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Merck KGaA, Darmstadt, Germany Highlights Novel Mechanisms with the Potential to Transform Standards of Care in Several Cancers, MS, and Lupus

On March 23, 2022 Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported an overview of its innovative pipeline with a focus on five mid- to late-stage assets with first-in-class and/or best-in-class potential at its R&D Update Call (Press release, Merck KGaA, MAR 23, 2022, View Source [SID1234610758]).

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"At Merck KGaA, Darmstadt, Germany we are working to translate our extensive expertise and deep knowledge in key tumors and neurological and immunological diseases with a goal to change treatment paradigms and improve patient outcomes," said Danny Bar-Zohar, Global Head of Development for the Healthcare business of Merck KGaA, Darmstadt, Germany. "With evobrutinib, xevinapant, and berzosertib, we have the opportunity to be not only first-in-class, but potential game-changers in how we treat MS, head & neck cancer and small cell lung cancer going forward."

Advancing Assets with Transformational Potential

Evobrutinib (BTK inhibitor) – A pioneering development program with a new mechanism of action (MoA) for the treatment of patients with relapsing multiple sclerosis (RMS) that has the potential to change the standard of care.

Oral, central nervous system (CNS)-penetrant, covalent Bruton’s tyrosine kinase inhibitor (BTKi) in development for RMS.
MoA combines potent B-cell inhibition to target acute inflammation (associated with relapses) with a central effect on microglia that aims to reduce chronic inflammation (associated with disease progression).
Comprehensive Phase II clinical data support best-in-class potential.
Evobrutinib is the first BTKi to have completed enrollment of the Phase III clinical trial program for relapsing multiple sclerosis, with data readout expected in Q4 2023.
Xevinapant (IAP antagonist) – As a potent oral antagonist of Inhibitor of Apoptosis Proteins (IAP) and the only IAP antagonist in late-stage development, xevinapant builds on our market-leading expertise in squamous cell carcinoma of the head and neck (SCCHN), aimed at maximizing the chances of a cure in locally advanced disease setting.

Ongoing Phase III TrilynX study for previously untreated unresectable locally advanced (LA) SCCHN in combination with platinum-based chemoradiotherapy.
Second global Phase III study to be initiated in the first half of 2022 to evaluate xevinapant in patients with cisplatin-ineligible LA SCCHN.
5-year update of OS data from Phase II study anticipated in 2022.
First launch expected in 2025.
Berzosertib (ATR inhibitor) – The lead candidate in our DNA Damage Response (DDR) inhibitor portfolio and the first ATR inhibitor with positive randomized clinical trial in any tumor type, seeks to exploit the synergistic effect of combining ATR inhibition with topoisomerase I inhibitors

Multiple mid-stage clinical trials in small cell lung cancer (SCLC) build on positive Phase II study results, with the goal of establishing a new standard of care in second-line SCLC.
Study planned for indication expansion in ovarian cancer and potentially in refractory GI cancers.
M1231 (MUC1/EGFR bi-specific ADC) – The first bi-specific ADC (antibody-drug conjugate) from our pipeline that aims to optimize targeting of cancer cells and overcome remaining safety limitations of conventional ADCs.

M1231 delivers a cytotoxic payload to tumor cells expressing both MUC1 and EGFR and has a highly controlled drug-antibody ratio, which is anticipated to increase tumor specificity, selectivity, and efficacy.
Phase I clinical study to characterize the safety and preliminary activity is well underway, and efficacy expansions into late-stage non-small cell lung cancer and esophageal squamous cell carcinoma are expected to begin in 2022.
Enpatoran (TLR7/8 inhibitor) – Oral therapy that aims to overcome limitations of available lupus therapies by providing selective inhibition of lupus-relevant disease drivers, which may increase efficacy while preserving immunity against infections.

