On February 27, 2023 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage precision oncology medicine company developing novel MasterKey therapies targeting families of oncogenic driver mutations in patients with genetically defined cancers, reported that its President and Chief Executive Officer, David M. Epstein, Ph.D., will present an update on the Company’s progress at the Cowen 43rd Annual Health Care Conference on Monday, March 6, 2023, at 12:50 p.m. ET in Boston, MA (Press release, Black Diamond Therapeutics, FEB 27, 2023, https://investors.blackdiamondtherapeutics.com/news-releases/news-release-details/black-diamond-therapeutics-present-cowen-43rd-annual-health-care [SID1234627717]).

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A live webcast of the presentation can be accessed by visiting the investors relations section of the Company’s website at: www.blackdiamondtherapeutics.com. A replay of the webcast will also be available and archived for 90 days following the event.

On February 27, 2023 Biomarin reported its Fourth Quarter and Full Year 2022 Total Revenues Driven by Strong Global Demand for VOXZOGO and Steady Growth of Enzyme Business (Press release, BioMarin, FEB 27, 2023, View Source [SID1234627716]).

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Financial Highlights (in millions of U.S. dollars, except per share data, unaudited)
Three Months Ended
December 31, Twelve Months Ended
December 31,
2022 2021 % Change 2022 2021 % Change
Total Revenues $ 537.5 $ 449.8 19 % $ 2,096.0 $ 1,846.3 14 %
Net Product Revenues Marketed by BioMarin (1)
$ 487.9 $ 414.9 18 % $ 1,913.6 $ 1,660.7 15 %
VIMIZIM Net Product Revenues
$ 152.1 $ 156.3 (3) % $ 663.8 $ 623.1 7 %
NAGLAZYME Net Product Revenues
$ 100.5 $ 83.1 21 % $ 443.8 $ 380.4 17 %
PALYNZIQ Net Product Revenues
$ 72.3 $ 63.8 13 % $ 255.0 $ 237.5 7 %
VOXZOGO Net Product Revenues $ 66.8 $ 5.8 1,052 % $ 169.1 $ 5.9 2,766 %
KUVAN Net Product Revenues
$ 53.6 $ 68.5 (22) % $ 227.6 $ 285.8 (20) %
BRINEURA Net Product Revenues
$ 42.6 $ 37.4 14 % $ 154.3 $ 128.0 21 %
ALDURAZYME Net Product Revenues
$ 37.6 $ 20.3 85 % $ 128.4 $ 122.8 5 %
GAAP Net Income (Loss) $ (0.2) $ (57.9) $ 141.6 $ (64.1)
GAAP Earnings (Loss) per Share – Basic $ (0.00) $ (0.32) $ 0.76 $ (0.35)
GAAP Earnings (Loss) per Share – Diluted $ (0.00) $ (0.32) $ 0.75 $ (0.35)
Non-GAAP Income (2)
$ 67.4 $ 7.1 $ 364.6 $ 242.8

December 31,
2022 December 31,
2021
Total cash, cash equivalents & investments $ 1,625.4 $ 1,521.7

(1) Net Product Revenues Marketed by BioMarin is the sum of revenues from VIMIZIM, NAGLAZYME, PALYNZIQ, KUVAN, VOXZOGO and BRINEURA for the three and twelve months ended December 31, 2022 and 2021, each calculated in accordance with Generally Accepted Accounting Principles in the United States (U.S. GAAP). Sanofi is BioMarin’s sole customer for ALDURAZYME and is responsible for marketing and selling ALDURAZYME to third parties.
(2) Non-GAAP Income for the historical periods presented is defined by the Company as reported GAAP Net Income/Loss, excluding net interest income (expense), provision for (benefit from) income taxes, depreciation expense, amortization expense, stock-based compensation expense, contingent consideration expense and, in certain periods, certain other specified items. Refer to Non-GAAP Information beginning on page 10 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the comparable information reported under U.S. GAAP.

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SAN RAFAEL, Calif., February 27, 2023 – BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the fourth quarter and full year ended December 31, 2022.
"As expected, in 2022 BioMarin delivered double-digit revenue growth and profitability for the full-year driven by the strong global launch of VOXZOGO, consistent growth of our enzyme business and continued focus on operational excellence," said Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin. "Our record-setting 2023 outlook underscores BioMarin’s proven and fully-scaled development and commercial capabilities and attention to sustainable growth. With global market expansion of VOXZOGO well underway, we turn our focus to the European commercial launch of ROCTAVIAN, the world’s first gene therapy approved for the treatment of severe hemophilia A. Our team in Germany is working with the leading hemophilia centers of excellence to drive awareness and uptake of ROCTAVIAN, now that it is commercially available. In the United States, we are actively preparing for the launch of ROCTAVIAN upon potential approval this year. We are encouraged by the level of interest from U.S. adult hemophilia A patients seeking information about ROCTAVIAN and are pleased that roughly 300 people have engaged directly with BioMarin to learn more. Acknowledging that many of these people may not be eligible for treatment with ROCTAVIAN, we are glad to see this level of engagement with the bleeding disorders community."

