Archive for the ‘Bone Marrow Stem Cells’ Category

Cell therapies involve the transfer of live cells into a patient to help treat, prevent or potentially cure diseases. One category of cell therapy focuses specifically on the use of stem cells, or cells within the body that have the potential to replace those that are lost through injury or disease. Their versatility and ability to transform allow them to replace problematic or deactivated cells with new, healthy ones is giving patients around the world a second chance at life.Stem cells are found all throughout the human bodyincluding the skin, muscle tissue and even deep inside bone marrow.

Bone marrow, the spongy substance that fills the inner cavities of our bones, is a rich source ofhematopoietic stem cells. These cells are particularly valuable for their ability to develop into all types of blood cells, including white blood cells, red blood cells and platelets. Due to their unique ability,hematopoietic cells can be used to treat certain types of cancer, such as leukemia and lymphomaand have become a staple in the field of regenerative medicine.

Bone marrow aspirate concentrate(BMAC) is a procedure that collects bone marrow from a patient's body and then concentrates it to create the optimal level of stem cells and other crucial growth factors, which can offer a variety of health benefits that traditional surgical methods simply can't offer. Stem cells and their descendants, known as progenitor cells, combined with other bone marrow cells and platelets, have the potential to restore function when injected directly into the patient's damaged tissue. The BMAC procedure is popularly used by physicians who practice orthopedic surgery, pain management and sports medicine. It has been shown torepair tissue damage, preserving function and strengthand in some cases has even beenused as an alternative for more intensive procedures such as joint and hip replacements.

Bone Marrow Aspirate Concentrate is currently being used to:

While there are many bone marrow concentrate technologies currently out on the market, there are none quite like theThermoGenesis PXPSystem. The PXPSystem is an automated, closed system designed for sterile bone marrow separation and concentration. The automated system utilizes highly sensitive sensors to reduce the amount of red blood cells (RBCs) from the initial bone marrow aspirate, providing physicians with a high-quality final product.Red blood cell contaminationis, by far, the biggest issue physicians encounter when using open, non-automated bone marrow processing systems. When high RBC contamination occurs in the bone marrow concentrate, it can impair cell function and diminish the overall effectiveness of the cell treatments. The PXPSystem is specifically designed to eliminate RBCs contamination head-on, boasting aRBC reduction of over 99 percent.

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The PXPSystem obtains bone marrow concentrates easily, consistently, and reliably, setting itself apart from any other competitors on the market today. The automated nature of the system eliminates factors created by human error and allows for increased precision and control. It gives its user the ability to harvest a precise volume of cell concentrate from the bone marrow aspirate, while producing consistently high mononuclear cells (MNCs) and CD34+ progenitor cell recoveries.

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Bone marrow aspirate is collected from the patient through a minimally invasive procedure, usually done under local or general anesthesia. After extraction, the aspirate is transferred into the PXP System and processed in a centrifuge to compartmentalize the aspirate into three separate chambers within the Disposable Cartridge - the central processing chamber, the red blood cell depletion chamber and the harvest chamber. The plasma, nucleated cells and RBCs are all sorted by density to create maximum separation of components. The RBCs are then removed and transferred to the depletion chamber, leaving users with a 6 ml harvest of enriched bone marrow concentrate (containing stem cells, platelets, growth factors) ready to be reintroduced into the patient.

The entire process only takes about twenty minutes from the moment the bone marrow aspirate is placed in the system to the point where it can be reinjected. For added convenience, the automated control module provides users with accurate data tracking and serves as a record for the entire process.

The PXPSystem is a tool for physicians looking for a quick, easy and efficient system for processing bone marrow. It is one of the most innovative systems available on the market and our mission is to make it even better. We are currently working with our partners in the field and evolving our products based on their feedback. Based on their response, we've begun designing a stripped-down version of the PXPSystem that requires less accessories and generates a smaller footprint, while still delivering a high-quality final product. Our applications are being developed with the needs of laboratories and physicians in mind, giving them the resources, they need to better serve their patients.

ThermoGenesis Holdings, Inc. (formerly Cesca Therapeutics Inc.), is a pioneer and market leader in the development and commercialization of automated cell processing technologies for the cell and gene therapy fields. We market a full suite of solutions for automated clinical biobanking, COVID-19 testing, point-of-care applications and large-scale cell processing and manufacturing with a special emphasis on the emerging CAR-T immunotherapy market. We are committed to making the world a healthier place by creating innovative solutions for those in need.

To see our full suiteof automated solutions,please visit the shop portion of our website today.

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Thermogenesis Holdings Inc. published this content on 08 December 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 09 December 2020 18:24:01 UTC

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The Technology Behind Bone Marrow Cellular Processing: The PXP System - Marketscreener.com

CAMBRIDGE, Mass.--(BUSINESS WIRE)--HighPassBio, an ElevateBio portfolio company dedicated to advancing novel targeted T cell immunotherapies, today discussed the ongoing Phase 1 trial of the companys lead product candidate, an engineered T cell receptor (TCR) T cell therapy targeting HA-1 expressing cancer cells in an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting. The Phase 1 clinical trial, which is being conducted by researchers at Fred Hutchinson Cancer Research Center, is designed to assess the feasibility, safety, and efficacy of this novel cell therapy in the treatment of leukemia following hematopoietic stem cell transplant (HSCT).

The prognosis for leukemia patients whove relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse, said Elizabeth Krakow, M.D., MSc., Assistant Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, principal investigator of the study, and presenting author. We have observed early promising indicators of anti-leukemic activity following treatment in this trial. We are eager to expand the trial to additional patients as we continue to research the feasibility, safety, and efficacy of this approach.

The abstract for the presentation titled Phase 1 Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress, can be found on the ASH website under the abstract number 137726.

To date, four patients, including one pediatric patient, have received a total of six infusions in the Phase 1 clinical trial. Patient characteristic data was shared in the oral presentation at ASH, including documented HA-1 TCR T cell persistence in blood and bone marrow up to 18 months. In some patients, clear in vivo anti-leukemic activity was observed at the first dose level, including a subject with aggressive, highly refractory T-ALL and early post-HCT relapse. No significant toxicities attributed to the T cells have been observed, including no infusion reactions or evidence of cytokine release syndrome or graft versus host disease.

The Phase 1 clinical trial is currently recruiting adult and pediatric patients who have residual disease or relapsed leukemia or related conditions following HSCT. As part of the trial, transplant patients and prospective donors may be recruited to participate in the genetic screening portion to determine eligibility. More details are available on clinicaltrials.gov under the study ID number NCT03326921.

About TCR-Engineered T Cell Therapy

A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the bodys immune system to respond to fight off and kill the tumor cells.

Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease.

Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patients native cells, and not by the cells from the stem cell transplant donor. HA-1, a known minor histocompatibility antigen, is expressed predominantly or exclusively on hematopoietic cells, including leukemic cells. There is evidence that T cells specific for HA-1 can induce a potent and selective antileukemic effect. HA-1 TCR T cell therapy is a new investigational immunotherapy for the management of post transplantation leukemia relapse.

About Leukemia post HSCT Treatment and the Risk of Relapse

Leukemia, a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, is the tenth most common type of cancer in the U.S. with an estimated 60,140 new cases and 24,400 deaths in 2016. Leukemia arises from uncontrolled proliferation of a specific type of hematopoietic (blood) cell that is critical for a functional immune system. As a result, when patients are given very high doses of chemotherapy to eradicate leukemic cells, most normal cells are killed as well, necessitating a transplant of hematopoietic stem cells from a donor to reconstitute the patients bone marrow and circulating hematopoietic cells. In some cases, the transplanted T cells from the donor can also recognize and eliminate the hematopoietic cells, including leukemia, from the recipient, thus preventing relapse. This can be described as a graft versus leukemia effect. Other hematologic disorders related to leukemia, like myelodysplastic syndrome (MDS), can also be treated in this way.

While HSCT can be curative, it is estimated that 25-50 percent of HSCT recipients relapse; leukemia relapse remains the major cause of allogeneic HSCT failure, and the prognosis for patients with post-HCT relapse is poor. Relapse occurs following allogeneic HSCT in approximately one-third of patients with acute leukemia who undergo the procedure, and most patients subsequently die of their disease.

About HighPassBio

HighPassBio, an ElevateBio portfolio company, is working to advance a novel approach to treating hematological malignancies by leveraging T cell receptor (TCR)-engineered T cells, known as TCR T cells. The companys lead program is designed to treat or potentially prevent relapse of leukemia in patients who have undergone hematopoietic stem cell transplant (HSCT). The technology was born out of research conducted at Fred Hutchinson Cancer Research Center by world renowned expert, Dr. Marie Bleakley.

About ElevateBio

ElevateBio, LLC, is a Cambridge-based creator and operator of a portfolio of innovative cell and gene therapy companies. It begins with an environment where scientific inventors can transform their visions for cell and gene therapies into reality for patients with devastating and life-threatening diseases. Working with leading academic researchers, medical centers, and corporate partners, ElevateBios team of scientists, drug developers, and company builders are creating a portfolio of therapeutics companies that are changing the face of cell and gene therapy and regenerative medicine. Core to ElevateBios vision is BaseCamp, a centralized state-of-the-art innovation and manufacturing center, providing fully integrated capabilities, including basic and translational research, process development, clinical development, cGMP manufacturing, and regulatory affairs across multiple cell and gene therapy and regenerative medicine technology platforms. ElevateBio portfolio companies, as well as select strategic partners, are supported by ElevateBio BaseCamp in the advancement of novel cell and gene therapies.

ElevateBios investors include F2 Ventures, MPM Capital, EcoR1 Capital, Redmile Group, Samsara BioCapital, The Invus Group, Surveyor Capital (A Citadel company), EDBI, and Vertex Ventures.

ElevateBio is headquartered in Cambridge, Mass, with ElevateBio BaseCamp located in Waltham, Mass. For more information, please visit http://www.elevate.bio.

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ElevateBio's HighPassBio Presents on Novel T Cell Receptor Cell Therapy for Leukemia Relapse at 62nd Annual ASH Meeting - Business Wire

This weekend brought some really significant news in the long-running effort to use gene editing to treat human disease. As most readers will have heard, Boston Childrens Hospital and a Vertex/CRISPR effort both published papers in the NEJM addressing sickle-cell anemia and beta-thalassemia. (Update: edit to fix attribution).

These diseases have long been linked when it comes to gene therapy ideas, because both of them have defects in the hemoglobin protein as their cause. And its long been thought that both could be treated by getting adults to re-express the fetal hemoglobin protein its on a different gene entirely, and thus does not have any of the genetic problems that affect the adult hemoglobin gene. The normal course of events is for babies to stop expressing the fetal form and switch over to regular hemoglobin, and its been worked out that a particular transcription factor called BCL11a is a key player in that transcriptional repression of the fetal hemoglobin gene. That plays right into the usual way that we tend to think about therapeutic possibilities: whether its enzymes, receptors, or expression of whole proteins, we have a lot more tools to mess things up and interrupt processes than we have to make them run faster or better. So the possibility of interrupting BCL11as function has been a tempting one for many years.

Its hard to do by traditional means, though. (Full disclosure: I have, at different times in my career, been involved with such efforts, but none have ever come near the clinic.) Transcription factors are notoriously hard to get a handle on with small molecule therapeutics, and many unsuccessful runs have been taken at BCL11a ligands to try to interrupt its functions in one way or another. My general impression is that the protein doesnt much care about recognizing small-molecule ligands (and its far from the only one in that category, for sure). Youd think that if you ran a few hundred thousand (or a few million) various molecules past any given protein that youd find a few of them that bind to it, but that assumption is too optimistic for most transcription factors. Youre also going to have a hard row to hoe (to use an old Arkansas expression) if you try to break up their interactions with their DNA binding sites: a significant amount of capital has gone down the chute trying to get that to work, with (as far as I can tell) not much to show for it.

Theres another complication: BCL11a has a lot of other functions. Every protein has a lot of other functions, but for transcription factors, the issue can be especially fraught. If you had a small molecule that really did interfere with its activity, what would happen if you just took a stiff dose of it? Probably a number of things, including some interesting (and not necessarily welcome) surprises. There have been a number of ideas about how to get around this problem, but a problem it is.

So its on to biological mechanisms. The BCH team reports on using RNA interference to do the job they get cells to express a short hairpin RNA that shuts down production of BCL11a protein, with some microRNA work to target this to the right cell lines. And the Vertex/CRISPR team, naturally, uses CRISPR itself to go in and inactivate the BCL11a gene directly. Both approaches take (and have to take) a similar pathway, which is difficult and expensive, but still the best shot at such therapies that we have. You want the fetal hemoglobin expressed in red blood cells, naturally, and red blood cells come from CD34+ stem cells in the bone marrow. Even if you havent thought about this, you might see where its going: you take a bone marrow sample, isolate these cells, and then do your genetic manipulation to them ex vivo. Once youve got a population of appropriately re-engineered cells ready to go, you go kill off the bone marrow in the patient and put the reworked cells back in, so theyre the only source there for red blood cells at all. A bone marrow transplant, in other words a pretty grueling process, but definitely not as much as having some sort of blood-cell-driven cancer (where the therapy uses compatible donor cells from someone else without such a problem), or as much as having full-on sickle cell disease or tranfusion-dependent thalassemia.

You can also see how this is a perfect setup for gene therapy: theres a defined population of cells that you need to treat, which are available in a specific tissue via a well-worked-out procedure. The problem youre trying to correct is extremely well understood in fact, it was the first disease ever characterized (by Linus Pauling in 1949) as purely due to a genetic defect . And the patients own tissue is vulnerable to chemotherapy agents that will wipe out the existing cell population, in another well-worked-out protocol, giving the newly reworked cells an open landscape to expand in. You have the chance for a clean swap on a defined target, which is quite rare. In too many other cases the problem turns out to involve a fuzzy mass of genetic factors and environmental ones, none of which by themselves account for the disease symptoms, or the tissue doesnt allow you to isolate the defective cells easily or doesnt allow you to clear them out for any new ones you might generate, and so on.

Both the Vertex/CRISPR and BCH techniques seem to work and in fact, to work very well. There are now people walking around, many months after these treatments, who were severely ill but now appear to be cured. Thats not a word we get to use very often. They are producing enough fetal hemoglobin, more than enough to make their symptoms completely disappear no attacks, no transfusions, just normal life. And so far there have been no side effects due to the altered stem cells. An earlier strategy from Bluebird (involving addition of a gene for a modified adult hemoglobin) also seems to be holding up.

These are revolutionary proofs of concept, but at the same time, they are not going to change the course of these diseases in the world not right now, anyway. Bone marrow transfusion is of course a complex process that costs a great deal and can only be done in places with advanced medical facilities. But what weve established is that anything that can cause fetal hemoglobin to be expressed should indeed cure these diseases that idea has been de-risked. As has the general idea of doing such genetic alteration in defined adult tissues (either RNA interference or CRISPR). From here, we try to make these things easier, cheaper and more general, to come up with new ways of realizing these same goals now that we know that they do what we hoped that they would. This work is already underway new ways to target the affected cell populations rather than flat-out chemotherapy assault, new ways to deliver the genetically altered cells (or to produce them on site in the patients), ways to make the switchover between the two more gradual, and so on. There are lot of possible ways, and we now know where were going.

