“Cancer.” The word itself holds gravity and emotion. Receiving a cancer diagnosis can be incredibly difficult at any stage in your life. But for those affected by osteosarcoma, a rare bone cancer that predominantly manifests in children and teenagers, the struggle can be intense. The estimated 1,000 people diagnosed with osteosarcoma in the United States each year should be worrying about soccer games, college applications, or what to do on Friday night. Not whether they’ll see their next birthday. 

For localized osteosarcoma, which doesn’t spread beyond its initial area, survival rates sit around 60-70%. These numbers fall if the cancer spreads. But the treatment for osteosarcoma, along with the burden of cancer, can have an immense physical, emotional, and mental toll.

“Osteosarcoma is one of the most challenging cancers to treat, with a grueling and sometimes deadly chemotherapy regimen — nine months of Doxorubicin, Methotrexate, and Cisplatin. The treatment is so toxic that about 10% of patients don’t survive it,” says Paul Romness, the Chair, CEO, and President of OS Therapies, a clinical-stage cancer immunotherapy company. ” I do know there is a great deal of chemo PTSD from the chemotherapy regiment these patients initially go through.”

OS Therapies is working to improve the treatment landscape for individuals living with osteosarcoma — necessary, given that, as Romness explains, “there have been no new treatments for osteosarcoma in over 40 years.”

But this could change. OS Therapies’ lead candidate, an immunotherapy called OST-HER2, recently showed statistically significant improvements in both event-free survival and overall survival in a Phase 2b trial. Says Romness, “Many clinicians and  trials have tried almost everything – CAR-T, Monoclonal Antibodies, and more – but in the end, it’s the immune system that can target cancer at the cellular level.”

Recently, Rareatives spoke with Romness about why osteosarcoma has been left behind in the era of precision medicine, what makes developing drugs for rare pediatric cancers so challenging, and why he believes we’re finally at point to genuinely change outcomes for this rare cancer.

What is Osteosarcoma?

Before we dive in, let’s explore what osteosarcoma is. Osteosarcoma is a rare bone cancer that begins in cells called osteoblasts, “which are highly specialized cells that make up the structure of bones,” says Romness. This cancer normally manifests in long bones in the arms or legs. Since pain is often the first symptom, osteosarcoma may be initially brushed off as “growing pains” in children or teens. Although osteosarcoma is considered rare, it is actually the most common bone cancer in children and young adults (ages 10-30). Males are usually affected more than females.

Right now, the cause of osteosarcoma is unknown. However, the National Organization for Rare Disorders (NORD) explains that risk factors include:

• Prior treatment with radiation therapy or anticancer drugs called alkylating agents
• Being male
• [Potentially] having RB1, WWOX, or TP53 gene mutations
• Being of African American or Hispanic/Latino descent
• Personally having, or having a family history of, Li-Fraumeni syndrome, Werner syndrome, Bloom syndrome, hereditary retinoblastoma, or Rothmund-Thomson syndrome
• Having Paget disease of bone or fibrous dysplasia

Beyond bone and joint pain, osteosarcoma may cause symptoms such as:

• Swelling near the affected area
• A mass that can be seen and/or felt
• Bones that fracture or break seemingly without a cause
• Loss of mobility / limited range of motion in the affected limb
• Fatigue
• Joint stiffness

What Makes Osteosarcoma So Challenging to Treat?

Osteosarcoma can be difficult to treat and may have a high possibility of recurrence. But why is that?

“In a word, stubborness,” Romness explains. “In a word, stubbornness. The malignant cells create a matrix that is resistant to typical cancer treatments such as radiation and chemotherapy, requiring extraordinarily high doses and extended treatment regimens. These sarcomas most often occur in the largest bones in the body, at critical locations such as the hip, shoulder, or head, with metastases most often occurring in the lungs and brain.”

He adds, “Resection or amputation is often necessary, and treatment has a mortality rate of ~10% on its own. Survivors of treatment and the disease are often disabled permanently.”

So let’s explore why targeting HER2 could improve outcomes for people with osteosarcoma.

Interviewing Paul Romness

Rareatives: Hi Paul! Thank you so much for speaking with me today. Can you tell me a bit more about yourself, your background, and OS Therapies?

Romness: I’ve been in the industry my entire career at JnJ [Johnson & Johnson], Amgen, and then Boehringer Ingelheim (BI). When my daughter’s best friend was diagnosed with osteosarcoma (OS) in February 2017, I knew I needed to do something. OS is a very rare and deadly bone cancer that is most commonly seen in teenagers. Like many other solid tumors, it becomes far more dangerous once it metastasizes to other parts of the body.

