Category Archives: Cell Therapy

All cells in the body contain the same genetic material. The difference between cells therefore depends solely on which genes are expressed or turned on. Now, researchers from the University of Copenhagen have gained new insights into how genes are turned on and off and how the cells forget their past while developing into a specific cell in the body. This new knowledge is published in Nature and will be crucial for stem cell therapy and potentially treating people with cancer.

Stem cells all share the potential of developing into any specific cell in the body. Many researchers are therefore trying to answer the fundamental questions of what determines the cells developmental fate as well as when and why the cells lose the potential of developing into any cell.

Now, researchers from the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) at University of Copenhagen have discovered how stem cells can lose this potential and thus can be said to forget their past. It turns out that the proteins called transcription factors play another role than the scientists thought. For 30 years, the dogma has been that transcription factors are the engines of gene expression, triggering these changes by switching the genes on and off. However, new research results published inNaturereveal something quite different.

We previously thought that transcription factors drive the process that determines whether a gene is expressed and subsequently translated into the corresponding protein. Our new results show that transcription factors may be more analogous to being the memory of the cell. As long as the transcription factors are connected to a gene, the gene can be read (turned on), but the external signals received by the cells seem to determine whether the gene is turned on or off. As soon as the transcription factors are gone, the cells can no longer return to their point of origin, explains Josh Brickman, Professor and Group Leader, DanStem, University of Copenhagen.

The question of how a cell slowly develops from one state to another is key to understanding cell behavior in multicellular organisms. Stem cell researchers consider this vital, which is why they are constantly trying to refine techniques to develop the human bodys most basic cells into various specific types of cells that can be used, for example, to regenerate damaged tissue.So far, however, investigating the signals required to make cells switch identity has been extremely difficult, since making all the cells in a dish do the same thing at the same time is very difficult.A protein centered viewpoint

The researchers developed a stem cell model to mimic a cells response to signaling and used it to, for first time, precisely determine the sequence of the events involved in a gene being turned on and off in response to a signal in stem cells. The researchers were able to describe how genes are turned on and off and under what circumstances a cell can develop in a certain direction but then elect to return to the starting-point.

Part of this work involved measuring how proteins in a cell are modified by phosphorylation using advanced mass spectrometry available through an important collaboration with Jesper Olsens Group at the Novo Nordisk Foundation Center for Protein Research.

Combining forces with the Olsen group in the CPR enabled us to provide a unique deep description of how individual proteins in a cell react to signals from the outside, continues Josh Brickman.

These results are surprising. Although the sequence of cell transcription processes could not previously be measured as accurately as in this study, the dogma was that transcription factors comprise the on-off switch that is essential to initiate transcription of the individual gene. This is not so for embryonic stem cells and potentially for other cell types.

Transcription factors are still a key signal, but they do not drive the process, as previously thought. Once they are there, the gene can be read, and they remain in place for a while after the gene is read. And when they are gone, the window in which the gene can be read can be closed again. You can compare it with the vapour trails you see in the sky when an airplane has passed. They linger for a while but slowly dissipate again, explains first author, William Hamilton, Assistant Professor at DanStem.

This discovery is first and foremost basic knowledge, which changes fundamental assumptions in molecular biology. The new results are especially important for researchers working on stem cells and cancer biology. They provide new insight into how cells develop, how pathways involved in development determine when cells change, and when the point of no return is reached. These pathways are also found frequently mutated in cancer and the findings in this study will be valuable to the study of malignant development.

In the project, we focused on the fibroblast growth factor (FGF)extracellular signalregulated kinase (ERK) signalling pathway, which is a signalling pathway from a receptor on the surface of a cell to DNA inside the cell nucleus. This pathway is dysregulated in many types of cancer, and we therefore hope that many of the data in this study will help to inform aspects of cancer biology by indicating new ways to specifically target this signalling pathway in cancer cells, concludes Josh Brickman.

They study was funded by the Novo Nordisk Foundation, the Independent Research Fund Denmark, the Danish National Research Foundation, the Human Frontier Science Program and the Lundbeck Foundation. It also involved an important collaboration with the group of ProfessorNaama Barkai, at the Weizmann Institute for Science, Rehovot, Israel.

Reference:Hamilton, et al. (2019) Dynamic lineage priming is driven via direct enhancer regulation by ERK.Nature DOI:https://doi.org/10.1038/s41586-019-1732-z

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Researchers Reveal How Cells Know Their Future and Forget Their Past - Technology Networks

CAMBRIDGE, Mass., Nov. 08, 2019 (GLOBE NEWSWIRE) -- Rubius Therapeutics Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines, today announced that the Company presented preclinical data supporting its lead artificial antigen presenting cell program, RTX-321, for the potential treatment of HPV 16-positive tumors at the Society for Immunotherapy of Cancer (SITC) 34th Annual Meeting. Last month at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer, Rubius Therapeutics presented data demonstrating that its Red Cell Therapeutics can be engineered to create a loadable system for personal neoantigens, unlocking a potential new use of our RED PLATFORM.

Current cell therapy approachesare limited by a number of challenges they requireharvesting and engineering a patients own T cells, undergo a lengthy manufacturing process, are limited in the number of targets that can be pursued, and, once administered to patients, can elicit unpredictable immune responses, including severe side effects. Today at SITC, we presented additional preclinical proof of concept data demonstrating that Rubius Therapeutics can engineer allogeneic artificial antigen presenting cells against a tumor-associated antigen that significantly expand antigen-specific T cells and nearly eliminates lung metastases in a melanoma mouse model with minimal, reversible toxicity, said Pablo J. Cagnoni, M.D., chief executive officer of Rubius Therapeutics. Separately, current personalized neoantigen approaches are promising, but do not adequately stimulate and expand the right subset of T cells to the levels required to achieve robust efficacy. Last month at AACR-NCI-EORTC, Rubius Therapeutics presented data showing that we can engineer our red cells to create a loadable system for personal neoantigens and dramatically expand primary T cells to induce an immune response, unlocking a potential new use of our RED PLATFORM.

Data Summaries

Red Cell Therapeutic Artificial Antigen Presenting Cells (aAPCs) at SITC

(P233) RTX-321, an Allogeneic Artificial Antigen Presenting Red Cell Therapeutic, Expressing MHC I-Peptide, 4-1BBL and IL-12, Promotes Antigen-Specific T Cell Expansion and Anti-Tumor Activity in HPV16+ Tumors

Loadable Red Cell Therapeutic Artificial Antigen Presenting Cells for Neoantigens at AACR-NCI-EORTC

(B062) Enabling the Rapid Generation of Allogeneic Artificial Antigen Presenting Cell (aAPC) Red Cell Therapeutics with a Loadable MHC System

