On June 7, 2021 Galapagos NV (Euronext & NASDAQ: GLPG) reported a share capital increase arising from subscription right exercises (Press release, Galapagos, JUN 7, 2021, View Source [SID1234583710]).

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Galapagos issued 10,940 new ordinary shares on 7 June 2021, for a total capital increase (including issuance premium) of €325,279.

Pursuant to the subscription right exercise program of Galapagos’ management board, members of the management board automatically are committed to exercise a minimum number of subscription rights, subject to certain conditions. In accordance with the rules of this program, one management board member exercised 5,000 subscription rights.

In accordance with Belgian transparency legislation1, Galapagos notes that its total share capital currently amounts to €354,418,623.11, the total number of securities conferring voting rights amounts to 65,522,521, which is also the total number of voting rights (the "denominator"), and all securities conferring voting rights and all voting rights are of the same category. The total number of rights (formerly known as warrants) to subscribe to not yet issued securities conferring voting rights is (i) 6,709,662 subscription rights under several outstanding employee subscription right plans, which equals 6,709,662 voting rights that may result from the exercise of those subscription rights, and (ii) one subscription right issued to Gilead Therapeutics to subscribe for a maximum number of shares that is sufficient to bring the shareholding of Gilead and its affiliates to 29.9% of the actually issued and outstanding shares after the exercise of the subscription right. This excludes the 2,736,250 subscription rights of Subscription Right Plan 2021 BE, Subscription Right Plan 2021 RMV and Subscription Right Plan 2021 ROW, which were created subject to acceptance. Galapagos does not have any convertible bonds or shares without voting rights outstanding.

On June 7, 2021 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the company has entered into a clinical trial collaboration agreement with Seagen Inc. to evaluate nirogacestat, SpringWorks’ investigational gamma secretase inhibitor, in combination with SEA-BCMA, Seagen’s investigational monoclonal antibody targeting B-cell maturation agent (BCMA), in patients with relapsed or refractory multiple myeloma (Press release, SpringWorks Therapeutics, JUN 7, 2021, View Source [SID1234583795]).

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Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase levels of membrane-bound BCMA and reduce levels of soluble BCMA, thereby enhancing the activity of BCMA-targeted therapies.

"We continue to make significant progress advancing nirogacestat as a potential best-in-class cornerstone of BCMA combination therapy for patients with multiple myeloma and are delighted to work with Seagen to study nirogacestat in combination with SEA-BCMA, our first collaboration with a monoclonal antibody targeting BCMA," said Saqib Islam, Chief Executive Officer of SpringWorks. "Our goal is to meaningfully improve clinical outcomes for patients with multiple myeloma and we look forward to generating clinical data using nirogacestat in combination with BCMA-directed therapies across modalities."

Under the terms of the agreement, Seagen will sponsor and conduct the Phase 1 study to evaluate the safety, tolerability and preliminary efficacy of the combination, and will assume all costs associated with the study, other than expenses related to the manufacturing of nirogacestat and certain expenses related to intellectual property rights. Seagen and SpringWorks will also form a joint development committee to manage the clinical study, which is expected to commence in the second half of 2021.

In addition to its ongoing clinical collaborations with BCMA-directed therapies, SpringWorks is conducting a global Phase 3, double-blind, randomized, placebo-controlled clinical trial (the DeFi Trial) to evaluate nirogacestat as a monotherapy in adults with progressing desmoid tumors.

About Nirogacestat
Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has six collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, two CAR T cell therapies, two bispecific antibodies and a monoclonal antibody. In addition, SpringWorks and Fred Hutchinson Cancer Research Center have entered into a sponsored research agreement to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA directed therapies using a variety of preclinical and patient-derived multiple myeloma models developed by researchers at Fred Hutch.

Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.

On June 7, 2021 Biofrontera AG (NASDAQ: BFRA; Frankfurt Stock Exchange: B8F) (the "Company"), an international biopharmaceutical company, reported preliminary, unaudited revenue for the month of May 2021 (Press release, Biofrontera, JUN 7, 2021, View Source [SID1234583646]).

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The Company’s preliminary, unaudited revenue from product sales in May 2021 amounted to approximately EUR 2,437 thousand, compared to EUR 1,172 thousand in May 2020, an increase of 108%.

Preliminary revenues from product sales in the US were around EUR 1,638 thousand compared to EUR 599 thousand in May 2020, an increase of 174%. In Germany, revenues from product sales amounted to approximately EUR 425 thousand, compared to EUR 540 thousand in May 2020, a decrease of 21%. Despite the pandemic, sales in Germany had developed positively last year, and in May in particular, we saw catch-up effects from the lock-down month of April 2020. In the rest of Europe, the Company generated product sales of around EUR 374 thousand, compared to EUR 33 thousand in May 2020, a plus of 1,041%.

