On May 21, 2024 Genmab A/S (Nasdaq: GMAB) reported that it has completed its acquisition of ProfoundBio, Inc., a clinical-stage biotechnology company developing next-generation antibody-drug conjugates (ADC)s and ADC technologies for the treatment of cancers in an all-cash transaction of USD 1.8 billion (subject to adjustment for ProfoundBio’s closing net debt and transaction expenses) (Press release, Genmab, MAY 21, 2024, View Source [SID1234643486]).

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With the completion of this strategic transaction, we are excited to welcome our new colleagues and their expertise in developing next-generation antibody-drug conjugates to our exceptionally talented R&D team," said Jan van de Winkel, Ph.D., President and Chief Executive Officer of Genmab. "We look forward to unlocking new opportunities as we strengthen our oncology portfolio and continue to work towards our goal of transforming the lives of patients with innovative antibody medicines."

The acquisition gives Genmab worldwide rights to ProfoundBio’s portfolio of next-generation ADCs, further broadening and strengthening its clinical pipeline. These programs include Rina-S, a potential best-in-class, clinical-stage, FRα-targeted, Topo1 ADC, currently in part 2 of a Phase 1/2 clinical trial, for the treatment of ovarian cancer and other FRα-expressing solid tumors. The addition of Rina-S to Genmab’s portfolio enables Genmab to deepen its presence in the gynecologic oncology space and establish a firm foundation in solid tumors. Based on the data from the ongoing Phase 1/2 clinical trial, which also indicates that Rina-S has the potential to address a broader patient population than first-generation FRα-targeted ADCs, Genmab intends to broaden the development plans for Rina-S within ovarian cancer and other FRα-expressing solid tumors. In January 2024, the U.S. Food and Drug Administration (U.S. FDA) granted Fast Track designation to Rina-S for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

In addition, the transaction provides Genmab with access to ProfoundBio’s novel ADC technology platforms, which complement Genmab’s already validated suite of proprietary technology platforms. The combination of the companies’ technology platforms could create new opportunities to generate and develop new medicines with the potential to transform the treatment of cancer and improve patients’ lives.

As previously disclosed in Company Announcement No. 26, following the closing of this acquisition, Genmab’s operating expenses, before expenses incurred by it in connection with the transaction, are anticipated to be at or moderately above the upper end of the previously disclosed guidance range of DKK 12.4 -13.4 billion. The anticipated increase reflects the incremental R&D investment to support the advancement of ProfoundBio’s clinical programs, primarily Rina-S. Genmab’s revenue guidance is unchanged and expected to be in the previously disclosed guidance range of DKK 18.7 – 20.5 billion. Genmab expects to update its guidance no later than in connection with its second quarter 2024 earnings.

On May 21, 2024 Molecular Targeting Technologies, Inc. (MTTI), reported that it will update findings on both 177Lu-EBTATE clinical and 225Ac-EBTATE preclinical work during the 2024 SNMMI meeting in Toronto June 8-11 (exhibition booth #1819) (Press release, EvaThera Theranostics, MAY 21, 2024, View Source [SID1234643485]).

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177Lu-EBTATE an EvaThera drug, is the first patented long-acting peptide targeted radiotherapeutic drugs. It selectively targets and binds to somatostatin receptor 2 on neuroendocrine and other tumors, which are then killed by the radionuclide payload. Evans blue in EBTATE binds to serum albumin, extending in vivo circulatory half-life and tumor residence time, enabling effective use of significantly lower radiopharmaceutical activity and fewer dosing cycles vs. the current standard of care (SOC). These benefits are also evident in recent studies of the 225Ac-EBTATE homolog.

Professor Zhaohui Zhu, MD, Peking Union Medical College Hospital, reflected "In our 3-year follow up on 30 patients* with metastatic neuroendocrine tumors (mNETs), 177Lu-EBTATE demonstrated good safety, with no nephro- or hepatoxicity and 86% disease control rate using 60% less radioactivity than 177Lu-DOTATATE. We observed low incidence of grade 3 hematoxicity (3.4% vs 15% of reported SOC) and no long-term nephrotoxicity of any grade."

