A full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts and over 636 companies covered across all sectors. Please visit our website, hcwco.com, for more information. Please join us for one-on-one meetings, corporate presentations, and panels that will be live and streaming from September ninth through eleventh. With that said, I'd like to introduce Sam Whiting, CMO and Head of R&D at Tempest Therapeutics. Thank you.
Thank you, Kyle. On behalf of Tempest Therapeutics, I thank H.C. Wainwright for the invitation to speak today. I will be making forward-looking statements. As a reminder, please refer to our SEC filings. This is an exciting and gratifying time for all of us at Tempest Therapeutics. Earlier this year, we received the second update of overall survival from the Morpheus study, a randomized global phase 2 study comparing our drug, amezalpat, plus the standard of care to standard of care alone in patients with hepatocellular carcinoma of the liver, also known as HCC. These patients were treated in the first-line setting. The data fully support a transition to a pivotal phase 3 study, a registrational study, that we've now successfully completed our pre-pivotal meeting with the FDA and received broad agreement on their proposed plan.
HCC is a deadly cancer with more than two hundred and thirty thousand patients treated globally in the first-line setting, but we also believe that amezalpat can help more patients than just HCC. We have favorable data in patients with kidney cancer and cholangiocarcinoma from our own phase 1 study. Tempest is also a diversified company with an additional drug in clinic that is poised to move forward this year in collaboration with the National Cancer Institute, and we have full control and ownership of all of the assets. We think that this makes us an interesting and undervalued asset. The Tempest pipeline, as shown here, includes amezalpat, which we'll be talking about today in the setting of hepatocellular carcinoma. This study, as I've described, is poised to start a registrational study early next year.
Our second drug, TPST-1495, is a first-in-class compound that inhibits prostaglandin signaling in a novel manner. This drug is planned to enter a phase 2 study in patients with FAP syndrome, funded and conducted by the National Cancer Institute Cancer Prevention Network. Our active research program continues discovery work into additional novel targets for cancer that we anticipate advancing into the clinic in the future. Am ezalpat is a first-in-class oral small molecule therapy that targets the master regulator of fatty acid oxidation, also called FAO metabolism. This transcription factor is called PPAR-alpha. PPAR-alpha functions to support cancer by three critical mechanisms. First, many cancers use metabolism of fats as an energy source, particularly in a setting of advanced, metastatic and hypoxic tumors as developed over the course of cancer growth.
Secondly, PPAR-alpha supports blood vessel growth, and genetic evidence shows that inhibiting PPAR-alpha reduces a key process called angiogenesis that cancers take advantage of to spread in the body. And then finally, the immune system is, of course, critical and important in fighting cancer, and this is especially true in the setting of immunotherapy being used, such as checkpoint inhibitors, to treat cancer. A class of bad immune cells called immune suppressor cells that inhibit the activity of immunotherapy utilize fatty acid oxidation as an energy source and can be inhibited with drugs such as amezalpat, a PPAR-alpha inhibitor. Importantly, hepatocellular carcinoma is the highest tumor in terms of PPAR-alpha expression and fatty acid oxidation gene expression of any tumor that we profiled, making it a critical target for advancement in our development program.
I'll enter now into the randomized phase 2 data. The study schematic is shown here. Importantly, this study is a global study run in the United States, Europe, and in Asia, in seven countries and in 26 sites. 70 patients in the first-line setting were first randomized, and then treated to receive either amezalpat, plus atezolizumab and bevacizumab, the standard of care regimen in first-line liver cancer, or that standard of care without amezalpat. Key study endpoints included confirmed objective response rate and also progression-free survival and overall survival, as well as safety. The study table summarizing efficacy endpoints is shown here, and the key thing is that really all of the efficacy endpoints that we looked at in this study were favorable for the amezalpat addition to standard of care.
This included a hazard ratio for overall survival of 0.65. That represents a 35% reduction in the risk of death for patients who received amezalpat plus standard of care versus standard of care alone. Shown here, a six-month improvement in the median overall survival, which is more than needed, really, for meaningful clinical benefit in patients when it comes to survival. Additional benefit in the study was shown in the form of progression-free survival and the confirmed objective response rate, shown here, 30% versus 13%. Also in key subgroup populations, including PD-L negative tumors that are immune quiet and difficult to treat with immune therapy. I'll show you those data later in the presentation. Also in patients with a key mutation that's common in patients with HCC, called beta-catenin mutation.
The Kaplan-Meier for survival is shown here. This demonstrates obviously a broad separation of the survival curves, favoring the amezalpat combination with standard of care, really from as early as three months into treatment. At the time of the longest follow-up on the far right-hand edge, a full 50% of patients on the amezalpat arm were still alive and in survival follow-up, compared to 30% of patients on the control arm. The risk of death, as I noted, was reduced by 35% by adding amezalpat to the standard of care versus the standard of care alone, and the median overall survival was improved by six months by this combination regimen. Showing the upper left-hand side of this slide are three tumors, with tumor cells and stromal cells in the tumor shown in purple and immune cells infiltrating the tumor shown in green.
These figures represent the classic immune profiles that are seen in cancer, ranging from what's called an immune desert tumor on the far left, where you can see lots of tumor and stroma and no immune cells, to immune-excluded tumors in the middle panel, where you can see the tumor positioned here is surrounded by immune cells, but there are no immune cells that have entered the tumor. And then immune-inflamed tumors, where you can see a mixture of immune cells throughout the tumor. These immune-inflamed tumors are the classic tumor type that benefits from immune therapy.
