Category Archives: Stem Cell Therapy

TMRR, in its recent market report, suggests that the Stem Cell Therapy market report is set to exceed US$ xx Mn/Bn by 2029. The report finds that the Stem Cell Therapy market registered ~US$ xx Mn/Bn in 2018 and is spectated to grow at a healthy CAGR over the foreseeable period.

The Stem Cell Therapy market research focuses on the market structure and various factors (positive and negative) affecting the growth of the market. The study encloses a precise evaluation of the Stem Cell Therapy market, including growth rate, current scenario, and volume inflation prospects, on the basis of DROT and Porters Five Forces analyses. In addition, the Stem Cell Therapy market study provides reliable and authentic projections regarding the technical jargon.

In this Stem Cell Therapy market study, the following years are considered to project the market footprint:

The content of the Stem Cell Therapy market report includes the following insights:

Request For Discount On This Report @ https://www.tmrresearch.com/sample/sample?flag=D&rep_id=1787&source=atm

On the basis of solution, the global Stem Cell Therapy market report covers the following solutions:

Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

Request Sample Report @ https://www.tmrresearch.com/sample/sample?flag=B&rep_id=1787&source=atm

The Stem Cell Therapy market study answers critical questions including:

All the players running in the global Stem Cell Therapy market are elaborated thoroughly in the Stem Cell Therapy market report on the basis of R&D developments, distribution channels, industrial penetration, manufacturing processes, and revenue. In addition, the report examines, legal policies, and comparative analysis between the leading and emerging Stem Cell Therapy market players.

Customize This Report @ https://www.tmrresearch.com/sample/sample?flag=CR&rep_id=1787&source=atm

Why choose TMRR?

Visit link:
Stem Cell Therapy Market Opportunity Analysis and Industry Forecast up to 2017 2025 - Jewish Life News

Reported Initial Clinical Data from FT500 Phase 1 Study in Advanced Solid Tumors, Supporting Safety and Tolerability of Multi-dose Treatment Paradigm for Off-the-shelf, iPSC-derived NK Cells

First Patients Treated with FT516, the First-ever Engineered iPSC-derived Cellular Immunotherapy, for AML and for B-cell Lymphoma in Combination with Rituximab

Initiated Enrollment of First-in-human Clinical Trial of FT596, the First-ever Cellular Immunotherapy Engineered with Three Active Anti-tumor Modalities

Ended Quarter with $261 Million in Cash, Cash Equivalents and Marketable Securities

SAN DIEGO, March 02, 2020 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, today reported business highlights and financial results for the fourth quarter ended December 31, 2019.

In 2019, we made tremendous progress in pioneering the clinical development of off-the-shelf, iPSC-derived cancer immunotherapy. Our FT500 program demonstrated that multiple doses of iPSC-derived NK cells can be delivered off-the-shelf to a patient in a safe manner without patient matching. Additionally, our FT516 program provided initial clinical evidence that engineered iPSC-derived NK cells may confer anti-tumor activity and deliver clinically meaningful benefit to patients. We also showed the unmatched scalability of our proprietary iPSC product platform, having manufactured hundreds of cryopreserved, infusion-ready doses of our iPSC-derived NK cell product candidates at a low cost per dose in our new GMP manufacturing facility, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. In 2020, we look forward to additional clinical data from our FT500 and FT516 programs, and initial clinical data from FT596, our ground-breaking iPSC-derived CAR NK cell product candidate for the treatment of B-cell malignancies designed to overcome many of the limitations inherent in current CAR T-cell immunotherapies. We also expect to begin clinical investigation of our off-the-shelf, iPSC-derived NK cell programs in multiple myeloma with planned IND submissions for FT538, the first-ever CRISPR-edited, iPSC-derived cell therapy, and for FT576, our multi-antigen targeted, CAR-BCMA product candidate. Finally, under our collaboration with Memorial Sloan Kettering, we strive to be the first group in the world to bring off-the-shelf, iPSC-derived CAR T-cell therapy to patients.

Clinical Programs

Preclinical Pipeline

Fourth Quarter 2019 Financial Results

Today's Conference Call and Webcast

The Company will conduct a conference call today, Monday, March 2, 2020 at 5:00 p.m. ET to review financial and operating results for the quarter ended December 31, 2019. In order to participate in the conference call, please dial 877-303-6229 (domestic) or 631-291-4833 (international) and refer to conference ID 9879730. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the Company's website at http://www.fatetherapeutics.com. The archived webcast will be available on the Company's website beginning approximately two hours after the event.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

Story continues

About FT500

FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (NCT03841110). The study is designed to assess the safety and tolerability of three once-weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies nivolumab, pembrolizumab or atezolizumab in patients that have failed prior ICI therapy. Despite the clinical benefit conferred by approved ICI therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or their disease progresses on these agents. One common mechanism of resistance to ICI therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations.

About FT516

FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, the FDA has allowed investigation of FT516 in an open-label, multi-dose Phase 1 clinical trial in combination with monoclonal antibody therapy, including PDL1-, PD1-, EGFR- and HER2-targeting therapeutic antibodies, across a broad range of solid tumors.

About FT596FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon dual receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in an open-label Phase 1 clinical trial as a monotherapy, and in combination with rituximab, for the treatment of advanced B-cell lymphoma and in combination with obinutuzumab for the treatment of chronic lymphocytic leukemia (NCT04245722).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Companys immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking Statements

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Companys results of operations, financial condition and sufficiency of its cash and cash equivalents to fund its operations, as well as statements regarding the advancement of and plans related to its product candidates, clinical studies and preclinical research and development programs, the Companys progress, plans and timelines for the manufacture and clinical investigation of its product candidates, the timing for the Companys receipt of data from its clinical trials and preclinical studies, the Companys development and regulatory strategy, and the therapeutic and market potential of the Companys product candidates. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in prior studies of the Companys product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Companys product candidates or in the initiation of, or enrollment of patients in, any clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties or delays in patient enrollment in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that the Companys expenditures may exceed current expectations for a variety of reasons. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Availability of Other Information about Fate Therapeutics, Inc.