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Gene Therapy, Absolutely and For Real | In the Pipeline - Science Magazine

WASHINGTON, Dec. 8, 2020 /PRNewswire/ --Genetic mutations linked with cancer can occur during childhood or even before birth and proliferate in the body for many years before causing cancer symptoms, according to a new study. The study, which traced the genetic origins of a blood cancer in 10 individuals, suggests there may be untapped opportunities to detect cancer warning signs much earlier and potentially intervene to prevent or slow cancer development.

"Our preliminary findings show these cancer driver mutations were often acquired in childhood, many decades before the cancer diagnosis," said senior study authorJyoti Nangalia, MD,of the Wellcome Sanger Institute and University of Cambridge. "Our results finally answer the common question posed by patients, 'How long has this cancer been growing?' as we were able to study how these particular cancers developed over the entire lifetime of individual patients."

The researchers analyzed bone marrow and blood samples from 10 people with Philadelphia-negative myeloproliferative neoplasms, a type of cancer that causes stem cells in the bone marrow to produce too many blood cells. In the majority of patients, this cancer is driven by a genetic mutation called JAK2V617F. By assessing JAK2V617F, other cancer-linked mutations and hundreds of thousands of other mutations that a person naturally acquires throughout life, the researchers were able to trace the ancestry of different blood cells and estimate the time at which each patient acquired JAK2V617F and other important mutations.

They determined that, in these 10 patients, the first cancer-linked mutations emerged as early as a few weeks after the start of life and up to the first decade of childhood despite clinical disease presenting many decades later in life.

"We were not expecting this," said Dr. Nangalia. "In fact, in one patient, the JAK2 mutation was acquired more than 50 years before their diagnosis."

While it is often assumed that most cancers are diagnosed within a few years of their emergence, the findings point to a more gradual, lifelong process in which a single cell acquires a cancer-linked mutation early in life and then slowly grows over decades, ultimately leading to cancer.

"Some of these cancer-linked mutations are found in healthy individuals as we get older, suggesting that aging causes them," said Dr. Nangalia. "However, aging per se doesn't drive such growth it simply takes a long time for the clones to grow." Sometimes, the growing clones pick up additional cancer-linked mutations along the way, accelerating their growth, researchers found.

"For these patients, we calculated how many of these cancer clones would have been present in the past, and our results suggest that these clones may have been detectable up to 10 to 40 years before diagnosis," said Dr. Nangalia. "In addition to detecting the mutations, the rate at which the mutated clones grew was also very important in determining whether, and when, cancer develops." The findings suggest that genetic testing could help identify people at risk for cancer much earlier than current methods allow, according to researchers.

The next steps would be to understand the factors that influence the different rates of cancer growth and determine whether there could be ways to intervene and slow the growth of cells with cancer-linked mutations. The researchers say their method for pinpointing the origin of this blood cancer could also be applied to other mutations and other blood cancers. "Understanding the timelines of development of different cancers is critical for efforts aimed at early cancer detection and prevention," said Dr. Nangalia.

Jyoti Nangalia, MBBChir,Wellcome Sanger Institute and University of Cambridge, will present this study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

SOURCE American Society of Hematology

http://www.hematology.org

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Researchers Trace the Origin of Blood Cancer to Early Childhood, Decades before Diagnosis - PRNewswire

What started out as a journey to better understand regulatory T cells has now led to an intriguing approach with an investigational cell therapy designed to prevent the risk of graft-versus-host disease (GVHD) and to improve relapse-free survival rates in patients undergoing hematopoietic stem cell transplantation (HSCT).

Data of a phase 1/2 trial recently showed that the first-generation precision cell treatment Orca-T compared with a historical control of standard HSCT demonstrated faster neutrophil (median, 12 days vs 14 days; P < .0001) and platelet engraftment (median, 11 days vs 17 days; P < .0001), decreased incidence of grade 2 or higher GVHD at 100 days (10% vs 30%, P = .005) and chronic GVHD at 1 year (3% vs 46%, P = .0002).1,2

The 1-year GVHD-free and GVHD relapse-free survival (GRFS) rates were 75% with the use of Orca-T vs 31% with standard HSCT (P < .0001). The comparator cohort was derived from contemporaneous patients who had been treated at Stanford University with a conventional allograft.

Along with feasibility of the approach, the results also highlight how Orca-T demonstrates potent anti-leukemic activity in patients who have active disease at HSCT, which suggests that the decrease of GVHD does not impact graft-vs-leukemia (GvL).

That is the most exciting part about the Orca-T story; it is the ability to do this with precision, with speed, and to export it to other sites. The results are intriguing, and very supportive, said Robert Negrin, a professor of medicine (blood and marrow transplantation), and chief of the Division of Blood and Marrow Transplantation at Stanford University.

In an interview with OncLive, Negrin, who is senior author on the trial, shared the evolution of Orca-T as a novel approach to HSCT, highlighted his robust experience with using this cell therapy at Stanford University, and how Orca-T is a potential prevention method for GVHD.

OncLive: Please provide some background to this therapeutic approach. What is the mechanism of action? How is it effective in patients undergoing transplant?

Negrin: This whole idea came from mouse studies many, many years ago, where we identified GVHD as being a dysregulated immune reaction that just keeps going, and going, and going. Like you and I, when we react to something, we have a reactionlet's say, influenza. Our body responds, and then we stop reacting and you get better. With GVHD, what we noticed in using a bioluminescent animal model is that the alloreactive T cells just keep going, going, and going and are unrelenting in mice, just like in people. The problem is very similar and affects certain organs in a very similar way.

Therefore, we went about trying to understand the use of so-called regulatory cells. These are cells that everybody has that help control immune reactions. We just applied them in this clinical scenario, first in mice work done by Matthias Edinger, MD, when he was a postdoctoral fellow many years ago [and other researchers]. All of them were very actively involved in these studies, and showed, somewhat surprisingly, that the administration of regulatory T cells could control this dysregulated immune response that we called GVHD.

Probably more surprising was that, at least in the animal models, it also allowed for the benefits of transplant, namely, the graft-vs-tumor effect and better immune recovery. This was in large part because GVHD also impacts the immune repertoire and where the immunity is developed in the recipient.

All of this was very nice in mouse models and was very elegant. We did a lot of studies, published a number of nice papers, and thought this would be a great idea because it sort of solved, or at least addressed, the principal problems after bone marrow transplantationnamely, avoidance of GVHD yet retention of graft-versus-tumor effects and better immunity. A lot of times, people say, "Oh, that sounds good in mice, but, that's too good to be true." And, theyll ask, "Will that all work in people?"

Where did the biggest challenges lie in this approach?

The big challenge came about to try to apply this to patients. We also have one other interesting point that is relevant. If we gave the regulatory T cells first, before the so-called conventional CD4+/CD8+ cells, that allowed for a lower dose of regulatory T cells. This is because a big challenge is the paucity of these cells; you and I don't have that many.

Then, the other big challenge was the technical ability to isolate in cells. What we do in mice is cell sorting, which is a standard technology. But, that was not developed in people because we're bigthere are a lot of cells, and cell sorting is rather slow, and it's very specific. To get enough cells takes a really long time. It's somewhat of a heroic thing to do in people, to get the adequate amount ourselves; of course, we don't really know what this proper cell dose is.

However, what we thought we learned was that the ratio of conventional to regulatory T cells was the key component. Also, if you give the regulatory T cells first, you can get fewer numbers. Those are things you can do in transplant. You can get the cell from the donor, and you can give cells in a certain sequence; all of those things are very doable. It seemed like an attractive thing to do in patients.

Then, the question was: Does it work? There are 3 groups that have really pioneered this work. The first study came from the University of Perugia in Italy. They did this in haploidentical transplantation; you cannot avoid immunosuppression in haploidentical transplants. They were able to show in several nice papers that you could do this strategy, and seemingly, get away with low risk of GVHD, and also low relapse. This is because the other issue is: how do you measure the graft-vs-tumor effect? There is no assay, and we have no test; you have to wait and see who relapses and who doesn't. Therefore, they also showed rather convincingly that you could reduce GVHD risk, yet, there was a very low risk of relapse in their high-risk patient population. Those were very important [data].

Another study from the University of Minnesota did this with umbilical cord blood. They expanded the regulatory T cells from a third cord blood unit, which is somewhat heroicit is another level of complexity to isolate the cells and then expand them. We did this in matched donorseither matched siblings or matched unrelated donors. We published a paper in JCI Insight several years ago showing the initial results, and they look quite favorable.

Therefore, what I think is most exciting about what Orca Bio has done is they are developing technology to isolate the cells more quickly, to be able to do this on a clinical scale, with precision, and with speed. Also, [they are developing the technology] to be able to distribute it to anybody, because the criticism of all these studies is that, "Oh, that's nice. But, this is a single-institution study. Is this really true? Can this be exported? Could this be something that [an organization] other than these [individual] centers are really focused in this area and have developed these technologies could really do? Orca Bio is developing the technology, and improving the technology, because it's still very cumbersome, and exporting the technology so that you could do this, theoretically, at any center.

That's what I think is most exciting about the Orca Bio abstract; it is demonstrating that this can be done. It certainly opens the door to prevention of GVHD. As we move into an era of using cell-based therapeutics, now, this opens up many other possibilities, because you use these regulatory cells and autoimmune disorders and organ transplant tolerance. There are many other cell types that have potential clinical utility, but getting them, and purifying them, is a big challenge. There are many other possibilities that one could think of.

Obviously, more time will be required to follow these patients, but they certainly are supportive of the idea that you can improve overall outcomes using this strategy. That's what we hope to be able to demonstrate further.

Please focus on the scalability of this approach. Through these types of collaborations, how do you see Orca-T potentially moving through the FDA pipeline?

In academia, we don't develop drugs. It's too much, we don't have the resources, we don't have the capability, and we don't have the monitoring capability that is required for multi-institutional studies. Where these commercial partners come in is, they can raise money for interesting concepts, which Orca Bio has done, and they can export this to other centers, and that's critically important.

As we've seen in the CAR T-cell [therapy] world, that can be a quite successful commercial business. Also going through the process of an FDA approvalwhich Orca Bio is moving along in that processand getting the right designations is critically important to commercial entities. In academia, it's important to us, but that's just not our focus.

We don't have the resources around, the people and the expertise to really drive things through that process. We're good at developing the studies and getting FDA approvals, and [investigational new drug applications], but not really [good at] developing drugs as a commercial entity. This collaboration is key to doing this successfully; for example, at Orca Bio, [they have] technology to separate cells more efficiently and effectively. They also have the resources to do a multi-institutional clinical trial, and the expertise to move something through and present it to the FDA. Those are key components.

Could you expand on the study and respective data from this phase 1/2 trial?

Here at Stanford Cancer Institute, we did find in our patients that giving low doses of immunosuppressive medications with a single agent seem to improve the outcomes, and it's remarkable how well these patients have gone through the transplant. It's a little bit hard to appreciate an abstract until you take care of these patients, and many of them just sort of move to the transplant with relatively little challenges. We have not seen greater risks of things like infection [or] disease recurrence; those are obviously things that will be followed.

When we look at the 1-year GVHD relapse-free survival rate, which is an endpoint that most transplant studies would agree is the most important end point, the overall outcomes are much more favorable compared with a historical control group.

The data are very encouraging, and the overall outcomes look very strong in a reasonable number of patients now. We think it's important for the community to hear about it, and to get it on everybody's radar, and be excited about trying to move this forward as a more standard therapy. This is still a clinical trial, so it's not, it's not part of any standard therapies yet. We are using this quite regularly and have been very encouraged by the ease of which patients go through the transplant. It's still an allogeneic transplant; there still are many challenges there. However, these patients seem to be doing quite well, we're very encouraged, and so we keep going.

How does this approach impact patient outcomes as it relates to quality of life (QoL)?

The hard end points of 1-year relapse-free survival is obviously the most important to patients. However, going through an allogeneic transplant is obviously an incredibly difficult thing. Fortunately, I've only seen it [from] the doctor side, not [as a] patient.

However, I've seen many, many patients, and the quality of their life as they go through this experience is very important to all of us. As we saw these patients go through these studies, we felt like we were capturing something that was really important, and that is the ease [at which] many patients went through this experience, which just seemed different. It's hard to capture that.

It's really important for patients to speak and, and the way patients speak is in different ways. One way is through the QoL measures that they answer. This is [what they find] important, this is what they experiencednot what we say is happening. That's really important to hear that voice too. Those are data we're trying to collect. It's not so easy, because going through a bone marrow transplant is a poor QoL for everybody. But, by just to trying to capture this, [Orca-T seems] better than what we what we thought.

How has this changed the mindset of cell-based approaches in the community?

What has changed is the belief in the concept of cell-based therapies. A lot of these things are somewhat fanciful. It is also important to show that we can translate from an animal model [to a human]. There is a lot of criticism of animal modeling, because people say, "Well, it's nice for animal models, but it doesn't really translate into the clinic." Actually, my view is that because we don't actually follow the animal models, there are many compromises one needs to make. When you translate studies from animals to humans, there are many differences, and it's really important to try to follow them as carefully as you can within the limitations of what is possible. We were very engaged in that and tried to follow as carefully as we could. To me, that is very encouragingthat you can study things in animals that generate new concepts and be able to translate that into a clinical trial.

Obviously, with all of the caveats of an early-phase clinical trial, more time needs to pass, more patients to be treated, and you need to export [the treatment] to other centers. That's a really important point, because there are many things that get lost because, "it's too complicated. It's too expensive. People can't do it." I don't think anybody can do high-speed cell sorting, as a clinical project in a standard or standard cell-processing laboratory. It's above the level of what most processing laboratories can do.

References

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Negrin Shines Light on the Orca-T Story in GVHD - OncLive

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, today announced final clinical results from its earlier completed Phase 1 clinical trial as well as development updates for its MGTA-145 stem cell mobilization therapy, including commencement of enrollment in a Phase 2 clinical trial in multiple myeloma, and its plans for a Phase 2 clinical trial in allogeneic stem cell transplant for patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS). The company also previously announced a clinical collaboration with bluebird bio to evaluate MGTA-145 for mobilizing and collecting stem cells in adults and adolescents with sickle cell disease (SCD). Additional preclinical results were also presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020, on the Magenta conditioning platform, including MGTA-117 program, which is a targeted antibody-drug conjugate (ADC) to prepare patients for stem cell transplant.

MGTA-145 Advancement to Phase 2 Development in Blood Cancers

The company announced that enrollment has started and is ongoing in a Phase 2 clinical trial of MGTA-145, used in combination with plerixafor, to mobilize and collect stem cells for autologous stem cell transplantation of multiple myeloma patients at Stanford University. Magenta expects that this trial will provide patient-level data on stem cell mobilization and collection, characteristics of the mobilized graft and engraftment in patients with multiple myeloma.

