On December 15, 2021 BeyondSpring Pharmaceuticals (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported new data highlighting the mechanism of action of plinabulin in the prevention of chemotherapy-induced neutropenia (CIN) at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held virtually and in person in Atlanta, Georgia from December 11-14, 2021 (Press release, BeyondSpring Pharmaceuticals, DEC 15, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-pharmaceuticals-announces-new-clinical-data-confirming-plinabulins-fast-onset-mechanism-of-action-in-the-prevention-of-chemotherapy-induced-neutropenia-at-the-63rd-ash-annual-mee [SID1234597188]). The data demonstrate that adding plinabulin to a myelosuppressive regimen rapidly reversed (within 24 hours) neutropenia and leukopenia in the PROTECTIVE-1 and -2 clinical studies by protecting progenitor stem cells in the bone marrow.

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"This clinical data provides evidence confirming the hypothesized progenitor stem cell protective mechanism of action for plinabulin, which further validates the positive Phase 3 data from the PROTECTIVE-2 clinical program. These data also build upon the rapid effect seen in clinical trials to date and support the opportunity for enhanced CIN prevention care with plinabulin," said Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies. "These data provide a strong rationale for combining plinabulin with pegfilgrastim, since the latter has a mechanism of action exerting CIN prevention in week 2 of the chemotherapy cycle while plinabulin shows a week 1 benefit. This early CIN benefit is critically important because these white blood cells are the body’s main source of defense against infection. If a cancer patient gets an infection due to CIN, it may affect their ability to finish chemotherapy for cancer treatment."

Dr. Ramon Mohanlal, executive vice president of research and development and chief medical officer at BeyondSpring Pharmaceuticals, added, "This presentation at ASH (Free ASH Whitepaper) provides mechanistic support for the observed benefit of plinabulin in the prevention of CIN, a condition that still has unmet medical need, despite the availability of the standard of care CIN prevention drug, G-CSF. In addition, the rapid onset of action is critical since week 1 of each chemotherapy cycle is when more than 75% of CIN cases occur, even with G-CSF. Investigating the nuances of how and when plinabulin works is a continuous part of our work in understanding this multifaceted therapy. We look forward to sharing more of these insights with the oncology community in future studies."

This poster was presented on Sunday, December 12, 2021 and is available on the ASH (Free ASH Whitepaper) website.

Poster Title: Plinabulin Rapidly (within 24 Hours) Reverses Myelosuppression Induced by Chemotherapy
Abstract Number: 2056
Key Findings:

This new data analysis from the PROTECTIVE-1 and 2 studies aimed to further evaluate plinabulin’s fast onset mechanism of action (MoA) and potential progenitor stem cell involvement in plinabulin’s fast onset MoA.
The comparison was made between cancer patients receiving plinabulin 40 mg (n=228) or not receiving plinabulin (n=172), and with all patients receiving myelosuppressive chemotherapy (docetaxel with or without doxorubicin and cyclophosphamide). Plinabulin 40 mg was given 30 minutes after chemotherapy.
Plinabulin rapidly (within 24 hours) reversed chemo-induced myelosuppression in both the PROTECTIVE-1 and 2 human studies. Plinabulin-mediated increases in cell numbers are dose-dependent and correlated among cells of the myeloid, lymphoid and erythroid lineages.
Neutrophils (p<0.0001; increase by >3x10E9/L with plinabulin and decrease by >0.5x10E9/L without plinabulin)
Monocytes (p=0.0023)
Eosinophils (p=0.0775)
Basophils (p<0.0001)
The data suggest that plinabulin targets granulocyte-monocyte-progenitor (GMP) stem cells (N, M, B and E progenitor) as well as progenitor cells further upstream in the hematopoietic lineage.
About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation from both U.S. and China FDA for the CIN prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.

On December 15, 2021 Alligator Bioscience AB ("Alligator") and Aptevo Therapeutics ("Aptevo") (NASDAQ: APVO) reported publication of an article in the December 15, 2021, issue of the peer-reviewed journal, Nature Communications on the mechanism of action of CD137 (4-1BB) targeting bispecific antibodies (Press release, Alligator Bioscience, DEC 15, 2021, View Source [SID1234597187]). Nature Communications is an open access, multidisciplinary journal dedicated to publishing high-quality research in all areas of the biological, health, physical, chemical and Earth sciences.

