Category Archives: Cell Therapy

The administration of a third dose of a SARS-CoV-2 mRNA vaccine yielded seroconversion responses in patients treated with hematopoietic cell transplantation or cellular therapy following initial failure of seroconversion after the first 2 vaccine doses.

The administration of a third dose of a SARS-CoV-2 mRNA vaccine yielded seroconversion responses in patients treated with hematopoietic cell transplantation (HCT) or cellular therapy, such as CAR T-cell therapy or bispecific T-cell engagers (BiTEs), following initial failure of seroconversion after the first 2 vaccine doses, according to results from a study published in Cancer Cell.1

Among 75 patients who received allogeneic HCT (n = 30), autologous HCT (n = 26), CAR T-cell therapy (n = 10), or BiTEs (n = 9), and did not undergo seroconversion following the primary administration series of an mRNA-based SARS-CoV-2 vaccine, 59% of all evaluated patients developed antibodies following the third dose. Specifically, seroconversion rates were 63% for patients who received autologous HCT, 58% for those who received allogeneic HCT, 40% for patients administered CAR T-cell therapy, and 67% among patients given BiTEs.

Notably, the use of the approved vaccines BNT162b2, mRNA1273, or a mix-and-match strategy, all produced similar results.

A third dose should be considered for every transplant, CAR T-cell therapy, and BiTE recipient, as often as possible, co-study author Muhammad Bilal Abid, MD, MRCP, an assistant professor of medicine in the divisions of Hematology/Oncology and Infectious Diseases at the Medical College of Wisconsin, said in an interview with OncLive. For patients who do not respond to a third dose, a subset of patients will benefit from the reassessment of antibodies. If a third dose does not work, go for a fourth dose [and] this should be discussed with an infectious disease colleague at the center. There is a multidisciplinary collaborative approach that we have to provide.

Patients who have received HCT or cellular therapy have experienced poor outcomes after developing COVID-19.2 Notably, these patient populations have also shown lower response rates to SARS-CoV-2 vaccines, with responses for patients who underwent HCT and cellular therapy ranging from 50% to 80% and 20% to 30%, respectively.3,4

This study aimed to investigate the serological response to a third booster dose of a SARS-CoV-2 vaccine in patients who had received HCT or cellular therapy and did not seroconvert following the 2-dose primary vaccination series. Notably, patients who developed COVID-19 prior to the administration of the third dose were excluded from the study. Patients who had antibody testing within 2 weeks of the booster were also excluded.

To determine if patients seroconverted following a second vaccine dose, the AdviseDx SARS-CoV-2 IgG II assay was used to detect immunoglobulin G antibodies directed against the receptor-binding domain of the SARS-CoV-2 S1 subunit of the spike protein. The same assay was used to detect response following the booster dose. Patients were required to have at least 28 days between the second dose and booster shot, plus 14 days to antibody titer testing after receiving the booster.

The median age of patients who underwent seroconversion to the booster dose was 70 years (range, 31-77) compared with 66 years (range, 35-81) in patients who did not seroconvert following the booster (P = .04). Among male patients, 53% experienced seroconversion compared with 71% of female patients. In patients who went less than 12 months between HCT or cellular therapy and vaccination, 56% had seroconversion with the booster compared with 61% who had a duration of 12 months or longer between therapy and vaccination.

In patients who had seroconversion with the booster dose, the median interval between the second dose and booster was 172 days (range, 28-296) compared with 165 days (range, 93-223) for patients who failed to achieve seroconversion. The median interval between booster and humoral response assessment was 58 days (range, 14-140) in the patients who had seroconversion vs 47 days (range, 18-127) in the patients who did not.

The study authors pointed out that several factors may contribute to the continued lower response rates among patients who received CAR T-cell therapies compared with HCT or BiTEs. Preexisting, profound immunosuppression in this patient population could play a role, along with heavy pretreatment status, which could include prior HCT, lymphodepletion chemotherapy, and bridging chemotherapy. Toxicities such as cytokine release syndrome and immune effector cellassociated neurotoxicity syndrome requiring corticosteroids and tocilizumab (Actemra) may also contribute to lower vaccine responses.

Continued blunted responses are concerning among [patients who receive] CAR T-cell therapies, Abid said. They are certainly an incongruence with other reported literature. Recipients of CAR T-cell therapy are profoundly immunosuppressed by the time they get the CAR T-cell therapy primarily because of their underlying disease being so refractory.