Financial Highlights:
•Total Revenues for the fourth quarter of 2022 were $537.5 million, an increase of 19% compared to the same period in 2021 despite continued erosion of the U.S. KUVAN market. The increase in Total Revenues was primarily attributed to the following:
•Higher VOXZOGO commercial sales due to continued global market expansion and rapid patient uptake following regulatory approvals in late 2021 and early 2022,
•Higher NAGLAZYME product revenues primarily driven by new patients initiating therapy and the timing of orders in countries that place large government orders, particularly in Europe and the Middle East, and
•Higher ALDURAZYME product revenues primarily due to the timing of order fulfillment to Sanofi. BioMarin ALDURAZYME revenues are driven by the timing of when the product is released and control is transferred to Sanofi,
•Lower KUVAN product revenues primarily due to generic competition as a result of the loss of market exclusivity in the U.S., consistent with expectations.
•GAAP Net Loss decreased to $0.2 million for the fourth quarter of 2022 compared to GAAP Net Loss of $57.9 million for the same period in 2021. The decreased net loss was primarily related to higher gross profit, driven by increased sales volume. This was partially offset by higher selling, general and administrative (SG&A) and research and development (R&D) expenses. The increase in SG&A expenses was largely due to severance costs associated with the Company’s organizational redesign announced in October 2022 and higher costs to support the commercial launch of VOXZOGO and ROCTAVIAN in the EU. The increase in R&D expenses was primarily attributed to higher spend for programs in our earlier-stage development portfolio.
•Non-GAAP Income increased to $67.4 million for the fourth quarter of 2022 compared to Non-GAAP Income of $7.1 million for the same period in 2021 driven by higher gross profit due to increased sales volume partially offset by higher SG&A and R&D expenses for the same reasons noted above.
New Product Approvals and Launches (ROCTAVIAN and VOXZOGO)
•The European launch of ROCTAVIAN is underway following EMA approval in the third quarter of 2022. Since approval, BioMarin continues to collaborate with German health insurers to secure novel Outcomes Based Agreements (OBAs) to enable access to ROCTAVIAN treatment. The first OBA has been completed, allowing for a significant percentage of people in Germany affected by severe hemophilia A to pursue treatment with ROCTAVIAN. Patient testing to determine eligibility for ROCTAVIAN treatment is ongoing throughout Germany.
•BioMarin’s Biologics License Application (BLA) for ROCTAVIAN is currently under review by the U.S. Food
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and Drug Administration (FDA) with a PDUFA target action date of March 31, 2023, subject to a potential three-month extension, if the FDA deems necessary during the review procedure. The Company recently submitted to the FDA positive results from three or more years of follow up from its ongoing global Phase 3 GENEr8-1 study of ROCTAVIAN, the largest and longest global Phase 3 study to date for any gene therapy in hemophilia with 134 participants. As part of the ongoing review, the FDA completed the Pre-License Inspection of the Company’s dedicated gene therapy facility in December 2022. BioMarin has provided responses to the comments and observations received at the close of the FDA inspection, and believes all are addressable. Also in the U.S., the Premarket Approval (PMA) application is under review at the Center for Devices and Radiological Health to support contemporaneous approval of a CDx along with the ROCTAVIAN BLA.
•Today, the Company provided full-year 2023 ROCTAVIAN guidance of between $100 million to $200 million. The estimated range acknowledges the inherent uncertainties of the global launch during 2023, and assumes contributions from Germany, the United States, if approved, with the amount dependent on potential approval timing, and small numbers of patients in other markets.
•The global expansion of VOXZOGO continues, with market access and reimbursement activities progressing, as anticipated. As of the end of January 2023, an estimated 1,264 children with achondroplasia were being treated with VOXZOGO. Treated children are included under the currently approved age ranges in Europe, 2 years old and older, the United States, for children 5 years old and older, and in Japan, approved for all ages from birth. There were 32 active markets contributing to VOXZOGO commercial expansion including the United States, Europe, Japan, Canada, Australia and Brazil.
Mid-stage Product Life Cycle Expansion Opportunities (VOXZOGO and ROCTAVIAN)
•During the fourth quarter, BioMarin submitted supplemental marketing applications in the U.S. and EU to expand VOXZOGO access to younger age groups, based on favorable results from a Phase 2 study in infants and young children. In January 2023, the European Medicines agency validated BioMarin’s application for extension of indications for VOXZOGO for the treatment of children under the age of two. The Company expects action by U.S. and EU health authorities on the applications in the second half of 2023. If age expansions are accepted, more than 1,000 additional children will be eligible for VOXZOGO treatment in the U.S. and Europe.
•Product expansion opportunities with ROCTAVIAN are supported by a number of clinical studies currently underway. Two additional studies are ongoing, one investigating ROCTAVIAN treatment in those with active or prior inhibitors, as well as one study investigating ROCTAVIAN in people with pre-existing antibodies against AAV5.
Earlier-stage Development Portfolio (BMN 255, BMN 331, BMN 351, BMN 349, BMN 293 (DiNA-001))
•BioMarin plans to showcase progress across its earlier-stage development pipeline at R&D Day in New York City on September 12, 2023. Invitations to the event will be circulated in June.
•BMN 255 for hyperoxaluria in chronic liver disease: The Company has concluded the multi-ascending dose phase of the First-in-Human study with BMN 255. In January 2023, BioMarin shared early data that demonstrated a rapid and potent increase in plasma glycolate following treatment with BMN 255, which is predicted to have a profound reduction in oxalate excretion in patients. BioMarin now plans to initiate and fully enroll an expanded study in patients with chronic liver disease and hyperoxaluria in 2023. The Company believes the availability of a potent, orally bioavailable, small molecule like BMN 255 may be able to significantly reduce disease and treatment burden in a patient population with significant unmet need.
•BMN 331 gene therapy product candidate for Hereditary Angioedema (HAE): Dosing continues in the Phase 1/2 HAERMONY study to evaluate BMN 331, an investigational AAV5-mediated gene therapy for people living with HAE. In January 2023, BioMarin shared that the first participant treated with the 6e13vg/kg dose demonstrated C1-Inhibitor levels that were approaching the therapeutically relevant range. A second participant is scheduled for dosing at the 6e13vg/kg dose level in the coming weeks.
•BMN 351 for Duchenne Muscular Dystrophy (DMD): Investigational New Drug application (IND)-enabling studies continue with BMN 351, an antisense oligonucleotide therapy for individuals with exon 51-skip-amenable DMD. BMN 351 was developed using familiar chemistry and superior biology, by targeting a novel,
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upstream, splice enhancer site demonstrating improved binding affinity and tolerability in preclinical models. Preclinical data suggest that restored expression of near-full-length dystrophin protein at levels of up to 40% will convert phenotypes from rapid loss to durable preservation of strength and ambulation. BioMarin is working towards beginning clinical studies with BMN 351 in 2023.
•BMN 349 for alpha-1 antitrypsin deficiency: Preclinical studies have demonstrated that BMN 349 is an orally bioavailable, small molecule that in preclinical studies has demonstrated that it is titratable with rapid onset and high potency and efficacy. Preclinical results have strong implications for potential improvement of current management, particularly for severe liver disease requiring rapid action. IND enabling studies are underway and BioMarin’s goal is to file an IND for BMN 349 in the second half of 2023.
•BMN 293 (formerly DiNA-001) for MYBPC3 hypertrophic cardiomyopathy (HCM): Preclinical studies are underway with BMN 293 following a collaboration announced in 2020 with DiNAQOR, a platform company that develops organ specific delivery of novel gene therapies to treat rare genetic cardiac and renal diseases. Mutations in the MYBPC3 gene are the most common cause of inherited HCM. Early investigations suggest that gene therapy-mediated gene transfer can lead to widespread expression of the gene product, cardiac myosin-binding protein C (MyBP-C), in cardiac tissue, which can normalize cardiac hypertrophy, improve relaxation kinetics and potentially alleviate functional deficits in individuals suffering from cardiomyopathy. BioMarin’s goal is to file an IND for BMN 293 in the second half of 2023.

