Category Archives: Cell Therapy

Mesothelin-directed CAR T-cell therapies, NF2 inhibitors, and EZH2 inhibitors are just 3 of a growing list of novel approaches under study in mesothelioma, renewing optimism in a field which has historically been colored with nihilism, said Marjorie G. Zauderer, MD.

Even just from when I started 10 to 12 years ago until now, the progress we have made has been slow, with only 1 approval, but its really snowballing now in terms of [our understanding of] biology and the discoveries and the models that we have to study and ask the right questions. We should all be optimistic about the things that we can do. Outcomes still have a long way to go, but theyre so much better than they used to be, said Zauderer.

In an interview with OncLive ahead of the 16th Annual New York Lung Cancers Symposium, Zauderer, co-director of the MSK Mesothelioma Program at Memorial Sloan Kettering Cancer Center (MSK), previewed her presentation on some of the new approaches in mesothelioma.

Zauderer: I was tasked with talking about some new approaches for mesothelioma, and its an interesting time for that disease. Last fall, we had our first FDA approval since 2003 or 2004, which was when pemetrexed was approved for use in mesothelioma. Last year, we had the approval of ipilimumab [Yervoy] and nivolumab [Opdivo], which is exciting. Although that regimen really makes a difference for a lot of people, there are still a lot of people where that isnt the right magic sauce. We are always trying to push that envelope.

Ill be talking about a couple of different research endeavors and clinical trials that are ongoing to help figure out who responds to immunotherapy, who should still get chemotherapy and who should get chemoimmunotherapywhich is a lot like how we treat lung cancer today. Then, of course, we are looking at different ways of triggering the immune system. Lots of different clinical trials are looking to exploit the expression of different proteins on the surface of mesothelioma. One area we at MSK have been really involved in is the development of T-cell CARs targeting mesothelin. [In my PER presentation,] Ill be talking about that a little bit and some of the T-cell studies going on elsewhere.

Then of course, we always think about targeted therapies, and thats certainly been incredibly successful in lung cancer, but we havent had the same degree of success in mesothelioma. In part, that is because the genes are different; theyre tumor suppressor genes instead of oncogenic activating genes. In my presentation, I will briefly cover different ways of exploiting NF2 alterations. There have also been studies looking at BAP1, PIK3CA mutations and sort of how we are starting to put together this very complicated interconnected network with rationally designed experiments based on good preclinical science that were trying to translate into the clinic.

Right now, there are a couple different mesothelin-directed T-cell programs. One that we have at MSK is the interpleural injection of our homegrown construct that was developed and created by Prasad S. Adusumilli, MD, FACS, of MSK, who is a physician-scientist that I work with. There is another construct from a company called TCR2 Therapeutics known as TC-210.

There are programs elsewhere across the country, and in the Northeast, where there are a couple of different constructs [being developed]. Each T cell is a little bit different in terms of the signature in terms of how the cells are manipulated, so that they target mesothelin. People are playing around with whether they are given intravenously or into the pleura or into the abdomen, as well as what chemotherapy to give before to prepare people for the treatment. How many times do you give it? How close together? There are a lot of different manipulations around that. Nobody really knows the right answer yet.

Another pathway that weve been thinking a lot about and how to target it is looking at NF2 alterations in mesothelioma because its a common mutation. There have been a lot of studies with PI3K and mTOR inhibitors, but to date, it hasnt really been as effective in mesothelioma as we would like.

There are some studies now looking at other functions of NF2 and inhibiting that with inhibitors of a molecule that puts together these cullin-RINGs. By blocking the formation of that cullin-RING, you stop this prooncogenic cascade. Combining that [agent] with some of the PI3K and mTOR inhibitors has been productive in animal models. Were starting to look at that [approach] in humans and translate that [to practice].

The other study is evaluating the EZH2 inhibitor tazemetostat [Tazverik], which was approved in the past couple of years for INI-deficient sarcomas. There was a phase 2 trial in mesothelioma that was a positive study. Its one of these constructs that didnt show a ton of shrinkage. There were a few patients who had real responses, but there was a tremendous amount of stable disease [SD]. The kinetics of the patients who had SD was that over a long period of time, they trended towards tumor shrinkage, which is different than a lot of the other ways that we think about these drugs as working. We often classically have thought about having a response up front, and then maintaining it. However, the idea that there might be an evolution to response over time is a really different way of thinking about the kinetics of response.

[We are looking at ways] to target P16 loss, which is common in mesothelioma and is usually associated with more aggressive disease. By interfering with the MTAP pathway where adenine is made, you can hopefully disrupt that signaling pathway. There is a construct thats in development, and there are some other ones that are coming to the clinic too.

Its an exciting time for research because we are starting to extrapolate from other cancers, how they approach their diseases and break mesothelioma down into different subtypes based on biology. One of the biggest barriers is when we look at the SEER [Surveillance, Epidemiology, and End Results] database of how and where patients are treated; so many patients dont get much treatment, if any, for their disease.

Being seen by a center that has experience doesnt mean that youre always going to get treatmentsometimes thats the right decision for a particular patient. Seeing someone who doesnt see 1 or 2 cases a decade, but who [treats patients with this disease] day in and out, brings a lot of expertise to [an individual patients] case. There are good data that surgical outcomes are better in high-volume centers. One of the barriers is getting the patients to the best regional center to manage their disease.

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Research With Cellular Therapy Ramps Up in Mesothelioma - OncLive

CAMBRIDGE, Mass.--(BUSINESS WIRE)--2seventy bio, Inc., (NASDAQ: TSVT), an emerging immuno-oncology company today announced its official launch as an independent, publicly traded company. 2seventy bio will trade on the Nasdaq Global Select Market, commencing tomorrow, November 5 under the ticker symbol TSVT.

Weve done the intense work to reach the start line and we are extremely excited to officially introduce 2seventy bio. 2seventy was created from an unrelenting desire to find new ways to outmaneuver cancer and give more time to the people we serve, said Nick Leschly, chief kairos* officer, 2seventy bio. Our organization is ready: from our bold and seasoned team to our deep scientific expertise and our strong financial foundation. Our commitment is to sustain the energy, passion and rigor that we have today as we establish the leading immuno-oncology cell therapy company with an aim to deliver transformative treatment options to people living with a range of difficult to treat cancers.

