On February 26, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the company will participate in the TD Cowen 44th Annual Health Care Conference in Boston, Massachusetts, on Monday, March 4, 2024 (Press release, Bristol-Myers Squibb, FEB 26, 2024, View Source [SID1234640443]). Roland Chen, M.D., senior vice president, Immunology, Cardiovascular & Neuroscience development, will answer questions about the company during a fireside chat at 9:50 a.m. ET.

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Investors and the general public are invited to listen to a live webcast of the session here. An archived edition of the session will be available following its conclusion.

On February 26, 2024 Bristol Myers Squibb (NYSE: BMY) reported that it has successfully completed its acquisition of RayzeBio, Inc. (NASDAQ: RYZB) (Press release, Bristol-Myers Squibb, FEB 26, 2024, View Source [SID1234640442]). With the completion of the acquisition, RayzeBio shares have ceased trading on the NASDAQ Global Market and RayzeBio is now a wholly owned subsidiary of Bristol Myers Squibb.

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"We are excited to complete this transaction, which adds radiopharmaceutical therapeutics (RPTs), one of the fastest-growing new modalities for treating patients with solid tumors," said Chris Boerner, Ph.D., Chief Executive Officer, Bristol Myers Squibb. "By strengthening and further diversifying our oncology pipeline beyond I-O, we will unlock exciting opportunities that support BMS’s growth in the back half of the decade and beyond. RayzeBio is a pioneer in the application of this novel modality, and we look forward to working with their talented team to accelerate their preclinical and clinical programs for the benefit of patients around the world."

This transaction brings a promising pipeline of RPTs to Bristol Myers Squibb, including RayzeBio’s lead program RYZ101 (225Ac-DOTATATE), which targets somatostatin receptor 2 (SSTR2), over-expressed in GEP-NETs and extensive stage small cell lung cancer (ES-SCLC). A Phase 3 clinical trial is currently enrolling patients to evaluate RYZ101 in patients with SSTR-positive GEP-NETs who have previously been treated with lutetium-177 based somatostatin therapies. RayzeBio previously reported the interim results of the Phase 1b portion of the ACTION-1 clinical trial, suggesting encouraging efficacy and tolerability. A Phase 1b clinical trial is also currently enrolling patients to evaluate RYZ101 as a first-line treatment of ES-SCLC in combination with standard-of-care therapy. The platform has the potential to be a significant IND engine to generate a number of candidates and comes with a state-of-the-art RPT manufacturing facility, which is expected to begin operating in the first half of 2024.

Bristol Myers Squibb’s previously announced tender offer to acquire all of the outstanding shares of RayzeBio common stock for a purchase price of $62.50 per share in cash, or approximately $4.1 billion, expired at one minute after 11:59 p.m., Eastern Time on February 22, 2024. Approximately 53,052,499 shares of RayzeBio common stock were validly tendered, and not validly withdrawn from the tender offer, representing approximately 86% of RayzeBio’s issued and outstanding shares of common stock. In accordance with the terms of the tender offer, all shares that were validly tendered and not validly withdrawn have been accepted for payment and Bristol Myers Squibb expects to promptly pay for all such shares.

Following completion of the tender offer, Bristol Myers Squibb completed the acquisition of RayzeBio through the merger of its wholly owned subsidiary Rudolph Merger Sub Inc. with and into RayzeBio, without a vote of RayzeBio’s stockholders pursuant to Section 251(h) of the General Corporation Law of the State of Delaware. As a result of the merger, each share of common stock of RayzeBio issued and outstanding and not tendered in the tender offer was converted into the right to receive an amount in cash equal to $62.50, without interest and less any required withholding taxes, the same price offered in the tender offer.

RayzeBio stockholders can direct questions regarding the tender offer to Georgeson LLC, the information agent for the tender offer, toll free at 1-888-815-8542 or by email at [email protected].

Advisors

BofA Securities, Inc., is serving as financial advisor to Bristol Myers Squibb, and Covington & Burling LLP is serving as legal counsel. Centerview Partners LLC is serving as financial advisor to RayzeBio, and Cooley LLP is serving as legal counsel.

On February 26, 2024 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update (Press release, BioCryst Pharmaceuticals, FEB 26, 2024, View Source [SID1234640441]).

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"The impressive growth we are seeing with ORLADEYO has put us in a position to accelerate our path to profitability while continuing to invest in our diverse pipeline of first-in-class or best-in-class molecules that we believe will deliver our next marketed product," said Jon Stonehouse, president and chief executive officer of BioCryst.

Program Updates and Key Milestones

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

ORLADEYO net revenue in the fourth quarter of 2023 was $90.9 million.

The total number of U.S. patients on paid or long-term free product reached 1,104 at the end of the fourth quarter (+30 percent y-o-y) with 71.5 percent of those patients on paid product.