Change in Non-GAAP Measures Beginning in 2023
Beginning with the first quarter of 2023, the Company defines Non-GAAP Income as GAAP Net Income excluding amortization of intangible assets, stock-based compensation expense, and certain other specified items. Reflecting this change in the Company’s full year 2022 financial results as detailed above would have lowered the Company’s full year 2022 Non-GAAP Income by $73.8 million and its full year 2022 Non-GAAP diluted earnings per share (EPS) by $0.38. The Company is also introducing a new Non-GAAP financial measure, Non-GAAP Diluted EPS, which is defined as Non-GAAP Income divided by Non-GAAP diluted shares outstanding. Refer to page 10 of this press release for a complete discussion of the Company’s current Non-GAAP financial information and reconciliations to comparable information reported under U.S. GAAP.
2023 Full-Year Financial Guidance (in millions, except % and EPS amounts)
Item 2023 Guidance
Total Revenues $2,375 to $2,500
Enzyme Product Revenues(1)
$1,700 to $1,850
ROCTAVIAN Revenues $100 to $200
VOXZOGO Revenues $330 to $380
Gross Profit % 77.5% to 79%
R&D % of Revenue 30% to 32%
SG&A % of Revenue 36% to 38%
GAAP Net Income $155 to $205
GAAP Diluted EPS $0.78 to $1.03
Non-GAAP Income (new method) $360 to $410
Non-GAAP Diluted EPS (new method) $1.80 to $2.05

(1) Enzyme Products include ALDURAZYME, VIMIZIM, NAGLAZYME, BRINEURA, and PALYNZIQ.
The full-year 2023 ROCTAVIAN revenue guidance range, provided above, represents global revenue estimates and assumes a U.S. approval in 2023, regardless of approval timing.
BioMarin will host a conference call and webcast to discuss fourth quarter and full year 2022 financial results today, Monday, February 27, 2023 at 4:30 p.m. ET. This event can be accessed through this link or on the investor section of the BioMarin website at www.biomarin.com.
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U.S./Canada Dial-in Number: 800-831-4163 Replay Dial-in Number: 800-645-7964
International Dial-in Number: 213-992-4616 Replay International Dial-in Number: 757-849-6722
No Conference ID
Conference ID: 9184#

On February 27, 2023 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported financial results for the fourth quarter and full year 2022, recent business highlights, and upcoming milestones (Press release, BeiGene, FEB 27, 2023, View Source [SID1234627715]).

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"We had an outstanding fourth quarter and 2022, with revenues from our two cornerstone medicines, BRUKINSA and tislelizumab, dramatically increasing as our global team continues to bring these innovative therapies to more patients and their caregivers," said John V. Oyler, Co-Founder, Chairman and Chief Executive Officer at BeiGene. "The final progression-free survival (PFS) analysis of the ALPINE trial demonstrating superior efficacy and a favorable cardiac safety profile compared to IMBRUVICA in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and the recent U.S. FDA approval for BRUKINSA in adult patients with CLL/SLL were the most impactful of many recent milestones for our company and a testament to our commitment to following the science."

"Our fourth quarter results continue to demonstrate BeiGene’s commercial capability as well as our commitment to driving operational and financial excellence," said Julia Wang, Chief Financial Officer at BeiGene. "With our strong cash position and total product revenue reaching $1.3 billion in 2022, BeiGene is well positioned to leverage its global scale and financial strength for long-term growth."

Fourth Quarter and Full Year 2022 Financial Results

Revenue for the fourth quarter and full year 2022 was $380.1 million and $1.4 billion, respectively, compared to $214.0 million and $1.2 billion in the prior-year periods. The increase in total revenue in the quarter compared to the prior year is primarily attributable to sales of our internally developed products, BRUKINSA and tislelizumab; sales of in-licensed products from Amgen; and collaboration revenue from the Novartis agreements.

Product revenues totaled $339.0 million and $1.3 billion for the fourth quarter and full year 2022, respectively, compared to $196.8 million and $634.0 million in the prior-year periods, and include:
Global sales of BRUKINSA of $176.1 million and $564.7 million for the fourth quarter and full year 2022, respectively, compared to $87.6 million and $218.0 million in the prior-year periods;
Sales of tislelizumab in China of $102.2 million and $422.9 million for the fourth quarter and full year 2022, respectively, compared to $54.4 million and $255.1 million in the prior-year periods;
Sales of Amgen in-licensed products in China of $27.7 million and $114.6 million for the fourth quarter and full year 2022, respectively, compared to $20.3 million and $58.8 million in the prior-year periods. We began selling Amgen’s BLINCYTO (blinatumomab) in August 2021. Additionally, prior-year period sales do not include sales of KYPROLIS (carfilzomib), which was launched in China in January 2022;
Sales of BMS in-licensed products in China of $21.4 million and $94.3 million for the fourth quarter and full year 2022, respectively, compared to $29.9 million and $89.7 million in the prior-year periods; and
Collaboration revenue totaled $41.1 million and $161.3 million for the fourth quarter and full year 2022, respectively, resulting from the partial recognition of the upfront payments from Novartis related to the tislelizumab and ociperlimab agreements, which were entered into in the first and fourth quarters of 2021. This compared to $17.2 million and $542.3 million in the prior-year periods. Full year 2021 collaboration revenue benefited from the timing of revenue recognition from the upfront license payment from Novartis under the tislelizumab agreement.
Cost of Sales for the fourth quarter and full year 2022 were $73.5 million and $286.5 million, respectively, compared to $48.5 million and $164.9 million in the prior-year periods. Cost of sales increased primarily due to increased product sales of BRUKINSA and tislelizumab, as well as sales of BLINCYTO, which commenced in August 2021, and KYPROLIS and POBEVCY, which commenced in January 2022;

Gross Margin as a percentage of global product sales for the fourth quarter and full year 2022 was 78.3% and 77.2%, respectively, compared to 75.3% and 74.0% in the prior-year periods. The gross margin percentage increased in both the quarter-over-quarter and year-over year periods primarily due to a proportionally higher sales mix of global BRUKINSA sales compared to other products in our portfolio and compared to lower margin sales of in-licensed products, as well as lower costs per unit for both BRUKINSA and tislelizumab, partially offset by lower average selling prices in China for both BRUKINSA and tislelizumab.

Operating Expenses for the fourth quarter and full year 2022 were $775.2 million and $2.9 billion, respectively, compared to $737.2 million and $2.5 billion in the prior-year periods.

R&D Expenses for the fourth quarter and full year 2022 were $446.0 million and $1.6 billion, respectively, compared to $430.5 million and $1.5 billion in the prior-year periods. The increase in R&D expenses was primarily attributable to increases in headcount and costs related to investment in our discovery and development activities, including our continued efforts to internalize research and clinical development activities, partially offset by lower fees paid to clinical research organizations (CROs) for clinical trials. Upfront fees related to in-process R&D for in-licensed assets totaled $48.7 million and $68.7 million in the fourth quarter and full year 2022, respectively, compared to $30.0 million and $83.5 million in the prior-year periods. Employee share-based compensation expense was $35.0 million and $139.3 million for the fourth quarter and full year 2022, respectively, compared to $30.6 million and $114.4 million in the prior-year periods; and
SG&A Expenses for the fourth quarter and full year 2022 were $329.0 million and $1.3 billion, respectively, compared to $306.5 million and $990.1 million in the prior-year periods. The increase in SG&A expenses was primarily attributable to increased headcount, largely related to continued expansion of our commercial teams, and higher external commercial expenses, including market access studies and promotional activities. Employee share-based compensation expense was $43.2 million and $163.8 million for the fourth quarter and full year 2022, respectively, compared to $32.4 million and $126.4 million for the prior-year periods.
Net Loss for the fourth quarter of 2022 was $445.3 million, or $0.33 per share and $4.29 per ADS, compared to $590.7 million, or $0.48 per share and $6.22 per ADS in the prior year period. The decrease in net loss is primarily attributable to improved operating leverage due to growing product revenues exceeding operating expense growth. The company expects this trend to continue into 2023. Net loss for full year 2022 was $2.0 billion, or $1.49 per share and $19.43 per ADS, compared to $1.5 billion, or $1.21 per share and $15.71 per ADS in the prior-year period. Net loss for 2022 was unfavorably impacted by other non-operating expenses of $223.9 million, primarily related to foreign exchange losses resulting from the strengthening of the U.S. dollar and the revaluation impact of foreign currencies held in U.S. functional currency subsidiaries. Net loss for the full year 2021 was positively impacted by the timing of revenue recognition related to the Novartis tislelizumab collaboration agreement. The company recognized $484.6 million in the full year 2021 of the $650.0 million upfront payment received.

