Boarding PassThis company is fighting against cancer drug resistance
Boarding Pass
This company is fighting against cancer drug resistance
UB-Therapeutics has raised nearly half a million dollars to address the issue of drug resistance in multiple myeloma cancer
“The idea for our approach was born out of a critical need to address the issue of drug resistance in multiple myeloma,” explained UB-Therapeutics. “We noticed that existing drugs targeting proteasome activity were initially effective, but patients developed resistance to them over time. This presented a significant challenge in the treatment of this disease.”
Multiple myeloma is a relatively uncommon cancer, accounting for about 10% of all hematological cancers. In the U.S., multiple myeloma accounts for about 1.8% of all new cancer cases. It primarily affects the elderly, with a median age at diagnosis of around 70 years. “The rising prevalence of hematological cancer is estimated to enhance the multiple myeloma market's growth rate. Furthermore, the rising geriatric population and an increasing number of obese populations will expand the multiple myeloma market.
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Dr. Dima Ghannam-Shahbari, Dr. Liora Sklair-Tavron, and Prof. Ashraf Brik, Ph.D.
(Photo: N/A)
“Eventually, we conceived the concept of inhibiting proteasome activity by binding to ubiquitin, a novel approach that hadn't been explored extensively in the context of multiple myeloma,” the company added.
While its product doesn’t exist yet, the founders expect to enter the ‘first-in-human’ trial within three years. You can learn more about their journey below.
Company Name: UB-Therapeutics
Sector: Healthcare
Product/Service description:
Our cancer treatment technology: novel cyclic peptides with potent anti-cancer activity. These peptides represent a promising approach to combat cancer by specifically targeting ubiquitin protein chains and disrupting their function.
Crafted with precision, our cyclic peptides are compact and incorporate non-proteinogenic amino acids, along with unique non-canonical features like N-methylation. These attributes enable them to tightly bind Lys48-linked Ubiquitin chains, a crucial element in cancer cell proliferation.
Unlike conventional small molecule, proteasome inhibitors like bortezomib, which directly target the proteasome's catalytic subunit, our cyclic peptides operate differently. They interfere with the recognition and subsequent proteasomal degradation of ubiquitinylated proteins, offering potential therapeutic advantages and circumventing resistance issues.
Extensive in vitro and in vivo studies showcase the efficacy of our cyclic peptides in blocking deubiquitinases and the proteasome, prompting apoptosis in cancer cells. Notably, they exhibit comparable activity to small molecule proteasome inhibitors while acting via a distinct mode of action.
Founder Bios:
Founder Prof. Ashraf Brik & CEO Dr. Dima Ghannam Shahbari:
Ashraf Brik is a Professor of Chemistry at the Schulich Faculty of Chemistry at the Technion-Israel Institute of Technology. Brik received his B.Sc. in Chemistry from the Ben-Gurion University of the Negev (1993-1996) and his M.Sc. degree in Organic Chemistry in 1998 from the Technion-Israel Institute of Technology.
Year of Founding: 2023
Last Investment Round: $415,415.25
Last Investment Stage: Pre-Seed
Date of Last Investment: February 2023
Total investment to date: $415,415.25
Investors (leading and all): Israel Innovation Authority
Current number of employees: 4
Open positions: N/A
How was the idea born?
The idea for our approach was born out of a critical need to address the issue of drug resistance in multiple myeloma. We noticed that existing drugs targeting proteasome activity were initially effective, but patients developed resistance to them over time. This presented a significant challenge in the treatment of this disease.
To overcome this problem, we explored a different mode of action. Our team brainstormed and researched various possibilities.
Eventually, we conceived the concept of inhibiting proteasome activity by binding to ubiquitin, a novel approach that hadn't been explored extensively in the context of multiple myeloma.
Taking this idea further, in collaboration with Prof. Hiroaki Suga we decided to focus on developing cyclic peptides, our objective was to identify a cyclic peptide that could directly bind to ubiquitin, thereby promoting the accumulation of specific proteins within cells. This accumulation, in turn, triggers a process known as programmed cell death, also referred to as apoptosis.
To identify the most promising candidate, we screened a wild cyclic peptide library and meticulously evaluated various compounds.
The potential application of this cyclic peptide as a targeted therapy for multiple myeloma and other relevant diseases holds great promise. By leveraging the cell's own natural processes, we aim to develop a more selective and effective treatment strategy that minimizes harm to healthy cells while efficiently eliminating diseased cells.
As with any innovative therapeutic development, we understand that more research and testing are required to ensure the safety and efficacy of this approach. Our team remains committed to advancing this groundbreaking discovery through further preclinical and clinical studies, with the goal of making a significant contribution to the field of oncology and improving patient outcomes.
What is the need for the product?
The product is a novel peptide-based protein degradation inhibitor drug candidate with a distinct mode of action for the treatment of MM. The distinct mechanism of action of this new drug candidate may be advantageous in terms of efficacy in patients that developed resistance to FDA-approved proteasome inhibitors (Velcade for example), drug safety profile, and avoidance of resistance mechanism associated with the other proteasome inhibitors.
This product is a chemical synthetic cyclic peptide(s) highly non-proteinogenic. It is a small peptide, with just 11 amino acids in the macrocycle, making it an undecamer cyclic peptide like cyclosporin (an immunosuppressant approved medication). The product can induce apoptosis in cancer cell lines in vitro and attenuate the growth of tumor cells in vivo. Cancer cells are highly dependent on proteasome activity to remove certain proteins and evade programmed cell death, which is behind the anti-cancer effects observed. The direct proteasome inhibitor, bortezomib (Velcade), and our product showed broadly similar effects and comparable efficacy.
