Stem Cell Clinic

Seer raises another $55M and finally reveals proteomic tech can it hold up? – Endpoints News

Two years ago, Omid Farokhzad left his prominent nano-medicine lab at Bostons Brigham and Womens Hospital and moved across the country to found a startup off technology that, he said, could change the field of proteomics and, with it, parts of medicine, agriculture and a range of fields.

Today, Farokhzad has finally revealed what that technology is. In aNature Communicationspaper, he showed how his company, Seer, and their lead product, called the Proteograph, can use nanoparticles to analyze the protein compositions in a single blood sample, like a fishing net webbing the contents of a particular swath of sea. Or to use the companys preferred metaphor like a sequencing machine reading out the base pairs on a particular strand of DNA.

Alongside the publication, Seer also announced a new $55 million round to help launch the product, bringing its total financing to over $150 million.

We now enable what was previously not possible, Farokhzad toldEndpoints News.Today about every 25 seconds, someone [can] sequence anothers human genome. This technology allows you to begin to interrogate the human proteome in an unbiased way, deep, in speed and scale.

Its a bold talk for a field full of it, although its now at least burnished by peer-reviewed data something that cannot be said for all of Seers competitors. The proteome has long been a source of fascination for scientists, for the simple fact that were built of proteins, and changes in the concentration or shape of proteins are what ultimately underlie changes in function and disease.

The problem is that its far harder to get a complete picture of someones proteins than it is of their genes. Genes are comparatively simple: 4 base pairs, each of which can only bind in one direction. Proteins can be made of up to 20 amino acids that bind in myriad ways. They can also change after translation. The technological or computing power simply did not exist to analyze all of them at a rate comparable to how researchers can analyze genes.

Thats changed to a degree in recent years. Several companies have popped up, most notably SomaLogic, offering to screen peoples blood for a limited set of proteins data have indicated correlates with disease. Researchers also have techniques to map out every protein in a blood sample, but it can take months.

Seer claims to be able to do screening in a fast and unbiased way, similar to how we can now analyze genes a quick and complete picture. A new company, called Nautlius, launched this year with over $100 million from prominent tech funds with a similar promise, but they are earlier stage and have yet to disclose their tech. And everyone is comparing themselves to Illumina, the $60 billion sequencing giant, which itself has a proteomics division.

The key variable that next-gen sequencing and in particular that Illumina technology changed was the ability to access the genome or the transcriptome in an unbiased, deep way, rapidly and at scale, Omead Ostadan, a former Illumina executive who was recently named Seers COO and president, told Endpoints. With Seers proteomics tech, you enable enormous depth and breadth analogous to the biologic insight that emerged when you could [first] access genomic information.

Seer has developed over 250 nanoparticles for its Proteograph. These different particles, when put in the blood, attract different proteins that bond to chemical groups on the surface, forming a corona, or a kind of molecular halo around the protein. Other proteins then bind to those proteins and so on. Not every nanoparticle will bind to every protein, but if you put in enough, the different coronas will give a kind of picture both of what proteins exist and if those proteins have changed shape.

As a proof of concept, the company looked at samples from early-stage non-small cell lung cancer patients and found proteins that correlated with disease.

This kind of analysis, Farokhzad said, could be used to diagnose patients early a goal shared by well-backed liquid biopsy companies like GRAIL and Karius. It could also, he said, be used to find new proteins associated with cancer, and those proteins could then become biomarkers or targets for new therapies. There are also applications in agriculture and environmental science.

For now, the company is focused on building new nanoparticles and launching the product next year, before finding new applications. Theyll have to seal partners and buyers, who in turn will be able to say if the product is just as transformational as they claim.

It sounds simple, but having lived through product development and commercialization, theres a lot to do, Ostadan said.