Cash, Cash Equivalents, Restricted Cash and Short-Term Investments were $4.5 billion as of December 31, 2022, compared to $6.6 billion as of December 31, 2021.

In the fourth quarter of 2022, cash used in operating activities was $318.2 million, primarily due to our net loss of $445.3 million, offset by non-cash charges of $127.3 million; capital expenditures were $121.4 million; and cash used in financing activities was $110.4 million;

In the fourth quarter of the prior year, cash used in operating activities was $507.8 million, primarily due to our net loss of $590.7 million, offset by non-cash charges of $92.7 million; capital expenditures were $115.0 million; and cash provided by financing activities was $3.4 billion, primarily due to the STAR Market offering in December of 2021; and

For the full year 2022, cash used in operating activities was $1.5 billion, primarily due to our net loss of $2.0 billion, inclusive of $223.9 million of other losses due primarily to the strengthening of the U.S. dollar and the related revaluation of foreign currencies held by U.S. functional currency subsidiaries, non-cash charges of $374.8 million and a decrease in our net operating assets and liabilities of $132.4 million.

For the full year 2021, cash used in operating activities was $1.3 billion, primarily due to our net loss of $1.5 billion and an increase in our net operating assets and liabilities of $118.3 million, partially offset by non-cash charges of $277.4 million; capital expenditures were $262.9 million; and cash provided by financing activities was $3.6 billion, primarily due to the net proceeds from the STAR Market offering in December of 2021.
Recent Business Highlights

Commercial Operations

Product sales increased 72.3% and 97.9% in the fourth quarter and full year of 2022, respectively, compared to the prior-year periods, primarily due to increased sales of our internally developed products, as well as increased sales of in-licensed products from Amgen and Bio-Thera;
Global sales of BRUKINSA totaled $176.1 million and $564.7 million in the fourth quarter and full year 2022, representing growth of 101% and 159%, respectively, compared to the prior-year periods; U.S. sales of BRUKINSA totaled $125.3 million and $389.7 million in the fourth quarter and full year 2022, respectively, representing growth of 124% and 237%, compared to the prior-year periods. U.S. sales growth continued in the quarter, driven again by increasing uptake in mantle cell lymphoma (MCL), Waldenström’s macroglobulinemia (WM), and marginal zone lymphoma (MZL). BRUKINSA sales in China totaled $40.9 million and $150.3 million in the fourth quarter and full year 2022, respectively, representing growth of 33% and 49% compared to the prior-year periods, driven by increases in all approved indications;
Sales of tislelizumab in China totaled $102.2 million and $422.9 million in the fourth quarter and full year 2022, respectively, representing growth of 88% and 66% compared to the prior-year periods. Continued increase in new patient demand from broader reimbursement and further expansion of our salesforce and hospital listings continued to drive increased market penetration and market share for tislelizumab;
Secured National Reimbursement Drug List (NRDL) inclusion of four additional indications in China, with nine approved tislelizumab indications now included. New indications covered as of March 1, 2023, are for:
Certain adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC);
Adult patients with advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, and certain patients with advanced colorectal cancer (CRC);
Adult patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have progressed after or are intolerant of prior first-line standard chemotherapy; and
As a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (NPC); and
KYPROLIS was included in the NRDL for the first time for the treatment of adult patients with R/R multiple myeloma who have received at least two prior therapies, including a proteasome inhibitor and an immunomodulatory agent. XGEVA was successfully renewed for NRDL inclusion for the treatment of patients with giant cell tumor of the bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity.
Regulatory Progress and Development Programs

BRUKINSA (zanubrutinib), a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to maximize BTK occupancy and minimize off-target effects, approved in more than 65 markets including the U.S., China, European Union (EU), Great Britain, Canada, Australia, South Korea and Switzerland in selected indications and under development for additional approvals globally. The global BRUKINSA development program includes more than 4,800 subjects enrolled to-date in 29 countries and regions.

In January 2023, announced U.S. FDA approval for the treatment of adult patients with R/R and first-line CLL/SLL;
Announced European Commission (EC) approval for the treatment of adult patients with treatment-naïve (TN) or R/R CLL;
Presented results from a final analysis of the Phase 3 ALPINE trial demonstrating superior PFS versus IMBRUVICA in adult patients with R/R CLL/SLL, as assessed by an independent review committee (IRC) and investigator, as part of a late breaking abstract session at the 64th American Hematology Society (ASH) (Free ASH Whitepaper) Annual Meeting, with simultaneous publication in The New England Journal of Medicine;
Presented other key data from the BRUKINSA clinical development programs at ASH (Free ASH Whitepaper) 2022, including an oral presentation of results from the MAGNOLIA trial in MZL and a poster with updated results in acalabrutinib-intolerant patients with B-cell malignancies;
Announced approvals in Brazil for the treatment of adult patients with WM and adult patients with R/R MZL who have received at least one anti-CD20-based regimen;
Received marketing authorization by the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain for the treatment of adult patients with CLL, and those with MZL who have received at least one prior anti-CD20-based therapy; and
Expanded BRUKINSA’s registration program globally, including 34 launches in 20 markets since January 1, 2022.
Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages; approved in China in 10 indications and under development for additional approvals globally. The global tislelizumab clinical development program includes more than 11,800 subjects enrolled to-date in 31 countries and regions.

Announced China National Medical Products Administration (NMPA) approval of BLA application for tislelizumab in combination with chemotherapy as a first-line treatment for patients with locally advanced unresectable or metastatic G/GEJ adenocarcinoma with high PD-L1 expression, which is the tenth approved indication in China for tislelizumab;
Announced acceptance by the NMPA of a supplemental biologics license application (sBLA) in patients with first-line unresectable or metastatic hepatocellular carcinoma (HCC);
Filed new drug application for tislelizumab in Brazil seeking marketing authorization for use in first- and second-line NSCLC and second-line esophageal cancer, marking BeiGene’s first application for tislelizumab in Latin America; and
Presented results from the RATIONALE-301 (NCT03412773), RATIONALE-305 (NCT03777657) and RATIONALE-306 (NCT03783442) trials at the 2023 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, including positive interim overall survival (OS) data for a combination of tislelizumab and chemotherapy in first-line gastric or gastroesophageal junction (G/GEJ) cancer patients whose tumors express PD-L1.
Ociperlimab (BGB-A1217), an investigational anti-TIGIT monoclonal antibody with competent Fc function. The global ociperlimab development program includes 17 countries and regions, and more than 1,600 subjects have been enrolled.