The study "Long acting 225Ac-EBTATE is highly efficacious against somatostatin receptor-2-positive small-cell lung cancer (SCLC)**" has been accepted for presentation at 2024 SNMMI. Professor Humphrey Fonge of the University of Saskatchewan commented, "225Ac-EBTATE (2x 30 kBq administered 10 days apart) was effective against SCLC with 80% complete remissions and 100% survival. Treatment yielded a 2-fold greater tumor growth inhibition when compared with 225Ac-DOTATATE, at 60% less administered radioactivity. Toxicity, as measured by body weight, blood counts, and chemistry showed that 225Ac-EBTATE was well tolerated at a highly effective dose. 225Ac-EBTATE shows great promise against SCLC." Chris Pak, President & CEO of MTTI commented: "We are pleased to learn that 177Lu-EBTATE exhibited no safety concerns and was effective at a lower dose than SOC in mNET patients. We are also encouraged that 225Ac-EBTATE out-performed 225Ac-DOTATATE, providing a 2-fold greater tumor growth inhibition in preclinical findings using a much lower dose of radioactivity. We look forward to advancing our clinical trials with these radiotherapeutic drugs in small-cell lung and other cancers."

On May 21, 2024 Edgewood Oncology, a clinical-stage biotechnology company focused on delivering BTX-A51 to patients with hematologic malignancies and genetically-defined solid tumors, reported that the first two patients with metastatic breast cancer were treated with BTX-A51, a multi-specific kinase inhibitor of casein kinase 1 alpha (CK1α) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9), that synergistically targets master regulators of cancer (Press release, Edgewood Oncology, MAY 21, 2024, View Source [SID1234643484]). BTX-A51 is being evaluated in a Phase 2a study for the treatment of estrogen receptor positive / human epidermal growth factor receptor 2 negative (ER+/HER2-) metastatic breast cancer with and without GATA binding protein 3 (GATA3) mutations.

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GATA3 is a protein that helps maintain healthy breast cells but mutations in this protein, which are found in approximately 15% of breast cancer cases, are associated with shorter progression free (PFS) and overall survival (OS). Moreover, these mutations are almost always accompanied by a wild type (non-mutated) p53 tumor suppressor protein. Recent studies have shown that targeting MDM2, a molecule that degrades the p53 protein, could be particularly effective in treating cancers with these GATA3 mutations. Due to its ability to reduce MDM2 expression, Edgewood Oncology is testing the hypothesis that BTX-A51 may be beneficial in this breast cancer sub-population.

"This represents an important milestone for both Edgewood Oncology and for patients with ER+/HER2- breast cancer, particularly those with a GATA3 mutation, who need better treatment options targeted to their underlying mutation profile," said Zung L. Thai, M.D., Ph.D., chief medical officer of Edgewood Oncology. "Moreover, while CDK4/6 inhibitors remain a cornerstone of current treatment regimens, resistance to these therapies poses a formidable challenge. By targeting CDK7 and CDK9, key regulators of cell cycle progression, BTX-A51 not only aims to circumvent this resistance but also to transform the treatment landscape."

The ongoing Phase 2a trial of BTX-A51 is a multicenter, open-label, nonrandomized, multiple dose study evaluating the safety, toxicity, pharmacokinetics and preliminary efficacy of BTX-A51 in patients with ER+/HER2- metastatic breast cancer with and without GATA3 mutations. Multiple sites for the clinical study are open for enrollment. For more information, visit clinicaltrials.gov (NCT04872166).

On May 21, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) has reassigned the previously announced Prescription Drug User Fee Act (PDUFA) goal date of the Biologics License Application (BLA) for the subcutaneous formulation of Opdivo (nivolumab) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20) (herein referred to as "subcutaneous nivolumab") across all previously approved adult, solid tumor Opdivo indications as monotherapy, monotherapy maintenance following completion of Opdivo plus Yervoy (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib (Press release, Bristol-Myers Squibb, MAY 21, 2024, View Source [SID1234643483]). The updated goal date is December 29, 2024.