Investors and others should note that the Company routinely communicates with investors and the public using its website (www.fatetherapeutics.com) and its investor relations website (ir.fatetherapeutics.com) including, without limitation, through the posting of investor presentations, SEC filings, press releases, public conference calls and webcasts on these websites. The information posted on these websites could be deemed to be material information. As a result, investors, the media, and others interested in Fate Therapeutics are encouraged to review this information on a regular basis. The contents of the Companys website, or any other website that may be accessed from the Companys website, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.

Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except share and per share data)(unaudited)

Condensed Consolidated Balance Sheets(in thousands)(unaudited)

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

See the article here:
Fate Therapeutics Reports Fourth Quarter 2019 Financial Results and Operational Progress with 2020 Outlook - Yahoo Finance

Introduction

CRISPR Therapeutics is a gene-editing company focused on the development of CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats)/CAS9(CRISPR-associated protein 9)-based therapeutics. The company is focused on translating revolutionary CRISPR/Cas9 technology into transformative therapies in therapeutics areas such as hemoglobinopathies, immuno-oncology, regenerative medicine and in vivo applications.

The Need for Gene Editing

Aberrant DNA sequences cause thousands of diseases that have not been treated by traditional small molecule and biologics as such treatments do not address the underlying genetics causes. Gene editing has the potential to provide curative therapies to many genetic diseases by precisely altering DNA sequences within the genomes of cells, which is done with the aid of enzymes cutting the DNA at specific locations. After a cut is made, natural cellular processes repair the DNA to either silence or correct undesirable sequences, potentially reversing their negative effects. As the genome itself is modified in this process, the change is permanent in the patient.

Gene editing also has other applications beyond treating genetically-defined diseases. It can also be applied to the engineering of genomes of cell therapies to make them more efficacious and safer. Cell therapies have been making a meaningful impact in certain therapeutics areas, such as oncology. An example of that is the approval of the CAR-Ts by Novartis (NVS) and Gilead (GILD).

The CRISPR/Cas9 Technology

As its name suggests, the company is utilizing CRISPR/Cas9 as its method of gene editing. Their technology is based on the work of their co-founder, Dr. Emmanuelle Charpentier, who is acknowledged as one of the key inventors of CRISPR-Cas9, and her collaborators.

Figure 1 Applications of CRISPR/Cas9 (Source)

The CRISPR/Cas9 technology is a versatile technology that can be used to disrupt, delete, correct or inset genes. It is used to make cuts in DNA at specific sites of targeted genes, and once the DNA is cut, the cell uses naturally occurring DNA repair mechanisms to rejoin the cut ends. If a single cut is made, a process called non-homologous end joining can result in the addition or deletion of base pairs, disrupting the original DNA sequence and causing gene inactivation. A larger fragment of DNA can also be deleted by using two guide RNAs that target separate sites. After cleavage at each site, non-homologous end joining unites the separate ends, deleting the intervening sequence. Alternatively, if a DNA template is added alongside the CRISPR/Cas9 machinery, the cell can correct a gene or even insert a new gene through a process called homology-directed repair.

Clinical Pipeline

CRISPRs lead product candidate is CTX001 which is being evaluated in -thalassemia and Sickle-Cell Disease (SCD). Both -thalassemia and SCD result from mutations in a gene that encodes a key component of hemoglobin, the molecule that carries oxygen in the blood. Both diseases require lifetime treatment that can result in the need for regular transfusion, painful symptoms and ultimately reduced life expectancy.

The companys approach to treat both diseases is to increase the levels of fetal hemoglobin (HbF), which is a naturally-occurring form of hemoglobin present in all people before birth. The company believes that HbF can substitute for the diseased hemoglobin in -thalassemia and SCD patients, therefore reducing or eliminating symptoms.

CTX001 first isolates a patients own blood stem cells, which is then edited with CRISPR/Cas9 to increase HbF expression, and then returned to the patient. The company believes that over time these edited blood stem cells will generate red blood cells that have increased levels of HbF, which may reduce or eliminate patients symptoms. CTX001 is co-developed and co-commercialized in an agreement with Vertex Pharmaceuticals (VRTX).

In November 2019, both companies announced interim data from the first 2 patients treated in CTX001. 1 patient with transfusion-dependent -thalassemia (TBT) received the treatment in the first quarter of 2019 and the other patient was treated for SCD in mid-2019. The safety and efficacy follow-up of both patients was 9 months and 4 months approximately.

The patient with TDT required 16.5 transfusions per year before enrolling in the clinical study. At nine months after the CTX001 infusion, the patient was transfusion independent. There were 2 serious adverse events (SAEs), although they were assessed to be not related to the administration of CTX001.The patient with SCD experienced seven vaso-occlusive crises (VOCs) per year before enrolling in the clinical study. Three SAEs occurred, none of which were considered related to CTX001. At four months after CTX001 infusion, the patient was free of VOCs. Both the TDT and SCD studies are ongoing and all patients will be followed for approximately two years following the infusion of CTX001. The Company has also mentioned that several additional patients have been enrolled in both trials.

