NeOnc Technologies Holdings, Inc.

Good morning, everyone. Welcome to the Neon Technologies Investment Conference, Paul, to discuss top-line results from the Phase 2845 of our NEO100-01 clinical style, the recurrent IDH1-Newton's 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's our founder and chief medical officer and chief scientific officer. We also have Dr. Josh Neman, who's our chief clinical officer. My name is Keithly Garnett. I serve as the chief financial officer. Today, we're also joined by one of our board members, Mr. Mayor Jim 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 meeting of Section 27A of the Securities Act of 1933 and Section 21E of the Securities 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 subject to known and unknown risk and circumstances and uncertainties that can 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 followed by the Securities Exchange Commission. We assume no obligation to revise or update any form of the statement except as required by law. With that, I will turn it over to Amir.

Thank you, Keithly. Good morning, ladies and gentlemen. Neo 100-1 Phase 2 met its primary endpoint. Survival is the standout result. Medium overall survival was 26.1 months, measured from the start of Neo 100, at recurrence, a setting which current salvage therapy delivers roughly only six to nine months. Durable control with tolerable Tom Chen, Amir Farrokh

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, which is NEO100 and NEO212. With NEO100-01, which are the results we'll be presenting today, This is an intranasal delivery of our lead drug, Neo 100. And 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're doing recurrent grade three or four astrocytoma brain tumors with IDH1 mutations. I will be talking to you a little bit about the background as to why we chose IH1 mutants. And we have completed now phase 2A. We will be going to the FDA soon to present these results. NEO100-O2 is given intranasally also. It's used for meningiomas and brain tumors. Meningiomes are most common benign brain tumor, but they can also become atypical or malignant, and we are treating the worst of the worst within a Phase II trial. Neo100-03 is given also intranasally. It's given for pediatric brain cancer. David Choi, Keithly Garnett Heshmatpour, David Choi, Keithly Garnett Heshmatpour, David Choi, Keithly Garnett Heshmatpour, NEO100 with temozolomide, our standard care drug. It's used in all brain tumors and we're currently in phase two. We have already finished phase one and those results have already been discussed and 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, that 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're not trying to cross the blood-brain barrier. As a result, what we're doing is we're using something called the cranial nerves of the brain. It's the first and the fifth cranial nerves that allow us to do the intranasal brain delivery. And you can see by this picture that basically the patient is going to be inhaling the drug, therefore intranasal, and allowing that drug then to penetrate to the brain and go to the tumor in a non-invasive manner. With NIL-212, our drug conjugation platform, what we're doing is that we're taking our lead acid, NIL-100, and we're conjugating it with the carbamide bond to, in this case, our standard care drug, T-Gazolemide. When we do that, we actually make a more stable compound, and there's a new chemical entity, and this is what we call NIL-212. 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, and approximately 2,400 per year are IDH1 mutations. The addressable market goes down to about 7,000 to 11,000 new cases in the United States. And 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. Now, this curve below, it 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 to death is usually about the same time as if you have a wild type. and we currently do not have any treatment for these recurrent patients. They will die from the 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. And their recurrence when they have months is only about six to nine months. So 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 para-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. And 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 Neo 100 works. I think it's important for us to understand how it works because this is crucial to what we do. So 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. And then inhibits RAS inhibition and inhibits cell cycle proliferation to the cell. We have demonstrated these effects in vitro and we have demonstrated this in vivo in the intracranial glial 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 tumors, resistant tumors. And the reason why it works so well is because it works not just on one pathway but multi-pathways. And this is our phase one trial that we have performed. And with the phase one trial, what we did was that we did a dose escalating study in 12 patients. And this, at that time, everybody was called a recurrent glioblastoma. We were expecting the usual timeline, about six to nine 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. And from this data, what we then looked at was basically some biomarkers of survival, and all these patients were found to have IDH1 mutation. So 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 2A trial using this criteria? And so 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 2A.