Additionally, through a collaboration with the National Marrow Donor Program/Be The Match, a global leader in facilitating allogeneic hematopoietic stem cell transplantation, Magenta plans to initiate a Phase 2 clinical trial in early 2021 using MGTA-145 to mobilize and collect stem cells from allogeneic donors for transplant in patients with AML, ALL and MDS. Allogeneic stem cell transplant provides a potentially curative therapeutic option for patients with these diseases. This clinical trial will evaluate stem cell mobilization, collection, cell quality, engraftment and the potential for reduced Graft-versus-Host Disease (GvHD), which is of particular importance in the allogeneic transplant setting.

MGTA-145 in Sickle Cell Disease

Magenta Therapeutics recently announced an exclusive clinical collaboration with bluebird bio to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in adults and adolescents with SCD.

The data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. bluebird bios experience with plerixafor as a mobilization agent in SCD aligns with Magentas combination therapy approach, utilizing MGTA-145 plus plerixafor with potential for safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

MGTA-145 Presentations at ASH

Magenta presented final clinical data from its MGTA-145 stem cell mobilization Phase 1 clinical trial in healthy volunteers at the ASH Annual Meeting. All primary and secondary endpoints were met in the study completed earlier this year.

The results demonstrate that a single dose of MGTA-145, in combination with plerixafor, rapidly and reliably mobilized high numbers of stem cells in a single day without the need for G-CSF for potential use in diseases that can benefit from autologous and/or allogeneic stem cell transplantation. The additional data also offer further confirmation that MGTA-145, in combination with plerixafor, was well tolerated and provides a rapid and reliable method to obtain large numbers of hematopoietic stem cells. Transplant of these cells in preclinical models resulted in enhanced, durable engraftment, in addition to highly immunosuppressive properties, leading to reduced GvHD.

Results from this study provide a robust dataset and proof of concept that MGTA-145, in combination with plerixafor, provides rapid and robust mobilization of stem cells and that these cells have better engraftment potential, are able to be gene modified and engraft and reduce GvHD in preclinical models compared to cells mobilized with other available agents. The data reinforce the availability of compelling opportunities for development in both the autologous and allogeneic transplant settings, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics.

The data were presented by Steven M. Devine, MD, Chief Medical Officer of the National Marrow Donor Program/Be The Match and Associate Scientific Director of the CIBMTR (Center for International Blood and Marrow Transplant Research).

Conditioning Program (MGTA-117 and CD45-ADC) Presentations at ASH

Magenta also provided updates on its conditioning platform at the ASH Annual Meeting, including MGTA-117 and CD45-ADC programs. Preclinical data from a study of MGTA-117 demonstrate that it is an effective, potent conditioning agent for transplant with anti-leukemic activity, significantly decreasing tumor burdens, leading to delayed tumor growth and increased median survival rates in animal models of AML. Ongoing GLP toxicology and GMP manufacturing progress continue to be supportive of advancing MGTA-117 towards an IND filing in AML and MDS.

Additionally, preclinical data from a study of Magentas CD45-ADC, a CD45-targeted conditioning agent designed to remove the cells that cause autoimmune diseases to enable curative immune reset, demonstrated the ability to achieve successful outcomes as a single agent in the most challenging disease model through fully mismatched allogeneic hematopoietic stem cell transplant, where only radiation or combinations of toxic chemotherapies are available, potentially providing patients the option of a reduced toxicity conditioning regimen. The company continues to evaluate this program preclinically.

About MGTA-145

MGTA-145 is being developed in combination with plerixafor to harness complementary chemokine mechanisms to mobilize hematopoietic stem cells for collection and transplantation. This new combination has the potential to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells to improve outcomes in autologous and allogeneic stem cell transplantation, which can rebuild a healthy immune system for patients with blood cancers, genetic diseases and autoimmune disorders.

MGTA-145 has the potential to replace the current standard of care for patients and allogeneic donors who currently rely on the use of granulocyte-colony stimulating factor (G-CSF) alone or in combination with plerixafor, which can take up to five days or longer to mobilize sufficient numbers of stem cells, often resulting in significant bone pain and other side effects.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with blood cancer, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145...

JERUSALEM, Dec. 8, 2020 /PRNewswire/ --NeuroGenesis, a clinical-stage biopharmaceutical company advancing innovative cell therapies to combat myelin-related neurodegenerative diseases, and Hadassah Medical Center announced today highly positive results from a placebo-controlled Phase 2 clinical trial, headed by Prof. Dimitrios Karussis, together with Dr. Petrou Panayiota and Dr. Ibrahim Kassis from Hadassah Medical Center in Jerusalem, assessing the impact of NG-01 autologous proprietary subpopulation of mesenchymal stem cells (MSCs) on patients with progressive multiple sclerosis (MS).

The results, recently published in Brain, a prestigious peer-reviewed journal published by Oxford University, and highlighted in the "Editor's Choice", show that:

"The treatment was well tolerated and the trial met all of its primary endpoints," said Professor Dimitrios Karussis, lead principle investigator and Director of MS Center at Hadassah Medical Center, Jerusalem. "The patients' improvement was in many cases quite remarkable and included regain of motor function and noticeable effects on their cognitive abilities."

Prof Karussis added, "Although we currently have several good treatment options for relapsing remitting MS, we fall short in providing effective treatment for progressive MS that could substantially suppress the progression of disability. This trial provides encouraging results and suggests a potential for a new approach that may not only slow down the progression of the disease but even induce improvement and promote repair mechanisms in progressive MS."

The technology is now further developed by NeuroGenesis, following a license from Hadasit, Hadassah Medical Center Technology Transfer Company.

Neurogenesis' technology entails collecting bone marrow from the patient. Then by utilizing a proprietary process, a unique subpopulation of bone marrow cells is identified, cultured and enhanced towards remyelinating biofactory cells (NG-01) that also possess neurotrophic immunolatory and neuroprotective properties. The NG-01 cell population is injected directly into the central nervoussystem (through the cerebrospinal fluid), where the cells home-in on the damaged area, take up residence and produce significant amounts of neurotrophic factors.

"Progressive MS is a chronic, debilitating disease with no satisfactory treatment to improve or reverse established disability," said Tal Gilat, CEO of NeuroGenesis. "We are therefore extremely pleased to witness the significant positive effect of our NG-01 cells. Following recent interactions with the FDA, we look forward to confirming and expanding these findings in a large multi-center MS trial, and continuing advanced studies in additional indications such as ALS."

About the Phase 2 trial of NG-01

The Phase 2, randomized, double-blind, placebo-controlled, clinical trial assessed the safety, tolerability and efficacy of transplantation of NG-01 in people with progressive MS. The study enrolled 48 participants with progressive MS which were randomized into 3 groups, receiving either an intrathecal or intravenous NG-01 injection, or a placebo injection.

The two predetermined primary endpoints of the trial were: (i) the safety of the intrathecal and intravenous NG-01 treatments assessed by incidence of adverse events versus those in the placebo-treated group; and (ii) the differences among the three groups in the Expanded Disability StatusScale(EDSS) score changes and the proportion of patients with treatment failure, as evidenced by an increase in EDSS (disease progression) score, at 6 and 12 months. Overall, the study duration was 14 months.

About Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease that causes damage in the myelin and the nerve cells of the central nervous system (demyelinating plaques in brain and spinal cord), resulting in cumulating neurological disability. The destruction of the myelin (the covering that protects nerves and promotes the efficient transmission of nerve impulses) causes secondary damage to the nerve cells and progressive atrophy. MS often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Motor problems are common in people with MS. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or paralysis of the muscles of the limbs, difficulty in walking, and poor sphincter control. The condition is also associated with visual problems, such as blurred or double vision or partial or complete vision loss. There is no known cure for multiple sclerosis.The existing treatments are mostly aimed to reduce the incidence of relapses of the disease and slow down the rate of neurological deterioration.

About NeuroGenesis

Neurogenesis is developing cell therapy for neurodegenerative diseases based on a unique approach for sustained delivery of high levels of remyelinating growth factors using the patient's own stem cells. The technology for this unique approach was licensed from Hadasit, theTechnology TransferCompany of Hadassah Medical Organization in Jerusalem, Israel. The Company's lead product is NG-01 for the treatment of progressive Multiple Sclerosis, (in which a placebo-controlled Phase 2 study has been completed and recently published). NG-01 were also tested in two successful Phase 2a trials in ALS patients. Up to today, more than 150 progressive MS and ALS patients from around the world have been treated with Neurogenesis'products via clinical trials (Phase 1 and Phase 2) and compassionate use treatments.

About Hadassah and Hadasit

For more than a century, Hadassah has set the standard of excellence for medical care and research in Israel. Our doctors and scientists are on the frontlines, uniquely positioned to pinpoint ever-evolving medical needs. Their experience and ingenuity have yielded new ideas with huge potential in all areas of medicine, including therapeutics, diagnostic medical devices, and digital health. Hadasit is the technology transfer company of Hadassah Medical Center in Jerusalem. We transform the cutting-edge research coming out of Hadassah into marketable medical technologies. We turn ground-breaking ideas into viable products and services that can change the world and better humanity.

NeuroGenesiscontact:Tsipi HaitovskyGlobal Media LiaisonNeuroGenesis+972-52-5989-892[emailprotected]

Hadassah contact:Hadar ElboimspokeswomanHadassah Medical Organization+ 972- 2-6776079[emailprotected]

SOURCE NeuroGenesis

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Hadassah Medical Center and Neurogenesis Announce Groundbreaking Results from a Phase 2 Study in Progressive Multiple Sclerosis treated with NG-01...

The following article features coverage from the ASH 2020 virtual meeting. Click here to read more of Oncology Nurse Advisors conference coverage.

Patients who received venetoclax with azacytidine for the treatment of higher-risk myelodysplastic syndrome (HR-MDS) had high overall survival rates and clinically meaningful improvements of dyspnea and fatigue through 48 weeks. These findings were presented during the American Society of Hematology (ASH) 62nd Annual Meeting and Exposition.

Jacqueline S. Garcia, MD, coauthor of this study, explained the mechanism of this therapy. Apoptosis is normally under tight control by the interaction between pro-survival and pro-biotic proteins. In HR-MDS, myeloblasts overexpress BCL-2 and blasts are generally highly prone to pro-apoptotic proteins. Azacytidine indirectly decreases other apoptotic proteins, which sensitizes cells to venetoclax. Venetoclax is a BCL-2 inhibitor, which induces death. Thus, these drugs have the potential to irreversibly commit the cell to death.

Patients (N=78) with HR-MDS who were not candidates for intensive chemotherapy were recruited for this ongoing, open-label, dose-escalation, phase 1b study. Study participants received venetoclax 400 or 800 mg for 28 days followed by an escalating dose (100, 200, and 400 mg) for 14 days in a 28-day cycle with azacitidine 75 mg/m2 subcutaneously or intravenously administered on the first 7 days of each cycle. Participants were assessed for adverse events and efficacy.

Patient group was 75% men, median age 71 years (range, 26 to 85) and 56% had very high-risk disease.

Of the 31 patients with baseline marrow data, the most frequent mutations were located in tumor protein p53 (TP53; 35.5%), additional sex combs like 1 (ASXL1; 19.4%), and stromal antigen 2 (STAG2; 16.1%).

All participants experienced at least 1 adverse event during the study. The most commonly observed events were constipation (54%), nausea (55%), and neutropenia (83%). Adverse events grade 3 or higher were experienced by 96% of patients and included febrile neutropenia (49%) and thrombocytopenia (42%). Few infections were observed, likely due to the antibiotic prophylaxis.

At 30 days, the mortality rate was 1% and 1.3% experienced disease progression. A total of 16 patients received post-study transplants (bone marrow, 7 patients; stem cell, 9 patients).

The objective response rate was 79%; in which 39.7% entered into complete remission, 39.7% into marrow complete remission, and 14.1% had stable disease.

The median duration of response was 12.9 months (range, 12.1 to 16.8), and among those who achieved complete remission, the median duration of response after remission was 13.8 months (range, 6.5 to 20.9). The median time to complete remission was 2.6 months (range, 1.2 to 19.6).

Physical function through 48 weeks was generally maintained and fatigue, dyspnea, and global health quality of life were improved among patients who received 400 mg of venetoclax for 14 days.

This study was limited by its small sample size and short duration; however, this study was still on-going, and a phase 3 trial has begun.

These results indicated venetoclax with azacitidine was efficacious, allowing for maintenance of physical functioning for up to 48 weeks among patients with HR-MDS who were not candidates for intensive chemotherapy.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Garcia JS, Wei AH, Borate U, et al. Safety, efficacy, and patient-reported outcomes of venetoclax in combination with azacitidine for the treatment of patients with higher-risk myelodysplastic syndrome: a phase 1b study. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstr 656.

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Venetoclax/Azacitidine Combination Efficacious for the Treatment of Older Patients With Higher-Risk Myelodysplastic Syndrome - Oncology Nurse Advisor

NEW YORK--(BUSINESS WIRE)--Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, today presents updated interim data from its Fanconi Anemia (FA) and Leukocyte Adhesion Deficiency-I (LAD-I) programs at the 62nd American Society of Hematology (ASH) Annual Meeting. The data are highlighted in two oral presentations.

We are highly pleased with the data presented at ASH demonstrating ongoing evidence of efficacy and durability using Process B in both FA and LAD-I as we move towards potential registration, said Gaurav Shah, M.D., Chief Executive Officer and President of Rocket. Follow-up data from the Phase 1 and 2 trials for FA continue to support RP-L102 as a potential hematologic treatment option in the absence of cytotoxic conditioning. In five of the seven patients treated as of October 2020, there was evidence of engraftment. In addition, stabilization of peripheral blood counts in two of the three patients with at least 12-month follow-up, which declined substantially in these patients prior to gene therapy, suggests a halt in bone marrow failure progression. We look forward to reporting longer-term follow-up on these patients in the first half of 2021.

Dr. Shah continued, Additionally, we continue to see encouraging evidence of efficacy for RP-L201 for the treatment of LAD-I. Patients have shown sustained CD18 expression of 23% to 40%, far exceeding the 4-10% threshold associated with survival into adulthood. These data, on top of our exciting results from our lentiviral program for PKD, show our steady progress across three of our five gene therapy programs. We are proud of this progress and are committed to advancing our investigational gene therapies through development for patients and families facing these devastating disorders.