Highly specific potential first-in-class immune modulator blocking the activation of Toll-like receptor (TLR)7 and TLR8, known to be activated in lupus.
Initiation of Phase II studies in systemic lupus erythematosus (SLE) / cutaneous lupus erythematosus (CLE) in the first half of 2022.
Advancing the broader pipeline and portfolio

Merck KGaA, Darmstadt, Germany will initiate 11 new studies in 2022 across the early- and late-stage pipeline, including a Phase III confirmatory study with tepotinib in EGFRm MET amplification in NSCLC, five proof-of-concept studies including trials of M1774, an oral ATR inhibitor being evaluated as both a monotherapy and in combination with PARP inhibitors; the JAVELIN Bladder Medley umbrella study in the first-line urothelial carcinoma, combining avelumab with novel investigational agents including our anti-TIGIT M6223 and Nektar Therapeutics’ interleukin-15 (IL-15) receptor agonist, NKTR-255, in the maintenance setting; two first-in-human studies involving M9140, a next-generation ADC based on an internally developed linker-payload technology; and M1069, our dual adenosine receptor antagonist.

"Our rapidly progressing pipeline of in-house–discovered and partnered assets with first-in-class potential demonstrate the deep expertise and collaborative mindset of our R&D organization," said Joern-Peter Halle, Global Head of Research for the Healthcare business of Merck KGaA, Darmstadt, Germany. "We expect exciting new entries and substantial advances of our early- and late-stage pipeline in the next few years."

To access the presentation and a recording, please visit the Company’s website at View Source

Merck KGaA, Darmstadt, Germany’s Commitment to Cancer

Merck KGaA, Darmstadt, Germany is a science-led organization dedicated to delivering transformative medicines with the goal of making a meaningful difference in the lives of people affected by cancer. Our oncology research efforts aim to leverage our synergistic portfolio in oncogenic pathways, immuno-oncology, and DNA Damage Response (DDR) to tackle challenging tumor types in gastrointestinal, genitourinary, and thoracic cancers. Our curiosity drives our pursuit of treatments for even the most complex cancers, as we work to illuminate a path to scientific breakthroughs that transform patient outcomes. Learn more at View Source

Merck KGaA, Darmstadt, Germany in Neurology and Immunology

Merck KGaA, Darmstadt, Germany has a long-standing legacy in neurology and immunology, with significant R&D and commercial experience in multiple sclerosis (MS). The company`s current MS portfolio includes two products for the treatment of relapsing MS – Rebif (interferon beta-1a) and MAVENCLAD (cladribine tablets). Merck KGaA, Darmstadt, Germany aims to improve the lives of patients by addressing areas of unmet medical needs. In addition to KGaA, Darmstadt, Germany`s commitment to MS, the company also has a pipeline focusing on discovering new therapies that have the potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE).

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Personalis to Present Data Demonstrating Breadth of NeXT Platform for Oncology at AACR Annual Meeting 2022

On March 23, 2022 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported it is presenting new data in scientific posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, which will be held in-person and online, April 8-13, 2022 (Press release, Personalis, MAR 23, 2022, View Source [SID1234610757]).

"These abstracts demonstrate the full range of our capabilities in advancing the field of oncology, from a rich understanding of molecular-level interactions through clinical applications in multiple disease indications. The work also builds on the company’s strong foundation of genomic data generated with solid tumor tissue and expands into liquid biopsy with a unique, exome-wide approach," said Richard Chen, M.D., Chief Medical Officer and SVP of R&D of Personalis.

Personalis is presenting five posters, outlined below. Further details can be found at this link.

Title: Applying NeXT Liquid Biopsy, an exome-scale platform, to monitor and discover somatic variants in a broad set of cancer types
Overview: Circulating tumor cell-free DNA (ctDNA) has become a biomarker for prognosis and disease monitoring. However, studies typically utilize assays limited to a small set of genes that may miss biologically important and clinically actionable mutations. To address this limitation, we have developed a whole-exome scale cfDNA platform, NeXT Liquid Biopsy, that enables sensitive detection and tracking of somatic mutations in plasma samples across ~20,000 genes. The NeXT Liquid Biopsy platform monitors tumor variants and discovers novel mutations in the plasma, through analysis of tumor, normal and plasma samples from the same patient. The NeXT Liquid Biopsy platform enables the identification of somatic variants in liquid biopsy samples, following interventions such as surgery and treatment therapies. Here, we have applied NeXT Liquid Biopsy to profile the shedding of somatic mutations from more than 100 pan-cancer patients on an exome scale, detecting variants in well-characterized cancer driver genes and many events outside of traditional panel footprints.

