Monthly Archives: October 2022

Stanford University researchers have discovered a rapid and sustainable way to synthetically produce a promising cancer-fighting compound right in the lab. The compounds availability has been limited because its only currently known natural source is a single plant species that grows solely in a small rainforest region of Northeastern Australia.

PhD students Edward Njoo, David Fanelli, Zach Gentry, and Owen McAteer. These researchers achieved the synthesis of the cancer-fighting compound EBC-46. (Image credit: Paul Wender)

The compound, designated EBC-46 and technically called tigilanol tiglate, works by promoting a localized immune response against tumors. The response breaks apart the tumors blood vessels and ultimately kills its cancerous cells. EBC-46 recently entered into human clinical trials following its extremely high success rate in treating a kind of cancer in dogs.

Given its complex structure, however, EBC-46 had appeared synthetically inaccessible, meaning no plausible path seemed to exist for producing it practically in a laboratory. However, thanks to a clever process, the Stanford researchers demonstrated for the first time how to chemically transform an abundant, plant-based starting material into EBC-46.

As a bonus, this process can produce EBC-46 analogs compounds that are chemically similar, but which could prove even more effective and potentially treat a surprisingly wide range of other serious maladies. These diseases, which include AIDS, multiple sclerosis, and Alzheimers disease, all share biological pathways impacted by EBC-46s target, a key enzyme called protein kinase C, or PKC.

We are very excited to report the first scalable synthesis of EBC-46, said Paul Wender, the Francis W. Bergstrom Professor in the School of Humanities and Sciences, professor of chemistry and, by courtesy, of chemical and systems biology at Stanford, and corresponding author of a study describing the results in the journal Nature Chemistry. Being able to make EBC-46 in the lab really opens up tremendous research and clinical opportunities.

Co-authors of the study are Zachary Gentry, David Fanelli, Owen McAteer, and Edward Njoo, all of whom are PhD students in Wenders lab, along with former member Quang Luu-Nguyen.

Wender conveyed the immense satisfaction the research team felt over the EBC-46 synthesis breakthrough. If you were to have visited the lab the first few weeks after they succeeded, said Wender, you wouldve seen my stellar colleagues smiling from ear to ear. They were able to do something many people had considered impossible.

Tigilanol tiglate initially turned up through an automated drug candidate screening process by QBiotics, an Australian company. In nature, the compound appears in the seeds of the pink fruit of the blushwood tree, Fontainea picrosperma. Marsupials such as musky rat-kangaroos that eat blushwood fruit avoid the tigilanol tiglate-rich seeds, which when ingested trigger vomiting and diarrhea.

Injecting far smaller doses of EBC-46 directly into some solid tumors modifies the cellular signaling by PKC. Specifically, EBC-46 is proposed to activate certain forms of PKC, which in turn influence the activity of various proteins in the cancerous cells, attracting an immune response by the hosts body. The resulting inflammation makes the tumors vasculature, or blood vessels, leaky, and this hemorrhaging causes the tumorous growth to die. In the case of external, cutaneous malignancies, the tumors scab up and fall off, and ways of delivering EBC-46 to internal tumors are being investigated.

In 2020, both the European Medicines Agency and the Food and Drug Administration in the United States approved an EBC-46based medication, sold under the brand name Stelfonta, to treat mast cell cancer, the most common skin tumors in dogs. A study showed a 75% cure rate after a single injection and an 88% rate following a second dose. Clinical trials have since commenced for skin, head and neck, and soft tissue cancers in humans.

Based on these emerging research and clinical needs coupled with the source seeds geographical limitations, scientists have considered setting up special plantations for blushwood trees. But doing so presents a host of issues. For starters, the trees require pollination, meaning the right sort of pollinating animals must be on hand, plus trees must be planted in appropriate densities and distances to aid pollination. Furthermore, seasonal and climate variations affect the trees, along with pathogens. Setting aside plots for blushwood trees further poses land use problems.

For sustainable, reliable production of EBC-46 in the quantities we need, Wender said, we really need to go the synthetic route.

