Stem Cell Clinic

Landmark Results for CaverStem Procedure Published in Journal of Translational Medicine to Create Paradigm Shift in Treatment of Erectile Dysfunction…

PHOENIX, Jan. 15, 2020 /PRNewswire/ -- Creative Medical Technology Holdings, Inc. (OTC: CELZ), a leading commercial stage biotechnology company focused on Urology, Neurology and Orthopedics using stem cell treatments, today announced publication of clinical trial data on CaverStem procedure for drug resistant erectile dysfunction (ED) patients in the Journal of Translational Medicine.

The peer reviewed publication describes a total of 140 patients treated with the CaverStem procedure (40 patients in primary trial and 100 in the clinical registry) that suffered from erectile dysfunction for whom standard drug interventions such as Cialis, Levitra, and Viagra (PDE-5) were ineffective.

The CaverStem trial, one of the largest clinical studies of a non-drug treatment for erectile dysfunction, supports the safety and efficacy of autologous, non-expanded bone marrow concentrate for treatment of ED patients.

We would like to thank all the patients and the Clinical teams which have made the CaverStem program possible. The independently monitored data demonstrated the safety of the program along with the real world clinical registry which demonstrated early efficacy signals, said Amit Patel, MD, MS, Board Member of the Company.

Its exciting to see the evolution of our patented cell based intervention first described in 2013 in the Journal of Translational Medicine (now being offered in the clinic through qualified physicians) having such a positive impact on the lives of treated patients, said Thomas Ichim PhD, co-inventor of CaverStem and Chief Scientific Officer at Creative Medical Technology Holdings, Inc.

The positive results reflected in the publication validates the many years of devotion and investment in the CaverStem Program, said Timothy Warbington, President and CEO of Creative Medical Technology Holdings, Inc. 2020 is setting up to be a breakthrough year for the company as we plan to partner this landmark publication with heavy investment in physician recruitment and consumer awareness to accelerate commercialization of CaverStem.

Link to the complete peer reviewed publication: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-02195-w

About Erectile Dysfunction Erectile dysfunction (ED) is characterized by the lack of ability to achieve and maintain penile erection for intercourse. Methods used to quantify ED include the Erectile Function Visual Analog Scale (EF-VAS) and the International Index of Erectile Function (IIEF-5), however clinically it is primarily diagnosed based on symptomology. In our aging society, ED is becoming an increasing problem. According to one study 39% of men at age 40 experience symptoms of ED, whereas by age 70 the incidence rises to 67%. In this latter age group, it is believed that 50-85% of ED cases are associated with hypertension, diabetes, cardiovascular disease and dyslipidemia. Overall, it is estimated that over 30 million American men suffer from this condition.

About Creative Medical Technology Holdings, Inc. Creative Medical Technology Holdings, Inc. is a commercial stage biotechnology company currently trading on the OTC under the ticker symbol CELZ. For further information about the company go to http://www.creativemedicaltechnology.com. For more information on our CaverStem procedure please go to http://www.caverstem.com.

Forward-Looking Statements OTC Markets has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This news release may contain forward-looking statements including but not limited to comments regarding the timing and content of upcoming clinical trials and laboratory results, marketing efforts, funding, etc. Forward-looking statements address future events and conditions and, therefore, involve inherent risks and uncertainties. Actual results may differ materially from those currently anticipated in such statements. See the periodic and other reports filed by Creative Medical Technology Holdings, Inc. with the Securities and Exchange Commission and available on the Commissions website at http://www.sec.gov.

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Landmark Results for CaverStem Procedure Published in Journal of Translational Medicine to Create Paradigm Shift in Treatment of Erectile Dysfunction...

Bluebird Bio taps ex-Celgene exec Heffron to lead its first gene therapy launch – FiercePharma

After a manufacturing specification delay, Bluebird Bio has officially launched Zynteglo, its first gene therapy, andtapped a new leader to run the operation.

Nicola Heffron, a former exec with Celgene, Shire and GlaxoSmithKline, has joined Bluebird as its European chief, Bloomberg reported, just as the company gets its rollout underway there. She is replacing Andrew Obenshain, whos moving up to the global leadership team.