Title: Accurate quantification of infiltrating B cell composition and clone diversity in tumor samples
Overview: The role of B cells as a prognostic biomarker remains elusive. For instance, infiltrating B cells in colorectal cancer have both positive and negative prognostic value. Thus, a scalable approach to quantify B cells and the B-cell receptor repertoire could yield novel insights into the role of B cells in tumor biology. To address this, we have developed immune cell quantification (InfiltrateIDTM) and immune receptor repertoire profiling (RepertoireIDTM) methods as part of the ImmunoID NeXT Platform, an augmented, immuno-oncology-optimized exome/transcriptome platform. We show that InfiltrateID and RepertoireID accurately capture the composition and clone diversity of infiltrating B cells in tumor samples. Furthermore, we apply the two methods to explore B cell infiltration and BCR repertoires across a set of more than 650 pan-cancer samples.

Title: Exome-scale longitudinal tracking of emerging therapeutic resistance in GIST via analysis of circulating tumor DNA
Overview: Gastrointestinal stromal tumors (GIST) are lethal tumors characterized by constitutively activating mutations to KIT or PDGFRA. Transient disease control in the first-line setting is achieved via inhibition of tyrosine kinase signaling using the KIT inhibitor imatinib. As patients progress through subsequent lines of therapy, a molecularly heterogeneous disease evolves, characterized by distinct subtypes and shifting repertoires of exon-specific KIT variants that directly impact treatment outcomes. This study uses tumor-informed exome-scale liquid biopsy to identify and track the evolution of multiple resistance mechanisms in patients receiving tyrosine kinase inhibitors (TKIs) to address the unmet need of comprehensive understanding of GIST evolution in response to therapy.

Title: A high sensitivity, tumor-informed liquid biopsy platform, designed to detect minimal residual disease at part per million resolution
Overview: Tumor-informed liquid biopsy approaches have proven promising for detecting minimal residual disease (MRD) and recurrence of cancer following surgical resection or other therapy. However, current liquid biopsy MRD assays typically detect ctDNA in a range above 30 to 300 parts per million (PPM), leaving a significant fraction of MRD cases undetected, particularly soon after surgery and in early-stage cancers where ctDNA can be at very low levels. To address this, Personalis has developed NeXT Personal, a tumor-informed liquid biopsy assay that achieves sensitivity down to 1 PPM, therefore enabling earlier detection of MRD and recurrence.

Title: Mono-allelic immunopeptidomics data from 109 MHC-I alleles reveals variability in binding preferences and improves neoantigen prediction algorithm
Overview: This study extends the previously published MHC-I, pan-allelic neoantigen prediction algorithm, SHERPA, with immunopeptidomics from 84 additional mono-allelic transfected cell lines, totaling data from 109 unique alleles. SHERPA achieves model generalizability and 98% population allelic coverage by integrating nearly 500 additional public immunopeptidomics samples. As a result, SHERPA identifies 1.38-fold more immunogenic epitopes than either NetMHCPan-4.1 and MHCFlurry-2.0 and reveals strong correlations between evolutionary divergence and influential binding pocket positions in the MHC allele.

Cyclica and Arctoris to Expand Partnership to Advance Drug Discovery Programs for Alzheimer’s Disease

On March 23, 2022 Cyclica Inc. ("Cyclica"), a neo-biotech with the vision to advance the most robust and sustainable drug discovery pipeline, and Arctoris Ltd. ("Arctoris"), a tech-enabled biopharma company that combines its unique automation with computational approaches to progress drug discovery, reported that they have agreed to expand their partnership to progress drug discovery programs for novel neurodegenerative targets with a focus on Alzheimer’s disease (Press release, Cyclica, MAR 23, 2022, View Source [SID1234610756]). This planned expansion of the partnership follows the results from an initial engagement that yielded positive results for targets related to both oncology and neurodegenerative disease.

