Pipeline

PIPELINE OVERVIEW

There is significant unmet need for effective therapies for those people whose lives are disrupted by highly debilitating and often fatal neurodegenerative diseases.

Using the NurOwn® technology platform, Cell-Gene company is focused on realizing the potential of life-changing autologous cellular therapies for the treatment of debilitating neurodegenerative diseases.

CLINICAL DEVELOPMENT PROGRAM FOR AUTOLOGOUS MSC-NTF CELLULAR THERAPY

We are conducting a phase 3 clinical trial of autologous MSC-NTF cellular therapy in Amyotrophic Lateral Sclerosis (ALS) and have initiated clinical development in Progressive MS. We are conducting preclinical studies to determine the potential for autologous MSC-NTF cells in other conditions, including Huntington’s Disease (HD), Parkinson’s Disease (PD) and Autism Spectrum Disorder.

ABOUT ALS

ALS is a relentlessly progressive neurodegenerative disease characterized by selective deterioration of cortical, brainstem, and spinal cord motor neurons. As motor neurons die, patients become weaker and lose motor function. For most patients, the disease leads to death within 3 to 5 years of diagnosis. Currently available treatment does not halt or reverse disease progression in ALS.1

There is significant unmet medical need for safe and effective therapy for people with ALS. Given that multiple factors are involved in the pathogenesis of ALS, stem cell therapy could potentially target several of the putative mechanisms involved in the onset and progression of the disease.

CLINICAL DEVELOPMENT PROGRAM FOR AUTOLOGOUS MSC NTF CELLS IN ALS

SUMMARY OF PHASE 2 TRIALS OF CELL-GENE COMPANY’S AUTOLOGOUS MSC-NTF CELLULAR THERAPY IN ALS

Autologous MSC-NTF cells have been administered to a total of about 70 ALS patients in three completed clinical trials, including two open-label trials in Israel and a multicenter, double-blind, placebo-controlled trial in the United States. Overall, the results show administration of autologous MSC-NTF cells is safe and well-tolerated.

Phase 2 (United States) Randomized, placebo-controlled, double-blind, single dose NCT02017912 | N = 48

Administration of autologous MSC-NTF cells was found to be safe and well tolerated with the majority of adverse events being mild or moderate in severity Reduction in rate of ALS disease progression was observed in the autologous MSC-NTF treatment group but not in the placebo treatment group, and the treatment effect was statistically significant in a subpopulation of participants with more rapid disease progression. CSF biomarkers confirmed the secretion of NTFs and a reduction in inflammatory activity in the patients treated MSC-NTF-treated. Results from this study have been presented at major medical congresses. NEALS and AAN2018.

Study

N

Outcomes

Phase 2 (United States)
Randomized, placebo-controlled, double-blind, single dose
 NCT02017912

ABOUT ALS PHASE 3 PIVOTAL TRIAL (NCT03280056)

Cell-Gene company is currently enrolling a phase 3 pivotal trial using repeat-administration of autologous MSC-NTF cells in ALS at six leading clinical sites in the United States, supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989).

The multicenter phase 3 study will enroll 200 patients with ALS randomized 1:1 to receive autologous MSC-NTF cells or placebo and will evaluate ALS Functional Rating Scale–Revised (ALSFRS-R) responder analysis as a primary efficacy outcome measure (NCT03280056). Read more about the phase 3 study.

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ABOUT THE ALSFRS-R

The ALS Functional Rating Scale–Revised (ALSFRS-R) is a widely accepted measure of disease progression in ALS that is used in clinical trials.2,3 It is a validated questionnaire that measures physical function in performing activities of daily living (ADLs). Other measures of disease progression commonly used in clinical trials include assessment of muscle strength and respiratory function.

The ALSFRS-R measures 12 aspects of physical function across four functional domains (bulbar, fine motor, gross motor, and respiratory).

The rate of decline in ALSFRS-R scores is an important predictor of survival and disease prognosis.⁴ Without treatment, the average rate of decline on the ALSFRS-R is about 1 point per month.⁵

Source: Cedarbaum JM, et al. J Neural Sci. 1999;169:13-21.

ABOUT PROGRESSIVE MS

Multiple Sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disorder that affects the brain and spinal cord.

There are multiple types of MS. The most common form of MS is relapsing-remitting MS (RRMS, 85% of MS patients), characterized by periods of relapse, with flare-ups or exacerbations of symptoms, and periods of remission. Progressive MS, includes both primary progressive MS (PPMS) and secondary progressive MS (SPMS), is characterized by a worsening of neurologic function and increase in disability over time.6 About 10% of people with MS are diagnosed with PPMS and about half of those diagnosed with RRMS will eventually transition to SPMS. Onset can occur at any age between 20-70. 7

There are no available therapies that halt the progression of established disability or result in functional improvement in progressive MS. Therapies addressing regeneration and repair may offer an innovative treatment option to address a currently unmet medical need. ⁸

Evidence from preclinical models of MS (EAE mouse model) suggests that MSC-NTF cells have the potential for immunomodulation, remyelination, and neuroprotection. ^9-11

In preclinical studies, intracerebroventricular administration of MSC-NTF cells in EAE mice delayed symptom onset and improved survival.

CLINICAL DEVELOPMENT
PROGRAM IN PROGRESSIVE MS

Cell-Gene company is now enrolling a phase 2 open-label trial using repeat-administration of autologous MSC-NTF cells in progressive MS as defined and diagnosed by the recent 2017 revised McDonald Criteria (NCT03799718).

RECENT CELL-GENE COMPANY PUBLICATIONS AND PRESENTATIONS

REFERENCES

1. Brown RH and Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017;377:162-172.

2. Cedarbaum JM, Stambler N, Malta E, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. J Neurol Sci. 1999;169(1-2):13-21

3. Leigh PN, Swash M, Iwasaki Y, et al. Amyotrophic lateral sclerosis: a consensus viewpoint on designing and implementing a clinical trial. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5:84-98.

4. Kaufmann P, Levy G, Thompson JL, et al. The ALSFRSr predicts survival time in an ALS clinic population. Neurology. 2005;64:38-43.

5. Castrillo-Viguera C, Grasso DL, Simpson E, et al. Clinical significance in the change of decline in ALSFRS-R. Amyotroph Lateral Scler. 2010;11:178-180.

6. Lublin FD, et al. Defining the clinical course of multiple sclerosis. Neurology. 2014;83:278-286.

7. Confavreux C and Vukusic C. Natural history of multiple sclerosis: a unifying concept. Brain. 2006;129:606-616.

8. Chataway J. Tackling progression in multiple sclerosis. Editorial. The Lancet Neurology June 2018.

9. Harris, VK, et al. Characterization of autologous mesenchymal stem cell-derived neural progenitors as a feasible source of stem cells for central nervous system applications in multiple sclerosis. Stem Cells Transl Med. 2012;1:536-547.

10. Martins LF, et al. Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF. Scientific Reports. 2017;7:4153. DOI:10.1038/s41598-017-03592-1; 11.

11. Rivera FR and Aigner L. Adult mesenchymal stem cell therapy for myelin repair in multiple sclerosis. Biol Res. 2012;45:257-268.