA for IV administration. In February 2023, the Company received a complete response letter from FDA requesting additional clinical data on the IV administration of Rylaze. There is no impact on the approved product labeling for Rylaze IM administration.

Corporate Development
Zanidatamab Agreement1:
•On October 19, 2022, the Company and Zymeworks Inc. announced an exclusive licensing and collaboration agreement1 and on December 21, 2022, Jazz and Zymeworks announced Jazz exercised its option to continue with the exclusive development and commercialization rights to zanidatamab in key markets, including the U.S., Europe and Japan.
•Initial focus is in BTC and GEA with potential to transform the current standard of care in multiple HER2-expressing cancers.
•In December 2022, Zymeworks announced positive top-line data from the pivotal HERIZON-BTC-01 clinical trial investigating zanidatamab as monotherapy in patients with previously treated HER2-amplified and expressing BTC. Zanidatamab as monotherapy produced a confirmed objective response rate (cORR) of 41.3% and median duration of response of 12.9 months in patients.
•In January 2023, the Company and Zymeworks announced the first overall survival data of 84% at 18 months from a Phase 2 trial of zanidatamab in combination with chemotherapy in 1L patients with HER2-expressing metastatic GEA.
•The pivotal trial, HERIZON-GEA-01, evaluating zanidatamab in 1L GEA is ongoing and top-line data are expected in 2024.
_______________________
1.Exclusive development and commercialization rights to zanidatamab across all indications in the United States, Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks.

Key Pipeline Highlights
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).
•Patient enrollment is ongoing and top-line data read-out is anticipated in late 2023.
•The Company received Fast Track Designation for JZP150 development in PTSD from FDA, underscoring the significant unmet medical needs of patients.

Suvecaltamide (JZP385):
•Suvecaltamide, a highly selective modulator of T-type calcium channels, is in clinical development for the treatment of essential tremor (ET) and Parkinson’s disease tremor.
•Patient enrollment is ongoing in the Phase 2b ET trial and top-line data read-out is anticipated in 1H24.
•In 4Q22, the first patient was enrolled in a Phase 2 trial in patients with Parkinson’s disease tremor.

JZP441:
•JZP441, is a potent, highly selective oral orexin-2 receptor agonist designed to activate orexin signaling with the potential to be applicable in the treatment of narcolepsy, IH and other sleep disorders.
•In 4Q22, the first participant was enrolled into the Phase 1 development program to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of JZP441 in sleep-deprived healthy volunteers.
•The Company expects initial proof of concept in healthy volunteers in 2023.

JZP815:
•The Company enrolled the first patient in a Phase 1 trial evaluating JZP815 in patients with advanced or metastatic solid tumors with MAPK pathway alterations.
•The pan-RAF inhibitor program is part of a novel class of next-generation precision oncology therapies that has the potential to benefit cancer patients with high unmet needs in multiple different solid tumors.

JZP898:
•JZP898 is an engineered IFNα cytokine pro-drug that is activated specifically within the tumor microenvironment where it can stimulate IFNα receptors on cancer-fighting immune effector cells. The aim is to minimize the severe toxicities that have been observed with systemically active recombinant IFNα therapy and maximize clinical benefit when administered as monotherapy or in combination with other agents. Type 1 interferon signal transduction by IFNα agonism is a clinically validated mechanism of action, and IFNα has been shown to work synergistically in combination with other proven therapies including immune checkpoint inhibitors, targeted therapies and chemotherapy. This allows for potential application across a wide range of cancer types, combination regimens and lines of therapy.
•The Company expects to file an Investigational New Drug application for JZP898 in the U.S. this year.

Financial Highlights
Three Months Ended
December 31, Year Ended
December 31,
(In thousands, except per share amounts) 2022 2021 2022 2021
Total revenues $ 972,123 $ 896,731 $ 3,659,374 $ 3,094,238
GAAP net loss $ (240,724) $ (35,351) $ (224,060) $ (329,668)
Non-GAAP adjusted net income (loss) $ (4,239) $ 262,012 $ 933,598 $ 992,824
GAAP loss per share $ (3.82) $ (0.57) $ (3.58) $ (5.52)
Non-GAAP adjusted EPS1,2
$ (0.07) $ 4.21 $ 13.20 $ 16.23

_______________________
1.Adjusted EPS for the year ended December 31, 2022, was impacted by $1.48 per share following the adoption of ASU 2020-06. There was no related impact on adjusted EPS for the three months ended December 31, 2022, as the potential issue of ordinary shares upon exchange of the Company’s Exchangeable Senior Notes was anti-dilutive.
2.The Company adopted ASU No. 2020-06, "Debt—Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging—Contracts in Entity’s Own Equity (Subtopic 815-40): Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity", (ASU 2020-06) on January 1, 2022. Following adoption, diluted EPS must be calculated using the if-converted method which assumes full conversion of our Exchangeable Senior Notes.

GAAP net loss for 2022 was $(224.1) million, or $(3.58) per diluted share, compared to $(329.7) million, or $(5.52) per diluted share, for 2021. GAAP net loss for 4Q22 was $(240.7) million, or $(3.82) per diluted share, compared to $(35.4) million, or $(0.57) per diluted share, for 4Q21.
Non-GAAP adjusted net income for 2022 was $933.6 million, or $13.20 per diluted share, compared to $992.8 million, or $16.23 per diluted share, for 2021. Non-GAAP adjusted net loss for 4Q22 was

$(4.2) million, or $(0.07) per diluted share, compared to non-GAAP adjusted net income of $262.0 million, or $4.21 per diluted share, for 4Q21.
Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release.