The company officially separates today from bluebird bio, Inc. and launches with a robust cell therapy pipeline across a range of hematologic and solid tumors including two candidates that are planned to enter the clinic in the first half of 2022. The portfolio also includes a development and 50/50 U.S. commercialization partnership with Bristol Myers Squibb (BMS) for ABECMA, a first-in-class, BCMA-directed CAR T cell immunotherapy for multiple myeloma approved in the U.S.

Unique Scientific Approach to Cell Therapy

Our differentiated cell therapy platform is built around the goal of delivering therapies that provide significant benefit to people living with cancer, said Philip Gregory, chief scientific officer, 2seventy bio. We begin with the foundational understanding that autologous CAR T cell therapy works, yet theres room to build and improve. We identify the unmet medical need, and we strive to understand where there are unique opportunities to change the path of disease. We then undertake a deliberate process to devise an engineered solution that relies on the robust toolbox of targeting, signaling, and enhancement technologies that we have established through our extensive experience and partnerships across industry and academia. Importantly, we are uniquely positioned to deliver these therapies to patients through a development strategy that is designed to efficiently test our hypotheses and quickly deliver answers not only for a given program, but across the technologies. By taking this approach, were able to apply learnings across the platform in rapid succession.

2seventy bios cell therapy pipeline includes approaches to hematologic malignancies and solid tumors, including two clinical studies expected to be initiated in the first half of 2022:

Blend of Strategic Collaboration and In-House Approach to Manufacturing

Integral to the delivery of 2seventy bios platform of cell therapies is the companys manufacturing network, including best-in-class partnerships with academic centers and industry, purpose-built for messenger RNA (mRNA) and lentiviral vector (LVV) production. This network also includes a planned build for an internal clinical cell therapy manufacturing capability at the companys headquarters in Cambridge, Massachusetts. This facility is designed to enable deep integration of Chemistry, Manufacturing and Controls (CMC) with research, correlative science, and clinical development, and enable the flexibility to rapidly innovate and learn as programs advance.

Launching with a Strong Financial Foundation and Leadership

2seventy bio is launching with a clear and differentiated strategy and is well-funded to deliver:

About 2seventy bio

Our name, 2seventy bio, reflects why we do what we do - TIME. Cancer rips time away, and our goal is to work at the maximum speed of translating human thought into action 270 miles per hourto give the people we serve more time. We are building the leading immuno-oncology cell therapy company, focused on discovering and developing new therapies that truly disrupt the cancer treatment landscape. With a deep understanding of the human bodys immune response to tumor cells and how to translate cell therapies into practice, were applying this knowledge to deliver next generation cellular therapies that focus on a broad range of hematologic malignancies, including the first FDA-approved CAR T cell therapy for multiple myeloma, as well as solid tumors. Our research and development is focused on delivering therapies that are designed with the goal to think smarter and faster than the disease. Importantly, we remain focused on accomplishing these goals by staying genuine and authentic to our why and keeping our people and culture top of mind every day.

For more information, visit http://www.2seventybio.com.

Follow 2seventy bio on social media: Twitter and LinkedIn.

2seventy bio is a trademark of 2seventy bio, Inc.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to: statements about our plans with respect to the development, manufacture or sale of our product candidates and the associated timing thereof, including the design and results of pre-clinical and clinical studies; the efficacy and perceived therapeutic benefits of our product candidates and the potential indications and market opportunities therefor; the strategic plans for 2seventy bio and potential corporate development opportunities; our ability to compete with other companies that are or may be developing or selling products that are competitive with our product candidates; and our ability to operate as a stand-alone company and execute our strategic priorities. Applicable risks and uncertainties include the risk that we may not achieve the expected benefits of the separation; the risk that the separation could harm our business, results of operations and financial condition; our lack of independent operating history and the risk that its accounting and other management systems may not be prepared to meet the financial reporting and other requirements of operating as an independent public company; the risk that we may be unable to make, on a timely or cost-effective basis, the changes necessary to operate as an independent company; the risk that dedicated financial and/or strategic funding sources may not be available on favorable terms or at all; the risk that the separation may adversely impact our ability to attract or retain key personnel; the risk that the separation may adversely impact the effectiveness of development and commercialization efforts by us and our partners; the risk of possible disruption to our business as a result of the separation; ; the risk that our BLAs and INDs will not be accepted for filing by the FDA on the timeline that we expect; the risk that our plans with respect to the preclinical and clinical development and regulatory approval of our product candidates may not be successfully achieved on the planned timeline, or at all; the risk that ABECMA will not be as commercially successful as we may anticipate; and the risk that we are unable to manage our operating expenses or cash use for operations. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in the Form 10 filed by 2seventy bio with the Securities and Exchange Commission (SEC) and declared effective by the SEC on October 18, 2021, as well as discussions of potential risks, uncertainties, and in 2seventy bios subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and 2seventy bio undertakes no duty to update this information unless required by law.

*Kairos: an Ancient Greek word meaning the right, critical, or opportune moment

1ABECMA has also received regulatory approval in the European Union, Canada, and Switzerland. Bristol Myers Squibb continues to assume sole responsibility for drug product manufacturing and commercialization outside the United States.

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2seventy bio Completes Spin Transaction and Launches Innovative Immuno-oncology Cell Therapy Company - Business Wire

Two kidney transplant patients who received a stem cell therapy developed by Talaris Therapeutics were able to come off all immunosuppressant drugs within a year, without any evidence of graft rejection.

The first findings from Talaris phase 3 trial of the cell therapy called FCR001 suggest it may be possible to eliminate the need entirely for patients to take what may be dozens of tablets daily after organ transplants, according to the US biotech.

While still preliminary, the experience with the two patients back up Talaris hope that giving a one-shot dose of FCR001 the day after an organ transplant could stimulate immune tolerance in the recipient, and avoid the side effects of current drug treatments such as infections, heart disease, and some forms of cancer.

The companys approach relies on administering haematopoietic stem cells from the individual who donated the organ, in order to generate what Talaris refers to as chimerism, with both donor and recipient cells present in the bone marrow. That allows the immune system to see the transplanted organ as self rather than foreign.

The first two recipients in Talaris FREEDOM-1 phase 3 trial had received FCR001 at least 12 months earlier, and showed stable kidney function, according to Talaris.

