On March 29, 2023 Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, reported financial results for the fourth quarter and full year ended December 31, 2022, and provided a business update (Press release, Bolt Biotherapeutics, MAR 29, 2023, View Source [SID1234629579]).

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"We believe the BDC-1001 Phase 1 results validate our Boltbody ISAC approach. Our design decisions enable us to deliver potent immune-stimulating antibody conjugates that can achieve positive clinical responses with acceptable tolerability, thereby, decoupling anti-tumor activity from the systemic safety issues that others have encountered. We are advancing into a thoughtfully designed, focused Phase 2 program evaluating BDC-1001 in patients with four different types of HER2-positive solid tumors where there remains important unmet medical need," said Randall Schatzman, Ph.D., Chief Executive Officer of Bolt Biotherapeutics.

"We are pleased to be entering into an agreement with Roche to supply pertuzumab in support of a new combination study with BDC-1001 and we look forward to investigating the impact of this combination in patients with HER2-positive metastatic breast cancer, while we continue to investigate BDC-1001 as monotherapy and work with our partner Bristol Myers Squibb to explore the combination with nivolumab. The progress in developing new immunotherapies in both our proprietary and partnered research programs demonstrates the potential of myeloid biology to provide important new treatment options to patients with cancer."

Recent Highlights and Anticipated Milestones

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Topline BDC-1001 Phase 1 dose-escalation results – Topline data from a multi-center, multi-dose Phase 1 clinical trial evaluating BDC-1001 as a single agent and in combination with nivolumab supports selection of a recommended phase 2 dose (RP2D) and initiation of a Phase 2 clinical program including two studies in four tumor types.
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Phase 2 BDC-1001 studies planned to initiate in 2023 – Clinical trials will include patients with HER2-positive breast, colorectal, endometrial, and gastroesophageal cancers at clinical sites in the U.S., multiple European countries, and South Korea evaluating BDC-1001 as monotherapy, in combination with pertuzumab, and separately, in combination with nivolumab.
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BDC-3042 to enter the clinic in 2023 – Investigational New Drug (IND)-enabling activities for a Phase 1 trial for BDC-3042 are proceeding on track. BDC-3042 is an agonistic antibody targeting Dectin-2, an immune-activating receptor expressed by TAMs in solid tumors. Preclinical studies demonstrate the ability of Dectin-2 agonistic antibodies to reprogram tumor-associated macrophages and drive anti-tumor activity.
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Continued progress with Boltbody ISAC collaborations – Collaborations with Genmab and Innovent developing next-generation Boltbody ISACs continue to progress. Both collaborations are exploring proprietary linker-payloads from the Boltbody ISAC platform, combining with Genmab’s proprietary bispecific antibodies in one collaboration and with Innovent’s proprietary antibodies in the other.
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Strengthened Bolt’s Board of Directors with appointment of Laura Berner – In December 2022, Laura Berner joined the Bolt Board of Directors. Ms. Berner brings extensive biopharmaceutical industry experience, having executed more than 50 transactions including research collaborations and product co-development and co-promotion partnerships. She currently serves as the Chief Operating Officer at TRexBio and has held multiple leadership positions spanning corporate strategy, business development, investor relations, and law.
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Cash, cash equivalents, and marketable securities were $192.8 million as of December 31, 2022 – Cash on hand, coupled with growing collaboration revenues, is expected to fund multiple key milestones and operations through 2025.

Upcoming Events

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BDC-3042 abstract accepted for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, Fla.
Title: Targeting tumor-associated macrophages to enhance anti-tumor immunity with the Dectin-2 agonistic antibody

Poster Board Number: 11

Abstract Presentation Number: 2964

Presenter: Justin A. Kenkel, Ph.D.

Details: Monday, April 17, 2023, 1:30 p.m. – 5:00 p.m. EDT

Location: Orange County Convention Center, Section 24

Fourth Quarter and Full Year 2022 Financial Results

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Collaboration Revenue – Collaboration revenue was $1.4 million for the quarter and $5.7 million for the full year ended December 31, 2022, compared to $0.5 million and $1.3 million for the same quarter and year in 2021. The collaboration with Genmab exploring Boltbody ISACs using Genmab’s proprietary bispecific antibodies accounted for $4.2 million in revenue for 2022 and the collaboration with Innovent exploring Boltbody ISACs using Innovent’s proprietary antibodies accounted for $1.5 million in revenue for 2022.

