Naturally Treat & Heal The Cause of Pain with Regenerative Therapies – The Mountaineer

By Dr. John C. Haasis III, M.D

Daisy Stem Cell Therapy

Your body is an amazing feat of engineering. Many complex physical, chemical, and neurological processes all work together to make you who you are. Too much medicine today focuses on treating a symptom rather than solving a problem. Regenerative therapies are a spectrum of cutting edge therapeutic techniques used to naturally treat and heal the cause of a painful condition rather than masking the symptom. Therapies such as the ones listed below stimulate and accelerate your own bodys natural ability to heal itself.

Stem Cells

Stem cells are undifferentiated cells, which allow them to develop into another type of cell that is required to repair or replace damaged tissue. Stem cell therapy can repair tissues that are too damaged to heal on their own. Stem cells can stimulate the formation of cartilage, tendon, ligaments, bone and fibrous connective tissues.

Allograft Tissues

A purified amniotic source that contains a healing matrix of cytokines, growth factors, and proteins that helps to rejuvenate and heal damaged tissue can be used via injection.

Exosomes

Exosomes are extracellular vesicles which can be used alone or in combination with stem cell therapy to speed up healing. Exosome therapy can be injected into the affected area for orthopedic injuries, used in aesthetic procedures for cosmetic enhancement or given intravenously for anti-aging.

Platelets

Platelet rich plasm (PRP) therapy utilizes platelets taken from the patients own blood to rebuild damaged tendons and cartilage. Platelets normally circulated within the blood stream and are responsible for blood clotting and initiating a healing response in an acute injury. Many acute injuries do not heal adequately and can lead to chronic pain and loss of function of the injured area. Platelet rich plasma (PRP) therapy allows us to harvest the patients own platelets and re-inject those platelets into sites of injury to initiate healing and improvement of function.

Technology

All procedures are performed under the guidance of ultrasound or a fluoroscopy unit to maximize results. We have incorporated the latest innovations in equipment, supplies, and protocols to optimize outcomes. In addition, we have partnered with leaders in the field, with proven track records, to provide the very best stem therapy products to our patients.

Dr. John C. Haasis III, M.D., is Medical Director and Founder of Daisy Stem Cell Therapy and Advanced Regenerative Medicine Centers of the Carolinas. With over 25 years of comprehensive and interventional pain management experience, Dr. Haasis has treated thousands of patients in our region.

Dr. Haasis received his undergraduate degree in Biology from Pennsylvania State University was accepted into a Ph.D. program at Temple University where he studied molecular biology. He received his medical degree from the Medical College of Pennsylvania in 1992, followed by Anesthesia and Pain management training at Duke University Medical Center. He currently enjoys a thriving practice with six office locations in NC and SC. Over the years, he and his staff have made it their mission to help people manage their pain and improve function so that they can enjoy life again.

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Naturally Treat & Heal The Cause of Pain with Regenerative Therapies - The Mountaineer

CAR T-Cell Therapy UCARTCS1A Shows Early Activity in Relapsed/Refractory Myeloma – OncLive

Expansion and persistence of UCARTCS1A was observed and was found to correlate with clinically meaningful antimyeloma activity and serum cytokine changes in very heavily pretreated patients with multiple myeloma. Also, the CAR T-cell product was noted to be detectable in patients, regardless of donor and batch.

These preliminary data validate CS1 as a target for CAR T-cell products in multiple myeloma and that UCARTCS1A is a promising potential therapy for [those with this disease], Krina K. Patel, MD, MSc, an associate professor of the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, said during a presentation on the results.

One of the benefits that comes with utilizing an allogeneic CAR T-cell approach over an autologous approach is that it affords the opportunity for off-the-shelf product availability, according to Patel. Patients are able to avoid a prolonged wait for the CAR T cells to be manufactured; the cells are able to be administered within a couple of weeks, Patel explained. In contrast, it can take 4 to 5 weeks to bring an autologous product to a treatment center.

Scalable manufacturing is another benefit of allogeneic approaches, and this can reduce costs and yield 100 or more doses from 1 batch of donor cells. Also, for allogeneic approaches, T cells are collected from healthy donors; these patients have not been given many steroids, chemotherapy, or have undergone autologous transplant. As such, their T cells will likely be more potent, Patel explained. Lastly, more flexible dosing is an option with allogeneic approaches; this allows for the possibility of redosing and alternate schedules.

UCARTCS1A is the first allogeneic CAR T-cell product developed to target CS1 and SLAMF7, both of which are highly and consistently expressed in multiple myeloma, according to Patel. The product knocks out the TRAC gene to avoid graft-versus-host disease through disruption of T-cell receptor (TCR) assembly. The product also knocks out CS1 to facilitate robust expansion and yield, while avoiding fratricide. Lastly, UCARTCS1A has a RQR8 safety switch, which is a CD20 mimotope that can use rituximab (Rituxan) to kill the cells, if necessary.

Previously, the CAR T-cell product demonstrated durable in vivo efficacy against MM1S tumors. Here, NSG mice were given a 5 x 105 MM1S myeloma cell line, which is known to be pretty aggressive, Patel noted; this was labeled with GFP and was given for 10 days. Subsequently, the mice received the CAR T cells. Investigators observed CAR-positive cells at day 4 and M protein, which is a surrogate marker for multiple myeloma in mice and patients.

We were able to see an early response, as well. However, eventually, the T cells went down, and the myeloma started to go back up, Patel added. Looking at the imaging, mice who [received] CAR T cells obviously did much better and lived longer and there was a dose-dependent response where the mice that got the higher dose did better, with a much longer survival. Investigators were also able to demonstrate that the mice that received the CAR T-cell therapy experienced improvement in lytic lesions over time.

MELANI-01 enrolled patients with confirmed multiple myeloma per International Myeloma Working Group criteria who relapsed following previous therapy for their disease. To be eligible for enrollment, patients needed to have an ECOG performance status of 0 to 2 and acceptable organ function. They could have not previously received an investigational drug or cell/gene therapy targeting CS1.

The key eligibility [for this trial] is similar to most cell therapy trials [that are done in] myeloma. However, for most of those trials, patients are not able to have previously received CAR T cells or BCMA-directed therapies, Patel said. In this trial, [those are not] ineligibility [criteria]. Our patients had really relapsed/refractory [disease.]

After going through screening, patients received lymphodepletion chemotherapy that was comprised of fludarabine at a daily dose of 30 mg/m2 for 3 days followed by cyclophosphamide at a daily dose of 1 g/m2, also for 3 days. The [cyclophosphamide] dose was 2 to 3 times higher than what [has been] used in most other trials, Patel noted.

