Cracking the CRISPR Code

Techonology Networks | January 07, 2019

Scientists at the Francis Crick Institute have discovered a set of simple rules that determine the precision of CRISPR/Cas9 genome editing in human cells. These rules, published in Molecular Cell, could help to improve the efficiency and safety of genome editing in both the lab and the clinic. Despite the wide use of the CRISPR system, rational application of the technology has been hindered by the assumption that the outcome of genome editing is unpredictable, resulting in random deletions or insertions of DNA regions at the target site. Before CRISPR can be safely applied in the clinic, scientists need to make sure that they can reliably predict precisely how DNA will be modified.
"Until now, editing genes with CRISPR has involved a lot of guesswork, frustration and trial and error," says Crick group leader Paola Scaffidi, who led the study. "The effects of CRISPR were thought to be unpredictable and seemingly random, but by analyzing hundreds of edits we were shocked to find that there are actually simple, predictable patterns behind it all. This will fundamentally change the way we use CRISPR, allowing us to study gene function with greater precision and significantly accelerating our science."

Spotlight

Standard oncology tumor models are implanted subcutaneously. However, there are growing concerns around subcutaneous models and their predictive value due to the lack of an organ-specific tumor microenvironment (TME). This is particularly important for I/O studies, as immunotherapy response is heavily dependent on the TME.

Spotlight

Standard oncology tumor models are implanted subcutaneously. However, there are growing concerns around subcutaneous models and their predictive value due to the lack of an organ-specific tumor microenvironment (TME). This is particularly important for I/O studies, as immunotherapy response is heavily dependent on the TME.

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INDUSTRIAL IMPACT

XtalPi and CK Life Sciences to collaborate in AI-empowered tumour vaccine research and development, opening a new paradigm for scientific innovation

XtalPi Inc. | November 25, 2022

XtalPi announced today that they are embarking on a strategic collaboration with CK Life Sciences, a member of the CK Hutchison Group. XtalPi and CK Life Sciences will leverage their respective expertise to jointly develop a novel AI tumour vaccine R&D platform to improve the discovery and design capabilities of tumour vaccines and accelerate the development of more vaccine types. The goal of this collaboration is to realize precision treatment for patients worldwide. According to public information, there were nearly 20 million newly diagnosed cancer patients worldwide in 2021, of which about 4.5 million cases came from China. Many cancer types lead to detrimental outcomes, with high morbidity and mortality, and there remains a large unmet clinical need. Tumour vaccines targeting different tumour neoantigens, tumour-associated antigens and tumour-specific antigens in patients can be designed for use as immunotherapy, to activate the patient's own specific immune responses. Currently, there are only two therapeutic tumour vaccines— sipuleucel-T for melanoma and Bacillus Calmette-Guérin for bladder cancer, as well as preventive tumour vaccines against human papillomavirus infection and hepatitis B infection approved by the U.S. Food and Drug Administration. Recently, several other tumour vaccines have entered clinical development and evidence of efficacy has begun to emerge. According to Mordor Intelligence, the global cancer vaccine market size was US$6.79 billion in 2021 and will increase at a compound annual growth rate of 11.53% from 2022 to 2026. The expected market size by 2026 will be approximately US$12 billion. Currently, the design and preclinical development process for tumour vaccines is complex and lengthy, hindering the efficiency and success rate of tumour vaccine research and development. Incorporating XtalPi's industry expertise in AI computation and robotic automation, this collaboration aims to build an AI tumour vaccine R&D platform that applies advanced AI algorithms and high-precision molecular modeling to predict and design a variety of tumour vaccines that can activate specific immune responses to kill tumours. The tumour vaccines will be screened and verified through automated experiments, and through integrating algorithmic feedback to optimise activity and efficacy, the platform is expected to generate preclinical tumour vaccine candidate compounds with robust immune activity. "As a company headquartered in the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone, XtalPi is committed to realising the synergies between Shenzhen and Hong Kong by creating a new paradigm for innovation in the Greater Bay Area. Empowered by the latest technological advancements in automation, artificial intelligence is accelerating more innovative and diverse areas in drug research and development. Together with CK Life Sciences, we are committed to overcome conventional limitations and discover diverse applications for cutting-edge technologies. We believe the AI cancer vaccine platform jointly developed by CK Life Sciences and XtalPi will inspire the global scientific community to progress vaccine research and development and fast-track key development milestones for cancer vaccines. We are confident that this collaboration will significantly facilitate the scientific research exchange in the Greater Bay Area." Dr. Shuhao Wen, co-founder and chairman of XtalPi Dr. Melvin Toh, Vice President and Chief Scientific Officer of CK Life Sciences, comments: "The R&D of tumour vaccines is one of the key development directions of CK Life Sciences. The cooperation with XtalPi will apply XtalPi's AI algorithm, molecular modeling and automated experiments to speed up the R&D process, improve the success rate, and increase the efficacy of tumour vaccines." About XtalPi Founded in 2014, XtalPi founders recognized a common hurdle in drug development having to do with solid polymorphism, which could be successfully tackled with quantum physics predictions. Since then, XtalPi has maintained its focus on identifying and then attacking traditional bottlenecks in biopharmaceutical R&D through innovative technologies. Through considerable capital investments in automation and personnel, XtalPi now has four locations worldwide and employs approximately 1000 employees. XtalPi has engaged in collaboration research with nearly all top-20 pharmaceutical companies in the world. Its ID4 platform combines physics-based simulations with experimental validation and refinement, automation for rapid synthesis, and machine learning to continuously improve prediction accuracy and process efficiency. About CK Life Sciences CK Life Sciences is listed on the Stock Exchange of Hong Kong. Bearing the mission of improving the quality of life, CK Life Sciences is engaged in the business of research and development, manufacturing, commercialisation, marketing, sale of, and investment in, products and assets which fall into three core categories - nutraceuticals, pharmaceuticals and agriculture-related. CK Life Sciences is a member of the CK Hutchison Group.