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Research and Development (R&D) Expenses – R&D expenses were $16.8 million for the quarter and $73.1 million for the full year ended December 31, 2022, compared to $22.5 million and $75.7 million for the same quarter and year in 2021. The decrease in R&D expenses was due to lower manufacturing expenses related to the timing of batch production of our product candidates, offset by higher clinical expenses related to the ongoing BDC-1001 clinical trial due to increase in patient activities.

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General and Administrative (G&A) Expenses – G&A expenses were $5.6 million for the quarter and $22.9 million for the full year ended December 31, 2022, compared to $5.1 million and $18.4 million for the same quarter and year in 2021. The increase in G&A expenses was due to higher personnel-related expenses due to an increase in headcount and higher office and facility-related expenses, offset by lower consulting and professional services expenses.

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Loss from Operations – Loss from operations was $21.0 million for the quarter and $90.3 million for the full year ended December 31, 2022, compared to $27.1 million and $92.8 million for the same quarter and year in 2021.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform
Bolt Biotherapeutics’ Boltbody ISAC platform unites the precision of antibodies with the power of the innate and adaptive immune system to reprogram the tumor microenvironment to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response, with the goal of generating durable therapeutic responses for patients with cancer.

On March 29, 2023 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported business highlights and financial results for the fourth quarter and year ended December 31, 2022 (Press release, Arcellx, MAR 29, 2023, View Source [SID1234629577]).

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"2022 was a stellar year for Arcellx, both from a business and clinical perspective. We completed a successful IPO in February, secured additional capital through a follow-on offering in June, and ended the year announcing a global partnership with Kite to co-develop and co-commercialize CART-ddBCMA in multiple myeloma. In parallel, we initiated two Phase 1 studies utilizing our dosable and controllable CAR-T technology, ARC-SparX, and our Phase 2 iMMagine-1 pivotal study and presented robust long-term data from our Phase 1 expansion study of CART-ddBCMA in multiple myeloma at ASCO (Free ASCO Whitepaper) and ASH (Free ASH Whitepaper). We also made significant progress on the manufacturing front, setting us up for scalable manufacturing in the future," said Rami Elghandour, Arcellx’sChairman and Chief Executive Officer. "Leveraging our balance sheet of $580 million in cash positions us to continue building on our strong foundation as we advance our pipeline programs. Our team, in collaboration with our colleagues at Kite, remains focused on completing enrollment of iMMagine-1, initiating iMMagine-2 in earlier multiple myeloma lines, and presenting longer-term data from our Phase 1 expansion study of CART-ddBCMA. We’re also beginning commercial planning as we prepare for U.S. market entry with the goal of meeting the demand of the many patients in need."

Recent Business Highlights

Announced strategic collaboration with Kite, a Gilead Company, to co-develop and co-commercialize the company’s late-stage clinical CART-ddBCMA program in multiple myeloma. On December 9, 2022, Arcellx and Kite, a Gilead Company, announced a strategic collaboration to co-develop and co-commercialize Arcellx’s lead product candidate, CART-ddBCMA, for the treatment of patients with relapsed or refractory multiple myeloma (rrMM). The collaboration leverages expertise across both companies, including Kite’s global cell therapy leadership and industry-leading reliable manufacturing. Arcellx received an upfront payment of $225 million

and a $100 million equity investment. Kite and Arcellx will co-commercialize and split profits in the United States and Arcellx will receive low to mid-teen royalties outside the U.S.

Presented continued robust long-term responses from lead product candidate, CART-ddBCMA, being evaluated in a Phase 1 expansion trial in patients with relapsed or refractory multiple myeloma at the 64th ASH (Free ASH Whitepaper) Annual Meeting and Exposition and provided additional pipeline progress. On December 11, 2022, Arcellx presented new clinical data from its ongoing Phase 1 expansion study of its novel, autologous CART-ddBCMA therapy, for the treatment of patients with rrMM during a presentation at the 64th ASH (Free ASH Whitepaper) Annual Meeting and Exposition. The data demonstrated 100% ORR and deep and durable responses were observed in patients with poor prognostic factors. Overall, 27 of 38 (71%) evaluable patients reached CR/sCR and 20 of 25 patients (80%) dosed >12 months ago or had their 12-month follow-up visit by November 22, 2022, had reached CR/sCR. Additionally, CART-ddBCMA continued to be well tolerated with no delayed neurotoxicity or parkinsonian-like events reported. Arcellx also announced that it had dosed patients in its pivotal iMMagine-1 Phase 2 clinical trial and that it had initiated its Phase 1 clinical trial of ACLX-002 for the treatment of patients with AML/MDS.