A larger group of five patients who were at least three months from the cell therapy maintained more than 50% chimerism in their T cells, which the biotech said was a sign of long-term, immunosuppression-free tolerance to the donated kidney in its phase 2 trials.

The FREEDOM-1 results reported at the American Society of Nephrology (ASN) meeting this week were accompanied by updated results from Talaris phase 2 study, in which all 26 patients originally weaned off immunosuppressants have continued to remain off them without rejecting their donated kidney.

Some transplant patients treated with Talaris therapy in earlier trials have now been off all immunosuppression for more than 12 years without signs of kidney rejection.

Talaris intends to enrol 120 subjects into the phase 3 trial, which is scheduled to generate results in 2023.

Earlier this year, Talaris raised $150 million via a Nasdaq listing that will be used to take FCR001 through the phase 3 programme in organ transplantation and as a treatment for rare autoimmune disease scleroderma.

It also recently started a phase 2 trial of the cell therapy to see if it is able to induce immune tolerance to a transplanted kidney in patients who received the transplant from a living donor up to a year prior to administration of FCR001.

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Talaris therapy ends need for immune drugs in transplant patients - - pharmaphorum

SINGAPORE, Nov. 03, 2021 (GLOBE NEWSWIRE) -- Tessa Therapeutics Ltd. (Tessa), a clinical-stage cell therapy company developing next-generation cancer treatments for hematological malignancies and solid tumors, today announced that data from its ongoing autologous and allogeneic cell therapy studies targeting lymphomas has been accepted for two separate poster presentations at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition being held from December 11-14, 2021.

The presentations include clinical data from a Phase II multi-center study evaluating safety and efficacy of CD30 CAR-T therapy (TT11) in patients with relapsed / refractory classical Hodgkin Lymphoma (R/R cHL) and another Phase I investigator-initiated study testing allogeneic off-the-shelf CD30 CAR EBVST therapy (TT11X) in patients with relapsed / refractory CD30+ lymphoma. Accepted abstracts will also be published online in the November supplemental issue of Blood, a publication of the American Society of Hematology.

Details of Presentations

Title: Safety and Efficacy Profile of Autologous CD30.CAR-T-Cell Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (CHARIOT Trial)Session Name: 704. Cellular Immunotherapies: Clinical: Poster III Abstract: #3847Presenting Author: Sairah Ahmed, M.D., MD Anderson Cancer CentreDate, Time and Location: December 13, 2021; 6:00 PM - 8:00 PM ET; Georgia World Congress Center, Hall B5

Title: Safety and efficacy of off-the-shelf CD30.CAR-modified Epstein-Barr virus-specific T cells in patients with CD30-positive lymphomaSession Name: 704. Cellular Immunotherapies: Clinical: Poster IAbstract: #1763Presenting Author: David Hon Quach, Instructor, Center for Gene Therapy, Baylor College of Medicine, Houston, TXDate, Time and Location: December 11, 2021; 5:30 PM - 7:30 PM ET; Georgia World Congress Center, Hall B5

About TT11 (CD30 CAR-T Therapy)

TT11 is a CAR-T therapy, which harvests a patients own T-cells and modifies them by introducing a CD30-directed Chimeric Antigen Receptor (CAR) to target and kill CD30+ cells in classical Hodgkin Lymphoma (cHL). CD30 is a well validated lymphoma target with homogeneous expression in 98% of cHL and a significant proportion of subsets of non-Hodgkin Lymphomas. Clinical data from two Phase 1/2 studies, published last year in the Journal of Clinical Oncologya, showed TT11 demonstrated strong safety and efficacy as a monotherapy for heavily pre-treated R/R cHL patients. A Phase 2 study was subsequently conducted this year evaluating TT11 among R/R cHL patients, results for which will be presented at 2021 ASH annual meeting.

About TT11X (Allogeneic CD30 CAR-EBVST Therapy)

TT11X is an allogeneic off-the-shelf therapy which augments Epstein bar virus-specific T-cells with CD30 CAR technology. The therapy is based on a proprietary allogeneic cell therapy platform developed from decades-long research and development on unique properties of Virus Specific T-cells (VSTs) by Tessas Scientific Co-Founder, Dr. Malcolm Brenner, and the team at Baylor College of Medicine. VSTs are highly specialized T cells with the ability to recognize and kill infected cells while activating other parts of the immune system for a coordinated response. Allogeneic VSTs without any form of genetic modification have demonstrated a strong safety profile and efficacy in early trials with minimal risk of GVHD. Preclinical studies have further demonstrated that CD30 targeting potentially helps improve allogeneic cell expansion and persistence. With this platform approach, Tessa aims to overcome the current challenges faced by allogeneic cell therapies and create more efficacious, reliable, and scalable therapies capable of targeting a broad range of cancers.

About Tessa Therapeutics

Tessa Therapeutics is a clinical-stage biotechnology company developing next-generation cell therapies for the treatment of hematological cancers and solid tumors. Tessas lead clinical asset, TT11, is an autologous CD30 targeting CAR-T therapy currently being investigated as a potential treatment for relapsed or refractory classical Hodgkin lymphoma (Phase 2). TT11 has been granted RMAT designation by the FDA and PRIME designation by European Medicine Agency. Tessa is also advancing an allogeneic off-the shelf cell therapy platform targeting a broad range of cancers in which Epstein Barr Virus Specific T Cells (EBVSTs) are augmented with CD30-CAR technology to prevent graft rejection. A therapy using this platform is currently the subject of a Phase 1 clinical trial in CD30-positive lymphoma. A third clinical asset evaluates novel combination therapy of HER2-CAR-T cells and binary oncolytic virus in an ongoing Phase 1 study targeting HER2 positive solid tumors. Tessa has its global headquarters in Singapore, where the company has built a state of the art, commercial cell therapy manufacturing facility. Tessas United States headquarters are in New Jersey. For more information on Tessa, visit http://www.tessacell.com.