Net U.S. patient growth totaled 321 in 2023, including new patients still on short-term quick start product at the end of the quarter.

The number of new ORLADEYO prescribers in the fourth quarter of 2023 (Q4 2023) was the largest number of new prescribers of any quarter in 2023.

Real-world data presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting reinforced prior data showing patients switching to ORLADEYO experience sustained attack reduction regardless of baseline attack rate or prior HAE prophylaxis treatment.

Access to ORLADEYO continues to expand to more HAE patients around the world. In Q4 2023, ORLADEYO was approved in Argentina, launched in Spain, and granted final pricing approval in Austria. In the first quarter of 2024, ORLADEYO secured final reimbursement in Italy.
"As the real-world evidence with ORLADEYO consistently underscores, patients are switching to ORLADEYO because they can achieve outstanding HAE attack control and tolerability with an oral, once-daily therapy, leading to life-changing results," said Charlie Gayer, chief commercial officer of BioCryst.

Fourth Quarter 2023 Financial Results

For the three months ended December 31, 2023, total revenues were $93.4 million, compared to $79.5 million in the fourth quarter of 2022. The increase was primarily due to $90.9 million in ORLADEYO net revenue in the fourth quarter of 2023, compared to $70.7 million in the fourth quarter of 2022. Revenue in the fourth quarter of 2023 also included $2.3 million of net revenue from RAPIVAB related sales, compared to $8.7 million in the fourth quarter of 2022.

Research and development (R&D) expenses for the fourth quarter of 2023 decreased to $70.1 million from $73.2 million in the fourth quarter of 2022 (-4 percent year-over-year), primarily due to the discontinuation of the BCX9930 and BCX9250 programs announced in December 2022 and November 2022, respectively. These reductions were partially offset by increased investment in BCX17725 and our other early-stage programs, including the $5 million upfront payment to Clearside Biomedical related to avoralstat, and ORLADEYO label expansion and life cycle investments, such as our ongoing ORLADEYO pediatric trial.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2023 increased to $64.4 million, compared to $50.2 million in the fourth quarter of 2022 (+28 percent year-over-year). The increase was primarily due to increased investment to expand and enhance the U.S. commercial team and international operations.

Interest expense was $24.6 million in the fourth quarter of 2023, compared to $26.5 million in the fourth quarter of 2022. The decrease was primarily due to a decrease in the amortization of interest associated with our royalty financing obligations, partially offset by an increase in interest expense associated with the Pharmakon debt refinancing secured in April 2023.

Net loss for the fourth quarter of 2023 was $61.7 million, or $0.31 per share, compared to a net loss of $71.5 million, or $0.38 per share, for the fourth quarter of 2022. Non-GAAP net loss for the fourth quarter of 2023 was $56.4 million, or $0.28 per share when excluding one-time costs associated with the R&D restructuring and the postponement of the expansion at our Discovery Center in Alabama, totaling $5.4 million. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Cash, cash equivalents, restricted cash and investments totaled $390.8 million as of December 31, 2023, compared to $443.9 million as of December 31, 2022. Net cash utilization for the fourth quarter of 2023 was $8.6 million.

Full Year 2023 Financial Results

For the full year ended December 31, 2023, total revenues were $331.4 million, compared to $270.8 million in the full year ended December 31, 2022. The increase was primarily due to $326.0 million of ORLADEYO net revenue in 2023, compared to $251.6 million in 2022. The increase in ORLADEYO net revenue was partially offset by a decrease in other net revenues of $13.8 million, primarily due to RAPIVAB stockpiling sales to complete the U.S. Department of Health and Human Services procurement contract during the year ended December 31, 2022.

R&D expenses in full year 2023 decreased to $216.6 million from $253.3 million in full year 2022 (-14 percent year-over-year), primarily due to the discontinuation of the BCX9930 and BCX9250 programs announced in December 2022 and November 2022, respectively. These reductions were partially offset by increased investment in BCX17725, increased investment in our other early-stage discovery programs, including the $5 million upfront payment to Clearside Biomedical related to avoralstat, ORLADEYO label expansion and life cycle investments, such as our ongoing ORLADEYO pediatric trial, and an increase in indirect costs to support our programs.

SG&A expenses in full year 2023 increased to $213.9 million, compared to $159.4 million in full year 2022 (+34 percent year-over-year). The increase was primarily due to increased investment in order to expand and enhance the U.S. commercial team and expanded international operations.

Interest expense was $108.2 million in full year 2023, compared to $99.1 million in full year 2022. The increase in interest expense was primarily associated with the interest accrued on the Tranche A Loan of $300.0 million under the Pharmakon Loan Agreement.

Other expense was comprised primarily of a loss on extinguishment of debt of $29.0 million on the repayment of the term loans under the Athyrium Credit Agreement and net foreign currency losses of $1.0 million, partially offset by interest income of $15.8 million for the year ended December 31, 2023. Other income was comprised of interest income of $5.1 million, partially offset by net foreign currency losses of $2.0 million for the year ended December 31, 2022.