The company is also working on allogeneic CAR-Ts with its gene-editing technology. Current generations of CAR-Ts such as Kymirah from Novartis (NVS) and Yescarta from Gilead (GILD) are autologous and derived from the patients own immune cells. Such treatments have several limitations and healthy-donor based allogeneic CAR-Ts have the potential to improve on the current generation of CAR-Ts.

CRISPR believes that CRISPR-edited allogeneic CAR-Ts has the potential to improve cell persistence as well as overall safety and potency. Its first 2 programs target well-validated targets with the potential to be best-in-class. CTX100 is an anti-CD19 CAR T targeting B-cell malignancies while CTX120 is an anti-B-Cell Maturation Antigen (BCMA) targeting multiple myeloma. Both trials are currently enrolling patients, although no interim data has been released.

A third allogeneic CAR-T, CTX130 is planned to eventually be advanced to clinical trials. CTX130 targets CD70 and will be used to treat both solid tumors, such as renal cell carcinoma, as well as T-cell and B-cell hematologic malignancies. Beyond immunology-oncology, the company also plans to utilize CRISPR/Cas9 in both Regenerative Medicines and In Vivo applications, although such efforts are still limited to preclinical development. Figure 2 illustrates the full clinical pipeline of the company.

Figure 2 CRISPR Therapeutics Clinical Pipeline (Source)

Financials and Competition

As of 31 Dec 2019, cash and equivalents were $943.8M, compared to $435.6 a year prior. The increase in cash was driven by several public offerings, as well as cash received from Vertex for milestone and option payments. The healthy cash pile should take them well into 2021 at the very least.

As the company is working in the gene therapy and cell therapy space, there are several notable competitors. They are often compared to Bluebird Bio (BLUE) who has received the approval of Zynteglo to treat TDT in Europe and in the process of filing a BLA with the FDA for US approval. Bluebird is also evaluating Lentiglobin in SCD. As both of Bluebirds product candidates are more advanced in terms of clinical development, they currently hold a competitive advantage unless CRISPR can prove that their treatments are best-in-class. Notably, Bluebird has faced several challenges with its pricing of Zynteglo as well as regulatory delays due to complex manufacturing and it remains to be seen whether CRISPR can overcome such challenges. Bluebird is also partnering with Bristol-Meyers Squibb (BMY) to develop bb2121 and bb21217 which are both autologous anti-BCMA CAR-T against multiple myeloma.

In the Allogeneic CAR-T space, there also several prominent names that include but are not limited to Allogene Therapeutics (ALLO), Cellectis (CLLS) and Precision Biosciences (DTIL). The main difference among these companies is primarily the choice of gene-editing tools with Allogene and Cellectis using TALEN while Precision is using ARCUS. All these companies are currently in a similar stage of clinical development, with multiple programs in Phase 1 and it remains to be seen who will emerge as a clear frontrunner, even though interestingly, Allogene is trading at a premium market cap compared to the other 2 companies.

In addition to healthy donors derived allogeneic therapies, Fate Therapeutics (FATE) is developing allogeneic therapies from induced pluripotent stem cells (iPSCs) as a renewable cell source. The advantage of this is that product consistency and potency will be improved, and the manufacturing process will be akin to the well-established biologics where they are produced from a single cell line. It is notable to note that Allogene is also investigating using iPSCs as a renewable cell source.

Also, Atara Biotherapeutics (ATRA) is developing an Epstein-Barr Virus (EBV)-based allogeneic T cell therapy platform. Their lead program is in Phase 3 and a BLA filing is expected by the second half of the year. That should put them in the lead position of commercializing an allogeneic T cell therapy and the company is gradually moving into CAR T space as well.

Lastly, there are also other companies such as Editas Medicine (EDIT) and Intellia Therapeutics (NTLA) which are focused on using CRISPR/Cas9 as a gene-editing tool. While both companies are also working on treatments for TDT and SCD, these are not their lead programs and CRISPR is further along than both companies in both therapeutics areas.

Conclusion

CRISPR Therapeutics is a gene-editing company utilizing CRISPR/cas9 to develop therapies in hemoglobinopathies, immuno-oncology, regenerative medicine and in vivo applications. While I consider the company to be a pioneer in CRISPR/Cas9, its market cap of around $3B seems generous for a company that has so far reported only interim data from 2 patients.

Also, there is a long ongoing-argument over the patents of CRISPR/Cas9 between the University of California, which CRISPR license their technology from, and the Broad Institute and Harvard College, of which Editass technology is based on.

With the uncertainty over the patent claims as well as the limited clinical data available, I am inclined to avoid investing in the company for now, although I would be keeping a keen eye on further clinical data, especially on allogeneic CAR-Ts.

As always, investors should do their due diligence before taking up any positions and consider their risk profiles and time horizon. I have covered several companies working on cell therapies and will continue to do so in the coming weeks and months.

Disclosure: I am/we are long ATRA, BLUE. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Continued here:
CRISPR Therapeutics: A Review Of Its Clinical Pipeline And Progress - Seeking Alpha

Dr. Steven Cyr has been treating patients using growth factors and stem cells contained in amniotic tissue and bone marrow aspirate to provide a potential for improved success with fusion procedures, when treating herniated discs, and for arthritic or damaged joints, with remarkable success. "The goal of any medical intervention is to yield improved outcomes with the ideal result of returning a patient to normal function, when possible," states Dr Cyr. He went on to elaborate that there are times when only a structural solution can solve problems related to spinal disorders, but even in that scenario, the use of stem cells or growth factors derived from stem cell products can possibly improve the success of surgical procedures. "I have patients previously unable to jog or run return to normal function and athletic ability after injections of growth factors and stem cell products into the knee joints, hip joints, and shoulder joints," he said. "This includes high-level athletes, professional dancers, and the average weekend warrior."