Cautionary Note on Forward Looking Statements

This press release contains forward-looking statements (within the meaning of the Private Securities Litigation Reform Act of 1995, to the fullest extent applicable) including, without limitation, with respect to various regulatory filings or clinical study developments of the Company. You can identify these statements by the fact that they use words such as anticipate, estimate, expect, project, intend, plan, believe, target, may, assume or similar expressions. Any forward-looking statements in this press release are based on managements current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the Companys financial results, the ability to raise capital, dependence on strategic partnerships and licensees, the applicability of patents and proprietary technology, the timing for completion of the clinical trials of its product candidates, whether and when, if at all, the Companys product candidates will receive marketing approval, and competition from other biopharmaceutical companies. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made, and disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the Companys views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. The Companys products are expressly for investigational use pursuant to a relevant investigational device exemption granted by the U.S. Food & Drug Administration, or equivalent competent body.

References:a. Ramos et al., J Clin Oncol 2020

Tessa Therapeutics Media ContactRitika Khetawat+65 6384 0755media@tessacell.com

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Tessa Therapeutics Announces Presentation of Autologous and - GlobeNewswire

Significant progress with rapidly evolving therapies, including blinatumomab, inotuzumab ozogamicin, and CAR T-cell therapy, has been made to extend the median overall survival and improve outcomes for patients with relapsed/refractory B-cell acute lymphoblastic leukemia.

Significant progress with rapidly evolving therapies, including blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa), and chimeric antigen receptor (CAR) T-cell therapy, has been made to extend the median overall survival (OS) and improve outcomes for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). Antibody-based therapies and CAR T-cell therapies are not mutually exclusive, according to Elias Jabbour, MD, who added that competitive options have the potential to be complementary if sequenced earlier.

Until recently, when somebody with ALL relapsed, the outcomes were bad and we didnt have anything [available to treat them], said Jabbour, a professor of medicine in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, in an interview with OncLive. Jabbour previewed his presentation on the practice-changing updates in relapsed/refractory B-ALL.

Over the past few years, weve [had] several options [become] available to our patients, [including] the bispecific engagers, antibody-drug conjugates [ADCs], and CAR T-cell therapies, first for pediatric and [adolescent and] young adult [AYA] patients and now for adult patients. Each [therapy] has shown a benefit when compared with standard of care. The question is: How do we optimize the [options] to improve outcomes in ALL? Jabbour asked.

Although not yet backed by level 1 evidence, a potentially promising therapeutic sequencing strategy could incorporate blinatumomab in combination with inotuzumab ozogamicin as frontline therapy followed by consolidative CAR T-cell therapy, Jabbour explained. He added that this strategy could begin to phase out the use of allogeneic stem cell transplant and chemotherapy in B-ALL because these approaches may not be optimal following CAR T-cell therapy.

Each [option] alone is not great enough. The value of treatment can be further improved, Jabbour said. This way we can offer these treatments, which are expensive and not [widely] available, in the most optimal way. We can improve the cure rate instead of giving every agent alone with minimal or acceptable benefit.

Over several decades, the 5-year OS rate for patients with ALL has increased from 26% between 1984 and 1989 to 59% between 2010 and 2019. Reasons for this success include the addition of TKIs like ponatinib (Iclusig) with or without blinatumomab to chemotherapy-based regimens in patients with Philadelphia chromosomepositive ALL, the addition of rituximab (Rituxan) to chemotherapy in Burkitt and preB-ALL, and the use of CAR T-cell therapy in B-ALL. Additionally, although still being fleshed out, the importance of minimal residual disease (MRD) as a predictive marker for progression has become understood in recent years.

In 2017, the FDA granted a full approval to the monoclonal antibody blinatumomab for the treatment of adult and pediatric patients with relapsed/refractory B-cell precursor ALL.1 The approval was based on findings from the phase 3 TOWER trial (NCT02013167), in which blinatumomab elicited a 44% complete remission (CR) with full, partial, or incomplete hematologic recovery (CRi) rate vs 25% with standard of care chemotherapy (P < .001).2 The median OS was 7.7 vs 4 months, respectively (HR, 0.71; 95% CI, 0.55-0.93; P = .01).

Another phase 3 study (NCT02101853) evaluated blinatumomab vs chemotherapy in children and AYA patients with B-ALL in first relapse.3 The 2-year disease-free survival rate was 54.4% with blinatumomab vs 39% with chemotherapy (HR, 0.70; 95% CI, 0.47-1.03; P = .03). The 2-year OS rates were 71.3% vs 58.4%, respectively (HR, 0.62; 95% CI, 0.39-0.98; P = .02).

Also in 2017, the ADC inotuzumab ozogamicin was approved by the FDA for the treatment of adults with relapsed/ refractory B-cell precursor ALL based on findings from the phase 3 INO-VATE trial (NCT01564784).4 Updated results showed a 73.8% CR/CRi rate with inotuzumab ozogamicin vs 30.9% with standard-of-care chemotherapy in this patient population (P < .0001).5

In an ongoing phase 1/2 study (NCT01371630), inotuzumab ozogamicin in combination with low-intensity minihyper-CVD (mini-HVCD), a chemotherapy regimen consisting of cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 for4 doses, demonstrated encouraging activity in patients with relapsed/ refractory Philadelphia chromosomenegative ALL.6

Long-term follow-up data from the study showed an overall response rate of 80% with inotuzumab ozogamicin plus miniHVCD, with a complete response rate of 57% among 96 patients treated.7 The MRD negativity rate among responders was 83%.

To further expand this regimen, another study evaluated sequential inotuzumab ozogamicin with mini-HVCD with or without blinatumomab as salvage therapy for patients with ALL in first relapse.8 The results showed a median OS of 16.5 months with the combination as first-line salvage therapy and 5.8 months as second-line or later salvage therapy, indicating that salvage status affects OS, Jabbour said.

In 2017, the CAR T-cell therapy tisagenlecleucel (Kymriah) became the first gene therapy to be approved in the United States.9 The regulatory decision made the therapy available for use in pediatric and AYA patients with relapsed/refractory B-ALL.

