Blog

A multicenter Phase II clinical trial led by researchers at The University of Texas MD Anderson Cancer Center demonstrated significant tumor shrinkage and disease control in patients with advanced pheochromocytoma and paraganglioma (PPGL), two rare and potentially life-threatening neuroendocrine tumors.

The results of this study, led by Camilo Jimenez, M.D., professor of Endocrine Neoplasia and Hormonal Disorders, were published today in the New England Journal of Medicine and presented concurrently at the 2025 European Society for Medical Oncology (ESMO) Congress (Abstract 1705O).

What was the primary finding of the trial?

The trial demonstrated that the HIF-2α inhibitor belzutifan showed meaningful antitumor activity with a 26% objective response rate, a significant achievement particularly for rare and difficult-to-treat cancers. These effects lasted an average of more than 20 months, indicating a sustained clinical benefit for those who responded to treatment.

It’s notable that nearly one-third of patients (32%) who were taking blood pressure medication were able to reduce their dosage by half for at least six months. This is an important finding, as PPGL tumors often produce excess hormones that raise blood pressure. These results suggest that belzutifan may have also helped manage symptoms related to hormone-secreting tumors.

The primary significance of this study is demonstrating that HIF-2α inhibition with belzutifan can achieve meaningful clinical benefit in patients with advanced, progressive PPGL. In a population with no remaining standard-of-care options, we observed durable disease control and a manageable safety profile, supporting the rationale for HIF-2α as a therapeutic target in this rare tumor type.”

Camilo Jimenez, M.D., Professor of Endocrine Neoplasia and Hormonal Disorders

Why is the LITESPARK-015 trial important?

Pheochromocytoma and paraganglioma (PPGL) are difficult-to-treat cancers that affect roughly 2,000 people annually in the U.S. One of the main drivers of tumor growth in PPGL is the HIF-2α protein. In healthy cells this protein adjusts to changes in oxygen levels, but genetic mutations or changes in cell metabolism can cause HIF-2α to become abnormally active, triggering signals that help the tumor grow and spread.

HIF-2α inhibitors, such as belzutifan, have been successful in shrinking tumors and slowing disease progression in other cancers driven by HIF-2α overactivity, such as kidney cancer and von Hippel-Lindau (VHL) disease. Building on this knowledge, researchers evaluated the effectiveness of these inhibitors in patients with advanced PPGL.

On the LITESPARK-015 Phase II trial, 72 patients with locally advanced, metastatic, unresectable PPGL who had exhausted all other standard-of-care treatment, were treated with belzutifan.

Is belzutifan approved to treat PPGL?

In May 2025, the Food and Drug Administration (FDA) approved belzutifan for the treatment of adult and pediatric patients ages 12 years and older with advanced, unresectable, or metastatic PPGL who do not require immediate surgery. Belzutifan is the first oral and only approved therapy for this disease, making it a new standard of care for this patient population. 

“The approval of belzutifan offers new hope. As an oral treatment, it has been shown to shrink tumors, reduce symptoms, and improve quality of life with low toxicity. It represents a meaningful step forward in care for people living with these rare cancers,” Jimenez said.

Timeline

2025 – FDA approves belzutifan for treatment of adult and pediatric patients 12 years and older with PPGL

2023 – FDA approves belzutifan for advanced renal cell carcinoma (RCC) after treatment with a PD‑1/PD‑L1 inhibitor and a VEGF tyrosine kinase inhibitor (VEGF‑TKI)

2021 – FDA approves belzutifan for adults with von Hippel‑Lindau (VHL) disease who require treatment for associated tumors (RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors), when surgery is not immediately necessary

In a landmark moment at the ESMO Congress 2025, pivotal studies have unveiled compelling evidence that a new class of anti-cancer agents-antibody-drug conjugates (ADCs)-can dramatically improve outcomes for patients with early-stage HER2-positive breast cancer. 

The results from the phase III DESTINY-Breast05 and DESTINY-Breast11 trials, presented in a Presidential Symposium, mark a paradigm shift in breast cancer treatment, positioning ADCs not only as powerful therapeutic agents when the disease has already progressed but also as potential new standards of care in patients with early disease.  

There is a particular need for therapies to ensure patients with HER2-positive early breast cancer achieve pathological complete response following neoadjuvant therapies-i.e., delivered before surgery-, and a high unmet need to treat residual disease in those who do not, to prevent the development of metastasis.”

Dr. Evandro de Azambuja from the Jules Bordet Institute, Brussels, Belgium

Currently, trastuzumab emtansine (T-DM1) is the only ADC approved for patients with HER2-positive early breast cancer who show residual invasive disease after neoadjuvant therapy and are at a high risk of recurrence. In the DESTINY-Breast05, Trastuzumab deruxtecan (T-DXd), a new-generation ADC delivering a topoisomerase I inhibitor, showed to improve invasive disease-free survival and disease-free survival by 53% compared with T-DM1 (for both: hazard ratio [HR] 0.47; 95% confidence interval [CI] 0.34–0.66; p<0.0001). Also, T-DXd confirmed its high brain activity, demonstrating a clinically meaningful improvement in brain metastasis-free interval over T-DM1 (HR 0.64; 95% CI 0.35–1.17). 

“The generally manageable safety profile and the superior efficacy data suggest that T-DXd should replace T-DM1 as the new standard of care for patients with HER2-positive, residual invasive breast cancer after neoadjuvant therapy,” notes de Azambuja. 