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Seer raises another $55M and finally reveals proteomic tech can it hold up? - Endpoints News

Potential Risks of Treatment with Unapproved Regenerative Medicine Products – FDA.gov

By: Peter Marks, M.D., Ph.D., Director, Center for Biologics Evaluation and Research

Protecting patients is at the core of what we do at the U.S. Food and Drug Administration. Now the FDA is providing additional resources to help consumers understand the risks associated with unapproved stem cell, exosome, and other products marketed as regenerative medicine products. The agency is also facilitating the reporting of side effects that may occur after their use. The FDAs receipt of this information is important to developing a better understanding of the risks associated with these products and to helping the agency identify those clinics and manufacturers putting patients at risk.

Several times in recent years, the FDA warned consumers who have been treated with, or who are considering use of, unapproved stem cell, exosome, or other products marketed as regenerative medicine products, about their potential risk. These illegal products are often marketed by clinics under the umbrella term of regenerative medicine as being safe and effective for treatment of a wide range of diseases or conditions (e.g., Alzheimers disease and other neurologic disorders, orthopedic conditions), even though they have not been adequately studied in clinical trials. And more recently, some of these clinics have been marketing or distributing their unproven products to treat complications related to COVID-19 claims that are not based on adequate clinical data.

Consumers may also have been told by clinics and health care providers that because some of these products are made from their own cells, the FDA does not need to review or approve the treatment. That is simply not true. Further, claims that a clinics FDA registration or inspection equates to FDA approval or a form of FDA endorsement, or that listing a clinical study on clinicaltrials.gov means that it has been reviewed and allowed to proceed by the FDA, are also false.

It is of utmost concern that unapproved regenerative medicine products that have no proven clinical benefit and that may cause serious harm are marketed to patients. Using these products may lead to delays in getting a proper diagnosis and could also discourage patients suffering from serious illnesses from receiving safe and effective treatments that may be available. Whats also concerning is that we know that because these products are not FDA-approved, its very likely that adverse events are underreported by health care providers who treat patients with these products, and by patients who may have been harmed. We therefore strongly encourage patients and their family members to ask questions before receiving these types of products has the product been approved by the FDA? Has the product been approved for this use? Is the product being studied in a clinical trial that has been reviewed and allowed to proceed by the FDA? Am I being charged for an unapproved product?

We encourage patients and their health care providers to report to the FDA any potential adverse events and complaints related to the use of these products using the FDAs MedWatch Adverse Event Reporting program. Stem cell, exosome, or other products marketed as regenerative medicine products may have the potential to treat many medical conditions and diseases. But for almost all these products, it is not yet known whether each product has any benefit or if the product is safe to use. We want to make sure patients understand these potential risks in order to protect themselves from being treated with and paying for an unproven and illegally marketed products. The FDA has posted a webpage for consumers that provides information about products marketed as stem cells, exosomes or other regenerative medicine products, including the conditions for which they are approved, and which products are not approved at all. The webpage also provides information on how to submit information about adverse events to the FDAs MedWatch Adverse Event Reporting Program.

Unfortunately, weve found numerous instances of products being marketed to patients without FDA approval, as well as products being manufactured with significant deviations from current good tissue practice (CGTP) and/or current good manufacturing practice (CGMP) requirements. These violations have included deficient donor eligibility practices, and inadequate aseptic practices to prevent product contamination violations that have the potential to place patients at risk. Patients have been harmed after being administered some of these violative products.

We encourage consumers who are considering treatment with regenerative medicine products to work with their health care providers to learn about the treatment being offered, and to visit our webpage. It is important to ask questions and understand the potential risks of treatment with unapproved products. The FDA will continue to work with the manufacturers of these products to support their development. But we will also continue to take appropriate action against those who put patients in harms way.

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Potential Risks of Treatment with Unapproved Regenerative Medicine Products - FDA.gov

GV’s David Schenkein comes in to help mentor and bankroll a gene therapy 2.0 player, intrigued by their ‘science heavy’ approach to conquering…

One of the leading programs for a new coronavirus vaccine was championed today as investigators from Oxford and AstraZeneca spelled out a dual hit with neutralizing antibodies as well as a surge in specific T cells targeted against the virus.

According to the study:

Humoral responses to SARS-CoV-2 spike protein peaked by day 28 postprime and cellular responses were induced in all participants byday 14. Neutralising antibodies were induced in all participants after a second vaccine dose. After two doses, potent cellular and humoral immunogenicity was present in all participants studied.