Presented Phase 1 clinical data for checkpoint inhibitor-experienced advanced NSCLC and extensive-stage small cell lung cancer (SCLC) (NCT04047862) at ESMO (Free ESMO Whitepaper)-IO 2022.
BGB-11417, an investigational highly selective and highly potent inhibitor of BCL-2, being developed as monotherapy or in combination with zanubrutinib +/- obinutuzumab in B-cell malignancies, in combination with azacytidine in AML and MDS and as monotherapy and in combination with dexamethasone and in combination with carfilzomib in multiple myeloma. The global BGB-11417 development program includes six countries and regions, and more than 350 subjects have been enrolled.

Presented Phase 1 clinical data for non-Hodgkin’s lymphoma, CLL, acute myeloid leukemia (AML) and multiple myeloma (MM) (NCT04883957, NCT04277637, NCT04771130, and NCT04973605) at ASH (Free ASH Whitepaper) 2022.
BGB-A445, an investigational non-ligand competing OX40 monoclonal antibody, being developed as monotherapy or in combination with tislelizumab.

Initiated patient dosing in a Phase 2 basket trial as monotherapy and in combination with tislelizumab in melanoma, renal cell cancer (RCC) and bladder cancer (NCT05661955).
Early-Stage Programs

Continued to advance our early-stage clinical pipeline of internally developed product candidates at dose escalation stage, including:
BGB-B167: an investigational first-in-class CEA x 4-1BB bispecific antibody, as a monotherapy and in combination with tislelizumab in patients with selected CEA-expressing advanced or metastatic solid tumors, including colorectal cancer (CRC);
BGB-A425: an investigational TIM-3 antibody, in combination with tislelizumab in patients with head and neck squamous cell carcinoma (HNSCC), NSCLC and RCC;
BGB-15025: an investigational, first-in-class hematopoietic progenitor kinase 1 (HPK1) inhibitor as monotherapy or in combination with tislelizumab in solid tumors;
BGB-16673: an investigational Chimeric Degradation Activating Compound (CDAC), targeting BTK protein degradation as monotherapy in B cell malignancies;
BGB-24714: an investigational Second Mitochondrial-derived Activator of Caspase, or SMAC, mimetic as monotherapy or in combination with paclitaxel in advanced solid tumors;
BGB-10188: an investigational PI3Kδ inhibitor as monotherapy or in combination with BRUKINSA in hematology malignancies, or in combination with tislelizumab in solid tumors; and
BGB-23339: a potent, allosteric investigational tyrosine kinase 2 (TYK2) inhibitor.
Collaboration Programs

In collaboration with Zymeworks, announced positive topline results for a Phase 2b clinical trial of zanidatamab in advanced or metastatic HER2-amplified biliary tract cancers (NCT04466891); and
In collaboration with Mirati, initiated patient enrollment for a Phase 2 clinical trial of sitravatinib in combination with tislelizumab in locally advanced unresectable or metastatic ESCC that progressed on or after anti-PD-(L)1 antibody therapy (NCT05461794).
Manufacturing Operations

Construction continues on the U.S. flagship manufacturing and clinical R&D facility at the Princeton West Innovation Campus in Hopewell, N.J. The property has more than one million square feet total of developable real estate, allowing for future expansion;
Completed expansion and Good Manufacturing Practices (GMP) certification of our state-of-the-art biologics facility in Guangzhou, China, bringing total capacity to 54,000 liters with an additional expansion of 10,000 liters expected in the second quarter of 2023; and
Continued construction on our new small molecule manufacturing campus in Suzhou, China. Phase 1 of construction is expected to add more than 559,000 square feet and expand production capacity to 600 million tablets/capsules, and to be completed in 2023. Once completed, qualified and approved, the total production capacity is expected to increase our small molecule manufacturing capability in China by up to 10 times current capacity.
Corporate Developments

Announced the launch of the Talk About It: Cancer and Mental Health program, designed to elevate the important intersection of mental health and cancer care to help improve health outcomes for cancer patients.
Expected Milestones

BRUKINSA

Submit supplemental New Drug Applications (sNDA) in the U.S. and EU in the first half of 2023 for PFS superiority versus IMBRUVICA in R/R CLL/SLL, as demonstrated in the Phase 3 ALPINE trial;
Continue to support NMPA review of sNDA for first-line CLL/SLL and WM in China, with a decision expected in the first half of 2023;
Continue to support Health Canada and Australian Therapeutic Goods Administration (TGA) reviews of sNDAs for CLL, with decisions expected in 2023; and
Continue to expand BRUKINSA’s registration program globally in new geographies and indications.
Tislelizumab

Continue to support NMPA review of BLA applications for tislelizumab in combination with chemotherapy as a first-line treatment in patients with unresectable locally advanced, recurrent or metastatic ESCC, with a decision expected in the first half of 2023; and for tislelizumab as a treatment for first-line hepatocellular carcinoma, with a decision expected in the second half of 2023;
Continue to support review by regulatory authorities of BeiGene’s applications for tislelizumab, including:
Australia’s TGA review of BLA for tislelizumab in first- and second-line NSCLC and second-line ESCC, with a decision expected in the second half of 2023, as well as New Zealand’s Medsafe review of BLA for tislelizumab in first- and second-line NSCLC and second-line ESCC; and
South Korea’s MFDS review of BLA for tislelizumab in second-line ESCC;
In collaboration with Novartis, continue to support review of marketing applications, including:
Ongoing FDA review of the BLA submission in second-line ESCC, including facilitating the scheduling of required inspections as soon as possible, with a decision expected in 2023;
European Medicines Agency (EMA) review of marketing authorization applications for tislelizumab in first- and second-line NSCLC and second-line ESCC, with a decision expected in 2023;
MHRA review of tislelizumab for treatment of first- and second-line NSCLC and second-line ESCC in Great Britain;
Swissmedic review of marketing authorization applications for tislelizumab in second-line ESCC and second-line NSCLC;
Support U.S. FDA regulatory submission by Novartis in 2023 for first-line gastric cancer and first-line unresectable ESCC;
Submit BLA to Japan’s Pharmaceutical and Medical Devices Agency (PMDA) in 2023 for first- and second-line ESCC; and
Announce final analysis data from pivotal trials in extensive-stage small cell lung cancer and first-line gastric cancer in 2023.
BGB-11417 (BCL-2)

Initiate global pivotal trial in first-line CLL in combination with BRUKINSA in the second half of 2023; and
Announce readouts from ongoing studies.
Ociperlimab (TIGIT)

Announce readouts for multiple Phase 2 studies in 2023, including:
For second-line ESCC in patients whose tumors express PD-(L)1 (NCT04732494);
For first-line HCC (NCT04948697);
For first-line NSCLC (NCT05014815); and
Complete enrollment in the Phase 3 AdvanTIG-302 trial in first-line NSCLC in 2023.
BGB-16673 (BTK CDAC)