Heffron is tasked with charting the course for Bluebirds first commercial launch of its first product, Zynteglo, to treatbeta thalassemia, a rare inherited disease marked by reduced production of oxygen-carrying hemoglobin in red blood cells.

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And Heffron knows a thing or two about blood disorders. Before Bluebird, she headed up global marketing for Celgenes myeloid portfolio, her LinkedIn profile shows.

Wednesday, Bluebird revealed that the $1.76 million-per-treatment gene therapy is now available in Germany. The University Hospitalof Heidelberg serves as the drugs first qualified treatment center inthe country, and Bluebird said its working with institutions that have expertise in stem cell transplant as well as in treating patients with [beta thalassemia] to establish more centers.

RELATED:Bluebird Bio readies Zynteglo launch as EU approves 'refined' manufacturing

During a presentation at the annual J.P. Morgan Healthcare Conference on Tuesday, Bluebird CEO Nick Leschly confirmed the companysvalue-based payment model for the costly onetime therapy. Under that arrangement,payments of 315,000 ($351,000) each are made in five installments over five years. Except for the first round of expenses, payers only pay the rest if Zynteglo delivers on its therapeutic promise.

So far, the reimbursement agreements Bluebird has penned using that model can coverabout half of Germanys patients, according to Leschly.

Novartis has also rolled out a similar program for its $2.1 million spinal muscular atrophy gene therapy Zolgensma.

Bluebird won its European nod for Zynteglo last year but delayed the launch after a manufacturing specification hiccup. The Cambridge, Massachusetts-based biotech has established a manufacturing network that includes both internal facilitiesand contract partners for itslentiviral vector and drug product, Leschly said Tuesday.

RELATED:ASH: Bluebird's multiple myeloma CAR-T follow-up shows promise in phase 1

In the U.S., Bluebird has started itsrolling submission for approval and is in talks with the FDA regarding the requirements and timing of the various components of the application. Its expecting to finish the process in the first half of 2020.

Outside of beta thalassemia, Bluebird is testing the same drug, also known as LentiGlobin, in sickle cell disease, which is also marked by an abnormality in hemoglobin.

According to phase 1/2 data presented at last years American Society of Hematology annual meeting in December, none of the 17 patients enrolled in group Cwhich used an improved stem cell harvest technique and a new manufacturing processrequired regular blood transfusions post-treatment. Nine patients had beenfollowed for at least six months at that data cutoff.

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Bluebird Bio taps ex-Celgene exec Heffron to lead its first gene therapy launch - FiercePharma

Actinium Pharmaceuticals Announces Iomab-ACT Program Gene Therapy Collaboration with UC Davis in Ongoing Clinical Trial for Patients with HIV-Related…

- Trial will replace currently used chemotherapy conditioning with apamistamab-I-131, Actinium's targeted conditioning ARC, to selectively eliminate lymphoma cancer cells and stem cells to enable engraftment of stem cell gene therapy

- Anti-HIV stem cell gene therapy intended to simultaneously treat patients' HIV-related lymphoma and develop immune cells resistant to HIV

NEW YORK, Jan. 13, 2020 /PRNewswire/ --Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium"), announced today that it has entered into an agreement with the University of California, Davis (UC Davis) to utilize Actinium's Antibody Radiation-Conjugate or ARC apamistamab-I-131 for targeted conditioning and replace the chemotherapy conditioning being used in an ongoing Phase 1/2 stem cell gene therapy clinical trial. In the trial, patients with relapsed or refractory HIV-related lymphoma are being treated with autologous stem cell gene therapy. This is the first gene therapy clinical trial that will utilize ARC based conditioning. The clinical trial will be conducted at UC Davis and may be expanded to additional sites in the future.

(PRNewsfoto/Actinium Pharmaceuticals, Inc.)