Key findings and details for each presentation are highlighted below. To access the presentations at the conclusion of the oral presentation, please visit: https://www.rocketpharma.com/ash-presentations/

Gene Therapy for Fanconi Anemia, Complementation Group A: Updated Results from Ongoing Global Clinical Studies of RP-L102The data presented in the oral presentation are from seven of the nine patients treated as of the cutoff date of October 2020 in both the U.S. Phase 1 and global Phase 2 studies of RP-L102 for FA. Seven patients had follow-up data of at least 2-months, and three of the seven patients had been followed for 12-months or longer. Key highlights from the presentation include:

Presentation Details:Title: Gene Therapy for Fanconi Anemia, Complementation Group A: Updated Results from Ongoing Global Clinical Studies of RP-L102Session Title: Gene Editing, Therapy and Transfer IPresenter: Agnieszka Czechowicz, M.D., Ph.D., Assistant Professor of Pediatrics, Division of Stem Cell Transplantation, Stanford University School of MedicineSession Date: Monday, December 7, 2020Session Time: 11:30 a.m. - 1:00 p.m. (Pacific Time)Presentation Time: 12:15 p.m. (Pacific Time)

Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Results from Phase 1The data presented in the oral presentation are from three pediatric patients with severe LAD-I, as defined by CD18 expression of less than 2%. The patients were treated with RP-L201, Rockets ex-vivo lentiviral gene therapy candidate. Patient L201-003-1001 was 9-years of age at enrollment and had been followed for 12-months as of a cutoff date of November 2020. Patient L201-003-1004 was 3-years of age at enrollment and had been followed for over 6-months. Patient L201-003-2006 was 7-months of age at enrollment and was recently treated with RP-L201. Key highlights from the presentation include:

Rockets LAD-I research is made possible by a grant from the California Institute for Regenerative Medicine (Grant Number CLIN2-11480). The contents of this press release are solely the responsibility of Rocket and do not necessarily represent the official views of CIRM or any other agency of the State of California.

Presentation Details:Title: Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Results from Phase 1Session Title: Gene Editing, Therapy and Transfer IPresenter: Donald Kohn, M.D., Professor of Microbiology, Immunology and Molecular Genetics, Pediatrics (Hematology/Oncology), Molecular and Medical Pharmacology, and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los AngelesSession Date: Monday, December 7, 2020Session Time: 11:30 a.m. - 1:00 p.m. (Pacific Time)Presentation Time: 12:30 p.m. (Pacific Time)

Conference Call DetailsRocket management will host a conference call and webcast today December 7, at 6:00 p.m. EST. To access the call and webcast, please click here. The webcast replay will be available on the Rocket website following the completion of the call.

Investors may listen to the call by dialing (866) 866-1333 from locations in the United States or +1 (404) 260-1421 from outside the United States. Please refer to conference ID number 50038102

About Fanconi AnemiaFanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have a Fanconi Anemia complementation group A (FANCA) gene mutation, which encodes for a protein essential for DNA repair. Mutation in the FANCA gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Increased sensitivity to DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is a gold standard test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patients blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as natural gene therapy provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells.

About Leukocyte Adhesion Deficiency-ISevere Leukocyte Adhesion Deficiency-I (LAD-I) is a rare, autosomal recessive pediatric disease caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is a key protein that facilitates leukocyte adhesion and extravasation from blood vessels to combat infections. As a result, children with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75% prior to the age of 2 and survival beyond the age of 5 is uncommon. There is a high unmet medical need for patients with severe LAD-I.

About Rocket Pharmaceuticals, Inc.Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket) is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, Pyruvate Kinase Deficiency (PKD) a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia and Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. Rockets first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. For more information about Rocket, please visit http://www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking StatementsVarious statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding its guidance for 2020 in light of COVID-19, the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon Disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket's ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rockets ongoing trials, our expectations regarding the delays and impact of COVID-19 on clinical sites, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed November 6, 2020 with the SEC. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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Rocket Pharmaceuticals Presents Positive Clinical Data from its Fanconi Anemia and Leukocyte Adhesion Deficiency-I Programs at the 62nd American...

GERMANTOWN, Md., Dec. 7, 2020 /PRNewswire/ -- Precigen Inc., a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced at the 62nd ASH Annual Meeting and Exposition (Abstract 2864) clinical progress and new data from the ongoing Phase 1/1b clinical study of PRGN-3006UltraCAR-Tin patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) and higher risk myelodysplastic syndrome (MDS) (clinical trial identifier: NCT03927261).

AML is a rapidly progressing disease with poor prognosis and high unmet need. Precigen's UltraCAR-T platform is designed to overcome limitations of currently available chimeric antigen receptor (CAR)-T therapies by utilizing an advanced overnight non-viral gene delivery manufacturing process at a medical center's cGMP facility without the need for ex vivo expansion. Current CAR-T cell therapies are limited due to, inter alia, the prolonged interval between apheresis to product infusion and an exhausted phenotype of T cells resulting from lengthy ex vivo expansion. As announced in November 2020, UltraCAR-T cells for the PRGN-3006 study are now manufacturedovernight using Precigen's proprietary UltraPorator device. PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T simultaneously expressing a CAR specifically targeting CD33; membrane bound IL-15 (mbIL15) for enhanced in vivo expansion and persistence; and a kill switch to conditionally eliminate CAR-T cells for an improved safety profile. CD33 is over-expressed on AML blasts with lesser expression on normal hematopoietic stem cells.

An investigator-initiated, non-randomized Phase 1/1b dose-escalation study to evaluate the safety and maximal tolerated dose of PRGN-3006 UltraCAR-T is currently ongoing in collaboration with the H. Lee Moffitt Cancer Center & Research Institute (Moffitt). The study population includes adult patients ( 18 years) with r/r AML and hypomethylating agent (HMA) failure, higher risk MDS or chronic myelomonocytic leukemia (CMML) patients with 5% blasts. To test the hypothesis that expression of mbIL15 on PRGN-3006 can promote UltraCAR-T cell expansion and persistence without the need for lymphodepletion and improve the overall safety profile, studysubjects receive the PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2). A multicenter expansion of the trial is planned.

Key findings:

A case study of the patient with the longest follow-up as of the data cutoff was also presented. This patient received, one day after gene transfer and without prior lymphodepletion, a very low dose, approximately three hundred thousand UltraCAR-T per kilogram (3 x 105 UltraCAR-T/kg) for a total of only 24 million UltraCAR-T. She is a 69 year old female with secondary AML (sAML) and four prior lines of therapy, including induction chemotherapy (IC), allogenic hematopoietic stem cell transplantation (allo-HSCT), HMA plus venetoclax (HMA+VEN), refractory to all therapy post allo-HSCT. The patient had approximately 40% peripheral blasts and 47% bone marrow blasts at baseline.

Case study findings:

"There is an urgent need for novel therapies for relapsed or refractory AML patients as the median overall survival for this patient population is less than six months. Current CAR-T approaches for AML have faced challenges due to long manufacturing durations resulting in subsequent delays in treatment," said David A. Sallman, MD, of Moffitt and lead investigator for the PRGN-3006 clinical study. "We are encouraged by the initial data, including safety and manufacturing success from patients treated with autologous UltraCAR-T cells, which were manufactured on-site with almost instant turnaround. We are excited by the expansion and continued persistence of PRGN-3006 UltraCAR-T cells in the patient case study for over seven months post-infusion without prior lymphodepletion and are looking forward to higher doses in the lymphodepleted and non-lymphodepletion cohorts."

"Currently commercialized CAR-T therapies have not demonstrated the persistence needed to drive sustained, durable responses," said Helen Sabzevari, PhD, President and CEO of Precigen. "The results from Dr. Sallman's patient case study are particularly encouraging as the patient received a very low dose of cells without any ex vivo expansion or activation and no lymphodepletion, which highlights the importance of membrane bound IL-15 in expansion and persistence of these cells and, we believe, differentiates the UltraCAR-T platform from other CAR-T's. In particular, expansion and persistence of UltraCAR-T cells in the patient's blood through seven months post-infusion show promise for the durability of PRGN-3006. We look forward to providing additional details for the PRGN-3006 study at our upcoming clinical update call this month."

About Acute Myeloid Leukemia (AML)AML is a cancer that starts in the bone marrow, but most often moves into the blood.1 Though consideredrare, AML is among the most common types of leukemia in adults.2 In 2019, it was estimated that 21,450 new cases of AML would be diagnosed in the US.2 AML is uncommon before the age of 45 and the average age of diagnosis is about 68.2 The prognosis for patients with AML is poor with an average 5year survival rate of approximately 25 percent overall, and less than a 5 percent 5year survival rate for patients older than 65.3 Amongst elderly AML patients ( 65 years of age), median survival isshort, ranging from 3.5 months for patients 65 to 74 years of age to 1.4 months for patients 85 years of age.3

About Myelodysplastic Syndrome (MDS)MDS are diseases of the bone marrow generally found in adults in their 70s.4 Incidence in the US is not known for sure, but estimates range from 10,000 each year and higher.4 Using International Prognostic Scoring System (IPSS-R), median survival for MDS patients can vary from less than one year for the "very high" IPSS-R risk group to more than eight years for the "very low" IPSS-R group.4

About PRGN-3006 UltraCAR-TPRGN-3006 UltraCAR-T is a multigenic autologous CAR-T cell treatment utilizing Precigen's non-viral Sleeping Beauty system to simultaneously express a CAR specifically targeting CD33, which is over expressed on acute myeloid leukemia blasts with lesser expression on normal hematopoietic stem cell populations and minimal non-hematopoietic expression; membrane bound IL-15 for enhanced in vivo expansion and persistence; and a kill switch to conditionally eliminate CAR-T cells for animproved safety profile. PRGN-3006 is being evaluated in collaboration with the Moffitt Cancer Center in a nonrandomized, investigatorinitiated Phase 1/1b dose escalation study to evaluate the safety and maximal tolerated dose of PRGN3006 UltraCAR-T (clinical trial identifier: NCT03927261). The study population includes patients with relapsed or refractory acute myeloid leukemia or higher risk myelodysplastic syndrome. The US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) for PRGN-3006 UltraCAR-T in patients with AML.

Precigen: Advancing Medicine with PrecisionPrecigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit http://www.precigen.com or follow us on Twitter @Precigen and LinkedIn.

TrademarksPrecigen, UltraCAR-T, UltraPorator and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking StatementsSome of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company's current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company's business, including the timing and progress of preclinical studies, clinical trials, discovery programs and related milestones, the promise of the Company's portfolio of therapies, and in particular its CAR-T therapies, and the Company's refocus to a healthcare-oriented business. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties, including the possibility that the timeline for the Company's clinical trials might be impacted by the COVID-19 pandemic, and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

References1 American Cancer Society. What is Acute Myeloid Leukemia (AML)?2 American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML)3 Thein, M., et al., Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer, 2013. 119(15): p.2720-74 American Cancer Society.Key Statistics for Myelodysplastic Syndromes

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SOURCE Precigen, Inc.

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Precigen Presents New Data Supporting the Safety, Clinical Activity, Expansion and Persistence of PRGN-3006 UltraCAR-T at the 62nd ASH Annual Meeting...

NEW YORK, Dec. 10, 2020 (GLOBE NEWSWIRE) -- BeyondSpring (the Company or BeyondSpring) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced the new data from its Phase 3 PROTECTIVE-2 Study 106 demonstrating that plinabulin in combination with pegfilgrastim offers greater protection against chemotherapy-induced neutropenia (CIN) than the standard of care, pegfilgrastim alone. The study not only met the primary and key secondary objectives, as previously disclosed on Nov. 16, 2020, but also demonstrated that the combination was 53% more effective than pegfilgrastim alone in reducing the incidence of profound neutropenia (absolute neutrophil count or ANC < 0.1 x 10E9 cells/L), 21.6% vs. 46.4%, respectively, p=0.0001, in patients with breast cancer undergoing chemotherapy with TAC (docetaxel, doxorubicin, and cyclophosphamide). Profound neutropenia (PN) is a well-known risk factor to increase the rates of infection, febrile neutropenia (FN), and hospitalization among patients undergoing chemotherapy. Of clinical importance, the combination has shown to reduce the odds of having FN by 41% in comparison to pegfilgrastim, based on reduction of profound neutropenia.

It is clinically meaningful to reduce FN risk by 41% in the combination, compared to pegfilgrastim alone, which is the only major breakthrough advancement in CIN prevention in the last 30 years. The CIN protection from plinabulin added to pegfilgrastim, particularly in the first week of chemotherapy when 75% of CIN-related complications occur before the effect of pegfilgrastim kicks-in in Week 2, fills the treatment gap in current standard of care, said Douglas Blayney, M.D., Professor of Medicine at Stanford Medical School, and global PI for the plinabulin CIN studies. The combination of plinabulin with pegfilgrastim represents a major advancement in offering protection against CIN, with the potential to reduce FN risk, in the care of cancer patients.

The data were presented via a poster at the 2020 San Antonio Breast Cancer Symposium (SABCS): Superior and Clinically Meaningful Protection Against Profound Neutropenia with the Plinabulin/Pegfilgrastim (Plin/Peg) Combination versus Peg In Breast Cancer Patients ReceivingTAC Chemotherapy. Profound neutropenia, an exploratory endpoint representing the most severe form of CIN, is associated with significant risk to patients and may require antibacterial or antifungal prophylaxis [Flowers JCO 2013]. It is attributed to both febrile neutropenia (48%) and infection (50%) [Bodey Cancer 1978]. In BeyondSprings PROTECTIVE-2 studies, patients with profound neutropenia had close to nine times the risk of FN compared to patients with no profound neutropenia. The new data presented at SABCS included:

This trial is a global, multicenter, randomized, double-blinded study in patients with breast cancer undergoing myelosuppressive chemotherapy with TAC (docetaxel at 75 mg/m2, doxorubicin at 50 mg/m2, and cyclophosphamide at 500 mg/m2) for the evaluation of protection against CIN, comparing plinabulin (40 mg) in combination with pegfilgrastim (6 mg) in 111 patients to pegfilgrastim alone (6 mg) in 110 patients. On Day 1, they received TAC and plinabulin or placebo, and on Day 2, they received pegfilgrastim. Topline data from the Protective-2 Phase 3 trial were reported on November 16, 2020 highlighting that the study met its primary endpoint as well as key secondary endpoints.

It is well recognized that CIN is directly related to chemotherapys ability to kill rapidly dividing cells. Unfortunately, fast dividing neutrophils in the bone marrow are adversely affected regardless of the chemotherapy type. As a result, we believe these outcomes are universally applicable to any chemotherapy, and are independent of cancer types, added Gordon Schooley, Ph.D., BeyondSprings Chief Regulatory Officer. As both the U.S. FDA and China NMPA recently awarded BeyondSprings Plinabulin CIN program with Breakthrough Therapy Designation status based on the interim phase 3 data of PROTECTIVE-2, and the Company now completing the PROTECTIVE-2 trial with positive and consistent results to the interim, we are well on track to submit our NDA for CIN in Q1 2021. The improved CIN prevention benefit of the Plinabulin/G-CSF combination would have the potential for CIN prevention of the myelosuppressive effects of different chemotherapeutic agents in millions of patients with multiple tumor types.

Ramon Mohanlal, M.D., Ph.D., BeyondSprings Chief Medical Officer and Executive Vice President, Research and Development concluded, Plinabulin represents a new treatment paradigm for CIN prevention, an area wherein G-CSF has established efficacy, but with short-comings due to its delayed onset of action, next day dosing requirement, bone pain induction, and platelet count reduction. Plinabulin has a fast onset mechanism of action, without causing relevant bone pain or thrombocytopenia, and can be given on the same day as chemotherapy. Plinabulin added to G-CSF offers superior prevention of CIN, and has the potential to avoid life-threatening infections and to improve short-term and long-term survival. Plinabulins anticancer activity from its immune-enhancing mechanism of action, together with its CIN preventive effects, has the potential to become a universal add-on to anti-cancer treatments in general.