Net loss for full year 2023 was $226.5 million, or $1.18 per share, compared to a net loss of $247.1 million, or $1.33 per share, for full year 2022. Non-GAAP net loss for full year 2023 was $192.2 million, or $1.00 per share when excluding the one-time loss on debt extinguishment of $29.0 million on the repayment of the term loans under the Athyrium Credit Agreement recognized in the second quarter of 2023, as well as the R&D restructuring and the postponement of previously planned capital expenditures at our Discovery Center in Alabama recognized in the fourth quarter of 2023, totaling $5.4 million. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Non-GAAP Pro forma Financial Measures

The information furnished in this release includes non-GAAP pro forma financial measures that differ from measures calculated in accordance with generally accepted accounting principles in the United States of America ("GAAP"), including financial measures labeled as "non-GAAP" or "adjusted."

We believe providing these non-GAAP measures, which show our pro forma results with these items adjusted, is valuable and useful since they allow the company and investors to better understand the company’s financial performance in the absence of these one-time events and allowed investors to more accurately understand our 2023 results and more easily compare them to future results. These non-GAAP pro forma measures also correspond with the way we expect investors and financial analysts to compare our results. Our non-GAAP pro forma measures should be considered only as supplements to, and not as substitutes for or in isolation from, our other measures of financial information prepared in accordance with GAAP, such as GAAP revenue, operating income, net income, and earnings per share.

Our references to our fourth quarter 2023 and full year 2023 "non-GAAP pro forma" financial measures of adjusted net loss and adjusted earnings per share constitute non-GAAP financial measures. They refer to our GAAP results, adjusted to show the results without the one-time loss on debt extinguishment on the repayment of the term loans under the Athyrium Credit Agreement, as well as the R&D restructuring and the postponement of previously planned capital expenditures at our Discovery Center in Alabama. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Financial Outlook for 2024

The company expects full year 2024 global net ORLADEYO revenue to be between $380 million and $400 million. The general pattern of revenue throughout 2024 is expected to be similar to past years, with the seasonal impact of prescription reauthorizations and the potential impact of the Inflation Reduction Act in the first quarter driving a quarter-over-quarter revenue decline in the first quarter, followed by a strong return to growth in the second quarter.

The company expects full year 2024 operating expenses to be between $365 million and $375 million, flat to expected full year 2023 operating expenses. The company now expects that R&D expenses in 2024 will be reduced by between $20 million and $30 million versus 2023. SG&A expenses are expected to increase by $20 million in 2024, primarily to support the continued U.S. and global growth of ORLADEYO to $1 billion in peak sales.

This operating expense outlook does not reflect non-cash stock compensation expense, or one-time expenses related to the previously announced workforce reduction implemented in the first quarter of 2024.

Based on the company’s disciplined approach to capital allocation, and the revenue expected from ORLADEYO, the company expects to achieve a full-year operating profit in 2024 (not including non-cash stock compensation), be approaching quarterly positive earnings per share (EPS) and positive cash flow in the second half of 2025 (not including non-cash stock compensation), and be profitable on an EPS basis, with positive cash flow, for full year 2026. The company expects it can achieve these financial milestones without raising additional funds and does not intend to draw the additional $150 million of debt available to it from Pharmakon.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 1-844-481-2942 for domestic callers and 1-412-317-1866 for international callers. A live webcast and replay of the call will be available online in the investors section of the company website at www.biocryst.com.

On February 26, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending approval of tislelizumab as a treatment for non-small cell lung cancer (NSCLC) across three indications (Press release, BeiGene, FEB 26, 2024, View Source [SID1234640440]):

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In combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of adult patients with squamous NSCLC who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
In combination with pemetrexed and platinum-containing chemotherapy for the first-line treatment of adult patients with non-squamous NSCLC whose tumors have PD-L1 expression on ≥50% of tumor cells with no EGFR or ALK positive mutations and who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
As monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab.
"Through three Phase 3 clinical trials enrolling nearly 1,500 patients across the world including in the European Union, tislelizumab has been shown to be an effective therapy for patients with treatment-naïve and treatment-resistant NSCLC," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "Today’s positive CHMP opinion brings us one step closer to providing an important treatment option to patients in Europe with lung cancer, which is among the most common cancers and a leading cause of cancer death in the region."

The Marketing Authorization Application (MAA) for NSCLC is based on results from three Phase 3 studies that enrolled 1,499 patients. First-line combination therapy results from RATIONALE 307 evaluating tislelizumab in advanced squamous NSCLC and from RATIONALE 304 evaluating tislelizumab in locally advanced or metastatic non-squamous NSCLC were published in JAMA Oncology and in the Journal of Thoracic Oncology, respectively. Second-line monotherapy results from RATIONALE 303 evaluating tislelizumab in previously treated advanced NSCLC were published in the Journal of Thoracic Oncology.