There may be promise in treating patients with spinal cord injury as well. SASpine CEO, LeAnn Cyr, states, "There are reports of patients gaining significant neurological improvement after being treated with stem cells." Dr Cyr continues, "Most patients with spinal cord injuries resulting from trauma also have mechanical pressure on the nerves that result either from bone fragments or disc material compressing the spinal cord that needs to be removed along with surgical stabilization of the spinal bones. There's significant potential that stem cells bring to the equation when treating these types of patients, and I am excited about the potential that these products offer to the host of treatments to address spinal conditions and arthritic joints."

For more information about SASpine's Stem Cell Treatment Program, visit http://www.saspine.com or call (210) 487-7463 in San Antonio or (832) 919-7990 in Houston.

Related Linkswww.facebook.com/saspinewww.instagram.com/surgical.associates.in.spine

SOURCE SASpine

https://www.saspine.com

Here is the original post:
SASpine to offer Stem Cell Therapy - PRNewswire

Arthritis is an umbrella term for a number of conditions that cause swelling and tenderness of one or more of the joints. Osteoarthritis and rheumatoid arthritis are the two most common types of arthritis. There's no cure for arthritis, but there are many treatments that can help slow it down and maintain quality of life, including this unusual one.

Osteoarthritis mainly affects the hands, spine, knees and hips, whereas rheumatoid arthritis usually affects the hands, feet and wrists.

Experts are researching ways to use stem cells therapy to help treat arthritis in the knee and other joints.

Many doctors already use stem cell therapy to treat arthritis, but it is not considered standard practice, with some even calling the treatment controversial.

READ MORE: Joe Swash health: I had to learn everything again Actors scary virus

There is a lot of debate around stem cell treatment and it is helpful for potential patients to understand what stem cells are and the issues surrounding their use in arthritis therapy.

How the treatment could help is by reducing inflammation in the body.

In arthritis, the immune system mistakenly attacks the tissue that lines the joints, which causes pain, inflammation, swelling and stiffness.

By reducing inflammation, stem cell therapy increases the presence of healthy cells in the body.

DONT MISS

And it would seem that stem cell therapy has sparked some interest from the royal family.

Princess Michael of Kent, the wife of the Queens cousin Prince Michael, recently appeared in a slick promotional video for a clinic in the Bahamas that offers similar joint therapy.

Look at that, the Princess declares proudly in the five-minute film, holding her right arm high above her head after stem-cell injections for a painful shoulder.

"Its amazing I think stem cells are the future, theres no doubt in my mind."

A stem cell is a type of cell not specialised to perform a specific role.

Instead, it has the unique ability to develop into one of many different types of cell. Stem cell therapy uses stem cells to replace dead and diseased cells within the body.

The human body contains over 200 different types of cell. Usually, each type has certain characteristics that allow it to preform a specific role.

Cells with similar roles group together to form tissues, which then organise to form the bodys organs.

Scientists source the stem cells from body tissue, either from an embryo or an adult human and isolate them in the laboratory.

After manipulating the cells to develop into specific types, they then inject the cells into the recipients blood or tissue.

Researchers are still investigating ways of using stem cells to control inflammation and regenerate damaged tissues.

Mesenchymal stem cells (MSCs) are types of stem cell that can develop into cartilage and bone. Synovial MSC therapy involves injecting these cells directly int the tissues surrounding the affected joints.

Some research shows that MSCs are also able to suppress the immune system and reduce the bodys inflammatory response.

This makes MSC therapy a promising treatment option for autoimmune conditions such as arthritis.

But for all the positive evidence supporting the treatment, it remains hugely controversial.

Most specialists say there is little robust evidence to show it works and it has not been approved by the UK medicines regulator, the National Institute for Health and Care Excellence. Leading health experts most standard approaches to treating arthritis is advising patients to lose weight and get more exercise.

In the US, Google has banned all advertising for products that contain stem cells or another regenerative therapy which uses blood cells, known as platelet-rich plasma, or PRP, because regulators describe the treatments as "new and exploratory".

And in the UK, experts have rubbished claims that Lipogems can treat arthritis.

Professor Chinmay Gupte, consultant orthopaedic surgeon and senior lecturer in knee surgery at Imperial College London, warns: These are extremely expensive treatments, and largely unproven. The problem is when youre desperate, youll try anything.

Read the original:
Arthritis treatment: A controversial treatment promoted by a certain royal could help - Express

Natural Killer cells have been engineered to attack blood cancers with excellent provisional results ... [+] from a small clinical trial.

A new cell-based immunotherapy for some types of blood cancer has posted promising initial results in a small clinical trial on patients who had exhausted all other treatment options.

The new study, led by researchers from MD Anderson Cancer Center was published yesterday in the New England Journal of Medicine and used a type of immune cell, called a Natural Killer (NK) cell. The NK cells were engineered to target a protein called CD19 found on B-lymphoblasts and which can become cancerous and cause several types of blood cancer. The study tested the treatment on 11 patients with either chronic lymphocytic leukemia (CLL) or non-Hodgkins lymphoma (NHL), finding a 73% response rate. Of the 8 people who responded, 7 maintained a complete response over a year after the initial treatment.

All our patients had failed conventional therapies and therefore there was no alternative treatment available for them, said said Katy Rezvani, M.D., Ph.D.,lead author of the paper and professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need, she added.

Most cell based therapies use a different type of modified immune cell; CAR T-cells. These therapies have shown initial promise in some types of blood cancer, but there have been several setbacks with side-effects in patients and the scaleability and cost of the technology. Importantly, the NK cells used on the patients in the new study were made from donated umbilical cord blood, whereas most CAR T-cell therapies currently rely on a long and expensive process of extracting T-cells from the patient themselves, genetically modifying them and expanding the cells before the therapy is ready for use.