Total Revenues
Three Months Ended
December 31, Year Ended
December 31,
(In thousands) 2022 2021 2022 2021
Xyrem $ 247,496 $ 288,765 $ 1,020,453 $ 1,265,830
Xywav 281,384 182,654 958,425 535,297
Total Oxybate 528,880 471,419 1,978,878 1,801,127
Epidiolex/Epidyolex1
206,998 193,786 736,398 463,645
Sativex1
4,721 4,649 16,825 12,707
Sunosi2
— 14,933 28,844 57,914
Total Neuroscience 740,599 684,787 2,760,945 2,335,393
Zepzelca
71,969 64,836 269,912 246,808
Rylaze 80,972 64,955 281,659 85,629
Vyxeos 30,266 34,764 127,980 134,060
Defitelio/defibrotide 40,653 42,511 194,290 197,931
Erwinaze/Erwinase — — — 69,382
Total Oncology 223,860 207,066 873,841 733,810
Other 3,067 1,030 6,643 9,798
Product sales, net 967,526 892,883 3,641,429 3,079,001
Royalties and contract revenues 4,597 3,848 17,945 15,237
Total revenues $ 972,123 $ 896,731 $ 3,659,374 $ 3,094,238

__________________________
1.Net product sales for Epidiolex/Epidyolex and Sativex are included from the acquisition of GW Pharmaceuticals plc, or GW, on May 5, 2021.
2.Net product sales for Sunosi U.S. are included until the date of divestment to Axsome Therapeutics, or Axsome, on May 9, 2022.

Total revenues increased 18% in 2022 and 8% in 4Q22 compared to the same periods in 2021.
•Neuroscience net product sales in 2022 increased 18% to $2,760.9 million compared to 2021 primarily driven by the inclusion of Epidiolex/Epidyolex net product sales for the full year and oxybate net product sales which increased 10% to $1,978.9 million. Neuroscience net product sales in 4Q22 increased 8% to $740.6 million compared to 4Q21 primarily driven by increased Xywav and Epidiolex net product sales, partially offset by the decline in Xyrem revenues, reflecting the continued adoption of Xywav by patients with narcolepsy.
•Oncology net product sales in 2022 increased 19% to $873.8 million compared to 2021 primarily driven by the inclusion of Rylaze net product sales for the full year, following its launch in July 2021. Oncology net product sales in 4Q22 increased 8% to $223.9 million compared to 4Q21 primarily driven by Rylaze net product sales, which increased 25% to $81.0 million.

Operating Expenses and Effective Tax Rate
Three Months Ended
December 31, Year Ended
December 31,
(In thousands, except percentages) 2022 2021 2022 2021
GAAP:
Cost of product sales $ 167,364 $ 136,153 $ 540,517 $ 440,760
Gross margin 82.7% 84.8% 85.2% 85.7%
Selling, general and administrative $ 383,203 $ 398,462 $ 1,416,967 $ 1,451,683
% of total revenues 39.4% 44.4% 38.7% 46.9%
Research and development $ 172,555 $ 155,443 $ 590,453 $ 505,748
% of total revenues 17.8% 17.3% 16.1% 16.3%
Acquired in-process research and development $ 375,000 $ — $ 444,148 $ —
Impairment charge $ — $ — $ 133,648 $ —
Income tax expense (benefit)(1)
$ (100,042) $ (12,467) $ (158,645) $ 216,116
Effective tax rate(1)
29.4% 27.8% 42.6% (191.5)%

_____________________________
1. The GAAP income tax benefit for 4Q22 and 2022, increased as a result of the tax impact of payments made for acquired in-process research and development (IPR&D) in those periods. The income tax benefit for 2022, also includes the tax impact of an impairment of acquired IPR&D related to nabiximols. The GAAP income tax expense for 2021, included an expense of $259.9 million related to the change in the statutory tax rate in the U.K.

Three Months Ended
December 31, Year Ended
December 31,
(In thousands, except percentages) 2022 2021 2022 2021
Non-GAAP adjusted:
Cost of product sales $ 93,386 $ 58,110 $ 251,941 $ 205,401
Gross margin 90.3% 93.5% 93.1% 93.3%
Selling, general and administrative $ 319,763 $ 328,656 $ 1,134,703 $ 1,105,048
% of total revenues 32.9% 36.7% 31.0% 35.7%
Research and development $ 160,105 $ 140,101 $ 521,085 $ 451,026
% of total revenues 16.5% 15.6% 14.2% 14.6%
Acquired in-process research and development $ 375,000 $ — $ 444,148 $ —
Income tax expense (benefit)(1)
$ (43,301) $ 37,254 $ 94,695 $ 148,764
Effective tax rate(1)
92.6% 12.3% 9.1% 13.0%

_____________________________
1. The non-GAAP adjusted income tax expense (benefit), for 4Q22 and 2022, includes the tax impact of payments made for acquired IPR&D in those periods.

Changes in operating expenses in 2022 and 4Q22 over the prior year periods are primarily due to the following:
•Cost of product sales increased in 2022 and 4Q22 compared to the same periods in 2021, on a GAAP and on a non-GAAP adjusted basis, due to an expense for past royalties payable under a settlement agreement with Otsuka Pharmaceutical Co., Ltd. In addition, cost of product sales, on a GAAP basis, in 2022 included increased inventory fair value step-up expense of $50.3 million compared to 2021, driven by the inclusion of a full year expense.