Dr. Lanasa added, "As we strengthen our global portfolio in solid tumors, this positive CHMP opinion marks another significant milestone in the European Union for tislelizumab only a few months after it was approved for the treatment of advanced esophageal squamous cell carcinoma. We will continue to follow the science and data to advance tislelizumab as a monotherapy and combination treatment to address unmet needs of patients across the world."

Tislelizumab, under the brand name TEVIMBRA, received approval from the European Commission for advanced or metastatic ESCC after prior chemotherapy in 2023 and is currently under review with the U.S. Food and Drug Administration. Tislelizumab is also under review by the FDA as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC. BeiGene has launched more than 17 potentially registration-enabling trials with tislelizumab with over 13,000 patients enrolled to-date, of which 15 have already reported positive readouts. In these clinical studies, tislelizumab has consistently demonstrated its ability deliver clinically meaningful improvements in survival and quality of life with a positive benefit-risk balance for cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed tislelizumab to date.

About RATIONALE 307
RATIONALE 307 (NCT03594747) is an open-label, randomized Phase 3 trial that enrolled 360 patients with advanced squamous NSCLC. The study met its primary endpoint with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in progression free survival (PFS), as well as higher objective response rates (ORRs) and a manageable safety/tolerability profile, regardless of PD-L1 expression. The median PFS was 7.7 months for tislelizumab in combination with paclitaxel and carboplatin (hazard ratio, HR: 0.45 [95% CI: 0.326-0.619]; P< 0.001) and 9.6 months for tislelizumab in combination with nab-paclitaxel and carboplatin (HR: 0.43 [95% CI: 0.308-0.60]; P< 0.001) versus 5.5 months for paclitaxel and carboplatin alone, at a median study follow-up of 8.6 months. The most common grade ≥3 treatment emergent adverse events were decreased neutrophil levels, neutropenia and leukopenia.

About RATIONALE 304
RATIONALE 304 (NCT03663205) is an open-label, randomized Phase 3 trial that enrolled 334 patients with locally advanced or metastatic non-squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in PFS compared to chemotherapy (HR: 0.65 [95% CI: 0.47-0.91]; P=0.0054) along with higher response rates and longer response duration. The median PFS in the overall and in the PD-L1≥50% populations was 9.7 months for tislelizumab in combination with platinum (carboplatin or cisplatin) and pemetrexed versus 7.6 months for platinum and pemetrexed alone and 14.6 months with tislelizumab in combination with chemotherapy vs. 4.6 months with chemotherapy alone (stratified HR: 0.31 [95% CI: 0.178-0.547]) respectively, at a median study follow-up of 9.8 months. The most common grade ≥3 treatment emergent adverse events were associated with chemotherapy and included neutropenia and leukopenia.

About RATIONALE 303
RATIONALE 303 (NCT03358875) is an open-label, randomized Phase 3 trial with tislelizumab versus docetaxel that enrolled 805 patients with advanced NSCLC who progressed on prior platinum-based chemotherapy. The study met its primary endpoint, with second- or third-line tislelizumab resulting in statistically significant and clinically meaningful improvement in overall survival (OS) compared with docetaxel in the intent-to-treat population (HR: 0.66 [95% CI: 0.56-0.79]; P<0.0001), regardless of PD-L1 expression. The median OS was 16.9 months for tislelizumab versus 11.9 months for docetaxel. At the final analysis, OS in the PD-L1 positive population was also significantly improved in favor of tislelizumab (median 19.3 versus 11.5 months, respectively; HR: 0.53 [95% CI: 0.41-0.70]; P<0.0001). The most commonly reported grade ≥3 treatment emergent adverse events were pneumonia, anemia and dyspnea.

About NSCLC
Lung cancer is the second most common type of cancer and the leading cause of cancer-related death worldwide.1 Lung cancer is the third most common cancer in Europe; NSCLC represents 85–90% of all lung cancers.2 In 2020, the number of new cases of lung cancer diagnosed in Europe was estimated at 477,534.3

About Tislelizumab
Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.

On February 26, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported its continued global expansion, rapid global and U.S. revenue growth, and innovative R&D strategy with the presentation of results from the fourth quarter and full year 2023 and business highlights (Press release, BeiGene, FEB 26, 2024, View Source [SID1234640439]).

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"BeiGene made great progress in the fourth quarter and full year 2023 toward our goal to become an impactful next-generation oncology innovator. We have solidified our leadership in hematology with the continued success of BRUKINSA’s global launch, led by U.S. and Europe," said John V. Oyler, Chairman, Co-Founder and CEO at BeiGene. "Our cost advantaged research and development and manufacturing have enabled us to build one of the largest and most exciting oncology pipelines in the industry. We look forward to a transformative year for BeiGene as we continue to deliver on operational excellence propelled by outstanding growth in revenue across new and existing geographies."