A good starting point for making EBC-46, Wender and colleagues realized, is the plant-derived compound phorbol. More than 7,000 plant species produce phorbol derivatives worldwide and phorbol-rich seeds are commercially inexpensive. The researchers selected Croton tiglium, commonly known as purging croton, an herb used in traditional Chinese medicine.

The first step in preparing EBC-46, Wender explains, jibes with an everyday experience. You buy a sack of these seeds, and its not unlike making coffee in the morning, said Wender. You grind up the seeds and run some hot solvent through them to extract the active ingredient, in this case a phorbol-rich oil.

After processing the oil to yield phorbol, the researchers then had to figure out how to overcome the previously insurmountable challenge of bedecking a part of the molecule, called the B ring, with carefully placed oxygen atoms. This is required to enable EBC-46 to interact with PKC and modify the enzymes activity in cells.

To guide their chemical and biological studies, the researchers relied on instrumentation at the Stanford Neuroscience Microscopy Service, the Stanford Cancer Institute Proteomics/Mass Spectrometry Shared Resource, and the Stanford Sherlock cluster for computer modeling.

With this guidance, the team succeeded in adding extra oxygen atoms to phorbols B ring, first via a so-called ene (pronounced een) reaction conducted under flow conditions, where reactants mix as they run together through tubing. The team then introduced other B ring groups in a stepwise, controlled manner to obtain the desired spatial arrangements of the atoms. In total, only four to six steps were required to obtain analogs of EBC-46 and a dozen steps to reach EBC-46 itself.

Wender hopes that the far broader availability of EBC-46 and its PKC-influencing cousin compounds afforded by this breakthrough approach will accelerate research into potentially revolutionary new treatments.

As we learn more and more about how cells function, were learning more about how we can control that functionality, said Wender. That control of functionality is particularly important in dealing with cells that go rogue in diseases ranging from cancer to Alzheimers.

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Breakthrough in production of cancer-treating drug - Stanford University News

ZUG, Switzerland and BOSTON, Sept. 28, 2022 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX130, the Companys wholly-owned allogeneic CAR T cell therapy targeting CD70, for the treatment of Mycosis Fungoides and Szary Syndrome (MF/SS).

The RMAT designation is an important milestone for the CTX130 program that recognizes the transformative potential of our cell therapy in patients with T-cell lymphomas based upon encouraging clinical data to date, said Phuong Khanh (P.K.) Morrow, M.D., FACP, Chief Medical Officer of CRISPR Therapeutics. "We continue to work with a sense of urgency to bring our broad portfolio of allogeneic cell therapies to patients in need.

Established under the 21st Century Cures Act, RMAT designation is a dedicated program designed to expedite the drug development and review processes for promising pipeline products, including genetic therapies. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such disease or condition. Similar to Breakthrough Therapy designation, RMAT designation provides the benefits of intensive FDA guidance on efficient drug development, including the ability for early interactions with FDA to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the biologics license application (BLA) and other opportunities to expedite development and review.

About CTX130 and COBALT TrialsCTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting Cluster of Differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1 single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 in adult patients. The COBALT-LYM trial is evaluating the safety and efficacy of CTX130 for the treatment of relapsed or refractory T or B cell malignancies. The COBALT-RCC trial is evaluating the safety and efficacy of CTX130 for the treatment of relapsed or refractory renal cell carcinoma. CTX130 has received Orphan Drug and Regenerative Medicine Advanced Therapy designations from the FDA.

About CRISPR TherapeuticsCRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Forward-Looking StatementThis press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Dr. Morrow in this press release, as well as regarding CRISPR Therapeutics expectations about any or all of the following: (i) the status of clinical trials and discussions with regulatory authorities related to product candidates under development by CRISPR Therapeutics including, without limitation, expectations regarding the benefits of RMAT designation; and (ii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential for initial and preliminary data from any clinical trial and initial data from a limited number of patients not to be indicative of final trial results; the potential that clinical trial results may not be favorable; potential impacts due to the coronavirus pandemic, such as the timing and progress of clinical trials; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics product candidates; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, quarterly report on Form 10-Q and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

CRISPR THERAPEUTICS standard character mark and design logo, CTX130 and COBALT are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.