Other studies will continue to explore the effectiveness of a third vaccine dose on these patient populations, along with research examining the effect of a fourth dose. Additionally, monoclonal antibodies could also have a role for aiding these patients.

We need to see the efficacy and safety data of monoclonal antibodies: sotrovimab [Xevudy] and Evusheld [tixagevimab and cilgavimab] in the preexposure setting for the prevention of progression of illness, Abid said. Thats something thats worth exploration.

Link:
COVID-19 Booster Yields Responses After Failure of Initial Vaccine Doses in Prior HCT or CAR T-Cell Therapy Recipients - OncLive

Frederick Lock, MD, spoke about clinicians can best utilize the treatment of axicabtagene ciloleucel for patients with large B-cell lymphoma.

Frederick Locke, MD, vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy as well as program co-leader of Immuno-Oncology at Moffitt Cancer Center in Tampa, Florida, spoke to CancerNetwork about axicabtagene ciloleucel (Yescarta; axi-cel) for patients with relapsed/refractory large B-cell lymphoma (LBCL) and how patients can best benefit from this treatment.1 The recent approval of the therapy was for patients who received frontline chemoimmunotherapy and relapsed within 12 months based on results from the phase 3 ZUMA-7 trial (NCT03391466) which compared axi-cel with standard of care therapy.2

The main thing for community oncologists to realize is that CAR T-cell therapy can be given to patients who are older and have comorbidities. It can be given to younger patients, and if patients need the FDA-approved label, they should be referred in for evaluation and consideration of CAR T-cell therapy. Unfortunately, theres some misinformation out there in the community, in the Twitterverse, and elsewhere. These clinical trials that led to this approval enroll patients who had a poor prognosis, patients with high tumor burden. In fact CAR T-cell therapy works better than chemotherapy for patients with large amounts of tumor [burden], so the community oncologists should recognize that what we all want is whats best for the patients. The data are clear that CAR T-cell therapy, if given as a second-line treatment offers the best outcomes for patients with LBCL.

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Frederick Locke, MD, Speaks to Clinicians on the Use of Axi-cel in LBCL - Cancer Network

In pursuit of its ongoing mission to achieve Victory Over Cancer, the V Foundation for Cancer Research announced its renewed support and a new $250,000 grant for the University of Floridas efforts to combat brain cancer in children. Combined with private support, a total of $600,000 in new funding will bolster critical research programs.

I am grateful for the V Foundations continued support, said Duane Mitchell, M.D., Ph.D., co-director of UFs Preston A. Wells Jr. Center for Brain Tumor Therapy and the Phyllis Kottler Friedman Professor in the Lillian S. Wells Department of Neurosurgery at UFs College of Medicine, part of UF Health, the universitys academic health center. The V Foundation is one of the nations premier supporters of cancer research. Its an incredible honor to be a beneficiary of their generosity for a number of years. This sustained level of commitment from the V Foundation is vital in enabling my team to bring our research to the next level.

Brain cancer is now the leading cause of cancerrelated death in children, due in part to significantimprovements in outcomes for pediatric patients with more common cancers such as leukemia. Among other areas, Mitchell and his team have advanced novel immunotherapy treatments for medulloblastoma, the most commonmalignant brain tumor in children.

When asked about this partnership, Shane Jacobson, V Foundation chief executive officer, said that Mitchells research is truly game-changing.

While science has made significant strides against pediatric cancers, there are still so many questions about brain cancer, Jacobson said. We applaud his forward-thinking approach to stopping the disease. He is offering children with cancer and their families hope for a brighter future. We look forward to seeing the impact of his success.

Under Mitchells leadership, UF Health has pioneered an approach for pediatric brain tumorscalled adoptive T cell immunotherapy. Adoptive T cell therapy involves expanding tumor-reactive killer T cells to large numbers outside of a patient, reprogramming the cells to specifically target brain tumor cells, then reintroducing these immune cells into the body. This approach is currently undergoing evaluation in a firstinhuman clinical trial at UF Health.

This research is the culmination of years of hard work, said Mitchell, associate director of innovation and discovery at the UF Health Cancer Center and director of the UF Clinical and Translational Science Institute. Thank you to all of our donors for providing us the opportunity to continue this important research and to realize our vision to make a transformative impact on childrens lives.