Updated findings from the phase 2 ELIANA trial (NCT02435849) demonstrated a 24-month OS rate of 66% with tisagenlecleucel in this patient population.10 On October 1 another CAR T-cell product, brexucabtagene autoleucel (brexu-cel; Tecartus) was approved by the FDA for use in adult patients with relapsed/refractory B-ALL.11

adult patients with relapsed/refractory B-ALL.11 The decision was based on findings from the phase 1/2 ZUMA-3 trial (NCT02614066), in which a single infusion of brexu-cel elicited a high response rate consisting of durable responses in patients with heavily pretreated relapsed/refractory B-ALL.12-13

Of 54 patients in the efficacy population, 64.8% (95% CI, 51%-77%) of patients who received brexu-cel had a CR/CRi (Table13). Over half of patients (51.9%) obtained a CR. Moreover, the median duration of remission (DOR) was 13.6 months (95% CI, 9.4-not estimable [NE]). The median DOR for those who achieved CR was not reached (95% CI, 9.6-NE) and the median DOR for those who achieved CRi was 8.7 months (95% CI, 1.0-NE).13

In previously reported data, nearly all responders (97%) had MRD negativity after treatment with brexu-cel. Regarding safety, grade 3 or higher cytokine release syndrome occurred in 24% of patients who received brexucel. Grade 3 or higher neurologic toxicities occurred in 25% of patients.12

We just started the journey with CAR T-cell therapy. There is no question that our management of toxicity will improve. We will gain more expertise, so what we see today may not be the case in 5 to 6 years, Jabbour said.

Jabbour also highlighted that accessibility remains another challenge of CAR T-cell therapy that needs to be overcome. The accessibility [of CAR T-cell therapy] is a problem today, but ALL is [also] a rare disease. We can only become experts if we have patients, Jabbour added.

Id like to know where CAR T-cell therapy benefits patients most. Activity has been shown across refractory populations, but we know that outcomes can be better in patients with minimal to no disease. That is where I see a role for CAR T-cell therapy. I try to cytoreduce and give CAR T-cell therapy after to offer the best outcomes, Jabbour said.

Capitalizing upon the success demonstrated with CAR T-cell therapy, research efforts are under way to evaluate improved CAR T-cell therapy designs, dual targeting CAR T-cell therapies, allogeneic products, and fractionated CAR T-cell therapies, Jabbour explained. Notably, CAR T-cell therapy could largely replace the need for allogeneic stem cell transplant for patients with B-ALL who have MRD in first remission.

We are in the best [era because] we have the tools to cure ALL. Everything is ready in our hands. The future involves using less chemotherapy but more targeted approaches. Some of [the targeted options] are in the refractory field right now, but they are moving rapidly to the frontline setting to change the field, Jabbour concluded.

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Treatment Sequencing Could Change With Complementary Combinations and CAR T Options in B-ALL - OncLive

PHILADELPHIA, Nov. 04, 2021 (GLOBE NEWSWIRE) -- Century Therapeutics (NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology, today announced that preclinical data from the Companys CNTY-101 program and CAR-iT platform will be presented in two posters at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition, on December 11-14, 2021 in Atlanta, Georgia and virtually.

The Company also announced today that it will host a virtual research & development update on Thursday, December 16, 2021 from 8:00 AM - 9:30 AM EST to share progress on its iPSC technology platform and pipeline. Eduardo Sotomayor, M.D., director of the Cancer Institute at Tampa General Hospital, will discuss the current treatment paradigm for B-cell malignancies. For additional information on how to access the event, please visit the Events & Presentations section of Centurys website.

Details of the two poster presentations are as follows:

Abstract Number: 1729Title: Development of Multi-Engineered iPSC-Derived CAR-NK Cells for the Treatment of B-Cell MalignanciesSession Name: 703. Cellular Immunotherapies: Basic and Translational: Poster I Session Date: Saturday, December 11, 2021 Session Time: 5:30 PM - 7:30 PM Presenter: Luis Borges, Chief Scientific Officer, Century Therapeutics

Abstract Number: 2771Title: Induced Pluripotent Stem Cell-Derived Gamma Delta CAR-T Cells for Cancer ImmunotherapySession Name: 703 Cell Therapies: Basic and TranslationalSession Date: Sunday, December 12, 2021Session Time: 6:00 PM 8:00 PMPresenter: Mark Wallet, Vice President, Immuno-Oncology, Century Therapeutics

Full abstracts are currently available through the ASH conference website.

About Century Therapeutics

Century Therapeutics (NASDAQ: IPSC) is harnessing the power of adult stem cells to develop curative cell therapy products for cancer that we believe will allow us to overcome the limitations of first-generation cell therapies. Our genetically engineered, iPSC-derived iNK and iT cell product candidates are designed to specifically target hematologic and solid tumor cancers. We are leveraging our expertise in cellular reprogramming, genetic engineering, and manufacturing to develop therapies with the potential to overcome many of the challenges inherent to cell therapy and provide a significant advantage over existing cell therapy technologies. We believe our commitment to developing off-the-shelf cell therapies will expand patient access and provide an unparalleled opportunity to advance the course of cancer care. For more information on Century Therapeutics please visit http://www.centurytx.com.

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Century Therapeutics Forward-Looking Statement

This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our clinical development plans, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as may, might, will, should, expect, plan, aim, seek, anticipate, could, intend, target, project, contemplate, believe, estimate, predict, forecast, potential or continue or the negative of these terms or other similar expressions. The forward-looking statements in this presentation are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control, including, among others: our ability to successfully advance our current and future product candidates through development activities, preclinical studies, and clinical trials; our reliance on the maintenance of certain key collaborative relationships for the manufacturing and development of our product candidates; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; the impact of the COVID-19 pandemic on our business and operations; the performance of third parties in connection with the development of our product candidates, including third parties conducting our future clinical trials as well as third-party suppliers and manufacturers; our ability to successfully commercialize our product candidates and develop sales and marketing capabilities, if our product candidates are approved; and our ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the Risk Factors section of our most recent filings with the Securities and Exchange Commission and available at http://www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

For More Information: Company: Elizabeth Krutoholow investor.relations@centurytx.comInvestors: Melissa Forst/Maghan Meyers century@argotpartners.comMedia: Joshua R. Mansbach century@argotpartners.com

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Century Therapeutics to Present at the 63rd American Society of Hematology Annual Meeting and Host Virtual Research & Development Update - Yahoo...

CAR T-cell therapy and bispecific antibodies for T-cell redirection are 2 recent immune strategies developed in the treatment of multiple melanoma.

Multiple Myeloma is a clonal plasma cell neoplasm characterized by bone lesions, renal impairment, cytopenias, and immunodeficiency. Despite significant therapeutic advancements in the past 2 decades that have resulted in improved survival, myeloma remains an incurable disease. The immune environment in which the cancer cells thrive is known to be a key player in the evolution of monoclonal gammopathies from premalignant stages to advanced malignancy. Further, immune dysregulationmarked by T-cell exhaustion, tolerance induction by tumor microenvironment, and tumor escape from immune surveillanceis important in the pathogenesis. Therefore, various immune strategies have been developed, including immune-enhancing drugs such as immunomodulatory drugs, checkpoint inhibitors, monoclonal antibodies, and, more recently, chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for T-cell redirection.