Investor Contact:Susan Kim+1-617-307-7503susan.kim@crisprtx.com

Media Contact:Rachel Eides+1-617-315-4493rachel.eides@crisprtx.com

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CRISPR Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX130 for the Treatment of Cutaneous T-Cell...

Mary Munson, PhD

Mary Munson, PhD, professor of biochemistry & molecular biotechnology and vice chair of diversity for the department, is one of 22 scientists named a fellow by the American Society for Cell Biology for 2022.

Election as a fellow is an honor bestowed upon society members by their peers. Fellows are recognized for their lifetime achievement in advancing cell biology, meritorious efforts to advance cell biology and its applications, and for their service to the society.

Dr. Munson will be among the new cohort of fellows to be formally recognized in Washington, D.C., in December at Cell Bio 2022, the joint meeting of the American Society for Cell Biology and the European Molecular Biology Organization.

I am honored to be recognized in this years cohort and to join such a distinguished group of cell biologists, said Munson.

An expert in the mechanistic basis for regulation of spatial and temporal membrane trafficking, Munson is interested in understanding how cargo arrives at the correct location at the right time throughout the cell and is either released to or internalized from the extracellular space. The Munson Lab aims to answer questions about membrane trafficking through a multifaceted approach that combines biochemical, structural and biophysical techniques with yeast and mammalian genetics, microscopy and cell biological methods.

Munson joined UMass Chan Medical School in 2001. Prior to joining the faculty, she was a postdoctoral fellow in the department of molecular biology at Princeton University, where she was awarded American Heart Association and National Institutes of Health fellowships. She was a double major in chemistry and biology at Washington University (St. Louis) and received her PhD from Yale University in molecular biophysics and biochemistry. In 2015, Munson was awarded the inaugural Bassick Family Worcester Foundation Award.

Since joining UMass Chan, Munson has been closely involved with teaching and curriculum development for the Morningside Graduate School of Biomedical Sciences and has been recognized by the institution several times for her outstanding contributions to curriculum development and student mentoring. She is the faculty advisor for the UMass Chan student chapter of the Society for Advancement of Chicanos/Hispanics and Native Americans in Science. She is a leader of the diversity action committee in the Department of Biochemistry &Molecular Biotechnology and leads the new Morningside Graduate School of Biomedical Sciences Faculty Focused on Inclusive Excellence committee, focused on engaging and educating faculty to promote diversity, equity and inclusion on campus.

She is the co-chair of the American Society for Cell Biologys Women in Cell Biology committee and a co-investigator of its AMP MOSAIC program. She recently became a trained facilitator for Entering Mentoring, a program sponsored by the Center for the Improvement of Mentored Experiences in Research to enable strong and supportive scientific mentors.

Munson joins Gregory J. Pazour, PhD, professor of molecular medicine; Thoru Pederson, PhD, the Vitold Arnett Professor of Cell Biology and professor of biochemistry & molecular biotechnology; and George B. Witman, PhD, professor emeritus of radiology, in being named fellows of the American Society for Cell Biology.

Related UMass Chan News storiesAt MLK tribute,Mary Munsonrecognized for commitment to diversity and inclusion in science fieldUMMS researcher co-directs project to enhance diversity in biomedical sciences workforce.Thoru Pederson named fellow of theAmerican Society for Cell BiologyGregory Pazour elected fellow of theAmerican Society for Cell Biology

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Mary Munson elected fellow of the American Society for Cell Biology - UMass Medical School

Though 2022 has been a down year for the biotechnology sector, notable decisions from the Food and Drug Administration have provided a few bright spots.

Two gene therapies came to market, providing a lift for a field thats been slowed by recent setbacks. The cancer drug Enhertu was approved for a newly defined tumor type known as HER2-low. The regulator also cleared a new medicine for ALS and a first-of-its-kind inflammatory disease drug.

The fourth quarter could yield some other medical milestones. An Alzheimers drug that unexpectedly succeeded in a large trial last week is under review. So are what could be the first treatment for a common form of vision loss, a closely watched HIV drug, and a type of anemia pill the FDA has already turned back twice.

Here are 5 FDA decisions to watch:

In the decade since the FDA made Makena available for the prevention of preterm births, the treatment has become a flashpoint in the debate over speedy drug approvals.