This means the new NK cell therapy can theoretically be produced in bulk and doesn't rely on extracting T-cells from the patient, which can be incredibly difficult, especially if the patient has received a lot of previous therapies which can affect T-cell numbers.

Strictly speaking, the manufacturing and engineering steps for CAR T and CAR NK cells are very similar. The main difference is that unlike commercial CAR T-cells, where one product is used to treat one patient (an autologous product),CAR NK cells are not patient specific, allowing for multiple doses to be manufactured from one donor that can then be used to treat multiple patients, said Rezvani.

CAR T-cell therapies, although posting some wonderful results, particularly in children with hard-to-treat, relapsed leukemias, do come with a lot of side effects, particularly neurotoxicity and cytokine release syndrome, which is life-threatening if not quickly treated. These toxicities were not seen in this initial, small trial, giving the researchers hope that perhaps this therapy may have fewer serious side-effects than other similar approaches.

As well as CAR T-cells, there is also another therapy already available which targets CD19, a drug called blinatumomab (Blincyto). What potential advantages does the new NK cell therapy have over this approach?

These are living cells that persist after infusion and will potentially continue to protect the patient from their cancer over time unlike blinatumomab that needs to be given as a continuous infusion and in multiple cycles, said Revzani. In addition, with the caveat of the small number of patients that we have treated so far and the relatively short follow up time, our approach appears to be less toxic, she added.

MD Anderson have licenced the development of this therapy and other similar B-cell targeting therapies to company Takeda Pharmaceuticals.

Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient settingenabling more patients to be treated effectively, quickly and with minimal toxicities, said Rezvani, adding that the team also plans to expand the trial to encompass other CD19-expressing malignancies such as B-cell leukemias.

Continued here:
New Immunotherapy Had Positive Results In Cancer Patients After Other Treatments Failed - Forbes

Early results from a phase I/II trial, published inThe New England Journal of Medicine, found that a majority of patients with either relapsed or refractory non-Hodgkins lymphoma (NHL) or chronic lymphocytic leukemia (CLL) treated with CAR NK cells had a response without the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease.1

Additionally, there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline; however, the maximum tolerated dose was not reached.

We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need, corresponding author Katy Rezvani, MD, PhD, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center, said in a press release.2

In this study cohort of 11 patients with relapsed or refractory CD-19 positive cancers, participants were given a single dose of cord blood-derived CD19 CAR NK cells at 1 of 3 dose levels. Five of the patients had CLL and the remaining 6 had NHL. All of the patients were treated with a minimum of 3 and a maximum of 11 lines of prior therapy. The first 9 participants treated were given CD19 CAR NK cells that were partially matched according to the individuals HLA type, but protocol allowed the last 2 patients to be treated with no HLA matching.

Eight (73%) of the participants had a response, and of those, 7 (4 with NHL and 3 with CLL) had a complete remission, while 1 had remission of the Richters transformation component, but had persistent CLL. The responses were rapid and observed within 30 days after infusion at all dose levels. The infused CAR NK cells expanded and persisted at low levels for at least 12 months.

According to the researchers, a proportion of patients treated with anti-CD19 CAR T cells have a subsequent relapse, with a 1-year progression-free survival of approximately 30% observed among patients with CLL and 45% seen among those with NHL.

In view of these outcomes, our study allowed for remission consolidation therapy with an immunomodulatory agent, anticancer drug, or hematopoietic stem-cell transplantation at the discretion of the treating physician, the authors wrote. However, the use of post-remission therapy in this study limits our assessment of the durability of response after CAR NK therapy.

Notably, researchers did observe high-grade transient myelotoxicity in the cohort, of which they attributed to the lymphodepleting chemotherapy. However, they were unable to assess whether the CAR NK cells contributed to the myelotoxicity.

Side effects experienced by the patients were primarily related to the conditioning chemotherapy given before cell infusion and were resolved within 1 to 2 weeks, according to Rezvani. Additionally, no patient required admission to an intensive care unit for management of treatment side effects.

Due to the nature of the therapy, weve actually been able to administer it in an outpatient setting, Rezvani said. We look forward to building upon these results in larger multi-center trials as we work with Takeda to make this therapy available more broadly.

References:

1. Liu E, Marin D, Banerjee P, et al. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors.The New England Journal of Medicine. doi:10.1056/NEJMoa1910607.

2. CD19 CAR NK-cell therapy achieves 73% response rate in patients with leukemia and lymphoma [news release]. Houston, Texas. Published February 5, 2020. app.bronto.com/public/viewmessage/html/6781/hemm7h92mwb6849npf2js0r4mhnrl/0bd003eb00000000000000000000000df096. Accessed February 6, 2020.

See original here:
Early Findings Show Promise of CAR NK-Cell Therapy in Leukemia, Lymphoma - Cancer Network

A retired Texan had endured 12 years of chemotherapy for blood cancer only to see the disease come back stronger and meaner each time.

It was long, hard and terrible, J.C. Cox, 66, said.

So when he was told that he could take part in a clinical trial of a newly modified form of immune therapy, he signed on.

In that small preliminary trial, the results of which were published Wednesday in the New England Journal of Medicine, nearly two-thirds of the patients, all of whom had cancer so advanced that just a decade ago there would have been no hope for them, went into complete remission. Cox was among that two-thirds.

The new treatment involves tweaking a type of therapy called CAR-T that helps the immune system home in on cancer cells. Those tweaks appear to have made it more effective than its predecessor while also leading to fewer side effects, the study found.