Fourth Quarter and Full Year 2022 Financial Highlights

Cash, cash equivalents, and marketable securities:
As of December 31, 2022, Arcellx had cash, cash equivalents, and marketable securities of $254.8 million. In January 2023, Arcellx and Kite closed its agreement to co-develop and co-commercialize Arcellx’s late-stage clinical program CART-ddBCMA in multiple myeloma. Upon closing the agreement, Arcellx received a $225 million upfront payment from Kite and a $100 million equity investment from Gilead. Arcellx expects that the cash on hand, subsequent to the closing, will fund its operations through BLA filing of CART-ddBCMA planned for the first half of 2025.

R&D expenses:
Research and development expenses were $25.9 million for the quarter ended December 31, 2022, compared to $13.4 million for the quarter ended December 31, 2021, an increase of $12.5 million. Research and development expenses were $149.6 million for the year ended December 31, 2022, compared to $46.9 million for the year ended December 31, 2021, an increase of $102.7 million. This increase for the year was primarily driven by the accounting for an expense of $63.3 million related to manufacturing services agreements. In accordance with ASC 842, the Company was required to expense the related right of use asset associated with an embedded lease which was determined to have no alternative future use. Other increases were related to higher external costs associated with the advancement of the company’s CART-ddBCMA clinical program, other pipeline candidates, and increased headcount.

G&A expenses:
General and administrative expenses were $14.1 million for the quarter ended December 31, 2022, compared to $7.3 million for the quarter ended December 31, 2022, an increase of $6.8 million. General and administrative expenses were $41.7 million for the year ended December 31, 2022, compared to $18.1 million for the year ended December 31, 2021, an increase of $23.6 million. These increases were driven by increased headcount and professional services costs such as legal, audit services, and consultants.

Net loss:
Net loss was $39.0 million and $20.7 million for the quarters ended December 31, 2022, and 2021, respectively; and $188.7 million and $65.0 million for the years ended December 31, 2022, and 2021, respectively.

On March 29, 2023 Enochian BioSciences Inc. (the "Company") reported that Dr. Anahid Jewett, a renowned cancer researcher in the field of immunotherapy for cancer presented proof-of-concept data from two sets of humanized mouse studies conducted independently by her laboratory at the University of California, Los Angeles (UCLA). The experiments demonstrated highly significant reductions in the weight and volume of pancreatic tumors following therapy with the Company’s proprietary technology combining cell-, gene- and immunotherapy. Those results correlated with strong immune responses, indicating proof-of-concept of the way the technology was intended to act.

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The results were part of an invited plenary lecture delivered by Dr. Jewett at the 8th Annual Innate Killer Summit in San Diego, California (relevant slides from the presentation can be viewed at: Presentation Excerpt–Innate Killer Summit_ENOB DC-11). The humanized mouse model is widely used to study cancer therapies that could potentially be applicable to human disease.

Pancreatic cancer is diagnosed in approximately 60,000 people in the USA each year; nearly 43,000 die. Because of limited treatment options, life expectancy is very poor – approximately 10 percent survival at 5 years.

Dr. Anahid Jewett, said: "I have been working in this field for three decades and designed the mouse model that we have used in my laboratory to study the Company’s potential cancer therapies. The results are some of the most impressive I have ever seen. The fact that we saw very similar highly statistically significant results across two independently conducted studies is particularly encouraging, indicating reproducibility of the findings. I look forward to continuing our work together towards clinical trials, and potentially offering hope to many who are suffering with diseases with few good treatment options."

"We are very excited by the promising results from the proof-of-concept studies conducted by Dr. Jewett and her colleagues at UCLA," said Dr. Mark Dybul, CEO of the Company. "While the evaluations focused on pancreatic cancer, the data suggest that the approach could be applicable to other solid tumors. The Company is aggressively pursuing the pipeline and hope to submit the Pre-Investigational New Drug (IND) to the US Food and Drug Administration in the coming weeks and an IND to investigate our drug candidate in several solid tumor types in the first quarter of 2024. Those applications will include a clinical approach for several solid tumors with a poor prognosis. Because of the Cancers we are focused on, we believe that we could potentially be eligible for accelerated development, including breakthrough drug or Fast Track designation by the FDA."

Dr. Dybul continued, "While we are laser focused on Cancer, the underlying technology which is the basis for our broader platform of cell-, gene- and immunotherapy could also be applied to certain chronic infectious diseases, including HIV. Several animal and "test tube" studies are in process to evaluate those approaches."