•Selling, general and administrative (SG&A) expenses, on a GAAP basis, decreased in 2022 and 4Q22 compared to the same periods in 2021, due to lower GW acquisition related transaction and integration expenses and lower Sunosi (solriamfetol) related costs, offset by restructuring costs and costs related to program terminations and increased investment in sales and marketing,

primarily relating to Xywav and, for the full year period, the inclusion of GW related headcount costs for the full year and the loss on the disposal of Sunosi. SG&A expenses, on a non-GAAP adjusted basis, increased in 2022 compared to 2021 primarily due to the inclusion of GW related headcount costs for the full year and increased investment in sales and marketing, offset by lower Sunosi related costs. SG&A expenses, on a non-GAAP adjusted basis, decreased in 4Q22 compared to 4Q21 primarily due to lower Sunosi related costs, offset by increased investment in sales and marketing.
•Research and development (R&D) expenses increased in 2022 and 4Q22 compared to the same periods in 2021, on a GAAP and on a non-GAAP adjusted basis, primarily due to the addition of costs related to zanidatamab, JZP898 and JZP441, and increased costs for JZP150, offset by a reduction in costs related to JZP458 (Rylaze), following its approval. R&D costs also increased in 2022, on a GAAP and on a non-GAAP adjusted basis, due to increased compensation related expenses driven by the inclusion of GW related headcount costs for the full period.
•Acquired in-process research and development (IPR&D) expense in 4Q22, on a GAAP and on a non-GAAP adjusted basis, related to payments of $375.0 million to Zymeworks, in connection with our licensing and collaboration agreement. Acquired IPR&D expense in 2022, on a GAAP and on a non-GAAP adjusted basis, also included upfront payments of $50.0 million to Sumitomo in relation to our licensing agreement and $15.0 million to Werewolf, in connection with our licensing and collaboration agreement.
•The impairment charge in 2022, on a GAAP basis, related to an acquired IPR&D asset impairment relating to the discontinuation of our nabiximols program.

Cash Flow and Balance Sheet
As of December 31, 2022, cash and cash equivalents were $881.5 million, and the outstanding principal balance of the Company’s long-term debt was $5.8 billion compared to $6.4 billion as of December 31, 2021. In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $500 million. For the year ended December 31, 2022, the Company generated $1,272.0 million of cash from operations. In September 2022 the Company made a voluntary payment of $300.0 million on the Dollar Term Loan and in March 2022 the Company repaid in full the $251.0 million remaining aggregate principal amount of the Euro Term Loan B.

2023 Financial Guidance
Jazz Pharmaceuticals’ full year 2023 financial guidance is as follows:

(In millions) Guidance
Revenues $3,675 – $3,875
–Neuroscience (includes Xyrem authorized generic royalties)
$2,675 – $2,825
–Oncology $950 – $1,050

(In millions, except per share amounts and percentages) GAAP Non-GAAP
Gross margin % 89%
93%1,6
SG&A expenses $1,197 – $1,277
$1,045 – $1,1052,6
SG&A expenses as % of total revenues 31% – 35% 27% – 30%
R&D expenses $739 – $797
$675 – $7253,6
R&D expenses as % of total revenues 19% – 22% 17% – 20%
Effective tax rate (32)% – (8)%
9% – 11%4,6
Net income $410 – $560
$1,240 – $1,3106
Net income per diluted share5
$5.90 – $7.90
$16.90 – $17.856
Weighted-average ordinary shares used in per share calculations5
75 75

____________________________
1.Excludes $135-$155 million of amortization of acquisition-related inventory fair value step-up and $14-$16 million of share-based compensation expense.
2.Excludes $152-$172 million of share-based compensation expense.
3.Excludes $64-$72 million of share-based compensation expense.
4.Excludes 41%-19% from the GAAP effective tax rate of (32%)-(8%) relating to the income tax effect of adjustments between GAAP net income and non-GAAP adjusted net income, resulting in a non-GAAP adjusted effective tax rate of 9%-11%.
5.Diluted EPS calculations for 2023 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 $28 million and $25 million, on a GAAP and on a non-GAAP adjusted basis, respectively, under the "if converted" method.
6.See "Non-GAAP Financial Measures" below. Reconciliations of non-GAAP adjusted guidance measures are included above and, in the table titled "Reconciliation of GAAP to non-GAAP Adjusted 2023 Net Income Guidance" at the end of this press release.

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 2022 full year and 4Q22 results and 2023 guidance.
Interested parties may register for the call in advance here or via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast.
A replay of the webcast will be available via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com.

On March 1, 2023 INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported financial results for the quarter and year ended December 31, 2022, and provided a business update (Press release, Inovio, MAR 1, 2023, View Source [SID1234627980]). INOVIO’s management will host a live conference call and webcast with slides at 4:30 p.m. Eastern Time today to discuss financial results and provide a general business update for the fourth quarter. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

INOVIO’s President and Chief Executive Officer, Dr. Jacqueline Shea, said, "The last year has been one of transition for INOVIO. We chose to make some difficult but essential decisions to best position our pipeline and organization for the future, and we are a stronger company because of it. We’ve honed our strategic vision, strengthened our financial position, and maintained our cash runway into first quarter 2025, enabling us to focus energy and resources on advancing candidates with scientific promise, achievable pathways to market, and strong commercial potential. Our continued commitment to financial discipline and operational excellence will guide us as we work to get those candidates across the finish line and ultimately deliver on the promise of DNA medicines for patients."