Patients then received treatment with UCARTCS1A. Patients were started at dose level 1, where they received 1 x 106/kg. One patient went on to dose level 2, which was 3 x 106/kg. Patients underwent their first disease evaluation at day 28.

The primary and secondary objectives of the study included safety and tolerability of UCARTCS1A, as well as determining the maximum-tolerated dose and efficacy of the product. Exploratory end points are examining expression of CS1 on multiple myeloma cells, UCARTCS1A expansion and persistence, and changes in serum biomarkers or immune cell reconstitution.

Patel shared information on 5 patients who received treatment with UCARTCS1A to date; 4 of the patients received dose level 1 (102-101, 102-109, 102-107, and 102-111) and 1 patient (102-113) received dose level 2.

Four of the 5 patients (102-101, 102-109, 102-107, and 102-113) had previously received over 11 lines of therapy and had most had previously received a BCMA-directed therapy. Just to put this into context, most of the autologous CAR T-cell trials that are done have patients who had a median of 5 to 6 prior lines of treatment, Patel noted.

One patient (102-111) had received only 4 prior lines of therapy and was the only patient who had cells expand and responded on dose level 1. However, the patient had very high-risk disease with 90% plasma cells. He had the most myeloma going into the trial, Patel said.

Notably, patient 102-113 who had received dose level 2 and also experienced an expansion of cells at day 7 had received 13 prior lines of therapy, including 2 prior BCMA-targeted CAR T-cell therapies, the last of which was administered just 5 months prior to the study.

Patient 102-111 was 55 years of age, had 4 prior lines of therapy and 90% of bone marrow involvement. He had relapsed within 6 months of every prior line of therapy and he never experienced more than a partial response (PR) to any of his prior treatments, according to Patel. When looking at his peripheral blood at day 28, investigators noted that the CD45+ CAR-positive lymphocytes was almost 72% and a subgroup of CD8+ effector cells that are TCRnegative CAR-positive cells, were about 46%.

[Some might] think that allogenic cells would not last very long, but for this patient, we definitely saw the majority of T cells still there that were CAR positive, Patel said. For him, we were able to get a bone marrow [sample] at month 3, where we could also see CD45+ CAR-positive cells at 60% in the bone marrow of all CD45+ cells. The CD8+ effector [cells] were at 92%.

Moreover, CAR-positive cells were observed in the patients peripheral blood starting at day 14; they peaked at day 21, and then started to decrease. However, some of these cells were still observed at day 80 to 86, according to Patel. The patients white blood cell count was low, while peripheral blood was high, until approximately day 28, before it started decreasing. However, the patients bone marrow remained high, even at day 77, in terms of the vector copy number of the CAR T cells.

This patient experienced grade 2 cytokine release syndrome (CRS) within the first week of cell infusion. The patient also developed hemophagocytic lymphohistiocytosis (HLH), which has previously been observed with other autologous CAR T-cell products in multiple myeloma. Investigators treated the patients with anakinra (Kineret), dexamethasone, etoposide, and the rituximab kill switch. The rationale for triggering the kill switch was because the patient had reactivation of HHV6, which developed into HHV6 encephalitis.

Per the FDA, we were monitoring HHV6 and HHV7 levels, as we do for most of our CAR T-cell therapy trials. We were monitoring this [and when his levels were high enough that we decided to treat], the patient got admitted for antivirals, improved, went home, and then came back with an encephalitis picture. Initially, we treated him dexamethasone and gave the rituximab kill switch thinking that if it was immune effector cell-associated neurotoxicity, we could kill off some of the cells. But in the end, it was HHV6 encephalitis.

Although the patient did improve, and he had double antiviral coverage, he eventually passed away on day 109 from organizing pneumonia in the context of prolonged lymphopenia in the absence of multiple myeloma progression.

At the time, he did not have any myeloma and he had [experienced] this response that he had never had before, a near complete response Patel explained. We looked at his bone marrow, which was minimal residual diseasenegative at the 10-5 level. However, because of the prolonged lymphopenia, he ended up with this infection.

Multiple factors may have contributed to the prolonged lymphopenia, including viral reactivation, concomitant antivirals, and recent prior stem cell transplant, Patel explained.

The other patient with expansion, patient 102-113, was observed to have 25% CD45+ CAR-positive lymphocytes in the peripheral blood at day 9, 77% of which were CD8+ effector cells, according to Patel. Notably, investigators were unable to collect a bone marrow sample from the patient. In the peripheral blood, investigators observed expansion at day 7 and then a peak, and then the vector copy number persisted over the time the blood samples were obtained.

This patient had previously received 14 lines of therapy, including 2 previous BCMA-directed CAR T-cell therapies and associated lymphodepleting regimens, autologous transplant, and venetoclax (Venclexta), as his last line of therapy. The patient did not have any options left and we saw this fantastic response, where the lambda light chains had gone done by almost 90%; his M protein had at least a PR by just day 14.

However, this patient had CRS and HLH, as well. We treated him with etoposide, anakinra, dexamethasone, and the rituximab kill switch and he had improvement in his platelet and his liver function tests, Patel added. The HLH clinically improved for him. However, at day 25, he passed away.

An autopsy revealed G5 hemorrhagic pancreatitis, although he had not exhibited any clinical signs of this condition during his hospital stay. Investigators also found disseminated mucormycosis and pseudomonal pneumonia.

Select serum cytokine changes over time were found to correlate with expansion of the CAR T-cell product. Cytokines were increased much more in the patients who expanded vs those who did not expand at all, Patel noted.

MELANI-01 is currently enrolling patients with protocol modifications, including restarting at dose level -1 (3 x 105). Moreover, lower doses of lymphodepleting chemotherapy are being administered now in an attempt to address lymphopenia and lead to added expansion. The trial will also have additional requirements for monitoring and managing patients with regard to opportunistic infections, as well as CRS and HLH.

Patel KK, Bharathan M, Siegel D, et al. UCARTCS1A, an allogeneic CAR T-cell therapy targeting CS1 in patients with relapsed/refractory multiple myeloma (RRMM): preliminary translational results from a first-in-human phase I trial (MELANI-01). 2021 American Society of Gene and Cell Therapy Annual Meeting; May 11-14, 2021; Virtual. Accessed May 13, 2021. Abstract 118.

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CAR T-Cell Therapy UCARTCS1A Shows Early Activity in Relapsed/Refractory Myeloma - OncLive

Rinri Therapeutics Secures Innovate UK Funding Grant for 3.2m Project to Advance its Novel Cell-Based Therapy to Restore Hearing Loss – PRNewswire

SHEFFIELD, England, May 13, 2021 /PRNewswire/ -- Rinri Therapeutics ('Rinri'), a biotechnology company developing a novel cell-based therapy to restore hearing loss, is delighted to announce that it has secured, a grant from Innovate UK, the UK's innovation agency. This grant will fund a 3.2 million project to further develop Rinri's novel stem cell therapy to reverse sensorineural hearing loss (SNHL) an area / a condition where there remains a significant global unmet need.

