BLIMP BioPharma, Inc.
Blimp-1 is a protein that has over 900 published articles detailing its role as a master regulator of cell growth, differentiation, migration and survival. Above is a cover article that outlines the role of Blimp-1 in one key part of the immune system, T-Cells. Blimp-1 also regulates another key member of the immune system, B-cells as discussed below. In many types of cancer, B & T-cells become transformed into cancer cells by a de-regulation of the Blimp-1 protein.
Blimp BioPharma, Inc. is leveraging this wealth of information in cancer cell formation as well as a variety of proprietary positions, to develop products that will modulate Blimp-1 protein to effectively re-regulate the immune systems response to cancer. This is call “Immunotherapy’. Immunotherapy has recently become a major thrust in cancer therapy, because a fully functioning immune system can help destroy cancer cells. In many cancers, the immune system (including T-cells and B-Cells) is suppressed by cancer cell production of immune suppressor proteins, including Blimp-1 protein.
Immunotherapy was recently identified as an extremely large $200 billion market opportunity.[1]
Blimp-1 modulation is both immunotherapy and biological therapy, targeting the cause of cancer and re-establishing the immune system anti-cancer systems to be a potentially curative therapy. By deploying targeted drug delivery systems to deliver immunotherapy, biotherapies and if needed chemotherapies, Blimp BioPharma is developing new types of drugs that can deliver the right drug at the right time to the right place, thus overcoming the deficiencies of conventional drugs that are not curative and extremely toxic.
Blimp BioPharma has formed several key partnerships with academic and commercial companies to develop potentially curative new drugs. Blimp BioPharma’s lab is located in the UC-Davis Innovation center is Davis, CA, as a featured Venture Catalyst Company associated with the UCD Office of Research.
About the Company
BLIMP BioPharma is a development stage drug company focused on treating diseases, such as cancer, caused by the under- or over-expression of the PRDM1 gene and BLIMP-1 protein. Our goals are to develop compelling proof that our products work in vitro and in vivo. Next, we intend to select a strategic partner that will buy the rights to develop and commercialize our products. We have many product opportunities based upon a broad and deep technology and intellectual property platform.
BLIMP BioPharma Techology and Product Opportunity
As the B-Lymphocyte Inducing Maturation Protein 1 (BLIMP1) name implies, this protein is responsible for translating immune system signaling to a large number of genetic pathways that control the differentiation of blood stem cells (progenitor B-cells) into very specific immune cells that are called plasma cells. Plasma cells make antibodies as a normal part of the immune system response to foreign substances, such as microbes, toxins and bad or dysfunctional cells. The normal functioning of PRDM1/ BLIMP1 is illustrated in the figure below.
In a large number of scientific studies, the normal functioning of BLIMP-1 as a “Master Regulator” of cell proliferation, differentiation, survival, cell mobility and migration has been demonstrated. Over-expression of the PRDM1 gene and BLIMP-1 protein can result in transformation of a stem cell to a cancer stem cell and subsequently, hyper-mutable tumor cells. Over-expression of BLIMP-1 provides a persistent message to produce new cells, with the properties of increased survival, the ability to metastasize, implant and form a set of protected cancer cells at distant locations in vital tissue. These hallmarks of cancer have been demonstrated to be associated with this gene and protein in a large number of cancers.
BLIMP BIOPHARMA’s First Product Candidate
We are working in conjunction with UC-Davis in the development of a targeted drug delivery system for bone cancer. Our UCD technological relationship is with Dr. Kit Lam, a hematologist/oncologist and specialist in bone cancer, especially myeloma, which is our first cancer target.
Dr. Lam is Chairman of the Department of Biochemistry and Molecular Biology at UC Davis in Davis, CA (https://basicscience.ucdmc.ucdavis.edu/Lam_Lab/). His lab has developed methods to target any type of cell with a nanoparticle carrying a drug payload, which comprises a targeted drug delivery system (see https://basicscience.ucdmc.ucdavis.edu/Lam_Lab/projects.html). Below is an illustration of this type of delivery system, using a liposome as the carrier of a drug, siRNA or both.
