On February 26, 2024 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the fourth quarter and year ended December 31, 2023 and provided a corporate update (Press release, Celldex Therapeutics, FEB 26, 2024, View Source [SID1234640444]).

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"In 2023, Celldex made transformational progress across the barzolvolimab development program, reporting multiple positive data sets across mast cell mediated diseases where patients desperately need better treatment options," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "We carried this momentum into 2024, presenting positive 12 week data from our ongoing Phase 2 CSU study that directly support the planned initiation of registrational studies in CSU this summer, a major milestone for barzolvolimab and Celldex."

"This year we will continue to build on our leadership position in mast cell biology—reporting data from multiple barzolvolimab studies, expanding barzolvolimab into additional mast cell mediated diseases and introducing our first bispecific for inflammatory diseases. We look forward to an exciting year."

Recent Program Highlights

Barzolvolimab – KIT Inhibitor Program

Barzolvolimab is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells.

Celldex is conducting Phase 2 clinical studies of barzolvolimab for the treatment of chronic spontaneous urticaria (CSU) and the two most common forms of chronic inducible urticaria (CIndU) – cold urticaria (ColdU) and symptomatic dermographism (SD). These randomized, double-blind, placebo-controlled Phase 2 studies are evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategies.

Celldex is currently planning two Phase 3 studies of barzolvolimab in CSU, which are expected to initiate this summer.

In November 2023, Celldex reported positive topline data from the Phase 2 CSU study and in February 2024, 12 week treatment results were reported at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in a late breaking oral presentation. Barzolvolimab achieved the primary efficacy endpoint of the study, with a statistically significant mean change from baseline to week 12 of UAS7 (weekly urticaria activity score) compared to placebo across multiple dosing groups and was well tolerated. Secondary and exploratory endpoints in the study, including ISS7 (weekly itch severity score) and HSS7 (weekly hives severity score) and responder analyses strongly support the primary endpoint results. Importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action. Patients on study will continue to receive barzolvolimab for 52 weeks and the Company plans to report 52 week data in the second half of 2024.

In October 2023, data on quality of life outcomes from the Phase 1b CSU study were presented at the European Academy of Dermatology & Venereology (EADV) Congress. The Dermatology Life Quality Index (DLQI) assesses patients’ perceptions of the impact of their disease across different aspects of their health-related quality of life and includes questions on symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. A rapid improvement in the DLQI was noted within 4 weeks in all barzolvolimab treated patients. DLQI improvement was sustained at doses ≥1.5mg/kg. Physician Global Assessment (PhysGA) for the treated cohorts also improved by week 1 and was sustained through week 24.

Enrollment to the Phase 2 CIndU study is nearing completion and 12 week primary endpoint data from this study is expected to be reported in the second half of 2024. The study is designed to enroll approximately 180 patients with ColdU or SD.

Celldex is currently planning for the initiation of a Phase 2 subcutaneous study in prurigo nodularis (PN) in early 2024. This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety profile of barzolvolimab in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable. Patients will receive barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week Treatment Phase.

Data from the Phase 1b randomized, double-blind, placebo-controlled study in patients with prurigo nodularis were reported in an oral presentation at the 12th World Congress on Itch (WCI) in November 2023. A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and barzolvolimab was generally well tolerated.
In July 2023, the first patient was dosed in the Phase 2 randomized, double-blind, placebo-controlled study in eosinophilic esophagitis (EoE); enrollment is ongoing. To optimize potential efficacy signal in this difficult to treat indication, we have recently amended the protocol to dose 300 mg every 4 weeks rather than 8 weeks. Approximately 75 patients will be enrolled in total.

Bispecific Antibody Platform

CDX-585 – Bispecific ILT4 & PD-1

CDX-585 combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. ILT4 is emerging as an important immune checkpoint on myeloid cells.

In May 2023, the first patient was dosed in the Phase 1 study of CDX-585. This open-label, multi-center study of CDX-585 is evaluating patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. Enrollment is ongoing in the dose-escalation portion of the study.

Fourth Quarter and Twelve Months 2023 Financial Highlights and 2024 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2023 were $423.6 million compared to $235.3 million as of September 30, 2023. The increase was primarily driven by net proceeds of $216.2 million from our November 2023 underwritten public offering, partially offset by cash used in operating activities of $32.5 million, which includes the $12.5 million payment to Shareholder Representative Services (SRS), the representative of the former stockholders of Kolltan Pharmaceuticals, Inc., pursuant to our settlement agreement. At December 31, 2023, Celldex had 55.9 million shares outstanding.

Revenues: Total revenue was $4.1 million in the fourth quarter of 2023 and $6.9 million for the year ended December 31, 2023, compared to $1.6 million and $2.4 million for the comparable periods in 2022. The increase in revenue was primarily due to an increase in services performed under our manufacturing and research and development agreements with Rockefeller University.

R&D Expenses: Research and development (R&D) expenses were $30.4 million in the fourth quarter of 2023 and $118.0 million for the year ended December 31, 2023, compared to $22.9 million and $82.3 million for the comparable periods in 2022. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial, barzolvolimab contract manufacturing, and personnel expenses.

G&A Expenses: General and administrative (G&A) expenses were $8.8 million in the fourth quarter of 2023 and $30.9 million for the year ended December 31, 2023, compared to $6.6 million and $27.2 million for the comparable periods in 2022. The increase in G&A expenses was primarily due to higher stock-based compensation, recruiting and barzolvolimab commercial planning expenses, partially offset by a decrease in legal expenses.

Changes in Fair Value Remeasurement of Contingent Consideration: The Company recorded a $6.9 million gain on fair value remeasurement of contingent consideration for the year ended December 31, 2022, primarily due to the Company’s decision to deprioritize the CDX-1140 program in the second quarter of 2022.

Litigation Settlement Related Loss: The Company recorded a loss of $15.0 million in the second quarter of 2022 related to the $15.0 million initial payment made to SRS pursuant to our settlement agreement. During the fourth quarter of 2023, the Company announced positive topline results from our Phase 2 clinical trial of barzolvolimab in patients with moderate to severe CSU, satisfying the "Successful Completion" of a Phase 2 clinical trial of barzolvolimab milestone, thus triggering the payment of the $12.5 million milestone pursuant to the settlement agreement.

Net Loss: Net loss was $43.3 million, or ($0.83) per share, for the fourth quarter of 2023, and $141.4 million, or ($2.92) per share, for the year ended December 31, 2023, compared to a net loss of $26.5 million, or ($0.56) per share, for the fourth quarter of 2022 and $112.3 million, or ($2.40) per share, for the year ended December 31, 2022. The litigation settlement related loss had a ($0.26) impact on net loss per share for the twelve months ended December 31, 2023.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at December 31, 2023 are sufficient to meet estimated working capital requirements and fund current planned operations into 2026.

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.