Initial data readouts for Phase 1 studies in B cell malignancies (NCT05006716, NCT05294731) in 2023.
BGB-A445 (OX 40)

Initial data readout for Phase 1 study in solid tumors (NCT04215978) in 2023.
BGB-15025 (HPK 1)

Initiate dose expansion in combination with tislelizumab in solid tumors (NCT04649385) in 2023.
Collaboration Programs

In collaboration with Leads Biolabs, initiate patient dosing of LBL-007, a novel investigational antibody targeting the LAG-3 pathway, in combination with tislelizumab, in umbrella studies comparing different tislelizumab combination regimens, including with BGB-A445 and ociperlimab (NCT05635708, NCT05577702), in 2023.
COVID-19 Impact and Response

We expect that the worldwide health crisis of COVID-19 will continue to have a negative impact on our operations, including commercial sales, regulatory interactions, inspections, filings, manufacturing, and clinical trial recruitment, participation, and data readouts. There remains uncertainty regarding the future impact of the pandemic both globally and specifically in China due to outbreaks and restrictions and potential impact on clinical, manufacturing and commercial operations. We are striving to minimize delays and disruptions, have put protocols and procedures in place, and continue to execute on our commercial, regulatory, manufacturing, and clinical development goals globally.

Financial Summary

Select Condensed Consolidated Balance Sheet Data (U.S. GAAP)

(Amounts in thousands of U.S. Dollars)

As of

December 31,

December 31,

2022

2021 1

(audited)

Assets:

Cash, cash equivalents, restricted cash and short-term investments

$

4,540,288

$

6,624,849

Accounts receivable

173,168

483,113

Property and equipment, net

845,946

587,605

Total assets

$

6,379,290

$

8,535,525

Liabilities and equity:

Accounts payable

$

294,781

$

262,400

Accrued expenses and other payables

467,352

558,055

Deferred revenue

255,887

407,703

R&D cost share liability

293,960

390,362

Debt

538,117

629,678

Total liabilities

1,995,935

2,402,962

Total equity

$

4,383,355

$

6,132,563

Condensed Consolidated Statements of Operations (U.S. GAAP)

(Amounts in thousands of U.S. dollars, except for shares, American Depositary Shares (ADSs), per share and per ADS data)

Three Months Ended

December 31,

Twelve Months Ended

December 31,

2022

2021 1

2022

2021 1

(unaudited)

(audited)

Revenue:

Product revenue, net

$

339,022

$

196,785

$

1,254,612

$

633,987

Collaboration revenue

41,073

17,194

161,309

542,296

Total revenues

380,095

213,979

1,415,921

1,176,283

Expenses:

Cost of sales – products

73,522

48,545

286,475

164,906

Research and development

446,023

430,485

1,640,508

1,459,239

Selling, general and administrative

328,984

306,501

1,277,852

990,123

Amortization of intangible assets

188

187

751

750

Total expenses

848,717

785,718

3,205,586

2,615,018

Loss from operations

(468,622

)

(571,739

)

(1,789,665

)

(1,438,735

)

Interest (expense) income, net

18,219

(4,482

)

52,480

(15,757

)

Other (expense) income, net

19,438

(10,583

)

(223,852

)

15,904

Loss before income taxes

(430,965

)

(586,804

)

(1,961,037

)

(1,438,588

)

Income tax expense

14,370

3,874

42,778

19,228

Net loss

(445,335

)

(590,678

)

(2,003,815

)

(1,457,816

)

Less: Net loss attributable to noncontrolling interest

—

—

—

—

Net loss attributable to BeiGene, Ltd.

$

(445,335

)

$

(590,678

)

$

(2,003,815

)

$

(1,457,816

)

Net loss per share attributable to BeiGene, Ltd., basic and diluted

$

(0.33

)

$

(0.48

)

$

(1.49

)

$

(1.21

)

Weighted-average shares outstanding, basic and diluted

1,348,916,108

1,235,346,414

1,340,729,572

1,206,210,049

Net loss per ADS attributable to BeiGene, Ltd., basic and diluted

$

(4.29

)

$

(6.22

)

$

(19.43

)

$

(15.71

)

Weighted-average ADSs outstanding, basic and diluted

103,762,778

95,026,647

103,133,044

92,785,388

[1] We revised certain prior period financial statements for an error related to the valuation of net deferred tax assets, the impact of which was immaterial to our previously filed financial statements in the first and second quarter of 2022 and the quarterly and annual periods of fiscal 2021 (see "Notes to the Consolidated Financial Statements, Note. 2 Summary of Significant Accounting Policies" and "Note 3. Revision of Prior Period Financial Statements" included in our Annual Report on Form 10-K for the fiscal year ended 2022).

BeiGene is a global biotechnology company that is developing and commercializing innovative and affordable oncology medicines to improve treatment outcomes and access for far more patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 9,000 colleagues spans five continents, with administrative offices in Basel; Beijing; and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGloba

On February 27, 2023 Anixa Biosciences, Inc. (NASDAQ: ANIX) ("Anixa"), a biotechnology company focused on the treatment and prevention of cancer and infectious diseases, reported that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance broadening protection of Anixa’s novel breast cancer vaccine technology (Press release, Anixa Biosciences, FEB 27, 2023, View Source [SID1234627713]). This technology was invented and developed at Cleveland Clinic and Anixa is the exclusive worldwide licensee.

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The patent is titled, "Vaccine Adjuvants and Formulations," and the lead inventor is the late Dr. Vincent Tuohy, of Cleveland Clinic. This patent covers additional intellectual property related to the formulation of Anixa’s breast cancer vaccine.

"We are pleased to receive this notice of allowance from the USPTO, confirming additional protection of our breast cancer vaccine technology," stated Dr. Amit Kumar, Chairman and CEO of Anixa. "This breast cancer vaccine has the potential to prevent Triple Negative Breast Cancer ("TNBC"), the deadliest form of breast cancer, and perhaps other forms of breast cancer that express alpha-lactalbumin. With our partners at Cleveland Clinic, we are currently performing clinical trials of this vaccine, and plan to present data from the trial at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April."

About Triple-Negative Breast Cancer
One in eight women in the U.S. will be diagnosed with an invasive breast cancer at some point in their lives. Approximately 10-15% of those diagnoses are TNBC, however TNBC accounts for a disproportionately higher percentage of breast cancer deaths and has a higher rate of recurrence. This form of breast cancer is twice as likely to occur in African-American women, and approximately 70% to 80% of the breast tumors that occur in women with mutations in the BRCA1 genes are triple-negative breast cancer.

About Anixa Bioscience’s Breast Cancer Vaccine
Anixa’s breast cancer vaccine, currently in Phase 1 trials, takes advantage of endogenously produced proteins that have a function at certain times in life, but then become "retired" and disappear from the body. One such protein is a breast-specific lactation protein, α-lactalbumin, which is no longer found post-lactation in normal, aging tissues, but is present in the majority of triple-negative breast cancers. Activating the immune system against this "retired" protein provides preemptive immune protection against emerging breast tumors that express α-lactalbumin. The vaccine also contains an adjuvant that activates an innate immune response, which allows the immune system to mount a response against emerging tumors to prevent them from growing. This vaccine technology was invented by the late Dr. Vincent Tuohy, who was the Mort and Iris November Distinguished Chair in Innovative Breast Cancer Research in the Department of Inflammation and Immunity at Cleveland Clinic’s Lerner Research Institute. Dr. Tuohy is named as inventor on the technology, which Cleveland Clinic exclusively licensed to Anixa Biosciences.

