On June 28, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending conditional marketing authorization of odronextamab to treat adults with relapsed/refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy (Press release, Regeneron, JUN 28, 2024, View Source [SID1234644595]). The European Commission is expected to announce a final decision in the coming months.

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

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

                  Schedule Your 30 min Free Demo!

FL and DLBCL are the two most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL). While FL is a slow-growing subtype, it is an incurable disease, and most patients will relapse after initial treatment. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment (e.g., relapsing or refractory to treatment). It is estimated that approximately 120,000 FL cases and 163,000 DLBCL cases are diagnosed annually worldwide. In Europe, it is estimated that approximately 15,000 FL cases and 31,000 DLBCL cases are diagnosed each year.

The positive CHMP opinion is supported by results from the Phase 1 ELM-1 and pivotal Phase 2 ELM-2 trials, which demonstrated robust, durable response rates and an acceptable safety profile of odronextamab in adults with R/R FL or R/R DLBCL. In a pooled safety population, the most common serious adverse reactions were cytokine release syndrome, pneumonia, COVID-19 and pyrexia.

The EMA previously granted odronextamab Orphan Designation for both FL and DLBCL. Odronextamab is currently under clinical development and has not been approved by any regulatory authority.

Regeneron continues to evaluate the use of odronextamab as a monotherapy and in combination across earlier lines of therapy in challenging-to-treat lymphomas. This includes the registrational ELM-1 and ELM-2 studies, the Phase 3 OLYMPIA development program, which is one of the largest clinical programs in lymphoma evaluating odronextamab in earlier lines of therapy and additional B-NHLs, as well as early-stage trials with chemotherapy-free combinations.

About the Odronextamab Clinical Trial Program
Odronextamab is an investigational CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.

ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including a cohort of patients who had progressed after CAR-T therapy.

ELM-2 is an ongoing, open-label, multicenter Phase 2 trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint is objective response rate according to the Lugano Classification as assessed by independent review committee, and secondary endpoints include complete response, progression-free survival, overall survival and duration of response.

In addition to the Phase 3 OLYMPIA development program, Regeneron is investigating odronextamab in combination with a costimulatory bispecific antibody, REGN5837 (CD22xCD28), and Regeneron’s PD-1 inhibitor cemiplimab for R/R aggressive B-NHL through the ATHENA-1 and CLIO-1 studies, respectively. For more information, visit the Regeneron clinical trials website, or contact [email protected] or +1 844-734-6643.

On June 28, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) cell therapies for patients with cancer, submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for lifileucel, a TIL cell therapy, for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor (Press release, Iovance Biotherapeutics, JUN 28, 2024, View Source [SID1234644594]). If approved, lifileucel will be the first and only approved therapy in this treatment setting in all European Union (EU) member states.

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

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

                  Schedule Your 30 min Free Demo!

Raj K. Puri, M.D., Ph.D., Executive Vice President, Regulatory Strategy and Translational Medicine, stated, "This EU regulatory submission is the first step toward expanding lifileucel into global markets with a high prevalence of advanced melanoma. The unmet need and strength of the clinical data will support approval of lifileucel as the first and only approved therapy for advanced melanoma patients in the EU who have progressed following standard of care therapies. Following the accelerated approval in the U.S., our global expansion strategy can more than double the number of patients with significant unmet need who may access lifileucel."

The MAA submission for lifileucel is supported by positive clinical data from the C-144-01 clinical trial in patients with advanced post-anti-PD1 melanoma. If the MAA for lifileucel is validated, which is anticipated in the third quarter of 2024, the Committee for Medicinal Products for Human Use (CHMP) is expected to issue a scientific opinion for the European Commission to adopt in 2025. Additional marketing submissions for lifileucel are on track in Canada and the United Kingdom during the second half of 2024 and in Australia in 2025. Each year, more than 20,000 people die from advanced melanoma in the U.S., EU, United Kingdom, Canada, and Australia.1

1. World Health Organization International Agency for Research on Cancer (IARC) GLOBOCAN 2022.

On June 28, 2024 Genmab A/S (Nasdaq: GMAB) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of conditional marketing authorization of epcoritamab (TEPKINLY), a T-cell engaging bispecific antibody administered subcutaneously, as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy (Press release, Genmab, JUN 28, 2024, View Source [SID1234644593]). The final European Commission decision on this indication for epcoritamab is anticipated later this year.

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

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

                  Schedule Your 30 min Free Demo!

"Many people living with follicular lymphoma that has either relapsed or is refractory to existing therapies experience significant treatment challenges with poor prognosis," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "This positive opinion recognizes the unmet need in the European Union for patients whose follicular lymphoma is considered difficult-to-treat and that epcoritamab may represent a new therapeutic option."

The CHMP opinion is supported by overall and complete response data from the Phase 1/2 EPCORE NHL-1 clinical trial in 128 patients with R/R FL treated with epcoritamab after two or more lines of systemic therapy. The study included patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent, patients who were refractory to last prior treatment, and patients whose disease progressed within two years of first systemic therapy. In the trial, the most common (≥10%) adverse reactions were CRS, injection site reactions, pyrexia, neutropenia, anemia, thrombocytopenia, diarrhea, nausea, headache, upper respiratory tract infection, pneumonia, and rash.

An additional cohort of 86 patients evaluated an optimized step-up dosing (SUD) schedule to reduce the incidence and severity of cytokine release syndrome (CRS), which is an associated side effect from immune-engaging cancer treatments. Hospitalization was not mandatory in the optimization cohort. The incidence of CRS was 49% (42 of 86 patients; 9% were grade 2) and there were no grade 3 or higher CRS events in the optimization cohort. The EPCORE NHL-1 results, including results from the optimization cohort, were recently published in the Lancet Haematology. Additionally, data from the optimization cohort were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, selected to be a part of Best of ASCO (Free ASCO Whitepaper) (July 19-20, Boston, MA), and were presented at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Congress.