In CAR-T therapy, doctors equip a patients own T-cells with a sensor that essentially sniffs out a protein on cancer cells, allowing them to glom onto the protein and then destroy the diseased cells. CAR-T therapy has been approved by the U.S. Food and Drug Administration to treat several types of blood cancer.

The altered T cells end up working like a heat-seeking missile, said study co-author Dr. Katayoun Rezvani, a professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center.

There were several drawbacks to CAR-T, including the time it took to make the revved up T cells which needed to be harvested from patients and then sent to a lab, their cost, and most important, the possibility of life-threatening side effects.

To try to make a cheaper, safer therapy that would potentially work for all patients, Rezvani and her colleagues switched from T-cells to a different type of immune cell, called natural killer cells.

Let our news meet your inbox. The news and stories that matters, delivered weekday mornings.

Natural killer cells are the best killers of virally infected and abnormal cells, she said. They can continue to patrol and recognize abnormal cells.

There were several advantages to the natural killer cells, not the least of which was that, unlike T cells, they wouldnt make the patients sick by spewing out a flood of inflammatory proteins, leading to a severe condition called a cytokine storm. Another big advantage was that the natural killer cells from one patient could be given to another without any tissue matching. That meant that such cells from healthy donors or from donated umbilical cord blood could be banked and ready to use at any time.

Presumably, this would cut down on the wait time and the costs of the therapy, because the treatments werent being tailor-made for each individual patient.

Rezvani and her colleagues genetically modified the natural killer cells to have a receptor (the R in CAR) for a protein that is on the surface of the cancer cells they were targeting. The receptor would lock onto the protein and then the cell would do its work.

The researchers also tweaked the natural killer cells in two other ways. Unlike T cells which live for a long time, natural killer cells normally have a lifespan of just a couple of weeks, so the researchers added a growth factor that would keep them around for a lot longer. And as a precaution, they also inserted a switch that would allow the researchers to kill off the altered cells if they became too abundant.

Rezvani and her colleagues tested the new treatment in 11 blood cancer patients. When the patients were checked two months after treatment, seven had no signs of cancer while one other showed improvement but not complete remission. The other three had no response to the treatment.

Cox was the eighth patient to receive the new treatment, and initially had misgivings.

I didnt have any other options, Cox, who received the treatment for non-Hodgkin lymphoma, said. But it was scary knowing I would be No. 8 and would be getting the biggest dose.

The trial had been set up to start with a low dose, and then wait to see if there were any serious side effects. If not, the plan was to increase the dose in later patients.

Coxs years of chemotherapy made him worry about possible side effects. But it was probably the easiest thing Ive ever done, he said.

The researchers themselves werent sure what to expect. We were amazed at the safety, Rezvani said. And it didnt seem to matter what dose we gave. This truly is a living drug. It gets inside of the patients body and starts growing and attacking the cancer cells.

Larger studies are needed, but if the treatment which has been licensed to Takeda Pharmaceutical Co. lives up to its early promise, Rezvani hopes to try it on other cancers, such as ones that affect the brain and the breasts.

The response of the patients in the new study is impressive, said Dr. David Porter, the director of cell therapy and transplantation at the University of Pennsylvania Health System. I think this is a major advance in the field of targeted cellular therapy.

Moreover, the natural killer treatments dont seem to have the same life-threatening complications as the original CAR-T therapy, Porter said in an email. Porter was involved with previous CAR-T research, but was not involved with this trial.

But, Porter cautioned, the study included a very small number of patients.

Cox wasnt sure what to expect when he went to be checked two months after receiving his treatment. The news was better than he could have imagined: there was no sign of his cancer.

I did a lot of crying, but they were happy tears, he said. I still get emotional when I talk about it.

Follow NBC HEALTH on Twitter & Facebook.

Continue reading here:
Immune therapy tweak offers new hope to blood cancer patients - NBC News

Stem cell bank Cyro-Save moved the umbilical cords it stores on behalf of parents to Poland, but part of that material has gone missing, according to newspaper AD. That left thousands of parents worried about the storage of their children's stem cells.Many parents have no idea where they stand. They are receiving unclear emails from different parties, and are unable to reach the company itself, the newspaper writes.

Cyro-Save has around 230 thousand customers worldwide, including several thousand in the Netherlands. Customers sent the companyblood and pieces of umbilical cord immediately after the birth of their child, to freeze and store in the event of the child becoming sick in future, so that it could be used for stem cell therapy.

According to AD, Cyro-Save's activities are scientifically controversial and even prohibited in some European countries. Under pressure from governments and financial problems, Cyro-Save moved 330 thousand samples of genetic material to the Polish company Famicord last year. This happened without the permission of the parents or the authorities. And a number of tanks are missing, the newspaper writes.

Authorities in multiple countries, including Belgium and Switzerland, are currently investigating the relocation of the material to Poland.

Famicord contacted parents, asking the to sign a contract with the company. But Dubai-based companyCSG Bio, which took over Cyro-Save, also claims that it has taken over Cyro-Save's stem cell activities and are advising parents not to go with the Polish company. Meanwhile, parents have no idea where their children's stem cells actually are.

Read this article:
Missing stem cells: Thousands of NL parents potentially affected - NL Times

Testing a new therapeutic in human subjects for the first time is a major step in the translation of any novel treatment from the laboratory bench to clinical use.

When the therapeutic represents a paradigm shift, reaching this milestone is even more significant.

After years of planning, preparation and hard work to establish a base camp, starting human clinical trials is the first step towards the summit itself: gaining regulatory approval for product sales.

Exosomes tiny packets of proteins and nucleic acids (e.g. mRNA and miRNA) released by cells, that have powerful regenerative properties ranging from promoting wound healing to stimulating brain injury recovery following stroke represent just such a paradigm-shifting potential advance in human medicine.

