PRISM Q&A CORNER
Paul Romness, CEO, OS Therapies
OS Therapies: Addressing Unmet Needs in Rare Cancer while Delivering Value to Shareholders
Bone cancer is rare, accounting for just one percent of all cancer cases. Despite advances in treatments for other types of cancer, the standard of care for primary bone cancers has remained largely unchanged.
Primary bone cancer originates within the bone itself, developing on the surface, in the outer layer, or from the center. As the tumor grows, cancer cells multiply, destroying the bone. If left untreated, the cancer can spread to other parts of the body.
The most common types of bone cancer include osteosarcoma, which predominantly affects children and young adults in the bones of the leg or arm; chondrosarcoma, which typically occurs in the pelvis, legs, or arms of middle-aged and older adults; and Ewing sarcoma, which arises in the pelvis, legs, or arms of children and young adults.
Although osteosarcoma is the most common form of bone cancer, it is considered extremely rare, with around 1,000 Americans diagnosed each year. Nearly half of these cases occur in individuals under the age of 20, according to the American Cancer Society. Osteosarcoma is aggressive, with the cancer spreading to the lungs in 25% of patients, leading to low survival rates.
One emerging company, OS Therapies (NYSE-A: OSTX), has recently made headlines following its successful IPO and strategic progress in developing a novel treatment for osteosarcoma. We had the chance to speak with CEO, Paul Romness, to learn more about the Company’s exciting advancements in this critical area.
The FDA has approved nine drugs for bone cancers, including Amgen’s (AMGN) XGEVA® and Novartis’ (NVS) Zometa, but the majority of these are indicated for secondary bone cancer – cancer that has spread to the bones – or multiple myeloma, a bone marrow cancer. There is a significant unmet medical need for effective treatments for primary bone cancers. Can you talk about your treatment in development?
To say the unmet need is significant is an understatement. In fact, there haven’t been any new treatments for osteosarcoma in the past 40 years. OST-HER2 is an innovative immunotherapy using a HER2 bioengineered form of the bacteria Listeria monocytogenes (Lm) to trigger a strong immune response against cancer cells expressing HER2. This off-the-shelf treatment is designed to prevent metastasis, delay recurrence, kill primary tumors expressing HER2, and increase overall survival.
Our approach involves giving the body a biologic infection that stimulates the immune system to generate T-cells, which then seek out and destroy micrometastases. The immune system has the unique ability to identify and eliminate cancer cells, ensuring that only harmful cells are targeted. This is a crucial aspect of our treatment, as it leverages the body’s natural defense mechanisms to combat cancer effectively.
We’re incredibly proud of the progress we’ve made with our OST-HER2 program. Our Phase 2b trial in patients with recurred, resected osteosarcoma is fully enrolled with a total of 41 patients dosed across 21 clinical trial sites in the United States. We were thrilled to report positive interim data in June 2024, and anticipate topline data in the fourth quarter of 2024.
OST-HER2 has received Rare Pediatric Disease Designation (RPDD) from the FDA, as well as Fast Track and Orphan Drug Designations from both the FDA and the European Medicines Agency (EMA).
We are currently seeking Breakthrough Therapy Designation for OST-HER2 for osteosarcoma from the FDA, based on the data from our Phase 2b clinical trial. Upon receiving a Biologics License Application (BLA) approval, the Company will be granted a Priority Review Voucher (PRV) based on the RPDD. This is a very valuable asset, as the voucher entitles the bearer to a regulatory review in approximately six months, rather than the standard ten months. Since the introduction of PRVs in 2009, 31 have been awarded by the FDA, mostly for drugs to treat rare pediatric diseases. Of these, 17 were sold to another drug sponsor for prices ranging from about $67 million to $350 million.
Given the recent FDA approval of GSK’s Ojjaara for myelofibrosis, following GSK’s nearly $2 billion acquisition of Sierra Oncology, and the substantial revenues generated by Incyte’s Jakafi ($2.6 billion in FY 2023) and Bristol Myers Squibb’s (BMY) Inrebic ($19 million in Q4 2023) for myelofibrosis, what do you believe is the market potential and value for OST-HER2 in addressing the significant unmet need for effective treatments for primary bone cancers like osteosarcoma?