Makena was developed by AMAG Pharmaceuticals and granted accelerated approval in 2011 based on a study showing it reduced the risk of preterm births which can jeopardize a babys health in women with a history of delivering early.

A study meant to confirm Makenas benefits took years to complete, however. When the results did arrive in 2019, Makena didnt perform meaningfully better than a placebo.

Since then, the fate of Makena has been the subject of a fight between the FDA, AMAG and the drugs current owner, Covis Pharma, which acquired AMAG in 2020. After an FDA advisory panel in 2019 recommended the regulator pull Makena from the market, the agency proposed doing so, arguing the available evidence does not show Makena is effective for its approved use.

Its developers, as well as some patient advocates and outside experts, have countered that doing so would be a mistake, claiming the drug still may help Black women at high risk of early births, who made up a larger portion of participants in the original trial than the confirmatory study.

A hearing on the issue has been delayed several times amid legal wrangling, extending the drugs time on market while its benefit remains unclear. The FDA specifically cited the case as an example of how lengthy and burdensome the withdrawal process may be when a company disagrees with the agency, according to a report on accelerated approvals published last week by the U.S. Department of Health and Human Services.

The back-and-forth could come to a conclusion this quarter. A three-day hearing of an FDA advisory panel will begin on Oct. 17 and feature discussions on the available confirmatory evidence as well as whether FDA should allow Makena to remain on the market.

GSKs daprodustat is the third anemia drug of its kind to be reviewed by the FDA. If the rejections of the first two are any indication, daprodustat could have a tough time when the agencys expert advisers meet to review it on Oct. 26.

Daprodustat is intended to be an oral alternative to injectable biologics like Epogen and Aranesp that boost red blood cell production and are used to treat anemia in patients with damaged kidneys. Those medicines have been standard treatments for years, but their use has been restricted because of the risk of heart problems.

GSKs drug is also meant to increase red blood cell levels, but by tricking the body into thinking its in a low-oxygen environment. The approach is meant to be both safer and more convenient for patients, and has spawned daprodustat as well as drugs from FibroGen and Akebia Therapeutics. All three are approved in Japan, and FibroGens is cleared for use in Europe.

But none are available in the U.S., where regulators have taken a tougher stance. In a meeting last year, the FDA and its expert reviewers challenged claims that FibroGens drug is safer than its injectable competitors. The agency rejected that medicine and demanded another trial. It then did the same to Akebias treatment in March.

GSK believes it has a better case. Unlike its rivals, daprodustat didnt perform worse than injectable drugs on measures of heart safety in the key studies supporting its application. There are still concerns, however. An editorial published in the New England Journal of Medicine alongside GSKs two large studies flagged the risk of cancer, and questioned the drugs benefit in patients who arent on dialysis, a group that makes up the majority of people with chronic kidney disease.

People with the wet form of age-related macular degeneration, a leading cause of vision loss, have many effective treatment options. The estimated 5 million people across the globe with geographic atrophy an irreversible eye disease that results from AMD dont. That could change if the FDA approves Apellis Pharmaceuticals pegcetacoplan later this year, however.

Pegcetacoplan is an injectable drug that blocks activation of the complement system, a part of the bodys innate immune response. In clinical testing, its shown the potential to slow growth of the lesions, or scar tissue, found in the eyes of people with geographic atrophy.

Yet Apellis doesnt have a clear-cut case. The drug missed statistical significance in one of its two Phase 3 studies. Apellis also hasnt yet proven that slowing lesion growth directly translates to improved vision. In August, the company reported patients in its late-stage trials didnt experience a visual acuity benefit after two years of treatment.

Apellis executives have expressed confidence the drugs benefit will become apparent with longer follow-up. We have trouble imagining a scenario where lesion size doesnt inevitably correlate with function, wrote Evercore ISI analyst Umer Raffat, in a research note.

A green light from the FDA could yield a drug that Jefferies analysts estimate could generate as much as $6 billion in yearly sales at its peak. A rejection or delay, meanwhile, could cost Apellis a chance to be first to market, as Iveric Bio plans to file for approval of a similar drug early next year.

