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Neuralstem announces Phase II clinical trial initiation for ischemic stroke stem cell therapy

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Neuralstem Inc, a developer of nervous system therapies based on its neural stem cell cell technology, have announced the initiation of a Phase II clinical trial which will evaluate the company’s lead stem cell candidate, NSI-566, as a possible treatment for ischemic stroke.

Ischemic strokes, which are the most common type of stroke, are estimated to make up 87% of the 15 million strokes which occur worldwide. The announcement of the Phase II trial follows the presentation of positive topline results of the Phase I study in the 2018 International Society for Stem Cell Research (ISSCR) abstract, which has treated patients suffering from motor deficits due to ischemic strokes. The trial will take place at Bayi Brain Hospital in Beijing, China, and managing the trial will be James Li, Ph.D., Executive Vice President of Asia Operations of Suzhou Neuralstem Ltd, a wholly owned subsidiary of Neuralstem, located in Suzhou, China.

“The Phase 2 study, which will be a randomized, double-blind, controlled study, is based on the encouraging results from the open-label Phase 1 safety study. It is intended to further test the safety and efficacy of NSI-566 to reverse paralysis in stroke patients with half of their body partially paralyzed,” said Dr. Karl Johe, CSO of Neuralstem.

Source: Neuralstem Announces Initiation of Phase 2 Clinical Trial of NSI-189 in Ischemic Stroke
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bluebird bio’s Thalassemia gene therapy granted accelerated assessment by the EMA

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Bluebird bio have announced that its transfusion dependent β-Thalassemia (TDT) treatment, the investigational gene therapy LentiGlobin, has been granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the EMA, for its upcoming marketing authorization application (MAA).

Bluebird bio have announced that its transfusion dependent β-Thalassemia (TDT) treatment, the investigational gene therapy LentiGlobin, has been granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the EMA, for its upcoming marketing authorization application (MAA).

LentiGlobin is an investigational gene therapy developed for treating adult and adolescent patients suffering with TDT and a non-β0/β0 genotype. The company aim to file an MAA for LentiGlobin with the EMA later in 2018. Accelerated assessments can reduce the active review time of an MAA from 210 days to 150 days, pending validation by the EMA. They are granted to products which the CHMP consider to be of major interest for public health and are representative of therapeutic innovation.

LentiGlobin’s accelerated assessment approval is supported by data from clinical studies, which includes the completed Phase 1/2 Northstar (HGB-204) study, the ongoing Phase 1/2 HGB-205 study, as well as available data from the Phase 3 Northstar-2 (HGB-207) study and the long-term follow-up study LTF-303.

Previously, LentiGlobin has been granted Priority Medicines (PRIME) eligibility and Orphan Medicinal Product designation, and is part of the EMA’s Adaptive Pathways pilot program, aims to improve timely access for patients to new medicines. The FDA have also granted LentiGlobin Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

“Transfusion-dependent β-thalassemia is a severe genetic disease that requires a lifetime of chronic blood transfusions for survival, and while these transfusions are life-saving, they are also associated with serious medical complications such as organ failure from iron overload,” said David Davidson, M.D., chief medical officer, bluebird bio. “Receiving accelerated assessment for LentiGlobin helps support our goal of delivering the first gene therapy to patients with TDT. We look forward to working in collaboration with the regulatory authorities on this potentially transformative treatment option.”

Source: bluebird bio’s LentiGlobin™ Gene Therapy Granted Accelerated Assessment by European Medicines Agency for the Treatment of Transfusion-Dependent β-Thalassemia Press Release

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FDA accept IND application for Celyad’s First-in-Class none-gene edited allogeneic CAR-T therapy

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Celyad have announced that the FDA have approved the company’s Investigational New Drug (IND) application for CYAD-101, the world’s first non-gene-edited allogeneic CAR-T clinical program targeting colorectal cancer.