AboutRubius Therapeutics

Rubius Therapeuticsis a clinical-stage biopharmaceutical company developing a new class of medicines called Red Cell Therapeutics. The Companys proprietary RED PLATFORMwas designed to genetically engineer and culture Red Cell Therapeutics that are selective, potent and off-the-shelf allogeneic cellular therapies for the potential treatment of several diseases across multiple therapeutic areas. Rubius initial focus is to advance RCT product candidates for the treatment of rare diseases, cancer and autoimmune diseases by leveraging three distinct therapeutic modalities cellular shielding, potent cell-cell interaction and tolerance induction. For more information, visitwww.rubiustx.com,or follow us onTwitterandLinkedIn.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding our expectations regarding the therapeutic potential of our RED PLATFORM, Red Cell Therapeutic artificial antigen presenting cells and RTX-321, our expectations regarding IND-enabling studies for RTX-321, our expectations regarding the potential therapeutic benefits of RTX-321, our expectations regarding the potential expansion of uses of our RED PLATFORM and our strategy, business plans and focus. The words may, will, could, would, should, expect, plan, goal, anticipate, intend, believe, estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. 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 risks and uncertainties related to the development of our RCT product candidates and their therapeutic potential and other risks identified in ourSECfilings including our Quarterly Report on Form 10-Q for the quarter endedJune 30, 2019, and subsequent filings with theSEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim 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 our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements.Contacts:Lori MelanonVice President, Corporate Communications and Investor Relations+1 (617) 949-5296lori.melancon@rubiustx.com

Media Contact:Dan Budwick1AB+1 (973) 271-6085dan@1abmedia.com

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Rubius Therapeutics Highlights Preclinical Oncology Data at Society for Immunotherapy of Cancer Annual Meeting and AACR-NCI-EORTC International...

Genetically editing a cancer patients immune cells using CRISPR/Cas9 technology, then infusing those cells back into the patient appears safe and feasible based on early data from the first-ever clinical trial to test the approach in humans in the United States. Researchers from theAbramson Cancer Center have infused three participants in the trial thus fartwo with multiple myeloma and one with sarcomaand have observed the edited T cells expand and bind to their tumor target with no serious side effects related to the investigational approach. Penn is conducting the ongoing study in cooperation with theParker Institute for Cancer Immunotherapy and Tmunity Therapeutics.

This trial is primarily concerned with three questions: Can we edit T cells in this specific way? Are the resulting T cells functional? And are these cells safe to infuse into a patient? This early data suggests that the answer to all three questions may be yes, says the studys principal investigatorEdward A. Stadtmauer, section chief of Hematologic Malignancies at Penn. Stadtmauer will present the findings next month at the 61stAmerican Society of Hematology Annual Meeting and Exposition.

The approach in this study is closely related to CAR T cell therapy, which engineers patients own immune cells to fight their cancer, but it has some key differences. Just like CAR T, researchers begin by collecting a patients T cells through a blood draw. However, instead of arming these cells with a receptor like CD19, the team first uses CRISPR/Cas9 editing to remove three genes. The first two edits remove a T cells natural receptors to make sure the immune cells bind to the right part of the cancer cells. The third edit removes PD-1, a natural checkpoint that sometimes blocks T cells from doing their job.

Our use of CRISPR editing is geared toward improving the effectiveness of gene therapies, not editing a patients DNA, says the studys senior authorCarl June, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center. We leaned heavily on our experience as pioneers of the earliest trials for modified T cell therapies and gene therapies, as well as the strength of Penns research infrastructure, to make this study a reality.

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Positive results in first-in-U.S. trial of CRISPR-edited immune... - ScienceBlog.com

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Autolus Therapeutics Plc(NASDAQ:AUTL)Q32019 Earnings CallNov 07, 2019, 8:30 a.m. ET

Operator

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics 3Q 2019 financial results conference call. [Operator instructions] As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Ms. Silvia Taylor, vice president, global corporate affairs and communications.

Ma'am, please go ahead.

Silvia Taylor -- Vice President, Global Corporate Affairs and Communications

Thank you, Joanna. Good morning or good afternoon, everyone, and thank you for taking part in today's call on the financial results and operational highlights for the third quarter of 2019. I am Sylvia Taylor, vice president of global corporate affairs and communications, as Joanna just introduced me. With me today are Dr.

Christian Itin, our chairman and chief executive officer; and Andrew Oakley, our chief financial officer. Before we begin, I would like to remind you that during this call, we will be making forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Our actual results, performance or achievements may be materially different from those expressed or implied by the forward-looking statements.

For a discussion of the risks and uncertainties relating to our business and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, please see the section titled Risk Factors in our annual report on Form 20-F filed on November 23, 2018, as well as discussions of potential risks, uncertainties and other important factors in our other periodic filings with the SEC. The forward-looking statements contained in this presentation reflect the company's views as of the date of this presentation regarding future events, and the company does not assume any obligation to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing the company's views as of any date subsequent to the date of this presentation. On Slide 3, you will see the agenda for today, and it is as follows: Christian will provide a brief introduction, and that will be followed by our operational highlights for the third quarter of 2019.

Andrew will next discuss the company's financial results, and then Christian will conclude with upcoming milestones and other concluding comments. And of course, we will welcome your questions following our remarks. So with that, I'd now like to turn the call over to Christian.

Christian Itin -- Chairman and Chief Executive Officer

Thank you, Sylvia, and good morning to all of you, and thank you for joining us. I'm pleased to review our progress in the third quarter of 2019, as well as some recent company highlights. On Slide 5, and as reported yesterday, we will have four oral and two poster presentations at ASH in December in Orlando. We are pleased that we will be presenting data across the majority of our clinical programs.

The focus will be on AUTO1 with three oral presentations alone. This coming weekend also, we will have a poster presentation with preclinical data on our first solid tumor program, AUTO6NG, at SITC. Turning to Slide 6. Let's start the discussion of our Q3 operational highlights with our highest priority program, AUTO1 in adult ALL.

We're pleased that earlier this week, the U.S. FDA granted AUTO1 orphan drug designation for treatment of acute lymphoblastic leukemia. Relapse and refractory B-cell acute lymphoblastic leukemia represents a significant commercial opportunity both in terms of the potential market size, as well as the high level of unmet need in the management of the disease. Worldwide, approximately 8,400 patients are diagnosed every year with about 6,000 of those patients coming from the U.S.

and the EU5 European countries. While response to initial combination chemotherapy regimen is encouraging, only 30 to 40% of adult ALL patients will achieve long-term remissions, and the median survival for adult patients with relapsed/refractory ALL is less than one year. While Kymriah, a CD19-targeting CAR-T therapy was approved for pediatric ALL patients in 2017, no CAR-T therapy has been approved for adult ALL patients to date. The only redirected T-cell therapy approved for adult ALL is blinatumomab or BLINCYTO, a bispecific CD19-targeting T-cell engager.

Blinatumomab has a 42 response rate -- 42% response rate, yet the durability of the responses is limited and its event-free survival is 31% at six months. Slide 7 shows that data from ASH abstract on ALLCAR19, our AUTO1 study in adults with recurrent refractory ALL. As of the data cutoff, July 24, 83% of the 12 of adult patients achieved MRD-negative molecular complete response at one month. In April of this year at the AACR Annual Meeting reported that a median follow-up of five months, six out of 10 patients were alive and disease-free.

