NeOnc Technologies Holdings, Inc. Common Stock Study result

Thank you, and good morning, everyone. Welcome to the NeOnc Technologies investor conference call to discuss top-line results from the phase IIa portion of our NEO100-01 clinical trial in recurrent IDH1 mutant high-grade glioma. Joining me on the call today, we have Amir Heshmatpour, our Chief Executive Officer and Executive Chairman. We also have Dr. Thomas Chen to my right, who is our Founder and Chief Medical Officer and Chief Scientific Officer. We also have Dr. Josh Neman, who is our Chief Clinical Officer. My name is Keith Garnett. I serve as the Chief Financial Officer. Today, we are also joined by one of our board members, Mr. Mehranjan Delshad, and other board members are participating through the webcast.

Before we begin, I would like to remind everyone that during this call, we will make forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These statements can be identified by words such as may, will, should, intend, expect, plan, anticipate, believe, estimate, predict, potential, continue, evaluating, and other similar terms. These statements reflect our current expectations and are subject to known and unknown risks and uncertainties that could cause actual results to differ materially. Among other things, results of preclinical studies and early clinical trials may not be predictive of results in future clinical trials. Announced or published data may change as more patient data becomes available and are subject to audits and verification procedures that can result in material changes to the final data.

Our product candidates are in clinical stages of development, are not approved for commercial sale, and might never receive regulatory approval or become commercially viable. We encourage you to review the Risk Factors section of our quarterly and annual reports on Form 10-Q and Form 10-K, as filed with the Securities Exchange Commission. We assume no obligation to revise or update any forward-looking statement except as required by law. With that, I will turn it over to Amir.

Thank you, Keith. Good morning, ladies and gentlemen. NEO100-01, phase II met its primary endpoint. Survival is the standout result. Median overall survival was 26.1 months, measured from the start of NEO100 at recurrence, a setting which current salvage therapy delivers roughly only 6-9 months. Durable control with tolerability, and supports chronical dosing. At this time, I would like to turn it over to Dr. Chen to go over the clinical data.

Good morning, everybody. My name is Tom Chen, I want to talk to you about some of our results and the background behind our studies. First of all, I want to emphasize to you that we are a recurrent brain cancer company. As a result, our main signal is going to be overall survival for our patients. We have four trials currently in progress. These trials are based on our two lead assets, NEO100 and NEO212. With NEO100-01, which are the results we will be presenting today, this is an intranasal delivery of our lead drug, NEO100. I should add for you that we are the only company that is doing intranasal delivery for brain cancer at this time. In terms of our indication, we are doing recurrent Grade 3 or 4 astrocytoma brain tumors with IDH1 mutations.

I will be talking to you a little bit about the background as to why we chose IDH1 mutants, we have completed now phase IIa. We will be going to the FDA soon to present these results. NEO100-02 is given intranasally also, is used for meningiomas and brain tumors. Meningiomas are the most common benign brain tumor, but they can also become atypical or malignant, we are treating the worst of the worst within a phase II trial. NEO100-03 is given also intranasally. It is given for pediatric brain cancer. Children can have brain cancers, unfortunately, their brain cancer is usually in very difficult areas of the brain to treat, such as the brain stem. We are currently in phase I trial with this. NEO212 is given orally. It is a conjugate of our NEO100 with temozolomide, our standard care drug.

It is used in all brain tumors, we are currently in phase II. We have already finished phase I, those results have already been discussed with the FDA in terms of future trial. Now, in terms of these two platforms that I was alluding to with NEO100 and NEO212. First of all, I want to introduce you a new delivery platform. As you know, all chemotherapy is currently given intravenously or orally. We want to do a novel delivery platform, which is called intranasal brain. With the intranasal brain delivery, what we are doing is that we are allowing the methodology to bypass blood-brain barrier. We are not trying to cross the blood-brain barrier. As a result, what we are doing is we are using something called the cranial nerves of the brain. It is the first and the fifth cranial nerve that allow us to do the intranasal brain delivery.