This Targeted Drug Delivery System carries two drug payloads, a conventional drug and a drug that blocks DNA from making a protein such as BLIMP-1, which is over produced in bone cancer
Variations in the expression of BLIMP-1 protein results in life-threatening pathologies, such as blood cancers, e.g., myeloma[2], leukemia[3], lymphoma[4] and epithelial cells cancers such as breast[5], lung[6] and colorectal cancer.[7]
Many scientific studies have measured the level of PRDM1/ BLIMP1 dysregulation in a variety of cancers. In almost all myelomas, BLIMP1 is over-expressed. As shown below, Lin, et. al reported that knockdown of PRDM1/ BLIMP1 expression causes apoptosis in multiple myeloma cell lines and plasmacytoma cells. However, Lin indentified that the apoptotic response was mediated by the knockdown of BLIMP1 which induced the pro-apopotic protein Bim, reduced the anti-apoptotic protein Mcl-1 and activated caspase 3 and caspase 9.[8]
Most importantly, RNA inhibition of BLIMP1 can increase myeloma cell death in combination with a standard of care drug, Velcade (bortezomib) as shown below. This is important to the success of BLIMP1 inhibition in clinical trials as BLIMP1 may be used in patients refractory to Velcade as well as in combination. Lin, et. al., summed up the actions of BLIMP1 in the text below.
BLIMP1 IS A VALIDATED TARGET IN OTHER CANCERS
· In lymphomas, PRDM1/ BLIMP1 is under-expressed in a large number of cases (more than 50% of DLBCL) and over-expressed in other forms of B and T cell lymphomas.
· In lung cancer, studies indicate that PRDM1/ BLIMP1 is over-expressed in 90% of cases of squamous cell carcinoma, the most common form of lung cancer.
· In colon cancer cells, PRDM1/ BLIMP1 over-expression has been treated in vitro by the use of short interfering RNA molecules that block the expression of the PRDM1/ BLIMP1 gene and protein. This inhibition of the BLIMP1 protein results in cell death via the apoptotic pathway.
In a recent report by Yan, et.al., PRDM1/ BLIMP1 was shown to bind to the p53 promoter and represses p53 transcription in colon cancer cells. Yan showed that knockdown of PRDM1/ BLIMP1 in these same cells and in primary human fibroblasts results in apoptosis and cell cycle arrest. This effect was confirmed to be the result of elimination of the PRDM1/ BLIMP1 repression of p53 and allowing a normal cell death, via the p53 apoptotic pathway, to be invoked.[9]
Intellectual Property
The BLIMP BioPharma business opportunity is protected by issued and pending patents that describe the ability to combine a targeted drug delivery system and therapeutic payload that can effectively and selectively destroy cancer cells. BLIMP BioPharma’s business strategy is to develop ‘first in class’ products that inhibit protein expression in cancer cells. BLIMP BioPharma has new IP in preparation that covers methods of inhibition, including small molecules, microRNA and RNAI therapeutic compounds.
Product Development and Financial Plan
BLIMP BioPharma’s financial plan incorporates product candidate development within the company’s affiliated, small pre-clinical lab and with business partners capable of moving the product candidate through pre-clinical studies and preparation of an application to test the product in humans via an investigational new drug (IND) filing with the FDA. The company intends to sell product candidates via a product development license to biopharmaceutical companies. Product licenses at early stages in development will enable BLIMP BioPharma to fund new product development.
As the company matures, the intent is to develop products with higher valuations by testing each successive product candidate in the later stages of product development. This strategic pathway may allow the company to build a large pipeline of cancer products, with the possibility of having each product generate increasing larger upfront license fees, milestone payments and royalty-based income.
BLIMP BioPharma met with potential strategic partners at the Life Sciences Innovation Northwest Meeting in Seattle, including pharmaceutical companies, Pharma VCs, other VCs and angels as well as institutions that expressed an interest in working with or helping the company locate in Seattle.