As of July 24th, 2019, data cutoff, that number remains consistent with seven of 12 patients or 58% remaining in MRD-negative remission at a median follow-up of nine months. This MRD response is measured by both flow cytometry, as well as PCR. As reported, AACR also -- and also summarized on Slide 8, none of the adult patients and none of the pediatric patients developed high-grade CRS, although in our adult patients, half of them had 50% or higher blast counts in the bone marrow at the start of therapy, which puts them at high risk for developing severe cytokine release syndrome. By ASH, we will have four additional months of follow-up and additional patients evaluable.

As reported at AACR, we only have patients -- only -- had only one patients transplanted post therapy and no further patient received transplant since. During our oral presentation at ASH next month, Dr. Claire Roddie will present additional follow-up data, including safety and efficacy. On Slide 8, I would like to provide some context on how this data fits into the landscape of adult ALL therapy.

As you can see in both adult and pediatric ALL, AUTO1 is differentiated and has the potential to be best in class. I'd like to highlight the consistency between the pediatric and adult data sets we've seen so far. Both show high molecular complete remission rate without inducing Grade 3 or higher cytokine release syndrome or requiring admission to the ICU for treatment of high-grade CRS. Also, the level of high-grade neurotoxicity is low.

While this is especially significant for the adult population who cannot tolerate high levels of toxicity, it is also significant in the pediatric population due to the high rates of severe CRS seen with Kymriah in these patients. With respect to efficacy in adult ALL, the complete response rate of 83% and the 58% rate of patients who remain in molecular remission at nine months for AUTO1 as detailed in the ASH abstract compared well to blinatumomab. This suggests a product profile that is emerging to be clearly differentiated from Blincyto and from other CD19 CAR-T approaches. If these findings are confirmed in our registration trial, AUTO1 has the potential to set a new standard of care in adult ALL.

On Slide 9, I'd like to summarize where we are with AUTO1 in adult ALL. This program will be the first Autolus program to move to pivotal stage. We have received feedback on our current study design from both the EMA and the FDA, and we will file a clinical trial authorization or CTA in the U.K. this month.

The IND is expected to be filed in the U.S. in the first quarter. The trial will be a single-arm study of approximately 100 patients in morphological relapse among sites in the U.S. and Europe.

The primary end point will the overall complete response rate, including complete response and complete response with incomplete hematologic recovery. Secondary end points will include MRD-negative complete response and event-free survival. And based on this design, we're targeting the second half of 2021 for a BLA filing. Moving on to pediatric ALL on Slide 10.

As a reminder, pediatric ALL is the most common cancer diagnosed in children with about 3,400 new cases diagnosed in the U.S. every year. While pediatric patients respond well to first-line treatment, 10 to 20% relapse or are refractory to treatment. Our development track in pediatric ALL will focus on AUTO1NG or next generation, and the pediatric investigational plan are paid for AUTO1.

The data from our AMELIA trial of AUTO3 in pediatric ALL has informed us on the encouraging role of dual-target antigen targeting. With AUTO3, as you recall, we have had robust clinical efficacy, yet the durability of such responses required further improvement. Thus, we will be moving forward in pediatric ALL using the AUTO1 construct through the development of AUTO1NG, which incorporates the CD19 CAR of AUTO1 and a novel CD22 CAR. The hypothesis for this next-generation version is to combine the favorable persistence properties observed in AUTO1 with the promising effect of dual targeting observed in AUTO3.

We will be presenting data from our trials of both AUTO1 and AUTO3 in the pediatric population next month at ASH. Additionally, we expect to initiate clinical evaluation of AUTO1NG in pediatric ALL in the first half of 2020. Moving to Slide 11 on our program in diffuse large B-cell lymphoma. We believe that DLBCL is a large commercial opportunity, given the market size and the aggressive nature of this disease.

DLBCL is the most common type of non-Hodgkin lymphoma. Approximately 24,000 patients are diagnosed every year in the U.S. alone. High-dose chemotherapy, combined with a monoclonal antibody led to remission in about 50% to 60% of patients.

Thus, we expect that addressable population to be approximately 10,000 patients in the U.S. and EU5 combined. DLBCL represents an aggressive -- and is an aggressive and rapidly progressing cancer. For patients who relapse or are refractory to first-line therapy, the current standard of care for second-line therapy consists of platinum-based chemotherapy regimen with rituximab.

Patients who respond to second-line therapy may go on to receive autologous hematopoietic stem cell transplantation or HSCT. Patients who are not candidates for HSCT or those who do not respond to second-line therapy or who relapse after HSCT are typically treated with a third-line salvage chemotherapy. These patients have a poor prognosis, and treatment is generally palliative to try to prevent further cancer growth without the intent to cure. On Slide 12, our DLBCL product candidate, AUTO3, is a dual-targeting CD19, CD22 CAR-T therapy.

The ASH abstract published this week shows that based on interim Phase 1 data, AUTO3 is active and well tolerated with no high-grade CRS observed. We plan to present additional interim Phase 1 data at ASH. The first U.S. patient has been enrolled in this study, and product has been delivered from our new manufacturing operation at the Cell and Gene Therapy Catapult at Stevenage to both U.S.

and U.K. clinical sites. Our AUTO3 program is on track for decision mid next year to advance the program to Phase 2. Slide 13 and our -- describes our multiple myeloma program.

As reported in Q2, we have stopped AUTO2 and will now move to a next-generation program. The Phase 1 experience will be presented in a poster. We aim to initiate clinical testing with a new program in the second half of 2020. On Slide 14, finally, I would like to conclude with a brief discussion of two other programs in our pipeline because they have the potential to bring additional value inflection in 2020.

Slide 14 talks about our T-cell lymphoma program. Patient enrollment in our Phase 1 study with AUTO4 will continue in the first quarter of next year with supply from the Catapult. As a result, we expect to present initial Phase 1 data in the second half of 2020. Finally, on Slide 15, to our lead program in solid tumors.

At our R&D Day in March, we focused on the heterogeneity of the solid tumor microenvironment and how the complexity and dynamic nature of these tumors pose particular challenges for effective therapies. T-cell therapies can be tailored to combat tumor complexity, and programming modules can be added to enhance activities in solid tumors. At SITC this Saturday, we will now present preclinical data on our AUTO6NG program designed to target GD2-positive tumors. This abstract is important because it shows the impact of advanced cell programming technologies in a solid tumor setting.

By adding IL-7 receptor chimeric protein, AUTO6NG demonstrated improved CAR persistence, and by adding dominant-negative TGF-beta receptor II protein and the truncated SHP2 protein, modified T cells were better able to combat the immunosuppressive tumor environment. The abstract also shows that in vivo delivery of AUTO6NG in a challenging mouse model exhibited potent antitumor activity and extended survival, whereas the clinical activity shown with -- while the clinically active AUTO6 could not do that. Based on these encouraging results which demonstrate the feasibility, safety and efficacy of AUTO6NG, we plan on initiating a clinical study in patients with refractory/relapsed neuroblastoma in the second half of next year. We're looking forward to discussing these results with those of you who will be at SITC this weekend.

