Molecule RRx-001 Receives Fast Track Designation From the FDA - EpicentRx

Molecule RRx-001 Receives Fast Track Designation From the FDA - EpicentRx

By Tony Reid, MD, PhD, Chief Executive Officer, EpicentRx and Bryan Oronsky, MD, PhD, Chief Development Officer, EpicentRx

Thank you so much. It's great to be able to get together with you again and share our recent data. This is actually very critical for us as a company. In late March, the FDA granted us fast track designation for our lead molecule RRx-001. This molecule is very interesting. It's basically a designer molecule with direct anti-inflammatory activity. It inhibits NLRP3 and also has the interesting property of upgrading NRF2. Furthermore, it has a fundamental function in releasing nitric oxide, which has vascular dilating activity and anti-inflammatory properties.


I believe that these two properties together provide us with an opportunity to address certain problems that are persistent in oncology, and one of them is oral mucositis. This is the reason for the fast track designation based on our PREVLAR study, where we substantially reduced oral mucositis in patients receiving chemotherapy and radiation.


As a practicing oncologist, I can attest to the severity of this problem. When we administer chemotherapy and radiation, patients can experience severe irritation of the mucosal membranes. Some patients have described it as having fragments of glass or barbed wire in their mouth. Often, this leads to treatment interruptions or even discontinuation. The fact that we can reduce the toxicities associated with oral mucositis in head and neck cancer patients is a significant step forward for both the patients and our company.


How does RRx-001 Molecule work to prevent or attenuate chemotherapy and radiation treatment-induced severe oral mucositis? What sets it apart from other treatments currently available on the market? 

And again, this is a critical component of our company and how we think about the treatment of cancer. Many of the therapies we have, such as chemotherapy and radiation, induce inflammation. In recent years, there has been a better understanding of the constellation of proteins that come together to induce inflammation. One of the critical proteins in this process is NLRP3, which helps bring together a whole series of proteins that trigger this inflammatory complex. We are a direct and selective inhibitor of NLRP3, and we believe this is important. That's why the FDA granted us fast track approval. The FDA will facilitate data acquisition and movement towards approval due to the findings in our PREVLAR study. I believe this sets us apart from other therapies because our approach specifically inhibits the inflammatory process in a fundamental way. What it allows us to do is stay on time and on target with our therapies. By reducing toxicities and keeping the therapies on schedule, we can improve outcomes.


What inspired the development of RRx-001 Molecule, and how has the drug evolved over time?

The founding of our company, EpicentRx, as well as, the coincidence of RRx-001 molecule, kind of happened on a wing and a prayer. We were looking for a new kind of molecule, right? Most molecules and compounds that enter clinical trials are sourced from either the rainforest or the oceans. However, these sources have mostly been tapped out at this point. We looked in an unusual place: the aerospace industry. The reason we explored that field is because most of the aerospace-derived compounds are explosive. When they explode in the air, the residue settles in the soil and water, making their toxicities mostly known in advance. We knew that most of these Aerospace compounds decompose into harmless byproducts, which was a significant hurdle to overcome in drug development.


You can have a great drug with tremendous efficacy, but when you reach toxicology studies, which are the most labor-intensive and costly studies, you might find that the drug is too toxic to enter clinical trials. However, we knew in advance that this drug would be relatively non-toxic, and the toxicology studies in animals confirmed that. When we entered clinical trials, we didn't have much knowledge about the mechanism of the drug.


We thought we had an anti-cancer compound. We didn't know much more, and the mechanism wasn't initially important. The FDA stated that as long as it's safe, we could enter clinical trials. So that's what we did. However, as we progressed, we really delved into understanding the mechanism. We put a lot of effort into figuring out how this drug works exactly. As mentioned by Dr. Reid earlier, we now see that the drug has anti-cancer activity. It sensitizes tumors to radiation, chemotherapy, and even immunotherapy. What sets this drug apart from others is its surprising additional property. Alongside its anti-cancer properties, it also acts as a pro-inflammatory molecule in tumors while acting as an anti-inflammatory and anti-oxidative agent in normal tissues. This is quite rare for a small molecule because most small molecules have a single-minded focus and perform the same activity regardless of the tissue, organ, or microenvironment they encounter. However, RRx-001 molecule is very unique in that it changes its activity depending on the environment it finds itself in.