As you can see by this picture that basically the patient is going to be inhaling the drug, therefore intranasal, allowing that drug then to penetrate to the brain and go to the tumor in a non-invasive manner. With NEO212, our drug conjugation platform, what we are doing is that we are taking our lead acid NEO100 and we are conjugating it with a carbamate bond to, in this case, our standard care drug temozolomide. When we do that, we actually make a more stable compound, there is a new chemical entity, this is what we call NEO212. Now, in terms of the IDH1 mutations, IDH1 mutations can occur in brain cancer. Brain cancers are usually divided up into primary brain cancers, into IDH1 wild types or IDH1 mutants. Currently, in the United States, there are 26,480 new primary brain cancers per year, approximately 2,400 per year are IDH1 mutations.

The addressable market goes down to about 7,000-11,000 new cases in the U.S. I want to say that all these IDH1 mutants, when they recur, and 100% of them basically do recur, they oftentimes do not have any further additional treatment. This curve below shows this very well. You see we have grade 3 IDH1 mutant astrocytomas and grade 4 IDH1 mutant astrocytomas. What we did was illustrate the fact that these IDH1 mutant astrocytomas can have longer lifespans than a wild type. But when they recur, look at the instance, their recurrence and to death is usually about the same time as if you have a wild type. We currently do not have any treatment for these recurrent patients. They will die from their disease.

As a result, what we have done is that we have taken a disease where patients initially have years, but when they recur, they have months. Their recurrence when they have months is only about 6-9 months. What do we do with these patients so that we can prolong their lifespan? Our answer is basically our drug, NEO100. It's an ultra-pure perillyl alcohol, which we're going to be delivering nose to brain. As you can see in this model, this nose to brain delivery is done with an inhalation mask, and there's a very portable machine that delivers the drug to it. As a result, this is a non-invasive treatment. We're giving this treatment currently four times a day, and it's given intranasally. This is a graph showing data, showing some of the mechanism behind how NEO100 works.

I think it's important for us to understand how it works because this is crucial to what we do. Our first main mechanism that we have discovered is that it induces ER stress. What I mean by ER stress is, ER stands for endoplasmic reticulum. The endoplasmic reticulum is the powerhouse of the cell. It's involved in protein synthesis. When we apply NEO100, we induce ER stress, and we shut down protein synthesis. When the cell is shut down from protein synthesis, it then undergoes apoptosis or cell death. Another mechanism is we found that it inhibits a pump called the sodium potassium ATPase, and that induces cell death as well, then inhibits RAS inhibition and inhibits cell cycle proliferation for the cell.

We have demonstrated these effects in vitro, and we have demonstrated this in vivo in the intracranial glioma model, and in in vivo, we demonstrate increased survival of the mice. This diagram summarizes what I've mentioned. As you can see that we're talking about a multi-mechanism delivery of action, and it works very well in patients with resistant tumors. The reason why it works so well is because it works not just on one pathway, but multi-pathways. This is our phase I trial that we have performed. With the phase I trial, what we did was that we did a dose-escalating study in 12 patients, and at that time, everybody was called a recurrent glioblastoma. We were expecting the usual timeline, about 6-9 months of survival.

But when we concluded the trial after our dose escalation, we actually found an overall survival of 12.5 months, which is about overall survival of 16 months, and this was much higher than we would expect from recurrent disease. From this data, what we then looked at was basically some biomarkers of survival, and all these patients were found to have IDH1 mutation. We found this biomarker of survival. We actually went back to the FDA and told the FDA that we have patients that were long-term survivors. They all had IDH1 mutations. Could we then run a phase II-A trial using this criteria? At this point, what I would like to do is turn over the presentation to Josh Neman, who will now present the data for our phase II-A.

Thank you, Tom. What I'd like to go over with you is our study design and our overall results. What this design is, as Tom mentioned, is that we are focused on recurrent IDH1 Grade 3 and Grade 4 gliomas. These are at recurrence, and as we have been speaking to you today, the survival collapses at recurrence to 6-9 months. The endpoint are to build a temporal durable disease control. This trial was run as a single-arm design. When NEO100 opened as a single-arm design, the approach at that point was according to a peer review publication, that at that point, 90% of brain tumor trials had a one-arm design, and that was because the design was not for randomized control.