On Slide 16, I want to share a few other updates before I turn the call over to Andrew to discuss our financials. On the manufacturing side, the Catapult site is fully operational and delivering all our clinical products for patients in both Europe and the U.S. In September, PPF Group announced that they had acquired mainly from Woodford Investment Management, an approximate 19% holding of Autolus. And control of all the remaining shares of Autolus by Woodford Investment Management are in the process of being transferred to Schroder UK Public Private Trust plc.

Finally, with regards to organizational changes, we announced last month that David Brochu has been named senior vice president, head of product delivery, to lead the transition of the company's manufacturing organization to deliver products for registration studies and ultimately commercial sale. Dave has 30 years of technology operations and engineering management expertise in the biopharmaceutical industry. He joined Autolus in March 2019 as vice president, technical operations. In addition, Vishal Mehta was named vice president and head of clinical operations throughout the transition of the company to move into the registration studies.

Vishal joined Autolus in January 2019 from Celgene, where he had the planning and execution of multiple clinical studies for CAR-T products. We're happy to be working with both of them in these expanded capacities. With that, I will turn the call over to Andrew for our third-quarter 2019 financial update. Andrew?

Andrew Oakley -- Chief Financial Officer

Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the three-month period, July through September of 2019. On Slide 18, net total operating expenses for the three months ended 30 September 2019 were $35.6 million. That was net of grant income of $0.3 million, and that compares to net operating expenses of $17.1 million, also net of grant income of $0.3 million, but that's the same period in 2018.

The increase was due, in general, to the increase in development activity, increased head count primarily in our development and manufacturing functions and the cost of being a public company. Research and development expenses increased to $27.3 million for the three months ended 30 September 2019 from $10.1 million for the three months ended 30 September 2018. Cash costs, which exclude depreciation, as well as share-based compensation, increased to $21.6 million from $9 million. The increase in research and development cash costs of $12.6 million consisted primarily of an increase of compensation-related costs of $5.2 million due to an increase in employee head count to support the advancement of our product candidates and clinical development, an increase of $3.6 million in research and development program.

Expenses related to the activities necessary to prepare, activate and monitor clinical trial programs, including the manufacturing and technical transfer activities required for AUTO1 to enable the commencement of the registration study in adult ALL and an increase of $2.6 million in facilities costs supporting the expansion of our research development, translational science capability and investment in manufacturing facilities and equipment, and lastly, an increase of $0.7 million in telecom software costs, as well as an increase of $0.5 million elsewhere. General and administrative expenses increased to $8.6 million for the three months ended 30 September 2019 from $7.3 million for the three months ended September 30, 2018. Cash costs, which again exclude the depreciation expense and share-based compensation, decreased to $5.6 million from $5.7 million. Compensation-related expenses decreased by $0.6 million.

IT, communication, general office expenses decreased by $0.7 million, and that was offset by legal and professional fees of 0.9 million and an increase of 0.3 million in very preliminary commercial expenses. Net loss attributable to ordinary shareholders was $27.2 million for the three-month period compared to $12.9 million for the same period in 2018. The basic and diluted net loss per ordinary share for the three months ended 30 September 2019 totaled $0.61 or 61 cents compared to a basic and diluted net loss per ordinary share of $0.33 for the three months ended 30 September 2018. Cash and cash equivalents at the end of the period totaled $229.4 million, and that compares with $247.1 million at the end of September in 2018.

And we anticipate that cash on hand provides us with the runway into the second half of 2021. With that, I will now hand the call back to Christian to give you a brief outlook on our expected upcoming milestones. Christian?

Christian Itin -- Chairman and Chief Executive Officer

Thank you, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones and news flow through 2020. Let's move to Slide 20. The upcoming 15 months will be an eventful period for us with multiple clinical milestones and opportunities for value creation.

Our chief operational focus will be our moving AUTO1 in adult ALL into registration trial in the U.K. and U.S. We also expect to report data across various programs and to progress a number of our other clinical candidates, specifically updates on our ongoing clinical trials, initiation of a Phase 1 study of AUTO1NG in pediatric ALL in the first half of next year, a go/no-go decision on Phase 2 initiation of AUTO3 in DLBCL middle of 2020, initiation of a Phase 1 study of AUTO6NG in neuroblastoma in the second half of 2020 and initiation of a Phase 1 study in the next-generation program in multiple myeloma also in the second half of 2020. In conclusion, on Slide 23, I'd like to recap the major messages from today's call.

First, AUTO1 is our foundational program and the first Autolus program expected to move into pivotal stage. Given the positive safety and efficacy profile today, we believe that AUTO1 has the potential to be a best-in-class CD19 CAR T in ALL. Secondly, our next priority is on AUTO3 in DLBCL with AUTO3NG as a next-generation opportunity. We expect to report full Phase 1 data for AUTO3 in middle of 2020 to reach a decision point on Phase 2 trial initiation thereafter.

Third, in the pediatric ALL, we have transitioned our focus on AUTO1 and AUTO1NG. While AUTO3 data confirmed the dual-targeting hypothesis, we believe the excellent persistence with AUTO1 is likely to drive long-term remissions. Looking ahead to 2020, we see opportunity for additional value steps for multiple myeloma, T-cell lymphoma and the GD2-positive tumor programs. The company has a strong balance sheet with 230 million in cash, which provides a run rate to the second half of 2021.

And finally, we're looking forward to seeing many of you at the upcoming SITC and ASH Annual Meetings. We'd now like to take your questions. Operator, please open the line.

Operator

[Operator instructions] Your first question comes from the line of Gil Blum from Needham & Company. Your line is open.

Gil Blum -- Needham and Company -- Analyst

Thank you for taking my question. Just a quick one about -- so AUTO6NG data that's coming out at SITC, we know that this is kind of a mix of T cells that were transected with two different vectors. What kind of analysis would you have to do in a product that's this complex before using it in human? Like, how would the product be defined?

Christian Itin -- Chairman and Chief Executive Officer

Well, first of all, thanks for joining, and thanks for your question. Obviously, what we're doing with AUTO6 is we're introducing a substantial amount of genetic information into a single cell. And that is actually a level of genetic information that you cannot deliver with a single vector. So you have to use two vectors to do that.

And this is now actually an approach that's been used in a number of programs that have gone through regulatory review and are actually currently the clinic for other types of indications and obviously have gone through the normal regulatory process and are active in development. Ultimately, what you have to show is you have to demonstrate the activity of the product as is and you design your safety studies, etc, to really understand the activity of the product as a whole. We have to understand, obviously, also that even when you look at a product that is transduced to the single vector that we have multiple types of differentiation state of T cells in there, which gives you quite a wide range of properties of these cells, just based on the differentiation state. So the products are complex to begin with.

And the programming on itself, we don't believe will add a significant element on top by adding the two vectors in of themselves. Vectors are designed to -- all of them actually recognize the target antigen so that the basic activity is actually shared among all transduced cells.

Gil Blum -- Needham and Company -- Analyst

All right. Maybe a bit of an odd question, but if Kymriah or ever used off-label in adults ALL? Is that -- anyone does that?