The project will be led by Rinri in collaboration with the Cell and Gene Therapy Catapult (CGTC), and the Universities of Sheffield and Nottingham.

Over the course of the project, the CGTC will help establish a process and analytical tools for clinical trial manufacture of Rinri's stem cell therapy for hearing loss, Sheffield University will further the nonclinical data package and Nottingham University will develop the necessary techniques for the first in human trial of Rinri's cell-based therapy to restore hearing loss.

Rinri's underlying technology, based on innovative stem cell research originating from the University of Sheffield, seeks to reverse SNHL by repairing the damaged cytoarchitecture in the inner ear. SNHL happens when there is damage to the hair cells in the cochlear and/or the auditory nerve. There are currently no pharmacological treatments available for SNHL despite the rapid increase in the number of patients that suffer from this condition globally.

Dr Simon Chandler, CEO of Rinri Therapeutics, commented: "We are delighted to receive this substantial grant from Innovate UK to conduct further important research into our stem cell therapy for hearing loss. We have made superb progress in refining and optimising our technology following our ground-breaking proof of concept data. This grant will be instrumental in supporting the development and initiating clinical studiesof our pioneering approach to reverse hearing loss."

Matthew Durdy, CEO of the Cell and Gene Therapy Catapult added: "Rinri's cutting-edge stem cell therapy is a very exciting development in the field, and we look forward to working with them to prepare for clinical manufacture. Combining forces under this Innovate UK funded grant will help accelerate the development of this promising technology."

Andrew Hogben, Head of Impact and Intellectual Property at the University of Sheffieldsaid: "Given Rinri was founded on pioneering research led by Professor Marcelo Rivolta at the University of Sheffield, we are really excited to participate in Rinri's Innovate UK funded project alongside Cell and Gene Therapy Catapult and Nottingham University to advance this novel treatment into the clinic."

Professor Douglas Hartley, from the School of Medicine at the University of Nottingham, said: "This significant award from Innovate UK is a substantial boost to our pioneering UK partnership that could lead to a revolution in the treatment of disabling hearing loss."

About Rinri Therapeutics

Rinri Therapeutics is a private biotechnology company developing advanced stem cell-based therapeutics to restore hearing. The company's pioneering technology seeks to reverse sensorineural hearing loss (SNHL) through the repair of the damaged cytoarchitecture in the inner ear. SNHL is estimated to affect 64 million patients in the US and 34 million in Europe. There are currently no pharmacological treatment options for SNHL patients.

Rinri, is backed by Boehringer Ingelheim Venture Fund (BIVF), UCB Ventures, BioCity, the University of Sheffield and the UK Future Fund. Rinri was founded in late-2018 and is headquartered in Sheffield, UK.

For more information, please visit: http://www.rinri-therapeutics.com

Contacts:

Rinri Therapeutics Dr Simon Chandler, CEO [emailprotected]

Citigate Dewe Rogerson Sylvie Berrebi, Frazer Hall E: [emailprotected] T: +44 (0)20 7638 9571

About Cell and Gene Therapy CatapultThe Cell and Gene Therapy Catapult was established as an independent centre of excellence to advance the growth of the UK cell and gene therapy industry, by bridging the gap between scientific research and full-scale commercialisation. With more than 330 employees focusing on cell and gene therapy technologies, it works with partners in academia and industry to ensure these life-changing therapies can be developed for use in health services throughout the world. It offers leading-edge capability, technology and innovation to enable companies to take products into clinical trials and provide clinical, process development, manufacturing, regulatory, health economics and market access expertise. Its aim is to make the UK the most compelling and logical choice for UK and international partners to develop and commercialise these advanced therapies. The Cell and Gene Therapy Catapult works with Innovate UK. For more information please visit ct.catapult.org.uk or visit http://www.gov.uk/innovate-uk.

For further information please contact

FTI Consulting for the CGT Catapult:

Michael Trace +44 (0) 203 319 5674 / [emailprotected]

George Kendrick +44 (0) 203 727 1411/ [emailprotected]

About The University of Sheffield With almost 29,000 of the brightest students from over 140 countries, learning along-side over 1,200 of the best academics from across the globe, the University of Shef-field is one of the world's leading universities. A member of the UK's prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teach-ing and research excellence across a wide range of disciplines. Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in. Sheffield has six Nobel Prize win-ners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields.

About The University of Nottingham The University of Nottingham is a research-intensive university with a proud heritage, consistently ranked among the world's top 100. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia - part of a globally connected network of education, research and industrial engagement. We are ranked eighth for research power in the UK according to REF 2014. We have six beacons of research excellence helping to transform lives and change the world; we are also a major employer and industry partner - locally and globally. Alongside Nottingham Trent University, we lead the Universities for Nottingham initiative, a pioneering collaboration which brings together the combined strength and civic missions of Nottingham's two world-class universities and is working with local communities and partners to aid recovery and renewal following the COVID-19 pandemic.

SOURCE Rinri Therapeutics

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Rinri Therapeutics Secures Innovate UK Funding Grant for 3.2m Project to Advance its Novel Cell-Based Therapy to Restore Hearing Loss - PRNewswire

With $52 Million Series A, Appia Bio Anticipates a Bright Future in Cell Therapy – BioSpace

Appia co-founder and chief executive officer, JJ Kang/Photo Courtesy of Appia Bio

Backed by $52 million in Series A financing led by 8VC and named after a feat of engineering in ancient Rome, Appia Bio jumped into the cell therapy fray this morning with a promising scalable technology platform.

The company is named after the Aqua Appia, which is the first Roman aqueduct. It was kind of a feat of engineering and it brought water to a lot more people, and that thematically connects well. We want to engineer these cells and provide a broader reach for cell therapy through allogeneic off-the-shelf, said Appia co-founder and chief executive officer, JJ Kang, Ph.D.

Appia is developing engineered allogeneic cell therapies from hematopoietic stem cells (HSCs) for cancer patients. Its ACUA platform utilizes the biology of lymphocyte development with CAR and TCR gene engineering to produce CAR-engineered invariant natural killer T (CAR-iNKT) cells from HSCs.

The Los Angeles-based biotech is spun out of the pioneering work ofLili Yang, Ph.D., an associate professor at the University of California, Los Angeles (UCLA).

In addition to the $52 million votes of confidence provided by 8VC, Two Sigma Ventures, and seed investors, Sherpa Healthcare Partners and Freeflow Ventures, Appias newly announced scientific board is packed to the brim with wisdom.