Mitchells research team plans to advance this treatment platform by using genomictechnology to identify patientspecific antigens in medulloblastoma tumors, which are the most common malignant brain tumors in children. Once isolated and expanded outside of the body, these T cells will recognize unique tumor targets, called neoantigens. If the objectivesof the study are met, Mitchells team could significantly enhance the specificity and potency of this already promising platform and translate the findings into innovative clinical trials for children battlingbrain cancer.

Mitchell expects that immune therapies such as adoptive T cell therapy will lead to more effective treatments for those who do not benefit from chemotherapy, radiation, surgery or a combination of those treatments.

Since 2012, The V Foundation has generously supported UF Health, giving a total of more than $1.5 million, including $1.3 million to pediatric causes.

Media contact: Todd Taylor attmtaylor4@ufl.edu or 317-590-4399

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Fighting pediatric cancer focus of V Foundation-UF Health collaboration - UF Health News

With further research, a selection of combination therapies could increase patient response in various cancer types.

Immunotherapy and radiotherapy have both improved survival rates for cancer, and combination therapies have potential to be even more effective and reduce recurrence. A recent review published in Frontiers in Oncology examined the mechanisms of immunotherapy and radiotherapy and how they can be combined and administered for maximum efficacy.

Radiotherapy is standard for cancerous tumors, with approximately 70% of patients with tumors being treated with it. It works by damaging the DNA of tumor cells within the irradiation field to control tumor growth. Data has increasingly shown that radiotherapy also leads to the release of myeloid-derived suppressor cells, M2-like tumor-associated macrophage, T-regulatory cells, N2 neutrophils, and immunosuppressive cytokines, promoting an immunosuppressive microenvironment.

Advances in technology have made radiotherapy more precise and effective, with proton heavy ion therapy being the most advanced option in the current treatment landscape. With the advancement of heavy ion therapy equipment and technology, the decline of treatment costs, and the advancement of research, heavy ion therapy will gradually be popularized in various countries across the world, study authors wrote.

Recent research has also found an abscopal effect caused by radiotherapy, further suggesting that radiotherapy affects not just the tumor site of treatment, but also the immune system.

Many preclinical studies have shown that irradiation triggers immunogenic cell death (ICD), which promotes the release of tumor-associated antigens, changes the tumor microenvironment (TME), and activates the immune system to exert an anti-tumor immune response, the authors wrote.

Radiation alone does not eradicate all malignant cells, though. Tumors with hypoxic cells can be resistant to radiotherapy compared with more oxygenated cells. Hypoxia can also lead to HIF signaling pathway activation, causing gene expression that can help tumors survive. A variety of other TME changes due to radiotherapy can also spur cell growth, and both short- and long-term adverse effects can occur.

Radiotherapy has seen advances in recent years, but as immunotherapy has gained traction, it has emerged as the most likely route to find a cancer cure, study authors wrote. The use ofimmune checkpoint inhibitors (ICIs) tumor vaccines, adoptive cell therapies, cytokine therapies, and other immunotherapies has increased in recent years.

Immunotherapy alone, however, is only used on a selection of tumor types in clinical practice and does not benefit all patients. Only approximately 10% to 30% of patients respond to single ICIs because of the complexity of cancer cell immune systems and tumor microenvironments (TMEs). Single ICIs or combination therapy is most likely to be effective in hot tumors, which have tumor-infiltrating lymphocytes (TILs), versus cold tumors, which do not have TILs. Immunotherapy can also lead to immune-related adverse events that can happen in all organs.

Given the resistance of hypoxic cells to radiotherapy and the generally low response to single immunotherapy, the 2 methods can be complementary. Radiotherapy can release tumor neoantigens, induce ICD, and have an anti-tumor effect in vivo.

Combinations of radiotherapy and immunotherapy have been increasingly studied, although large-scale clinical data are still limited. These combinations include ICIs and radiotherapy, tumor vaccine and radiotherapy, adoptive cell therapy and radiotherapy, and cytokine therapy plus radiotherapy.

Combining radiotherapy with ICIs targeting programmed cell death receptor 1 and programmed cell death ligand 1is one promising option that has been approved in certain advanced lung cancers and has been most effective in non-small cell lung cancer. However, many of these patients are still resistant to ICIs.