"Cyclica’s platform and capabilities in combination with the biological assay development of Arctoris will enable us to yield meaningful results and advance research development for patients suffering from Alzheimers and other neurodegenerative diseases. The potential of combining our two specialties is very promising and we are extremely optimistic about the impact this partnership is expected to have on patients," shares Naheed Kurji, Co-Founder, President and CEO of Cyclica.

Dr. Martin-Immanuel Bittner, MD DPhil FRSA, CEO of Arctoris, comments by sharing, "Our joint drug discovery program focuses on dual specificity inhibitors – a very promising yet also challenging modality. Cyclica is one of the leaders in this space, leveraging their structure-based and AI-directed molecule design for polypharmacology, while at Arctoris we have built a particular expertise in complex mechanistic enzymology and advanced cell-based models in neurodegeneration. This is a highly synergistic partnership, and I am excited about what we can achieve together for patients around the world in an indication area in dire need of new and better treatment options."

Cyclica and Arctoris have long-term plans for their partnership as discussions are already underway about tackling additional therapeutic targets.

Applied DNA to Participate in the 2022 Virtual Growth Conference Presented by Maxim Group LLC and Hosted by M-Vest on March 28th – 30th from 9:00 a.m. – 5:00 p.m. EDT

On March 23, 2022 Applied DNA Sciences, Inc. (NASDAQ: APDN), a leader in cell-free, enzymatic DNA production, reported that CEO Dr. James A. Hayward is invited to present at the 2022 Virtual Growth Conference presented by Maxim Group LLC and hosted by M-Vest, on March 28th – 30th from 9:00 a.m. – 5:00 p.m. EDT (Press release, Applied DNA Sciences, MAR 23, 2022, View Source [SID1234610755]). Dr. Hayward’s presentation will be available on-demand for the duration of the conference via the sign-up link: Sign up here to access the presentation

During the virtual conference, investors will hear from executives from a wide range of sectors, including Biotech, Clean Energy, Electric Vehicles, Financial Services, Fintech & REITs, Gaming & Entertainment, Healthcare, Healthcare IT, Infrastructure, Shipping and Technology/Media/Telecom. The conference will feature company presentations, fireside chats, roundtable discussions, and live Q&A with CEOs moderated by Maxim Research Analysts.

This conference will be live on M-Vest. To attend, sign up to become an M-Vest member: Click Here to Reserve your seat

Navidea Biopharmaceuticals Reports Fourth Quarter 2021 Financial Results

On March 23, 2022 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported its financial results for the fourth quarter and year-to-date for the period ended December 31, 2021 (Press release, Navidea Biopharmaceuticals, MAR 23, 2022, View Source [SID1234610753]).

Alexander L. Cappello, Chair of Navidea’s Board of Directors, said, "We remain focused on our mission of developing precision immunodiagnostic agents and immunotherapeutics to enhance patient care. We are confident that our strong management team, supported by our experienced and active Board of Directors, can continue to execute on our business plan and fulfill the vision we have for Navidea."