Appia is co-founded by Nobel laureate winner and former president of theCalifornia Institute of Technology, Dr. David Baltimore. Edmund Kim, Ph.D., former VP of corporate development atKite Pharma(Gilead Sciences), comes on board as chief operating officer, while Jeff Wiezorek, MD, former head of cell therapy development at Kite and a previous student of Baltimores, joins as chief medical officer.

One of those guys, Jeff, has been a post-doc with me, so hes well-trained, quipped Baltimore.

In an exploding and crowded field, how does Appia differentiate itself?

I think in being an off-the-shelf allogeneic cell, charged and ready to go, said Baltimore. The secret here is Lili Yang, who figured out how to grow very large numbers of iNKT cells from a single harvest of hematopoietic stem cells. So we can make large numbers of cells to treat many multiples of patients from a single donor source. And we can prepare that ahead of time. So that means that no matter what their own HLA [human leukocyte antigen] is, these cells can be used therapeutically.

AQUA is also able to leverage these iNKT cells in a scaleable manner.

The big step forward with this technology is that starting from these hematopoietic stem cells, we can drive to the these invariant NKT cells that are actually naturally quite rare. Through this platform, we can produce a lot of these cells and do so in a scaleable, fullyex vivomanner that gives us a path forward for industry use for commercialization, said Kang.

Appia is now ready to power its extensive research forward into the clinic.

We have space now and we have money, we have people, said Baltimore. Were in the process of the technology transfer. The second step is to show that it will work in animal systems. Lili has done that, but we want to be able to show that we can do that. Then is the big step: Preparing ourselves for initial clinical trials. That will be a little ways down the road, but with the investments that we have now, we should be in a position to carry that step through.

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With $52 Million Series A, Appia Bio Anticipates a Bright Future in Cell Therapy - BioSpace

Genenta Phase I/II Glioblastoma Data at ASGCT Show Temferon Delivered Tumor-Focused Interferon ExpressionData presented at the 2021 American Society…

MILAN, Italy and NEW YORK, May 14, 2021 (GLOBE NEWSWIRE) -- Genenta Science, a clinical-stage biotechnology company pioneering the development of an investigational hematopoietic stem progenitor cell immuno-gene therapy for cancer (Temferon), will present new clinical data from a Phase I/IIa study of Temferon in patients affected by glioblastoma multiforme (GBM) in an oral presentation at the 2021 American Society for Gene and Cell Therapy (ASGCT) Annual Meeting, taking place virtually on May 11-14, 2021.

The data presented at ASGCT are from Genentas ongoing trial of Temferon in patients with GBM. The presentation focuses specifically on patients who have undergone a follow-up surgical procedure for their cancer. In addition to being a treatment option, follow-on surgery provides investigators with an opportunity to understand the impact of therapies at a cellular and molecular level.

The ASGCT presentation shows that genetic markers of Genentas Temferon were detectable in tumor specimens from all four patients with progressive disease who underwent follow-on surgery. Furthermore, the expression of interferon- (IFN) responsive gene signatures in those tumors was increased compared with pre-treatment levels, which suggests that interferon- (IFN-) had been released locally in the tumor by cells derived from Genentas investigational treatment.

Carlo Russo, Chief Medical Officer at Genenta Science, said: These preliminary results provide exciting indications that Temferon acts in the way we anticipated even in the relatively inaccessible setting of glioblastoma multiforme. The data are encouraging and in line with our pre-clinical results, with early evidence that Temferon delivers biological effects that may impact the progression of individual lesions.

One of the four patients had two lesions removed at the second surgery; one was a prior lesion that had not been removed during the first surgery and was stable; the other was a relapsing progressing lesion that had developed at the first surgery site. Compared with the progressing tumor, the stable lesion displayed a higher proportion of T cells and Tie2 Expressing Monocytes (TEMs) within the myeloid infiltrate and had a higher IFN-response signature.

The data presented at ASGCT also supported the initial safety and tolerability profile of Temferon. Concentrations of IFN- in the plasma and cerebrospinal fluid of patients remained low, while IFN- responses were identified in myeloid cells that infiltrate tumors. Temferon-derived differentiated cells also persisted in peripheral blood and bone marrow for up to 18 months at lower levels, indicating the potential durability of the intervention. No dose limiting toxicities have been identified.

Presentation Details:

Title: Changes in the Tumor Microenvironment in Patients with Glioblastoma Multiforme Treated with IFN-a Immune Cell & Gene Therapy (TEM-GBM_001 Study)

Time: Friday May 14, 2021 at 1.30 PM Eastern Time (7.30 PM CET)

Presenting: Carlo Russo, CMO

To access the abstract please visit https://annualmeeting.asgct.org/

About Genenta Science

Genenta (www.genenta.com) is a clinical-stage biotechnology company pioneering the development of a proprietary hematopoietic stem cell gene therapy for the treatment of a variety of cancers. Temferon is based on ex-vivo gene transfer into autologous hematopoietic stem/progenitor cells (HSPCs) to deliver immunomodulatory molecules directly via tumor-infiltrating monocytes/macrophages (Tie2 Expressing Monocytes - TEMs). Temferon, which is under investigation in a Phase I/IIa clinical trial in newly diagnosed glioblastoma multiforme patients, is not restricted to pre-selected tumor antigens nor type and has been designed to reach solid tumors, one of the main unresolved challenges in immuno-oncology. Genenta is based in Milan, Italy, and New York, USA.

About Glioblastoma Multiforme Glioblastoma multiforme (GBM) is a rapidly-growing cancer of the glial cells that support the nerve cells within the brain. The main treatment for GBM is surgery to reduce the bulk of the tumor, which can prolong the lives of patients and to improve quality of life. A second round of surgery is increasingly considered to have significant benefit in prolonging the lives of patients with GBM. Even with treatment, GBM virtually always recurs, typically resulting in death within the first 15 months from diagnosis.

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Genenta Phase I/II Glioblastoma Data at ASGCT Show Temferon Delivered Tumor-Focused Interferon ExpressionData presented at the 2021 American Society...

Fascination with stem cell sensation leads to Fulbright scholarship – Monash University

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12 May 2021

PhD student Meg McFetridge has received a coveted Fulbright Future Scholarship

Meg McFetridge was first inspired by mechanobiology in her honours year, watching stem cells on hydrogel surfaces. One end of the hydrogel was soft, the other end stiff, with a stiffness gradient in between. When the stem cells felt the soft end they became fat; on the stiff end they turned to bone. I couldnt get it out of my head.

Four years later that fascination, her aptitude and a project Meg has devised as a PhD student have earned her a coveted Fulbright Future Scholarship for postdoctoral research at Cornell University, Ithaca, New York for eight months.