Christian Itin -- Chairman and Chief Executive Officer

Well, what we do know is that the products, obviously, are not part of the normal payment process that you can actually get -- actually have them used in. If they're used off label or not, that's difficult for us to tell. There's certainly a possibility within oncology for products to be used off label, but it's something we can't judge. And I don't think there's any information out there on what it might be and how many patients might actually be impacted.

Gil Blum -- Needham and Company -- Analyst

Got you. And just the last one. I know we're getting an update on AUTO2, but when could we expect updates on the new program in multiple myeloma?

Christian Itin -- Chairman and Chief Executive Officer

Yes. So the next-gen version for the multiple myeloma program we expect to update when we're actually entering into clinical trials and obviously, during the course of next year have opportunity to provide an update on the design of the program, and we'll do it at that point in time.

Gil Blum -- Needham and Company -- Analyst

Thank you for taking my questions and congrats on the quarter.

Christian Itin -- Chairman and Chief Executive Officer

Thank you so much. Thanks for joining.

Operator

Your next question comes from the line of Jim Birchenough from Wells Fargo. Your line is open.

Jim Birchenough -- Wells Fargo Securities -- Analyst

Hi guys, thanks for the call and congrats on the progress toward the AUTO1 pivotal. Just on that pivotal question, could you maybe speak to, No. 1, are there going to be any entry criteria whether it's tumor burden or other features that will reduce the risk of severe CRS or neurotoxicity? And then maybe if you could discuss what the efficacy hurdle is there, if there's some lower bound of the confidence interval you need to shoot for at some point estimate of response, just so we have a frame of reference. And then I've got a follow-up.

Christian Itin -- Chairman and Chief Executive Officer

Yes. First of all, thanks for joining, Jim. With regards to the pivotal study that we're planning to do here, obviously, when you look at the inclusion criteria, we're including patients that actually are in formal relapse. And in other words, these are patients that have more than 5% blasts in the marrow, which is kind of when you have a morphological relapse.

So all these patients have manifest disease, and obviously, given the speed at which the disease moves, can actually have quite a range. And as you see with the data that we have shown at AACR and we'll update at ASH, and approximately half the patients have a massive level of tumor burden, but all patients are in formal relapse.

Jim Birchenough -- Wells Fargo Securities -- Analyst

And just in terms of the efficacy hurdle?

Christian Itin -- Chairman and Chief Executive Officer

In terms of the efficacy hurdle, when we look at the current programs, you'd expect and you'd see kind of well from our own programs that we've shown today is that you want to show a robust molecular complete remission rate because that's your entry ticket for a transformational activity. And then, obviously, you want to have durability of effect. So, we would clearly want to improve substantially over and above the durability of effect that we've seen with blinatumomab in this patient population. Remember that was 31% at six months.

We believe that we want to see somewhere in the range of the double of that at that point in time.

Jim Birchenough -- Wells Fargo Securities -- Analyst

Terrific. And then just on AUTO3 and the go/no-go decision in DLBCL in mid-2020, is durability of response going to be the key there? Or maybe you could speak to what the criteria are for go/no-go. And I guess if there was a durability that was adequate in ALL, is there something different about DLBCL where you might still get away with a win there? Just trying to understand the go/no-go.

Christian Itin -- Chairman and Chief Executive Officer

Yes. The disease settings are quite different between leukemia, acute leukemia and DLBCL. What we need to be able to do in leukemia is we need to be able to put pressure on the tumor for very long periods of time. We're talking 18 months, 24 months to get to transformational activity, and we're actually going to be showing kids that are now really long-term -- have long-term observation on the AUTO1 experience.

When you look at DLBCL, it is quite different. What you need to induce is you need to induce a complete remission. And typically, the complete remission that you can induce and observe at three months or at the latest at six months depending on the program is a very good measure for long-term benefit in that patient population. And the effect that it can induce is, obviously, one that happens relatively quickly, usually within three months' period of time.

Most of those patients have accomplished or have achieved their CR. And at that point, most of the patients, if you look at the Yescarta data, the JCAR-17 data, the Kymriah data, this can actually sustain that activity. And so what we want to see is, we want to see a robust CR rate, as well as, obviously, have a good sense for the durability of those CRs as well at that point in time.

Jim Birchenough -- Wells Fargo Securities -- Analyst

Just a final question, Christian. Reimbursement -- inpatient reimbursement for Kymriah and Yescarta has been difficult from what we've heard, and we've heard from a number of consultants that the move to outpatient is going to be really important in advance of getting some CAR-T specific reimbursement code for the inpatient setting. And so how important is it to you to have features in your cell that lend themselves to outpatient delivery? And is there some way to incorporate that into a trial design?

Christian Itin -- Chairman and Chief Executive Officer

I think it is important when you think about the overall cost of therapy, obviously, there is the actual cost of the therapeutic itself, of the drug itself, but there's also a significant cost associated with managing the patients. And obviously, the more severe your adverse events are, the higher the costs are for the management of the patients. And what cause challenges, particularly in DLBCL reimbursement in the U.S. and elsewhere, is that that portion of patient management cost was initially not properly covered.

And that caused the major issue for the hospitals who were treating these patients. That is now actually being resolved. It's also in part resolved for the Medicare patient, but it remains a significant driver of the overall cost of therapy. So actually, having products that have no high-grade CRS, cytokine release syndrome, that have limited or minimal neurotoxicity is important because it allows you to actually consider giving the patient the therapy and then actually have the patient in an outpatient setting from there on forward.

And as you see with all the programs, it is a progression in terms of the information and the experience you have with the product. What you want to make sure is that it captures much information related to that intensity of patient management during the course of your pivotal study even if your patients are initially mostly treated as inpatients, and then obviously with increased experience of the products, will move more toward an outpatient setting. But it's absolutely crucial to collect that information also when you have conversations with payers because it is a key element of the value assessment as well.

Jim Birchenough -- Wells Fargo Securities -- Analyst

Well, thanks for taking the questions.

Christian Itin -- Chairman and Chief Executive Officer

Thank you very much.

Operator

Your next question comes from the line of Matt Phipps from William Blair. Your line is open.

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Autolus Therapeutics Plc (AUTL) Q3 2019 Earnings Call Transcript - The Motley Fool

Arizona has been called "the wild, wild west" of regenerative medicine.

The Valley is one of the most popular places in the country for stem cell clinics. The new and controversial therapy is being marketed and practiced all over Phoenix and Scottsdale.

The less invasive procedure promises to heal pain, nearly anywhere in their body. It is advertised as effective, safe, and ethical, but outside experts and industry insiders say consumers need to do their research to avoid being exploited, and potentially spending thousands in cash on a worthless injection.

"IT HAS GREAT POTENTIAL"

The world of regenerative medicine is still being explored and developed.

"It actually gives you really good results," explained Dr. Matthew Hernandez, a naturopathic physician with Ethos.

"There's a lot of hope and promise, generally around the prospects for stem cells," said ASU Professor Emma Frow.

"Were still in the developmental stage. Stem cell therapy has been around for less than ten years. Thats new in medicine," said Dr. Steven Sorr, a naturopathic physician who runs Source of Health in Scottsdale.