Can you describe the clinical trials that RRx-001 Molecule has undergone, including their results and any side effects observed in patients? 

So when I first became aware of EpicentRx and RRx-001 molecule, I was an investigator. I ran the clinical and translational research program at UCSD, and I've run hundreds of clinical trials. I was interested in it because it was a phase one clinical trial, the first-in-man clinical trial. I was the first investigator to actually administer this to a patient. It was intriguing to me because its molecular structure was somewhat akin to nitroglycerin. I believe most physicians and laypeople would understand that nitroglycerin is a molecule that releases nitric oxide and has intrinsic vascular dilating effects. In oncology, this is crucial because most tumors are hypoxic and have poor perfusion of the tumor tissue. Having a molecule that could affect the vascular flow of tumors was really intriguing.

Another aspect that fascinated me was its small molecule nature. We had other drugs out there, such as Avastin, that could alter blood flow (red blood cell(s) or white blood cell(s)) in a tumor, but they were large molecules like antibodies that didn't penetrate into a tumor very well. What intrigued me initially about our clinical trials was that this small molecule, RRx-001, had a known mechanism of nitric oxide release and the ability to penetrate cells. Its clean structure and active leaving group that bound into cysteines were also fascinating. Many tumors over express cysteines, which is critical in oncology since we have many drugs that bind to and damage DNA, leading to side effects. Here was a molecule that could alter blood flow and bind to proteins, including those critical in oncology development.


I was completely fascinated by this molecule and excited to bring it in as an investigator. It was just one of many dozens of trials I was running. However, it stood apart because the very first patients I treated showed immediate activity of the molecule. Upon infusion of this drug, we could observe vascular dilation in these patients. The fundamental mechanism of action, the venous dilation we hoped to target to the tumor, was immediately evident. Additionally, the small molecule's ability to penetrate into the tumor and bind cysteines, retaining the nitric oxide release within the tumor matrix, was an intriguing aspect. I was thrilled to conduct the trial. In the phase one trial, we observed some patients who had positive response ratess and prolonged stable disease. It was well tolerated, with the exception of discomfort caused by vascular dilation at the site of infusion.

Therefore, the proof of the molecule's activity was immediately evident in the venous dilation and associated discomfort. That was my initial involvement with it. We clearly observed activity across various tumor types, and EpicentRx has been able to conduct a wide range of trials, leveraging the drug's activities as a nitric oxide-releasing agent that affects the vasculature, immune system, and inflammatory processes.


What are the next steps for RRx-001 Molecule in terms of clinical development and FDA approval? 

So, the next steps, I think, as I mentioned in the earlier response, we were a bit uncertain at the very outset, right? We knew that it was an anti-cancer molecule. However, we didn't have a firm grasp on the mechanism, and we didn't know where the molecule would fit best. With that in mind, we tried very hard to explore various indications to determine the best fit for the molecule. After all this time, we have narrowed it down to two, or rather, three particular indications that make a lot of sense for this drug.


What were the indication of this study on Molecule RRx-001?

The first indication, of course, is small cell lung cancer in combination with a platinum doublet consisting of cisplatin and atopic side. This is because we are currently in a phase three trial for this combination.


The second indication is very promising, as mentioned by Dr. Reid, because we have obtained fast track designation from the FDA. It is for the treatment of severe oral mucositis in first-line head and neck cancer.


The third indication, which we haven't aggressively pursued yet but are closely examining, holds great potential due to the drug's mechanistic fit. It is for the treatment of cancers with liver-predominant metastases, such as colorectal cancer or even hepatocellular carcinoma. The drug would be delivered via intra-arterial hepatic arterial infusion.


How do you envision RRx-001 Molecule fitting into the broader landscape of cancer treatment, and what impact do you hope it will have on patient outcomes? 