With tumor vaccines, which do not elicit tumor-eliminating immune response alone, radiotherapy may enhance immune response in vivo through several mechanisms. Various trials are underway investigating this combination.

Adoptive cell therapy, which is done by isolating immunoreactive cells from patients and reintroducing them to target antigen-specific tumor cells, is another increasingly studied treatment option that includes chimeric antigen receptor (CAR) T-cell therapy. Approximately 90% of patients experience relapse with CAR T-cell therapy, and early data show that radiotherapy may promote CAR T-cell effectiveness in solid tumors.

Cytokines, which regulate innate and adaptive immunity, have been shown to have significant anti-tumor activity but have dose-limiting severe toxicity that inhibits their efficacy. Studies are ongoing, but there may be potential for radiotherapy with adjuvant cytokine treatment or cytokine treatment followed by radiotherapy to increase effectiveness.

Study authors also highlight the development of multifunctional nanomaterials that can deliver immunomodulators and other drugs to tumors and improve the immunosuppressive environment. Multifunctional nanomaterials also have potential for use as radiosensitizers, potentially improving the effects of radiotherapy.

Overall, while some studies point to the effectiveness of combination radiotherapy and immunotherapy to improve treatment response, it is still unclear what sequence these therapies should be administered in and what the optimal timing is. The ideal radiotherapy fraction and dose selection are also questionable, as are the best immunotherapy-radiotherapy combinations for maximum anti-tumor response.

Toxicity and safety are also causes for further research, and it is still not clear which biomarkers are most useful to determine which patients may respond best to certain therapy combinations.

If the results of more and more clinical trials are positive, it will determine how best to integrate these models and optimize synergy, study authors wrote.

Reference

Yu S, Wang Y, He P, et al. Effective combinations of immunotherapy and radiotherapy for cancer treatment.Front Oncol. Published online February 7, 2022. doi:10.3389/fonc.2022.809304

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Review Highlights Progress and Potential in Immunotherapy Plus Radiotherapy for Cancer Treatment - AJMC.com Managed Markets Network

Allogene Therapeutics, Inc.

ODD Follows FDA Fast Track Designation Granted for ALLO-605 in Q2 2021

ALLO-605 is in Phase 1 in the IGNITE Trial and Part of Allogenes Multi-Pronged Strategy Targeting BCMA

BCMA Program Clinical Updates are Planned for Late 2022

SOUTH SAN FRANCISCO, Calif., April 27, 2022 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation (ODD) to ALLO-605, the Companys next-generation AlloCAR T product candidate targeting BCMA for the treatment of multiple myeloma.

ALLO-605 is the Companys first TurboCAR product candidate. TurboCAR is a proprietary, next generation platform technology based on a programmable cytokine signaling, designed to control T cell exhaustion and to improve T cell function and potency. These properties may enable CAR T products to succeed in more difficult to treat hematologic malignancies and solid tumors. The FDA granted Fast Track designation to ALLO-605 in Q2 2021 based on the potential for the product candidate to address an unmet need for patients who have failed other standard multiple myeloma therapies. The Phase 1 study evaluating ALLO-605 is ongoing.

Orphan-drug designation marks an important step towards developing our anti-BCMA portfolio for patients with multiple myeloma and making allogeneic CAR T products readily available for patients, said Rafael Amado, M.D., Executive Vice President of Research and Development and Chief Medical Officer. We look forward to providing an update on our BCMA clinical assets by the end of the year with an eye toward prioritizing a strategy for the next stage of development.

Orphan-drug designation is granted by the FDA to a drug or biologic intended to treat a rare disease or condition, which generally includes a disease or condition that affects fewer than 200,000 individuals in the U.S. ODD granted therapies entitle companies to development incentives including tax credits for clinical testing and prescription drug user fee exemptions. If a product that has ODD subsequently receives the first FDA approval for the designated disease, the FDA may not approve any other applications to market the same biologic for the same indication for seven years, except in limited circumstances. ODD does not convey any advantage in, or shorten the duration of, the regulatory review or approval process.