The proposed new agent will be part of the armamentarium to treat multiple myeloma. The ways of administration and the combination with other drugs will be evaluated in the next pre-clinical studies.
Over the course of the project, two peptides will be evaluated, one will be selected for future work.
How is it changing the market?
One of the promising approaches to cancer treatment is finding molecules that bind specifically ubiquitin protein chains which could interfere with their function and therefore negatively affect cancer cells. In the presented technology, we have developed novel cyclic peptides with potential anti-cancer therapeutic activity. These peptides are small, have non-proteinogenic amino acids, and are rich in non-canonical features like N-methylation, which tightly bind Lys48-linked Ub chains. The cyclic peptides block the action of deubiquitinases and the proteasome, induce apoptosis in vitro, and attenuate tumor growth in vivo. Importantly, these cyclic peptides show in vitro and in vivo activity comparable to a small molecule proteasome inhibitor and similarly induce apoptosis in cancer cells. However, they act through a different mode of action. Whereas the immediate target of small molecules proteasome inhibitors such as bortezomib is the chymotrypsin-like β5 catalytic subunit of the proteasome, the cyclic peptides impair the recognition and subsequent proteasomal degradation of ubiquitinylated proteins. This different mechanism may have therapeutic advantages, as it can avoid the innate and acquired resistance associated with direct proteasome inhibitors.
How big is the market for the product and who are its main customers?
Multiple myeloma is a relatively uncommon cancer, it accounts for about 10% of all hematological cancers. In the United States, multiple myeloma accounts for about 1.8 percent of all new cancer cases (about 35,000 new patients were diagnosed in 2021). It primarily affects the elderly, with a median age at diagnosis of around 70 years. The rising prevalence of hematological cancer is estimated to enhance the multiple myeloma market's growth rate. Furthermore, the rising geriatric population and an increasing number of obese populations will expand the multiple myeloma market.
Data Bridge Market Research analyses that the multiple myeloma market was valued at USD 23.53 billion in 2021 and is expected to reach USD 38.94 billion by 2029, registering a CAGR of 6.50% during the forecast period of 2022 to 2029. Market, which is now controlled by Revlimid, an immunomodulator, and Velcade, a proteasome inhibitor.
Does the product exist already? If not - at what stage is it and when is it expected to hit the market?
The product doesn’t exist yet. We expect to enter the “first-in-human” trial within three years.
Who are the main competitors in this sector and how big are they?
Proteosome inhibitors are the main competitors.
According to Technavio's analyst, the proteasome inhibitors market size is expected to be valued at $2.2 billion by 2026 with a CAGR of 7.4%
What is the added value that the founders bring to the company and the product?
The founders of the company bring significant added value to both the company and the product through their expertise, experience, and achievements in their respective fields:
Prof. Ashraf Brik, Ph.D. (Founder) Prof. Ashraf Brik is a distinguished figure in the field of Chemistry, particularly in Bioorganic Chemistry. With a vast academic background and extensive research experience, he has made significant contributions to the development of chemical approaches for preparing modified proteins. His pioneering work in preparing ubiquitinated peptides and proteins has opened new possibilities in understanding the ubiquitin signal in health and disease. This breakthrough has immense implications in drug discovery and offers potential solutions for addressing drug resistance in various diseases, including multiple myeloma. His expertise, coupled with his numerous publications in top journals, international awards, and editorial roles, adds credibility and scientific excellence to the company's endeavors.
Dr. Dima Ghannam-Shahbari (CEO) Dima Ghannam-Shahbari brings valuable expertise as a Ph.D. biologist with a strong background in cancer research. Her extensive experience in both basic and translational research, encompassing various aspects of cancer biology and therapeutic approaches, is crucial for driving the company's mission forward. Her contribution to managing multiple projects, establishing new models, and guiding fellow researchers adds efficiency and organization to the company's research and development activities. Dima's academic achievements and experience in academia and industry make her a vital asset in overseeing the company's strategic direction and operations.
Liora Sklair-Tavron (Senior Consultant) Dr. Liora Sklair-Tavron is a seasoned professional with over 20 years of diverse research and development experience in the biopharmaceutical industry. Her expertise spans drug discovery, preclinical and clinical development, and regulatory affairs across various therapeutic areas. Dr. Sklair-Tavron's impressive career trajectory at several reputable bio-pharmaceutical companies demonstrates her capability in leading successful drug discovery initiatives and product development. With her strong academic background, postdoctoral studies at Yale University Medical School, and significant publication record, she adds valuable insights and guidance to the company's R&D projects. Additionally, her role as a project management consultant for biotech start-ups brings valuable industry knowledge and efficiency to the company's operations.
Overall, the founders' collective expertise in Chemistry, Biology, Cancer Research, Drug Discovery, and Product Development, along with their impressive academic achievements, international recognition, and industry experience, significantly enhance the company's potential for success. Their combined knowledge and contributions create a strong foundation for advancing innovative solutions and making a meaningful impact in various fields of medical research and drug development.
What will the money coming in from the round be used for?
It will be used for the development of a stable and effective formulation for our cyclic peptide, for the planning of our regulatory roadmap, and for R&D.
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