Dr. Mehrdad Abedi, Professor, Hematology and Oncology at UC Davis and study lead, said, "This collaboration represents an exciting combination of revolutionary technologies that could further our ability to treat patients with HIV and other life-threatening diseases with gene therapy. Despite the advances made in the field of gene therapy, the reliance on non-targeted chemotherapy and external radiation as conditioning regimens is less than optimal and poses a problem that we hope to reduce or eliminate as part of this collaboration by replacing our conditioning regimen in this study with Actinium's ARC based targeted conditioning. Advances in HIV therapies have dramatically improved patient survival, but current therapies require life-long daily use to keep the HIV virus at bay, can have severe side effects, may be overcome by HIV resistance and do not address the needs of all patients like those in this study with HIV-related lymphomas. We envision a future where a single treatment of our stem cell gene therapy can cure patients of their lymphoma and HIV leaving the patient with a new immune system that can fight, be resistant to and prevent the mutation of HIV. Apamistamab-I-131's demonstrated antitumor effect against lymphoma and ability to condition patients in a targeted manner with a demonstrated tolerable safety profile in the bone marrow transplant setting makes it an ideal conditioning agent for this patient population. Based on these factors and extensive supporting clinical data in the Iomab-B program, we selected this ARC as the conditioning agent for the next phase of our trial as we believe antibody radiation-conjugates are more advanced and hold distinct advantages over novel but unproven conditioning technologies such as Antibody Drug Conjugates and naked antibodies that are beginning to be developed albeit at the preclinical stage."

In the current clinical trial, the anti-HIV stem cell gene therapy is produced by taking a patient's own or autologous, blood forming stem cells and genetically modifying them via gene therapy with a combination of three anti-HIV genes. The intended result is for the gene modified bone marrow stem cells to produce a new immune system and newly arising immune cells that are resistant to HIV via a single treatment. Conditioning is necessary prior to adoptive cell therapies such as gene therapy to eliminate certain cell types such as immune cells and stem cells in the bone marrow so the transplanted cells can engraft. Until now, conditioning in this trial, as is typical, used a multi-drug chemotherapy regimen administered over several days. This approach is non-targeted, associated with toxicities that impairs patients and restricts the use and efficacy of cellular therapy. Apamistamab-I-131, which requires just one therapeutic administration, will displace the non-targeted chemotherapy to condition patients in a targeted manner with the goal of reducing conditioning related toxicities and improving patient outcomes. Actinium and UC David will cross-reference their respective Investigational New Drug applications and will work collaboratively to obtain necessary regulatory and institutional approvals. In this clinical collaboration, Actinium will provide drug product, support for its administration and certain trial costs. UC Davis will be responsible for the production of the anti-HIV stem cell gene therapy and overall conduct of the study and its cost.

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Dr. Dale Ludwig, Actinium's Chief Scientific Officer, said, "We are excited to be working with Dr. Abedi on this clinical study and we appreciate his recognition of the value of our Iomab-ACT targeted conditioning program may provide in support of gene stem cell therapy. This targeted approach using our CD45 ARC, enables both anti-tumor activity and effective conditioning with the potential for reduced toxicity compared to non-targeted chemotherapy and external radiation in the bone marrow transplant setting. Supported by extensive clinical investigation in 12 trials and over 300 patients, a single therapeutic dose of apamistamab-I-131 is sufficient for conditioning and, due to its dual activity, even a patient with active disease could expect to receive therapy within two weeks, which is anticipated to lead to better outcomes compared to chemotherapy, external beam radiation, or exploratory approaches such as naked antibodies or Antibody Drug Conjugates. In addition, CD45, the target of apamistamab-I-131, is ideal for targeted conditioning, as it is not expressed outside of the haemopoietic system and, because it is a poorly internalizing receptor. An ARC approach which does not require internalization of its radionuclide warhead for target cell killing, is anticipated to be more viable and more effective than Antibody Drug Conjugate approaches which need to internalize their payloads. Given the potential of this ARC targeted conditioning technology for bone marrow transplant, we are grateful to Dr. Abedi for the opportunity to advance the Iomab-ACT program into the promising field of gene stem cell therapy."

Sandesh Seth, Actinium's Chairman and Chief Executive Officer, said, "Actinium is thrilled to be working with UC Davis and honored to now be part of this important trial. It has become evident that better conditioning regimens are needed for cell and gene therapies to reach their full potential. Our team is proud to be the first company to establish a clinical stage targeted conditioning portfolio for both cell and gene therapy. We are pleased to extend our ARC technology for targeted conditioning into these rapidly advancing fields and we are committed to establishing a strong leadership position in enabling these adoptive cell therapies fully realize their great potential for improving patients' lives."

