The FDA has given the green light to a first-ever clinical trial to assess the ApoGraft technology for haploidentical bone marrow transplantations to be conducted at Washington University School of Medicine in St. Louis. Sponsor is Cellect Biotechnology Ltd., (NASDAQ: APOP) an Israeli developer of innovative technology enabling functional selection of stem cells. The potential is huge in that their technology, if proven, could pave the way to enable researchers and pharma with tools to rapidly isolate stem cells in quantity and quality powering stem cell-based treatments and procedures in a wide variety of applications in regenerative medicine. But a review of finances shows risk.
Washington University School of Medicine St. Louis and Cellect executed an Accelerated Clinical Trials Agreement back in July, 2019. The market forces driving Cellect’s opportunity hypothesis: the FDA anticipated 200 cell-therapy-based INDs annually as the age of regenerative medicine approaches—in response, the FDA anticipates hiring 50 reviewers to focus on cell-based therapies. Cellect presents that up to 10 to 20 cell and gene-based therapy approvals per annum will be the norm by 2025. There will be a big demand for ventures that can produce high-quality stem cells efficiently and economically.
Underlying Elements of ApoGraft Technology
According to Cellect’s website, their ApoGraft Technology turns production of stem cells into a simple, safe and inexpensive process. Cellect positions itself at the forefront of the “Regenerative Medicine” market. As we move into the heart of the 21st century, Cellect positions a profound shift in medicine now occurs. Instead of using drugs, chemistry or radiation in trying to repair unhealthy cells, tissues and organs, regenerative medicine is all about replacing these bad or unhealthy cells with new ones.
While Cellect notes there are hundreds of emerging novel treatments in various clinical trial stages—they all share the same challenge. The lack of raw materials. Cellect informs us that unlike 3D printing, regenerative medicine requires the use of stem cells as building blocks for creating replacement. We all have stem cells in our bodies, but they are very scarce and different to isolate from mature cells. A stem cell isolation and harvesting process is complicated, taking weeks and costing hundreds of thousands of dollars and actually is often toxic to the patient.
Current procedures are far from enabling safe and affordable stem cells for revolutionary treatments for mass numbers of patients. Enter Cellect, which positions its ground breaking technology for safe and cost effective production of stem cells to solve this critical barrier to regenerative medicine for the masses. They leverage over 15 years of research behind ApoGraft technology.
Hematopoietic Stem and Progenitor Cells (HSPCs)
HSPCs are key—a renewable pool of precursors that generate the immune and hematopoietic systems throughout life, exist primarily in the bone marrow but also in the blood (including umbilical cord blood). Responsible for the constant renewal of blood and immune system cells (e.g. lymphocytes, monocytes and macrophages, neutrophil, erythrocytes, and platelets), a small number of these HSPCs can expand to generate a very large quantity of daughter HSPCs. This phenomenon is used in bone marrow transplantation when a small number of HSPCs reconstitute the hematopoietic system.
The physiological site of HSPC is the marrow of long bones and vertebrae of adults—approximately 1 in every 10,000 to 15,000 bone marrow cells is thought to be a stem cell. They may pass the bone marrow barrier, and hence may travel in the blood from the bone marrow in one bone to the other. Only a small number of progenitor cells circulate in the bloodstream and the proportion in the blood is very low. The ability to harvest directly from peripheral blood is augmented by injecting granulocyte-colony stimulating factor (GCSF) prior to harvesting.
What is the Regulatory Status of ApoGraft?
It has received orphan drug designation status from the FDA; its commercial sponsor—Cellect—has requested to the FDA that it be designated a Regenerative Medicine Advanced Therapy (RMAT) under the 21st Century Cures Act. The RMAT designation is intended to facilitate expedited development, review, and approval for important new regenerative medicine therapies for which preliminary evidence indicates the potential to address a serious life-threatening disease or condition. RMAT-designated products may be eligible for priority review and accelerated approval—thus dramatically shortening time to market and commercial value.
Commencing December 31, 2019, the Washington University School of Medicine St. Louis study will involve 36 participants. Titled “A Phase I Study of ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients,” the study puts the Cellect ApoGraft regenerative technology to the Phase I test.
The Fundamental Challenge
When a patient needs an urgent hematopoietic stem cell transplantation (HSCT), finding a donor remains a challenge. The ability to obtain half matched stem cells from any family member represents a significant breakthrough in the field.
Haploidentical haplo-HSCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post-transplant cellular immunotherapy. However, significant risks are involved as haplo-HSCT has a high risk of GRAFT versus Host Disease (GvHD) and poor immune reconstitution when GvHD is prevented by all existing methods of vigorous ex vivo or in vivo T-cell depletion.
Consequently, researchers have employed different approaches to investigate how to mitigate complications such as graft rejection, severe GvHD, and prolonged immune suppression. Novel experimental utilization of T regulatory cells, alloreactive natural killer (NK) cells and other T cell subsets represent significant promise, according to Cellect.
Hypothesis of Study
The Cellect ApoGraft is based on the findings that GvHD can be prevented by Fas receptor mediated selective depletion of T cell subsets, ex vivo. The clinical investigative team hypothesizes that the use of ApoGrafts for haplo-HSCT will be safe, and reduce rates of GVHD without affecting Graft-versus-Leukemia (GvL).
Who is Cellect Biotechnology?
Publicly traded in NASDAQ as “APOP,” this venture is based out of Israel. The company presently trades at $2.30 per share with a very low market capitalization—rendering the firm near penny stock status. 54% of the company is held by insiders and the two largest external shareholders include Renaissance Technologies, LLC and Wedbush Securities, Inc. Wedbush Securities, Inc.
In their most recent quarterly earnings, they reported a quarterly loss of $1.4 million ($0.01 per share) compared to $1.9 million last year. They report to posses about $6 million in cash. It should be noted that they are exploring options to maximize shareholder value, which could represent a M&A, business combination, in-licensing or other strategic transaction. They appear to be very prudent with precious cash reserves and undoubtedly are addressing a major nascent market. TrialSite News‘ takeaway is the forthcoming study represents a solid business development opportunity for the venture—e.g. successful results could lead to business opportunity via partnership, etc.
Zhifu Xiang, MD, PhD, of Washington University School of Medicine and Associate Professor in the Division of Oncology’s Bone Marrow Transplantation & Leukemia Section in the Department of Medicine
John Dipersio, M.D, Ph.D., chief of the Division of Oncology in the Department of Medicine at Washington University.Source: Yahoo Finance