CAR T cells are T lymphocytes genetically modified by viral vectors or nonviral technology such as DNA transposons to express a synthetic receptor to target a specific antigen. The single chain variable fragment (ScFV) on the ectodomain of the CAR recognizes tumor-associated antigens on the surface of tumor cells, binds to them, and initiates a cascade of cytotoxic signaling, that leads to tumor lysis.

The ectodomain is linked to the intracellular domains by a hinge/transmembrane region, commonly derived from CD8 or IgG4. The intracellular portion is the signaling domain. In the first generation of CARs, this included only the CD3 signaling

domain, which lacked a proliferation profile. The second- and third-generation CARs now include 1 (second generation) or 2 (third generation) costimulatory domains that are typically 4-1BB, CD28, and/or OX-40 to promote efficient T-cell signaling and persistence. Fourth-generation CARs (TRUCKs), which further affect the tumor microenvironment to induce cytokine production after the CAR recognizes the target antigens, and fifth-generation CARs are being developed to further improve CAR efficiency and longevity.

On the other hand, bispecific antibodies use patients unengineered T cells. The off-the-shelf antibody is designed so that 1 end binds to a multiple myeloma cell and the other end binds to a killer T cell. The first bispecific antibody for multiple myeloma was developed with an ScFV that attached to the tumor antigen and another that attached to CD3 of the T cell receptor complex of the T cell with a linker. The halflife was short and continuous infusion was required. Since then, bispecific antibodies are manufactured with an Fc segment that increases the half-life so that the agent can be administered weekly or less frequently; this is the treatment of choice in ongoing clinical trials. New agents in development include trispecific antibodies that may have a costimulatory protein or target dual myeloma antigens or antibodies that engage natural killer cells.

There are several tumor antigens being investigated as suitable targets for CAR T-cell and T-cell redirected therapies, such as CD38, CD138, SLAMF7, CD19, and more. However, the most widely studied target for both CAR T-cell therapies and for bispecific antibody therapies is B-cell maturation antigen (BCMA).

BCMA is a cell surface receptor in the tumor necrosis factor receptor superfamily member 17 (TNFRSF17). It is deemed an ideal antigenic target because it is expressed specifically on normal and malignant plasma cells but not on hematopoietic stem cells, and has higher expression on myeloma cells than normal plasma cells. It plays a key role in B-cell maturation and differentiation and promotes myeloma cell growth by binding to its ligands BAFF and APRIL. Expression of BCMA increases with progression from MGUS to advanced myeloma.

Based on encouraging results from the first major global multicenter phase 1 anti- BCMA CAR T study (NCT02658929) conducted in relapsed or refractory multiple myeloma1, investigators initiated the pivotal phase 2 KarMMa trial (NCT03361748).2 The results of this trial were updated at the 18th International Myeloma Workshop (IMW) held in Vienna, Austria, in September.3

Idecabtagene vicleucel (ide-cel; Abecma), formally bb2121, is an anti-BCMA second-generation CAR construct with a 41BB costimulatory domain. Among 128 patients enrolled in the KarMMa study, 84% were triple-class refractory. At a median follow-up of 24.8 months, the overall response rate (ORR) was 73%, with complete response (CR) or stringent CR (sCR) reported in 33% of responders. Minimal residual disease (MRD) was negative in 79% of complete responders. Further, responses were attained at a median of 1 month (range, 0.5-8.8) and the median duration of response (DOR) was 10.9 months.

The median progression-free survival (PFS) was 8.6 months and median overall survival (OS) was 24.8 months. DOR and PFS were improved in the higher-dose ranges and in complete responders. Similar degrees of responses were observed in all subgroups, including Revised International Staging System for multiple myeloma III criteria, extramedullary disease, and high tumor burden. In terms of adverse effects (AEs), cytopenias were observed in 97% of patients. Grade 3/4 neutropenia was seen in 89% of patients, grade 3/4 thrombocytopenia was seen in 52%, and grade 3/4 infections in 23%. Cytokine release syndrome (CRS) was seen in 84% of patients: 78% at grade 1/2, 6% at grade 3 or higher. CRS occurred at a median onset of 2 days and median duration was 5 days. Neurotoxicity was reported in 18% of patients, 4% of whom reported the AE as grade 3 or higher. Results of the study led to FDA approval of the first, commercially approved CAR T-cell product in March.

CARTITUDE-1 was a phase 1b/2 study (NCT03548207)4 that used a different CAR T product, ciltacabtagene autolecleucel (cilta-cel). Updated findings were presented from Usmani et al5 at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and at IMW from Jagannath et al.6

Cilta-cel is a lentiviral vector-based anti-BCMA construct with a 41BB costimulatory domain. The BCMA-catching domain targets 2 different epitopes simultaneously, increasing the binding affinity, and is the same CAR construct as in the Chinese trial LEGEND-2 (NCT03090659).

In CARTITUDE-1, 97 patients with a median of 6 prior lines of therapy were enrolled. At baseline, 88% were triple-class refractory and 99% were refractory to their last line of therapy. At a median follow-up of 18 months, the ORR was 98% for all patients and included an sCR rate of 80%. Responses were attained at a median of 1 month and deepened over time. The median DOR was 21.8 months overall (95% CI, 21.8-not estimable) and was not reached in patients with sCR. MRD negativity was achieved in 92.0% of evaluable patients.

The 18-month PFS rate was 66% (95% CI, 54.9%-75.0%) and the 18-month OS rate was 80.9% (95% CI, 71.4%-87.6%). These results far surpass outcomes with other nonT-cell mediated novel agent therapies in triple-class refractory patients.