CYAD-101, the first allogeneic CAR-T cell product developed by Celyad, encodes the autologous CYAD-01 CAR-T as well a TCR signalling inhibitor, the novel peptide known as TCR Inhibiting Molecule (TIM). Altering or eliminating TCR signalling could potentially limit or eliminate Graft versus Host Disease (GvHD). The TIM peptide is encoded in conjunction with the CAR construct in CYAD-101, which enables allogeneic T cell production via a single transduction step. The manufacturing process used for the production of CYAD-101 is very similar to the process used for Celyad’s clinical autologous CAR-T cell products. Utilizing cells manufactured from healthy donors may allow better reproducibility and lower manufacturing costs.

Following the IND approval, the FDA has indicated that the ‘Allo-SHRINK’ trial for the evaluation of safety and clinical activity of CYAD-101 in patients with unresectable colorectal cancer in combination with standard chemotherapy can proceed. Cyad-01, Celyad’s lead oncology candidate, has previously been assessed in a single dose escalation Phase I clinical trial for safety and clinical activity of multiple administrations of autologous CYAD-01 cells in seven refractory cancers including five solid tumors and two hematological tumors.

“Celyad is the first company clinically evaluating a non-gene edited CAR-T candidate, which, we believe, offers significant advantages over gene edited approaches. Our non-gene edited program consists of a family of technologies aimed at reducing or eliminating T cell receptor (TCR) signaling without requiring genetic manipulation. CYAD-101 is part of a robust clinical development plan, establishing the foundations of next generation CAR-T products.” commented Dr Christian Homsy, CEO of Celyad.

Source: Celyad Announces FDA Acceptance of IND Application for CYAD-101, a First-in-Class Non-Gene Edited Allogeneic CAR-T Candidate Press Release

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Pfizer to begin Phase III program for Investigational Hemophilia B Gene Therapy

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Pfizer and Spark Therapeutics have announced the initiation of a Phase III open-label, multi-center, lead-in study for the evaluation of efficacy and safety of current factor IX prophylaxis replacement therapy for hemophilia B in the usual care setting.

The initiation of this program follows the transfer of responsibility for Spark’s hemophilia B gene therapy program to Pfizer. The efficacy data gathered in the lead in study for factor IX prophylaxis will serve as the within-subject control group for patients enrolling in the next stage of the Phase III study, evaluating the investigational gene therapy fidanacogene elaparvovec (previously known as SPK-9001 and PF-06838435) for hemophilia B.. Patients who have previously completed at least six months in the lead-in study will be enrolled in the interventional portion of the upcoming Phase II program.

Fidanacogene elaparvovec is a novel, investigational vector containing a bio-engineered adeno-associated virus (AAV) capsid and a high-activity human coagulation factor IX gene. Once treated, researchers hope that the patients will be able to produce factor IX themselves, instead of the current common treatment of self-injection of plasma-derived or recombinant factor IX.

In May 2018, Pfizer and Spark released data for 15 patients in the ongoing fidanacogene elaparvovec phase I/II clinical trial for the treatment of severe/moderately severe haemophilia B. This data demonstrated all 15 patients had discontinued routine infusions of factor IX concentrates, and there were no reported serious adverse events or thrombotic events as of the data cut off of May 7th.

“We are pleased to have transitioned fidanacogene elaparvovec to Pfizer following the positive results of the ongoing Phase 1/2 clinical trial,” commented Katherine A. High, MD, President and Head of Research & Development, Spark Therapeutics. “The initiation of the Phase 3 program marks an important milestone toward our goal of one day potentially freeing patients with hemophilia B of the need for regular infusions, while potentially eliminating spontaneous bleeding.”

Source: Pfizer Initiates Pivotal Phase 3 Program for Investigational Hemophilia B Gene Therapy Press Release

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Voyager provides clinical update on Parkinson’s disease gene therapy

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Voyager Therapeutics, a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases have announced positive interim results from their Phase I posterior trajectory trial of VY-AADC, concluding that the posterior approach will continue to serve as the preferred surgical route of administration.