Dr. Shea continued, "Discussions are underway regarding next steps for our candidates with the greatest potential for impact, including INO-3107 as a potentially life-changing treatment for Recurrent Respiratory Papillomatosis (RRP) and INO-4201 as an Ebola vaccine booster. Today we also shared data from REVEAL2, the second trial in our program evaluating VGX-3100 as a treatment for cervical high-grade squamous intraepithelial lesions (HSIL). While the investigational biomarker-selected population did not achieve statistical significance, trial results did achieve statistical significance in the all-participants population. The overall evidence of viral clearance observed is encouraging as it builds upon the growing body of work pointing to the potential of our DNA Medicines platform in HPV diseases. We will certainly take that into consideration as we assess next steps for VGX-3100 and our broader portfolio. I believe that our increased experience with HPV therapeutics, coupled with our strengthened strategic focus over the past year, positions INOVIO to make meaningful advancements in our mission to bring innovative, life-saving DNA medicines to market."

Corporate Updates

REVEAL2 Data Results for VGX-3100 in Cervical HSIL

INOVIO reported results for REVEAL2. The company previously announced this trial was no longer pivotal and would not lead to a biologics license application (BLA) for a biomarker-selected population, as the U.S. Food and Drug Administration (FDA) had indicated that one or more additional trials would be required.

REVEAL2 was the second Phase 3 trial evaluating VGX-3100 for efficacy, safety, tolerability, and immunogenicity in treating HPV-16/18-related cervical HSIL. Trial participants included 203 women, 18 years of age or older, with histologically-confirmed cervical HSIL associated with HPV-16 and/or HPV-18, but who were otherwise healthy (NCT03185013). Participants received either VGX-3100 or placebo at weeks 0, 4 and 12 (randomized 2:1). In April 2022, the trial was amended to utilize a biomarker-selected population as the primary population, based on prior analysis that this investigational biomarker had the potential to identify women more likely to respond to treatment with VGX-3100.

In this trial, statistical significance was not achieved in the investigational biomarker-selected population for the endpoint of lesion regression and viral clearance. However, statistical significance was achieved in the all-participants population for the endpoint of lesion regression and viral clearance.

The percentage of participants in the investigational biomarker-selected population meeting the primary endpoint was 28.6% (6/21) in the treatment group, versus 0% (0/4) in the placebo group (p=0.115; difference in percentage 28.6, 95%CI: -24.6, 50.4), which was not statistically significant.

The result for the secondary endpoint of regression of HSIL and clearance of virus in the all-participants population of 203 participants (134 participants in the treatment group, 69 in the placebo group) was statistically significant, with 27.6% (37/134) of the participants meeting the endpoint in the treatment group, versus 8.7% (6/69) in the placebo group (p=0.001; difference in percentage 18.9, 95%CI: 7.8, 28.6).

In particular, in the all-participants population of REVEAL2, viral clearance was observed in 37.3% (50/134) in the 3-dose treatment group versus 8.7% (6/69) in the placebo group. Given the importance of viral clearance in removing the underlying cause of the HPV-related diseases, this data may have positive implications for our other HPV-related programs.

An ad-hoc integrated efficacy analysis of the results for both REVEAL1 and REVEAL2 shows statistical significance in both the biomarker-selected and all-participants populations. For the combined biomarker-selected population of 92 participants (68 participants in the treatment group, 24 in the placebo group), the percentage of participants meeting the endpoint was 54.4% (37/68 in the treatment group, versus 12.5% (3/24) in the placebo group (p<0.001; difference in percentage 41.9, 95%CI: 20.4, 57.0). For the combined all-participants population of 404 participants (272 participants in the treatment group, 132 in the placebo group), the percentage of participants meeting the endpoint was 25.0% (68/272 in the treatment group, versus 9.8% (13/132) in the placebo group (p<0.001; difference in percentage 15.2, 95%CI: 7.4, 22.1).

This combined data set will be used as supportive data in future regulatory interactions involving VGX-3100. As in REVEAL1, VGX-3100 was well-tolerated in REVEAL2. There were no treatment-related serious adverse events and most adverse events were considered to be mild to moderate.

INOVIO will continue to evaluate the results to determine the path forward for VGX-3100 in our HPV programs and plans to submit the data for publication in a peer-reviewed journal later this year. The Phase 3 trial of VGX-3100 in Greater China is currently ongoing, and INOVIO is working together with its development partner ApolloBio under our collaboration agreement, with the shared goal of advancing a treatment with the potential to improve the lives of patients in that market.

Clinical Highlights

Over the last year, positive data were announced for multiple programs in clinical development, including:

INO-3107 – RRP
INOVIO announced positive results from a Phase 1/2 clinical trial evaluating INO-3107 for the treatment of HPV 6 and HPV 11-related RRP in adults. Results from the first cohort of 21 participants showed a statistically significant improvement in the clinical endpoint of the number of surgical interventions needed to control papilloma growth, with a median decrease of three surgical interventions. In the second cohort of 11 patients, which delivered INO-3107 via exploratory side port needle, 10 of the 11 patients (91%) saw a reduction in number of surgeries in the year following initial treatment, with measurement beginning at Day 0, the start of trial therapy. Of these 10, four patients needed no surgery. There was a median decrease of three surgical interventions when comparing the year following treatment to the year prior, which was also statistically significant. In the year prior to treatment, the range of surgical interventions for these 11 patients was 2 to 8 and the median was 5. In both cohorts, INO-3107 was well-tolerated and immunogenic.