When we started OS Therapies, the OS stood for Osteosarcoma – that is still our primary goal. But now OS stands for Overall Survival, which is a primary endpoint for the FDA and other regulatory bodies. With OST-HER2, we are laser focused on approval. If we get approved for the delay or prevention of metastasis in OS, we will then pivot to other solid tumors.

How does OS Therapies support the patient community?

We value patient-centricity at OS Therapies. Having worked at JnJ – in fact, our office is in the JnJ JLABS in New York City! – I, very early on, embraced the JnJ Credo that prioritized Patients, Care Givers, Our Community, and Shareholders, in that order. We started OS Therapies because of Olivia and she is on our Board of Directors.

But along the way, I have met many parents who have lost their child to OS. For them, I have shaved my head 4 times to raise money for St. Baldrick’s. The last time was this past summer with another Board member Avril McKean Dieser, who lost her son Edward in January 2024. Additionally, Serena Sebuda, who participated in our trial and received OST-HER2 therapy, now serves on our Patient Advocacy Advisory Board and has recently attended FDA meetings.

We also collaborate with many osteosarcoma-specific organizations and patient advocacy groups, many of whom invested in the company and Phase 2b clinical trial. These include the OS Collaborative, the MIB Agents FACTOR Conference, the Team Arnav Foundation, the Osteosarcoma Institute, the Canines-N-Kids Foundation, the Children’s Cancer Research Fund, and the Tyler Trent Foundation.

Patients have always been, and always will be our primary mission!

How does osteosarcoma’s status as a rare cancer impact research investment and pharmaceutical interest?

Osteosarcoma is an extremely rare disease. When I read that the previous sponsor was giving up their Phase 2b-ready asset in osteosarcoma, I knew why. The threshold to be considered an orphan drug in the US is 200,000 cases per year. Osteosarcoma has only  800-1,200 new diagnoses in the US annually. Therefore, pharmaceutical companies are reluctant to invest in new treatments as they don’t expect a great enough return despite the extreme unmet medical need.

When we started OS Therapies, all we had was the human OS indication. But now we have all the other indications for other solid tumors, as well as canines. In the US, 30,000 – 40,000 dogs develop OS each year, and most don’t survive beyond a year. In fact, it’s the leading disease-related killer of dogs. Previously, OST-HER2 was conditionally USDA approved for canines, and we are working the regulatory path for our four-legged friends to get that back on the market with a commercial partner. 

On the human side, though, through our small and agile team, our dedicated mission, and through the available regulatory incentives such as the rare pediatric priority review voucher program, we believe we have a model that will allow us to commercialize the first new treatment for Osteosarcoma in decades.

As we get closer to FDA, EMA and HMRA approval for osteosarcoma, we will get more attention from institutional investors and pharmaceutical interests.

Now, moving more to the science, why focus on HER2-expressing cancers?

Cancer uses HER2 to set-up vascularization when it metastasizes to the lungs and brain. Since the micro-metastases are looking for oxygen and soft tissue, where better to find them than in the lungs and the brain. By targeting HER2, we are going where the cancer wants to go, and that way our therapy can incept the micro-metastases before they can land and set up vascularization.

How does immunotherapy work differently than chemotherapy when you’re targeting osteosarcoma?

That question really highlights the next-generation approach of our treatment. Traditional chemotherapy is non-specific blanket coverage (poison) that stops every cell in the body from dividing by breaking the DNA in the cell nucleus. This is why side effects are often severe, including heart disease and even follow-on cancers. It’s still used because of the basic principle that cancerous cells divide faster than their healthy neighboring cells and are more affected by the chemo.

Unfortunately, the rapidly mutating cancer cells will often develop resistance to chemotherapy molecules. Like a fever, chemo becomes a race to see who can hang on longer. More modern approaches leverage the acute toxicity of chemotherapy molecules and also include delivery mechanisms to increase target specificity and reduce off-target side effects, including antibody-drug conjugates such as those in OST’s tADC program. 

Immunotherapy, however, and ours in particular, is not cytotoxic on its own. Instead, the treatment provides a signal to the body’s own immune system that certain cells need to be cleaned up and removed, or lysed. The side effects observed have been minimal and are associated with a generalized immune response. OS Therapies’ OST-HER2 leverages the relatively unique bacterial lifecycle of Listeria monocytogenes to deliver those signaling proteins directly to the antigen presenting cells that roam the body and are the front lines of cellular immunity. 

I’d love to learn more about OST-HER2 and its mechanism of action.

Listeria is a soil dwelling bacteria and common foodborne pathogen. It was first identified and developed as treatment for cancer by Yvonne Patterson and Nicola Mason at the University of Pennsylvania some years ago. The single-celled gram-positive bacteria has a lifecycle different from those of many other pathogenic bacteria. Instead of travelling through the bloodstream to infect the host, Listeria buds from cell to cell. The body is adapted to deal with either type of infection, but a cell-to-cell spreading pathogen requires a much more targeted immune response.