The characteristic motor degeneration in Parkinson’s disease is largely due to the death of dopamine neurons in the substantia nigra, a part of the brain which converts levodopa to dopamine, in a reaction catalyzed by the enzyme AADC. Neurons in the substantia nigra release dopamine into the putamen where the receptors for dopamine reside, and in Parkinson’s, neurons in the substantia nigra degenerate and the enzyme AADC is markedly reduced limiting the brain’s ability to convert oral levodopa to dopamine. However, the intrinsic neurons in the putamen do not degenerate. VY-AADC, which has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA, is comprised of the adeno-associated virus-2 capsid and a cytomegalovirus promoter to drive AADC transgene expression, and has been designed to deliver the AADC gene directly into neurons of the putamen where dopamine receptors are located, bypassing the substantia nigra neurons, allowing the neurons of the putamen to express the AADC enzyme to convert levodopa into dopamine. This could potentially enhance the conversion of levodopa to dopamine and provide clinically meaningful improvements by restoring motor function in patients and improving symptoms following a single administration.

In the Phase I trial of VY-AADC, eight patients with Parkinson’s were successfully dosed with the therapy, administered through the posterior trajectory and using the same dose as given to patients in the third cohort of the previous Phase 1b trial. This trajectory resulted in a greater average coverage of the putamen (50%) and saw a reduction of 2-3 hours in total procedure time in comparison to cohorts 1, 2 and 3 from the Phase 1b trial that employed a transfrontal, or top of the head, delivery approach into the putamen. Treatment with VY-AADC has been well tolerated in all eight patients, with no serious adverse events reported so far. Following six months from administration, there has been increased AADC enzyme activity in the patients, as well as improved motor function in the four of the eight patients who have been assessed (assessed in a clinically-meaningful manner and consistent with results from Cohorts 2 and 3 from the Phase 1b trial during the same period of time).

Voyager have also announced feedback from the FDA regarding a Type C meeting which saw the discussion of the regulatory pathway for VY-AADC for the treatment of Parkinson’s disease in patients with motor fluctuations that are refractory to medical management. Based on this feedback, voyager plans to to submit for review a biologics license application (BLA) for VY-AADC based on the non-clinical and clinical safety and efficacy data gathered so far, including the potential to file a BLA based on safety and efficacy results from the Phase 2 trial, or from the Phase 3 trial if needed.

Source: Voyager Therapeutics Receives FDA Guidance on Development Path for VY-AADC for Parkinson’s Disease and Provides Clinical Update Press Release

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Nohla Therapeutics bags $56 million in Series B financing to fund cell therapy platform

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Nohla Therapuetics, a Seattle based developer of universal, off-the-shelf cell therapies for patients with hematologic malignancies and other critical diseases, have announced that an additional $11 million has been raised after the second closing of its Series B financing, bringing the total raised to $56 million. The funding will support the ongoing clinical development of dilanubicel, the company’s lead cell therapy product.

The investors who participated in the second closing include the University of Tokyo Edge Capital, Schroder Adveq and Premier Partners, joining the initial Series B investors made up of Fidelity Management and Research Company, Celgene Corporation, ARCH Venture Partners, 5AM Ventures, Alexandria Venture Investments and AML Biotech Partners.

The additional funding will financially support Nohla’s ongoing clinical development of dilanubicel, a universal, off-the-shelf stem and progenitor cell therapy designed to provide patients with short-term bone marrow function, while also providing long term immunologic benefits with the potential for improved survival. Unlike autologous or patient-specific allogeneic cell therapies, dilanubicel does not require Human Leukocyte Antigen (HLA) tissue matching. Last month, Nohla received Priority Medicine (PRIME) status for Haematological malignancies in the European Union for the product. Dilanubicel is currently under evaluation in two ongoing Phase II trials for patients with hematologic malignancies undergoing an allogeneic transplant, and acute myeloid leukemia (AML) patients with chemotherapy-induced myelosuppression following high-dose chemotherapy. Results from the study will be published later this year.