Strategic Partners
Biopharmaceutical companies, our potential strategic partners, have demonstrated a large appetite for products such as BLIMP BioPharma (BBP) is developing. Large drug companies are seeking ‘first in class’ drugs in this category of therapeutic innovation for a variety of reasons, including the important recognition that products like BBP’s can inhibit proteins that cause cancer. This approach was thought to be ‘undruggable’ in the past. BBP’s product opportunities are under review at several Pharmacos.
Management Team
The BLIMP BioPharma management team has extensive experience in developing new products and partnering with biopharma companies. BBP’s executive/consultant team includes industry veterans with decades of experience in pharmaceutical product development, marketing and strategic business development. Dr. Lonnie Bookbinder leads BBP’s management team. Lonnie started his award-winning career at Lederle Labs (now Pfizer) in marketing, sales and clinical research. Lonnie migrated to the biotechnology arena as Director on the In Vivo Business Unit at Immunomedics (a public monoclonal antibody company), served as VP of Corporate Development at Ribi ImmunoChem (now GSK) and most recently was COO, CEO and founder of several oncology based companies. Dr. Bookbinder led the business development teams of these companies to multiple high value pharmaceutical strategic partnerships. On behalf of BBP, Lonnie works with a patent attorney with a PhD in molecular biology; a medicinal chemist with extensive experience in molecular biology and small molecule development; two clinical oncologists specializing in myeloma, as well as in vitro myeloma stem cell and BLIMP1 transgenic mouse myeloma models. In addition, Lonnie works with consultants in business development and targeted drug delivery systems, a hematopathologist and a director of a NYC cancer center.
Summary
In summary, BLIMP BioPharma has a very unique opportunity to be a leading participant in the growth and development of the personalized medicine field through the development of products that are highly specific to an individual’s cancer. The technology and product development strategies the company is deploying may lead to a much higher level of survival in cancer patients with a chance for curative therapy as a result of the company’s focused efforts.
The initial milestones of fund-raising, management team formation and filing of new proprietary positions is currently underway giving a fast start to corporate development. The next set of milestones is the completion of ‘ in vivo, proof of concept’ studies in animal models of cancer. To this end, BBP has formed a strategic partnership with two institutions, and their leading oncologists in myeloma to move forward with pre-clinical and clinical studies of BLIMP1 inhibition in myeloma. Similarly, an oncology collaboration with the NCI, Columbia and Weill Cornell Medical Schools is primed and awaiting funding.
In these settings, there will be submissions of grant proposals to the NCI and foundations to gain non-dilutive support as well as the support of biopharmaceutical companies VC groups for early entry into relationship with BLIMP BioPharma. The company is currently entertaining several offerings that may allow locally-based funding by economic development agencies and angel investors.
The future of BLIMP BioPharma is entrenched in a rich, deep and broad platform of business opportunities. BLIMP1 actions and activities were first uncovered at Harvard and Stanford by pre-eminent scholars. Since the initial discoveries over 900 papers have been published on PRDM1/BLIMP1 gene and protein. In addition to multiple oncology product opportunities, modulation of BLIMP1 protein is anticipated in a variety of other diseases in auto-immune diseases, vaccines, dermatology and other indications. The initial focus on cancer will be followed by products for other diseases caused by de-regulation of the Blimp-1 protein.
Contact Information:
Lonnie Bookbinder, MBA, PhD., CEO
Cell: 425 394 3774
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[1] http://moneymorning.com/2016/03/22/how-to-profit-on-the-200-billion-immunotherapy-market/
[2] Blood.2009 Jun4;113(23):5911-9.
[3] Leukemia Lymph 2008Mar; 49(3):477-87.
[4] Nucleic Acids Res 2010 April 26 (online)
[5] Mol Cell Biol 2009 Jul; 29, (14): 3832-44.
[6] Zhonghua 2007 Nov1;173(9):5361-71
[7] PNAS 2007 104(6): 1841-1846Leukemia Lymphoma
[8] Cancer Res 2007 Dec 15;67(24):11914-23
[9] Proc Natl Acad Sci 2007 February 6; 104(6);1841-6