The first commercial exosome therapeutics conference was held in Boston in September 2019 and over 15 companies participated.

This conference signals the emergence of exosomes as a new class of regenerative medicine products.

So far, just one or two of the companies working in the novel field of exosome-based therapies have reached the pivotal point and transitioned into human clinical trials. In this article we survey the field, starting with the pace-setters.

During the past few years, a handful of universities and research hospitals have carried out small scale, first-in-human Phase I clinical trials using exosomes. In each case where the study results are available, the exosome treatment was found to be safe and well-tolerated.

But the field has hotted up in the past few months, with the first companies reaching the pivotal point of testing exosome-based products in people.

On 28th January 2020, Melbourne-based Exopharm announced the first dosing under its first human clinical trial, becoming the first company to test exosomes potential for healing wounds in people.

The PLEXOVAL Phase I study will test Exopharms Plexaris product, a cell-free formulation of exosomes from platelets, which in preclinical animal studies have shown a regenerative effect, improving wound closure and reducing scarring.

The main readouts of the PLEXOVAL study the results of which are expected to be available sometime after mid-2020 will be safety, wound closure and scarring.

Joining Exopharm at the front of the pack is Maryland-based United Therapeutics.

Founded in 1996, United Therapeutics specialises in lung diseases and has a portfolio of FDA-approved conventional small molecule and biologic drugs on the market for a range of lung conditions.

On 26th June 2019, United Therapeutics announced approval for a Phase I trial (NCT03857841) of an exosome-based therapy against bronchopulmonary dysplasia (BDP), a condition common in preterm infants that receive assisted ventilation and supplemental oxygen.

Recruitment has commenced but dosing has not been announced. The study is due to conclude by December 2021. BDP is characterised by arrested lung growth and development, with health implications that can persist into adulthood.

Human clinical trials of a stem cell therapy for BDP, by Korean stem cell company Medipost, are already underway. However as with many stem cell therapies recent animal studies have shown that is the exosomes released by stem cells that are responsible for the therapeutic effect.

United Therapeutics therapy, UNEX-42, is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells. The company has not released any information about how its exosomes are produced or isolated.

A little behind the two leaders, three other companies have announced their aim to initiate their first clinical trials of exosome therapeutics within the next 12 months.

Launched in 2015, Cambridge, Massachusetts-based Codiak has long been considered among the leaders in developing exosome-based therapies.

Rather than exploiting the innate regenerative potential of select exosome populations, Codiak is developing engineered exosomes that feature a defined therapeutic payload. The companys initial focus has been to target immune cells, leveraging the immune system to combat cancer.

The company plans to initiate clinical trials of its lead candidate, exoSTING, in the first half of 2020. The therapeutic is designed to trigger a potent antitumor response from the patients own immune system, mediated by T cells. A second immuno-oncology candidate, exoIL-12, is due to enter clinical trials in the second half of 2020, the company says.

In nearby New Jersey, Avalon Globocare is also developing engineered exosomes. Its lead product, AVA-201, consists of exosomes enriched in the RNA miR-185, which are produced using engineered mesenchymal stem cells.

In animal tests, miR-185 suppressed cancer cell proliferation, invasion and migration in oral cancer. In July 2019, the company announced plans to start its first exosome clinical trial before the close of 2019. As of February 2020, however, no further announcement regarding this clinical trial has been made.

Avalon has also made no further announcement on a second planned clinical trial, also intended to start during the fourth quarter of 2019, of a second exosome candidate, AVA-202.

These angiogenic regenerative exosomes, derived from endothelial cells, can promote wound healing and blood vessel formation, the company says. The planned Phase I trial was to test AVA-202 for vascular diseases and wound healing.

Meanwhile, Miami-based Aegle Therapeutics plans to begin a Phase I/IIa clinical trial of its exosome therapy, AGLE-102, during 2020. AGLE-102 is based on native regenerative exosomes isolated from bone marrow mesenchymal stem cells.

After initially focussing on burns patients, in January 2020 to company announced had raised the funds to commence an FDA-cleared clinical trial of AGLE-102 to treat dystrophic epidermolysis bullosa, a rare paediatric skin blistering disorder. The company says it plans to commence this clinical trial in the first half of 2020.

A number of companies are in the preclinical phase of exosome therapy research.

Some of these companies have been set up specifically to develop exosome-based products. In the UK, Evox co-founded by University of Oxford researcher Matthew Wood in 2016 is developing engineered exosomes to treat rare diseases.

The company has developed or sourced technology that allows it to attach proteins to exosomes surface, or to load proteins or nucleic acids inside the exosome, to deliver a therapeutic cargo to a target organ.

Its lead candidate targets a lysosomal storage disorder called Niemann-Pick Disease type C, using exosomes that carry a protein therapeutic cargo. Evox says it plans to submit the Investigational New Drug (IND) application to the FDA during 2020, paving the way for the first clinical trial. It currently has five other candidates, for various indications, at the preclinical stage of development.

In Korea, Ilias and ExoCoBio are developing exosome therapeutics. Ilias founded by faculty from the Korean Advance Institute of Science and Technology specialises in loading large protein therapeutics into exosomes.

It is currently carrying out preclinical research toward treating sepsis, preterm labour and Gauchers disease. ExoCoBio is focusing on the native regenerative capacity of exosomes derived from mesenchymal stem cells, including to treat atopic dermatitis.

New companies continue to enter the exosome space. In August 2019, Carmine Therapeutics was launched, with the aim to develop gene therapies that utilize exosomes from red blood cells to deliver large nucleic acid cargoes. The company is targeting the areas of haematology, oncology and immunology.