That's actually shown for the atezolizumab regimen in the right-hand corner, where you can see that overall response rate is improved in PD-L1 positive, immune-positive tumors and in immune-infiltrated tumors, and progression-free survival also is better in immune-inflamed tumors than in immune cold tumors. In this randomized phase II study shown here is the control arm, the standard of care arm, where we're looking at the patients with the largest tumor response here on the far right of the slide. Then underneath this, the immune profile of the tumor on biopsy as the patient went on to study. What's clear in this is that the patients with the strongest tumor responses are positioned over tumors that on biopsy are red. That includes both the PD-L1 positive and the immune-inflamed tumors.
You can see a real scarcity of gray PD-L1-negative tumors and blue or orange immune desert or immune-excluded tumors in the patients responding to treatment on the control arm. That's dramatically different in the arm with amezalpat added to the standard of care. Here, again, on the right-hand side, we show patients with the strongest immune tumor responses to therapy, including a complete response in this bright green patient. And then underneath that, the tumor profile shows a wide number, a broad number of immune negative tumors, including PD-L1 negative in gray on this top bar, and immune desert and immune-excluded tumors in blue and orange in the second row of the table. This is, again, in sharp contrast to the standard of care.
It's also in contrast to what's typically seen with immune therapy in the treatment of cancer and supports the immune mechanism of amezalpat and how it improves the immune profile of tumors to allow for better therapy. On this slide, we show the overall survival benefit according to key subgroups of patients treated on this study, including immune-positive and immune-negative tumors, patients with good and bad performance status or functional status, patients with high and low tumor markers, patients with metastatic disease or liver-localized disease, and also invasion of blood vessels, and then the different etiologies or causes of hepatocellular carcinoma that are commonly seen, including viruses and non-viral causes like metabolic disease and alcohol.
On this end of the graph here, we show the forest plot, which is shown in the blue diamond, the comparison of the amezalpat arm to the standard of care arm in a blue diamond, and then the broad line surrounding the diamond is the confidence interval, and what you can see as you run down this panel is a consistent benefit for amezalpat plus standard of care in every category, good and bad prognostic patients, high and low tumor markers, et cetera, that indicates the broad benefit of amezalpat in addition to standard of care, compared to standard of care in this randomized comparison. The safety profile of the amezalpat combination in the study was quite favorable.
We now know that the triplet, including the standard of care plus amezalpat, is very similar to the standard of care alone when it comes to high-grade adverse events, as well as serious adverse events, and adverse events leading to treatment interruption or dose reduction or withdrawal of treatment, as well as the dose intensity of the standard of care drugs, whether they're administered alone or administered in combination with amezalpat. This is a very favorable safety profile that we believe is a beneficial and will appeal to patients and doctors, but also will allow for successful development of the triplet regimen in patients with liver cancer. So amezalpat at this point is poised in the form of the triplet regimen to enter a phase III global registrational trial.
The basis for this study is the improved overall survival is the most fundamental and important endpoint in the study, a 35% reduction in the risk of death for patients treated with amezalpat compared to standard of care. A six-month improvement in median overall survival compared to the standard of care. A much larger percentage of patients alive in follow-up on the amezalpat arm of the study compared to the control arm. And then key survival benefit that's maintained across subpopulations, including immune-compromised tumors, patients with high tumor markers or poor health and poor performance status. The safety profile is very favorable. We have recently, within the last month, come out of a what's called an end of phase II meeting or a pre-pivotal meeting with the Food and Drug Administration.
This was a very successful meeting for the company. We had broad agreement on essentially all of the critical aspects of the study that was proposed. And now moving forward, as we aim to start this study early next year, we know that we have the FDA on board with the plan. Finally, I'll note that, as I said before, amezalpat is an oral therapy, small molecule therapy, easy to make. There are potential market advantages for both cost of goods and for patient preference with an oral therapy compared to other intravenous therapies. So the study design is shown here. This is the study design coming out of the successful meeting with the FDA, reflecting agreement with the FDA on all of the key aspects of the development plan.
As importantly, I think, to stress in terms of predicting the outcome of the pivotal study, this study replicates very closely the phase 2 study that was positive. The difference being that this study is larger, has additional size, patient numbers, and statistical power in order to demonstrate a statistical significance for regulatory purposes. If we are to obtain either the same result that we saw in the phase 2, or actually importantly, a not as good result in the phase 3, would still be considered by the FDA to be statistically significant, and could lead to a successful filing and approval of the drug. I wanna return briefly here to the first-line market and just state again that hepatocellular carcinoma is a terrible disease.
It's a terminal diagnosis when advanced. It is a global epidemic with more than two hundred and thirty thousand patients, as I said, treated in the first-line setting. And there is a very strong both medical need, regulatory need, and business need for developing better therapies to treat patients in the first-line setting. So, finishing up here, we are positioned with a diversified portfolio of compounds, including our lead asset, amezalpat, which is positioned now to go into a pivotal registrational study in patients with first-line liver cancer. But we also have favorable data from our phase 1 study in patients with renal cell carcinoma and cholangiocarcinoma.
Renal cell carcinoma looked good enough in our phase 1 program that we are poised for development with funding provided that would move into renal cell carcinoma as the next indication for Tempest's plan for amezalpat. As I noted, our TPST-1495 drug, a novel first-in-class inhibitor of prostaglandin signaling, is getting ready to go into a phase 2 study that will be conducted and funded by the Cancer Prevention Network of the National Cancer Institute. Our research team continues with aggressive and insightful profiling of potential novel targets that we could pursue at this point. That ends the presentation. I wanna thank H.C.
Wainwright again for the opportunity to present, and my colleagues at Tempest Therapeutics for the great work that's gotten our company where we are today. Thank you.
Thank you, Sam. And I just wanna thank all of our presenters for taking part in what has been a very productive and informative series of presentations. We appreciate the time and the effort. We're very grateful for your flexibility and your presence at our conference this year, and just wanna thank you again from the H.C. Wainwright team.