Apamistamab-I-131's demonstrated conditioning and antitumor effect in lymphoma1

Actinium's apamistamab-I-131 ARC has been studied as a targeted conditioning agent in over 300 patients in the bone marrow transplant setting in the Iomab-B Program and is currently being studied in a pivotal Phase 3 clinical (SIERRA) trial in patients with relapsed or refractory acute myeloid leukemia. Clinical proof of concept has been established with Iomab-B for targeted conditioning in high-risk, relapsed or refractory lymphoma patients prior to an autologous stem cell transplant where a favorable safety profile with no dose limiting toxicities and minimal non-hematologic toxicities observed and promising efficacy with median overall survival not reached (range: 29 months to infinity) and 31% of patients in prolonged remission at a median of 36 months follow up (range: 25 41 months)1.

1) Cassaday et al. Phase I Study of a CD45-Targeted AntibodyRadionuclide Conjugate for High-Risk Lymphoma. AACR Clin Cancer Res Published OnlineFirst September 3, 2019

About Actinium Pharmaceuticals, Inc.

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, apamistamab-I-131 (Iomab-B) is being studied in the ongoing pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over fifty percent enrolled and promising single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. Apatmistamamb-I-131 will also be studied as a targeted conditioning agent in a Phase 1/2 anti-HIV stem cell gene therapy with UC Davis and is expected to be studied with a CAR-T therapy in 2020. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 alpha ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 100 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc.

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Investors:Hans VitzthumLifeSci Advisors, LLCHans@LifeSciAdvisors.com(617) 535-7743

Media:Alisa Steinberg, Director, IR & Corp Commsasteinberg@actiniumpharma.com(646) 237-4087

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Hemogenyx’s CAR-T Cells are Effective Against AML in vitro – GuruFocus.com

LONDON, UK / ACCESSWIRE / January 15, 2020 / Hemogenyx Pharmaceuticals plc (LSE:HEMO) ("Hemogenyx" or the "Company"), the biopharmaceutical group developing new therapies and treatments of blood diseases, is pleased to announce the following update on its activities.

As previously announced, Hemogenyx's CDX product has the potential to treat Acute Myeloid Leukemia (AML) directly as well as providing a benign conditioning regimen for blood stem cell replacement therapy. The Company has now carried out extensive work developing treatments for AML and has to date obtained encouraging results.

Hemogenyx has successfully constructed and in vitro tested Chimeric Antigen Receptor (CAR) programmed T cells (HEMO-CAR-T) for potential treatment of AML. HEMO-CAR was constructed using Hemogenyx's proprietary humanized monoclonal antibody against a target on the surface of AML cells. The Company has demonstrated that HEMO-CAR was able to programme human T cells (converted them into HEMO-CAR-T) to identify and destroy human AML derived cells in vitro.

Following the successful completion of these tests, in vivo tests of the efficacy of HEMO-CAR-T against AML are being conducted utilising a model of AML using Advanced peripheral blood Hematopoietic Chimera (ApbHC) - humanized mice developed by Immugenyx, LLC, a wholly-owned subsidiary of Hemogenyx.

Vladislav Sandler, Chief Executive Officer, commented, "We are encouraged by this new data which demonstrates our continuing progress in the development of novel treatments for blood cancers such as AML. The development of HEMO-CAR-T expands Hemogenyx's pipeline and advances it into a cutting-edge area of cell-based immune therapy. We are excited to have developed another product candidate that should, if successful, provide a new and potentially effective treatment for blood cancers for which survival rates are currently very poor."

About AML and CAR-T

AML, the most common type of acute leukemia in adults, has poor survival rates (a five-year survival rate of less than 25% in adults) and is currently treated using chemotherapy, rather than the potentially more benign and effective form of therapy being developed by Hemogenyx. The successful development of the new therapy for AML would have a major impact on treatment and survival rates for the disease.