Katie Fanning, President and CEO of Nohla Therapeutics commented “We have achieved a number of significant milestones in the first half of 2018 including further advancement of our lead product, dilanubicel. This additional funding will support our ongoing clinical development of dilanubicel in allogeneic transplant and acute myeloid leukemia, as well as support the advancement of discovery programs from our platform.”

Source: Nohla Therapeutics Announces Second Closing of $56 Million Series B Financing Press Release

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Pluristem and Thermo Fisher to collaborate on cell therapy industrialization

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Pluristem Therapeutics, a developer of placenta-based cell therapy products, has entered into a strategic collaboration with Thermo Fisher Scientific with the aim to advance fundamental knowledge of cell therapy industrialization and to improve quality control across the end-to-end supply chain.

This agreement will combine Pluristem’s cell therapy manufacturing, clinical development and quality control expertise with Thermo Fisher’s cell therapy development and bioproduction scaleup experience. The goal of the collaboration is to enable mass production of millions in therapeutic dose of regenerative medicines through the transformation of cell therapy manufacturing into a large scale, high capacity industry. At present there are over 850 companies working on the development of regenerative medicines and advanced therapies, and approximately 900 clinical trials being conducted, with several approved and marketed products worldwide. In order to address unmet medical needs, change is required in the supply chain of equipment, consumables, reagents and storage systems.

“From early on, our strategy was to build an in-house manufacturing facility. Having achieved that, we are now in a unique position within the industry, and have a broad understanding of its needs. Thermo Fisher, known for its biopharmaceutical infrastructure, materials supply, logistics, and manufacturing expertise is a perfect partner for Pluristem. This initiative has the potential to advance the industry significantly, allowing regenerative medicine to realize its potential, treating millions of patients globally while reducing healthcare spending. We look forward to a long-term, mutually beneficial partnership,” commented Pluristem President and Co-CEO Yaky Yanay.

Source: Pluristem Signs Collaboration Agreement With Thermo Fisher Scientific
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Axovant Announces Global Licensing Agreement for Oculopharyngeal Muscular Dystrophy Gene Therapy

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Axovant Sciences have announced an agreement giving them the exclusive global rights to ACO-AAV-OPMD, part of the investigational ‘Silence-and-Replace’ gene therapy program for the treatment of oculopharyngeal muscular dystrophy (OPMD) from Benitec Biopharma.

Silence-and-Replace gene therapy technology suppresses mutant protein production while restoring expression of functional protein through the delivery of a combination of DNA-directed RNA interference (silence) along with a functional copy of the gene (replace) in a single vector construct. This method can be applied to various genetic diseases including autosomal dominant disorders caused by nucleotide repeat expansion.

AXO-AAV-OPMD is an investigational gene therapy that has been granted Orphan Drug Designation by the FDA and European Commission, and is currently in preclinical development, with a planned placebo-controlled clinical study due to begin in 2019. There are currently no approved products for the treatment of OPMD, which is caused by mutations in the gene coding for polyA-binding protein nuclear 1 (PABPN1), which can lead to formation of intranuclear inclusion bodies causing muscle cell pathology.. This investigational therapy is given as a single administration directly into target muscle tissue, utilizing an AAV vector to silence the mutant PABPN1 gene which causes OPMD and replacing it with a functional copy. Data from mouse models of OPMD showed AXO-AAV-OPMD provided up to 86% inhibition of PABPN1 expression, while restoring functional PABPN1 up to 63% of normal levels.

Axovant will pay Benitec an upfront payment of $10 million for rights to the AXO-AAV-OPMD program and five additional investigational gene therapy products, as well as payments tied to development, regulatory and commercial sales milestones. Benitec will also receive 30% of the net profits on worldwide sales of AXO-AAV-OPMD and tiered royalties on the other gene therapy products that result from this collaboration. “The Silence-and-Replace technology is a unique approach in gene therapy, using a single vector to suppress mutant protein production while also restoring expression of the functional protein, and could be an elegant solution to tackling autosomal dominant genetic disorders,” commented Fraser Wright, PhD, Chief Technology Officer of Axovant.