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The article titled, CD137 (4-1BB) co-stimulation of CD8 T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation, details the mechanism of action of 4-1BB targeting bispecific antibodies. This work was published in collaboration by internationally renowned 4-1BB expert, Professor Ignacio Melero, and his team at the University of Navarra, Pamplona, Spain. Professor Melero’s data supports the bispecific antibodies, such as ALG.APV-527, targeting 4-1BB, and link 4-1BB signaling in cis (directly to tumor targets, such as 5T4), are more efficient at stimulating the anti-tumor response than bispecific agents that link 4-1BB signaling in trans to adjacent non-tumor cell targets such as the stroma.

"This study unveils an important mechanism for tumor-cell targeting therapies for cancer. Bispecific antibodies targeting 4-1BB offer a synthetic biology that can be very useful in cancer immunotherapy. In this study, we found a spatial requirement in regard to antigen recognition and 4-1BB co-stimulation. This means that the T cells can detect the antigen on the same cell that is providing natural or artificial 4-1BB co-stimulation. This type of co-stimulation, and the ensuing immune system activation and survival, is far more potent. The bispecific antibody from Alligator Bioscience and Aptevo Therapeutics, ALG.APV-527, is a tool that shows this potent 4-1BB co-stimulation in the tumor microenvironment and has the potential to provide a superior therapy to treat cancers," stated Ignacio Melero, MD, PhD, Cima and Clínica Universidad de Navarra, Spain.

"We are very pleased to have been selected for publication in a high-ranking peer-reviewed journal such as Nature Communications. This is very encouraging and validates the superior mechanism and design of ALG.APV-527. The data further highlights the strong positioning of ALG.APV-527 in the bispecific 4-1BB antibody field," said Søren Bregenholt, CEO at Alligator.

"The publication of Professor Melero’s findings further support the potential of ALG.APV-527 overall, to evoke an effective tumor-targeting immune response with fewer adverse events. This work highlights the potential differentiating benefit of ALG.APV-527 to induce stronger and more tumor-directed T cell responses with the potential for improved safety and efficacy in patients and represents a significant contribution from the scientific teams at Aptevo and Alligator. We are proud of their achievements and know their work will continue producing invaluable data going forward," commented Marvin White, CEO of Aptevo.

The complete article is available in print and in digital format which can be viewed via the following link: (link to article).

About ALG.APV-527

ALG.APV-527 is a 4-1BB and tumor-binding immunomodulatory antibody. 4- 1BB has the ability to stimulate the immune cells (anti-tumor specific T cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. The tumor-binding part of ALG.APV-527 targets the 5T4 tumor-associated antigen. 5T4 is a protein expressed in multiple tumor types, as well as certain types of aggressive tumor cells (tumor-initiating cells), but at low levels or not at all in normal tissue, making 5T4 a compelling target molecule for cancer therapy.

Alligator and Aptevo are advancing ALG.APV-527 into Phase I clinical development. The companies will continue to explore licensing opportunities as ALG.APV-527 moves into clinical development.

On December 15, 2021 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported the appointment of Sara Kenkare-Mitra, Ph.D., as President and Head of Research and Development (Press release, Alector, DEC 15, 2021, View Source [SID1234597186]). In this newly created role, Dr. Kenkare-Mitra will lead all aspects of the company’s immuno-neurology and oncology R&D efforts, including oversight of the research, development, clinical, manufacturing, regulatory, and related functions. Dr. Kenkare-Mitra will report to Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector.

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Dr. Kenkare-Mitra joins Alector from Genentech where, as Senior Vice President, Development Sciences, she served as a member of the research and development leadership team, overseeing the transition of molecules from discovery to the clinic and their continued translation into medicines through clinical development. During her 23-year tenure, she led a large, integrated global organization of approximately 650 employees, and played a key role in the filing of more than 100 Investigational New Drug/clinical trial applications around the world, and the approval of 15 medicines for diverse diseases, including cancers and neurological diseases.