CAR-T therapy is a treatment in which a patient's own T cells, a type of immune cell, are modified to recognize and kill the patient's cancer cells. The procedure involves: isolating T cells from the patient, modifying the isolated T cells in a laboratory using a CAR gene construct (which allows the cells to recognize the patient's cancer); amplifying (growing to large numbers) the newly modified cells; and re-introducing the cells back into the patient.

Market Abuse Regulation (MAR) Disclosure

Certain information contained in this announcement would have been deemed inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 until the release of this announcement.

Enquiries:

Hemogenyx Pharmaceuticals plc

http://www.hemogenyx.com

Dr Vladislav Sandler, Chief Executive Officer & Co-Founder

[emailprotected]

Sir Marc Feldmann, Executive Chairman

SP Angel Corporate Finance LLP

Tel: +44 (0)20 3470 0470

Matthew Johnson, Vadim Alexandre, Soltan Tagiev

Peterhouse Corporate Finance Limited

Tel: +44 (0)20 7469 0930

Lucy Williams, Duncan Vasey

US Media enquiries

Tel: +1 (323) 646-3249

Lowell Goodman

[emailprotected]

About Hemogenyx Pharmaceuticals plc

Hemogenyx Pharmaceuticals plc ("Hemogenyx") is a publicly traded company (LSE: HEMO) headquartered in London, with its wholly-owned US operating subsidiaries, Hemogenyx LLC and Immugenyx LLC, located in New York City at its state-of-the-art research facility and a wholly-owned Belgian operating subsidiary, Hemogenyx-Cell SPRL, located in Lige.

Hemogenyx is a pre-clinical stage biopharmaceutical group developing new medicines and treatments to bring the curative power of bone marrow transplantation to a greater number of patients suffering from otherwise incurable life-threatening diseases. Hemogenyx is developing several distinct and complementary product candidates, as well as a platform technology that it uses as an engine for novel product development.

For more than 50 years, bone marrow transplantation has been used to save the lives of patients suffering from blood diseases. The risks of toxicity and death that are associated with bone marrow transplantation, however, have meant that the procedure is restricted to use only as a last resort. Hemogenyx's technology has the potential to enable many more patients suffering from devastating blood diseases such as leukemia and lymphoma, as well as severe autoimmune diseases such as multiple sclerosis, aplastic anemia and systemic lupus erythematosus (Lupus), to benefit from bone marrow transplantation.

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact [emailprotected] or visit http://www.rns.com.

SOURCE: Hemogenyx Pharmaceuticals PLC

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Celgene exec jumps to head bluebird bio ops in Europe, where its $1.8M gene therapy Zynteglo is now available – Endpoints News

Days after shaking hands with German regulators over the launch and coverage of its beta-thalassemia gene therapy, bluebird bio has wooed a Celgene exec to lead its European operations.

Nicola Heffron, a biopharma vet with stints across Eli Lilly, GSK and Shire, jumps from a brief tenure overseeing marketing for Celgenes myeloid portfolio in Summit, NJ. She will now be based in Zug, Switzerland.

Shes replacing Andrew Obenshain as he joins CEO Nick Leschly and the leadership team in Boston, according to Bloomberg, which first reported the news. Obenshains new title is chief of wings.

On Monday bluebird announced that Germany will be the first country to commercially offer Zynteglo, their procedure encoding A-T87Q-globin gene in CD34+ cells extracted from patients. Under their value-based payment scheme, the $1.8 million price is divided into five installments. After an initial payment is made at the time of infusion, the payers wait and see and only pay if the patients continue to be transfusion-free.

Multiple statutory health insurances have signed onto the plan, bluebird said, and University Hospital of Heidelberg will host the first qualified treatment center.

The biotech has been busy sorting out manufacturing specs and talking to individual countries since the EU issued an historic OK last June. Its sanctioned for a specific group of beta-thalassemia patients those who are 12 years and older, transfusion dependent, do not have a 0/0 genotype and for whom hematopoietic stem cell transplantation is appropriate but a donor is not available.

For patients with TDT, lifelong chronic blood transfusions are required in order to survive, bluebird chief commercial officer Alison Finger emphasized in a statement. Their one-time infusion promises to do away with the transfusions for good.

A rolling BLA submission to the FDA has begun, bluebird added.

