Good morning, everyone. I'm Steven Klupt. I'm a senior research associate here at Chardan, and I'm joined now by Venkat Nelabhotla, Chief Executive Officer and Co-founder at Vyome, as well as Dr. Shiladitya Sengupta, Vyome Co-founder and board member. Vyome is a clinical-stage company working in immuno-inflammatory and rare diseases, listed on Nasdaq since last year. Its lead program is VT-1953, which is a topical gel for the symptoms of malignant fungating wounds, an indication for which there's no FDA-approved therapy. Thank you both for being here. Start by telling us what is Vyome, and how do you think about the company?
Yeah. A quick background about myself. I'm an MBA with more than 30 years of operating experience in pharma biotech. Thanks Steven, and thanks for this opportunity. Quickly to summarize in three bullets about Vyome. One is we focus on those programs where there's a big unmet need or there are no FDA-approved therapies with a smarter clinical development so that it is absolutely capital efficient. The second aspect is we actually manage lean operations with significant capital efficiency, and the third is a clean capital structure in terms of the way we manage our capital, which is simple common stock.
Hi, I'm Shiladitya Sengupta. I'm a professor of medicine at Harvard Medical School and founder of Vyome. I love developing drugs, and that's the reason why we started Vyome. I work on inflammation. I've been working on this beat for more than 25 years now, taking drugs to clinics. At Vyome, what we are trying to do is take existing drugs, figure out unmet clinical needs in patients, and position them based on mechanisms to address those needs. Known risks of existing drugs and unmet needs of patients. That's the bridge that we do. That's what Vyome is about.
Perfect. Thank you both. Let's go back to something you said, Venkat. Let's talk a little about the financials. Vyome is a hyper cost-efficient company, and the financials bear that out. Your total operating expenses for the second quarter were just about $874,000. That is a fraction of what a typical clinical-stage Nasdaq company would be burning. What is it about how you develop drugs that makes that number possible?
Yeah. I think the first and foremost philosophy is that we manage lean operations. We obviously need everything that is required for a public company operations. We leverage the Indian scientific as well as cost advantages in developing drugs, including a lot of backend support work to CxO team here. We use specialist consultants since we are in potentially orphan drug indications who actually work on various aspects with FDA requirements. That is how we manage our hyper cost-efficient operations.
So let us move on a little. Your corporate deck notes that your 2% gel has already been through five clinical studies, including chronic dosing out to 90 days. For a company at this stage, how much does that existing safety database change what you need to do to bring this program to market?
Yeah. The drug has been tested on almost 450 patients. I mean, over 400 patients at least, and had a pretty clean safety profile. That basically at least gives me a lot of comfort as we are developing the drug. It sets the baseline for the safety that we can expect. The goal is to test it out in clinics in malignant fungating wound, and it is the efficacy endpoint that becomes more important. Safety is less of a concern for me now, given all that data that exists. We are trying to minimize the risk and then focus on the efficacy right now.
Yeah. It sounds like you can count on the safety now.
Yeah.
For people who've not come across malignant fungating wounds, the condition is a tumor that breaks through the skin. The dominant symptom is an odor that is severe enough to isolate the patient from their loved ones and has significant impacts on quality of life. Describe that and describe the patient that you're trying to help.
Yeah. Malignant fungating wound is a rare indication. Okay? It happens in about 10% of advanced cancer patients, so very typical in breast cancer, for example, or head and neck cancer. What happens is the cancer breaks through the skin in the last stages of the patient. It's a horrible condition for anybody who's not seen this. Because the tumor is growing out, it cuts off all the blood supply, so there is a lot of exudates, like pus formation. There's a lot of infection in that area. It smells so bad that you cannot actually enter the ward, the room or the ward where the patient is in. Okay? Imagine you're caring for a loved one who has this, you can't enter the room.
Impact on the patient is horrible, so they go into psychological depression, and this is happening in the last six to 10 months or 12 months of their life. If you can actually treat the symptoms that these patients are going through, you transform their lives, and that's what we wanted to do. That's been our goal. Venkat talked about cost efficiency. It's also the fact because we have it's a rare indication that the pilot study that we did, the data is pretty compelling. That basically helps us make a cost-efficient clinical trial. This is what the disease is basically, that's what we're treating.