On February 27, 2023 Chinook Therapeutics, Inc. (Nasdaq: KDNY), a biopharmaceutical company focused on the discovery, development and commercialization of precision medicines for kidney diseases, reported financial results for the fourth quarter and year ended December 31, 2022 and provided corporate updates (Press release, Chinook Therapeutics, FEB 27, 2023, View Source [SID1234627712]).

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"During 2022, we made excellent progress across our pipeline, including driving strong enrollment of our phase 3 ALIGN, phase 2 AFFINITY and phase 1/2 BION-1301 clinical trials, generating compelling clinical data from our atrasentan and BION-1301 programs for IgA nephropathy (IgAN), initiating our phase 1 clinical trial of CHK-336 in healthy volunteers and continuing to advance our preclinical programs for rare, severe chronic kidney diseases," said Eric Dobmeier, president and chief executive officer of Chinook Therapeutics. "Our mission at Chinook is to change the course of kidney care by developing therapies that make dialysis and transplant unnecessary for patients living with kidney disease. With our strong financial position and growing team, we look forward to an exciting 2023 when we will be presenting data from all three of our clinical programs at medical conferences, commencing a phase 3 study of BION-1301 in patients with IgAN mid-year and reporting topline proteinuria data from the ongoing phase 3 ALIGN study of atrasentan."

2022 and Recent Accomplishments

Atrasentan

Atrasentan is a potent and selective endothelin A (ETA) receptor antagonist that has potential therapeutic benefit in multiple chronic kidney diseases by reducing proteinuria and having direct anti-inflammatory and anti-fibrotic effects to preserve kidney function. The phase 3 ALIGN trial is evaluating atrasentan in patients with IgAN and the phase 2 AFFINITY basket trial is evaluating atrasentan in patients with proteinuric glomerular diseases.

Enrollment in the phase 3 ALIGN trial of atrasentan now exceeds 270 patients. The interim proteinuria endpoint analysis will be performed on the first 270 patients enrolled.

In response to review of the statistical analysis plan for the ALIGN trial, Chinook received correspondence from the U.S. Food and Drug Administration (FDA) last week recommending that evaluation of the interim proteinuria endpoint analysis for accelerated approval in the ALIGN trial be delayed from week 24 to week 36. The FDA referenced the likelihood that the later timepoint would allow for a greater amount of eGFR data to be evaluated at the time of accelerated approval. Chinook plans to engage with the FDA as soon as possible to discuss their advice. If Chinook shifts the interim proteinuria endpoint analysis of the ALIGN trial to 36 weeks, topline proteinuria data would be expected in the fourth quarter of 2023. Therefore, Chinook is updating its timing to report topline proteinuria data from the ALIGN trial to the second half of 2023.

Chinook has completed enrollment of the IgAN patient cohort of the AFFINITY trial, and continues to enroll the other cohorts, including patients with focal segmental glomerulosclerosis (FSGS), Alport syndrome and diabetic kidney disease in combination with SGLT2 inhibitors. Chinook plans to report additional data from cohorts of the AFFINITY trial in the second half of 2023.

In November 2022, the United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 11,491,137, titled, "Methods of Improving Renal Function," which is directed to methods of treating patients with IgAN with atrasentan, and expires in 2040 absent any patent term extensions.

Several presentations on atrasentan were delivered at nephrology conferences throughout 2022, including:

Updated interim data from the IgAN patient cohort of the phase 2 AFFINITY trial demonstrated consistent and clinically meaningful proteinuria reductions in patients with IgAN already on a maximally tolerated and stable dose of a RAS inhibitor. Specifically, atrasentan demonstrated mean reductions in 24-hour urine protein creatinine ratio (UPCR) of 38.1% at six weeks of treatment, 48.3% at 12 weeks of treatment and 54.7% at 24 weeks of treatment. After 24 weeks of treatment, 15 of the 19 patients (79%) who had completed this visit had greater than a 40% reduction in UPCR. There were no meaningful changes in blood pressure or acute eGFR effects, suggesting proteinuria reductions were not primarily due to hemodynamic effects of atrasentan, and there were no increases in BNP or mean bodyweight, suggesting minimal fluid retention. Atrasentan was well-tolerated, with no treatment-related serious adverse events. (ASN Kidney Week 2022)

Preclinical research on single-cell RNA-seq of a mouse model of IgAN, revealing a prominent expansion of failed repair proximal tubular epithelial cells, which was reversed by atrasentan but not by ACE inhibition. (ASN Kidney Week 2022)

Preclinical mechanistic data describing atrasentan’s effect to block mesangial cell injury and the pathogenic transcriptional networks driving IgAN progression in a model system. (59th ERA Congress)

BION-1301

BION-1301 is a novel anti-APRIL monoclonal antibody currently in phase 2 development for patients with IgAN. BION-1301’s potentially disease-modifying approach to treating IgAN by reducing circulating levels of galactose-deficient IgA1 (Gd-IgA1) has been demonstrated clinically in both healthy volunteers and patients with IgAN.

Chinook has finalized trial design, is conducting site and country feasibility and completing global regulatory interactions to enable initiation of a phase 3 trial of BION-1301 in mid-2023.

Chinook has completed enrollment of 30 patients in Cohort 2 of Part 3 of the ongoing phase 1/2 trial of BION-1301. Patients in Cohort 2 receive a subcutaneous (SC) dose of 600 mg of BION-1301 every two weeks. Chinook plans to report additional data from Cohorts 1 and 2 in the first and second half of 2023.

Chinook presented interim data from Cohorts 1 and 2 in a poster presentation at ASN Kidney Week 2022 in November, further demonstrating BION-1301’s disease-modifying potential in IgAN by generating rapid and durable reductions in mechanistic biomarkers and corresponding clinically meaningful proteinuria reductions within three months of initiating treatment, which was consistent across both cohorts.

In Cohort 1, patients transitioned from intravenous (IV) dosing at 450 mg every two weeks to SC dosing at 600 mg every two weeks after at least 24 weeks of treatment. Reductions in IgA and Gd-IgA1 were maintained beyond 52 weeks of treatment. Reductions in IgM, and to a lesser extent IgG, were also observed. BION-1301 demonstrated mean reductions in 24-hour UPCR of 30.4% in seven patients at 12 weeks of treatment, 48.8% in eight patients at 24 weeks of treatment, 66.9% in eight patients at 52 weeks of treatment, 67.4% in four patients at 76 weeks of treatment and 71.0% in two patients at 100 weeks of treatment.