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About ALLO-605ALLO-605, a next-generation AlloCAR T known as a TurboCAR, is an investigational product that targets the B-cell maturation antigen (BCMA) for the treatment of patients with relapsed/refractory multiple myeloma and other BCMA-positive malignancies. This study uses ALLO-647, Allogene's proprietary monoclonal antibody (mAb), as a part of its differentiated lymphodepletion regimen. ALLO-605 incorporates Allogenes proprietary TurboCAR technology, which allows for cytokine activation signaling to be engineered selectively into CAR T cells. Preclinical results with ALLO-605 were presented at the American Society of Hematology (ASH) annual meeting in December 2020. In June 2021, ALLO-605 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed/refractory multiple myeloma. The Phase 1 study evaluating ALLO-605 is underway.

About Allogene TherapeuticsAllogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T) products for cancer. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of off-the-shelf CAR T cell products with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit http://www.allogene.com and follow @AllogeneTx on Twitter and LinkedIn.

Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the timing and ability to progress the IGNITE trial, including to provide an update at year-end on the IGNITE trial and other Allogene BCMA strategies; the potential for promising pre-clinical data to translate to positive clinical data; the ability to manufacture AlloCAR T products; and the potential benefits of TurboCAR technology and AlloCAR T products. Various factors may cause differences between Allogenes expectations and actual results as discussed in greater detail in Allogenes filings with the SEC, including without limitation in its Form 10-K for the year ended December 31, 2021. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

AlloCAR T and TurboCAR are trademarks of Allogene Therapeutics, Inc.

Allogenes AlloCAR T programs utilize Cellectis technologies. The anti-BCMA AlloCAR T programs are licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to these AlloCAR T programs.

Allogene Media/Investor Contact:Christine CassianoChief Communications Officer(714) 552-0326Christine.Cassiano@allogene.com

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Allogene Therapeutics Receives FDA Orphan-Drug Designation for ALLO-605, its First TurboCAR T Cell Product Candidate, for the Treatment of Multiple...

CAR T-cell immunotherapy may become the alternative option to current life-long retroviral therapy for HIV patients

By BRANDON NGUYEN science@theaggie.org

According to the Joint United Nations Programme on AIDS/HIV or UNAIDS, around 38 million people worldwide live with HIV, a retrovirus that destroys a hosts own immune cells and can progress into AIDS if left untreated. To put this into perspective, around 150,000 people are living with HIV but 68% of them are virally suppressed due to adherence to life-long retroviral therapy.

In efforts to search for an alternative option to life-long treatment, UC Davis Health has commenced a study testing the efficacy of Chimeric Antigen Receptor T-cell Therapy (CAR T-cell Therapy) and its potential as a cure for HIV. CAR T-cell therapy involves the removal of a patients immune systems T-cells and genetically modifying them to recognize and attack HIV-afflicted cells in the host.

Dr. Mehrdad Abedi, a professor of internal medicine, hematology and oncology at UC Davis Health and the principal investigator of the study, further explained the process in administering CAR T-cell therapy to a patient.

For this study, we will educate the cells by inserting a gene to target cells that have been infected by the HIV virus, Abedi said. The idea is these modified cells will attach to the HIV-infected cells and destroy the cells that are infected while also stopping the infected cells ability to replicate.

Modification of human patient T-cells into CAR T-cells has revolutionized patient care, especially for cancer patients. This technology has become widely used in the field of oncology and blood cancer patients, as training ones T-cells to recognize tumors from normal, healthy cells is a novel method to search and destroy tumor cells throughout the blood. This would be impossible with radiation or surgery.

Dr. Paolo Troia-Cancio, a clinical professor of medicine with the infectious disease division and co-investigator for the HIV study, described how the study came about as a result of success stories of patients with HIV and cancer.

It has been shown to be possible to cure HIV because so far there have been three individuals that have been cured of HIV, but they have required bone marrow transplants, Troia-Cancio said. Two of the three patients were administered more conventional allergenic bone marrow transplants and the third person got a transplant from cord blood stem cells. I hope with this type of research that we take what we have learned from these three individuals and apply them in a way that we could modify a patients immune system in a way to make it resistant to HIV.

However, bone marrow transplants are not the ideal or first option for patients with HIV.

While these stories provide inspiration and hope to finding a cure for HIV, a bone marrow transplant is not a realistic option for most patients, Abedi said. Such transplants are highly invasive and risky, so they are generally offered only to people with cancer who have exhausted all other options.

Nonetheless, these three fortunate cases offer hope for a cure, or at least a functional cure, which Troia-Cancio explained as patients being able to control their HIV without medication. With an optimistic outlook for HIV patients, Troia-Cancio underscored the potential for CAR T-cell therapy to revolutionize the healthcare industry in treating other immunological disorders.