Key Business and Pipeline Highlights

•Product revenues for the quarter, $630.5 million, and full year, $2.2 billion, increased 86% and 75% from prior-year totals;
•Disciplined management of operating expense growth drove operating loss decreases of 18% and 33% on a GAAP basis and 28% and 47% on an adjusted basis for the quarter and full year;
•Solidified BRUKINSA’s position as a BTK inhibitor of choice with U.S. Food and Drug Administration (FDA) approval of a label update to include superior progression-free survival (PFS) results at a median follow up of 29.6 months from the Phase 3 ALPINE trial comparing BRUKINSA against IMBRUVICA (ibrutinib) in previously treated patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL);
•Expanded global label for BRUKINSA with European Commission approval for the treatment of adult patients with R/R follicular lymphoma (FL) who have received at least two prior systematic treatments, making it the first BTK inhibitor ever approved in this indication and the BTK inhibitor with the broadest label in the class;
•Demonstrated leadership in hematology and strength of the Company’s pipeline with 25 abstracts presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December, including:
◦Updated results from the ALPINE trial demonstrating sustained PFS superiority at a median follow up of 39 months for BRUKINSA against IMBRUVICA for the treatment of adult patients with R/R CLL;
◦Phase 1/2 trial data for sonrotoclax demonstrating safety and tolerability in combination with BRUKINSA with deep and durable responses in treatment-naïve CLL; promising single-agent activity in patients with R/R marginal zone lymphoma; and promising efficacy and safety in combination with dexamethasone in multiple myeloma (MM) with t(11,14); and
◦First-in-human data for BTK CDAC BGB-16673 demonstrating notable clinical responses and a tolerable safety profile in heavily pretreated patients with B-cell malignancies, including those with BTKi-resistant disease.
•Expanded the global impact of anti-PD-1 antibody TEVIMBRA (tislelizumab) with a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval as a treatment for non-small cell lung cancer (NSCLC) across three indications, EMA acceptance of submission for the treatment of adult patients with first-line esophageal squamous cell carcinoma (ESCC), and regulatory reviews ongoing in 10 markets, including the U.S. and Europe; and

•Advanced innovative R&D strategy by entering five New Molecular Entities (NMEs) into the clinic in 2023, including potential best-in-class CDK4 inhibitor BGB-43395.

Fourth Quarter and Full Year 2023 Financial Highlights

Revenue for the fourth quarter and full year 2023 was $634.4 million and $2.5 billion, respectively, compared to $380.1 million and $1.4 billion in the prior-year periods. The increase in total revenue in the quarter compared to the prior year is primarily attributable to product sales growth in the Company’s major markets. For the fourth quarter and full year 2023, the U.S. was the largest market the Company derived revenue from, with revenue of $313.2 million and $1.1 billion, respectively, compared to $155.4 million and $502.6 million in the prior-year periods. The Company expects this trend to continue in 2024 as U.S. sales of BRUKINSA continue to grow.
Three Months Ended December 31, Twelve Months Ended December 31,
(in thousands, except per share amounts) 2023 2022 2023 2022
Net product revenues $ 630,526 $ 339,022 $ 2,189,852 $ 1,254,612
Net revenue from collaborations $ 3,883 $ 41,073 $ 268,927 $ 161,309
Total Revenue $ 634,409 $ 380,095 $ 2,458,779 $ 1,415,921
GAAP loss from operations $ (383,795) $ (468,622) $ (1,207,736) $ (1,789,665)
Adjusted loss from operations* $ (267,224) $ (372,480) $ (752,473) $ (1,420,225)

* For an explanation of our use of non-GAAP financial measures refer to the "Use of Non-GAAP Financial Measures" section later in this press release and for a reconciliation of each non-GAAP financial measure to the most comparable GAAP measures, see the table at the end of this press release.

Product Revenue totaled $630.5 million and $2.2 billion for the fourth quarter and full year 2023, respectively, compared to $339.0 million and $1.3 billion in the prior-year periods, and include:
•Global sales of BRUKINSA of $413.0 million and $1.3 billion for the fourth quarter and full year 2023, respectively, compared to $176.1 million and $564.7 million in the prior-year periods;
•Sales of tislelizumab of $128.0 million and $536.6 million for the fourth quarter and full year 2023, respectively, compared to $102.2 million and $422.9 million in the prior-year periods;
•Sales of Amgen in-licensed products of $51.1 million and $188.3 million for the fourth quarter and full year 2023, respectively, compared to $27.7 million and $114.6 million in the prior-year periods.
Gross Margin as a percentage of global product sales for the fourth quarter and full year 2023 was 83.2% and 82.7%, respectively, compared to 78.3% and 77.2% in the prior-year periods. The gross margin percentage increased in both the quarter-over-quarter and year-over-year period due to a proportionally higher product sales mix of global BRUKINSA compared to other products in our portfolio and compared to lower margin in-licensed products, as well as lower costs per unit for both BRUKINSA and tislelizumab.