The above data are available on BeyondSpringswebsite in the Posters section.

About PlinabulinPlinabulin, BeyondSprings lead asset, is a differentiated immune and stem cell modulator. Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia (CIN). The durable anticancer benefits of Plinabulin have been associated with its effect as a potent antigen-presenting cell (APC) inducer (through dendritic cell maturation) and T-cell activation (Chem and Cell Reports, 2019). Plinabulins CIN data highlight the ability to boost the number of hematopoietic stem / progenitor cells (HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs could explain the ability of Plinabulin not only to treat CIN, but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.

About CINPatients receiving chemotherapy typically develop chemotherapy-induced neutropenia (CIN), a severe side effect that increases the risk of infection with fever (also called febrile neutropenia, or FN), which necessitates ER/hospital visits. The updated National Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylactic G-CSFs, such as pegfilgrastim, to include not only high- risk patients (chemo FN rate>20%), but also intermediate-risk patients (FN rate between 10-20%) to avoid hospital/ER visits during the COVID-19 pandemic. The revision of the NCCN guidelines effectively doubles the addressable market of patients who may benefit from treatment with plinabulin, if approved, to approximately 440,000 cancer patients in the U.S. annually. Plinabulin is designed to provide protection against the occurrence of CIN and its clinical consequences in week 1, for early onset of action after chemotherapy. CIN is the primary dose-limiting toxicity in cancer patients who receive chemotherapy treatment.

About BeyondSpringBeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative cancer therapies. BeyondSprings lead asset, plinabulin, a first-in-class agent as an immune and stem cell modulator, is in a Phase 3 global clinical trial as a direct anticancer agent in the treatment of non-small cell lung cancer (NSCLC) and Phase 3 clinical programs in the prevention of CIN. The U.S. FDA granted Breakthrough Therapy designation to plinabulin for concurrent administration with myelosuppressive chemotherapeutic regimens in patients with non-myeloid malignancies for the prevention of chemotherapy-induced neutropenia (CIN). BeyondSpring has strong R&D capabilities with a robust pipeline in addition to plinabulin, including three immuno-oncology assets and a drug discovery platform using the protein degradation pathway, which is being developed in a subsidiary company, Seed Therapeutics, Inc. The Company also has a seasoned management team with many years of experience bringing drugs to the global market. BeyondSpring is headquartered in New York City.

Cautionary Note Regarding Forward-Looking StatementsThis press release includes forward-looking statements that are not historical facts. Words such as "will," "expect," "anticipate," "plan," "believe," "design," "may," "future," "estimate," "predict," "objective," "goal," or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring's current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company's future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet our expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSprings most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law.

Media Contacts

Investor Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 617-430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, Ph.D.LifeSci Communications+1 646-627-8387darren@lifescicomms.com

Link:
BeyondSpring Announces New Positive PROTECTIVE-2 Phase 3 Registrational Trial Results at the 2020 San Antonio Breast Cancer Symposium - BioSpace

Thats how Valerie Mitchell of Joliet is expressing the pre-holiday news that her son Owen Buell, 2, is showing no evidence of disease in regards to the neuroblastoma hes been fighting all year.

We are really happy, Mitchell said. I still cannot believe he is cancer-free. Everyone is really overjoyed about it, especially being around Christmastime.

On Friday, Owen had a number of scans including CT MRI, MIBG and an echocardiogram, along with bone marrow and hearing tests. Mitchell said. All scans came back clear, she said.

He fought as hard as he could and beat cancer, Mitchell said.

But Owen must remain cancer-free for the next five years before the word remission can be used, she said. In addition, Owen also has more treatments ahead of him: six months of immunotherapy, which Mitchell said will be extremely painful and hard on the body.

Owen will need a five to six-day stay in the hospital each month and a pain pump just to receive the treatments, Mitchell said. But the treatment is necessary to eliminate any remaining cancer cells in Owens body; otherwise new tumors or spots of cancer may form.

Were all really tired, Mitchell said. But we can push through knowing that hes going to be cancer-free. Its just one more step and then he should be good.

When Owen was diagnosed in February, he had two tumors and 21 spots of cancer, Mitchell said. His father Brian was working a job and a half at the time and he and Mitchell shared the family van.

Since then, Owen has undergone many scans, a central line placement, five rounds of chemotherapy, surgery to remove tumors, a stem cell harvest, two stem cell transplants that required a three-month hospital stay, 12 rounds of radiation and 10 days of being intubated in the hospitals intensive care unit, Mitchell said.

Owen now also has damage to one kidney and high blood pressure, Mitchell said. The COVID-19 pandemic made treatments even harder on Owen and his family, she added, especially since Owen's brothers Elliott and Bentley, age 4.were just 7 and 4 when Owen was diagnosed.

We didn't have the help everyone was offering in fear Owen would catch this virus, Mitchell wrote on her Facebook page. We couldn't go anywhere in between treatment to cheer Owen up. We couldn't bring him into the store to pick out a new toy or get him out of the house. He couldn't go swimming; he couldn't go to any arcades; he couldn't even have his father or siblings by his side undergoing surgery or chemo. It wasn't/ isnt fair that Owen had to suffer as much as he did. But we are happy he is still here.

Mitchell said the family celebrated Owens good news with pizza, cake and silly string. And she said Owen is going to go crazy with happiness when he sees all the Christmas gifts toys theyve bought for him.

In the meantime, Owen is enjoying the holiday season like any other 2-year-old.

Hes already playing with the Christmas tree bulbs, Mitchell said.

Donate to the "Help for baby Owen Buell and his Family" GoFundMe page at bit.ly/3n0MThy.

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Joliet 2-year-old gets pre-holiday gift: tests that show he's cancer-free - The Herald-News

GAITHERSBURG, Md., Dec. 07, 2020 (GLOBE NEWSWIRE) -- NexImmune, a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to employ the bodys own T cells to generate a specific, potent and durable immune response that mimics natural biology, today announced that City of Hopes Monzr Al Malki, M.D., delivered an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition featuring initial data from the Phase 1/2 trial of NEXI-001 in AML. Entitled Preliminary Results of the First-in-Human Study of NEXI-001, a Multi-Antigen Specific CD8+ T Cell Product, in Acute Myeloid Leukemia (AML) Patients with Relapsed Disease after Allogeneic Hematopoietic Cell Transplantation (Allo-HSCT) Demonstrate Early Signs of Safety, Tolerability and Robust Immune Responses, the presentation included responses following a single infusion of the experimental therapy.

These data represent safety and tolerability results from the first five patients treated and reflect a median of four months of follow-up with infusion doses ranging from 50-200 million total T cells. As noted by Dr. Al Malki in his presentation, there have been no cases of acute Graft versus Host Disease (aGvHD), Cytokine Release Syndrome (CRS), immune cells-associated neurological syndromes (ICANs), or infusion related reactions (IRRs) reported to-date, nor have there been any treatment-related adverse events (AEs) observed.

Biomarker data characterizing initial immunologic responses for the first three patients analyzed were also shared. Absolute lymphocyte counts, or ALC, were followed over time after the administration of lymphodepleting therapy, and showed a rapid return to baseline levels for each patient assessed (range 3 to 35 days). In addition, data on T cell reconstitution after lymphodepletion demonstrated that a single infusion of NEXI-001 T cells triggered a broad, rapid and robust immune response, inclusive of both CD8+ and CD4+ T cell types. TCR analysis showed the presence, persistence, expansion and migration of individual NEXI-001 T cell clones from the peripheral blood to the bone marrow of each patient. Finally, the immune phenotype of individual T cell subtypes in each NEXI-001 product were maintained in the peripheral blood of each patient at all time points measured, up to two months. These included sustained populations of T stem-cell-like memory and T central memory subtypes.

Early results from this Phase 1/2 trial suggest that infusion of the NEXI-001 product is well-tolerated and capable of triggering early, robust and persistent cell-mediated immune responses, said Dr. Al Malki, the trials lead investigator and associate clinical professor in City of Hopes Department of Hematology & Hematopoietic Cell Transplantation. The initial data are encouraging, and we look forward to dosing more patients with longer follow-up in order to more fully characterize the clinical potential of this exciting new cell therapy.

Relapse after allo-HSCT is the leading cause of death in patients with AML and represents a significant challenge for treating physicians. There are no approved therapies, and current treatment options are limited. Donor lymphocyte infusions (DLIs) represent the current standard of care but are associated with modest Graft versus Leukemia (GvL) responses and high rates of life-threatening GvHD-associated toxicities. There is significant need for new cellular therapies with potential to enhance the benefits of GvL while decreasing the incidence of GvHD-related toxicities.

Han Myint, M.D., Chief Medical Officer at NexImmune, added, While still early in this trial, we believe the initial data reported, combined with the unique and consistent composition of each NEXI-001 product, may offer a cell therapy with potential to decouple the benefits of GvL from the toxicities associated with GvHD, which would be transformative for both allogeneic stem cell transplant patients and the physicians that provide care for them.

About the Phase 1/2 NEXI-001 Clinical TrialThe first clinical trial with NEXI-001 is a prospective, multi-center, open-label, single-arm, dose-escalating Phase 1/2 study that aims to enroll between 22 to 28 patients. The primary objective is to assess the safety and tolerability of a single infusion of NEXI-001 T cells in patients with AML who have either minimum residual disease (MRD) or relapsed disease after a human leukocyte antigen (HLA)-matched allo-HSCT. Secondary objectives include signals of immunologic responses and preliminary anti-tumor activity. Additional analysis will assess the in vivo persistence, proliferation, functionality and TCR repertoire of NEXI-001 T cells as measured in blood and bone marrow samples.

This study includes two phases. The initial Safety Evaluation Phase determines the safety and tolerability of a single infusion of NEXI-001 at escalating dose levels. In the second part of the study, the Dose Expansion Phase, investigators further define safety and will also evaluate the initial efficacy of NEXI-001 T cells at the dose established in the Safety Evaluation Phase. Once a Recommended Phase II Dose has been determined, safety, tolerability and initial clinical response will become the objectives of the expansion phase of the trial, which is expected to begin in [the first quarter] of 2021.

NEXI-001 products contain populations of CD8+ T cells directed against HLA 02.01-restricted peptides from the WT1, PRAME and Cyclin A1 antigens, each of which is commonly over-expressed on AML blasts and leukemic stem cells. Each NEXI-001 product is composed of T cell memory subtypes that combine anti-tumor potency with long-term persistence. Of significance to this Phase 1/2 trial, each patient-specific experimental cell therapy product also contains very low proportions of T cell subtypes with potential to cause GvHD-related toxicities.

About NexImmuneNexImmune is a clinical-stage biotechnology company developing unique approaches to T cell immunotherapies based on its proprietary Artificial Immune Modulation (AIM) technology. The AIM technology is designed to generate a targeted T cell-mediated immune response and is initially being developed as a cell therapy for the treatment of hematologic malignancies. AIM nanoparticles act as synthetic dendritic cells to deliver immune-specific signals to targeted T cells and can direct the activation or suppression of cell-mediated immunity. In cancer, AIM-expanded T cells have demonstrated best-in-class anti-tumor properties as characterized by in vitro analysis, including a unique combination of anti-tumor potency, antigen target-specific killing, and long-term T cell persistence. The modular design of the AIM platform enables rapid expansion across multiple therapeutic areas, with both cell therapy and injectable products.

NexImmunes two lead T cell therapy programs, NEXI-001 and NEXI-002, are in Phase 1/2 clinical trials for the treatment of relapsed AML after allo-HSCT and multiple myeloma refractory to at least three prior lines of therapy, respectively. The Companys pipeline also has additional preclinical programs, including cell therapy and injectable product candidates for the treatment of solid tumors, autoimmune disorders and infectious diseases.

For more information, visit http://www.neximmune.com.

Media Contact:Mike BeyerSam Brown Inc. Healthcare Communications312-961-2502mikebeyer@sambrown.com

Investor Contact:Chad RubinSolebury Trout+1-646-378-2947crubin@soleburytrout.com

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Preliminary Results from NexImmune's Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition - GlobeNewswire

HealthA new stem cell treatment could restore eyesight in some people

Friday, 4th December 2020, 3:18 pm

Researchers discovered that the cells of damaged retinas could be repaired by injecting genetically modified stem cells into the eye.

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The news comes as comedian Al Murray pushed for stem cell donors to come forward, ahead of a charity gig for blood cancer organisation DKMS.

Heres everything you need to know about the scientific discovery - and how you can donate your own stem cells to save the lives of people with blood cell diseases.

Stem cells are produced by bone marrow, and they have the ability to grow into different types of blood cells such as red and white blood cells and platelets.

A stem cell or bone marrow transplant replaces damaged blood cells with healthy ones and can be used to treat conditions affecting the blood cells, like leukaemia and lymphoma.

The transplant involves destroying the unhealthy blood cells and replacing them with the stem cells removed from the blood or bone marrow.

Often, stem cells are taken from one person - usually a close family member or a match with the same or similar tissue type - and they are transferred to the person that needs them.

How could they be used to treat vision damage?

Researchers in Barcelona recently discovered that modified stem cells could potentially help to cure problems with vision.

They found that the cells of damaged eye retinas send out a rescue signal to attract the stem cells that can repair damage.

Stem cells were genetically engineered to make them more sensitive to those signals.

The modified stem cells were transplanted back into mice and human tissue samples and the researchers found that they flocked to the retina cells in large numbers.

In turn, that kept the tissue of the retina alive and functioning.

The new technique is a breakthrough in stem cell research as it suggests stem cells could help to improve sight, and potentially could cure blindness in the future.

Retinal damage is currently incurable and can cause visual disabilities and blindness, especially in older people.

How can stem cells treat conditions?

Stem cells can already be used to treat a number of conditions where the bone marrow is damaged and unable to produce its own healthy blood cells.

Transplants can be used to treat people suffering from different forms of cancer, with someone elses tem cells replacing the patients blood cells that are damaged or destroyed.

Conditions that stem cell transplants can treat include leukemia and lymphoma, which are cancers affecting white blood cells, myeloma, which affects plasma cells, severe aplastic anaemia (bone marrow failure), and other blood disorders.

A stem cell transplant will usually only be carried out if other treatments have been exhausted, but it could save someones life.

How can I donate stem cells?

When its not possible to use someones own stem cells to treat their condition, they need to come from a donor.

However, to improve the chances of the transplant being successful, the donated cells need to have a very similar genetic marker to the patients.

As the number of donors has recently decreased, charities are urgently encouraging healthy people to donate stem cells.

You are able to register to be a donor on the NHS Blood and Transplant website.

The Anthony Nolan charity also takes sign ups, and is specifically looking for younger donors between age 16 and 30.

You will be asked to fill out an application form and will be sent a swab pack so you can be added to the register.

If you ever come up as a match for a patient, you will be contacted by the charity.

Even if you cant join the register, you can donate to Anthony Nolan to help to grow the stem cell register.