I think, as we've pointed out before, it's an intrinsically interesting molecule. Nitric oxide, in and of itself, is a fascinating compound that affects both vasculature and inflammatory processes. The fact that we can have a small molecule that can bring a nitric oxide delivery system to the tumor microenvironment and trigger vascular changes as well as inflammatory and immunotherapy changes is very critical. Moreover, if you think in the broader context of oncology, we've made a lot of progress in the last several decades. When you look at cancers, most of them have multiple mutations that grant them the ability to replicate quickly, invade into tissues, avoid the immune system, and self-replicate. Because of that, we have to have multiple different therapies that can work together in a synergistic way to help fight cancer. I believe this is exactly where RRx-001 molecule is going to find its greatest opportunities because of its properties, essentially its tripartite structure. We can help alleviate toxicities, allowing chemo therapies and other therapies to deliver their greatest potential. Additionally, we can augment the activities of other critical molecules like immunotherapies and targeted small molecules.


So, in the broader landscape, as you were saying, I envision using this very creatively and effectively to help combine multiple therapies into an effective constellation of treatments, with RRx-001 molecule contributing to reduced toxicity and improved efficacy.


Can you speak to any potential challenges or barriers that may arise as you work towards bringing RRx-001 Molecule to market, and how do you plan to address these?

I believe the main obstacle is that RRx-001 molecule is an entirely new molecule, which can be seen as both a blessing and a curse. In fact, we have received a new generic name, Nibrozetone, from the World Health Organization (WHO) as an International Non-proprietary Name (INN). This new name highlights the fact that RRx-001 molecule is a completely novel molecule with a unique mechanism of action, unlike any other pharmaceutical drug developed before. This is a significant achievement, making the drug the first of its kind and a promising breakthrough.


However, this uniqueness also presents a challenge. Since RRx-001 molecule doesn't fit into any existing categories or precedents, regulatory agencies and potential partners find it difficult to evaluate its potential. There is no blueprint or established framework to rely on when assessing the drug. To address this issue, we are actively promoting the remarkable dual properties of RRx-001 molecule. It acts as the holy grail of cancer therapy by potentiating the activity of other agents such as radiotherapy, chemotherapy, and immunotherapy, while also protecting against the dose-limiting toxicities associated with these treatments.


Additionally, RRx-001 molecule possesses various anti-inflammatory properties. It is worth mentioning that the drug is undergoing intensive development for neurodegenerative diseases like Parkinson's disease, ALS, and motor neuron disease. These fascinating characteristics of RRx-001 molecule mean that it can potentially be effective in multiple disease processes, including cancer, autoimmune diseases, and autoinflammatory diseases. While this versatility is a blessing, it can also be seen as a curse since it may give the impression of a cure-all or snake oil. However, it is important to note that RRx-001 molecule is an NLRP3 inhibitor, a well-known class of compounds with activity in many different disease indications, and RRx-001 molecule follows the same trend.


To overcome the challenges posed by RRx-001's uniqueness, we are actively participating in various conferences, writing numerous manuscripts, and providing detailed descriptions of the drug's mechanism and properties.


What other products or developments is EpicentRx currently working on, and how do they fit into the company's overall mission and goals? 

EpicentRx has a second platform that consists of a tumor-selective oncolytic antivirus. Essentially, it is an oncolytic virus that functions as a transcriptionally regulated expression vector. What we express is a TGFβ receptor trap. Now, this is crucial because TGFβ is one of the primary cytokines involved in immune suppression. In the normal process of wound healing, immune system suppression is necessary to facilitate healing. Unfortunately, cancers have exploited this process and over express TGFβ as a means to evade the immune system. In certain tumors, such as colon cancer, a specific subset called CMC4 is characterized by the over expression of TGFβ, leading to a very poor prognosis. Over expression of TGFβ is observed in a wide variety of tumor types. Having an expression vector that can over express a trap to neutralize TGFβ allows us not only to directly kill tumor cells through the oncolytic process, but also to reverse immune suppression.

We have compelling preclinical data and emerging clinical data demonstrating the high effectiveness of this vector on its own and potentially in combination with various immunotherapeutic agents. Therefore, we are extremely excited about the other half of our company that focuses on this antiviral vector. In fact, we see them as complementary, as both of them impact the immune system and the tumor microenvironment in different yet synergistic ways. By treating with RRx-001 molecule, for example, to induce vascular dilation, and then following up with an antivirus that selectively kills tumor cells while neutralizing TGFβ, we can create an effective one-two combination. Furthermore, this combination can work not only on its own but also in conjunction with other immunotherapy, small molecules, and chemotherapeutic agents that are currently available or will be introduced in the future.