Fourth Quarter 2021 Highlights and Subsequent Events

Continued to work on financing for the Company. We have engaged with an investment bank and options are being pursued.
Initiated and enrolled into the Company’s NAV3-33 Phase 3 trial in rheumatoid arthritis ("RA") titled "Evaluation of Tc 99m Tilmanocept Imaging for the Early Prediction of Anti-TNFα Therapy Response in Patients with Moderate to Severe Active Rheumatoid Arthritis."
Continued enrollment into the Company’s NAV3-32 Phase 2b trial comparing Tc99m tilmanocept imaging to histopathology of joints of patients with active RA. Eleven patients out of an originally estimated maximum of 24 based on subject pathotype are now enrolled with both imaging and biopsy performed.
Completed enrollment in the Company’s NAV3-35 Phase 2b study, "Development of a Normative Database for Rheumatoid Arthritis (RA) Imaging with Tc99m Tilmanocept."
Completed the investigator-initiated Phase 2 trial being run at the Massachusetts General Hospital evaluating Tc99m tilmanocept uptake in atherosclerotic plaques of HIV-infected individuals. An abstract was presented at the Conference on Retroviruses and Opportunistic Infections in February 2022.
Signed research agreement with the University of Pennsylvania evaluating Tc99m tilmanocept as a prognostic marker for glioblastoma.
Signed a Letter of Intent with the image analysis company MIM Software, Inc., to be the Company’s commercial partner for image quantification of Tc99m tilmanocept imaging in RA.
Filed two new provisional patent applications. The first is related to new methods of attaching chemotherapeutics to the Manocept platform, and the second relates to maximizing target-tissue uptake and off-target competitive blocking. These have important implications for pipeline applications.
Michael Rosol, Ph.D., Chief Medical Officer for Navidea, said, "The clinical research team continues to work diligently to advance the technology in key disease areas, with an emphasis on our RA program. The NAV3-33 Phase 3 trial is enrolling, we continue to enroll into the NAV3-32 Phase 2b trial comparing tilmanocept imaging to synovial tissue biopsy samples of RA patients, and we have completed our normative database trial enrollment. Concurrent with all of this, we continue to make progress in our therapeutics pipeline, and we expect to keep advancing these towards the clinic."

Financial Results

Total net revenues for the fourth quarter of 2021 were $50,000, compared to $219,000 for the same period in 2020. Total net revenues for the full year of 2021 were $532,000, compared to $914,000 in 2020. The decrease was primarily due to decreased grant revenue related to Small Business Innovation Research grants from the National Institutes of Health supporting Manocept development and decreased royalty and license revenue from sales of Tc99m tilmanocept in Europe, offset by the partial recovery of debts previously written off in 2015 and receipt of reimbursement from Cardinal Health 414, LLC of certain R&D costs.
Research and development ("R&D") expenses for the fourth quarter of 2021 were $1.4 million, compared to $1.3 million in the same period in 2020. R&D expenses for the full year of 2021 were $5.1 million, compared to $4.9 million in 2020. The net increase during the year to date was primarily due to increased regulatory consulting, employee compensation, travel, recruiting and general office expenses, coupled with net increases in drug project expenses, including increased Manocept therapeutic and Tc99m tilmanocept development costs, offset by decreased Manocept diagnostic development costs.
Selling, general and administrative ("SG&A") expenses for the fourth quarter of 2021 were $2.3 million, compared to $1.7 million in the same period in 2020. SG&A expenses for the full year of 2021 were $7.5 million, compared to $6.7 million in 2020. The net increase during the year to date was primarily due to termination of our former Chief Executive Officer, coupled with increased consulting services related to European distribution of Tc99m tilmanocept, director compensation related to additional board members and increased board compensation rates, insurance costs, losses on the abandonment of certain intellectual property, recruiting fees, travel and general office expenses, offset by decreases in legal and professional services, employee compensation, investor relations costs, European annual registration fees, facilities costs and franchise taxes.
Navidea’s net loss attributable to common stockholders for the fourth quarter of 2021 was $3.7 million, or $0.12 per share, compared to $3.0 million, or $0.11 per share, for the same period in 2020. Navidea’s net loss attributable to common stockholders for the full year of 2021 was $11.7 million, or $0.40 per share, compared to $11.4 million, or $0.48 per share, in 2020.
Navidea ended the fourth quarter of 2021 with $4.2 million in cash and cash equivalents.
Conference Call Details

Investors and the public are invited to dial into the earnings call through the information listed below, or participate via the audio webcast on the company website. Dr. Michael Rosol, Chief Medical Officer, and Erika Eves, Vice President of Finance and Administration, will host the call and webcast to discuss the financial results and provide an update on recent developments and clinical progress. Management will be available to answer questions live immediately following the earnings announcement and prepared remarks portion of the call.

To participate in the call and webcast, please refer to the information below:

A live audio webcast of the conference call will also be available on the investor relations page of Navidea’s corporate website at www.navidea.com. In addition, the recorded conference call can be replayed and will be available for 90 days following the call on Navidea’s website.