In Cohort 2, SC BION-1301 treatment resulted in rapid and sustained reductions in IgA and Gd-IgA1, IgM, and to a lesser extent IgG, through 24 weeks of treatment, highly consistent with Cohort 1. BION-1301 demonstrated mean reductions in 24-hour UPCR of 28.7% in 15 patients at 12 weeks of treatment and 53.8% in 9 patients at 24 weeks of treatment, similar to reductions observed at the same timepoints in Cohort 1.

In both cohorts, BION-1301 was well-tolerated, with no serious adverse events or treatment discontinuations due to adverse events, and no anti-drug antibodies observed.

BION-1301 was granted orphan drug designation for the treatment of primary IgAN by the European Commission in July 2022.

CHK-336

CHK-336 is an oral small molecule lactate dehydrogenase A (LDHA) inhibitor with liver-targeted tissue distribution that Chinook is developing for the treatment of patients with primary hyperoxaluria (PH) and other kidney stone disorders driven by endogenous overproduction of oxalate.

The phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial evaluating CHK-336 in healthy volunteers is ongoing, and initial data from this trial is expected in the first half of 2023.

Chinook presented a poster on CHK-336 at ASN Kidney Week 2022, demonstrating preclinical efficacy in PH1 and PH2 mouse models, and the potential for benefit in non-genetic hyperoxalurias caused by oxalate overproduction was also described.

Precision Medicine Research & Discovery
Chinook is focused on the discovery and development of novel precision medicines for rare, severe chronic kidney diseases (CKDs) with defined genetic or molecular drivers of disease initiation and progression, and efficient development paths. Chinook has multiple preclinical programs across the discovery, target validation, lead identification and lead optimization stages to generate future clinical pipeline candidates. Chinook is leveraging its ongoing strategic collaboration with Evotec to identify and validate novel targets and enable patient stratification strategies through access to the NURTuRE CKD Patient Biobank, which provides comprehensive PANOMICS characterization of thousands of CKD patients with prospective clinical follow-up and retained bio-samples of urine and blood for exploratory biomarker analysis.

Chinook delivered an oral presentation at ASN Kidney Week 2022 in November on a multi-omics approach to the characterization of IgAN in the NURTuRE cohort, integrating clinical, histological, transcriptomic and serum proteomic data to gain deeper insights into patient stratification and IgAN disease pathogenesis. Also at ASN, Chinook presented a poster in collaboration with Evotec on a human data-driven, patient-centric and multi-omics-enabled target identification framework focused on common cellular and molecular mechanisms of CKD by leveraging the NURTuRE and QUOD patient cohorts.

Chinook delivered an oral presentation at the 59th ERA Congress in May 2022 on the approach used in collaboration with Evotec to leverage the NURTuRE CKD biobank to generate mechanistic disease understanding for patient-centric, integrated target and biomarker discovery that will enable the development of novel precision treatments for CKD patient subsets.

Corporate

Chinook recently announced the appointment of Andrew Oxtoby as Chief Commercial Officer. Under Andrew’s leadership, Chinook will develop its go-to-market strategy and build a commercial organization in preparation

for the potential launch of atrasentan and future pipeline products. Andrew brings to Chinook over 20 years of experience in marketing, sales, finance and commercial leadership roles at Aimmune Therapeutics and Eli Lilly and Company.

Sairopa B.V. (Sairopa) entered into an exclusive agreement with Exelixis, Inc. in November 2022 for the development of ADU-1805, a monoclonal antibody targeting SIRPα, and received an upfront payment of $40.0 million. The U.S. Food and Drug Administration (FDA) recently cleared Sairopa’s Investigational New Drug (IND) Application to evaluate the safety and pharmacokinetics of ADU-1805 in adults with advanced solid tumors, which triggers a $35.0 million milestone payment that will be paid to Sairopa in the first quarter of 2023. Under the terms of the agreement, Sairopa is eligible to receive additional payments if Exelixis exercises its option and upon achievement of specified development, commercial and net sales milestones, as well as tiered royalties on net sales worldwide. As of December 31, 2022, Chinook owned approximately a 36% interest in Sairopa and has one seat on its board of directors. Chinook will hold its shares in Sairopa until there is a liquidation event, at which time, in accordance with the CVR agreement, 50% of any net proceeds will accrue to the benefit of the CVR holders, net of deductions permitted, including taxes and certain other expenses.

Chinook closed a $120.7 million public offering in May 2022, which included the exercise in full of the underwriters’ option to purchase additional shares of common stock.

Chinook announced an outreach initiative in collaboration with the IgA Nephropathy Foundation and Komodo Health in April 2022, leveraging data and technology to drive awareness of IgAN and engage key medical providers at nephrology practices across the U.S., with the goal of ensuring patients have access to optimal support and treatment options earlier in their disease journey.

Fourth Quarter and Full Year Ended December 31, 2022 Financial Results

Cash Position – Cash, cash equivalents and marketable securities totaled $385.3 million as of December 31, 2022, compared to $355.1 million as of December 31, 2021.

Revenue – Revenue for the quarter and year ended December 31, 2022 was $0.5 million and $6.1 million, respectively, compared to $51.2 million and $51.6 million for the same periods in 2021. The higher revenue amounts in 2021 were primarily due to $41.2 million non-cash revenue recognized under Chinook’s license agreement with SanReno Therapeutics and a $10.0 million milestone payment earned under the collaboration agreement with Merck.

Expenses –

Research and development expenses for the quarter and year ended December 31, 2022 were $43.0 million and $141.2 million, respectively, compared to $24.9 million and $97.0 million, respectively, for the same periods in 2021. The increase was primarily due to higher employee-related costs, including stock-based compensation expense, an increase in licensing and contract research and manufacturing costs, consulting and outside services fees, as well as facilities and other costs to continue the progression of our research and clinical programs.

General and administrative expenses for the quarter and year ended December 31, 2022 were $9.8 million and $36.3 million, respectively, compared to $7.7 million and $31.9 million, respectively, for the same periods in 2021. The increase was primarily due to higher employee-related costs, including stock-based compensation expense, higher consulting and outside services costs to support our operations, and other costs. These increases were partially offset by a decrease in facilities costs.

The change in fair value of contingent consideration and contingent value rights liabilities for the quarter and year ended December 31, 2022 resulted in expenses of $7.3 million and $12.0 million, respectively, compared to expenses of $5.8 million and $27.3 million, respectively, for the same periods in 2021. The increase in these non-cash expenses in the quarter ended December 31, 2022 was primarily due to an increase in the fair value of the contingent value rights liability related to the preferred shares in Sairopa mainly as a result of Sairopa entering into a license agreement with Exelixis in November 2022. The decrease in the year ended December 31, 2022 was primarily due to a higher fair value in 2021 that included the impact of earning a milestone payment under the license agreement with Merck.

Net Loss – Net loss for the quarter ended December 31, 2022 was $62.6 million, or $0.90 per share, compared to net income of $7.5 million, or $0.15 per basic share for the same period in 2021. Net loss for the year ended December 31, 2022 was $187.9 million, or $2.92 per share, compared to $102.9 million, or $2.26 per share for the same period in 2021.