How do you see the field of cancer treatment evolving in the coming years, and how does EpicentRx plan to stay at the forefront of these developments? 

I think that's actually a continuation of the prior question. As we were discussing, cancer is the result of the evolution of multiple different mutations. The field of oncology has made progress in this regard, as chemotherapy can be directly cytotoxic. Additionally, we can kill cancer cells using small molecules that target mutated pathways. For example, immunotherapies can target new antigens in tumors and shape the tumor microenvironment, thereby altering susceptibility to treatment. This is where EpicentRx comes into play. Our platforms are designed to have limited toxicities and can be combined effectively with other therapies. Both of our platforms possess direct antitumor activity and the ability to synergize with agents that affect oncolytic processes and immunotherapy. We believe in attacking the multi-mutational dimension of cancers with various therapeutics, and we see ourselves as an integral part of this evolving environment.


Is there anything else you would like to add about EpicentRx, RRx-001 Molecule, or the future of cancer treatment in closing?

We have been accepted for two presentations at ASCO, and we're going to be talking about Adapt OH1 as well as RRx-001 molecule in both presentations at ASCO coming up in a few weeks. We're very excited about that. I would like to elaborate further on what I mentioned before: cancer is a series of multi-mutational events, and it provides us with an opportunity to collaborate with a wide range of companies. We're excited to work with other people in this field to help improve therapies and treatments for patients. It's a desperate need. As a practicing clinician, I still see patients who suffer from severe diarrhea or other complications that we can help alleviate with RRx-001 molecule or with therapies that have failed immunotherapy; we can reverse that trend and adapt. I believe both of those are real opportunities for us, and we look forward to collaborating with other companies to explore combining them in dynamic and effective ways.


What is Molecule RRx-001?

Molecule RRx-001, is a novel investigational drug that has garnered attention in the field of oncology. It belongs to a class of compounds called dinitroazetidines, which are designed to have a unique mechanism of action and therapeutic potential in the treatment of various cancers.

RRx-001 is being developed as a potential anti-cancer agent by multiple biopharmaceutical companies and research institutions. It is classified as a radiosensitizer and a hemoglobin modifier, meaning it has the ability to enhance the effects of radiation therapy while also improving oxygenation within tumors.

The primary mechanism of action of RRx-001 involves the modulation of redox (oxidation-reduction) systems in the body. It works by altering the balance of reactive oxygen species (ROS) and antioxidants, which play a critical role in cell signaling and survival. By selectively targeting cancer cells, RRx-001 aims to induce oxidative stress, disrupt tumor cell metabolism, and promote cell death.

One of the unique characteristics of RRx-001 is its ability to enhance the effectiveness of radiation therapy. Tumors often develop hypoxic regions, which have low oxygen levels, making them more resistant to radiation. RRx-001 improves tumor oxygenation by modifying the binding properties of hemoglobin, the molecule responsible for transporting oxygen in the blood cells. By increasing oxygen delivery to hypoxic tumor regions, RRx-001 can enhance the sensitivity of cancer cells to radiation therapy, leading to improved treatment outcomes.

In addition to its radiosensitizing properties, RRx-001 has shown potential as an immunomodulator. Preclinical and clinical studies have suggested that it can stimulate the immune system, promote anti-tumor immune responses, and enhance the efficacy of immunotherapies. This makes RRx-001 an exciting candidate for combination therapy approaches, where it can be used in conjunction with other anti-cancer treatments to achieve synergistic effects.

Clinical trials investigating the safety and efficacy of RRx-001 are currently underway in various types of cancer, including lung cancer, brain cancer, and pancreatic cancer, among others. These studies aim to assess its potential benefits as a standalone treatment or in combination with existing therapies.

It is important to note that while RRx-001 shows promising results in early studies, it is still an investigational drug and has not yet received regulatory approval for widespread clinical use. Further research and clinical trials are necessary to fully understand its therapeutic potential, determine optimal dosing regimens, and evaluate its long-term safety profile.

