Funding opportunities

Funding Type: 
Strategic Partnership III Track A
Grant Number: 
Principle Investigator: 
Funds requested: 
$14 323 318
Funding Recommendations: 
Grant approved: 
Public Abstract: 

The proposed project is designed to assess the safety and preliminary activity of escalating doses of human embryonic stem cell derived oligodendrocyte progenitor cells (OPCs) for the treatment of spinal cord injury. OPCs have two important functions: they produce factors which stimulate the survival and growth of nerve cells after injury, and they mature in the spinal cord to produce myelin, the insulation which enables electrical signals to be conducted within the spinal cord.

Clinical testing of this product initiated in 2010 after extensive safety and efficacy testing in more than 20 nonclinical studies. Initial clinical safety testing was conducted in five subjects with neurologically complete thoracic injuries. No safety concerns have been observed after following these five subjects for more than two years. The current project proposes to extend testing to subjects with neurologically complete cervical injuries, the intended population for further clinical development, and the population considered most likely to benefit from the therapy. Initial safety testing will be performed in three subjects at a low dose level, with subsequent groups of five subjects at higher doses bracketing the range believed most likely to result in functional improvements. Subjects will be monitored both for evidence of safety issues and for signs of neurological improvement using a variety of neurological, imaging and laboratory assessments.

By completion of the project, we expect to have accumulated sufficient safety and dosing data to support initiation of an expanded efficacy study of a single selected dose in the intended clinical target population.

Statement of Benefit to California: 

The proposed project has the potential to benefit the state of California by improving medical outcomes for California residents with spinal cord injuries (SCIs), building on California’s leadership position in the field of stem cell research, and creating high quality biotechnology jobs for Californians.

Over 12,000 Americans suffer an SCI each year, and approximately 1.3 million people in the United States are estimated to be living with a spinal cord injury. Although specific estimates for the state of California are not available, the majority of SCI result from motor vehicle accidents, falls, acts of violence, and recreational sporting activities, all of which are common in California. Thus, the annual incidence of SCI in California is likely equal to or higher than the 1,400 cases predicted by a purely population-based distribution of the nationwide incidence.

The medical, societal and economic burden of SCI is extraordinarily high. Traumatic SCI most commonly impacts individuals in their 20s and 30s, resulting in a high-level of permanent disability in young and previously healthy individuals. At one year post injury, only 11.8% of SCI patients are employed, and fewer than 35% are employed even at more than twenty years post-injury (NSCISC Spinal Cord Injury Facts and Figures 2013). Life expectancies of SCI patients are significantly below those of similar aged patients with no SCI. Additionally, many patients require help with activities of daily living such as feeding and bathing. As a result, the lifetime cost of care for SCI patients are enormous; a recent paper (Cao et al 2009) estimated lifetime costs of care for a patient obtaining a cervical SCI (the population to be enrolled in this study) at age 25 at $4.2 million. Even partial correction of any of the debilitating consequences of SCI could enhance activities of daily living, increase employment, and decrease reliance on attendant and medical care, resulting in substantial improvements in both quality of life and cost of care for SCI patients.

California has a history of leadership both in biotechnology and in stem cell research. The product described in this application was invented in California, and has already undergone safety testing in five patients in a clinical study initiated by a California corporation. The applicant, who has licensed this product from its original developer and recruited many of the employees responsible for its previous development, currently employs 17 full-time employees at its California headquarters, with plans to significantly increase in size over the coming years. The successful performance of the proposed project would enable significant additional jobs creation in preparation for pivotal trials and product registration.

Review Summary: 

Executive Summary

This application proposes to use embryonic stem cell-derived neural cells, called oligodendrocyte progenitor cells (OPCs) to treat patients with spinal cord injury (SCI). An initial Phase 1 trial has been conducted in patients with injuries to the thoracic region of the spinal cord. The current proposal is to treat patients with injuries to the cervical region of the spinal cord, which is the patient population considered most likely to benefit from the therapy. The project plan comprises a Phase 1/2a clinical study that will test several increasing dose levels of the candidate therapeutic and assess safety and look for signs of neurological improvement. In addition, the project plan includes manufacturing and assay development activities in preparation for later stage clinical development.

Significance and Impact

- Spinal Cord Injury (SCI) is a devastating medical condition with no available treatment at the present time. If therapeutically effective, the proposed therapy could have a highly significant impact on the treatment of SCI.

- A positive result with the proposed therapy would become a high visibility achievement for the entire field of stem cell-based/regenerative medicine.

- The Target Product Profile is adequate and well-conceived and identifies reasonable goals for the disease indication and the desired activity, efficacy, safety and dosing of the intended therapeutic.

- The high long term costs associated with care of patients with SCI support the development of a treatment that will provide even a modest improvement in patient cost of care.

- The proposal is highly responsive to the RFA, using an embryonic stem cell-derived cell therapy to treat spinal cord injury.

- While there are no approved treatment options for patients with SCI, there are a number of ongoing clinical trials to treat SCI, including some with competing cell therapy products.

Scientific Rationale and Risk/Benefit

- The rationale behind the selection of SCI patients with cervical injuries as the target population is sound. The proposed dose range is also well justified.

- The proposed study builds upon the safety profile demonstrated by an earlier Phase 1 study in patients with SCI. The availability of clinical data is a strength of the proposal, and there is preliminary evidence for safety in humans.

- Some reviewers questioned the strength of the preclinical efficacy data.

Therapeutic Development Readiness

- Clinical grade material is available that has been used in a previous trial so manufacturing for this phase 1/2a study has already been completed.

- The regulatory path has been identified and the preclinical plan to support the proposed phase 1/2a study has largely been completed.

Design and Feasibility

- The design and feasibility of the proposed clinical study is appropriate with realistic timeframes, achievable milestones, and well defined go/no go decision points.

- The previous clinical experience along with the current availability of sufficient cell therapeutic to support the proposed study make the goal of completing the trial very reasonable.

- Reviewers felt that the choice of patient population is wise as it improves the likelihood of seeing benefit and because there are good outcome measures. The inclusion and exclusion criteria are appropriate.

- The proposed Phase 1/2a study is a key and necessary study in the development of the proposed therapeutic candidate for spinal cord injury.

- The proposal includes plans to make manufacturing changes to support future development during the award period. Reviewers expressed concern regarding the manufacturing plan and strategy to support future development, which they viewed as risky.

Principal Investigator (PI), Development Team and Leadership Plan

- Reviewers praised the quality of the team and the significant expertise and experience represented. It is likely that the project will be carried out effectively and as planned.

- The PI has an excellent track record in the field of stem cell biology.

- The clinical investigators have excellent track records in this field and are highly capable of conducting the proposed trial.


- Some reviewers felt that the budget is appropriate for the proposed project and activities. Others commented that the CRO/Clinical Management costs in the budget may be high considering the small number of patients to be enrolled in the study.

Collaborations, Assets, Resources and Environment

- Appropriate assets and resources are in place.

- Clinical sites are excellent with track records in SCI, appropriate imaging facilities and clinical center infrastructure.

  • Hassan Movahhed
  • Stewart Abbot
  • Warren Sherman