Operating Expenses
The following table summarizes operating expenses for the fourth quarter 2023 and 2022, respectively:
GAAP Non-GAAP
(in thousands, except percentages) Q4 2023 Q4 2022 % Change Q4 2023 Q4 2022 % Change
Research and development $ 493,987 $ 446,023 11 % $ 437,383 $ 404,186 8 %
Selling, general and administrative $ 416,547 $ 328,984 27 % $ 361,435 $ 275,648 31 %
Amortization(1)
$ 1,838 $ 188 878 % $ — $ — NM
Total operating expenses $ 912,372 $ 775,195 18 % $ 798,818 $ 679,834 18 %

The following table summarizes operating expenses for the full year 2023 and 2022, respectively:
GAAP Non-GAAP
(in thousands, except percentages) FY 2023 FY 2022 % Change FY 2023 FY 2022 % Change
Research and development $ 1,778,594 $ 1,640,508 8 % $ 1,558,960 $ 1,474,919 6 %
Selling, general and administrative $ 1,504,501 $ 1,277,852 18 % $ 1,284,689 $ 1,077,977 19 %
Amortization(1)
$ 3,500 $ 751 366 % $ — $ — NM
Total operating expenses $ 3,286,595 $ 2,919,111 13 % $ 2,843,649 $ 2,552,896 11 %

(1)Relates to BMS product distribution rights intangible asset that was fully amortized as of December 31, 2023, when the rights reverted back to BMS under the terms of the Settlement Agreement.

Research and Development (R&D) Expenses increased for the fourth quarter and full year 2023 compared to the prior-year periods on both a GAAP and adjusted basis primarily due to investing in new platforms/modalities to advance preclinical programs into the clinic and early clinical programs into late stage. Upfront fees related to in-process R&D for in-licensed assets totaled $31.8 million and $46.8 million in the fourth quarter and full year 2023, respectively, compared to $48.7 million and $68.7 million in the prior-year periods.

Selling, General and Administrative (SG&A) Expenses increased for the fourth quarter and full year 2023 compared to the prior-year periods on both a GAAP and adjusted basis due to continued investment in the global commercial launch of BRUKINSA primarily in the U.S. and Europe.

Net Loss
GAAP net loss improved for the fourth quarter and full year 2023, as compared to the prior-year periods, primarily attributable to reduced operating losses and the non-operating gain of $362.9 million related to the BMS arbitration settlement for full year 2023.
For the fourth quarter of 2023, net loss per share was $0.27 per share and $3.53 per ADS, compared to $0.33 per share and $4.29 per ADS in the prior-year period. Net loss for full year 2023 was $0.65 per share and $8.45 per ADS, compared to $1.49 per share and $19.43 per ADS in the prior-year period.
Cash, Cash Equivalents, and Restricted Cash
Year Ended December 31,
2023 2022
(in thousands)
Cash, cash equivalents and restricted cash at beginning of period $ 3,875,037 $ 4,382,887
Net cash used in operating activities (1,157,453) (1,496,619)
Net cash provided by investing activities 60,004 1,077,123
Net cash provided by (used in) financing activities 416,478 (18,971)
Net effect of foreign exchange rate changes (8,082) (69,383)
Net decrease in cash, cash equivalents and restricted cash (689,053) (507,850)
Cash, cash equivalents and restricted cash at end of period $ 3,185,984 $ 3,875,037

Cash Used in Operations in fourth quarter and full year 2023, was $221.6 million and $1.2 billion, respectively, compared to $318.2 million and $1.5 billion in the prior-year periods, driven by improved operating leverage.
For further details on BeiGene’s 2023 Financial Statements, please see BeiGene’s Annual Report on Form 10-K for the year of 2023 filed with the U.S. Securities and Exchange Commission.

Regulatory Progress and Development Programs
Key Highlights
•Solidified BRUKINSA as a BTK inhibitor of choice with PFS superiority label update from the FDA, approvals in R/R FL in Europe and Canada
•Expanded TEVIMBRA global reach with pending regulatory submissions in 10 markets, including the U.S. and Europe
•Enrolled first patients in a Phase 3 global trial of sonrotoclax in first-line CLL and expansion cohorts with registration potential for BTK CDAC