Meanwhile, a wave of companies originally set up to develop live stem cell therapies are diversifying into stem cell derived exosome production and research.

It is now generally acknowledged that stem cell exosomes are the main therapeutically active component of stem cells, and that medical products based on exosomes will be safer to apply, and easier and cheaper to make and transport, than live cell therapies.

Originally established to produce neural stem cells for other research organisations, Aruna Bio has developed proprietary neural exosomes that can cross the blood brain barrier.

The company is now developing an exosome therapy for stroke. In October 2019, the Athens, Georgia-based company said had raised funding to support the research and development to enable its first IND application to the FDA in 2021.

In the UK, ReNeuron has also focussed on stroke, and has several clinical trials underway assessing its CTX stem cells to promote post stroke rehabilitation. The company is also working with third parties to investigate the drug- and gene therapy delivery potential of exosomes derived from CTX stem cells.

Switzerland-based Anjarium is also developing an exosome platform to selectively deliver therapeutics.20 The company is focussing on engineering exosomes loaded with therapeutic RNA cargo and displaying targeting moieties on its surface.

California-based Capricor has commenced clinical trials of a cardiosphere-derived stem cell therapy for the treatment of Duchenne muscular dystrophy (DMD).

At an earlier phase, its regenerative exosome therapy CAP-2003 is in pre-clinical development for a variety of inflammatory disorders including DMD.

A number of other stem cell companies, including TriArm, Creative Medical, AgeX Therapeutics and BrainStorm Cell Therapeutics, are reported to be investigating exosome-based therapies derived from their stem cell lines.

Exopharms position as a frontrunner in bringing exosomes into humans is no lucky accident. The companys operations are based around its unique, proprietary method for manufacturing and isolating exosomes, known as LEAP technology.

As academics and observers of the exosome field have pointed out, reliable and scalable exosome manufacture has threatened to be a major bottleneck that limits the translation of exosome therapeutics into clinical use. The standard laboratory-scale method for collecting the exosomes produced by cultured cells has been to spin the liquid cell culture medium in an ultracentrifuge, or pass it through a fine filter.

The most common technique used so far, the ultracentrifuge, has major scalability limitations. Issues include the high level of skill and manual labour required, the time-intensive nature of the process, and the associated costs of reagents and equipment. It is impossible to imagine collecting enough exosomes for a late stage clinical trial this way.

Another issue is the low purity of the exosomes collected. These techniques sort the contents of cell culture medium by their mass and/or size. Although the exosomes are concentrated, they could be accompanied by other biological components present in the cell culture medium that happen to be a similar size or mass to the exosome.

Importantly, a biotechnology company needs a proprietary step in the process to make a proprietary product over which it has exclusivity. Exopharms LEAP technology is a good example of a proprietary manufacturing step. Ultracentrifuge is not a proprietary process.

So the big players in the emerging exosome field have generally placed a strong emphasis on developing their manufacturing and purification capability.

Exopharm developed a chromatography-based purification method, in which a patent-applied-for inexpensive functionalised polymer a LEAP Ligand is loaded into a chromatography column. The LEAP Ligand sticks to the membrane surface of exosomes passed through the column. Everything else in the cell culture medium mixture is simply washed away. The pure exosome product is then eluted from the column and collected for use. As well as being very scalable, the technique is versatile. LEAP can be used to produce a range of exosome products, by isolating exosomes from different cell sources.

Codiak, similarly, says it has developed scalable, proprietary chromatography-based methods to produced exosomes with comparable identity, purity, and functional properties as exosomes purified using methods such as ultracentrifugation. Chromatography is a flow-based technique for separating mixtures. In an April 2019 SEC filing, the company said it is establishing its own Phase 1/2 clinical manufacturing facility, which it is aiming to have fully-operational by first half 2020.

Avalon GloboCare teamed up with Weill Cornell Medicine to develop a standardised production method for isolating clinical-grade exosomes. Aegle also says it has a proprietary isolation process for producing therapeutic-grade exosomes. And Evox emphasises the GMP compliant, scalable, commercially viable manufacturing platform it has developed.

At Exopharm, the manufacturing technique that has allowed the company to leap ahead of the pack and into human clinical trials is its proprietary LEAP platform. Overcoming the exosome production and isolation bottleneck was exactly the problem the companys scientists set out to solve when Exopharm formed in 2013.

In addition to the Plexaris exosomes, isolated from platelets, currently being tested in human clinical trials, Exopharm is progressing toward human clinical trials of its second product, Cevaris, which are exosomes isolated from stem cells.

Exosomes are now under development by around 20 companies across the world. The leaders in the field are now entering clinical trials with both nave exosome products and engineered exosome products. A number of cell therapy companies are also moving across into the promising exosome product space.

The coming years promise dynamic changes, with partnerships and eventually product commercialization. Exopharm is a clear leader in this emerging field.

(Featured image by Darko Stojanovic from Pixabay)

DISCLAIMER: This article was written by a third party contributor and does not reflect the opinion of Born2Invest, its management, staff or its associates. Please review our disclaimer for more information.

This article may include forward-looking statements. These forward-looking statements generally are identified by the words believe, project, estimate, become, plan, will, and similar expressions. These forward-looking statements involve known and unknown risks as well as uncertainties, including those discussed in the following cautionary statements and elsewhere in this article and on this site. Although the Company may believe that its expectations are based on reasonable assumptions, the actual results that the Company may achieve may differ materially from any forward-looking statements, which reflect the opinions of the management of the Company only as of the date hereof. Additionally, please make sure to read these important disclosures.

Read more:
Biotech companies leading the way with exosome human clinical trials - Born2Invest