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The application is based on results from CheckMate -67T, the first Phase 3 trial of the subcutaneous formulation of nivolumab to evaluate and demonstrate noninferior pharmacokinetics, efficacy and consistent safety vs. its intravenous formulation. If approved, subcutaneous nivolumab has the potential to be the first and only subcutaneously administered PD-1 inhibitor.

About CheckMate -67T

CheckMate -67T is a Phase 3 randomized, open-label trial evaluating subcutaneous administration of Opdivo co-formulated with Halozyme’s proprietary recombinant human hyaluronidase, rHuPH20, or subcutaneous nivolumab (nivolumab and hyaluronidase) compared to intravenous Opdivo, in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior systemic therapy. This trial presents an opportunity to potentially bring a subcutaneous formulation of Opdivo to patients. A total of 495 patients were randomized to either subcutaneous nivolumab or intravenous Opdivo. The co-primary endpoints of the trial are time-averaged serum concentration over 28 days (Cavgd28) and trough serum concentration at steady-state (Cminss) of subcutaneous nivolumab vs. intravenous Opdivo. Objective response rate (ORR) is a key secondary endpoint.

On May 21, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that it will present clinical trial data for selected programs from the Company’s diversified immuno-oncology pipeline at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting in Chicago, Illinois, from May 31 to June 4, 2024 (Press release, BioNTech, MAY 21, 2024, View Source [SID1234643482]). Moreover, in support of the Company’s ongoing CAR-T cell and individualized mRNA programs, BioNTech will also present epidemiological and real-world data from two observational studies in patient populations for which product candidates are being developed in the Company’s respective clinical programs.

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"Our aim is to develop innovative treatment options across the continuum of cancer disease and establish new treatment paradigms that have the potential to address the fundamental challenges of treating cancer to drive meaningful improvements in the long-term survival rates for patients," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "The data from the interventional and observational studies that we will present at this year’s ASCO (Free ASCO Whitepaper) are of relevance for progress towards our goal as they will contribute to informing the direction of further development of several of our priority product candidates as well as the design of planned pivotal and later-stage clinical trials across all three key pillars of our diversified oncology pipeline, including novel immunomodulators, targeted therapies such as cell therapies and ADCs, and mRNA-based therapeutic cancer vaccines."

Highlights of BioNTech’s updates to be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting 2024:

•Updates on several Phase 1b/2a trials investigating BNT327/PM8002 as a monotherapy in patients with solid tumors will be presented. BNT327/PM8002 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with VEGF-A neutralization to create a cycle of vascular normalization and immunostimulation in the microenvironment of the tumor. Two posters will provide clinical data updates for cohorts with advanced cervical cancer, platinum-resistant recurrent ovarian cancer and advanced non-small cell lung cancer ("NSCLC"). The product candidate is being developed in collaboration with Biotheus Inc. ("Biotheus").
•Initial results from the randomized, open-label, Phase 2 trial (NCT05117242) with the bispecific antibody candidate BNT311/GEN1046 (acasunlimab) alone or in combination with pembrolizumab in patients with previously treated metastatic NSCLC ("mNSCLC") will be presented. BNT311/GEN1046 combines PD-L1 checkpoint inhibition with 4-1BB costimulatory activation. The product candidate is being developed in collaboration with Genmab S/A ("Genmab").
•BioNTech will present preliminary data of an epidemiological study (NCT04813627) that correlates post-operative circulating tumor DNA ("ctDNA"), a cancer biomarker for minimal residual disease, with disease-free survival in patients with colorectal cancer ("CRC"). This observational study provides supportive epidemiological and prognostic data for the ongoing interventional Phase 2 trial (NCT04486378) with the individualized neoantigen-specific immunotherapy ("iNeST") candidate autogene cevumeran (BNT122, RO7198457) in ctDNA-positive, high-risk stage II/stage III adjuvant CRC. Autogene cevumeran is jointly being developed by BioNTech and Genentech Inc. ("Genentech"), a member of the Roche Group.
•BioNTech will present an analysis of real-world data that investigated the overall survival, treatment patterns and prognostic variables of patients with testicular germ cell tumors receiving palliative chemotherapy. This analysis will inform the design of BioNTech’s planned pivotal trial with the Company’s CAR-T cell therapy candidate BNT211 in patients with germ cell tumors. BNT211 combines an autologous CAR-T cell therapy candidate targeting the oncofetal antigen Claudin-6 ("CLDN6") and an investigational CLDN6-encoding CAR-T cell amplifying RNA vaccine ("CARVac").