In terms of safety, cytopenias were universal and 92 of 97 patients experienced any-grade CRS; 95% were grade 1/2 and had a median time of onset of 7 days and duration of 4 days. All-grade neurotoxicity was reported for 21% of patients, 10% of whom had neurotoxicity of grade 3 or higher. Although most neurotoxic events occurred in the setting of CRS, 12 patients had late neurotoxicity, 6 of whom resolved, 1 had ongoing neurotoxicity, and 1 died because of neurotoxicity. There were 21 deaths on study: 2 occurred in fewer than 100 days, 10 deaths were because of disease progression, and 6 were because of treatmentrelated AEs. Late recovery (greater than 1 month) of grade 3/4 cytopenias from first onset was seen in 10% of patients with neutropenia and 26% of those with thrombocytopenia.

At the American Society of Hematology (ASH) Annual Meeting 2020, Shah et al7 presented an analysis that compared efficacy outcomes seen in the KarMMa trial with those reported from the MAMMOTH study,8 which was a retrospective observational study of conventional care regimens in patients with triple-class refractory multiple myeloma.

The MAMMOTH study, which has been used in other comparative studies, has been a benchmark for investigators to compare therapeutic maneuvers in patients with triple-class exposed relapsed or refractory multiple myeloma who have received various standard-of-care therapies. The analysis applied matching-adjusted indirect comparisons to assess the efficacy of ide-cel and conventional care and showed that, in a matched population, ide-cel treatment was associated with a significantly higher ORR, PFS, and OS than conventional care.

Cilta-cel was similarly compared with conventional treatment in the MAMMOTH study and was presented by Costa et al at ASCO 2021.9 The MAMMOTH data set was used to identify patients with multiple myeloma refractory to anti- CD38 monoclonal antibodies who would meet eligibility for CARTITUDE-1 and who received conventional therapy. The intention-to-treat population (ITT) in CARTITUDE-1 was defined as patients who underwent apheresis, and a modified ITT population was defined as subset of patients who received cilta-cel at the recommended phase 2 dose (RP2D).

ORR, PFS, and OS for both the ITT population and modified ITT population in CARTITUDE-1 vs matching MAMMOTH cohorts were found to be superior. Specifically, the ORR in the ITT cohort was higher in CARTITUDE-1 compared with the MAMMOTH counterpart (84% vs 28%). Patients in the CARTITUDE-1 ITT cohort vs MAMMOTH cohort had improved PFS and OS rates at 12 months, 73% vs 12% and 83% vs 39%, respectively. Comparing the modified ITT cohorts, patients in CARTITUDE-1 had superior ORR (96% vs 30%), 12-month PFS rate (79% vs 15%) and 12-month OS rate (88% vs 41%).

Therefore, in patients with relapsed or refractory multiple myeloma beyond therapy with immunomodulatory drugs, proteasome inhibitor, and anti-CD38 monoclonal antibody, treatment with ide-cel or cilta-cel is associated with higher response rate and superior PFS and OS when compared with conventional treatment.

Other CAR T trials were reported at ASH 2020 and are being studied in various phase 1/2 trials. Research is directed at improving the efficacy and persistence of CAR products, which vary by source of product (autologous vs allogeneic CAR T cells), choice of vector (lentiviral, retroviral, or nonviral DNA transposon technology), use of humanized ScFv to prevent immunogenicity, CD4/CD8 ratio controlled to enrich for central memory phenotype to improve longevity of CAR T cells, dual target constructs to prevent relapses because of antigen escape, CARs against non-BCMA targets to treat BCMA negative relapses, and more.

Bispecific antibodies are in earlier stages of development than CAR T. The majority of anti bodies target BCMA, although there are some targeting antigens other than BCMA that have great potential in patients who have relapsed post BCMA-targeted therapies with BCMAnegative plasma cells.

Teclistamab is an anti-BCMA/anti-CD3 bispecific antibody with intravenous and subcutaneous formulations. Results of the MajesTEC-1 study (NCT03145181) were published in Lancet.10,11 Investigators treated 157 patients with a median of 6 prior lines of therapy, of whom 82% were triple-class refractory, 90% were refractory to their last regimen, and 85% were previously transplanted were enrolled to a dose escalation/ expansion study. A total of 40 patients received the RP2D of 1500 g/kg. At RP2D, the median time to response was 1 month and median time to CR was 3 months.

At a median follow-up of 7.2 months, median DOR was not reached (7.2-not reached). The ORR was 65% in the RP2D group, 58% had a very good partial response (VGPR) or better, and 40% had a CR or better. Importantly, the majority of patients in CR were MRD negative at 10-6. Among responders, 85% were alive and progression free at follow-up. The most common AEs of any grade were CRS, all grade 1 or 2 (70%), and neutropenia (65%). Grade 3 or 4 AEs occurred in 80% of patients, with the most common being neutropenia (40%), anemia (28%), and thrombocytopenia (20%). Infections occurred in 45% of patients and were grade 3 or higher in 23%.

Talquetamab is an anti-GPRC5D/CD3 first-in-class duo antibody. Results from the phase 1 MonumenTAL-1 trial (NCT04634552) were presented by Chari et al at ASH 202012 and updated at IMW by van de Donk et al.13

GPRC is highly expressed in poor-risk myeloma, and in hair follicles. In the MonumenTAL-1 trial, 174 patients with a median of 6 prior lines of therapy were enrolled, 102 to the intravenous arm and 72 to the subcutaneous formulation arm, in dose escalation and expansion cohorts. At baseline 71% of patients were triple-class refractory and 86% were refractory to last line of therapy; 21% of patients had received prior BCMA-targeted therapies.

The ORR was 70% at the RP2D, and 50% of responders had a VGPR or better, with a median time to first confirmed response of 1 month. Responses were durable and deepened over time, with 81% of responders continuing on treatment after a median follow-up of 6.3 months. CRS was reported in 79% of patients; 4% had CRS of grade 3/4. Median time to onset of CRS was a day after subcutaneous dose, and the duration was 2 days. Neurotoxicity was reported in 7% of patients (grade 1/2) and was mostly in the context of CRS. Grade 1/2 skin-related AEs were seen in 75% of patients and nail-related AEs in 18%. Dysgeusia was reported in 57% of patients. A phase 2 expansion study (MonumenTAL-2) is recruiting. Patients will receive talquetamab at the RP2D.