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How do you donate stem cells? Donating cells can help treat cancer, blindness and other conditions - heres how - The Scotsman

Groundbreaking research in stem cells has propelled scientists understanding of neurodegenerative diseases, including Parksinsons. Could stem cell therapies one day help cure Alzheimers?

Clinical trials of stem cell therapies are now underway to repair the damaged cells of people with Parkinsons disease and age-related macular degeneration. Being Patient spoke with Jack Price, professor of developmental neurobiology at Kings College London and author of the book The Future of Brain Repair, about the potential and challenges of repairing the brain with stem cell therapy.

Being Patient: What is stem cell therapy?

Prof. Jack Price: Its the transplantation of stem cells, either directly into the brain or in a way that gives them access to the brain and influence the brain, to bring about a therapeutic effect.

Being Patient: Are there stem cells in the brain?

Prof. Jack Price: For many years, neuroscientists didnt think there were stem cells in the brain. We now know there are. We know about a population [of stem cells] thats become very important in our understanding of Alzheimers disease and in mood disorders like anxiety and depression. These are stem cells that are found in a part of the brain called the hippocampus.

But by and large, the brain doesnt have stem cells, unlike skin and other tissues in the body. The blood is the classic [example]: Theres a population of stem cells in the bone marrow that regenerates blood all the time.

Being Patient: What makes stem cells so special and why are they a focus of research?

Prof. Jack Price: The definition of stem cells is a population of cells that gives rise to other types of cells. In neural stem cells, precursor cells can make adult brain cells, nerve cells, glial cells, all the different cell types that make up the brain. If you have a disease like Alzheimers or any other neurodegenerative disease, where we know the key pathology is the loss of nerve cells, your brain doesnt normally have the ability to replace those lost brain cells. The idea was [that] if you put stem cells where the loss of brain cells has taken place, maybe those stem cells would replace the lost cells.

Being Patient: What is the potential of stem cell therapy in treating neurodegenerative diseases?

Prof. Jack Price: Theres a piece of absolutely brilliant stem cell science that was done by Shinya Yamanaka in Kyoto in 2006. He showed you could effectively take any cell through a very straightforward genetic manipulation that he discovered, [and] turn them into what we call pluripotent stem cells, which are cells that can make any cell type in the body. They also have an ability that other stem cells generally dont: They can build tissue. If you grow them in a little culture dish, they can start to make little pieces of brain called organoids or cerebroids. This was a groundbreaking technology.

In Parkinsons disease, theres enormous progress and clinical trials are underway now. We know more about the pathology of Parkinsons disease [than in Alzheimers]. The pathology of Alzheimers turns out to be quite complex, and weve had, over the years, quite a few ideas about how it worked. But [turning] those into actual therapies hasnt quite worked as we expected, and we keep having to go back and rethink whats going on in Alzheimers.

The pathology of Parkinsons disease is also difficult. Its not trivial. But at the same time, one thing is clear: a lot of the pathology is associated with the loss of a particular population of nerve cells the midbrain dopaminergic cells. We can start with these pluripotent stem cells and make them make precisely the right type of dopaminergic cell that we know is lost in Parkinsons disease.

This is built on 30 [to] 40 years of research of people trying to find exactly the right cell type to work [with] in Parkinsons disease. They had some early success and fell backwards. But this technology looks much more precise than everything anybodys ever tried before.

In age-related macular degeneration, the disease of the eye where you lose your retinal photoreceptors, there are very clever strategies now where people are using these pluripotent stem cells to make a thing called a retinal pigment epithelium. It lies behind the retina, but its what supports the photoreceptors. It turns out, thats what goes wrong in age-related macular degeneration.

Being Patient: Are there any stem cell therapy approved to treat brain disorders?

Prof. Jack Price: There are no licensed stem cell therapy for any brain disorders anywhere in the world for the simple reason [that] nobody has shown one works. There are a lot of stem cell clinics in the U.S. and somewhat fewer elsewhere who are offering cell therapies that are untested. Theyll put stem cells into you for any disorder youve got. Those cell therapies do not work.

A lot of genuine companies are trying to get these cell therapies to work in clinical trials and falling flat on their face quite often, despite their best efforts. 90% of clinical trials fail, and thats clinical trials of conventional drugs by drug companies that know what theyre doing.

What do you suppose is the chance with a stem cell therapy [that] we dont really understand how it works, [that] we dont quite know how to manufacture it properly, [and that] we dont quite know what cells we really want, of working? The chance is almost zero.

The interview has been edited for length and clarity.

Contact Nicholas Chan at nicholas@beingpatient.com

View original post here:
Repairing the Brain With Stem Cells? A Conversation With Prof. Jack Price - Being Patient

An effective new treatment to restore vision is on the horizon that works by injecting genetically modified stem cells into the eye to mend the damaged retina.

Researchers found that the cells of damaged retinas send out a rescue signal to attract the stem cells that repair eye damage.

The i newsletter latest news and analysis

They identified two of these cell signals known as Ccr5 and Cxcr6 and then genetically engineered the stem cells to make them more sensitive to those signals.

When these modified stem cells were transplanted back into mice and human tissue samples in the lab they flocked to the retina cells in much greater numbers, keeping the tissue of the damaged retina alive and functioning.

The technique holds promise for improving sight in people with poor vision and potentially even to cure blindness altogether but the researchers cautioned that any such development was some years away and required much bigger studies to confirm their findings.

One of the main hurdles in using stem cells to treat damaged eyesight is low cell migration and integration in the retina, says Pia Cosma, at the Centre for Genomic Regulation in Barcelona.

After the cells are transplanted they need to reach the retina and integrate through its layers. Here we have found a way to enhance this process using stem cells commonly found in the bone marrow, but in principle can be used with any transplanted cells, Dr Cosma said.

There is still considerable work to be done, but our findings could make stem cell transplants a feasible and realistic option for treating visual impairment and restoring eyesight, she said.

Retinal damage, which is currently incurable, inevitably leads to visual disabilities and in most cases blindness. With a growing and ageing population, the number of people affected by retinal damage is estimated to increase dramatically over the next few decades.

Stem cell therapies have been touted as one way of treating degenerative retinal conditions. Stem cells can be transplanted into the eye, releasing therapeutic molecules with neuroprotective and anti-inflammatory properties that promote the survival, proliferation and self-repair of retinal cells. The stem cells can also generate new retinal cells, replacing lost or damaged ones.

The researchers used mesenchymal stem cells, which are found in bone marrow and can differentiate into lots of types of cells, including retinal cells that respond to light.

Mesenchymal stem cells can also be easily grown outside an organism, providing abundant starting material for transplantation compared to other cell sources such as hematopoietic stem cells.

The study is published in the journal Molecular Therapy.

Excerpt from:
Treatment to restore vision by injecting stem cells into the eye could help people with damaged eyesight - iNews

This article was originally published here

J Pharmacol Exp Ther. 2020 Nov 30:JPET-AR-2020-000277. doi: 10.1124/jpet.120.000277. Online ahead of print.

ABSTRACT

ONO-4641 is a second-generation sphingosine 1-phosphate (S1P) receptor modulator that exhibits selectivity for S1P receptors 1 and 5. Treatment with ONO-4641 leads to a reduction in magnetic resonance imaging disease measures in patients with relapsing-remitting multiple sclerosis. The objective of this study was to explore the potential impact of ONO-4641 treatment based on its immunomodulatory effects. Severe aplastic anemia is a bone marrow (BM) failure disease, typically caused by aberrant immune destruction of blood progenitors. Although the T helper type-1-mediated pathology is well described for aplastic anemia, the molecular mechanisms driving disease progression remain undefined. We evaluated the efficacy of ONO-4641 in a mouse model of aplastic anemia. ONO-4641 reduced the severity of BM failure in a dose-dependent manner, resulting in higher blood and BM cell counts. By evaluating the mode of action, we found that ONO-4641 inhibited the infiltration of donor-derived T lymphocytes to the BM. ONO-4641 also induced the accumulation of hematopoietic stem cells in the BM of mice. These observations indicate, for the first time, that S1P receptor modulators demonstrate efficacy in the mouse model of aplastic anemia and suggest that treatment with ONO-4641 might delay the progression of aplastic anemia. Significance Statement ONO-4641 is a second-generation sphingosine 1-phosphate (S1P) receptor modulator selective for S1P receptors 1 and 5. In this study, we demonstrated that ONO-4641 regulates the trafficking of T lymphocytes along with hematopoietic stem and progenitor cells leading to alleviation of pancytopenia and destruction of bone marrow in a bone marrow failure-induced mouse model mimicking human aplastic anemia.

PMID:33257316 | DOI:10.1124/jpet.120.000277

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Sphingosine 1-phosphate Receptor Modulator ONO-4641 Regulates Trafficking of T Lymphocytes and Hematopoietic Stem Cells and Alleviates Immune-Mediated...

Newswise Researchers from The University of Kansas Cancer Center are involved in the presentation of nearly 50 research studies at the 62ndAmerican Society of Hematology (ASH) Annual Meeting, to be held virtually Dec. 5-8 because of the COVID-19 pandemic. With more than 18,000 members from nearly 100 countries, the ASH is the world's largest professional society serving both clinicians and scientists around the world who are working to conquer blood diseases.

The KU Cancer Center is one of only 71 cancer centers designated by the National Cancer Institute because they meet rigorous standards for transdisciplinary, state-of-the-art research focused on developing new and better approaches to preventing, diagnosing and treating cancer. Its catchment area includes the state of Kansas as well as western Missouri.

These 49 research studies represent the hard work of our many researchers focused on blood diseases, said Roy Jensen, M.D., director of the KU Cancer Center. This includes innovations in immunotherapy, advances in leukemia and significant work in stem cell transplants. While the conference is virtual this year, the KU Cancer Center will be well represented.

While a full list of abstracts involving KU Cancer Center researchers can be found online, three of the most significant are listed below.

# # #

About The University of Kansas Cancer Center:

The University of Kansas Cancer Center is transforming cancer research and clinical care by linking an innovative approach to drug discovery, delivery and development to a nationally-accredited patient care program. Our consortium center includes cancer research and health care professionals associated with the University of Kansas Medical Center and The University of Kansas Health System; the University of Kansas, Lawrence; The Stowers Institute for Medical Research; Childrens Mercy; and in partnership with members of the Masonic Cancer Alliance.

About the University of Kansas Medical Center:

The University of Kansas Medical Centers mission is to educate exceptional health care professionals through a full range of undergraduate, graduate, professional, postdoctoral and continuing education programs in the schools of Medicine, Nursing and Health Professions. KU Medical Center also advances the health sciences through world-class research programs; provides compassionate and state-of-the-art patient care in an academic medical center environment; and works with communities in every Kansas county to improve the health of Kansans.

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Cancer center is a contributor to 49 research studies at the 62nd American Society of Hematology Annual Meeting - Newswise

NEW YORK, Dec. 03, 2020 (GLOBE NEWSWIRE) -- IN8bio, Inc., a clinical-stage biotechnology company focused on developing innovative allogeneic, autologous and genetically modified gamma-delta T cell therapies for the treatment of cancers (IN8bio or the Company), today announced an upcoming presentation that provides an update of the ongoing Phase I clinical trial of their product candidate INB-100 at the 62nd American Society of Hematology Annual Meeting & Exposition (ASH), which will take place virtually from December 5 to 8, 2020. INB-100 is designed for the treatment of patients with leukemia undergoing hematopoietic stem cell transplantation with haploidentical donors.

The poster and accompanying narrated slide presentation is titled, First-in-Human Phase I Trial of Adoptive Immunotherapy with Ex Vivo Expanded and Activated gamma delta T-Cells Following Haploidentical Bone Marrow Transplantation and Post-BMT Cyclophosphamide and reviews the study design and provides a brief update on enrollment and patient status.

The company reported that, as of abstract submission, three female subjects with acute leukemia had been enrolled in the INB-100 Phase 1 trial, of whom two had been dosed, and that no treatment-related adverse events had been recorded. The trial is continuing to enroll and treat patients. The abstract for the presentation can be found at https://ash.confex.com/ash/2020/webprogram/Paper142876.html.

The poster and slide presentation are jointly authored by the scientific and physician investigators from IN8bio and The University of Kansas Cancer Center (KU Cancer Center), and will be presented by the studys Principal Investigator, Dr. Joseph McGuirk, Schutte-Speas Professor of Hematology-Oncology, Division Director of Hematological Malignancies and Cellular Therapeutics and Medical Director, Blood and Marrow Transplant at KU Cancer Center.

This preliminary data report from KU Cancer Center with our allogeneic product candidate, INB-100, demonstrates the absence of significant GvHD in these initial patients, said William Ho, Chief Executive Officer of IN8bio. This suggests that gamma delta T-cells delivered as an off-the-shelf allogeneic cell therapy may be well tolerated and have significant potential to treat patients with serious and life-threatening cancers.

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Dr. McGuirk, commented, Potentially curative stem cell transplants using partially matched donors -- called haploidentical transplants have greatly expanded access to stem cell transplantation. The infusion of donor-derived gamma delta T-cells from the stem cell donor, offers the hope of diminishing this risk of relapse and curing more patients.

About IN8bioIN8bio is a clinical-stage biotechnology company focused on developing novel therapies for the treatment of cancers, including solid tumors, by employing allogeneic, autologous and genetically modified gamma-delta T cells. IN8bios technology incorporates drug-resistant immunotherapy (DRI), which has been shown in preclinical studies to function in combination with therapeutic levels of chemotherapy. IN8bio is currently conducting two investigator-initiated Phase 1 clinical trials for its lead gamma-delta T cell product candidates: INB-200 for the treatment of newly diagnosed glioblastoma, which is a difficult to treat brain tumor that progresses rapidly, and INB-100 for the treatment of patients with acute leukemia undergoing hematopoietic stem cell transplantation. For more information about the Company and its programs, visit http://www.IN8bio.com.

Forward Looking StatementsCertain statements herein concerning the Companys future expectations, plans and prospects, including without limitation, the Companys current expectations regarding the curative potential of its product candidates, constitute forward-looking statements. The use of words such as may, might, will, should, expect, plan, anticipate, believe, estimate, project, intend, future, potential, or continue, the negative of these and other similar expressions are intended to identify such forward looking statements. Such statements, based as they are on the current expectations of management, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond the Companys control. Consequently, actual future results may differ materially from the anticipated results expressed in such statements. Specific risks which could cause actual results to differ materially from the Companys current expectations include: scientific, regulatory and technical developments; failure to demonstrate safety, tolerability and efficacy; final and quality controlled verification of data and the related analyses; expense and uncertainty of obtaining regulatory approval, including from the U.S. Food and Drug Administration; and the Companys reliance on third parties, including licensors and clinical research organizations. Do not place undue reliance on any forward-looking statements included herein, which speak only as of the date hereof and which the Company is under no obligation to update or revise as a result of any event, circumstances or otherwise, unless required by applicable law.