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Tolero Pharmaceuticals Announces First Patient Dosed in Phase 2 Zella 202 Study of Investigational Agent Alvocidib in Patients with Relapsed or…

SALT LAKE CITY, Jan. 15, 2020 /PRNewswire/ -- Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today announced that the first patient has been dosed in a Phase 2 study evaluating the investigational agent alvocidib, a potent CDK9 inhibitor, in patients with acute myeloid leukemia (AML) who have either relapsed from or are refractory to venetoclax in combination with a hypomethylating agent (HMA). The open-label, randomized study has two parts and will evaluate the safety and efficacy of alvocidib in monotherapy or in combination with low-dose cytarabine.

"Patients with AML who are resistant to or progressed following treatment with the BCL-2 inhibitor venetoclax in combination with an HMA have limited treatment options, and it has been well established in the literature that a key potential mechanism of resistance to BCL-2 targeted therapy is the switch to a dependence on MCL-1," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "The initiation of this study marks an important step toward understanding the potential of alvocidib as a monotherapy or in combination with low-dose cytarabine for these patients. We believe that patients whose cancers have progressed following treatment with venetoclax may be sensitive to alvocidib and this trial will help us to better understand this hypothesis."

The primary objective of the Phase 2 study is to determine the rate of combined complete remission (CR) and CR with incomplete hematological recovery (CRi), of alvocidib and alvocidib in combination with low-dose cytarabine in patients with AML. Secondary objectives include establishing the recommended treatment regimen for the second part of the study and evaluating the median overall survival (mOS) and CR rate. Additional secondary outcome measures include evaluating event-free survival (EFS), duration of composite CR (CRc), safety and tolerability of the regimen and mortality.

In the first part of the study, patients who are refractory to or have relapsed on venetoclax in combination with an HMA will be randomized into two arms. In Arm 1 of the study, patients will receive combination therapy of alvocidib and low-dose cytarabine. In Arm 2 of the study, patients will receive alvocidib monotherapy. In the second part of the study, patients will receive the regimen based on the outcome of the first part.

The trial is being conducted at sites in the United States. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at http://www.ClinicalTrials.gov(NCT03969420).

About AlvocidibAlvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in the Phase 2 studies, Zella 202 in patients with acute myeloid leukemia (AML) who have either relapsed from or are refractory to venetoclax in combination with azacytidine or decitabine (NCT03969420) and Zella 201 in patients with relapsed or refractory MCL-1 dependent AML, in combination with cytarabine and mitoxantrone (NCT02520011). Alvocidib is also being evaluated in Zella 101, a Phase 1 clinical study evaluating the maximum tolerated dose, safety and clinical activity of alvocidib in combination with cytarabine and daunorubicin (7+3) in newly diagnosed patients with AML (NCT03298984), and Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes (MDS) in combination with decitabine (NCT03593915). In addition, alvocidib is being evaluated in a Phase 1 study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).

About CDK9 Inhibition and MCL-1MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.1In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.2MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.1,3The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).4,5Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.4Inhibition of CDK9 has been shown to block MCL-1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.1

About Tolero Pharmaceuticals, Inc. Tolero Pharmaceuticals is a clinical-stage biopharmaceutical company researching and developing treatments to improve and extend the lives of patients with hematological and oncological diseases. Tolero has a diverse pipeline that targets important biological drivers of blood disorders to treat leukemias, anemia, and solid tumors, as well as targets of drug resistance and transcriptional control.

Tolero Pharmaceuticals is based in the United States and is an indirect, wholly-owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd., a pharmaceutical company based in Japan. Tolero works closely with its parent company, Sumitomo Dainippon Pharma, and Boston Biomedical, Inc., also a wholly-owned subsidiary, to advance a pipeline of innovative oncology treatments. The organizations apply their expertise and collaborate to achieve a common objective - expediting the discovery, development and commercialization of novel treatment options.

Additional information about the company and its product pipeline can be found at http://www.toleropharma.com.

Tolero Pharmaceuticals Forward-Looking Statements This press release contains "forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products.The forward-looking statements in this press release are based on management's assumptions and beliefs in light of information presently available, and involve both known and unknown risks and uncertainties, which could cause actual outcomes to differ materially from current expectations. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

References

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How Exosomes Could Lead To Stroke Recovery – Technology Networks

Its been almost a quarter of a century since the first drug was approved for stroke. But whats even more striking is that only a single drug remains approved today.

