In late July 2024 OS Therapies, a clinical-stage biopharmaceutical company focusing on the identification, development, and commercialization of treatments for osteosarcoma and other solid tumors announced the pricing of its initial public offering of 1,600,000 shares of common stock at a public offering price of $4.00 per share, raising gross proceeds of $6.4 million.
Osteosarcoma is a solid tumor of the bone that predominantly occurs in children and young adults. It is an extremely challenging and often aggressive cancer that has particular treatment challenges due to its location, changing genotypes, and high recurrence rates. Standard treatment includes surgery and chemotherapy.[1]
The incidence of osteosarcoma is bimodal, peaking at 18 and 60 years of age, and is slightly more common in males. The key pathophysiological mechanism involves several possible genetic drivers of disease, each linked to bone formation, causing malignant progression and metastasis. While there have been significant improvements in the outcome of patients with localized disease (with event-free survival outcomes exceeding 60%) in patients with advanced, metastatic, or recurring disease, event-free survival outcomes remain poor at less than 30%[1]
A vector-based off-the-shelf immunotherapeutic vaccine
OST-HER2, a biologic therapeutic candidate being developed by OS Therapies, is a Listeriamonocytogenes (Lm-) vector-based off-the-shelf immunotherapeutic vaccine designed to prevent metastasis, delay recurrence, and increase overall survival in patients with osteosarcoma and other solid tumors. The proposed OST-HER2 mechanism of action is based on innate and adaptive immune stimulating responses activated by the Lm vector. This treatment generates T-cells that can eliminate or slow potential micrometastases that can grow into recurrent osteosarcoma and other solid tumors, including breast cancer.
T-cell responses home in on HER2 expressed by the tumor and then kill the cell, releasing additional tumor targets. There are currently no approved adjuvant treatments for recurrent osteosarcoma in the United States.
Positive data from a Phase 1 clinical trial of OST-HER2 in patients with HER2-expressing solid tumors in breast cancer and other cancers. Additionally, the Company announced positive preclinical efficacy data for OST-HER2 in multiple models of breast cancer.
Trial results
A total of twelve (12) patients with a history of HER2 positive cancer were enrolled in the Phase 1b clinical study, comprised of ten (10) patients with breast cancer, one (1) patient with esophageal cancer, and one (1) patient with GE junction cancer.
OST-HER2 was determined to be safe and well tolerated in patients with HER2-expressing solid tumors, including at the dose currently being used in the Company’s ongoing Phase 2b clinical trial in recurrent, resected osteosarcoma (AOST-2121, NCT04974008). The Company previously announced positive AOST-2121 interim data and is now in active discussions with the US FDA regarding a Breakthrough Therapy (BTD) designation application submitted for OST-HER2 based on the interim results.
The Company is focused on approval for OST-HER2 in osteosarcoma and plans to expand development into breast cancer and other HER2-expressing cancers such as esophageal and colorectal cancer.
In addition, the company announced positive data from multiple preclinical models of breast cancer.
The key data for OST-HER2 include:
- 78% reduction in tumor size (3mm for OST-HER2 treated vs. 14mm for control arm) in FVB/N HER2 transgenic mouse model of breast cancer treatment at day 75
- 33% prevention of breast cancer in OST-HER2 treated mice vs. 0% prevention of breast cancer in FVB/N HER2 transgenic model of breast cancer prevention at week 50
- 20% reduction of tumor size for OST-HER2 plus HER2-targeted antibody vs. HER2-targeted antibody alone Tg tumor regression model of breast cancer at day 42
- 65% reduction in the cellular concentration of metastatic cells for OST-HER2-treated mice compared with controls in the brain metastasis model of primary breast cancer
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.
Ongoing clinical trials
Currently, the company has fully enrolled a potentially pivotal Phase 2b clinical trial in recurred, resected osteosarcoma, dosing 41 patients with OST-HER2 at 21 clinical trial sites across the United States, with topline data expected in the fourth quarter of 2024 following the release of interim data in June 2024. OST-HER2 has received Rare Pediatric Disease Designation (RPDD) from the Food and Drug Administration (FDA), and Fast Track and Orphan Drug Designations by the FDA and European Medicines Agency (EMA).
OS Therapies is seeking Breakthrough Therapy Designation for OST-HER2 for osteosarcoma from the FDA based on data from its Phase IIb clinical trial. Upon any Biologics Licensing Authorization (BLA) from the FDA for OST-HER2 in osteosarcoma, the Company will be granted a Priority Review Voucher based upon the RPDD. OST HER2 has also completed a Phase 1 clinical trial primarily in breast cancer patients, in addition to strong preclinical data demonstrating efficacy on a standalone basis and in combination with HER2-targeting therapeutic antibodies such as trastuzumab (Herceptin®; Roche/Genentech).
The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD), Orphan Drug Designation (ODD), and Fast Track Designation (FTD) for OST-HER2 in Osteosarcoma.
Antibody-drug conjugates
In addition, OS Therapies is advancing a next-generation antibody-drug conjugate (ADC) technology platform, also known as tunable ADC (tADC), which features tunable, tailored antibody-linker-payload candidates.
This platform leverages the company’s proprietary silicone linker technology, enabling the delivery of multiple payloads per linker.
The total addressable market for human osteosarcoma is estimated at $1.72 billion. The global market for ADCs is anticipated to reach $19.8 billion by 2028, according to data from MarketsandMarkets.
On August 1, 2024, OS Therapies’ common stock started trading on the NYSE American Stock Exchange under the symbol OSTX.
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Clinical trials
Osteosarcoma Maintenance Therapy With OST31-164 (OST-164-01) – ClinicalTrials.gov ID NCT04974008
Reference
[1] Beird HC, Bielack SS, Flanagan AM, Gill J, Heymann D, Janeway KA, Livingston JA, Roberts RD, Strauss SJ, Gorlick R. Osteosarcoma. Nat Rev Dis Primers. 2022 Dec 8;8(1):77. doi: 10.1038/s41572-022-00409-y. Erratum in: Nat Rev Dis Primers. 2022 Dec 30;8(1):82. doi: 10.1038/s41572-022-00416-z. PMID: 36481668.
Featured image: Doctor examining an x-ray slide with a patient wearing a pink bra waiting in the background. Photo courtesy: © 2016 – 2024 Fotolia/Adobe. Used with permission.
DOI:10.14229/onco.2024.08.05.001