The phase II study was investigator initiated, 15 patients, 10 on the drug, five on the vehicle with twice daily dosing over 14 days. Walk us through what that showed.
Yeah. This was a pilot phase II study. Patients basically had severe form of malignant fungating wound, malodorous malignant fungating wound. You could actually smell it almost 10 feet away, with full dressings on. And in those patients, we have been able to reduce the odor significantly. The statistic, it is, I think P value was 0.01 versus placebo, even though this was a small study. We reduced pain, that was a significant reduction. We also monitored their psychological state, and there was a significant improvement in patient-reported outcomes. I think that gives me a lot of comfort that we have a very strong efficacy signal.
Just to add that, given the severity of the disease that throws up the symptoms, it's pretty easy to actually distinguish, that's what the phase II IIT study proved between active and placebo.
Yeah. For example, placebo, there was no improvement. In fact, some of the patients actually worsened.
Yeah, it's pretty remarkable to get that kind of statistical significance with 15 patients. Let's talk a little about the science. You have described VT-1953 as a dual inhibitor hitting both DNA gyrase and the MD-2 TLR interaction. Odor in these wounds is usually blamed on bacteria. That's why off-label metronidazole is used. But what does the inflammatory arm add?
Yeah. There's another aspect to it. Metronidazole is used off label. Just to give you a perspective that Japan, for example, considered the disease significant enough that they actually worked with the company to get metronidazole approved. The regulators worked with the company. They requested the company to develop the study. Metronidazole doesn't work in gram-positive bacteria. It only works in anaerobic bacteria, actually. Most of the bacteria that is colonizing malignant fungating wound is actually not being addressed by metronidazole. It's basically metronidazole doesn't even address more than 50% of the cause of the symptoms. Now, coming to VT-1953, it has a broad effect. It kills pretty much all the bacteria that is colonizing the wound. That's number one. Number two, it inhibits toll-like receptors.
What happens is if the bacteria dies in the wound, or if there's a lot of bacteria, that would actually activate this immune signaling and causes a lot of inflammation and pain and exudates. That is then blocked by using VT-1953. So you need a dual balance because you're trying to help these patients live a normal life or have a better quality of life, and that's what we are doing. That's the second mechanism, the inflammatory aspect.
Yeah. If I may add.
The other side of the story of VT-1953, it's potentially orphan drug designatable. The application is pending with the FDA, and they've asked for some additional information, which is publicly disclosed. We had one round of review of endpoints being unprecedented because there's no FDA-approved drug for this. That itself is a big unmet need, and the commercial potential as estimated by third-party analysts were kind of pegged at the total addressable market at $2.2 billion for this indication in the U.S. alone. Just to add one scientific discussion that's going on, FDA actually called for a meeting with the clinicians and patients on August 25th, I think, to discuss chronic non-healing wounds with respect to managing symptoms and what patients are expecting. There's a huge awareness that's happening in FDA about this type of problems.
I think we're almost out of time, so we'll have one more question. You've mentioned that the clear separation, the low variance in phase II mean that you can do a pivotal study with relatively few patients. That certainly seems borne out by the statistical results that you've gotten from phase II with already a small number of patients. So help us understand how a registrational program in an orphan indication gets done cheaply and efficiently.
Yeah. So on that, so we had, as I said, one round of discussion with FDA through a written response, and obviously being unprecedented endpoint, they asked for more information. It's a very collaborative process that FDA is engaged with because from their August 25th meeting, they're interested in this kind of indications and helping drugs to launch. So in terms of pivotal, yes, relatively it'll be smaller, but still one has to go through whatever is required for FDA. I can't put a number. Earlier, I think we talked about closer to 100. That was also disclosed. But we'll have to see the next round of interaction, a type C that is planned, which is also disclosed in our June 10-Q, and then based on that, we'll take it from there.
All right. Well, thank you both. This has been very enlightening. Thank you both. This is Vyome, everybody. They'll be around if you'd like to speak with them later. Thank you