The FDA will make a decision by Nov. 26.

For three years, analysts and investors have debated whether a cancer drug developed by Mirati Therapeutics, a small San Diego biotech, can top a rival one from Amgen that's become the crown jewel of the larger company's oncology business.

The two companies have traded clinical trial readouts showing their drugs can effectively shrink tumors driven to growth by mutations in a gene, called KRAS, that for decades was considered undruggable. Last spring, Amgen turned its positive data into a first-of-its-kind approval for its drug, now sold as Lumakras.

Now it's Mirati's turn in front of the FDA, as its drug adagrasib is under review with a decision deadline of Dec. 14. Should it win approval, Mirati would compete for market share with Amgen, which has the benefit of recent data confirming its drug beat chemotherapy in a larger study of patients with non-small cell lung cancer.

But Lumakras failed to show it could extend patients lives, leaving an opening for Mirati to do better. The company is currently enrolling a bigger trial that's meant to confirm adagrasib's benefit.

By Dec. 27, Gilead Sciences should know whether its second attempt at getting a key HIV drug approved in the U.S. has succeeded.

The first try ended with an FDA rejection because of concerns about potential adverse interactions between the drug, known as lenacapavir, and the specific glass vials in which it was contained. Gilead said it has since addressed those manufacturing-related issues by using vials made from a different glass. The treatment won its first approval in Europe in September.

A similar outcome in the U.S. would bolster the commercial prospects for an important addition to Gileads arsenal of HIV medicines. Lenacapavir has a unique way of binding to the protein shell that surrounds the virus, and its benefits appear long-lasting. In a small study, an injection of the drug every six months, in combination with other antivirals, kept the virus in check for heavily pretreated patients who had developed resistance to multiple therapies.

Gilead has been evaluating potential combinations of lenacapavir and other drugs, including Merck & Co.s islatravir, although that latter therapy has raised safety concerns over the last year. Gilead is also testing whether its drug works as a preventive treatment.

In a note to clients earlier this year, RBC Capital Markets analyst Brian Abrahams wrote that his team expects the FDA to approve lenacapavir for heavily pretreated HIV patients a relatively small indication that could generate peak annual sales of about $200 million in the U.S.

But given lenacapavirs various advantages, including the ability to be combined with other treatments and administered in multiple ways, the RBC team argues the drug could become the backbone of Gileads HIV franchise within several years and ultimately achieve more than $4 billion in yearly sales at its apex.

Will lecanemab, an experimental Alzheimer's drug that succeeded in a large clinical trial last week, become a backbone therapy for the neurodegenerative disease? Doctors and researchers aren't yet sure, as only limited data have been disclosed by lecanemab's developers, Eisai and Biogen.

They'll get much more information Nov. 29, when the companies present fuller study results at a medical meeting in San Francisco. The results are likely to be pored over and debated, as they represent the first clearly positive data from a Phase 3 trial of a drug meant to treat Alzheimer's underlying cause.

Theyre also likely to help the FDA decide whether to approve lecanemab on an accelerated basis. Using data from an earlier study, Eisai filed an application earlier this year, and a decision is expected by Jan. 6 on the basis of the treatments ability to clear toxic plaques from the brain.

The new trial results were meant to confirm those preliminary findings. Now that theyre positive, Eisai has a stronger case and the FDA a potentially easier judgment call.

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5 FDA decisions to watch in the fourth quarter - BioPharma Dive

CAMBRIDGE, England--(BUSINESS WIRE)--Cell coding company bit.bio has announced an expansion to its product portfolio - ioGlutamatergic Neurons TDP-43M337V disease model and early access to its ioMicroglia cell product.

Despite considerable research efforts and funding, the development of therapies for devastating diseases like Alzheimers disease (AD), Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) has been challenging. Due to a lack of standardised, easy to use and readily accessible human cell models, scientists have relied on animal models and cell lines that differ considerably from human biology.

bit.bios latest cell products provide a scalable source of human cells and will enable scientists to study neurodegenerative diseases in a human context. With consistency across batches and a scalable supply, bit.bios products will significantly reduce experimental variability in non-clinical studies and improve the translatability and reproducibility of research findings. These unique product features have the potential to transform research and drug discovery.