Category Asset Recent Milestones
Regulatory Approvals BRUKINSA
•Received FDA approved label update to include superior PFS results in adult patients with R/R CLL/SLL based on results from the Phase 3 ALPINE trial
•Received approval from European Commission and authorization from Health Canada for the treatment of adult patients with R/R FL in combination with obinutuzumab who have received at least two prior lines of systemic therapy
•Received regulatory approval in four additional markets for R/R and treatment-naïve (TN) CLL
TEVIMBRA
•Received China National Medicinal Products Administration (NMPA) approval as first-line treatment in patients with unresectable hepatocellular carcinoma
•Received approval from the UK Medicines and Healthcare Regulatory Agency (MHRA) as second-line treatment in patients with advanced ESCC
Regulatory Submissions Tislelizumab
•Received a positive opinion from the CHMP of the EMA recommending approval as a treatment for NSCLC across three indications
•Received NMPA acceptance of a supplemental Biologics License Application (sBLA) submission for the treatment of previously untreated extensive stage small cell lung cancer (ES-SCLC) in combination with chemotherapy
•Received NMPA acceptance of a sBLA submission for treatment plus platinum-based chemotherapy followed by adjuvant treatment of adult patients with resectable Stage II or IIIA NSCLC
•Received EMA acceptance of submission for the treatment of adult patients with first-line ESCC

Clinical Activities BRUKINSA
•Announced positive follow-up data from the Phase 3 ALPINE study in R/R CLL/SLL versus IMBRUVICA at ASH (Free ASH Whitepaper) showing sustained PFS benefit and persistently lower rates of cardiovascular events
Tislelizumab
•Enrolled first patient in a Phase 1 clinical trial evaluating subcutaneous injection in the first-line treatment of patients with advanced or metastatic NSCLC
Sonrotoclax (BGB-11417)
•FDA granted orphan designations for multiple myeloma (MM), Waldenstrom’s macroglobulinemia (WM), acute myeloid leukemia (AML), and mantle cell lymphoma (MCL)
•Enrolled first patient in a global pivotal trial in combination with BRUKINSA in first-line CLL
•Presented data at ASH (Free ASH Whitepaper) demonstrating:
◦Sonrotoclax is safe and tolerable in combination with BRUKINSA with deep and durable responses in TN CLL
◦Encouraging data with potential to be first BCL2i approved in MM with t(11,14)
◦Promising single-agent activity in patients with R/R MZL

BTK CDAC
(BGB-16673)
•Presented data at ASH (Free ASH Whitepaper) from ongoing first-in-human study demonstrating notable clinical responses and a tolerable safety profile in heavily pretreated patients with B-cell malignancies, including those with BTKi-resistant disease
•Enrolled first patients in R/R MCL expansion cohort with potential for registration
•Fast Track and Orphan Drug designations received from FDA for R/R MCL

Anti-LAG3
(LBL-0071)
•In partnership with Leads Biolabs, first subject enrolled in a Phase 2 study as first-line treatment in patients with inoperable locally advanced or metastatic ESCC in combination with tislelizumab and chemotherapy
Early development
•Fully enrolled the first two cohorts in Phase 1 clinical trials for NME BGB-43395 (CDK4 inhibitor)

Anticipated Upcoming Milestones
Key Highlights

•Secure FDA approval for BRUKINSA in combination with obinutuzumab in R/R FL, making it the BTK inhibitor with the broadest label in the class
•Receive FDA approval for tislelizumab in first- and second-line ESCC, demonstrating global expansion of innovative solid tumor portfolio
Category Asset Anticipated Milestones
Anticipated Regulatory Approvals BRUKINSA
•Receive FDA approval in combination with obinutuzumab for the treatment of adult patients with R/R FL who have received at least two prior lines of systemic therapy in March 2024 and NMPA approval in June 2024
Tislelizumab
•Receive FDA approval for the treatment of second line ESCC in first half of 2024
•Receive FDA approval for the treatment of first-line unresectable, recurrent, locally advanced, or metastatic ESCC with a target PDUFA in July 2024
•Receive EMA approval for the treatment of first line metastatic NSCLC in combination with chemotherapy and second line metastatic NSCLC as monotherapy in the first half of 2024
•Receive NMPA approval for the treatment of previously untreated ES-SCLC in combination with chemotherapy in the third quarter of 2024
•Receive NMPA approval for the first-line treatment of inoperable, locally advanced, or metastatic gastric or gastroesophageal junction (G/GEJ) carcinoma in the second quarter of 2024

Anticipated Regulatory Submissions BRUKINSA
•Submit an sNDA for a new tablet formulation with the EMA and Health Canada in the first of half of 2024 and the FDA in the second half of 2024
Tislelizumab
•Submit a marketing application with the Japan PMDA for the treatment of first- and second-line ESCC in the first half of 2024
•Submit an sBLA with the EMA for the first-line treatment of inoperable, locally advanced, or metastatic G/GEJ carcinoma in the first quarter of 2024

