Funding opportunities

Multicenter Ph2b Trial of [REDACTED] for Dual Cord Blood Transplantation in Patients with Hematological Malignancy or Myelodysplastic Syndrome

Funding Type: 
Strategic Partnership III Track A
Grant Number: 
Funds requested: 
Funding Recommendations: 
Recommended if funds allow
Grant approved: 
Public Abstract: 
We are a California corporation that has a broad platform technology applicable to all cell therapy and much of regenerative medicine. While other companies concentrate on developing a particular cell type for therapy (what we refer to as the "hardware") Our technology ensures that the cells go where they need to go once they are placed in the body (what we refer to as the "software"). Our product is an enzyme that is used to treat cells before they are placed in the body. The enzyme places a sugar on the surface of the cell that acts like a GPS signal to the body and directs the cells to sites of inflammation, ischemia or tissue damage. Our first clinical indication is for stem cell transplantation in patients with hematological malignancies. This uses adult stem cells obtained from umbilical cord blood. We have safety and preliminary efficacy data from 16 patients as part of an ongoing clinical trial. These results will be presented in December at the American Society for Hematology (ASH) meeting. The purpose of the current proposal is to extend these very promising results to a multicenter trial that includes California clinical sites. If we can repeat our current results in a randomized trial that includes multiple clinical sites then we will have a clinical proof of concept for our platform technology that will allow us to complete corporate partnership deals and launch additional trials for other cell types and disease states.
Statement of Benefit to California: 
The company has been operating in a virtual mode (i.e., operating primarily through subcontractors) in order to mitigate costs until it could begin clinical trials. The lead product is currently in an investigator-sponsored IND for stem cell transplantation in patients with hematological malignancies. This involves treating umbilical cord blood, an adult stem cell source, prior to infusing the cells into the patient. To date, 16 patients have been transplanted with treated cells and safety and strong preliminary data on efficacy have been obtained. The intent of the current proposal is to start a multi-center trial that will include clinical sites in California, one of which has already been recruited. The potential benefits to the State are both health-related and economic. According to the American Cancer Society, in 2013 there are estimated to be 5,210 cases of leukemia, 7,280 cases of non-Hodgkin's lymphoma, 2,270 cases of myeloma and 990 cases of Hodgkin's lymphoma in California. Our technology has the potential to make stem cell transplants safer and more effective for these patients. Further, if we can confirm our current clinical efficacy data in a multicenter trial, we will have established proof of concept for our technology. This will allow for rapid follow on trials for a variety of cell types and disease states for which we currently have preclinical data. This will allow the company to transit from its virtual mode to a mid-size biopharma company, providing jobs and economic benefit to California. Approval of our lead compound for stem cell transplantation will allow us to complete deals with major pharmaceutical companies, to grow and expand its technologies, and to extend its relationships with major clinical sites as it matures into an independent biopharma company located in the State of California.
Review Summary: 
Executive Summary Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment strategy for restoring normal hematopoietic function in patients with select hematologic malignancies after high dose chemotherapy. Umbilical cord blood (UCB) as a source of hematopoietic stem cells (HSC) has a number of advantages compared to other stem cell sources but is hampered by the low cell dose, which results in slower engraftment and an elevated risk of engraftment failure. The objective of this proposal is to further clinical development of a technology to improve engraftment of HSC obtained from umbilical cord blood, for use in patients with hematological malignancies requiring a stem cell transplant. The proposed approach involves ex vivo enzymatic modification of the stem cells prior to transplantation to enhance homing to bone marrow, with the goal of enhancing engraftment and overcoming the reduced time to recovery typically observed with cord blood transplants. The applicant proposes to conduct a Phase 2b, randomized, multicenter study of the safety and efficacy of the approach in patients with hematologic malignancies or myelodysplastic syndromes receiving dual cord blood transplants. Project-related activities will include production of sufficient quantities of product to complete the multicenter trial. Significance and Impact - It would be a significant advancement if cord blood could be used with greater assurance of engraftment; if the delayed HSC engraftment associated with UCB could be overcome; UCB could become the preferred source for HSCT. - While some reviewers thought that the effect of the proposed approach would be incremental, others disagreed, arguing that any significant improvement in time to engraftment would be clinically meaningful and would be a notable advancement in the field, arguing even that the proposed approach could have a ‘game-changing’ impact on the transplant field and could change the practice of medicine. - This is a novel approach and it is reasonable to move forward although there are other competing approaches under development. - The advantage of the proposed technology over other technologies in development is that the other approaches require unique central processing capabilities whereas the proposed technology is very straight forward, practical, and useable. - The anticipated effects on engraftment could translate into improved patient survival and reduced hospital stay, potentially leading to reduced costs and improved quality of life. - The TPP is not well done and does not clearly delineate the optimal from minimal product attributes. - The application of this technology within the continuum of care was viewed as a strength of the approach. Scientific Rationale and Risk/Benefit - Strong scientific rationale and a favorable benefit/risk ratio for this stage of development have been adequately demonstrated. - Data from appropriate and well-designed preclinical proof of concept studies provide a convincing scientific rationale for the approach and for development of the product. - Preliminary clinical data suggest that the product is safe and may be efficacious. However, key information was missing from the application, which impacted interpretation of the Phase 1/2a data. Therapeutic Development Readiness - The IND has received FDA clearance and an initial Phase 1/2a trial is ongoing. - The FDA has not yet provided feedback regarding the acceptability of the proposed Phase 2 trial. Design and Feasibility - A flaw in the design of the Phase 2 clinical study is that the patient preparation regimen as currently defined introduces a confounding variable. The applicant will need to stratify for that confounding variable at the time of randomization. - The application did not contain a justification of sample sizes; there is no assurance that the study is powered appropriately to demonstrate a clinical meaningful effect. - Reviewers questioned several aspects of the trial design such as the broad age range of patients to be included in the study. However, they commented that these study design problems are potentially correctable. - While some reviewers questioned the enrollment assumptions and felt it may be difficult to complete the study in the proposed 4-year time frame, others commented that the timeline seems feasible if anticipated additional sites are initiated early in the development timeline. - The proposed therapeutic approach is straightforward, practical and usable. - The regulatory pathway is straightforward and the product has been granted orphan drug status. - It was acknowledged that many of the criticisms and issues might be addressable in the near future as additional information became available. - Enthusiasm for the application was dampened by the fact that it was poorly written and contained numerous errors and inconsistencies. Principal Investigator (PI), Development Team and Leadership Plan - The lead clinical investigator is an outstanding investigator with strong experience in UCB transplantation and is probably the ideal clinician to lead the proposed Phase 2 clinical trial. - The applicant has assembled a good team; the development team is experienced in both translation of novel technologies and expert in the current technology. - The clinical sites involved are all world class with reputable investigators and extensive experience in running trials. - The study design contained a number of errors and inconsistencies which reduced confidence in the PI. Budget - Some aspects of the budget may be low, although other aspects are appropriate. Collaborations, Assets, Resources and Environment - No concerns.
  • Carol Danielson
  • Stewart Abbot

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