Dr Mark Kotter, CEO and Founder of bit.bio said:

The products we are announcing today address an area of high unmet clinical need where high failure rates in drug development are common and no effective treatments exist. I look forward to seeing how our customers will use them to develop new insights and treatments for these devastating conditions.

This is another step towards our vision of an exciting future in which precision reprogrammed human cells will accelerate biomedical innovation and a new generation of cures. The launch of two new cell products for research and drug discovery in neurodegenerative diseases validates our cell identity coding platforms ability to create and manufacture any human cell type consistently at scale.

Today, AD and FTD, the leading causes of early onset dementia, have no treatment options to stop or slow their onset. Similarly, current treatment options for ALS, the most common motor neuron degenerative disease, are limited. ioGlutamatergic Neurons TDP-43M337V, have a mutation in the TAR DNA binding protein gene that codes for the TDP-43 protein, which is known to cause both FTD and ALS. The disease model cells and the genetically matched control, ioGlutamatergic Neurons, mature rapidly, are highly reproducible between batches, and have unprecedented scalability. These key features make them ideally suited to high-throughput screening applications for early drug discovery. Being able to compare data from the physiologically-relevant disease models to those of the control offers the potential to identify and investigate the effects of the genetic mutation on the disease mechanisms of FTD and ALS.

Increasing evidence suggests that microglia contribute to the onset and progression of AD and are involved in the pathogenesis of ALS and FTD. Therefore they may represent an additional therapeutic target. However, speed, variability, and scalability continue to be major challenges with commonly used microglia. ioMicroglia, now available as part of an early access program, address these challenges allowing scientists to work with consistent, functional cells that are ready for experimentation within just 10 days.

Dr Farah Patell-Socha, VP Research Products at bit.bio, said:

Human cells are key to disease research, drug discovery, and clinical translation. However, traditional methods of producing human cells have long, laborious, protocols that often result in heterogenous cell populations and can lead to data variability. Our latest products provide robust, standardised tools for neurodegenerative research and drug discovery, paving the way for high-throughput screening and drug target validation in human iPSC-derived models that was previously impossible, and bringing huge benefits to medicine as a result.

The latest disease models are now available to order on the bit.bio website

Scientists can register interest in early access ioMicroglia vials, and find full physiological data on the bit.bio website

Notes to editors

About bit.bio

bit.bio is a synthetic biology company providing human cells for research, drug discovery and cell therapy. It has released six ioCells research products into the market and is currently building out its clinical pipeline.

bit.bios foundational opti-oxTM precision reprogramming technology enables highly consistent and scalable manufacture of human cells. The activation of cell type-defining transcription factor programs inserted into genomic safe harbour sites allows deterministic reprogramming of induced pluripotent stem cells (iPSC) into highly defined and mature human cells. bit.bios discovery platform is based on a deep synthetic biology tech stack and uses large scale experimentation and machine learning to identify combinations of transcription factor genes that encode cell identity.

bit.bio has assembled a team of pioneers with world-leading expertise in stem cell and synthetic biology, manufacturing, and clinical translation. The board is chaired by serial entrepreneur Dr Hermann Hauser and includes Sir Gregory Winter (Nobel Prize for Medicine) and biotech veteran Alan Roemer (co-founder Roivant and Pharmasset).

The company was spun out of the University of Cambridge in 2016. It is at Series B stage and has raised a total of $200M capital from Arch Ventures, Foresite Capital, Milky Way, Charles River Laboratories, National Resilience, Tencent, and Puhua Capital, and others.

For more information visit bit.bio

About ioMicroglia

ioMicroglia are iPSC-derived (induced pluripotent stem cell) immune cells, which will boost research into the physiology and diseases of the central nervous system, such as Alzheimers disease, Parkinsons disease and ALS.

ioMicroglia joins a growing portfolio of stem-cell derived human cells available from bit.bio, with the goal of empowering biomedical innovation towards a new generation of cures through precision reprogramming of human iPSCs. Microglia are immune cells which act as the first line of defence for the central nervous system, from both external and internal threats, and are a key research target when investigating immunological mechanisms in the brain. They are also key in supporting drug discovery into the modulation of microglia activation which can be used as a potential preventative strategy for Alzheimers disease.