I was completely speechless, she said of the news. The woman on the end of the phone who told me Id got the scholarship was so excited; I was barely able to speak.

The Fulbright is highly prestigious, its a great thing for Monash too. It demonstrates the quality of the doctoral program that it can produce highly competitive postdoctoral scholars.

The Fulbright Program is the flagship foreign exchange scholarship program of the US. Its Future Scholarship will provide Meg with, among other benefits, a monthly stipend, full visiting researcher scholar fees, a round-trip airfare to New York, enrichment opportunities in Australia and the US with other international Fulbright scholars, and access to a professional network of distinguished Australian and American Fulbright alumni.

Meg, who will submit her PhD in August, works in her primary supervisor Professor Sharon Ricardos lab and is co-supervised by Professor Mibel Aguilar and Dr Mark Del Borgo.

She will conduct research in the US into a project she has devised in mechano-microscopy.

Cells and tissues push and pull on their surrounds to feel out where they are and what they need to do, she said. Mechano-microscopy is an umbrella term for a group of microscopy techniques that allow us to look at the complex relationship between cells and their physical environment. The Adie lab at Cornell University has developed a microscope thats one of a kind it combines multiple microscopy modes to get a complete picture of this interaction.

This microscope will allow us to tackle fundamental research questions in mechanobiology that have previously been near impossible to answer.

Meg moved to Monash, having completed honours at the University of Western Australia, after reading about a project for her PhD. This project offered me new challenges because its more translational than my previous work. The other thing about Monash is we have excellent facilities and a thriving research community which attracted me to make the move.

Her PhD project aimed to develop hydrogels to deliver stem cell therapy. In the long term were working towards safe and effective stem cell therapy for a broad range of diseases; in the short term were doing basic science to understand how we can create artificial environments that guide stem cells in the right direction.

During my PhD the fascination with mechanobiology was nagging me to ask what the cells were feeling in my hydrogels, but I didnt have the scope or the facilities to do so; thats why I need to go to Cornell, she said.

Meg, who will leave for the US early next year, hopes to act as a bridge between the fantastic research community here and researchers overseas who have the specialist equipment and are making advances in the field.

She has previously won poster awards at local and international conferences and was selected by Monash to be one of 35 students globally to take part in the two-week intensive SPARK Global Biomedical Innovation and Entrepreneurship Training Course in August 2019.

There were 81 Australian Fulbright awardees this year: 41 students and 40 scholars (including Meg).

About the Monash Biomedicine Discovery Institute at Monash University Committed to making the discoveries that will relieve the future burden of disease, the newly establishedMonash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Spanning six discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection and Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia.Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery

Media Enquiries Monash Media - Wendy Smith T: +61 425 725 836 E:wendy.smith1@monash.edu

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Fascination with stem cell sensation leads to Fulbright scholarship - Monash University

Safety and Efficacy of Consolidation Therapy with Ipilimumab Plus Nivolumab after Autologous Stem Cell Transplantation – DocWire News

This article was originally published here

Transplant Cell Ther. 2021 May;27(5):391-403. doi: 10.1016/j.jtct.2020.12.026. Epub 2020 Dec 30.

ABSTRACT

Autologous hematopoietic stem cell transplantation (ASCT) is a standard-of-care treatment for many hematologic malignancies. Progression of disease after ASCT is the primary cause of treatment failure. In this Phase Ib trial, we studied the safety and clinical effect of combined checkpoint inhibition therapy (CPIT) with ipilimumab and nivolumab as a consolidation strategy after ASCT for patients with high-risk diffuse large B cell lymphoma (DLBCL), mature T cell lymphoma (TCL), and multiple myeloma (MM). Starting at 14 to 28 days after ASCT, patients received ipilimumab (1 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 16, and 22) and nivolumab (3 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, and 26). Patients received a median of 5 doses of ipilimumab and 8 doses of nivolumab. Thirty-five patients were included in the intent-to-treat population. Ninety-four percent of the patients experienced immune-related adverse events (irAEs) of any grade. Ninety-seven percent of irAEs resolved spontaneously or after holding study drugs and instituting high-dose corticosteroid therapy. Progression-free and overall survival at 18 months post-ASCT for each disease cohort were 85.7% and 100% for primary refractory DLBCL, 28.6% and 57.1% for relapsed DLBCL, not evaluable and 80% for frontline TCL, 25% and 75% for relapsed TCL, 57.1% and 87% for high-risk transplant-nave MM, and 40% and 100% for MM relapsed within 3 years of first ASCT. We conclude that combined CPIT appears to be tolerable as a consolidation strategy after ASCT and in addition to the potential clinical efficacy observed in some subsets of disease, T cell receptor repertoire, T regulatory cell phenotype, and gut microbiota profiles provide a biologic rationale warranting further study of this approach.

PMID:33965177 | DOI:10.1016/j.jtct.2020.12.026

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Safety and Efficacy of Consolidation Therapy with Ipilimumab Plus Nivolumab after Autologous Stem Cell Transplantation - DocWire News

Munshi Explains Staging, Prognosis, and Treatment for a Patient With Acute Graft-vs-Host-Disease – Targeted Oncology

During a virtual Targeted Oncology Case-Based event, Pashna N. Munshi, MD, associate clinical director, Stem Cell Transplant and Cellular Immunotherapy Program, assistant professor of Medicine, Georgetown University School of Medicine at MedStar Georgetown University Hospital, discussed the case of a 48-year-old male patient with acute graft-versus-host-disease (GVHD).

Targeted OncologyTM: What factors contribute to the risk of acute GVHD in a patient like this one?

MUNSHI: A lot of donor-recipient factors and other conditions increase the risk of acute GVHD. [These include] gender matching, human leukocyte antigen disparity, degree of mismatch, and having an older donor. Theres also [blood group] incompatibility and definitely CMV mismatched status. Though now that the FDA has approved letermovir [Prevymis] for patients who are undergoing allogeneic transplant if they have a CMV-positive donor,1 were seeing very little CMV reactivation. That has been a bit of a game changer for the good.

Patients have an increased risk of GVHD if they receive a transplant from a peripheral blood stem cell source versus a bone marrow graft, because the peripheral blood has more T cells in its composition. The myeloablative regimens [are associated with greater risk of GVHD than] reduced-intensity regimens.2

Do you agree with these poll results? Would you start with systemic therapy for this patient?

It can get a little tricky whether you want to give patients systemic steroids or wait and see if something gentler might work. I tend to agree that, at this point, the patient needs to immediately start with systemic steroids, because there are 2 organ systems involved. Once the lower gastrointestinal [GI] tract gets involved, it surely portends a poor prognosis if the grade becomes worse. And they become refractory to steroids very quickly: 50% of these patients will eventually not respond to steroids.