Contact:IN8bio, Inc.Kate Rochlin, Ph.D.+1 646.933.5605info@IN8bio.com

Investor Contact:Julia Balanova+ 1 646.378.2936jbalanova@soleburytrout.com

Media Contact:Ryo Imai / Robert Flamm, Ph.D.Burns McClellan, Inc.212-213-0006 ext. 315 / 364Rimai@burnsmc.com / rflamm@burnsmc.com

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IN8bio announces first-in-human Phase 1 trial Update from The University of Kansas Cancer Center using INB-100, IN8bios Gamma Delta T-cell product...

Final Report will add the analysis of the impact of COVID-19 on this industry.

According to the latest industry research Bone Marrow Transplant Market share is predicted to gain better growth in upcoming years. Global Bone Marrow Transplant market report is one of the best sources of research data which provided by industry experts. Report gives facts about Covid-19 impact, geographical breakdown, top manufactures, type wise and applications wise segmentation. In Bone Marrow Transplant market report the growth rate, revenue, market shares, sales, production, consumption, manufacturers in particular areas are regionally analysed.

Experts also states challenges, risks, driving factors, trends, opportunities in Bone Marrow Transplant market so the investors, new participants, and stakeholders get good clarification with Bone Marrow Transplant market industry.

Get a Sample Copy of the Report at- https://www.industryresearch.co/enquiry/request-sample/13652362

Bone marrow transplant refers to the replacement of diseased or damaged bone marrow with healthy tissue or bone marrow stem cells in order to treat blood cancer or various cases of anemia. Depending on the source of bone marrow or stem cells, bone marrow transplant procedures are classified as peripheral stem cell transplant (PSCT) or conventional bone marrow transplant.

Bone Marrow Transplant Industry Segmentation:

Bone Marrow Transplant Market by Top Manufacturers:Lonza Group Ltd., Merck Millipore Corporation., Sanofi-Aventis LLC., AllCells LLC., STEMCELL Technologies., American Type Culture Collection (ATCC) Inc. By ProcedureAutologous Bone Marrow Transplant, Allogeneic Bone Marrow TransplantBy Disease IndicationLeukemia, Lymphoma, Myeloma, Myelodysplasia, Myeloproliferative Neoplasms, Aplastic Anemia, Solid tumors, Sickle cell Anemia, OthersBy End UserHospitals, Multispecialty Clinics, Ambulatory Surgical Centers

The study procedure elaborates the analysis of several features affecting the industry, with the government policy, Bone Marrow Transplant market forecast environment, technological innovation, competitive landscape, historical data, present trends in the market, forthcoming technologies and the technical progress in associated industry.

What the Bone Marrow Transplant Market Trend Report Offers:

Inquire or Share Your Questions If Any Before the Purchasing This Report- https://www.industryresearch.co/enquiry/pre-order-enquiry/13652362

Bone Marrow Transplant market report is outcome of comprehensive primary and secondary research accepted by analysts having years of experience in the Bone Marrow Transplant industry. All the qualitative and quantitative aspects of the industry have been covered and the collected information has been examined and accessible in the form of easily understandable charts, graphs and tables.

In addition, report analyses Bone Marrow Transplant market size and forecast of product, region and application and different analysis essentials like type section, business section, channel segment etc. cover totally different segment market size, each volume and value. Moreover, cover different industries clients data, that is incredibly necessary for the manufacturers.

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Detailed TOC of 2019-2024 Global and Regional Bone Marrow Transplant Industry Production, Sales and Consumption Status and Prospects Professional Market Research Report

Chapter 1 Bone Marrow Transplant Industry Overview

1.1 Definition

1.2 Brief Introduction by Major Type

1.3 Brief Introduction by Major Application

1.4 Brief Introduction by Major Regions

1.4.1 United States

1.4.2 Europe

1.4.3 China

1.4.4 Japan

1.4.5 India

Chapter 2 Production Bone Marrow Transplant Market Analysis

2.1 Global Production Market Analysis

2.1.1 2012-2017 Global Capacity, Production, Capacity Utilization Rate, Ex-Factory Price, Revenue, Cost, Gross and Gross Margin Analysis

2.1.2 2012-2017 Major Manufacturers Performance and Market Share

2.2 Regional Production Market Analysis

2.2.1 2012-2017 Regional Market Performance and Market Share

2.2.2 United States Market

2.2.3 Europe Market

2.2.4 China Market

2.2.5 Japan Market

2.2.6 India Market

2.2.7 Rest Regions Market

Chapter 3 Bone Marrow Transplant Sales Market Analysis

3.1 Global Sales Market Analysis

3.1.1 2012-2017 Global Sales Volume, Sales Price and Sales Revenue Analysis

3.1.2 2012-2017 Major Manufacturers Performance and Market Share

3.2 Regional Sales Market Analysis

3.2.1 2012-2017 Regional Market Performance and Market Share

3.2.2 United States Market

3.2.3 Europe Market

3.2.4 China Market

3.2.5 Japan Market

3.2.6 India Market

3.2.7 Rest Regions Market

Chapter 4 Consumption Market Analysis

4.1 Global Consumption Market Analysis

4.1.1 2012-2017 Global Consumption Volume Analysis

4.2 Regional Consumption Market Analysis

4.2.1 2012-2017 Regional Market Performance and Market Share

4.2.2 United States Market

4.2.3 Europe Market

4.2.4 China Market

4.2.5 Japan Market

4.2.6 India Market

4.2.7 Rest Regions Market

Chapter 5 Production, Sales and Consumption Market Comparison Analysis

5.1 Global Production, Sales and Consumption Market Comparison Analysis

5.2 Regional Production, Sales Volume and Consumption Volume Market Comparison Analysis

5.2.1 United States

5.2.2 Europe

5.2.3 China

5.2.4 Japan

5.2.5 India

5.2.6 Rest Regions

Chapter 6 Major Manufacturers Production and Sales Market Comparison Analysis

6.1 Global Major Manufacturers Production and Sales Market Comparison Analysis

6.1.1 2012-2017 Global Major Manufacturers Production and Sales Market Comparison

6.2 Regional Major Manufacturers Production and Sales Market Comparison Analysis

6.2.1 United States

6.2.2 Europe

6.2.3 China

6.2.4 Japan

6.2.5 India

6.2.6 Rest Regions

Chapter 7 Major Type Analysis

7.1 2012-2017 Major Type Market Share

Chapter 8 Major Application Analysis

8.1 2012-2017 Major Application Market Share

Chapter 9 Bone Marrow Transplant Industry Chain Analysis

9.1 Up Stream Industries Analysis

9.1.1 Raw Material and Suppliers

9.1.2 Equipment and Suppliers

9.2 Manufacturing Analysis

9.2.1 Manufacturing Process

9.2.2 Manufacturing Cost Structure

9.2.3 Manufacturing Plants Distribution Analysis

9.3 Industry Chain Structure Analysis

Browse Complete TOC Here: https://www.industryresearch.co/TOC/13652362#TOC

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Bone Marrow Transplant Market Size, Segmented by Type of Deployment, Application, And Region Growth, Trends, And Forecast - The Haitian-Caribbean...

For the first time, researchers have demonstrated how the gut microbiome the community of microorganisms living in the gut can influence the immune system in humans. Their work could lead to new treatments for immune-related conditions.

The researchers at Memorial Sloan Kettering Cancer Center in New York, NY, tracked the recovery of patients gut microbiota and immune system after bone marrow transplants (BMTs) following treatment for blood cancers.

Healthcare professionals use chemotherapy and radiation therapy to destroy cancerous blood cells in conditions such as leukemia and lymphoma. After completion of the treatment, which also kills healthy immune cells, specialists inject patients with stem cells from a donors blood or bone marrow.

These donated cells slowly restore patients ability to make their own blood cells.

However, patients have to take antibiotics in the first few weeks after the transplant because they are still vulnerable to infections. These upset the balance of their gut microbiota, killing friendly bacteria and allowing dangerous strains to thrive.

Once patients immune systems are strong enough, they can stop taking the antibiotics, which allows their gut microbiota to recover.

The researchers at Sloan Kettering used this unique opportunity to study how the microbiota affects the immune system.

The scientific community had already accepted the idea that the gut microbiota was important for the health of the human immune system, but the data they used to make that assumption came from animal studies, explains systems biologist Joao Xavier, who is co-senior author of the paper with his former postdoc Jonas Schluter.

The parallel recoveries of the immune system and the microbiota, both of which are damaged and then restored, gives us a unique opportunity to analyze the associations between these two systems, says Dr. Schluter, who is now an assistant professor at NYU Langone Health in New York, NY.

Using blood and fecal samples from more than 2,000 patients treated at the cancer center between 20032019, the researchers were able to track daily changes in their gut microbiota and the number of immune cells in their blood.

Our study shows that we can learn a lot from stool biological samples that literally would be flushed down the toilet, says Dr. Xavier. The result of collecting them is that we have a unique dataset with thousands of data points that we can use to ask questions about the dynamics of this relationship.

The researchers used a machine-learning algorithm to identify patterns in the data, which included information about patients medications and the side effects they experienced.

One of the findings was that the presence of three types of gut bacteria called Faecalibacterium, Ruminococcus 2, and Akkermansia was associated with increased blood concentrations of immune cells called neutrophils.

By contrast, two types called Rothia and Clostridium sensu stricto 1, were associated with reduced numbers of these immune cells.

Computer simulations by the researchers predicted that enriching microbiota with the three friendly genera would speed up the recovery of patients immune systems.

This research could eventually suggest ways to make BMTs safer by more closely regulating the microbiota, says co-author Marcel van den Brink.

The study appears in Nature.

Concluding their paper, the authors write:

Our demonstration that the microbiota influences systemic immunity in humans opens the door toward an exploration of potential microbiota-targeted interventions to improve immunotherapy and treatments for immune-mediated and inflammatory diseases.

A previous study found that having a greater diversity of bacterial species in the gut is associated with a better chance of survival after a stem cell transplant. This research also found that a low diversity of bacteria increased the likelihood of potentially fatal graft-versus-host disease, when the donor immune cells attack the recipients tissues.

In 2018, the Sloan Kettering researchers published results from a clinical trial in which they used fecal transplants to restore patients microbiota after treatment for blood cancer.

They used the patients own fecal matter, which had been collected and frozen before the bone marrow transplant and antibiotic treatment disrupted their gut microbiota.

Original post:
Gut bacteria can help rebuild the immune system - Medical News Today

Vancouver, British Columbia--(Newsfile Corp. - December 1, 2020) - Hemostemix Inc. (TSXV: HEM) (OTCBB: HMTXF), a clinical stage biotechnology company with a patented stem cell technology platform, has successfully, following lengthy litigation, obtained its entire clinical trial database from Medrio Inc., which was hosting the database for Aspire Heath Science LLC. For more details on the litigation, please refer to today's news release.

For more information, please view the InvestmentPitch Media "video" which provides additional information about this news and the company. If this link is not enabled, please visit http://www.InvestmentPitch.com and enter "Hemostemix" in the search box.

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The company's principal business is to develop, manufacture and commercialize blood-derived stem cell therapies to treat various diseases not adequately addressed by current therapeutics. The company's process for harvesting stem cells is less invasive, as the stem cells are taken from a patient's blood, which is a simplified process as compared to taking stem cells from fatty tissue or bone marrow.

Critical limb ischemia or CLI, a severe blockage in the arteries of the lower extremities, which markedly reduces blood-flow, is deadliest form of peripheral arterial disease or PAD, with limited treatment options and no current approved drug treatments. The company's lead product, ACP-01 is the subject of a Phase II clinical trial of its safety and efficacy in patients with advanced CLI, who have exhausted all other options to save their limb from amputation.

Hemostemix owns 91 patents related to its products and manufacturing processes and has entered into a contract with a new clinical research organization which is completing the midpoint statistical analyses of the efficacy of ACP-01. A winner of the World Economic Forum Technology Pioneer Award, Hemostemix developed and is commercializing its lead product ACP-01.

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Hemostemix announced the abstract and interim results presented to the 41st annual Canadian Society for Vascular Surgery meeting, which noted healing of ulcers and resolution of ischemic rest pain occurred in 83 per cent of patients studied by lead investigators at the University of British Columbia and the University of Toronto with outcomes maintained for up to 4.5 years.

Thomas Smeenk, CEO, stated: "As every biotech investor knows, it is all about the data! Blinded, we will know in short order if our HS 12-01 midpoint results equal the interim clinical trial results that 83 per cent of patients followed for up to 4.5 years experienced. Fortunately, we have a lot of data of the efficacy of ACP. For example, we have the clinical trial results of the 41 patients treated for cardiomyopathy. And, we have the results of the 106 ischemic heart disease patients on maximal medical therapy who had no option for revascularization, who experienced significant improvement."

Hemostemix is addressing a huge potential market. According to The Sage Group LLC, in the United States alone, approximately 20 million people are affected by PAD, and it is estimated that approximately 7 to 8 million people in the United States and Europe suffer from CLI. The Sage Group estimates that in the United States, medical costs attributable to CLI amount to US$25 billion annually.

The company has also announced a non-brokered private placement. The company is looking to raise gross proceeds of up to $2.5 million from the placement of up to 250 million units priced at $0.01 per unit. The units consist of 1 share and 1 warrant, with each warrant exercisable at $0.05 for 12 months, subject to an acceleration clause. The shares are currently trading at $0.01. However, the company has obtained shareholder approval for a 20 for one share consolidation.

In addition to accredited investors, this placement is available under certain security exemptions to existing shareholders, friends and family, and those investors having received advice under the investment dealer exemption.

For more information, please visit the company's website at http://www.hemostemix.com, contact Thomas Smeenk, President, CEO and Co-Founder at 905-580-4170 or by email at TSmeenk@hemostemix.com.

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DUBLIN--(BUSINESS WIRE)--The "Multiple Myeloma Drugs Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2020-2025" report has been added to ResearchAndMarkets.com's offering.

The global multiple myeloma drugs market grew at a CAGR of around 9% during 2014-2019. Looking forward, the publisher expects the market to witness moderate growth during the next five years.

Multiple myeloma, or Kahler's disease, refers to a form of blood cancer that primarily affects the plasma cells. Some of the most common types of multiple myeloma drugs include chemotherapeutic agents, corticosteroids and immunomodulatory agents. These pharmaceutical drugs aid in promoting bone healing, prevent hypercalcemia, bone fracture, spinal cord compression and anemia, while minimizing the need for chemotherapy. The chemotherapeutic agents include various anthracycline antibiotics and alkylating agents, such as melphalan, doxorubicin, vincristine and liposomal doxorubicin. The targeted therapy drugs include proteasome inhibitor, such as bortezomib, and various other compounds, including dexamethasone, prednisone and thalidomide.

Significant developments in the healthcare sector, along with the increasing prevalence of hematological cancer, is one of the key factors driving the growth of the market. Multiple myeloma is usually caused by specific genetic abnormalities, and the treatment of this disease involves drugs that modulate the immune system and aid in enhancing the efficiency of chemotherapies, radiation therapies, stem cell transplants and platelet transfusion.