Preliminary unaudited revenues

Due to commercial rounding, rounding differences may occur in tables.

Due to the pandemic, the monthly sales development is compared with sales in 2019 for increased transparency. As such, a slight increase of 1% in May 2021 total product sales was achieved in all markets compared to May 2019. In more detail, May 2021 sales were up by 1% in Germany and by 55% in the remaining European markets compared to May 2019. In the USA, product sales decreased by 7%. The decline was mainly caused by no or lower sales of Aktipak and Xepi, respectively, while sales of Ameluz were at a comparable level.

The recovery in product sales compared to 2020 as well as to 2019, which has been perceived since mid-March 2021, thus continued in May 2021. This indicates a significant recovery of the COVID-19 situation.

On June 7, 2021 Thermo Fisher Scientific, the world leader in serving science, and the University of Sheffield, a leading institution with a global reputation for research excellence, reported that they have joined forces to develop advanced end-to-end workflows for the characterization and monitoring of complex oligonucleotide and mRNA products (Press release, Lifescience Newswire, JUN 7, 2021, View Source [SID1234583662]). This collaboration brings together the University of Sheffield’s extensive research expertise and Thermo Fisher’s cutting-edge sample preparation, liquid chromatography (LC), high resolution accurate mass (HRAM) mass spectrometry (MS) and data interpretation software technologies to enable the development of streamlined analytical workflows and robust fit-for-purpose processes.

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Thermo Fisher brings magnetic bead technology to this collaboration, providing access to sample preparation protocols that are simple to create and modify for optimal reliability and sample-to-sample consistency. These novel sample preparation techniques will be combined with the high-performing Thermo Scientific Orbitrap Exploris 240 Mass Spectrometers, which are designed to deliver quantitative precision and accuracy regardless of sample complexity, the depth of insight required or the presence of unknown compounds. For a complete workflow solution, the Thermo Scientific Dionex DNAPac RP Oligonucleotide Columns will enable high-resolution analysis of synthetic and modified oligonucleotides, while the Thermo Scientific BioPharma Finder Integrated Software will facilitate comprehensive interpretation and data visualization for more confident characterization of oligonucleotide and mRNA products.

"Recently we have witnessed a pressing need for more robust and accurate methods for the characterization and monitoring of oligonucleotide and mRNA products, to ensure generation of a rich level of information that can drive timely production of an ever-growing pipeline of novel vaccines and drug products," explained Eric Grumbach, director of pharma, biopharma vertical marketing, Thermo Fisher Scientific. "Our collaboration with the University of Sheffield will enable us to effectively meet this need through powerful analytical workflows and best practices. We will also optimize current approaches by streamlining sample preparation techniques for mRNA sequencing using nuclease digestion, ion-pairing chromatography and novel separation methods without ion-pairing."

"Having the right tools is essential for the reliable analysis and characterization of oligonucleotide and mRNA products," said Professor Mark Dickman, deputy faculty director of research and innovation, Engineering, University of Sheffield. "Our decades-long research experience and expertise combined with Thermo Fisher’s support and access to industry-leading technology gives us the means to further expand our testing capabilities in this rapidly evolving space, ultimately facilitating the discovery and development of cutting-edge therapeutics."

Thermo Fisher Scientific will showcase its newest products, software solutions and collaborations in a company-hosted virtual event, "Innovation Summit: Shaping the Future of LC-MS in Life Science Together," from June 8-10, 2021. Register here to learn more.

To find out more about Thermo Fisher’s complete workflow solutions, please visit Orbitrap Exploris 240 Mass Spectrometers, Thermo Scientific Dionex DNAPac RP Oligonucleotide Columns and BioPharma Finder Integrated Software.

On June 7, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported updated results from the first-in-human study of the Bcl-2 inhibitor lisaftoclax (APG-2575) in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies (Press release, Ascentage Pharma, JUN 7, 2021, View Source;ascentage-pharma-delivers-oral-presentation-featuring-updated-data-demonstrating-promising-efficacy-and-safety-of-bcl-2-inhibitor-lisaftoclax-apg-2575-in-patients-with-relapsed-or-refractory-cllsll-301307266.html [SID1234583678]). The findings were reported in an oral presentation at the 57th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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As one of the Chinese biotechnology companies that have been increasingly visible at international scientific congresses in recent years, Ascentage Pharma has entered the fourth year in which its clinical advances have been selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting. This year, results from four of the company’s clinical trials were selected for presentations at the meeting, and of these data, the two oral presentations have received widespread and avid interest from research and medical communities. Updated data on lisaftoclax have demonstrated favorable preliminary safety and efficacy, including an objective response rate (ORR) of 80% and a favorable tolerability profile, with manageable adverse events (AEs) in patients with R/R CLL/SLL. Moreover, no dose-limiting toxicity (DLT) was observed at the maximum tested dose of 1,200 mg. The maximum tolerated dose (MTD) has not been reached, and no laboratory or clinical tumor lysis syndrome (TLS) has been reported.