In summary, RRx-001 is an innovative investigational drug with unique properties as a radiosensitizer, hemoglobin modifier, and immunomodulator. Its potential to enhance the effects of radiation therapy, improve tumor oxygenation, and stimulate the immune system make it a promising candidate for improving cancer treatment outcomes. Continued research and clinical trials will provide further insights into its efficacy and safety, potentially leading to its future use as an important tool in the fight against cancer.


9 Key Takeaways about the Molecule RRx-001

  1. FDA granted fast track designation to EpicentRx's lead molecule RRx-001, a designer molecule with direct anti-inflammatory activity.

  2. RRx-001 inhibits NLRP3 and upgrades NRF2, and it releases nitric oxide with vascular dilating activity and anti-inflammatory properties.

  3. RRx-001 shows promise in reducing oral mucositis, a severe side effect of chemotherapy and radiation, in head and neck cancer patients.

  4. RRx-001 is a direct and selective inhibitor of NLRP3, differentiating it from other available treatments.

  5. RRx-001 was initially developed without a clear understanding of its mechanism, but it was found to have anti-cancer activity and sensitizes tumors to various treatments.

  6. Clinical trials have demonstrated RRx-001's ability to induce vascular dilation and penetrate tumors, with some positive responses and prolonged stable disease observed.

  7. RRx-001 is being developed for small cell lung cancer, severe oral mucositis in head and neck cancer, and potential liver-predominant metastases treatment.

  8. RRx-001's unique properties make it a valuable addition to cancer treatment by reducing toxicities, improving efficacy, and synergistically combining with other therapies.

  9. The main challenge is the novelty of RRx-001, lacking existing frameworks for evaluation and understanding of its potential.


Tony Reid, MD, PhD - About The Author, Credentials, and Affiliations

Dr. Tony Reid, MD, PhD, is a distinguished medical professional and the Chief Executive Officer of EpicentRx. With an extensive background in both medicine and research, Dr. Reid has made significant contributions to the field of oncology. He holds a medical degree (MD) and a doctorate (PhD), showcasing his deep understanding of medical science.


As the CEO of EpicentRx, Dr. Reid leads the company in its mission to develop innovative cancer therapies and revolutionize the treatment landscape. With his visionary leadership and expertise, he drives the strategic direction of the organization, fostering collaborations with researchers, clinicians, and industry partners.


Dr. Reid's impressive credentials include numerous scientific publications, reflecting his commitment to advancing medical knowledge and improving patient outcomes. His relentless dedication to finding novel solutions for cancer patients has earned him recognition and respect in the medical community.


Beyond his role at EpicentRx, Dr. Reid actively participates in scientific conferences and engages in academic pursuits, sharing his expertise with colleagues and aspiring medical professionals. Through his multifaceted background and unwavering passion for oncology, Dr. Tony Reid continues to shape the future of cancer treatment and bring hope to countless individuals affected by this devastating disease.


Bryan Oronsky, MD, PhD - About The Author, Credentials, and Affiliations

Bryan Oronsky, MD, PhD, serves as the Chief Development Officer at EpicentRx where he drives the development and advancement of innovative therapies within the organization.


EpicentRx - About the Company

EpicentRx is a pioneering biotechnology company focused on revolutionizing cancer treatment and improving patient outcomes. With a strong commitment to innovative science and cutting-edge technologies, EpicentRx is dedicated to developing novel therapeutic approaches that harness the body's immune system to fight cancer.

Through extensive research and collaboration with leading scientists and medical professionals, EpicentRx has developed a deep understanding of the complex mechanisms underlying cancer growth and progression. This knowledge drives their pursuit of targeted therapies and personalized medicine solutions to effectively combat the disease.

EpicentRx's mission is driven by a desire to make a meaningful impact on the lives of patients battling cancer. By pushing the boundaries of scientific discovery and therapeutic innovation, the company strives to provide hope and improved treatment options to individuals facing this devastating disease.

With a dedicated team of passionate scientists, clinicians, and industry experts, EpicentRx is committed to advancing the field of cancer therapeutics and bringing transformative treatments to patients worldwide.

Molecule RRx-001 Receives Fast Track Designation From the FDA - EpicentRx

Tony Reid, MD, PhD and Bryan Oronsky, MD, PhD discuss Molecule RRx-001 Receives Fast Track Designation From the FDA - EpicentRx