BioNTech has established a diversified clinical oncology pipeline based on its modular multi-platform approach. The Company is advancing more than 20 clinical programs in unmet medical need solid tumor indications, including mRNA-based immunotherapies, targeted therapies entailing cell therapies and antibody-drug conjugates (ADCs), and novel immunomodulators. These candidates are currently being evaluated in more than 30 clinical studies, including nine programs in advanced Phase 2 trials and two candidates in pivotal Phase 3 trials. BioNTech is advancing key programs into late-stage development with the aim to have ten or more potentially registrational trials in its oncology pipeline by the end of 2024. The Company aims to launch its first cancer immunotherapy in 2026. By 2030, BioNTech plans to obtain approvals for a total of ten cancer indications across various drug classes.
The full abstracts will be available on the ASCO (Free ASCO Whitepaper) Annual Meeting website. Click here for further information on BioNTech’s pipeline candidates.

Full poster details:

Candidate: BNT327/PM8002
Session title: Lung Cancer—Non-Small Cell Metastatic
Abstract Title: A Phase Ib/IIa Trial to Evaluate the Safety and Efficacy of PM8002, a Bispecific Antibody Targeting PD-L1 and VEGF-A, as a Monotherapy in Patients with advanced NSCLC
Location: Hall A, Poster Board 397
Abstract Number: 8533
Date: Monday, June 3, 2024
Time: 1.30 PM-4.30 PM CDT

Candidate: BNT327/PM8002
Session title: Gynecologic Cancer
Abstract Title: Efficacy and Safety of PM8002, a Bispecific Antibody Targeting PD-L1 and VEGF-A, as a Monotherapy in Patients with Solid Tumors: Clinical Data from Advanced Cervical Cancer and Platinum-resistant Recurrent Ovarian Cancer Cohorts
Location: Hall A, Poster Board 395
Abstract Number: 5524
Date: Monday, June 3, 2024
Time: 9.00 AM-12.00 PM CDT

Candidate: BNT326/YL202
Session title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Abstract Title: YL202/BNT326, a HER3-targeted ADC, in patients with locally advanced or metastatic non-small cell lung cancer and breast cancer: Preliminary results from a first-in human phase I trial
Location: Hall A, Poster Board 179
Abstract Number: 3034
Date: Saturday, June 1, 2024
Time: 09:00 AM – 12:00 PM CDT

Candidate: BNT311/GEN1046 (acasunlimab)
Session Title: Developmental Therapeutics—Immunotherapy
Abstract Title: Acasunlimab (DuoBody-PD-L1x4-1BB) alone or in combination with pembrolizumab (pembro) in patients (pts) with previously treated metastatic non-small cell lung cancer (mNSCLC): initial results of a randomized, open-label, phase 2 trial
Location: Hall A, Poster Board 12
Abstract Number: 2533
Date: Saturday, June 1, 2024
Time: 9.00 AM-12.00 PM CDT

Candidate: Autogene cevumeran (BNT122, RO7198457)
Session Title: Gastrointestinal Cancer—Colorectal and Anal
Abstract Title: Preliminary results correlating post-operative ctDNA status with disease-free survival in Stage II (high risk) / III Colorectal Cancer Patients in the BNT000-001 epidemiology study
Location: Hall A, Poster board 189
Abstract Number: 3526
Date: Saturday, June 1, 2024
Time: 1.30 PM-4.30 PM CDT

Candidate: BNT211
Session Title: Genitourinary Cancer—Prostate, Testicular, and Penile
Abstract Title: Real-world evidence of overall survival (OS) and treatment patterns of patients (pts) with testicular germ cell tumors (DCT) receiving palliative chemotherapy in the United States
Location: Poster board 356
Abstract Number: 5038
Date: Sunday, June 2, 2024
Time: 9.00 AM – 12.00 PM CDT