There are other diseases where CAR T-cells are being looked at, Troia-Cancio said. So I think theres a potential for this therapy to become more widely used for other areas where having essentially a modified immune system could potentially lead to either long term control or omission or even a cure for a disease.

Written by: Brandon Nguyen science@theaggie.org

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CAR T-cell therapy currently in UC Davis Health clinical trial study as potential cure for HIV - The Aggie - The Aggie

The funding will be used to develop Aurion Biotechs first candidate, AURN001, a cell therapy aiming to treat corneal edema.

Aurion Biotech is a clinical-stage biotech firm that is aiming to restore vision to millions of patients with its regenerative therapies. According to the firm, the raised funds will be used to file an IND to the US Food and Drug Administration (FDA) in order to begin clinical trials.

Additionally, Aurion wants to submit an NDA to the Japan Pharmaceuticals and Medical Devices Agency (PMDA).

Image: Stock Photo Secrets

Funds will be used to advance the clinical development of our cell therapy for corneal edema [AURN001], secondary to corneal endothelial disease, Judith McGarry, vice president marketing at Aurion told BioProcess Insider.

The endothelium is a single layer of cells in the human cornea; it regulates hydration of the cornea. When those cells degrade or die (due to disease or surgical trauma), they do not regenerate. Once those cells are gone, the cornea become swollen and cloudy, ultimately causing loss of vision.

The cell therapy was developed by Shigeru Kinoshita and his colleagues at Kyoto Prefecture University of Medicine (KPUM) in Japan. Aurion acquired this technology in 2020 and is preparing to submit a Japanese new drug application (J-NDA).

First, our inventor was able to figure out how to get human corneal endothelial cells (HCECs) to replicate in the lab (keep in mind, they do not replicate in the body). With this patented process, the cells from a single donor can be manufactured to treat up to 100 eyes, said McGarry.

She continued: This alone is a significant benefit since there is a global shortage of donor corneas available for transplant. Second, the cell therapy procedure itself is relatively straightforward, and can be performed in an outpatient setting, in approximately 15 minutes. The ophthalmologist makes an incision into the anterior chamber of the patients eye, and polishes off the diseased endothelial cells. Then, via another incision, the ophthalmologist injects HCECs in solution into the anterior chamber. The cells quickly settle into place, along the stroma of the cornea [and] the patient lies face down for a couple of hours, to facilitate adhesion.

The $120 million financing was led by Deerfield Management, and included current investors Flying L Partners, Falcon Vision, KKR, Visionary Ventures, and Petrichor Healthcare Capital Management. Furthermore, funds will be paid out to Aurion based on specific achievements of clinical and operational milestones.

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Aurion $120m to advance cell therapy candidate - BioProcess Insider - BioProcess Insider

MONTREAL, April 13, 2022 (GLOBE NEWSWIRE) -- ExCellThera Inc. (ExCellThera), an advanced clinical-stage biotechnology company delivering molecules and bioengineering solutions to expand and engineer various cell lines for use in next generation cell and gene therapies, announced today the publication of a scientific article entitled UM171 expansion of cord blood improves donor availability and HLA matching for all patients, including minorities. The study by Dumont-Lagac et al., was recently published in the peer-reviewed medical journal Transplantation and Cellular Therapy.

Using data from the Be The Match donor and cord blood registry, the retrospective study concluded that expansion with UM171:

UM171 is the proprietary molecule used in ExCellTheras lead technology, ECT-001, a cell therapy under development being evaluated in several clinical trials in the United States and Canada.

A persistent problem under the current standard of care for allogeneic stem cell transplantation is finding a suitable donor for all patients. While cord blood units cryopreserved in public banks offer a readily available source of stem cells for transplantation, the low number of cells they contain have hampered their use. This new study demonstrates how expanding small cord blood units results in a greater access to transplantation.

The results of this study are supported by what we have seen in our clinical trials, where weve been able to identify a cord suitable for expansion for all patients enrolled, no matter their ethnic origin, said Dr. Pierre Caudrelier, Chief Medical Officer of ExCellThera. Furthermore, thanks to the low starting cell dose requirement for UM171 expanded grafts, about half of the patients in our first Phase I/II trial benefited from better HLA matching than would have been possible without expansion.