"Each year, thousands of people in Europe are diagnosed with follicular lymphoma and it’s an upsetting reality that many of them will experience relapse and refractory disease," said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. "Patients deserve new treatment options, and this positive opinion is the first step to bringing epcoritamab to more patients who need it."

About the EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part; an expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL), including FL. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. The expansion part generated pivotal data from patients with FL and DLBCL. The optimization part evaluated additional CRS mitigation strategies during cycle 1. The primary endpoint of the expansion part was overall response rate (ORR) as assessed by an Independent Review Committee (IRC). Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab.

About Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.i Although FL is an indolent lymphoma, it is considered incurable with conventional therapy and patients who achieve remission also often experience relapse.iii,iv,ii Generally, with each relapse, the remission and time to next treatment is shorter.iii,iv

About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.v

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), and a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

On June 27, 2024 Oncopeptides, a biotech company focused on difficult-to-treat cancers, reported that the first candidate drug based on the company´s unique platform for Small Polypeptide based innate Killer Engagers (SPiKE) has been selected (Press release, Oncopeptides, JUN 27, 2024, View Source [SID1234646776]).

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

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

                  Schedule Your 30 min Free Demo!

The SPiKE platform uses multi-specific constructs, able to bind to multiple targets simultaneously. The first drug candidate, OPSP1, is a bi-specific construct designed to both engage natural killer cells, a type of immune cell, and target cancer cells. The goal of OPSP1 is to prove the ability of the SPiKE platform to activate these natural killer cells. To do this, OPSP1 targets a specific protein called BCMA that is expressed in some cancers including multiple myeloma. By targeting this protein, Oncopeptides will be able to assess how well the SPiKE platform can activate natural killer cells to fight cancer, a crucial step before continued clinical development of the SPiKE platform.

"There is significant potential in NK cell-mediated therapy for difficult-to-treat cancers," says Dr. Karl-Johan Malmberg, professor at Oslo University and Karolinska Institutet. "Despite the substantial advancements in current treatments, the reality is that resistance to these therapies often develops. This underscores the urgent need for new and innovative treatment options to address this unmet medical need."

NK cell-mediated therapy represents a promising avenue in cancer immunotherapy, with ongoing research aimed at overcoming existing challenges and enhancing its therapeutic potential. As a next step for Oncopeptides, a first-in-human clinical trial will be designed to evaluate the safety, efficacy, and overall therapeutic potential of OPSP1.

"The ability to show a promising product pipeline behind its flagship product is important for a growing biotech company. Following the accomplishments we have seen with our first technology platform PDC, where we have an approved product, we are excited to also announce progress with SPiKE, our second technology platform," says Sofia Heigis, CEO of Oncopeptides. "This milestone is a major step forward in our ambition to ensure that Oncopeptides can continue to provide hope for patients suffering from difficult-to-treat cancers, and value to shareholders investing in our science."

A pre-clinical project for the SPiKE platform has received a financial grant from the Eurostars 3-program, co-financed by the European Union research and innovation program "Horizon Europe" and is driven by an international research consortium that includes world-leading expertise from the department of Cancer Immunology at Oslo University Hospital, Pharmatest Services Ltd in Turku, Finland and the Royal Institute of Technology in Stockholm (KTH), from where the technology originally stems. With this grant, Sweden’s Innovation Agency, Vinnova, has provided Oncopeptides resources to develop pre-clinical proof of concept for a novel synthetic small polypeptide for the treatment of multiple myeloma.

On June 27, 2024, Coherus BioSciences, Inc. (the "Company") entered into an exclusive license and distribution agreement (the "License Agreement") with Apotex, Inc. ("Apotex"), pursuant to which, the Company has granted to Apotex an exclusive license under the Company’s rights to toripalimab to commercialize toripalimab within Canada (Filing, 8-K, Coherus Biosciences, JUN 27, 2024, View Source [SID1234644648]). As previously disclosed, on February 1, 2021, Coherus BioSciences, Inc. (the "Company") announced that it had entered into the exclusive license and commercialization agreement (the "Collaboration Agreement") with Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences") for the co-development and commercialization of toripalimab, Junshi Biosciences’ anti-PD-1 antibody, in the United States and Canada. Pursuant to the Collaboration Agreement, the Company has the right to grant sublicenses to third parties to commercialize toripalimab within Canada.

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

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

                  Schedule Your 30 min Free Demo!

Pursuant to the License Agreement, Apotex agreed to pay to the Company an upfront payment of $6.25 million United States Dollars ("USD"). In addition, Apotex agreed to pay to the Company the USD equivalent of up to an aggregate of up to $51.5 million Canadian Dollars ("CAD") in milestone payments in connection with the achievement of certain regulatory and sales milestones with respect to toripalimab in Canada. Finally, Apotex agreed to pay to the Company a low double-digit percentage of any future net sales of toripalimab in Canada that the Company will subsequently pay to Junshi Biosciences pursuant to the Collaboration Agreement.

The License Agreement term continues until the tenth year after the first commercial sale of toripalimab in Canada, subject to an extension for a subsequent ten year term at the option of Apotex. Apotex may terminate the License Agreement for any reason after a specified notice period, the License Agreement will terminate automatically if the rights granted to the Company by the Collaboration Agreement are terminated, if there is material breach that is not cured, if there are certain challenges to licensed patents by Apotex and in the case of certain insolvency events.

The foregoing description of the material terms of the License Agreement is qualified in its entirety by reference to the full text of the License Agreement, which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024.