"It encourages your own body to heal itself," said Janet McConnell, a 63-year-old bodybuilder who "had cartilage damage several years ago."

Instead of a surgery that would have derailed her competition training for months, she opted for injections.

"Three years ago, instead of the surgery, I had a PRP treatment," said McConnell. "It was very effective."

Years later, she returned to Dr. Hernandez for another round.

For most, Stem Cell and Platelet Rich Plasma (PRP) therapy is a mystery. "It's kind of controversial and experimental," said Matthew Riddle, Director of Sales for Celling Biosciences.

The treatments concentrate platelets or stem cells, usually from the patient's own blood. Experts say it is important to always ask the doctor or provider where the "growth factors" are coming from, because in order to ensure they are alive they should be coming from the patient's own blood, fat, or bone marrow. Otherwise, patients can receive "dead" stem cells, which are not nearly as effective.

"We are very adamant to use the patient's own cells," said Riddle, who uses a centrifuge to separate out the blood, saline and growth factors that will be re-injected. "When we inject that into an area, we are telling your body to go heal that spot," said Dr. Hernandez.

"Stem cell treatment is really about trying to take the stem cells out of your body and...inject them back into another part of your body, in order to try and heal whatever part of the body is suffering," said Professor Frow.

"IT'S THE NEW WAVE"

According to researchers, Scottsdale and Phoenix are two of the seven "hot spot" cities in the country.

Arizona State University professors Emma Frow and Dave Brafman spent years studying the industry , and mapping out dozens of clinics in the Valley. They believe there are many more, as some intentionally practice under the radar. "I don't believe right now that there is enough evidence to suggest that they work," said Professor Frow.

"They are unregulated, unproven and for-profit," added Professor Brafman.

The profits are plentiful. "There's cash involved, so this isn't covered by insurance," said Dr. Hernandez.

"PREYING ON PEOPLE'S PAIN"

The thousands in cash is one of many reasons the burgeoning industry is ripe for exploitation.

"The other piece too, it is it is new and upcoming," said Dr. Hernandez.

Many potential patients do not know the first thing about the procedure they are being sold, and doctors say many fall for sales tactics that are practiced at traveling seminars.

"They are preying on people's pain," said Dr. Sorr. "I think its really unethical and it upsets me."

Dr. Sorr believes the seminars are "a scam" that specifically targets an elderly clientele.

"They wine you and dine you. They go through a little dinner presentation and it is not the doctor, it's a marketing agency," he said.

The doctor told ABC15 he has had clients who have been duped, even after he told them they were not ideal candidates for stem cell or PRP therapy.

"It really broke my heart that he spent thousands upon thousands of dollars for something that was worthless.

"I don't agree with how they are done," said Dr. Hernandez. "They inject people and they get money. That's not practicing medicine, that is selling."

Both naturopathic physicians told ABC15 that some patients do not need the treatment, or will get subpar results from the injections. They say it is well known in the industry that some practices will continue to sell in order to reap the thousands in cash.

"ALL OF IT FALLS ON THE PATIENT"

Right now, there is little regulation or oversight of the industry in Arizona.

"Really all of it the falls on the patient, with very little recourse if things go wrong," said Dr. Emma Frow.

During the course of our investigation, ABC15 discovered the Arizona Medical Board and County Health Department do not take complaints or oversee the people performing injections. The federal government has also been slow to implement widespread regulation.

"The FDA has their hands tied," said Dr. Sorr. "There are too many people out there that are doing this that havent had the proper training, they dont have the right experience, the right tools and all that."

There are some larger regulations in Arizona, governing who can handle a needle and perform injections.

Unlike other industries though, including massage therapy, there is no board that checks on licensing or investigates complaints involving botched procedures or alleged fraud.

"The state medical boards, need to become a little bit more involved in sort of identifying, or responding to claims," said Professor Brafman.

"I don't think it would hurt to have it, for sure. At the end of the day it's about protecting the public," said Dr. Hernandez.

For thousands of Arizonans, like Janet McConnell, regenerative medicine has helped heal chronic pain. Before spending thousands thousands though, do your research. "Always get a second opinion," said Dr. Sorr.

"I think this is really a case of buyer beware, or consumer beware," said Professor Frow.

If you are planning on undergoing a stem cell or PRP treatment, click here for questions experts say you should always ask ahead of time.

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Arizona the "wild west" of stem cell therapy; experts say promising therapy ripe for exploitation - ABC15 Arizona

Sponsored content brought to you byCell Therapy Overview

CAR-T therapies have quickly shifted the direction of treatments for aggressive diseases, such as blood cancers, where previous treatments were limited. There are currently over 1000 cell and gene therapy trials and two approved cell therapies, axicabtagene ciloleucel and tisagenlecleucel, but determining cellular fitness is still a top need in moving the next generation of cell therapy treatments forward.

Both autologous and allogeneic options are among the cutting-edge therapies of today, which also comprise T cells, NK cells, and more, while using technologies like CRISPR and TALEN to address blood cancers and solid tumor. CRISPR, for example, has paved the way for new possibilities in the cell therapy space, including providing a way for researchers to develop a renewable source of NK cells to be optimized for cell therapies,1 as well as enabling more specific and targeted edits to cells in general.

Because cell therapy relies on immune cells from patients, or healthy donors in the case of allogeneic therapies, development and production is more complicated. To ensure that these cell products are potent and effective, knowing how to engineer potency and durability throughout the development and bioprocessing stages is crucial.

Knowledge of the powerful functional T cell drivers can give complex engineered immune cell therapies the edge that they need in this competitive and fast-paced environment. Legacy technologies, such as bulk ELISA or flow cytometry, can give estimates of a samples cytokine secretions, but miss the highly functional cell subsets that correlate to in vivo response. Bulk analysis is unable to analyze single cell function or identify which cells are secreting specific cytokines. Flow cytometry involves fixing and permeabilizing cells and can only provide estimates of cellular function. RNA-Seq can estimate function as well, but only shows a 0.4 correlation from RNA to protein.2 These limitations from legacy technologies remain challenges in determining function of cell products.

To address this challenge and need, IsoPlexis functional T cell biology is rooted in the ability to directly identify what each T cell secretes in a highly multiplexed manner, for the first time. High multiplexing of simultaneous true cytokines reveals most consistently intense and potent T cells. The IsoPlexis system can discover true function in single cell subsets, or highly polyfunctional cells, which correlates to response and reveals highly differentiated T cell insights.

In the initial phase of approved cell therapies, researchers published data using IsoPlexis single-cell functional cytokine detection system to demonstrate the enhanced ability to detect underlying cell therapy product heterogeneity. IsoPlexis single-cell cytokine based PCA visualizations (Figure 1) of the CAR-T product, published in JITC,3 revealed the potential to visualize donor differences.

Figure 1. Visualizing CAR-T cell functional groups and donor differences.