The key advantage of ioMicroglia is that it addresses two of the major challenges encountered with commonly used human iPSC-derived microglia production protocols: namely speed and variability. ioMicroglia allows scientists to work with functional microglia that are ready for experimentation within 10 days versus 8-10 weeks with classical differentiation protocols. Moreover, ioMicroglia show high batch-to-batch consistency in morphology, key marker expression and functionality, in contrast to classical differentiation protocols.

ioMicroglia show key functional and phenotypic traits in culture including expression of TMEM119, P2RY12, and IBA1, and the ability to phagocytose invasive microorganisms, apoptotic cells or amyloid beta peptides associated with Alzheimers disease. Inflammatory properties are also maintained in bit.bios cells, further widening the potential applications of their use in translatable laboratory research. The ioMicroglia cells can also be co-cultured with bit.bios ioGlutamatergic Neurons whilst retaining microglial functionality, in order to recreate physiological conditions present in the central nervous system.

The new ioMicroglia cells are produced using bit.bios opti-ox platform which has once again proved its effectiveness in manufacturing physiologically relevant, consistent and reproducible cells at scale in a matter of days. Alongside bit.bios existing catalogue of cell types, ioMicroglia are a hugely useful resource for researchers investigating neurodegenerative disease.

About the TDP-43 disease models

Following the launch of its Huntingtons disease model earlier in 2022, ioGlutamatergic Neurons TDP-43 M337V/WT and ioGlutamatergic Neurons TDP-43 M337V/M337V are the second and third products in the companys ioDisease Model portfolio. The ioDisease Model cells take advantage of precision cell reprogramming and CRISPR/Cas9 genetic engineering, to produce highly characterised human induced pluripotent stem cell (hiPSCs)-derived excitatory neurons with disease-relevant mutations..

Frontotemporal dementia (FTD) is the second leading cause of early onset dementia following Alzheimer's disease. It involves atrophy of the frontal and temporal regions of the brain affecting language, memory, and behaviour. Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degenerative disease and is characterised by progressive degeneration of both upper and lower motor neurons.

The disease models are engineered with a disease-relevant M337V mutation in the TARDBP gene, which codes for the TAR DNA-binding protein 43 (TDP-43). This mutation in the TDP-43 protein promotes cytoplasmic mislocalisation and aggregation, which is implicated in the pathology of ALS and FTD. These disease models offer a fast and easy-to-use system for investigations into the impact of gene function on disease progression. One of the key advantages is the availability of a genetically matched control, which enables researchers to make true comparisons as they can attribute observed differences to the single genetic modification.

Excerpt from:
bit.bio Adds Two New Human Cell Products to Address the Translation Gap and Accelerate Research and Drug Discovery for Neurodegenerative Disease -...

Laser Focus World magazine recently highlighted University of Cincinnati research in its weekly "Photonics Hot List" YouTube show.

The show highlighted recently published research out of the lab of UC's Jiajie Diao, PhD, that shows early indications that light can be used as a treatment for certain diseases, including cancer.

Hundreds of mitochondria are constantly coming together (a process called fusion) and dividing into smaller parts (a process called fission) to stay balanced in healthy cells. But when mitochondria are not functioning properly, there is an imbalance of this process of fission and fusion, which can lead to a number of mitochondrial diseases, including neurodegenerative diseases like dementia and certain cancers.

The researchers used light to activate proteins that bring together parts of the cell to achieve mitochondrial fission, helping to bring cells back into balance.

We found that it can recover the mitochondrial function, said Diao, associate professor in the Department of Cancer Biology in UCs College of Medicine and a University of Cincinnati Cancer Center member. Some of the cells can even go back to normal. This proves that by just using some simple light stimulation we can at least partially recover the mitochondrial function of the cell.

Watch the Photonics Hot List segment. (Note: Segment begins around 2:51 mark.)

Read more about Diao's research.

Featured photo at top of Jiajie Diao working in his lab. Photo/Colleen Kelley/UC Marketing + Brand.

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Laser Focus World highlights UC research that uses light to restore cell function - University of Cincinnati