Various other bispecific antibodies are in clinical trials, including Regeneron 5458, another anti-BCMA/anti-CD3 bispecific antibody with very encouraging results reported at ASH last year.14 The ORR was 63% and responses were achieved by 1 month. The median DOR was 6 months, and among responders with more than 6 months of follow-up, 83% had ongoing responses for up to 13 months and 74% of responders remained on treatment. TNB-383B is a fully human triple-chain BCMA CD3 bispecific antibody with a unique anti-CD3 moiety for target lysis with minimal cytokine release and 2 anti-BCMA moieties. It is administered intravenously every 3 weeks without step-up dosing. Data for 58 patients from the ongoing first-in-human study were presented at ASH 2020.15 Safety data were comparable with results of other studies.

Cevostamab is another nonBCMA bispecific antibody. The target antigen is FcRH5, which is found on nave and memory B cells and plasma cells. The anti-FcRH5/anti-CD3 is administered intravenously every 3 weeks, and data were presented at ASH 2020 last year as well.16 Finally, CC-93269, a bispecific antibody with 1 CD3 and 2 BCMA binding sites, shows encouraging early data as well.

Future directions for bispecific antibodies include understanding resistance mechanisms, studying them in combination with various agents, and understanding sequencing strategies.

Because myeloma is marked by clonal heterogeneity, combinations of drugs with different mechanisms of action and nonoverlapping toxicities are frequently used with success. With the arrival of this new era of powerful immunotherapeutic tools such as CAR T and T-cell redirective agents, a sound understanding of their optimal use is key to maximizing their potential.

See more here:
Therapeutic Frontiers for Relapsed/Refractory Multiple Myeloma Expand With CAR T and Bispecific Antibodies - OncLive

The scientists, Christopher Rathnam and colleagues, say they have designed a way of controlling the formation of 3D spheroids made from stem cells, while enhancing the spheroids ability to differentiate into functional neurons.

The technology led to an increase in stem cell survival and differentiation two challenges with existing stem cell therapy systems in a mouse model of spinal cord injury, noted the team in a paper published inScience Advances

We believe that our technology platform is an ideal candidate for improving many other types of cell therapies that require high cell survival and effective control of cell fate, making it useful not only for treating [spinal cord injuries] but also for various other diseases and disorders, said the authors.

Although stem cell therapy holds enormous potential for treating debilitating injuries and diseases of the CNS, the team outlined how low survival and inefficient differentiation have restricted its clinical applications.

Recently, 3D cell culture methods, such as stem cellbased spheroids and organoids, have demonstrated advantages by incorporating tissue-mimetic 3D cell-cell interactions, said the experts.

However, a lack of drug and nutrient diffusion, insufficient cell-matrix interactions, and tedious fabrication procedures have compromised their therapeutic effects in vivo, they added.

To address these issues, the Rathnam led team developed a method in which biodegradable manganese dioxide nanosheets guide the rapid assembly of neural stem cells, derived from human induced pluripotent stem cells (iPSCs), into 3D spheroids.

The technique also enables controlled drug release inside the core of the spheroids, which could help to improve cell survival and differentiation, they said.

To evaluate the efficacy of the structures, which they termed synthetic matrix-assisted and rapidly templated (SMART) spheroids, the researchers implanted them at injury sites in a mouse model of spinal cord injury.

As controls, they injected cell suspensions and conventional neurospheres, formed without the use of their novel nanosheets, at the spinal cord injury sites, with the same total number of cells per animal and at the same concentrations.

They found significantly higher cell survival and improved neuronal differentiation efficiency for the SMART neurospheres compared with the controls both 7 days and 1 month after injection.

Read more:
Team finds way to enhance stem cell therapy for CNS injuries - BioPharma-Reporter.com

Dive Brief:

Takeda, which has made cell and gene therapy a research focus, is turning to partnerships and acquisitions to help fill out its pipeline. In addition to the GammaDelta deal, the large drugmaker recently struck a deal with newly launched Ensoma Therapeutics and, earlier this month, Poseida Therapeutics.

GammaDelta is well known to Takeda, which in 2017 took an equity stake in the company and negotiated an exclusive option to buy it later on.

Takeda has now cashed that chip, agreeing to pay an undisclosed upfront fee and, potentially, other conditional payments. The companies expect the deal to close in the first quarter of Takeda's fiscal year 2022, which equates to between April and June of next year.

The deal will give Takeda access to GammaDelta's allogeneic cell therapy research and another platform based around recruiting the innate immune system to battle tumors. Takeda has also invested in cancer therapies based on natural killer cells, another component of innate immunity.

According to Takeda, GammaDelta's research covers both non-engineered as well as genetically modified allogeneic cell therapies. Its first, dubbed GDX012, is derived from the blood of healthy donors and is meant to treat AML, a blood cancer that's proven more difficult to treat using cell therapy than some other leukemias and lymphomas.

The first dose was delivered to a patient in a Phase 1 trial of the therapy last month, GammaDelta said on Sept. 15.

GammaDelta was built upon research conducted by scientists at Kings College London and the Francis Crick Institute in the U.K. Venture capital firm Abingworth seeded the company with initial funding and joined Takeda in committing as much as $100 million in the 2017 deal that laid the foundation for Wednesday's acquisition announcement.

Excerpt from:
Takeda reels in a cell therapy research partner with 'build-to-buy' deal - BioPharma Dive

Juventas has grabbed a $63 million series C to advance its CASI Pharmaceuticals-partnered drug CNCT19.

The new swag will be used toward an NDA for the cell therapy as it eyes a future sales plan for the drug.

CASI, which said it welcomed the fundraise, currently shares global co-commercial and profit-sharing rights with Juventas and indirectly owns a 12% equity stake in Juventas. The biotechs latest raise was led by CICC Capital.

This comes amid a biotech boom in China, which is looking to boost its internal life science reputation and know-how especially in new area like CAR-T as a number of startups have grabbed meaty funding rounds in the past year.

RELATED: China's IASO nets $108M to advance cell therapies, antibodies for cancer, autoimmune disease

The therapy was originally created at the Institute of Hematology at the Chinese Academy of Medical Sciences, a leading hematology center in China, and is designed to treat patients with acute lymphoblastic leukemia and relapsed non-Hodgkin lymphoma by targeting CD19.

Juventas' pipeline also includes a CD19/CD20 CAR-T that is currently in pre-IND development for non-Hodgkin lymphoma, along with other cellular-based products in preclinical and exploratory studies, according to a release.

See original here:
Juventas Cell Therapy closes a $63M funding round as it eyes a big push for blood cancer hopeful - FierceBiotech