Furthermore, rising consumer awareness regarding the benefits of biologic therapy drugs, which utilize the body's immune system to identify and attack the myeloma cells, is also providing a boost to the market growth. Additionally, various technological advancements, such as the development of microRNA therapeutics and nanomedicines for the treatment of multiple myeloma, is acting as another growth-inducing factor. These medicines are used to facilitate the delivery of macromolecular agents into the bone marrow and catalyze antitumor responses. Other factors, including the rising healthcare expenditures and extensive research and development (R&D) activities in the field of medical sciences, are projected to drive the market further.

Companies Mentioned

Key Questions Answered in This Report:

Key Topics Covered:

1 Preface

2 Scope and Methodology

2.1 Objectives of the Study

2.2 Stakeholders

2.3 Data Sources

2.3.1 Primary Sources

2.3.2 Secondary Sources

2.4 Market Estimation

2.4.1 Bottom-Up Approach

2.4.2 Top-Down Approach

2.5 Forecasting Methodology

3 Executive Summary

4 Introduction

4.1 Overview

4.2 Key Industry Trends

5 Global Multiple Myeloma Drugs Market

5.1 Market Overview

5.2 Market Performance

5.3 Market Forecast

6 Market Breakup by Therapy

6.1 Targeted Therapy

6.1.1 Market Trends

6.1.2 Market Forecast

6.2 Biologic Therapy

6.2.1 Market Trends

6.2.2 Market Forecast

6.3 Chemotherapy

6.3.1 Market Trends

6.3.2 Market Forecast

6.4 Others

6.4.1 Market Trends

6.4.2 Market Forecast

7 Market Breakup by Drug Type

7.1 Immunomodulatory Drugs

7.1.1 Market Trends

7.1.2 Market Forecast

7.2 Proteasome Inhibitors

7.2.1 Market Trends

7.2.2 Market Forecast

7.3 Histone Deacetylase Inhibitors

7.3.1 Market Trends

7.3.2 Market Forecast

7.4 Monoclonal Antibody Drugs

7.4.1 Market Trends

7.4.2 Market Forecast

7.5 Steroids

7.5.1 Market Trends

7.5.2 Market Forecast

7.6 Others

7.6.1 Market Trends

7.6.2 Market Forecast

8 Market Breakup by End-User

8.1 Men

8.1.1 Market Trends

8.1.2 Market Forecast

8.2 Women

8.2.1 Market Trends

8.2.2 Market Forecast

9 Market Breakup by Distribution Channel

9.1 Hospital Pharmacies

9.1.1 Market Trends

9.1.2 Market Forecast

9.2 Retail Pharmacies

9.2.1 Market Trends

9.2.2 Market Forecast

9.3 Online Pharmacies

9.3.1 Market Trends

9.3.2 Market Forecast

9.4 Others

9.4.1 Market Trends

9.4.2 Market Forecast

10 Market Breakup by Region

10.1 North America

10.2 Asia Pacific

10.3 Europe

10.4 Latin America

10.5 Middle East and Africa

11 SWOT Analysis

12 Value Chain Analysis

13 Porters Five Forces Analysis

14 Price Indicators

15 Competitive Landscape

15.1 Market Structure

15.2 Key Players

15.3 Profiles of Key Players

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Outlook on the Multiple Myeloma Drugs Global Market to 2025 - by Therapy, Drug Type, End-user, Distribution Channel and Region -...

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Imago BioSciences, Inc., (Imago) a clinical-stage biotechnology company developing innovative treatments for myeloid diseases, today announced the expansion of its global Phase 2b clinical study evaluating bomedemstat (IMG-7289) for the treatment of advanced myelofibrosis (MF) into Hong Kong, where the first patient has now been enrolled and dosed at the Department of Medicine, Queen Mary Hospital and the University of Hong Kong. Myelofibrosis is a rare bone marrow cancer that interferes with the production of blood cells.

In addition to Hong Kong, the Phase 2b study continues to actively enroll patients in the U.S., U.K., and E.U. The study is in the final stages of completing enrollment and continues to dose patients to evaluate safety, tolerability and efficacy.

Patients with myelofibrosis around the world are still in need of new treatment options, said Hugh Young Rienhoff, Jr. M.D., Chief Executive Officer, Imago BioSciences. We are progressing well with enrollment and are pleased to continue expanding our global Phase 2 study into new geographies like Hong Kong. We are encouraged by the signs of clinical activity and safety of bomedemstat as a treatment alternative for patients who do not benefit from the current standards of care.

Bomedemstat is an inhibitor of lysine-specific demethylase 1 (LSD1), an epigenetic regulator critical for self-renewal of malignant myeloid cells and the differentiation of myeloid progenitors. Data presented at the 25th European Hematology Association (EHA) Annual Congress in June demonstrated that the first-in-class LSD1 inhibitor was well tolerated with no dose-limiting toxicities or safety signals. Furthermore, recent data demonstrates the potential of bomedemstat as a monotherapy in intermediate-2 and high-risk patients with myelofibrosis who have become intolerant of, resistant to or are ineligible for a Janus Kinase (JAK) inhibitor.

Bomedemstat was recently granted PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA) for the treatment of MF. The EMA reviewed bomedemstat non-clinical and clinical data from the ongoing Phase 2 study. The PRIME initiative was launched by the EMA in 2016 to provide proactive and enhanced support to the developers of promising medicines with the view of accelerating their evaluation to reach patients faster.

About Bomedemstat (IMG-7289)

Bomedemstat is an orally available small molecule discovered and developed by Imago BioSciences that inhibits lysine-specific demethylase 1 (LSD1 or KDM1A), an enzyme shown to be vital in cancer stem/progenitor cells, particularly neoplastic bone marrow cells. In non-clinical studies, bomedemstat demonstrated robust in vivo anti-tumor efficacy across a range of myeloid malignancies as a single agent and in combination with other therapeutic agents. Bomedemstat is an investigational agent currently being evaluated in ongoing clinical trials (ClinicalTrials.gov Identifier: NCT03136185, NCT04262141, NCT04254978 and NCT04081220).

Bomedemstat has U.S. FDA Orphan Drug and Fast Track Designation for the treatment of myelofibrosis and essential thrombocythemia, Orphan Drug Designation for treatment of acute myeloid leukemia and PRIME designation by the European Medicines Agency for the treatment of MF.

Bomedemstat is being evaluated in two open-label Phase 2 clinical trials for the treatment of advanced myelofibrosis (MF) and essential thrombocythemia (ET), bone marrow cancers that interfere with the production of blood cells. MF patients who are resistant to a Janus Kinase (JAK) inhibitor are eligible for the study of bomedemstat. ET patients who have failed one standard of care treatment are eligible for the bomedemstat ET study.

About Imago BioSciences

Imago BioSciences is a clinical-stage biopharmaceutical company focused on discovering and developing novel therapeutics for the treatment of hematologic disorders targeting epigenetic enzymes. Imago has developed a series of compounds that inhibit LSD1, an epigenetic enzyme critical for cancer stem cell function and blood cell differentiation. Imago is advancing the clinical development of its first LSD1 inhibitor, bomedemstat, for the treatment of myeloid neoplasms. Imago BioSciences is backed by leading private, corporate, and public investors including Farallon Capital Management, LLC., funds and accounts advised by T. Rowe Price Associates, Inc., funds and accounts managed by Blackrock Advisors, LLC., Surveyor Capital (a Citadel company), Irving Investors, Kingdon Capital Management, a fund managed by Blackstone Life Sciences, Frazier Healthcare Partners, Omega Funds, Amgen Ventures, MRL Ventures Fund, HighLight Capital, Pharmaron, Greenspring Associates and Xeraya Capital. The company is based in South San Francisco, California. To learn more, visit http://www.imagobio.com, http://www.myelofibrosisclinicalstudy.com, http://www.etclinicalstudy.com and follow us on Twitter @ImagoBioRx, Facebook and LinkedIn.

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Imago BioSciences Expands Phase 2 Clinical Trial of Bomedemstat (IMG-7289) for the Treatment of Myelofibrosis into Hong Kong - Business Wire

The mRNA technology used to create the Pfizer and Moderna vaccines for COVID is being applied to ... [+] many other medical treatments in addition to vaccines.

While the vaccines for Covid-19 seem to have been created in record time, the technology making them possible has been decades in development. The two vaccine candidates produced by Pfizer/BioNTech and Moderna are unlike any other vaccine thats come before. Should they achieve commercial success, it could usher in a new era of medical science not just for vaccines, but for cancer treatments, blood disorders, and gene therapy.

The two new vaccines are the first ever to use mRNA, which stands for messenger RNA, to generate immunity. Historically, vaccines have used dead or weakened viruses to imitate an infection, spurring the body to make antibodies against that virus without danger of getting sick. Measles, polio, and some seasonal flu shots are examples of vaccines made with whole virus particles.

Other vaccines use only certain fragments of the virus, called antigens, that provoke an immune response. To make this type of vaccine, the genetic code for the desired viral antigen molecule is put into yeast or bacteria cells. These microbes can be grown rapidly and inexpensively, and they can churn out massive quantities of antigen. Then the molecule must be purified to clinical standards so that its safe to inject into healthy people. Prevnar and Gardasil are examples of this type of vaccine.

These methods work well, but they require enormous research and development efforts. A laboratory could spend years optimizing the methods for producing one virus protein, but those methods wouldnt automatically translate to mass-producing a different protein.

For every new protein, you start over. Its a brand-new procedure every step of the way, explains immunologist Drew Weissman of the Perelman School of Medicine at the University of Pennsylvania. Weissman is one of the pioneering scientists behind the mRNA vaccine.

The way I see it, the mRNA platform is much better, its much quicker, and its cheaper, says Weissman. Thats the trilogy of what you need to improve vaccines. With mRNA, the steps are the same, no matter what virus the vaccine is targeting. This makes it easily customizable. Once an mRNA manufacturing facility is up and running, it can easily be deployed to make vaccines against any number of viral antigens.

A strand of mRNA carries the instructions for making one protein. Your cells normally make their own mRNA strands and use them as blueprints to manufacture all the proteins your body needs to function.

The vaccine slips a new strand of mRNA into the cell, like an extra page in the blueprint. This mRNA contains the instructions for making the coronavirus spike protein, and the cell reads it the same way it reads its own mRNAs, using it to build the viral protein. The immune system recognizes that protein as foreign, and starts making antibodies against it. Then, if youre exposed to the actual virus, those antibodies will be available to stop the infection. Astonishingly, in animal tests, mRNA vaccines appear to induce immunity that lasts much longer than live virus vaccines.

The beauty of mRNA is that its temporary. Your cells wont keep cranking out spike protein forever. Like an Instagram story, the mRNA fades away after a certain amount of time, because you dont need to keep making coronavirus protein forever in order to maintain the protective immunity.

Another big advantage of mRNA is that its rapidly customizable. Once scientists know the genetic sequence of a viral protein, they can make the mRNA in the lab and package it into a vaccine in a matter of weeks.

Originally envisioned as a way to deliver gene therapy, mRNA had to overcome some serious challenges before arriving at todays big moment. In 2005, Weissman and his colleague, Katalin Karik, solved one of the most difficult problems facing mRNA. In its natural form, the molecule sparks an excessive immune reaction, igniting inflammation that damages the body. To avoid this, they changed the structure of the mRNA just enough to fool the immune sentries.

Similar to DNA, RNA is made up of a series of chemical letters, a kind of code that the cell translates to make a protein. Modifying the chemical structure of one of those letters allowed the information to remain intact, and eliminated the signal that triggered the bodys immune alarms.

Before the coronavirus pandemic hit, Weissmans lab was working on vaccines for influenza, herpes, and HIV. Those will all be going into phase I clinical trials within the next year, he says. But vaccines are only the beginning of what mRNA can do.

Often in the case of genetic diseases, the problem is that a broken gene fails to produce a protein that the body needs for healthy function. The idea of gene therapy is simple: send in a healthy copy of the broken gene, which the cells can use to make the protein. Most times, researchers use viruses to deliver the gene, but viruses can cause problems of their own. Delivering mRNA to the cell without a virus circumvents some of these issues.

To ferry the mRNA into cells, it is encapsulated in a fatty coating called a lipid nanoparticle (LNP). Weissmans lab has been experimenting with ways to modify the LNP so that it can home in on certain cell types.

In sickle cell disease (SCD), a broken hemoglobin gene prevents blood cells from carrying oxygen ... [+] efficiently, and causes them to take on a rigid, sickle-shaped form.

My lab has figured out how to specifically deliver the LNP to bone marrow stem cells, Weissman says. This could lead to an inexpensive and practical cure for sickle cell anemia. An mRNA molecule can be programmed to encode the beta-hemoglobin gene, which is defective in sickle cell disease. That mRNA would be sent directly to the bone marrow cells using the specially targeted LNPs, enabling the bone marrow to produce healthy red blood cells that contain functioning beta-hemoglobin.

All that would need to be done is to give people a single intravenous injection of the mRNA LNP, and youll cure their sickle cell anemia, Weissman says. By contrast, the current FDA-approved gene-editing therapy for sickle cell requires the patients bone marrow be removed, treated, and then returned to the bodyan expensive and invasive procedure. The mRNA treatment could be simple enough to deliver in lower-income countries, where sickle cell disease impacts the health of millions of people.

An up-and-coming strategy for fighting cancer is a so-called cancer vaccine, which uses immune cells called dendritic cells (DCs). DCs perform surveillance for the immune system. When they detect something that shouldnt be there, whether its a virus, a bacteria, or even a cancer cell, the DCs chew it up, break it into its component molecules, and then show those foreign molecules to the immune cells that make antibodies.

Dendritic cells chew up viruses or other foreign bodies, and present the pieces to other immune ... [+] cells. T cells and B cells both play a role in mounting a long-lasting immunity against the pathogen.

When cancer grows slowly, though, it can slip past the DC surveillance network. To give the immune system a boost, a patients DCs are taken out and artificially loaded with tumor-specific proteins, or antigens. Back inside the body, the cells stimulate the generation of antibodies against the tumor.

Using mRNA to deliver the tumor antigen information to the DCs could provide a way to make this process easier, cheaper, and safer. BioNTech is currently conducting clinical trials on cancer vaccines for triple-negative breast cancer, metastatic melanoma, and HPV-positive head and neck cancers. Called FixVac, the vaccines include multiple tumor antigens that are frequently found across different patients. Early data published in September 2020 showed promise, suggesting that the mRNA therapy generates a lasting immune response, comparable to more expensive methods.

Karik, who is now a senior vice president at BioNTech, and Weissman both speak with an air of inevitability, as if they have only been waiting patiently for the world to catch up with their discovery. The two scientists told their stories recently at the 2nd annual mRNA Day celebration in San Diego, hosted by Trilink BioTechnologies in honor of their recently opened facility there. After hearing the tumultuous history of the technology and seeing promising new data, one attendee asked, what would you say was the turning point for mRNA therapeutics?

Karik responded simply, When people read our [2005] paper. We were waiting for somebody to respond, we did a lot of experiments, but we waited and waited. It was just too early for most people.

Weissman agreed. I think we were early, he said. It finally caught on, and it will hopefully change the world.

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The New Coronavirus Vaccine Is Changing The Future Of Medicine - Forbes