In both cohorts, patients received four doses of INO-3107: on Day 0, and Weeks 3, 6, and 9. Surgery was performed once in the two weeks prior to the first dose in order to establish a disease baseline, but any surgery performed following Day 0, including in the dosing window, was counted against the efficacy endpoint.

Conversations with regulators regarding development plans for INO-3107 are ongoing. INOVIO will present the Phase 1/2 trial results for INO-3107 at the 103rd Annual Meeting of the American Broncho-Esophageal Association at the 2023 Combined Otolaryngology Spring Meetings in May.

INO-4201 – Ebola Booster for rVSV-ZEBOV (Ervebo)
In a recently announced Phase 1b clinical trial in healthy adult participants who previously received a single injection of Ervebo, INO-4201 was found to be well-tolerated and boosted humoral responses in 100% (36 of 36) of treated participants. INOVIO believes these data indicate that DNA medicines could be an important part of global medical countermeasures against infectious diseases, either as primary vaccines or boosters to existing vaccines. INOVIO is currently in discussions with collaborators and potential partners regarding the next steps for the program.

INO-5401 – GBM
In 2022, INOVIO announced promising results from a Phase 1/2 trial of INO-5401 and INO-9012 in combination with PD-1 inhibitor Libtayo (cemiplimab) in newly diagnosed GBM patients. The data from this trial showed encouraging median overall survival data from 52 patients and evidence of antigen-specific T cells that may infiltrate GBM tumors.

INO-3112 – HPV-Related Cancers
In February 2022, updated results were published in Clinical Cancer Researchwhich included an improved Overall Response Rate (ORR) from a Phase 1b/2a trial in which the safety and tolerability, anti-tumor activity, and immunogenicity of INO-3112, when used in combination with durvalumab, a PD-L1 checkpoint inhibitor, was evaluated as a potential treatment for HPV-related head and neck cancer. The ORR was updated from 22.2% with three complete responses and three partial responses, to an ORR of 27.6% with four complete responses and four partial responses. As previously announced, the INO-3112 program was returned to INOVIO in 2021 from AstraZeneca.

Fourth Quarter 2022 Financial Results

As of December 31, 2022, cash and cash equivalents and short-term investments were $253.0 million compared to $401.3 million as of December 31, 2021. As of December 31, 2022, INOVIO had 253.1 million common shares outstanding and 271.0 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding options, restricted stock units, convertible preferred stock, and convertible debt.

Total revenue was $125,000 and $10.3 million for the quarter and year-ended December 31, 2022, respectively, compared to $839,000 and $1.8 million for the same period in 2021, respectively. The year-over-year increase in revenue resulted from the fulfillment of obligations under INOVIO’s contract with the U.S. Department of Defense.

Total operating expenses were $56.1 million and $277.8 million for the quarter and year-ended December 31, 2022, respectively, compared to $106.3 million and $303.0 million for the same period in 2021.

INOVIO’s net loss for the quarter and year-ended December 31, 2022 was $54.5 million, or $0.22 per basic and diluted share, and $279.8 million, or $1.17 per basic and diluted share, respectively, compared to net loss of $106.9 million, or $0.50 per basic and diluted share, and $303.7 million, or $1.45 per basic and diluted share, for the quarter and year-ended December 31, 2021, respectively.

Operating Expenses

Research and development (R&D) expenses for the quarter and year-ended December 31, 2022, were $42.1 million and $187.7 million, respectively, compared to $92.3 million and $249.2 million, respectively, for the same periods in 2021. The year-over-year decrease in R&D expenses was primarily related to lower drug manufacturing, outside services and clinical study expenses related to INO-4800 and VGX-3100, expenses related to the acquisition and installation of manufacturing equipment for INO-4800 during 2021 which were non-recurring, lower engineering services and expensed equipment related to our CELLECTRA 3PSP device array automation project, lower expensed inventory related to the CELLECTRA 2000 device and lower employee stock-based compensation. These decreases were offset by $29.2 million lower contra-research and development expenses recorded from grant agreements, $14.4 million of increased drug manufacturing costs related to our COVID-19 variant studies and DARPA COVID-19 dMAb grant and other variances.

General and administrative (G&A) expenses were $14.0 million and $90.2 million, respectively, for the quarter and year ended December 31, 2022, versus $14.0 million and $53.8 million, respectively, for the same periods in 2021. The year-over-year increase in G&A expenses was primarily due to a $14.0 million non-cash expense related to the settlement of INOVIO’s securities class action litigation, including the issuance of INOVIO common stock as part of the settlement, $14.3 million in higher legal expenses, primarily related to litigation matters, $6.9 million in one-time severance expenses and $1.6 million in higher employee compensation, among other variances.

INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s annual report on Form 10-K for the year ended December 31, 2022, which can be accessed at: View Source

Financial Guidance

INOVIO expects to maintain its cash runway into the first quarter of 2025. This projection includes its cash burn estimate of approximately $32 million for the first quarter 2023 and its ongoing expectation that cash burn will decrease incrementally from there into the first quarter of 2025. These projections do not include any funds that may be raised through the Company’s existing at-the-market program or other capital-raising activities.