How would you stage this patients GVHD?

There are many criteria for staging GVHD. The criteria that most clinical trials use are the Mount Sinai Acute GVHD International Consortium [MAGIC] criteria.3 They are adapted from the Glucksberg criteria, which are very similar.4

Three organ systems [are involved in] acute GVHD: the skin, the liver, and the GI tract. Skin involvement is graded on the basis of the body surface area involved. Liver involvement is graded on the basis of the total bilirubin level. Upper GI involvement is graded on the basis of anorexia, nausea, and vomiting, and it just comes in stage 0 or stage I, depending on if its persistent or not. To determine lower GI tract involvement, we measure stool volume, especially when patients are admitted to the hospital. But once they go home, we cant do that, so we ask them how many times a day they have diarrhea. Is it watery? Is it muddy? Whats the volume? Is it large or small?

The patient can characterize the stool and tell their doctor how many times per day: 4 times, 5 times, 6 times. This patient is having 4 episodes per day; that puts them in stage I lower GI GVHD. But with a 60% body rash, that puts them in stage III skin GVHD. So really getting up there with skin, but not so much yet for GI. Once each organ [involvement is] staged, theres an aggregate score based on the combination of these organs. Then we come up with the grade.

In this patient, with a stage III rash, stage I upper GI, and stage I lower GI GVHD, they have a total score of a grade 2 acute GVHD. This is still in the mild to moderate zone. Anything above grade 2 is considered very severe GVHD.

Would you recommend that this patient receive systemic steroids?

In the scheme of things, somebody who didnt have symptoms and now is having active symptoms, especially with lower GI tract involvement, definitely needs high-dose steroids to get in there and [stop] the inflammation.

On what would you base a prognosis for this patient?

We can risk stratify these patients on the basis of the stage of organ involvement.5 Broadly, they can be at a standard risk or at a high risk [of poor response to treatment, mortality, and transplant-related mortality]. The patient is at high risk once they have very active GI involvement [or] if they have 2 organs involved. This is one more reason to think about starting these patients early on steroids. Why is this important? Because once a patient has high-risk GVHD, the chance of response to steroids is even lower, and once they dont respond to steroids, there is a higher [risk of] transplant-related mortality. The probability of transplant-related mortality is 44% for patients with high-risk acute GVHD flares, [versus] 22% for patients with low-risk GVHD [P < .001]. These are a few things to think about. Act very swiftly if a patient has 2-organ involvement, especially the lower GI tract.

Can biomarkers guide treatment decisions in this case?

In the field of GVHD, biomarkers are a very exciting advancement. We want a prognostic model of which patients will get GVHD. Can biomarkers in the blood [help] prevent GVHD and improve transplant outcomes?

A large prospective trial was done through the Bone and Marrow Transplant Clinical Trials Network where a set of 6 biomarkers were tested at several time points after the transplant.6 They saw that they could predict when GVHD happened by using these biomarkers. They could see that as the levels of these biomarkers increased, the patients had higher scores of GVHD. Once treatment was started, if specific biomarkers went down it was predictive of response at day 28 [56% vs 17%; odds ratio, 6.32; P = .001] and also predictive of [decreased] transplant-related mortality by day [180 (49% vs 87%; P < .0001)]. If all these biomarkers went up aggressively, overall survival was lower [P < .0001].

The MAGIC Consortium also tried to test biomarkers.7 They looked at 2 biomarkers, REG3Athe regenerating islet-derived 3-alpha, which is specific for the GI tract and ST2. Looking at these 2 biomarkers, they came up with an algorithm of prediction. On the basis of how these biomarkers responded at the time of GVHD and to treatment, they could predict mortality by 6 months. In clinical practice, it is difficult to use this day in and day out. We still use our clinical skills to assess the degree of GVHD. But all patients eventually get treated the same waywith high-dose steroidsdespite biomarkers being elevated or not.

At this point, [biomarker data] may tell us an association rather than a causality. Were not openly using biomarkers to guide our practice, but I think were learning to use them a bit more and knowing that theres something out there that could be used as a predictive tool. It is an exciting development.

Are there alternatives to systemic steroids?

Steroids remain the mainstay. We need to see if we can move to other therapies that are coming down the pipeline.

Data from the REACH1 [NCT02953678] and REACH2 [NCT02913261] trials led to ruxolitinib [Jakafi] approval.8,9 If we can use ruxolitinib in an up-front setting, [maybe we] can use the newly approved rho-kinase or ROCK2 inhibitors as well.10 We want to think about steroid-sparing agents. Maybe biomarkers can guide us in the future for that. But right now, in terms of, Do I start my patient on treatment? or Will they respond to this treatment, I find that [biomarkers are] still not a very useful tool because at the end of the day, the patients all still need to be started on steroids.

The minute you see that your patient is not responding to steroids, very quickly start them on a JAK2 inhibitor.

How do you dose steroids?

This patient received 2 mg/kg of prednisone per day for 14 days. Two mg/kg is a very high dose. The standard is 1 to 2 mg/kg.11 There are data to show that 2 mg isnt any different from 1 mg.12 But a lot of times, if its a very active, severe flare, we will use 2 mg/kg. Im not sure if I would have done 2 mg/kg in this case, but its certainly not out of the realm of treating these patients.

The goals of primary therapy for acute GVHD are to stabilize the organ manifestations, or improve them, and limit long-term treatment toxicity. We want to improve functional capacity and prevent any reduction in quality of life. First-line therapy is always with corticosteroids. Now ruxolitinib is approved for second-line therapy.8 There have been data to show that it can improve overall survival.

How do you taper glucocorticosteroids after achieving initial response?

If the patient is taking 2 mg/kg of steroids, an average 70-kg person, thats over 100 mg of steroids. After 2 weeks, they probably are not getting up from a seated position anymore with all the muscle wasting that can happen.

[As soon as they start to show improvement, it would be safe to start to taper the dose.] Traditionally, [the patient receives the full dose for] at least a week or 10 days. Then it is traditional to decrease the dose 10% every 5 to 7 days, gently coming down, making sure that the patient is not having any flares.

Describe the multidisciplinary teambased approach that you use for acute GVHD.

The incidence of acute GVHD in the patient population is anywhere from 30% to 50%, despite the best [efforts at] prophylaxis. Most patients will get some form of acute GVHDit can go up to even 80%. This [necessitates] a multidisciplinary team approach. If the patient is having diarrhea, theyre having malnourishment. Theres nausea or anorexia, so theyre not eating on top of that. Then theres skin rash, so the risk of infections and cellulitis. Theyre in pain. A dermatologist probably should be involved at some point. A nutrition team is also needed. If theyre on high-dose steroids, physical therapy should be involved up front. So early involvement of a whole team is very important. Thats usually how I treat my patients and usually how centers of excellence continue to treat active patients with GVHD after transplantation.