Dr. Asher Chanan-Khan, MD, of Mayo Clinic, and the Global Principal Investigator of this study, commented: "Lisaftoclax is a potent, selective Bcl-2 inhibitor which can both induce apoptosis and inhibit tumor cell growth. In this first-in-human study in the US and Australia, lisaftoclax showed a favorable safety profile and promising antitumor activity in patients with R/R CLL/SLL, and potential disease control in several other hematologic malignancies. In view of the preliminary safety and clinical activity observed in this Phase I study, we look forward to further evaluating the antitumor activity of lisaftoclax in individual hematologic malignancies and solid tumors."

"The initial objective response rate of 80%, together with a favorable safety profile and no TLS despite a daily dose ramp-up, demonstrated by lisaftoclax in patients with R/R CLL/SLL are particularly encouraging and once again support the best-in-class potential of lisaftoclax," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "At this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, we have announced results from multiple studies, including that of lisaftoclax, in two oral presentations and two poster presentations. I am very proud of these advances, which attest to Ascentage Pharma’s robust capabilities in global innovation. Moving forward, we will remain committed to our mission of addressing unmet clinical needs in China and around the world, and strive to accelerate our clinical programs in the hope of soon benefitting patients."

An overview of the four abstracts presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting:

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

Highlights of the oral presentation on lisaftoclax at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting:

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

Abstract: #7502

This first-in-human global Phase I study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and MTD/recommended Phase II dose (RP2D) of lisaftoclax in patients with R/R CLL and other HMs. Lisaftoclax was orally administered once daily in a 28-day cycle. Patients with CLL or intermediate-high TLS risk were initiated on a daily ramp-up schedule until the dose assigned before the study cycles.
As of April 15, 2021, 36 patients had been enrolled and treated with lisaftoclax at doses ranging from 20 to 1,200 mg, with a median of 2 (range: 1-13) prior lines of treatment. These patients had been diagnosed with R/R CLL/SLL (n=15), multiple myeloma (MM, n=6), follicular lymphoma (FL, n=5), Waldenström macroglobulinemia (WM, n=5); and either acute myeloid leukemia (AML), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), myelodysplastic syndromes (MDS), or hairy cell leukemia (HCL; n=1 each). These patients received a median of 6 cycles (range: 1-24) of treatment with lisaftoclax.
Lisaftoclax was well tolerated, with manageable AEs. No DLT was observed even at the maximum dose of 1,200 mg. The MTD has not been reached, and no laboratory or clinical TLS has been reported. Hematologic treatment-related adverse events (TRAEs) of any grade in more than 10% patients included neutropenia and anemia, while nonhematologic TRAEs included fatigue, diarrhea, constipation, and nausea.
In the 15 evaluable patients with R/R CLL/SLL, 7 (46.7%) each were assessed as Rai stage III-IV or intermediate-high per International Prognostic Index (IPI). Patients in this cohort received a median of 9 (range: 5-24) cycles of treatment, and 12 patients achieved partial responses (PRs), for an ORR of 80% and a median time to response of 2 (range: 2-8) treatment cycles.
Among 21 patients with R/R non CLL/SLL, who received a median of 3 (range: 1-13) prior lines of treatment, 20 were evaluable. Of these individuals, 1 with t (11;14)-mutant MM achieved minor response (MR) after 2 treatment cycles. A total of 10 (50%) patients in this cohort achieved stable disease (SD) or deeper responses.
The preliminary PK profile showed that exposures increased with lisaftoclax at doses ranging from 20 to 1,200 mg (average half-life: 4-5 hours). On BH3 profiling, lisaftoclax rapidly triggered changes in Bcl-2 complex in CLL/SLL patient samples, which were consistent with rapid clinical reductions in absolute lymphocyte counts (ALCs).
In conclusion, efficacy and safety data showed that the Bcl-2 inhibitor lisaftoclax offers a potential alternative treatment for patients with R/R CLL/SLL and other HMs, with a daily ramp-up schedule that may be more patient-friendly and a favorable preliminary safety profile.