In an additional study, researchers used the IsoPlexis single-cell platform to correlate pre-infusion cell product data, using a metric termed Polyfunctional Strength Index (PSITM), with objective response in vivo for the first time. Importantly, existing technologies like flow cytometry and bulk ELISA did not correlate with response (Figure 2), as published in Blood.4 In contrast to flow-based systems, where cells must be fixed and permeabilized, halting biological function and trapping cytokines within the cells, IsoPlexis single-cell cytokine system measures true secretions of the full range of functional cytokines, which recruit other immune cells, destroying the tumor.

Figure 2. Polyfunctional Strength Index (PSITM) is uniquely predictive to patient response.

IsoPlexis correlative CAR-T cellular fitness metrics are defined by their ability to capture truly released cytokine function of each cell. This knowledge is being applied in advanced bioprocessing with cell product biomarkers (Figure 3) and in donor selection in allogeneic cell therapies by leaders in the cell therapy field.

Figure 3. Novel finding: CAR T cell polyfunctionality associated with outcomes.

Excerpt from:
Introduction to Cell Therapy - Clinical OMICs News

European regulations might be responsible for lower numbers of advanced therapy clinical trials running in the region when compared to the US and Asia.

Europe has historically been a pioneer in advanced therapies, such as cell and gene therapy. Europe was the first region to approve a gene therapy, and it boasts the highest number of marketing authorizations of advanced therapies worldwide.

However, in the past four years, the number of clinical trials with advanced therapies has stalled in Europe, growing by just below 2%. Meanwhile, the number of trials went up in North America and Asia by 36% and 28%, respectively, in the same period.

This conclusion was drawn from the analysis of the 2,097 clinical trials of advanced therapies conducted worldwide between 2014 and the first half of 2019. The study was carried out by the Alliance for Regenerative Medicine (ARM), an international community of stakeholders in the development of new medical technologies.

Current EU regulations could be to blame. Any clinical trial that is conducted across multiple European countries requires separate review and approval in each country.

When national authorities review clinical trial authorizations independently, they may have diverging opinions that create a delay for the companies, said Annie Hubert, Senior Director of European Policy at the ARM.

The issue becomes even bigger with advanced therapies, as the requirements regarding testing donors and starting materials vary across different countries.

In particular, gene therapies are the most affected. The study found that while in North America 71% of advanced therapy trials involve any form of gene therapy or gene editing, in Europe that percentage is only 55%.

Gene therapies face an additional hurdle in Europe; they are considered genetically modified organisms and must therefore additionally comply with GMO regulation, which falls under the umbrella of environmental or agricultural legislation depending on the country.

The complexity in the GMO regulation may be the reason why we see fewer clinical trials with gene therapy in Europe compared to other regions, Hubert told me.

A company that applies for a clinical trial with a gene therapy needs to secure the review and approval by the GMO authority in that country on top of having the approval for the clinical trial for the medicinal product. There have been situations where, for the same gene therapy, the decision from different GMO authorities in Europe was different.

The study concluded that streamlining the regulatory process might make Europe more competitive in the development of advanced therapies. This can already be seen in certain European countries, such as Belgium, Denmark and Switzerland, where the amount of clinical trials is actually higher than in the US when accounting for their size.

Belgium for instance has an approval time of 15 days for phase I clinical trials. That acts as an incentive, said Hubert. In the UK and in Denmark, companies have access to a central point of contact that liaises with the GMO authorities and facilitates the review of clinical trial applications.

The European Commission has been aware of these issues for several years. Previous studies reported that the current clinical trial legislation, which dates to 2001, resulted in a decline in the overall number of clinical trials running in Europe.

The Commission has already created new regulations that seek to address some of these problems through a centralized application system where one national authority takes the lead in reviewing the application, while the others can either agree or disagree with it.

However, there have been delays in the creation of the application platform and the regulations have not yet been implemented. Hubert expects this could happen sometime in late 2020 or 2021.

I think we need to be realistic. Any significant change will probably take a number of years before we can see the number of clinical trials increasing significantly in Europe.

See the article here:
EU Regulations Are Holding Back Gene and Cell Therapy Clinical... - Labiotech.eu

BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, today announced that hemophilia A gene therapy clinical data and hemoglobinopathies ex vivo gene-edited cell therapy data will be featured in poster presentations at the 61st Annual Meeting of the American Society of Hematology (ASH). The ASH abstracts, which were submitted on August 3, 2019, were released online this morning. The conference will take place in Orlando, FL, from December 7-10, 2019.

Gene Therapy

The SB-525 poster will show updated Alta study data including durability of Factor VIII (FVIII) levels, bleeding rate, factor usage, and safety, for all five patients in the high dose cohort of 3e13 vg/kg, with approximately 4 months to 11 months of follow-up after treatment with SB-525.

As of the abstract submission date, four patients in the 3e13 vg/kg cohort achieved FVIII levels within the normal range with no bleeding events reported up to 24 weeks post-administration. These patients did not require FVIII replacement therapy following the initial prophylactic period of up to approximately 3 weeks post-SB-525 administration. The fifth patient in the 3e13 vg/kg cohort had only recently undergone treatment with SB-525 at the time of the abstract submission. As previously reported, one patient had treatment-related serious adverse events (SAEs) of hypotension and fever, which occurred approximately 6 hours after completion of the vector infusion and resolved with treatment within 24 hours, with no loss of FVIII expression. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, said Bettina Cockroft, M.D., M.B.A., Chief Medical Officer of Sangamo, commenting on the published abstract. We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND.

Ex Vivo Gene-Edited Cell Therapy

The ST-400 beta thalassemia poster will show preliminary results from the first three patients enrolled in the Phase 1/2 THALES study. In this study, hematopoietic stem progenitor cells (HSPCs) are apheresed from the patient, edited to knock out the erythroid specific enhancer of the BCL11A gene, and cryopreserved prior to infusion back into the patient following myeloablative conditioning with busulfan. The first three patients all have severe beta thalassemia genotypes: 0/0, homozygous for the severe + IVS-I-5 (G>C) mutation, and 0/+ genotype including the severe IVS-II-654 (C>T) mutation, respectively.

As of the abstract submission date, Patient 1 and Patient 2 had experienced prompt hematopoietic reconstitution. Patient 1 had increasing fetal hemoglobin (HbF) fraction that contributed to a stable total hemoglobin. After being free from packed red blood cell (PRBC) transfusions for 6 weeks, the patient subsequently required intermittent transfusions. Patient 2 had rising HbF levels observed through 90 days post-infusion. For both patients, as of the most recent follow-up reported in the abstract, on-target insertions and deletions (indels) were present in circulating white blood cells. Patient 3 had just completed ST-400 manufacturing at the time of abstract submission. As previously disclosed, Patient 1 experienced an SAE of hypersensitivity during ST-400 infusion considered by the investigator to be related to the product cryoprotectant, DSMO, and which resolved by the end of the infusion. No other SAEs related to ST-400 have been reported and all other AEs have been consistent with myeloablation. No clonal hematopoiesis has been observed. Longer follow-up will be required to assess the clinical significance of these early results. ST-400 is being developed as part of a global collaboration between Sangamo and Sanofi, along with support through a grant from the California Institute for Regenerative Medicine (CIRM).