"Sara has an impressive background as a scientist, drug developer and leader, with a successful track record of building high-performing teams and fostering innovation in the development of new medicines," said Dr. Rosenthal. "As we continue to advance and grow our immuno-neurology and oncology programs, her expertise across all aspects of drug development and her passion for translational medicine will be invaluable to our team. I’m pleased to welcome Sara, and I look forward to partnering with her."

"Alector’s approach to harnessing the body’s innate immune system has the potential to transform the treatment of neurological diseases and certain cancers. With a combination of pioneering science and an exceptional team, we have a significant opportunity to play an important role in developing innovative treatments for patients in need," said Dr. Kenkare-Mitra. "I’m excited to join Alector and work closely with the team to fully realize the potential of the company’s deep portfolio."

Prior to joining Alector, Dr. Kenkare-Mitra held roles of increasing responsibility at Genentech over the course of 23 years. She most recently served as Senior Vice President, Development Sciences in Genentech’s research and early development unit. During her tenure, she served as a member of Genentech’s research review committee, development review committee and early-stage portfolio committee, as well as an ad-hoc member of the late-stage review committee. Dr. Kenkare-Mitra received her Ph.D. in Pharmaceutical Chemistry from the University of California, San Francisco, where she also stayed on as a Post-Doctoral Fellow in Clinical Pharmacology before joining Genentech. Dr. Kenkare-Mitra also holds adjunct faculty positions in the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco and at the University of the Pacific in Stockton. Dr. Kenkare-Mitra is an elected member of the National Academy of Medicine (NAM) and the American Association for the Advancement of Science (AAAS). She has been widely recognized for her work in the industry with awards such as the American Association of Pharmaceutical Scientists’ Alice E. Till Advancement of Women in Pharmaceutical Sciences Recognition, Endpoints’ 20 Most Extraordinary Women in Biopharma, Fierce Pharma’s Fiercest Women in the Life Sciences, and the University of California, San Francisco’s Distinguished Alumnus of the Year.

On December 15, 2021 Akoya Biosciences, Inc., (Nasdaq: AKYA), The Spatial Biology Company, reported its next-generation of innovations to enable unbiased spatial phenotyping at unprecedented speeds, setting a new standard in spatial biology (Press release, Akoya Biosciences, DEC 15, 2021, View Source [SID1234597185]). The comprehensive roadmap includes additions to the instrument portfolio and novel chemistries that, collectively, make it the most integrated suite of solutions spanning discovery, translational and clinical research.

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As part of the instrument portfolio expansion, the company announced the imminent launch of the PhenoCycler-Fusion System, a transformational platform that allows researchers to map a million cells in as little as 10 minutes. The new system combines the strengths of the company’s best-in-class ultrahigh multiplex cycling technology, CODEX, and the industry-leading high-speed imaging capabilities of its Vectra Polaris system, into an integrated platform that is positioned to revolutionize spatial discovery and translational research. This fusion of the company’s foundational technological capabilities delivers ultrahigh multiplexed imaging at single-cell and subcellular resolution across entire slides, more than ten times faster than traditional methods.

To underscore the powerful future of this integrated spatial phenotyping portfolio, Akoya is rebranding its existing products. Effective January 2022, CODEX will become PhenoCycler, the Phenoptics workflow will be renamed as the PhenoImager workflow, and the Vectra Polaris instrument will become the PhenoImager HT instrument.

In addition to enabling unbiased spatial discovery through rapid whole-slide imaging, the PhenoCycler-Fusion has a tunable workflow that allows researchers to run large panels in discovery mode and focused panels in high throughput mode. This unique capability accelerates the translation of spatial biomarker signatures onto the PhenoImager HT instrument for clinical research applications.

With the PhenoCycler-Fusion at the core of its strategic roadmap, Akoya also previewed upcoming innovations in its reagent chemistry. For the first time, the company will enable spatial transcriptomics capabilities on its platforms, leveraging a novel RNA chemistry. Incorporating both proteomic and transcriptomic analysis capabilities from the same tissue sample makes PhenoCycler-Fusion the only practical solution for complete multiomic assessment of cellular phenotypes, with whole-slide spatial context.