How do you determine if a patients GVHD is steroid refractory?

The strict definition of steroid refractoriness or resistance is if theres progression of acute GVHD within 3 to 5 days of starting high-dose steroids, or theres failure to improve within 1 week of starting these steroids, or theres incomplete response after more than 28 days of any immunosuppressive treatment.13 So, by and large, in 3 days or a maximum of 7 days, [it will be clear] if the patients GVHD is going to be steroid refractory or not.

Steroid dependence is [defined as when] the patients GVHD initially responded to steroids, but the disease flares when the dose is tapered, so they cannot be taken off the steroids.

Steroid intolerance is when the patient develops [unacceptable toxicity from steroids such as] uncontrolled diabetes or myopathies. Then it becomes hard to keep them on steroids.

What are the treatment options for patients with steroid-refractory GVHD?

Ruxolitinib now has been FDA approved for steroid-refractory acute GVHD, and its a category 1 definition.8,11 Ibrutinib [Imbruvica] has also been approvedits only FDA-approved indication is for chronic GVHD.14 There are many other treatment options [in the National Comprehensive Cancer Network guidelines].11 Oncologists always end up using some combination or other depending on which of these different immune suppression medications they are comfortable using.

What new treatments are in the pipeline?

In terms of BTK inhibitors, I dont think theres anything other than ibrutinib at this time point. There are many JAK inhibitors being studied.15 Baricitinib is another JAK inhibitor thats actively being studied for chronic GVHD, as well as for pulmonary GVHD.16 Then there are other rho-kinase inhibitors, called ROCK2 inhibitors. This is really making waves. Were very excited about this drug because the response rates are very high, about 70%.10 Its a smaller study, but clearly it has antifibrotic pathways. So I think thats going to be used much more in the up-front setting.

Then theres also alpha-1 antitrypsin, which targets the liver and macrophages and has very promising results from trials done at Dana-Farber Cancer Institute and Michigan.17 So I think were going to see very different characteristics of how to approach GVHD.

What data support the use of ruxolitinib in this setting?

The REACH1 study led to the approval of ruxolitinib for steroid-refractory acute GVHD.9,18 In this phase 2 trial, patients with steroid-refractory acute GVHD got ruxolitinib (5 mg twice a day) with or without a calcineurin inhibitor. They were allowed to remain on steroids. The primary end point of this trial was overall response rate [ORR] at day 28. They also looked at response rates at day 56 and day 100, biomarkers, failure-free survival, and durability of these responses. The ORR at day 28 was very high: 54.9%.18 The best ORR, which was at any given time during the treatment, which was as high as 73.2%. The median time to response was 7 days. So this was very quick. The median duration of response was 345 days, with more than 6 months follow-up. Nonrelapse mortality at 6 months was 44.4%. There were deaths from infections, etc, but not related directly to ruxolitinib.

Subsequently there was a phase 3 trial, REACH2.19 They looked at higher doses of ruxolitinib in steroid-refractory acute GVHD. They started off with 10 mg [of ruxolitinib] twice a day. This study had a similar primary end point of ORR at day 28. This was compared with best available therapy. This was done in Europe, so [the comparison was to the] best available therapy used in Europe, like anti-thymocyte globulin, sirolimus [Rapamune], etanercept [Enbrel], photopheresis, or other therapies; all things that we would use in the United States as well. They looked at similar key secondary end points, [including] duration of response at day 56.

The ORR for ruxolitinib was 62% at day 28, compared with the best available therapy arm, which was 39% [odds ratio, 2.64; 95% CI, 1.65 to 4.22; P < .001].19 Durable overall response at day 56 [was higher in the ruxolitinib group than it was in the control group (40% vs 22%, odds ratio, 2.38; 95% CI, 1.43-3.94; P < .001)].19

The lower grade acute GVHD, which was grade 2, had the highest complete response rate with ruxolitinib: 50.9% compared with just 26.4% with best available therapy.19 This is quite remarkable to have a complete response in GVHD so quickly. When you get to higher grades of GVHD, the complete response rate for ruxolitinib is not as impressive; its less than 30%. But its still much higher than the [response rates of] other therapies we would have otherwise treated these patients with in steroid-refractory disease. The key point is to diagnose steroid refractoriness early. Then get ruxolitinib in there to break the cycle and break the progression of organ grade to something higher.

The loss of response wasnt statistically significant. The estimated cumulative incidents for the loss of response at 6 months was 10% in ruxolitinib compared with 39% in the control arm.19 So patients continued to maintain responses, which, again, is what we want to see. We dont want to see flares if they come off steroids.

[Of the 4 organ systems involved in GVHD], the skin responses were the best with ruxolitinib. Lower GI and liver GVHD did have good responses, but the responses were not as remarkable. Ruxolitinib is an ideal drug in this setting, on the basis of the organ responses.

A secondary end point was failure-free survival, basically indicating a time point from randomization to either nonrelapse-related death or any new GVHD. This was not statistically significant because it was not designed to compare ruxolitinib survival outcomes with control therapy. But there were 5.0 months median failure-free survival with ruxolitinib compared with 1.0 month with control [hazard ratio for relapse or progression of hematologic disease, nonrelapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35-0.60]. That tells you that the responses were maintained, and the treatment was still working.

[Most of the adverse events associated with ruxolitinib] were expected; the bone marrow is recovering so its a bit fragile. [The most common was] thrombocytopenia. You can reduce the dose of ruxolitinib down to 5 mg adjusted accordingly or support patients with transfusions. CMV reactivation was also common. But again, with letermovir, that happens less and less.

References: 1. Merck receives FDA approval of Prevymis (letermovir) for prevention of cytomegalovirus (CMV) infection and disease in adult allogeneic stem cell transplant patients. News release. Merck. November 9, 2017. Accessed April 7, 2021. https://bit.ly/3fS6S0Q

2. Scott BL. Long-term follow up of BMT CTN 0901, a randomized phase 3 trial comparing myeloablative (MAC) to reduced intensity conditioning (RIC) prior to hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplasia (MDS) (MAvRIC Trial). Biol Blood Marrow Transplant. 2020;26(3):S11. doi:10.1016/j.bbmt.2019.12.07

3. Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10. doi:10.1016/j.bbmt.2015.09.001

4. Martino R, Romero P, Subira M, et al. Comparison of the classic Glucksberg criteria and the IBMTR Severity Index for grading acute graft-versus-host disease following HLA-identical sibling stem cell transplantation. International Bone Marrow

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Munshi Explains Staging, Prognosis, and Treatment for a Patient With Acute Graft-vs-Host-Disease - Targeted Oncology

Omeros’ Narsoplimab Pivotal Trial Data to Be Shared as an Oral Presentation at the European Hematology Association Congress – Business Wire

SEATTLE--(BUSINESS WIRE)--Omeros Corporation (Nasdaq: OMER) today announced that data on organ function improvement from Omeros pivotal trial of narsoplimab for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) will be shared as an oral presentation at the 2021 European Hematology Association (EHA) Virtual Congress. The presentation, entitled Narsoplimab (OMS721) Treatment Contributes to Improvements in Organ Function in Adult Patients with High-Risk Transplant-Associated Thrombotic Microangiopathy, will be delivered by Miguel-Angel Perales, M.D., Chief of Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center.