Zanidatamab2
•In partnership with Jazz Pharmaceuticals and Zymeworks, submit a BLA with the NMPA for treatment of HER2-amplified inoperable and advanced or metastatic biliary tract cancer in the second half of 2024
Anticipated Clinical Activities Sonrotoclax
•Complete enrollment in a global Phase 2 trial in R/R MCL with potential for registration in the second quarter of 2024
Ociperlimab
(Anti-TIGIT)
•Complete enrollment in the Phase 3 AdvanTIG-302 trial in first-line NSCLC in the first quarter of 2024 

Tarlatamab3
(DLL3 x CD3 bispecific T-cell engager)

•In partnership with Amgen, begin China enrollment in a global Phase 3 trial in limited-stage small cell lung cancer in the second half of 2024
Early development
•Initiate first-in-human trials for at least 10 NMEs in 2024, including pan-KRAS inhibitor, MTA cooperative PRMT5 inhibitor, EGFR degrader, CDK2 inhibitor, ADCs, and bispecific immune cell engagers
•In partnership with Amgen3, enroll first patient in China in a Phase 1 study in metastatic castration-resistant prostate cancer for xaluritamig (AMG 509, STEAP1 x CD3 XmAb T-cell engager molecule4) in the first half of 2024

1 Leads Biolabs collaboration; BeiGene has commercial rights excluding China
2 Jazz/Zymeworks collaboration; BeiGene has commercial rights in APAC (excluding Japan), Australia, New Zealand
3 Amgen collaboration; BeiGene will have commercial rights in China and tiered mid-single digit royalties on net sales outside of China
4 XmAb is a registered trademark of Xencor, Inc.

Manufacturing Operations
•Neared completion of $800 million U.S. flagship biologics manufacturing and clinical R&D facility at the Princeton West Innovation Campus in Hopewell, New Jersey, which is expected to be operational in July 2024; the property has more than 1 million square feet of total developable real estate allowing for future expansion;

•Completed construction on new small molecule manufacturing campus in Suzhou, China. Phase 1 of construction added more than 559,000 square feet and expanded production capacity to 1 billion solid dosage form units annually; and

•Completed construction of a 250,000-square-foot ADC production facility and additional 170,000-square-foot biologics clinical production capabilities at our state-of-the-art biologics facility in Guangzhou, China, which brings the total capacity to 65,000 liters.

Corporate Developments
•Acquired an exclusive global license to a differentiated CDK2 inhibitor from Ensem Therapeutics, Inc., complementing the Company’s early development pipeline in breast cancer and other solid tumors.

Financial Summary
Select Condensed Consolidated Balance Sheet Data (U.S. GAAP)
(Amounts in thousands of U.S. Dollars)
As of
December 31, December 31,
2023 2022
(audited)
Assets:
Cash, cash equivalents, restricted cash and short-term investments $ 3,188,584 $ 4,540,288
Accounts receivable, net 358,027 173,168
Inventories, net 416,122 282,346
Property, plant and equipment, net 1,324,154 845,946
Total assets $ 5,805,275 $ 6,379,290
Liabilities and equity:
Accounts payable $ 315,111 $ 294,781
Accrued expenses and other payables 693,731 467,352
Deferred revenue 300 255,887
R&D cost share liability 238,666 293,960
Debt 885,984 538,117
Total liabilities 2,267,948 1,995,935
Total equity $ 3,537,327 $ 4,383,355

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,
2023 2022 2023 2022
(unaudited) (audited)
Revenue
Product revenue, net $ 630,526 $ 339,022 $ 2,189,852 $ 1,254,612
Collaboration revenue 3,883 41,073 268,927 161,309
Total revenues 634,409 380,095 2,458,779 1,415,921
Cost of sales – products 105,832 73,522 379,920 286,475
Gross profit 528,577 306,573 2,078,859 1,129,446
Operating expenses
Research and development 493,987 446,023 1,778,594 1,640,508
Selling, general and administrative 416,547 328,984 1,504,501 1,277,852
Amortization of intangible assets 1,838 188 3,500 751
Total operating expenses 912,372 775,195 3,286,595 2,919,111
Loss from operations (383,795) (468,622) (1,207,736) (1,789,665)
Interest income , net 16,274 18,219 74,009 52,480
Other income (expense), net 16,749 19,438 307,891 (223,852)
Loss before income taxes (350,772) (430,965) (825,836) (1,961,037)
Income tax expense 16,781 14,370 55,872 42,778
Net loss (367,553) (445,335) (881,708) (2,003,815)
Net loss per share $ (0.27) $ (0.33) $ (0.65) $ (1.49)
Weighted-average shares outstanding—basic and diluted 1,353,005,058 1,348,916,108 1,357,034,547 1,340,729,572
Net loss per American Depositary Share ("ADS") $ (3.53) $ (4.29) $ (8.45) $ (19.43)
Weighted-average ADSs outstanding—basic and diluted 104,077,312 103,762,778 104,387,273 103,133,044