In addition, Akoya also previewed a novel protein chemistry that supports the development of universal barcoded antibodies to run on both its PhenoCycler-Fusion and PhenoImager instruments, enabling researchers to optimize the same spatial phenotyping assay from discovery, all the way to clinical research.

"Our comprehensive roadmap for unbiased, multiomic spatial phenotyping will enable our customers to further accelerate their use of our platforms, enabling more rapid discovery and validation of predictive biomarkers," said Brian McKelligon, Chief Executive Officer of Akoya Biosciences. "We’re excited to see how the scientific community will apply these innovations in advancing our understanding of biology and human health."

The PhenoCycler-Fusion System will be shipped in limited quantities to selected sites in December 2021, with a full commercial launch set for January 2022. More details on the universal RNA and protein chemistries will be revealed throughout 2022. To stay up-to-date on the launch, sign up at akoyabio.com/fusion.

A recording of Akoya’s Spatial Day Event can be accessed at akoyabio.com/spatialday.

On December 15, 2021 Bionaut Labs, a company focused on revolutionizing the treatment of central nervous system disorders (CNS) with its Bionaut precision medicine treatment modality, and Candel Therapeutics, Inc. (Nasdaq: CADL), a late clinical-stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported a strategic collaboration to investigate the use of Bionaut’s remote-controlled microscale robots for precision delivery of Candel’s oncolytic viral immunotherapy agents to specific brain tumors (Press release, Bionaut Labs, DEC 15, 2021, View Source [SID1234597181]).

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Bionaut Labs will apply its micro-robotic technology under the guidance of an integrated electro-magnetic control system to deliver Candel’s oncolytic viruses directly to brain tumors in a minimally invasive manner. The parties will jointly research the use of the Bionaut platform in the preclinical setting with an aim of advancing to clinical trials. The agreement enables both parties to retain unencumbered rights to their respective platforms, as well as rights for future clinical development together.

"With the goal of maximizing the benefit to patients, Candel continues to evaluate expansion of our clinically validated oncolytic viral immunotherapy approach into additional subsets of patients with high-grade glioma using novel methods, such as the Bionaut platform, to deliver our investigational medicines," said Paul Peter Tak, MD, PhD, FMedSci, President and CEO of Candel Therapeutics. "We look forward to this collaboration with Bionaut Labs in the hope that it will ultimately lead to better outcomes for patients living with brain cancer."

"Bionaut Labs is excited to partner with Candel, a leader in developing oncolytic viruses for multiple cancers, to advance much-needed treatment options for brain cancer patients leveraging our transformative Bionaut platform technology," said Michael Shpigelmacher, co-founder and CEO, Bionaut Labs. "The research we plan to jointly undertake validates our approach and will enable advancement of our technology as we continue our mission of helping patients suffering from debilitating brain diseases who lack effective treatments. We look forward to working with Candel, as this collaboration has the potential to re-envision the standard of care for high-grade gliomas and make a meaningful difference in patients’ lives."

Terms of the agreement were not disclosed.

About Bionaut Treatment
A Bionaut is a novel treatment modality that uses remote-controlled microscale robots to deliver biologics, nucleic acids, small molecule, gene or cellular therapies locally to targeted CNS disease areas. Through precise targeting, Bionaut therapeutics could offer better efficacy and safety that cannot be achieved by other traditional treatment or delivery modalities.

Bionauts can be constructed in different designs with custom geometries and surface characteristics. Smaller than a millimeter, they contain moving parts controlled remotely by a magnetic controller, allowing them to safely reach the target and release a therapeutic payload from the cargo compartment. Engineering flexibility provides a broad foundation for designing Bionaut therapies for nearly any disease of interest.

Bionaut Labs has demonstrated safe and controlled navigation of its therapeutic Bionaut to and from the treatment locus in the brain, in a large animal in vivo model. Furthermore, the Company has successfully treated human glioma tumors established in mice, utilizing guided delivery of therapeutic cargos directly into these tumors to eliminate systemic toxicity. These results pave the way to the clinical trials of the Bionaut platform.