The results largely confirm what was already previewed: One dose was sufficient to elicit some antibody response in over 90% of people, and a second dose pushed it to 100%, at levels similar to whats observed in convalescent patients. Spike-specific effectors T cells were observed as early as day 7, peaking at day 14 and maintained up to day 56 as expected with adenoviral vectors.

In a media briefing, AstraZeneca biopharma R&D head Mene Pangalos noted that the ongoing Phase III trials will almost certainly be testing two doses, as it would be the safest approach to making sure we hit efficacy. Lower doses can then be worked out in the future.

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GV's David Schenkein comes in to help mentor and bankroll a gene therapy 2.0 player, intrigued by their 'science heavy' approach to conquering...

2 immunotherapies merged into single, more effective treatment – Washington University School of Medicine in St. Louis

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Mouse study suggests strategy may work against variety of cancers

Researchers at Washington University School of Medicine in St. Louis have combined two types of immunotherapy into a single treatment that may be more effective and possibly safer than current immunotherapies for blood cancers. Shown is a type of immune cell called a memory-like natural killer cell (right) attacking a leukemia cell (left). In the new study, the researchers modified the natural killer cells to help them find the leukemia cells more effectively.

Some of the most promising advances in cancer treatment have centered on immunotherapies that rev up a patients immune system to attack cancer. But immunotherapies dont work in all patients, and researchers have been searching for ways to increase their effectiveness.

Now, researchers at Washington University School of Medicine in St. Louis have combined two immunotherapy strategies into a single therapy and found, in studies in human cells and in mice, that the two together are more effective than either alone in treating certain blood cancers, such as leukemia. Evidence also suggests that the new approach could be safer than one of the most recent cellular immunotherapies to be approved by the FDA, called CAR-T cell therapy, in which the immune systems T cells are engineered to target tumor cells. Cell-based immunotherapies are most commonly used against blood cancers but can be harnessed against some solid tumors as well, such as prostate and lung tumors and melanoma.

The study appears online in the journal Blood.

In the new research, the scientists have harnessed the technology used to engineer CAR-T cells and, instead of modifying specialized immune cells called T cells, they have used similar technology to alter different immune cells called natural killer (NK) cells. The resulting immunotherapy combines the benefits of both strategies and may reduce the side effects that are sometimes seen in CAR-T cell therapy. In some patients, for example, CAR-T cell therapy causes a cytokine storm, a life-threatening overreaction of the immune system.

Immunotherapies show great promise for cancer therapy, but we need to make them more effective and more safe for more patients, said co-senior author Todd A. Fehniger, MD, PhD, a professor of medicine. This combined approach builds on the treatment strategy that we developed for leukemia patients using natural killer cells. We can supercharge natural killer cells to enhance their ability to attack cancer cells. And at the same time, we can use the genetic engineering approaches of CAR cell therapy to direct the natural killer cells to a tumor target that would normally be overlooked by NK cells. It fundamentally changes the types of cancer that NK cells could be used to treat, both additional blood cancers and potentially solid tumors as well.

In past work, Fehniger and his colleagues showed that they could collect a patients own NK cells, expose the cells to a specific recipe of chemical signals that prime the cells to attack tumors, and then return the primed cells to patients for therapy. This chemical exposure is a sort of basic training for the cells, according to the investigators, preparing the NK cells to fight the cancer. When the cells are then returned to the body, they remember their training, so to speak, and are more effective at targeting the tumor cells. Because their training has given the NK cells a memory of what to do when they encounter tumor cells, the researchers dubbed them memory-like NK cells.

In small clinical trials conducted at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, such cells were effective in putting some patients with leukemia into a lasting remission, but they didnt work for everyone. Some tumor cells still evaded the memory-like NK cells, despite the cells basic training. To help the cells find the tumor cells, so their basic training can kick in and kill the correct target, the researchers modified the memory-like NK cells with the same CAR (chimeric antigen receptor) molecule that is typically used to target T cells to tumor cells. The CAR molecule is flexible and can be modified to direct the cells to different tumor types, depending on the proteins on the surfaces of the cancer cells.