About ExCellThera Inc.

ExCellThera is a clinical-stage cell expansion and engineering company delivering molecules and bioengineering solutions to expand and engineer various cell lines for use in novel one-time curative therapies for patients with hematologic malignancies and other diseases. ExCellTheras most advanced technology, ECT-001, a cell therapy, combines a proprietary molecule, UM171, and an optimized culture system. In pursuit of better treatments for patients, the company is building out its cell expansion and engineering platform, as well as supporting best-in-class clinical trials. excellthera.com

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ExCellThera announces new publication showing its ECT-001 cell therapy improves transplant access for all patients - BioSpace

By The ASCO Post StaffPosted: 4/13/2022 12:05:00 PM Last Updated: 4/13/2022 1:12:21 PM

A new chimeric antigen receptor (CAR) T-cell product had an acceptable safety profile and showed early signs of efficacy as a monotherapy and in combination with an mRNA vaccine in patients with solid tumors, according to preliminary data from a phase I/II clinical trial presented by Haanen et al during the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract CT002).

CAR T-cell therapy has revolutionized the treatment options for hematologic malignancies, but its application in solid tumors has been challenging. One of the main limitations is that most of the proteins present on solid tumors that could be used as targets are also found at low levels on normal cells, making it difficult to specifically direct the CAR T cells against tumor cells and spare healthy ones, said lead author John Haanen, MD, PhD, a medical oncologist at the Netherlands Cancer Institute (NKI), Amsterdam. Other challenges include the limited persistence of CAR T cells observed in solid tumors and their difficulty reaching the tumors and penetrating the center of the mass.

Dr. Haanen and colleagues are conducting a first-in-human open label, multicenter clinical trial to evaluate the safety and preliminary efficacy of a previously developed CAR T-cell product that targets CLDN6, a tumor-specific antigen widely expressed in various solid tumors but silenced in healthy adult tissues. This therapy was tested in preclinical models in combination with a CLDN6-encoding mRNA vaccine (CARVac) that favors the expansion of the CAR T cells. As Dr. Haanen explained, this combined treatment, called BNT211, resulted in expansion of the transferred CAR T cells and higher persistence in the blood, which in turn improved tumor cell killing.

Methodology and Findings

The investigators recruited patients with relapsed or refractory advanced, CLDN6-positive solid tumors to test the CLDN6 CAR T-cell therapy alone and in combination with CARVac.

The trial included two parts in which increasing doses of CLDN6 CAR T cells were given as monotherapy (part 1) and in combination with CARVac (part 2), following lymphodepletion to reduce the number of T cells present in the body and make room for the transferred CAR T cells. In part 2, CARVac was administered every 2 or 3 weeks up to 100 days after the CAR T-cell transfer, and one patient received maintenance vaccinations every 6 weeks. Overall, 16 patients had been treated at the time of this reporting.

Approximately 40% of patients developed manageable cytokine-release syndrome without any signs of neurotoxicity. Other adverse events included cytopenia and abnormal immune responses, all of which were resolved. Administration of CARVac resulted in transient flu-like symptoms that lasted up to 24 hours. CLDN6 CAR T treatment and CARVac appeared to be safe, with only limited and manageable adverse events, said Dr. Haanen.

Among the 14 patients who were evaluable for efficacy, at 6 weeks after infusion, four patients with testicular cancer and two with ovarian cancer experienced a partial response, with an overall response rate of nearly 43%. Among the study participants who had a partial response, four patients received CAR T cells as a monotherapy and two patients were treated with the CAR TCARVac combination. The disease control rate was 86%. In all evaluable patients, deepening of initial partial responses was observed at 12 weeks after infusion. This resulted in one complete response that has continued 6 months after infusion.

It is remarkable that most of the patients with testicular cancer showed clinical benefit at dose level 2, and the responses we have observed can be deep, including one ongoing complete remission, said Dr. Haanen.

Study Implications

The infusion of CLDN6 CAR T, alone or in combination with CARVac, is safe and holds promise for patients with CLDN6-positive cancers, Dr. Haanen added. CLDN6 was never targeted before with cellular therapy, but in our study, this approach is already showing efficacy that may be better than the data from other CAR T trials in solid tumors.

However, Dr. Haanen cautioned that these data are very early, with few patients having been treated, so no major conclusions can be drawn at this time.