Conference Call / Webcast Information

INOVIO’s management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO’s financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

On March 1, 2023 ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that on February 28, 2023, the Compensation Committee of the Company’s Board of Directors approved, in aggregate, grants of non-qualified stock option awards to purchase 49,450 shares of its common stock and restricted stock units ("RSUs") covering 15,200 shares of its common stock to three new employees under the ImmunoGen, Inc. Inducement Equity Incentive Plan, as amended (the "Inducement Plan") (Press release, ImmunoGen, MAR 1, 2023, View Source [SID1234627979]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

The Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of ImmunoGen (or following a bona fide period of non-employment), as an inducement material to such individual’s entering into employment with ImmunoGen, pursuant to Rule 5635(c)(4) of the Nasdaq Listing Rules.

The options have an exercise price of $3.88 per share, which is equal to the closing price of ImmunoGen’s common stock on the Nasdaq Global Select Market on February 28, 2023. Each option will vest as to 25% of the shares underlying such option on the first anniversary of the grant date and as to an additional 6.25% of the shares underlying the option quarterly thereafter, subject to each such employee’s continued employment on each vesting date. Each RSU will vest as to 25% of the shares underlying the RSU award on the first anniversary of the grant date and as to an additional 25% of the shares underlying the RSU award annually thereafter, subject to such employee’s continued employment on each such vesting date. Each option and RSU is subject to the terms and conditions of the Inducement Plan and the terms and conditions of a stock option agreement and an RSU agreement covering the respective grants.

On March 1, 2023 Immunocore Holdings plc (Nasdaq: IMCR), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious diseases and autoimmune conditions, reported its financial results for the fourth quarter and year ended December 31, 2022, and provided a business update (Press release, Immunocore, MAR 1, 2023, View Source [SID1234627978]).

"We are proud that KIMMTRAK, the world’s first commercialized TCR therapy, has been approved in over 30 countries for patients with metastatic uveal melanoma. In 2023, we will make it available to even more patients with launches planned in additional countries and through enrollment of cutaneous melanoma patients into our registrational tebentafusp trial," said Bahija Jallal, Chief Executive Officer of Immunocore. "We are also focused on progressing our PRAME clinical programs with ongoing expansion arms in multiple tumor types. Our platform continues to deliver first-in-class oncology programs, like PIWIL1, and several infectious disease candidates."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Full Year and Fourth Quarter 2022 Highlights (including post-period)

Financial Results

Total net product and net pre-product revenue (or "net sales") arising from the sales of KIMMTRAK (tebentafusp) were £42.3 million (or $51.1 million) in the fourth quarter of 2022, of which £32.1 million (or $38.8 million) was in the United States, £10.1 million (or $12.2 million) in Europe and £0.1 million (or $0.1 million) in international regions. For the year ended December 31, 2022, the Company generated total revenue from the sale of KIMMTRAK and tebentafusp in the amount of £116.8 million (or $141.1 million), of which £80.4 million (or $97.2 million) was in the United States, £35.5 million (or $42.9 million) in Europe and £0.9 million (or $1.1 million) in international regions.

R&D expenses for the year 2022 were £89.2 million (or $107.9 million), compared to £73.2 million for the year 2021. Selling and Administrative expenses for the year 2022 were £93.7 million (or $113.2 million), compared to £88.4 million for the year 2021.

Net loss for the fourth quarter of 2022 was £25.2 million (or $30.4 million) compared to a net loss of £39.4 million in the same period in 2021, and full year net loss for 2022 was £41.24 million (or $49.8 million) compared to a full year net loss of £131.5 million in 2021.

The fourth quarter basic and diluted loss per share for was $0.63, compared to $1.21 on December 31, 2021. Basic and diluted loss per share for the year ended December 31, 2022 was $1.09, compared to $4.19 for 2021.

Cash and cash equivalents for the year ended December 31, 2022 were £332.5 million (or $401.6 million). The Company’s current cash position and projected KIMMTRAK revenue provides a projected cash runway into 2026.

KIMMTRAK (tebentafusp-tebn) for metastatic uveal melanoma

During the fourth quarter of 2022, the Company continued to add new accounts prescribing KIMMTRAK in the United States, Germany, and France. As of December 31, 2022 there were 240 new accounts prescribing KIMMTRAK in the United States, which brings the capture rate of these accounts, according to the Company’s internal estimates, to 50% of potentially eligible patients. There were 100 new accounts prescribing KIMMTRAK in Germany and France, which brings the capture rate to approximately 80% of the eligible patient population. In the United States, Germany, and France the commercial team is focused on treating patients closer to home. In the three countries where KIMMTRAK is commercially available the real-world mean duration of treatment for KIMMTRAK continues increasing to the 9 months observed in the Phase 2 and 3 clinical trials.

During the fourth quarter of 2022, the Company received numerous awards and positive recognitions for KIMMTRAK’s clinical benefit. In November, the Company was awarded the SCRIP award in the UK in the ‘Best New Drug’ category, and in December, the prestigious Prix Galien France 2022 award in the ‘Medicine in Innovative Therapeutics’ category, for KIMMTRAK. KIMMTRAK’s clinical benefit to patients was recognized with Germany’s G-BA (Gemeinsamer Bundesausschuss) granting the therapy a considerable added benefit rating, as well as in France, where the HAS transparency committee granted an ASMR III and a SMR rating of important. These recommendations build upon the positive recommendations by American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and National Comprehensive Cancer Network (NCCN) in the second quarter of 2022. KIMMTRAK was approved by the U.S. Food and Drug Administration; the European Commission; and health authorities in the United Kingdom, Australia and Canada in the first half of 2022.