In a publication appearing this month in the journal Translational Stroke Research, animal scientists, funded by the National Institutes of Health, present brain-imaging data for a new stroke treatment that supported full recovery in swine, modeled with the same pattern of neurodegeneration as seen in humans with severe stroke.

It was eye opening and unexpected that you would see such a benefit after having had such a severe stroke, said Steven Stice, Georgia Research Alliance Eminent Scholar and D.W. Brooks Distinguished Professor in the University of Georgias College of Agricultural and Environmental Sciences. Perhaps the most formidable discovery was that one could recover and do so well after the exosome treatment.

Stice and his colleagues at UGAs Regenerative Bioscience Center report the first observational evidence during a midline shiftwhen the brain is being pushed to one side to suggest that a minimally invasive and non-operative exosome treatment can now influence the repair and damage that follow a severe stroke.

Exosomes are considered to be powerful mediators of long-distance cell-to-cell communication that can change the behavior of tumor and neighboring cells. The results of the study echo findings from other recent RBC studies using the same licensed exosome technology.

Many patients who suffer stroke exhibit a shift of the brain past its center linethe valley between the left and right parts of the brain. Lesions or tumors will induce pressure or inflammation in the brain, causing what typically appears as a straight line to shift.

Based on results of the exosome treatment in swine, it doesnt look like lesion volume or the effects of a midline shift matter nearly as much as one would think, said Franklin West, associate professor of animal and dairy science in the UGA College of Agricultural and Environmental Sciences. This suggests that, even in some extremely severe cases caused by stroke, youre still going to recover just as well.

Trauma from an acute stroke can happen quickly and can cause irreversible damage almost immediately. Time is brain, a phrase coined by stroke advocacy organizations in the late 1990s, captures the importance of acting on the first signs of stroke. In less than 60 seconds, warns the Stroke Awareness Foundation, an ischemic stroke kills 1.9 million brain cells.

Data from the teams research showed that non-treated brain cells near the site of the stroke injury quickly starved from lack of oxygen and diedtriggering a lethal action of damage signals throughout the brain network and potentially compromising millions of healthy cells.

However, in brain areas treated with exosomes that were taken directly from cold storage and administered intravenously, these cells were able to penetrate the brain and interrupt the process of cell death.

Basically, during a stroke, these really destructive free radicals are all over the place destroying things, said Stice, director of the RBC. What the exosome technology does is communicate with jeopardized cells and work like an anti-inflammatory agent to interrupt and stop further damage.

According to the teams results, neuroimaging is an essential tool for evaluating brain tissue and managing stroke recovery.

In this observational study, the team analyzed brain images taken 24 hours after stroke. They then applied recovery scores, commonly used in human practice, based on swine gait, cadence, walking speed and stride length. By recording the relationship between brain measurements and functional outcomes, the new assessment scales can better help physicians predict how quickly a person will recover in real time.

What Im trying to do with this assessment data is come up with something that we can implement in the clinics right nowtodayto help with predicting patient outcomes, said Samantha Spellicy, a neuroscience graduate student and first author on the publication.

Spellicy, who is currently training under Stice, began her first two years at the Medical College of Georgia at Augusta University and has plans to return to MCG after completing her Ph.D. She anticipates a return to stroke care and one day using the same outcome assessments presented in the study with human patients.

When a patient arrives in emergency with a stroke, the available clinician would not be left crunching an arbitrary number based on some standardized scale assessment, Spellicy said. Instead, the clinician could take more of a personalized approach based on the patients midline shift measurement, and, say for instance, OK, in three months youre going to get better, but youre going to have issues with your gait. Lets talk to a specialist now to target that exact condition.

As for the future of the exosome treatment, Spellicy and the RBC team anticipate that the patented neural exosome technology, called AB126, will be filed for clinical trials by 2021.

Reference

Spellicy et al. (2019) Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model. Translational Stroke Research. DOI: https://doi.org/10.1007/s12975-019-00753-4

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How Exosomes Could Lead To Stroke Recovery - Technology Networks