Without question it’s a very robust market. While we haven’t established the price yet, once commercialized, we see the market for the drug at around $500-700 million a year. The total addressable market for human osteosarcoma is estimated at $1.72 billion. This highlights the significant potential for OST-HER2 to make a substantial impact both clinically and commercially.
OS Therapies has always maintained a strong connection to the osteosarcoma patient community. Recently, you’ve announced the formation of both an Osteosarcoma Patient Advocacy Advisory Board and a Nationally Recognized Scientific and Medical Advisory Board for Osteosarcoma. Can you discuss how these boards will influence your work and the development of treatments for osteosarcoma?
Certainly. From the very start we’ve been inspired by the strength of this small but mighty community. Their courage motivates us to push forward in our pursuit of clinical success. The Patient Advocacy Advisory Board was established to ensure that the voices of the osteosarcoma community are heard, especially as we prepare to engage with the FDA. This board will provide crucial insights and perspectives, particularly as we work toward a potential Biologics License Application (BLA) for OST-HER2 following the completion of the ongoing clinical trial.
Simultaneously, the Scientific and Medical Advisory Board (SMAB) will support the Company by evaluating the safety and efficacy of OST-HER2. Their role includes comparing OST-HER2 to the current standard of care in osteosarcoma and offering expert guidance on clinical trial outcomes and regulatory strategies.
We’re genuinely excited about the potential of this technology. OS Therapies is developing OST-tADC, a proprietary next-generation Antibody Drug Conjugate (ADC) platform. This advanced technology incorporates pH-sensitive silicon-based linkers and coatings, trademarked as SiLinkers™, which selectively release multiple therapeutic agents within the tumor microenvironment, where pH levels are lower than in the rest of the body. This approach aims to maximize therapeutic effects while minimizing damage to healthy cells. Our unique advantage lies in using silicone to wrap the payload and connect it to the ADC. We’ve successfully completed initial safety and efficacy proof of concept in various murine cancer models, and as the program progresses, we see multiple out-licensing opportunities.
Investors are very familiar with the numerous M&A deals over the last 18 months in the oncology space. ADCs, or antibody drug conjugates, are a way of delivering medicines specifically to the cancer. AbbVie has even stated that ADCs may take the place of chemotherapy in the next 10 years.
One of the best-selling ADCs on the market is AstraZeneca (AZN) and Daiichi Sankyo’s Enhertu, which brought in combined sales of $2.5 billion in 2023, almost double the year before. The two companies formed a $7 billion alliance around Enhertu in 2019, and since then, the drug has secured multiple approvals and changed the way some breast cancers are treated.
You mention breast cancer treatment. Breast cancer is the most common cancer among women and the second leading cause of cancer deaths in women, with a therapeutics market size of over $30 billion. OS Therapies announced positive safety data from a Phase 1 clinical trial of OST-HER2 in HER2-expressing breast cancer, as well as preclinical efficacy in models of breast cancer. Can you provide some additional details on this application?
Absolutely, I’d be happy to elaborate. OST-HER2 has also completed a Phase 1 clinical trial primarily in breast cancer patients, showing strong preclinical data both on its own and in combination with HER2-targeting therapeutic antibodies like Herceptin®. In our Phase 1b trial targeting HER2-expressing solid tumors, 10 out of 12 patients treated were breast cancer patients. The dose selected for our ongoing Phase 2b clinical trial in osteosarcoma was well tolerated in these breast cancer patients, which is very encouraging.
Our preclinical breast cancer models have shown promising results, including a 78% reduction in tumor size in treated tumors compared to controls. Additionally, there was a 33% prevention rate of breast cancer in OST-HER2 treated mice versus none in the control group. Furthermore, combining OST-HER2 with a HER2-targeted antibody resulted in a 20% reduction in tumor size compared to the antibody alone.
In the brain metastasis model of primary breast cancer, there was a 65% reduction in the concentration of metastatic cells in OST-HER2-treated mice compared with controls. These results are exciting as they demonstrate the potential of OST-HER2 to treat primary tumors and prevent metastasis and recurrence.
We are enthusiastic about this additional application for OST-HER2 and look forward to providing further updates as we continue our research and clinical trials.