The Company is undergoing reimbursement discussions in a number of countries, including Germany and France where the Company is currently receiving revenues. The Company expects reimbursement decisions in one additional major European country by mid-2023 and up to five smaller countries by end of 2023.

In November 2022, the Company and Medison Pharma Ltd. ("Medison") amended and restated their exclusive distribution agreement for KIMMTRAK originally entered into in September 2021. Medison is the exclusive distribution partner for KIMMTRAK in Canada, Australia, New Zealand, Israel, Central and Eastern Europe, and following this amendment South and Central America, and the Caribbean.

Tebentafusp Phase 2/3 trial in advanced melanoma

The Company is screening patients in its Phase 2/3 clinical trial of tebentafusp in patients with previously treated advanced melanoma. The trial will enroll patients with advanced melanoma, excluding uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase inhibitor (TKI). Patients will be randomized to one of three arms including tebentafusp, as monotherapy or in combination with an anti-PD1, and a control arm. The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of overall survival (OS) and circulating tumor DNA (ctDNA) reduction.

IMC-F106C targeting PRAME-A02 in multiple solid tumors

The Company’s planned global expansion of the clinical trial footprint for PRAME-A02 studies is underway, with additional patients now being recruited into the Phase 1/2 monotherapy and combination expansion arms in order to characterize the breadth of clinical activity across multiple tumor types. Initial Phase 1 data with IMC-F106C targeting PRAME (PRAME-A02) was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, and the Company initiated four expansion arms—cutaneous melanoma, ovarian, non-small cell lung cancer (NSCLC), and endometrial cancers. The combinations with standards-of-care (checkpoint inhibitors, chemotherapy, and tebentafusp) will position the Company to explore IMC-F106C in earlier lines of treatment. The Company expects to report data from the monotherapy and combination arms by the first half of 2024.

Expansion of PRAME franchise: IMC-T119C (PRAME-A24) & IMC-P115C (PRAME-A02 HLE)

In January 2023, the Company revealed the addition of two new PRAME ImmTAC candidates for solid tumors to the pipeline. Building on enthusiasm for IMC-F106C targeting PRAME HLA-A02, the Company has expanded its franchise targeting PRAME.

IMC-F106C is an ImmTAC targeting PRAME for patients with HLA-A02, which is expressed in approximately 40% of Western populations (United States, Canada, EU). In order to expand the potential of TCR therapy targeting PRAME, the Company is developing IMC-T119C, a first-in-class ImmTAC product candidate targeting a PRAME peptide presented by HLA-A24. HLA-24 is an HLA-type that is estimated to be present in 60% of people in Japan and 15-20% in Western populations.

In addition, the Company is developing IMC-P115C, a half-life extended (HLE) ImmTAC product candidate targeting PRAME-A02, with the aim of improving patient convenience. IMC-P115C targets the same PRAME-A02 peptide and uses the same CD3 end and TCR specificity as IMC-F106C.

The Company plans to submit investigational new drug applications (INDs) for these two ImmTAC candidates in 2024.

First-in-class ImmTAC candidate – IMC-R117C (PIWIL1)

In January 2023, the Company announced an ImmTAC targeting a novel protein for colorectal and other gastrointestinal cancers. The Company has leveraged its proprietary peptidomic database to validate a novel target, PIWIL1. PIWIL1 is believed to play a role in tumor progression and is expressed across a range of tumors including colorectal, which is historically insensitive to immune checkpoints, as well as gastro-esophageal, and pancreatic cancer. PIWIL1 is also reported to be a negative prognostic marker. The Company believes IMC-R117C is the first PIWIL1 targeted immunotherapy and plans to submit an IND in the fourth quarter of 2023.

IMC-C103C targeting MAGE-A4

In December 2022, the Company presented Phase 1 data for IMC-C103C in a poster presentation at the ESMO (Free ESMO Whitepaper) Immuno-Oncology 2022 Congress.

In February 2023, Genentech accepted Immunocore’s proposal to cease co-funding the development of MAGE-A4 HLA-A02 targeted programs, except for Immunocore’s equal share of the wind-down costs of the IMC-C103C Phase 1 clinical trial. The clinical trial with IMC-C103C is nearing completion and Immunocore does not plan to enroll additional patients. Immunocore is eligible to receive development and commercial milestone payments plus royalties from Genentech on any sales of MAGE-A4 HLA-A02 targeted products arising under the Genentech agreement.

ImmTAV clinical programs

In February 2023, the Company presented initial safety and pharmacodynamic activity data with IMC-C113V, the first soluble TCR therapy for people living with Human Immunodeficiency Virus (HIV), at the Conference on Retroviruses and Opportunistic Infections (CROI) 2023. IMC-M113V is an immunotherapeutic approach designed to specifically eliminate CD4+ cells that are persistently infected with HIV (‘reservoirs’). All doses (1.6 mcg, 5 mcg, and 15 mcg) of IMC-M113V were well tolerated and not associated with cytokine release syndrome or neurotoxicity of any grade. There were no serious adverse events, nor significant changes in hematology or chemistry. Plasma viral load remained suppressed throughout dosing and follow-up. In addition, transient, dose-dependent increases in serum IL6 occurred 8-24 hours post-infusion. Five out of the ten participants who received the 15-mcg dose showed a >4-fold rise in IL6, which had been prespecified as indicative of pharmacodynamic activity based on prior experience from clinical trials with KIMMTRAK.

