On February 1, 2022 Twist Bioscience Corporation (NASDAQ:TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, and Abcam (AIM:ABC; NASDAQ:ABCM), a global innovator in life sciences reagents and tools, reported a licensing agreement under which Abcam will use a proprietary Twist VHH phage library for antibody discovery, development and commercialization for diagnostic and research applications (Press release, Abcam, FEB 1, 2022, View Source [SID1234607583]).

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Phage display complements other antibody discovery methods, and offers several benefits for tackling challenging targets. The synthetic nature and the diversity of each Twist library (up to 10 billion variants) enable the rapid identification of antibodies against challenging targets that would otherwise fail due to toxicity or lack of immunogenicity. The recombinant format enables easier genetic engineering and maximizes in vitro manufacturing ensuring batch-to-batch reproducibility and scalability from bench to bedside.

Alejandra Solache, Ph.D., SVP R&D at Abcam said, "Twist’s phage library complements our leading recombinant antibody discovery capabilities, adding further scale and diversity and increasing the likelihood of identifying antibodies with the desired properties against emerging or established targets. The partnership supports Abcam and Twist’s commitment to deliver antibodies that have the potential to accelerate the development of innovative research tools, diagnostics and therapeutics."

Under the terms of the agreement, Twist Bioscience grants Abcam the right to engage in research and development activities using Twist single domain (VHH) synthetic antibody library. Abcam has the option to nominate, license and commercialize antibody sequences for diagnostic and research use, in return for license fees and commercial milestone payments. Twist retains the rights to the same sequences for therapeutic application.

Emily M. Leproust, Ph.D., CEO and co-founder of Twist said, "This partnership is an important milestone in Twist’s journey as it allows us to access the research and diagnostic market through Abcam’s commitment to advance discovery, development and commercialization of the resulting antibodies. In addition, this agreement lays the foundations for a long term collaboration with Abcam to drive new commercial opportunities. Importantly, because Twist retains the rights to develop the sequences for therapeutic uses, this partnership has the potential to benefit our internal pipeline as well."

VHH Antibody Libraries

Antibodies contain two variable domains, the heavy and the light chains. A VHH antibody, also known as a nanobody or single domain antibody, is the antigen binding domain of the heavy chain, with three complementary determining regions (CDRs), or areas where antigens bind to the antibody. Twist’s VHH library uses novel methods that combine synthetic and natural approaches to maximize diversity in the 10 billion antibody library, creating high quality VHH libraries for use against any protein target. The small size of the VHH antibodies allow them to access targets that traditional antibodies cannot, with tight binding affinity. The modular nature of VHH antibodies supports creation of bi- or multi-specific antibodies ideal for developing next generation therapies specific to oncology, autoimmune disease and virology.

On February 1, 2022 Targovax ASA (OSE: TRVX), a clinical-stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that it has entered into a two-year research collaboration with Prof. Michael Uhlin of the Department of Clinical Science, Intervention and Technology at Karolinska Institutet in Stockholm, Sweden, to develop and characterize novel ONCOS oncolytic viruses (Press release, Targovax, FEB 1, 2022, View Source [SID1234607550]).

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Dr. Uhlin is a professor of clinical immunology at Karolinska Institutet specializing in onco-immunology, transplantation and lymphocyte biology. Under the collaboration agreement with Targovax, Prof. Uhlin will establish and coordinate a research team dedicated to pre-clinical in vitro and in vivo evaluation of novel ONCOS oncolytic adenoviruses, including circular RNA delivery vectors. The research collaboration has an initial term of two years, which may be extended if successful.

Dr. Victor Levitsky, Chief Scientific Officer of Targovax, said: "Prof. Uhlin is a highly accomplished scientist with deep experience in translational and clinical immunology. His expertise and research capabilities will play a critical role as we build our portfolio of next generation ONCOS constructs over the coming years. To achieve our ambitious goals of expanding into novel immunotherapy mechanisms, such as circular RNA delivery, access to high-caliber scientists with the relevant skill-set and state-of-the-art infrastructure will be essential. This is precisely what we get through this collaboration with the Karolinska Institute."

Prof. Michael Uhlin, Group Leader at the Department of Clinical Science, Intervention and Technology at Karolinska Institutet, added: "The team at Targovax has generated a compelling set of clinical data for their lead candidate ONCOS-102, which they are now applying to enhance their platform with next generation armed viral immunotherapies. I find it highly scientifically interesting to support Targovax in understanding the biology and immunological activity of this innovative class of oncolytic delivery vectors. It will be exciting to participate in the characterization and optimization of novel ONCOS candidates as potential future treatment options for patients with challenging solid tumors".