Dr. Perales oral presentation will be available on demand through the EHA Virtual Congress platform to registered meeting attendees beginning Friday, June 11, 2021 at 9:00 am CEST / 3:00 am EDT. The presentation abstract (S241) can be accessed on EHAs website.

About Hematopoietic Stem Cell Transplant-associated Thrombotic Microangiopathy

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a significant and often lethal complication of stem cell transplantation. This condition is a systemic, multifactorial disorder caused by endothelial cell damage induced by conditioning regimens, immunosuppressant therapies, infection, graft-versus-host disease, and other factors associated with stem cell transplantation. Endothelial damage, which activates the lectin pathway of complement, plays a central role in the development of HSCT-TMA. The condition occurs in both autologous and allogeneic transplants but is more common in the allogeneic population. In the United States and Europe, approximately 25,000 to 30,000 allogeneic transplants are performed annually. Recent reports in both adult and pediatric allogeneic stem cell transplant populations have found an approximately 40-percent incidence of HSCT-TMA, and high-risk features may be present in up to 80 percent of these patients. In severe cases of HSCT-TMA, mortality can exceed 90 percent and, even in those who survive, long-term renal sequalae (e.g., dialysis) are common. There is no approved therapy or standard of care for HSCT-TMA.

About Narsoplimab

Narsoplimab, also known as OMS721, is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement. Importantly, inhibition of MASP-2 does not appear to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection. Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2.

A biologics license application (BLA) is under priority review by the U.S. FDA for use of narsoplimab in the treatment of HSCT-TMA, and the drug is in Phase 3 clinical programs for immunoglobulin A (IgA) nephropathy and atypical hemolytic uremic syndrome (aHUS). Narsoplimab is also being evaluated for the treatment of COVID-19 as a part of the I-SPY-COVID-19 platform trial sponsored by Quantum Leap Healthcare Collaborative. The FDA has granted narsoplimab breakthrough therapy designations for HSCT-TMA and for IgA nephropathy; orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies, for the treatment of HSCT-TMA and for the treatment of IgA nephropathy; and fast track designation for the treatment of patients with aHUS. The European Medicines Agency has granted orphan drug designation to narsoplimab for treatment in HSCT and for treatment of primary IgA nephropathy.

About Omeros Corporation

Omeros is a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting inflammation, immunologic diseases (e.g., complement-mediated diseases and cancers) and central nervous system disorders. Its commercial product OMIDRIA (phenylephrine and ketorolac intraocular solution) 1%/0.3% continues to gain market share in cataract surgery. Omeros lead MASP-2 inhibitor narsoplimab targets the lectin pathway of complement and is the subject of a biologics license application under priority review by FDA for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy. Narsoplimab is also in multiple late-stage clinical development programs focused on other complement-mediated disorders, including IgA nephropathy, atypical hemolytic uremic syndrome and COVID-19. OMS906, Omeros inhibitor of MASP-3, the key activator of the alternative pathway of complement, is in a Phase 1 clinical trial, and the companys PDE7 inhibitor program OMS527, targeting addiction and movement disorders, has successfully completed a Phase 1 trial. Omeros pipeline holds a diverse group of preclinical programs including a proprietary-asset-enabled antibody-generating technology and a proprietary GPCR platform through which it controls 54 GPCR drug targets and their corresponding compounds. One of these novel targets, GPR174, modulates a new cancer immunity axis recently discovered by Omeros, and the company is advancing GPR174-targeting antibodies and small-molecule inhibitors. For more information about Omeros and its programs, visit http://www.omeros.com.

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Omeros' Narsoplimab Pivotal Trial Data to Be Shared as an Oral Presentation at the European Hematology Association Congress - Business Wire

Icy Microneedle Patch Delivers Cell Therapy, Then Melts – Freethink

City University of Hong Kong (CityU) scientists have created a new microneedle patch to deliver cell therapies but rather than using traditional materials for their needles, they used ice.

The challenge: Cell therapies use living cells to treat medical conditions. Stem cell transplants are a form of cell therapy, as are some types of cancer immunotherapy.

These cells are typically transplanted into the patient via an implant, injection, or surgical graft. Not only can those delivery methods be painful and invasive, they also carry a risk of infection and must be administered by an experienced professional.

That limits the use of cell therapy to people who are willing to subject themselves to the transplantation process and who also have access to professionals capable of administering them.

Ice, ice baby: Microneedle patches are a growing trend in drug delivery. They're usually about the size of a postage stamp and are covered in tiny needles made of biodegradable substances packed with drugs.

Press the patch down on the skin like a band aid, and the needles break off from the back of the patch. They then dissolve into the skin, painlessly delivering the drug.

CityU created the microneedles for its patch out of ice, packed with living cells, coated in a protective medium.

Ice is easier to make and work with than the materials traditionally used for dissolving micropatches, but it melts just as readily. Even better, the icy microneedles can preserve the viability of living cells something other types of patches can't do.

The freezing cold water: Because the microneedles are made of ice, they would have to be transported and stored frozen, which could be a limiting factor in some places.

Additionally, the icy microneedle patch performed well when used to deliver a cell therapy to mice as a proof of concept, but it still needs to be proven safe and effective in humans.

What's next: If CityU's microneedle patch is cleared for use in people, it could have applications even beyond cell therapy.

"This device can also package, store, and deliver DNA, vaccines, and more."

"This device can also package, store, and deliver other types of bioactive therapeutic agents, such as proteins, peptides, mRNA, DNA, and vaccines," lead researcher Xu Chenjie said in a press release.

"I hope this device offers an easy-to-use and effective alternative method for the delivery of therapeutics in clinics."

We'd love to hear from you! If you have a comment about this article or if you have a tip for a future Freethink story, please email us at [emailprotected].

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Icy Microneedle Patch Delivers Cell Therapy, Then Melts - Freethink