The Company has started enrolling people living with HIV in the multiple ascending dose (MAD) part of the trial, to identify a safe and tolerable dosing schedule that could lead to reduction in the viral reservoir and control of HIV after stopping antiretroviral therapies (ART), or functional cure. The MAD trial will enroll up to 28 participants.

In the second quarter of 2022, the Company presented data from the first three patients in the first-in-human clinical trial of IMC-I109V for chronic hepatitis B at the EASL International Liver Congress. In this first cohort, the three patients received a single dose of 0.8 mcg, based on the minimum anticipated biological effect level (MABEL). The dose in this initial cohort was well tolerated and was not associated with adverse events and resulted in a transient, small decrease in serum HBsAg with concomitant minor increase in alanine transaminase (ALT). The Company is enrolling patients in the single ascending dose portion of the trial.

Corporate and financial updates

In December 2022, the Company entered into an agreement with Gadeta B.V., to develop the first gamma delta (γδ) TCR ImmTAC for solid tumors, including colorectal cancer. Immunocore will collaborate with Gadeta on ‘201 γδ-TCR target discovery and has an option to develop ImmTAC therapies derived from the ‘201 TCR as part of the research collaboration.

Financial Results

Basic and diluted loss per share was £0.54 (or $0.63) and £0.90 (or $1.09) for the quarter and year ended December 31, 2022, respectively, as compared to a basic and diluted loss per share of £0.90 and £3.10, respectively, for the same periods in 2021. Total operating loss for the quarter and year ended December 31, 2022, was £22.3 million (or $27.0 million) and £39.6 million (or $47.8 million), respectively, as compared to £37.8 million and £135.2 million respectively for the same periods in 2021.

For the fourth quarter and year ended December 31, 2022, we generated total revenue from the sale of therapies of £42.3 million ($51.1 million) and £116.8 million ($141.1 million), respectively, due to the sale of KIMMTRAK and tebentafusp, of which £32.1 million ($38.8 million) and £80.4 million ($97.2 million), respectively was in the United States, £10.1 million ($12.2 million) and £35.5 million ($42.9 million), respectively, was in Europe, and £0.1 million ($0.1 million) and £0.9 million ($1.1 million), respectively, was in the rest of the world. We received marketing approval for KIMMTRAK in the United States, Europe and other territories in the year ended December 31, 2022, and did not have marketing approval for, and thus no product revenue from, KIMMTRAK in the year ended December 31, 2021.

For the fourth quarter and year ended December 31, 2022, our research and development ("R&D") expenses were £27.1 ($32.8 million) and £89.2 million (or $107.9 million), respectively as compared to £20.1 million and £73.2 million for the quarter and year ended December 31, 2021. These increases were due to increased expenses in connection with our IMC-F106C program and increased headcount and laboratory costs. The Company expects R&D expenses to increase in future periods as the Company advances its trials and further develops clinical and preclinical pipeline candidates.

For the quarter and year ended December 31, 2022, our selling and administrative expenses were £43.1 million ($52.1 million) and £93.7 million (or $113.2 million), respectively, compared to £24.4 million and £88.4 million for the quarter and year ended December 31, 2021. These increases were related to higher selling and distribution costs following regulatory approval of KIMMTRAK and an increase in headcount costs (excluding share-based payment charges, which reduced in 2022). Our administrative expenses also increased in the fourth quarter of 2022 due to approximately $15 million of non-cash foreign exchange losses, primarily on U.S. dollar balances.

Cash and cash equivalents were £332.5 million (or $401.6 million) as of December 31, 2022, as compared to £237.9 million (or $321.1 million) as of December 31, 2021. We expect that our existing cash, along with anticipated revenue from KIMMTRAK, will be sufficient to fund our planned operating expenses, financial commitments and other cash requirements into 2026.

We maintain our books and records in pounds sterling. For the convenience of the reader, we have translated pound sterling amounts as of and for the period ended December 31, 2022 into U.S. dollars at a rate of £1.00 to $1.2077.

Audio Webcast

Immunocore will host a conference call today, March 1, 2023 at 8:00 A.M. ET/ 1:00 PM GMT, to discuss the fourth quarter and full year 2022 financial results and provide a business update. The call will also be available via webcast by visiting the Events & Presentations section on Immunocore’s website. A replay of this webcast will be available for 30 days.

Conference Call Details:
U.S. (toll-free): 877-405-1239
International (toll): +1 201-389-0851

###

About KIMMTRAK
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

About Phase 3 IMCgp100-202 Trial
IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated mUM. KIMMTRAK demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity
KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).

About KIMMTRAKConnect
Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273.

On March 1, 2023 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported that management will participate in the following investor conferences in March (Press release, Elevation Oncology, MAR 1, 2023, View Source;utm_medium=rss&utm_campaign=elevation-oncology-to-participate-at-upcoming-investor-conferences [SID1234627977]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Cowen 43rd Annual Health Care Conference
Date: Tuesday, March 7
Panel Title: GI/GU Oncology
Panel Time: 12:50 p.m. ET

Oppenheimer 33rd Annual Healthcare Conference
Date: Wednesday, March 15
Presentation Time: 8:00 a.m. ET

A live webcast and replay of the event will be available on the Events page of the Company’s Investor Relations website at View Source