The Listeria in OST-HER2 has been engineered to be unable to escape from the cells it encounters by truncating the lysterolysin-o protein, which is a perforin that the bacteria typically uses to escape the phagolysosome of the antigen presenting cells that capture it. Instead, the immune cell is able to break down the Listeria and the signaling proteins that are encoded on the cell surface are delivered to the immune system, activating CD4 and CD8 T-Cells that hunt cancer cells one-by-one, a level of specificity that is unmatched.

The HER2 protein is the source of the epitopes included in OST31-164, but with our platformed approach we can swap plasmids in the bacteria to better suit indications of interest, such as breast, colorectal, or other solid tumors. In fact, in each laboratory experiment we have conducted to examine the immune response to the treatment, we have observed spreading beyond the HER2 pathway to include other individual oncogenes, which highlights the consistent multi-faceted immune responses observed.

Why choose a vaccine as opposed to an alternate delivery method?

I would describe us using a platformed approach. The Listeria vector shares similarities with but is distinct from a traditional vaccine. Listeria provides an ideal vehicle with which to modulate the immune system. Unlike other immunomodulators which are susceptible to immuno-senescence and developed resistance, Listeria results in an acute immune response each time it is delivered, typically within the hour. That immune response tells the body to secrete lymphocytes (white blood cells) known as Killer T-Cells, which then travel throughout the body to identify and destroy those micro-metastases. After four hours, we shut down the Listeria with an antibiotic, but the immune system continues to stimulate the T-cell response. Further, due to the cellular immunity required to clear the pathogen, the body mounts a full immune response each time the treatment is administered.

Swapping the signaling proteins included in the plasmid has allowed the program to be developed for a number of other indications such as prostate, non-small cell lung cancer, and cervical cancer. OST-HER2 for Osteosarcoma remains the most advanced program in the platform.

From what I understand, you’ve completed your Phase 2b trial. What have your results shown?

We have completed the Phase 2b trial and are taking these results to the regulators. From a safety standpoint, the FDA has had no questions about the safety profile of OST-HER2, and the results look good so far. 

In our trial, we measured Event Free Survival (EFS) at the suggestion of the FDA and continue to follow Overall Survival (OS). Comparator data for EFS has been challenging, but our EFS over the 48-week treatment phase of the trial was 35%, compared to the 20% that was the previous standard in the literature. Overall, survival outcomes appear to be tracking even better, and we presented additional data on October 10, 2025. 

Patient side effects have been transient, typically associated with infusion, and often resolve very quickly post infusion. We have had at least one patient request to continue treatment after the study, and patients continuing to participate in Listeria surveillance and survival follow up speaks to their willingness to help push this treatment forward.

Serena Sebuda, who participated in our trial and is now on our Osteosarcoma Patient Advisory Board, had seven prior surgeries to remove lung metastases before receiving our therapy. She has now been cancer-free for over three years.

As you look to the future, what do you hope for those affected by cancer?

Before we started OS Therapies, we started OS Collaborative to encourage more and better treatments. OS Therapies was an extension of those ideas into action. I hope to continue this action moving forward. We are all in a community that must work together to advance new therapies that will someday (hopefully soon) offer new treatment options.

I do hope, pray and believe we will someday get rid of chemotherapy at least in this one rare cancer. If I am a part of that, my life will be complete. But what if we can increase survival and potentially reduce or eliminate chemotherapy in other solid tumors? Now that would be amazing!

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About Paul Romness

Mr. Paul Romness leads OS Therapeutics with over 25 years of experience in the biopharmaceutical industry having served every function within major companies like Johnson & Johnson, Amgen and Boehringer Ingelheim. He has been directly involved in the launch of 9 major products in the industry covering indications for oncology, surgery, HIV, FSD, COPD, IPF, cardiovascular and diabetes. Throughout his professional career and within his community he has focused on and advocated for unmet medical need and getting treatments to patients. Mr. Romness has a B.S. in Finance from American University and a Masters of Health Policy from George Washington University Medical Center.

About OS Therapies

OS Therapies (OST) is a clinical stage cancer immunotherapy company focused on the identification, development and commercialization of new treatments for Osteosarcoma (OS) and other solid tumors.

OS Therapies (OST) was launched to meet significant unmet need for new treatments in cancers of the bone in kids and adults. Osteosarcoma is an extremely challenging and often aggressive cancer that has particular treatment challenges due to location, changing genotypes, and high recurrence rates.

You can find OS Therapies on LinkedIn, Facebook, Instagram, and X.