The resulting hybrid cells were more effective in treating mice with leukemia than memory-like NK cells alone, leading to longer survival for mice treated with CAR memory-like NK cells. The researchers also found the therapy to be effective despite the fact that the mice were given relatively low doses of the cells.

One aspect of this study I find most exciting is how nicely these hybrid NK cells expand in the mice to respond to their tumors, said co-senior author Melissa Berrien-Elliott, PhD, an instructor in medicine. We can provide a tiny dose and see an incredible amount of tumor control. To me, this highlights the potency of these cells, as well as their potential to expand once in the body, which is critical for translating these findings to the clinic.

Fehniger also pointed out that an advantage of NK cells in general and for biological reasons that the scientists are still working to understand NK cells dont trigger a dangerous immune response or the long-term side effects that T-cell therapy can cause in attacking the patients healthy tissues, a condition called graft-versus-host disease.

In all of the clinical trials exploring any type of NK cells, we dont see the troublesome side effects of cytokine release syndrome or neurotoxicity that we see with CAR-T cells that can profoundly affect patients, Fehniger said. These side effects can be life-threatening and require intensive care. Were still working to understand how NK cells are different. But if you can get the benefits of CAR-T cells with few if any of the side effects, thats a reasonable line of research to pursue. Another benefit of this safer therapy is the potential to give these cells to patients at an earlier stage in their disease, rather than using them as a last resort.

Other groups have developed CAR-NK cells, but a major difference is that other groups NK cells came from donated cord blood or induced stem cells, rather than adult donors or the patients themselves.

The other groups have artificially differentiated stem cells into something that resembles an NK cell, Fehniger said. With that strategy, theres no guarantee that those cells will have all the properties of typical mature NK cells. In contrast, were starting with adult NK cells, so were more confident that they will have all the inherent properties and behavior of adult NK cells, which we have already shown to be effective in certain types of cancer patients, especially those with leukemia. Inducing memory properties adds to their persistence and effectiveness against many cancer types.

Over the next several years, we would like to be able to scale up this process to produce enough cells for a first-in-human clinical trial, and investigate their effectiveness in different types of human blood cancers, he said.

This work was supported by the Howard Hughes Medical Institute; the National Institutes of Health (NIH), grant numbers F32CA200253, T32HL00708843, K12CA167540 and R01CA205239; and a NIH SPORE in Leukemia, grant number P50CA171063. Additional funding was provided by the Siteman Cancer Center through NIH grant number P30CA091842; the Leukemia and Lymphoma Society; the V Foundation for Cancer Research; the Childrens Discovery Institute at Washington University School of Medicine; the Jamie Erin Follicular Lymphoma Research Fund; and the Steinback Fund.

Berrien-Elliott and Fehniger are inventors on patents related to this study that have been filed by Washington University. Fehniger has received research support from ImmunityBio, Compass Therapeutics, and HCW Biologics, and advises Kiadis, Nkarta, Indapta, and Orca Biosystems. Other authors report serving as a consultant for Kiowa Hakka Kirin and C4 Therapeutics; receiving research funding from Bristol Myers-Squibb, Verastem Pharmaceuticals, Innate Pharmaceuticals, Genentech/Roche, Celgene, and Corvus Pharmaceuticals; having direct ownership of equity in and a consultancy with Wugen; serving on the consulting/advisory committee for Rivervest, Bioline, Amphivena and Bluebird, Celegene, Incyte, NeoImuneTech, and Macrogenics and ownership investment in Magenta and WUGEN.

Gang M, Marin ND, Wong P, Neal CC, Marsala L, Foster M, Schappe T, Meng W, Tran J, Schaettler M, Davila M, Gao F, Cashen AF, Bartlett NL, Mehta-Shah N, Kahl BS, Kim MY, Cooper ML, DiPersio JF, Berrien-Elliott MM, Fehniger TA. CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas. Blood. July 2, 2020.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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2 immunotherapies merged into single, more effective treatment - Washington University School of Medicine in St. Louis