On March 29, 2023 Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company") and/or certain of its subsidiaries amended and restated (i) the Second Amended and Restated Participation Agreement, dated as of March 2, 2022, and effective as of March 3, 2022 (the "Second A&R Participation Agreement" and, as so amended and restated, the "Third A&R Participation Agreement"), by and among Old Saw Mill Holdings LLC, a wholly owned subsidiary of the Company (the "Lessee"), Bank of America, N.A., as administrative agent (in such capacity, the "Administrative Agent"), BA Leasing BSC, LLC, an affiliate of Banc of America Leasing & Capital, LLC, as lessor (in such capacity, the "Lessor"), and a syndicate of financial institutions as rent assignees (collectively with the Lessor, the "Participants"), which Second A&R Participation Agreement had amended and restated the Amended and Restated Participation Agreement that was entered into on May 2, 2019 (the "First A&R Participation Agreement") to amend and restate the Participation Agreement originally entered into on March 3, 2017 (the "Original Participation Agreement," and as amended and restated by the First A&R Participation Agreement and the Second A&R Participation Agreement, the "Previously Existing Participation Agreement"); and (ii) certain related agreements that were originally entered into in March 2017 and subsequently amended and restated in each of May 2019 and March 2022 (as previously amended and restated, and together with the Previously Existing Participation Agreement, collectively, the "Previously Existing Agreements") (Filing, 8-K, Regeneron, MAR 29, 2023, View Source [SID1234629525]). The Previously Existing Agreements provided for a $720.0 million lease financing that was originally completed on March 3, 2017 for the Company’s corporate headquarters and other rentable area consisting of approximately 150 acres of predominately office buildings and laboratory space located in the towns of Mount Pleasant and Greenburgh, New York (the "Facility").

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As described in greater detail below, the Third A&R Agreements (as defined below) amended and restated the Previously Existing Agreements, among other things, in order to revise certain covenants, representations and warranties, and events of default to be substantially similar to those set forth in the Credit Agreement, dated as of December 19, 2022 (the "Credit Agreement"), by and among Regeneron, as a borrower and guarantor, certain subsidiaries of Regeneron as subsidiary borrowers, JPMorgan Chase Bank, N.A., as administrative agent, and the lenders party thereto from time to time. The Company’s entry into the Credit Agreement was previously reported in its Current Report on Form 8-K filed with the United States Securities and Exchange Commission on December 20, 2022. The Third A&R Agreements did not change the maturity date of the advances under the Second A&R Participation Agreement or the term of the Second A&R Lease (as defined below). The yield that is payable to the Participants on their outstanding advances under the Second A&R Participation Agreement also remains unchanged under the Third A&R Agreements.

Third A&R Participation Agreement

On March 27 2023, the Lessee entered into the Third A&R Participation Agreement with the Administrative Agent, the Lessor, and the other Participants, which amends and restates the Second A&R Participation Agreement. The Third A&R Participation Agreement and certain related documents govern the $720.0 million lease financing that was previously advanced in March 2017 to finance the purchase price for the Facility and to reimburse the Company for certain payments previously made by it in connection with such acquisition.

Third A&R Lease

In connection with the Third A&R Participation Agreement, the Lessee also entered into a Third Amended and Restated Lease and Remedies Agreement, dated as of March 27, 2023 (the "Third A&R Lease"), with the Lessor, which amends and restates the Lessee’s lease of the Facility and certain related assets that was originally entered into in March 2017 by the Lessee and the Lessor and previously amended and restated on May 2, 2019, pursuant to the Amended and Restated Lease and Remedies Agreement, and on March 2, 2022, pursuant to the Second Amended and Restated Lease and Remedies Agreement (the "Second A&R Lease"). Pursuant to the Second A&R Lease, the term of the lease was extended for a five-year period ending in March 2027. Pursuant to the Third A&R Lease, the Lessee continues to grant a security interest in certain of its assets and rights to secure certain obligations under the Third A&R Agreements and certain related documents. The Third A&R Lease continues to be a triple-net lease requiring the Lessee, among other things, to pay during the term of the Third A&R Lease all maintenance, insurance, taxes, and other costs arising out of the use of the Facility (which are offset in part by payments received by the Lessee from third-party tenants to whom certain parts of the Facility are subleased from the Lessee). The Third A&R Lease also continues to require that the Lessee make monthly payments of basic rent during the remaining term of the Third A&R Lease in an amount equal to the yield payable to the Participants on their outstanding advances under the Third A&R Participation Agreement. Such advances continue to accrue yield at a variable rate per annum based on the one-month forward-looking Secured Overnight Financing (SOFR) term rate, plus a spread adjustment, plus an applicable margin that varies with the Company’s debt rating and total leverage ratio.