The first three patients enrolled in the THALES study all have severe beta thalassemia genotypes that result in almost no endogenous beta globin production. The increases in fetal hemoglobin and presence of on-target indels in circulating blood cells suggests successful editing using zinc finger nucleases. The results are preliminary and will require additional patients and longer-term follow-up to assess their clinical significance, said Adrian Woolfson, BM., B.Ch., Ph.D., Head of Research and Development. It is important to note that myeloablative hematopoietic stem cell transplantation reboots the hematopoietic system, and that sufficient time is required for the stem cells to fully repopulate the marrow and for new blood cells to form. In other myeloablative conditioning studies in a similar patient population, full manifestation of the effects of gene modification in the red blood cell compartment has taken as long as 12 months or more to become evident.

Sanofis in vitro sickle cell disease poster details a similar approach to ST-400, using mobilized HSPCs from normal donors and SCD patients and utilizing the same zinc finger nuclease for gene editing, delivered as transient non-viral RNA, and designed to disrupt the erythroid specific enhancer of the BCL11A gene, which represses the expression of the gamma globin genes, thereby switching off HbF synthesis. Results from ex vivo studies demonstrated enriched biallelic editing, increased HbF, and reduced sickling in erythroid cells derived from non-treated sickle cell disease patients. Sanofi has initiated a Phase 1/2 trial evaluating BIVV003, an ex vivo gene-edited cell therapy using ZFN gene editing technology to modify autologous hematopoietic stem cells using fetal hemoglobin to produce functional red blood cells with higher BhF content that are resistant to sickling in patients with severe sickle cell disease. Recruitment is ongoing.

About the Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 gene therapy in patients with severe hemophilia A. SB-525 was administered to 11 patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11 vg/kg, 2e12 vg/kg, 1e13vg/kg and 3e13vg/kg) with expansion of the highest dose cohort by 3 additional patients. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency.

About the THALES study

The Phase 1/2 THALES study is a single-arm, multi-site study to assess the safety, tolerability, and efficacy of ST-400 autologous hematopoietic stem cell transplant in 6 patients with transfusion-dependent beta thalassemia (TDT). ST-400 is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology. The THALES study inclusion criteria include all patients with TDT (0/0 or non- 0/0) who have received at least 8 packed red blood cell transfusions per year for the two years before enrollment in the study. The FDA has granted Orphan Drug status to ST-400.

About Sangamo Therapeutics

Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, in vivo genome editing, and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Forward-Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the Company's ability to develop and commercialize product candidates to address genetic diseases with the Company's proprietary technologies, as well as the timing of commencement of clinical programs and the anticipated benefits therefrom. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the outcomes of clinical trials, the uncertain regulatory approval process, uncertainties related to the execution of clinical trials, Sangamo's reliance on partners and other third-parties to meet their clinical and manufacturing obligations, and the ability to maintain strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that Sangamo and its partners will be able to develop commercially viable product candidates. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission and Sangamo's most recent Quarterly Report on Form 10-Q. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Sangamo Announces Gene Therapy and Ex Vivo Gene-Edited Cell Therapy Data Presentations at the American Society of Hematology Annual Meeting - Business...

The Phase 3 clinical trial testing BrainStorm Cell Therapeutics cell therapy candidateNurOwn inamyotrophic lateral sclerosis (ALS) patients is continuing as planned after a second safety assessment by the trials independent Data Safety Monitoring Board (DSMB) found no reasons to stop, the company announced.

The DSMBs recommendation comes after a pre-specified interim analysis of the first 106 ALS patients treated repeatedly with NurOwn in this randomized, placebo-controlled clinical trial.

After reviewing all of the safety data as of September 30th, the DSMB has recommended the study continue without any changes in the protocol. We did not identify any significant safety concerns, Carlayne Jackson, MD, a professor of Neurology and Otolaryngology UT Health San Antonioand the DSMB chairperson, said in a press release.

DSMBs consist of research experts who monitor the progress of a clinical trial and review safety and efficacy data while the study is ongoing. This panel can recommend that a trial be stopped early because of safety concerns or evidence a therapy is not working as intended, or if the trials main goals have already been reached.

NurOwn consists of mesenchymal stem cells (MSCs; stems cells able to generate various cell types) collected from a patients bone marrow. These MSCs are expanded and matured into a specific cell type called MSC-NTF by growing them under conditions that induce them to secrete high levels of neurotrophic factors (NTFs) that support the growth, survival, and maturation of nerve cells.

MSC-NTF cells also deliver immune system regulating cytokines, small proteins important in cell signaling or messaging, to sites of damage, BrainStorm reports. It is thought this will help to slow or stabilize disease progression.

The double-blind Phase 3 trial (NCT03280056),fully enrolledat its six U.S. sites, is investigating use of NurOwn in 200 ALS patients whose symptoms became evident within two years of the studys start. Patients are randomized 1:1 to either NurOwn or placebo, given via intrathecal (spinal canal) injection every two months.

The studysprimary measures of safety and efficacy are being determined using the ALS functional rating scale score (ALSFRS-R; a score of abilities like swallowing, speech, handwriting, walking, etc.) in patients after 28 weeks of treatment compared to placebo.

A secondary goal is assessing how biomarkers, such as cell-secreted neurothrophic factors, inflammatory agents, andcytokines, change in the blood and cerebrospinal fluid (the liquid surrounding the brain and spinal cord) after treatment with NurOwn.

BrainStorm is expecting to have topline trial data by the end of 2020, which will potentially support the submission of a Biologics License Application (BLA) to theU.S. Food and Drug Administration requesting approval.

We are very pleased with the DSMB recommendation that the Phase 3 clinical trial continue without any protocol modification. This represents an important clinical trial advancement for BrainStorm and for the development of NurOwn as an innovative cellular therapy approach for ALS patients, added Ralph Kern MD, BrainStorms chief operating officer and chief medical officer.

This clinical trial is being funded by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989), and other types of investment.

NurOwn was given orphan drug status by both theFDA and the European Medicines Agency (EMA) as apotential ALS treatment.

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queens University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimers disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.

Total Posts: 5

Ins Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.

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Phase 3 Trial of ALS Cell Therapy, NurOwn, Gets Thumbs Up in Safety Review by Monitoring Board - ALS News Today

University of Pennsylvania scientists are piloting the use of special imaging markers to track the movement of one cancer therapy within the body.

Theyre doing so to gauge the success of CAR T, an immunotherapy that involves genetically modifying a patients immune cells and inserting them back into the body to kill cancer. Such therapy has revolutionized care for some cancers, but doctors need help viewing the travel of cells to measure progress. Early results of the experiment were detailed last month in Molecular Therapy.

"Currently, the only way to know whether a gene or cell therapy is still present in the body is to regularly biopsy tumors or draw blood, which offer very crude measurements of the therapy, Mark Sellmyer, MD, PhD, an assistant professor of radiology at Penn Medicine and lead author of the study, said in a statement. With our technology, clinicians would be able to see, quantitatively, the number and location of CAR T cells that have lasted in the body over time, which is an indicator of the therapy's durability and potential efficacy.

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Researchers use imaging tags, PET/CT scanner to better track cancer therapies - Radiology Business