On February 1, 2022 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is biologically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics for the treatment of cancer and autoimmune diseases, reported that the executive management team will present and host meetings with investors at the virtual Guggenheim Healthcare Talks and SVB Leerink Global Healthcare Conference in February (Press release, Rubius Therapeutics, FEB 1, 2022, View Source [SID1234607568]).

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Pablo J. Cagnoni, M.D., president and chief executive officer, will provide a corporate update through fireside chats at Guggenheim Healthcare Talks | Idea Forum | Oncology Day on February 10, 2022, 08:00 a.m. EST and at the 11th Annual SVB Leerink Global Healthcare Conference on February 18, 2022, 1:00 p.m. EST. Live audio webcasts for these events will be available within the Investors & Media section of the Rubius Therapeutics website. Archived replays will be accessible for 90 days following the events.

On February 1, 2022 SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported the publication of comprehensive preclinical research on the company’s ability to engineer multiple immune cell types to drive MHC-I antigen presentation, a critical advance in the ability to drive a patient’s killer T cells to fight multiple diseases (Press release, SQZ Biotech, FEB 1, 2022, View Source [SID1234607584]). The cell engineering findings, published online and in the February 15th edition of the Journal of Immunology, are part of the body of work supporting the development of SQZ Antigen Presenting Cell (APC) and SQZ Enhanced Antigen Presenting Cell (eAPC) cancer vaccine therapeutic programs currently in clinical development.

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The journal publication follows the December 2021 oral presentation at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) congress reporting that the company’s lead APC therapeutic candidate induced a radiographic, symptomatic, histologic response as a monotherapy in a late line head and neck cancer patient.

"We are excited to publish the comprehensive dataset that has long underpinned our conviction in the SQZ APC platform’s potential for patient impact," said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. "These data demonstrate the ability of microfluidic squeezing to engineer antigen presentation in T cells, B cells, NK cells, and monocytes, thereby empowering these immune cells to activate endogenous CD8 killer T cells – a powerful and highly specific arm of the immune system. Our early clinical trial data presented at ESMO (Free ESMO Whitepaper)-IO demonstrated our multi-cell engineering mechanism at work, and we are excited about the potential to implement this approach across multiple tumor types."

CD8, or Killer, T cells play a critical role in combating diseases, however, a major bottleneck for CD8 T cell activation is displaying the desired disease associated antigen(s) to these T cells through the MHC-I pathway. In this journal article, SQZ scientists and their collaborators describe how they overcome this fundamental biological problem through the delivery of antigens directly into the cytosol of immune cells by microfluidic squeezing.

"What’s exciting about our platform is the ability to efficiently insert many types of antigen cargo directly into a cell’s cytosol for presentation to killer T cells, and the ability to engineer other immune system cells to target disease," said Howard Bernstein, M.D., Ph.D., chief scientific officer at SQZ Biotechnologies. "Our enhanced APCs, which recently received FDA IND clearance to commence a clinical trial, represent a further advancement of the concept by delivering five different mRNAs into a patient’s monocytes, B cells, T cells, and NK cells in a single step. We are exploring an exciting frontier in cell therapy and look forward to assessing its potential for patient impact in our clinical trials."

Major Journal Study Findings

Enabling Cancer Vaccine Development

In this study, the authors demonstrate preclinically that cytosolic delivery of antigens through microfluidic squeezing enables direct MHC-I antigen presentation to CD8 T cells by diverse immune system cell types, overcoming a major challenge in the development of cancer vaccine therapeutics
Study authors also showed they could expand beyond the more commonly used dendritic cells to induce T cell activation. MHC-I presentation was demonstrated in engineered T cells, B cells, Natural Killer cells, and monocytes – broadening their potential use and impact in therapeutic design
Tumor Protection and Immunization

In vivo study findings showed that engineered B cells, T cells, or mixed peripheral blood mononuclear cells (PBMCs), were all capable of activating endogenous immune responses across multiple antigens
These immune responses were able to protect mice in prophylactic studies, drive tumor regression in therapeutic studies, and form long-term memory that protects against future tumor challenge
Authors further found that this protection correlates with tumor infiltration of antigen-specific cells with nearly 90 percent of infiltrating CD8 T cells being specific for the tumor antigen delivered using the Cell Squeeze technology
Efficient, Scaled Manufacturing

Study authors compared the viability and delivery of engineered cells using research-scale and manufacturing-scale Cell Squeeze chips. They found that delivery of different cells types within PBMCs was similar across research-scale and manufacturing-scale chips, and study authors demonstrated successful increase from millions to billions of cells processed using manufacturing-scale chips

On February 1, 2022 Tollys Presented the Corporate Presentation (Presentation, Tollys, FEB 1, 2022, View Source [SID1234607551])

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