Third A&R Guaranty

The Company continues to guarantee all of the Lessee’s obligations under the Third A&R Participation Agreement, the Third A&R Lease, and certain related documents pursuant to a Third Amended and Restated Guaranty, dated as of March 27, 2023 (the "Third A&R Guaranty," and together with the Third A&R Participation Agreement and the Third A&R Lease, collectively, the "Third A&R Agreements"), made by the Company and its wholly owned subsidiaries, Regeneron Healthcare Solutions, Inc. and Regeneron Genetics Center LLC, each as a subsidiary guarantor (together with other subsidiaries of the Company (other than certain excluded subsidiaries), collectively, "Subsidiary Guarantors" and, each, a "Subsidiary Guarantor"). The Third A&R Guaranty provides that a Subsidiary Guarantor will become jointly and severally liable with the Company as a guarantor under the Third A&R Guaranty only at such time as such Subsidiary Guarantor has an outstanding borrowing under the Credit Agreement. As of the date hereof, no Subsidiary Guarantor has any outstanding borrowing under the Credit Agreement.

Financial and Operating Covenants; Other Terms

The Third A&R Agreements contain operating covenants and a maximum total leverage ratio financial covenant, which are substantially similar to the covenants set forth in the Credit Agreement, except for such matters specifically relating to the Facility or the lease financing nature of the transactions contemplated by the Third A&R Agreements. Operating covenants include, among other things, limitations on (i) the incurrence of certain indebtedness by the Company’s subsidiaries, (ii) certain liens on assets of the Company and its subsidiaries and liens on the Facility, and (iii) certain fundamental changes and the disposition of assets by the Company and its subsidiaries. The Third A&R Agreements contain other customary covenants, representations and warranties, and events of default. The Third A&R Lease also continues to include certain early termination events relating to the occurrence of certain material events of loss or material environmental events relating to the Facility.

Maturity Date; Additional Extension Option; Termination

Pursuant to the Third A&R Agreements, March 3, 2027 continues to be the maturity date for the $720.0 million advances and the end of the term of the Lessee’s lease of the Facility from the Lessor, at which time all amounts outstanding thereunder will become due and payable in full. The Third A&R Participation Agreement and the Third A&R Lease include an option for the Lessee to elect to extend the maturity date of the Third A&R Participation Agreement and the term of the Third A&R Lease for an additional five-year period, subject to the consent of all the Participants and certain other conditions. The Lessee also has the option prior to the end of the term of the Third A&R Lease to (a) purchase the Facility by paying an amount equal to the outstanding principal amount of the Participants’ advances under the Third A&R Participation Agreement, all accrued and unpaid yield thereon, and all other outstanding amounts under the Third A&R Agreements and certain related documents or (b) sell the Facility to a third party on behalf of the Lessor, in each case, subject to certain terms and conditions set forth in the Third A&R Participation Agreement and the Third A&R Lease. Outstanding advances under the Third A&R Participation Agreement and outstanding obligations under the Third A&R Lease may be prepaid at any time without premium or penalty, subject to customary breakage costs. The expiration date and the extension term of the Third A&R Agreements described in this paragraph remain the same as the corresponding expiration date and extension term of the Previously Existing Agreements.

On March 29, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Commission (EC) approved Libtayo (cemiplimab) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with ≥1% PD-L1 expression (Press release, Regeneron, MAR 29, 2023, View Source [SID1234629524]). This includes patients that have no EGFR, ALK or ROS1 aberrations and whose tumors are metastatic or locally advanced and not candidates for definitive chemoradiation.

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"Today’s approval considerably expands the number of people in Europe with advanced non-small cell lung cancer who are eligible for Libtayo-based first-line treatment, including those with PD-L1 expression ranges most commonly seen in real-world practice," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "We are proud that Libtayo continues to distinguish itself among PD-1 pathway blockers, as just one of two PD-1 inhibitors to be approved for use across squamous and non-squamous forms of advanced NSCLC in both combination and monotherapy settings. This marks the fifth approval for Libtayo in Europe."

Lung cancer is the leading cause of cancer death worldwide. In recent years, more than 2.2 million annual new cases have been diagnosed globally. Approximately 80-85% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages.