Disclosure: The study was sponsored by BioNTech SEs subsidiary BioNTech Cell & Gene Therapies GmbH. NKI received research grants from BioNTech. Dr. Haanen is on the scientific advisory board of BioNTech. Financial compensation goes to NKI. For full disclosures of all study authors, visit abstractsonline.com.

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New CAR T-Cell Therapy for Solid Tumors Was Safe and Showed Early Efficacy - The ASCO Post

SAN DIEGO--(BUSINESS WIRE)--Stemson Therapeutics Corp., a private biotechnology company developing an iPSC-derived autologous cell therapy to regenerate healthy hair follicles, announced today that Paul Laikind, serial entrepreneur and former CEO of cell therapy company ViaCyte, has joined the Stemson Board of Directors. Paul brings significant company building and therapeutics development experience to the Stemson Board.

We welcome Paul as an important addition to our board of directors, said Matt Posard, Stemsons executive chairman of the board. With more than 35 years of experience founding and leading therapeutics development companies from preclinical to clinical stage development and from start-up through IPO, Paul will provide valuable guidance to accelerate Stemsons progress.

I am delighted and honored to join Stemsons Board of Directors, said Paul. Stemsons unique combination of novel technologies to bioengineer hair follicles not only has the potential to help millions of people suffering from hair loss, but can more broadly advance the capabilities for cell therapy development across the industry. I look forward to working with the team and supporting their journey.

Paul Laikind, PhD, was CEO of ViaCyte from 2012 until 2020, where he lead the development of the first stem cell-derived cell therapies designed to replace pancreatic beta cells for the treatment of Type 1 Diabetes. Paul led the company from the preclinical stage through the introduction of two product candidates into clinical trials before retiring at the end of 2020. A third product that Viacyte developed in collaboration with CRISPR Tx recently also entered clinical development.

Dr. Laikind served as Chief Business Officer and Senior Vice President of the Sanford Burnham Medical Research Institute from 2009 2011, focusing on enhancing the translational capabilities of the institute. From 1999 - 2009, Paul was cofounder and CEO of Metabasis Therapeutics, which concentrated on therapeutics development for metabolic and liver diseases. He took Metabasis from founding through IPO, and from preclinical to clinical stage development, with five products in the clinic. From 1986 1999, Paul cofounded and served as Vice President of Corporate Development at Gensia Pharmaceuticals where they developed small molecule therapies for the treatment of cardiovascular, neurological and inflammatory diseases. During that time, he cofounded and served as an advisor to Viagene from 1988 1994, the first commercially focused gene therapy company developing proprietary gene delivery technology to treat HIV, cancer and inherited disorders. Gensia, Viagene and Metabasis each completed successful initial public offerings and were eventually acquired for combined proceeds of over $3.5 billion.

Throughout his career, Dr. Laikind has played a leadership role in the evolving biotechnology industry. He serves or has served on the board of industry organizations including BIO, BIOCOM, CONNECT, and Alliance for Regenerative Medicine.

Paul earned his PhD in Biochemistry from the University of California, San Diego, and is a veteran of the US Navy.

We are very lucky to have Paul join us. The next stage of Stemsons development is to advance our first product toward human clinical trials, stated Geoff Hamilton, cofounder and CEO of Stemson Therapeutics. Pauls tremendous business leadership experience and industry relationships, as well as his involvement developing similar technologies to Stemsons while at ViaCyte, will help us guide the company toward that goal.

About Stemson Therapeutics

Stemson Therapeutics is a pre-clinical stage cell therapy company founded in 2018 with a mission to cure hair loss by leveraging the regenerative power of Induced Pluripotent Stem Cells. Based on the breakthrough innovation by Stemson Therapeutics co-founder, Dr. Alexey Terskikh, Stemson uses iPSC to regenerate the critical cells required to grow hair and which are damaged or depleted in patients suffering from hair loss. The iPSC-derived cells are used to grow de novo hair follicles, offering a new supply of hair to treat people suffering from various forms of Alopecia. Today, there are no available treatments capable of growing new hair follicles. Stemsons world class team of scientists, advisors and collaborators are passionate about delivering a scientifically based, clinically tested cure for hair loss to the millions of hair loss sufferers who seek help for their hair loss condition. Stemson Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.stemson.com.

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Paul Laikind, PhD, Joins Stemson Therapeutics Board of Directors - Business Wire