The use of T-DXd also showed impressive findings earlier in the treatment pathway- before surgery- as reported in the DESTINY-Breast11 trial where 927 untreated patients with high-risk HER2-positive early breast cancer received either the ADC followed by standard HER2-targeted therapy (THP) or the conventional anthracycline-based regimen (ddAC-THP). The cycles of T-DXd, sequenced with THP, led to a significant increase in the rate of pathological complete response at surgery (67.3% versus 56.3%; p=0.003). “The T-DXd regimen has also the added advantage of an improved safety profile compared with the anthracycline-containing regimen,” comments de Azambuja noting the relevant reduction in cardiac toxicities which was observed with the ADC compared with the conventional treatment. 

“In conjunction, these two studies establish T-DXd as a critical treatment option for early-stage HER2-positive breast cancer, ultimately providing a new tool for treatment tailoring for what was once considered the most aggressive subtype of breast cancer, and which today represents the one with the highest chance of cure,” highlights Dr Paolo Tarantino from the Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. 

After having reshaped the treatment of multiple types of metastatic cancers over the last few years, novel ADCs such as T-DXd are now “raising the bar” in the curative setting due to innovations in their design and mechanism of action. However, their use presents new challenges that need to be addressed. “For instance, 

toxicity profiles must be carefully defined and substantial effort to prevent permanent or fatal toxicities is required. Dosing, duration and sequencing of ADCs must also be optimised to achieve maximal efficacy with the least side-effects, and equally critical is the identification of predictive biomarkers that may allow better tailoring of ADC therapy and minimise overtreatment,” clarifies Tarantino. 

The presentation of the DESTINY-Breast05 and DESTINY-Breast11 trials results at the ESMO Congress 2025 cements the event’s role as a catalyst for global oncology progress. With ADCs now demonstrating superiority in both pre- and post-surgical settings, the oncology community stands at the threshold of a new chapter-one defined by smarter targeting, earlier intervention and deeper biological understanding. 

“Besides the immediate practical impact, in fact, data presented today are expected to have a broader impact on the future of ADC research, marking the formal entrance of the new generation of drugs in the curative arena. This is a therapeutic strategy with tremendous potential, which we are only just starting to unleash, promising to reduce rates of recurrence and improve survival across multiple cancers in the years to come,” concludes Tarantino.

Story Continues

This means that, based solely on DCF, the market is pricing in a far more optimistic future than current cash flow projections justify.

Result: OVERVALUED

Head to the Valuation section of our Company Report for more details on how we arrive at this Fair Value for Innodata.

Our Discounted Cash Flow (DCF) analysis suggests Innodata may be overvalued by 383.8%. Find undervalued stocks or create your own screener to find better value opportunities.

The price-to-earnings ratio, or PE ratio, is a widely used valuation tool for profitable companies like Innodata because it directly ties the stock price to the company’s actual earnings. This makes it a powerful metric for investors looking to connect valuation with real financial performance.

However, what counts as a “normal” or “fair” PE ratio can swing widely based on how fast a company is expected to grow and how much risk it carries. Investors are often willing to pay a higher multiple for businesses with rapid growth prospects or lower perceived risk, and less for companies facing challenges or slower expansion.

Right now, Innodata trades at a PE ratio of 59.26x. For context, this is well above the average among its peers at 46.38x, and far higher than the broader Professional Services industry average of 24.94x. On a purely surface level, that makes Innodata look expensive.

But not all businesses deserve the same PE just because they are industry peers. This is where Simply Wall St’s proprietary “Fair Ratio” comes in. This metric combines company-specific details such as growth rates, profit margins, risks, industry trends, and market cap to determine what a reasonable PE should be for Innodata right now.

Innodata’s Fair Ratio is calculated at 22.44x, which is well below both its current multiple and the peer group. Since this method tailors the benchmark to the company’s actual profile, it can be more insightful than simply comparing industry averages that may not fully take into account what makes Innodata unique or risky.

Since Innodata’s current PE ratio of 59.26x is significantly higher than its Fair Ratio of 22.44x, the stock appears overvalued based on this approach.

Result: OVERVALUED

PE ratios tell one story, but what if the real opportunity lies elsewhere? Discover companies where insiders are betting big on explosive growth.

Earlier we mentioned there is an even better way to understand valuation, so let’s introduce you to Narratives. A Narrative is your unique perspective on Innodata: it is the story you believe about the company’s future, brought to life by your own assumptions about its upcoming revenue, profit margins, and fair value.

Rather than relying just on standard ratios or consensus estimates, Narratives help you connect what is happening in the real world, such as new AI demand, changing competition, or regulatory shifts, to a financial forecast and a fair value, all in a structured, accessible way.

On Simply Wall St’s Community page, Narratives make it easy for millions of investors to map their view of the company to the numbers and instantly see if their assumed fair value is above or below the current market price. This guides smarter buy or sell decisions with facts tailored to their belief.

Because Narratives update dynamically when new headlines or company results come in, your view always keeps pace with reality. For example, the most bullish Innodata Narrative recently set a fair value as high as $75.00 per share, driven by expectations of booming AI demand and margin expansion. The most bearish view is just $55.00, reflecting risks like shrinking clients or margin pressure. Which story sounds most convincing to you?

Do you think there’s more to the story for Innodata? Create your own Narrative to let the Community know!

This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include INOD.

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com