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CELL AND GENE THERAPY

Casma Therapeutics Raises $46.0 M in Series C Funding

Casma Therapeutics, Inc. | November 21, 2022

Casma Therapeutics, Inc., a biotechnology company engaging the autophagy system to provide innovative new medicines, announced the closing of a Series C financing round of $46.0 million. New investors participating in the round include Amgen Ventures, LLC, Astellas Venture Management, Eisai Co., Ltd., Euclidean Capital, Mirae Asset, and Ono Venture Investment. Current investors Eventide Asset Management, LLC, Schroders Capital, The Column Group, Third Rock Ventures, and other funds also participated in the financing. Dr. Hiromichi Kimura, Investment Director of Astellas Ventures, has joined the board of directors. Dr. Tomotaka Okino of Ono Venture Investment and Amgen Ventures have joined as board observers. Casma will use proceeds to advance its lead program for MYD88 mutant lymphoma through preclinical and into IND enabling studies. “The closing of this financing has strengthened our resources to continue advancing our drug pipeline focused on autophagy-based degradation. We are thrilled to welcome several top-tier investors who recognize the potential of our biological platforms and therapeutic assets targeting well-known high-value and traditionally undruggable targets.” Keith Dionne, Ph.D., Chief Executive Officer of Casma Therapeutics, Inc "Casma’s autophagy-based degradation platform, PHLYT™, is unique and impressive,” commented Dr. Kimura. “Along with a rich pipeline of autophagy degraders, the company has also established a highly qualified team with extensive scientific experience in drug development. We expect that this round of funding will accelerate development of Casma’s pipeline assets, especially its degrader for MYD88 mutant tumors.” About Casma Therapeutics, Inc. Casma Therapeutics, Inc. is developing novel cellular degradation approaches based on the autophagy pathway to open new target areas for drug discovery and development that will profoundly impact the lives of patients. Autophagy is a conserved cellular process that contributes to overall cellular homeostasis. The autophagy machinery targets large and complex disease targets such as organelles, protein aggregates and large signaling complexes and before directing them to the lysosome for elimination. By selectively degrading disease targets by autophagy, Casma expects to arrest or reverse the progression of disease in multiple oncology, inflammation, neurodegeneration, and metabolic disorders.

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CELL AND GENE THERAPY

Adicet Bio Reports Inducement Grants under Nasdaq Listing Rule 5635(c)(4)

Adicet Bio, Inc. | September 06, 2022

Adicet Bio, Inc. a clinical-stage biotechnology company discovering and developing allogeneic gamma delta CAR T cell therapies for cancer, today announced it granted inducement awards on August 31, 2022 under Adicet’s 2022 Inducement Plan as a material inducement to employment to five individuals hired by Adicet in August 2022. The employees received, in the aggregate, non-qualified stock options to purchase 114,200 shares of Adicet’s common stock with an exercise price of $14.16 per share, the closing price of Adicet’s common stock as reported by Nasdaq on August 31, 2022. One-fourth of the shares underlying each employee’s option will vest on the one-year anniversary of each recipient’s start date and thereafter the remaining three-fourths of the shares underlying each employee’s option will vest in thirty-six substantially equal monthly installments, such that the shares underlying the option granted to each employee will be fully vested on the fourth anniversary of the recipient’s start date, in each case, subject to each such employee’s continued employment with Adicet on such vesting dates. All of the above-described awards were granted outside of Adicet’s stockholder-approved equity incentive plans pursuant to Adicet’s 2022 Inducement Plan, which was adopted by the board of directors in January 2022. The awards were authorized by the compensation committee of the board of directors, which is comprised solely of independent directors, as a material inducement to the employees entering into employment with Adicet in accordance with Nasdaq Listing Rule 5635(c)(4). About Adicet Bio, Inc. Adicet Bio, Inc. is a clinical-stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer. Adicet is advancing a pipeline of “off-the-shelf” gamma delta T cells, engineered with chimeric antigen receptors and T cell receptor-like antibodies to enhance selective tumor targeting, facilitate innate and adaptive anti-tumor immune response, and improve persistence for durable activity in patients.

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