"The Phase 3 EMPOWER-Lung 3 trial showed significant improvements across primary and key secondary endpoints, including overall survival in the cemiplimab plus chemotherapy arm," said Prof. Martin Reck, Head of Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. "As a treating physician of this patient population, I welcome a new treatment option for patients in Europe, as we continue to strive for better outcomes for patients with advanced non-small cell lung cancer."

"With lung cancer being the leading cause of cancer mortality globally, ongoing research is imperative to find more treatment options for people impacted by this disease," said Anne-Marie Baird, Ph.D., President, Lung Cancer Europe. "This approval highlights continued progress in first-line treatment options for people impacted by advanced lung cancer in Europe."

Libtayo is currently approved in the EU and other countries for the treatment of certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC), advanced NSCLC and advanced cervical cancer. The Libtayo combination was also approved by the U.S. Food and Drug Administration (FDA) for advanced NSCLC regardless of PD-L1 expression in November 2022.

About the Phase 3 Trial
The EC approval is based on data from the global Phase 3 EMPOWER-Lung 3 trial, a randomized, multicenter trial investigating a first-line combination treatment of Libtayo and platinum-doublet chemotherapy (Libtayo combination), compared to platinum-doublet chemotherapy alone. The trial enrolled 466 patients with locally advanced or metastatic NSCLC, as well as squamous or non-squamous histologies across all PD-L1 expression levels and with no EGFR, ALK or ROS1 aberrations. Notably, the trial was designed to closely resemble a patient population with varied disease presentations seen in everyday clinical practice. Among those enrolled, 43% had tumors with squamous histology, 15% had locally advanced disease and 7% had a history of brain metastases.

Patients were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) administered intravenously every 3 weeks for 108 weeks, plus platinum-doublet chemotherapy administered every 3 weeks for 4 cycles. The trial was stopped early based on a recommendation by the Independent Data Monitoring Committee after the Libtayo combination demonstrated a significant improvement in overall survival (OS). Results of the trial at the primary analysis were published in Nature Medicine in August 2022.

At the primary analysis (median follow-up: 16 months), the trial showed a statistically significant improvement in the primary endpoint of OS for patients treated with the Libtayo combination compared to chemotherapy alone in the overall population (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.53 to 0.93). Among the 70% of patients in the trial expressing PD-L1 ≥1% (n=327), efficacy results for the Libtayo combination arm (n=217) compared to chemotherapy alone (n=110) showed a:

22-month median OS versus 13 months, representing a 45% relative reduction in the risk of death (HR: 0.55; 95% CI: 0.39 to 0.78).
9-month median progression-free survival (PFS) versus 6 months (HR: 0.48; 95% CI: 0.36 to 0.63)
48% objective response rate (ORR) versus 23%
16-month median duration of response (DOR; range: 2 to 19+) versus 5 months (range: 2 to 19+)
At the time of the pre-specified final analysis (median follow up: 28 months), patients with PD-L1 expression ≥1% treated with the Libtayo combination continued to show clinically meaningful survival and PFS benefits compared to chemotherapy alone.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo. Among patients treated with the Libtayo combination evaluated for safety in the trial (n=312), adverse reactions occurring in at least 10% included anemia (44%), alopecia (37%), musculoskeletal pain (27%), nausea (25%), fatigue (23%), peripheral neuropathy (21%), hyperglycemia (18%), decreased appetite (17%), alanine aminotransferase increased (16%), aspartate aminotransferase increased (15%), neutropenia (15%), constipation (14%), dyspnoea (13%), rash (13%), thrombocytopenia (13%), vomiting (12%), diarrhea (11%), insomnia (11%), weight decreased (11%) and hypoalbuminemia (10%). Adverse reactions were serious in 25% of patients and led to permanent discontinuation of the Libtayo combination in 5% of patients.

In December 2022, Libtayo in combination with chemotherapy was added to the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Magnitude of Clinical Benefit Scale (score: 4 out of 5), for patients with advanced NSCLC across squamous and non-squamous histologies, and irrespective of PD-1 expression levels.

About Regeneron in Oncology
At Regeneron, we’re applying more than three decades of scientific innovation with the goal of developing paradigm-changing therapies for patients with cancer. Our oncology portfolio is built around two foundational approaches – our approved PD-1 inhibitor Libtayo and investigational bispecific antibodies – which are being evaluated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop potentially synergistic treatments for a wide range of solid tumors and blood cancers.

If you are interested in learning more about our clinical trials, please contact us ([email protected] or 844-734-6643) or visit our clinical trials website.