CASI Pharmaceuticals, Inc.

Thanks for everybody to joining Cassie's update call. So we felt, this is Dr. Wei Wuxi, I'm the chairman and CEO of Cassie Pharmaceuticals. We felt it's important to give our investors an update on the new programs we have just licensed in I apologize a little bit ahead of time. I'm talking too much and lost a little bit of my voice. With that said, with all the typical disclaimers, let's go to slide number three. And joining the call will be our CFO Wei Hao and our CMO Alex is on the call. So the, so it's a real quick call. Uh, Cassie highlights, uh, Cassie is really a commercial stage, uh, uh, company. Uh, we really, our first drug launch evil Mallard really did it very well with our, you know, very, uh, well organized commercial team. Uh, our 2024 year project in revenue is around $15 million. The data should be announced. The actual number should be coming out soon. And we are projecting a 50% growth in 2021 for our first product. And what I always say, it's always the most difficult part of building biotech company is to launch the first product. With our first product launch, we now have truly built a fully integrated pharmaceutical company We actually have another molecule for transplant called ThyroTipa. We're initiating regulatory submission and registration studies in China in 2021. But one of our most exciting programs is the Chinese Domestic CD19 Kachi Therapy. We are on track to this therapy not only got the breakthrough therapy designation in China, we are actually on track to find NDA in 2021. And we obviously have a few more molecules that we have updated our investor. The DI-1206 is a molecule we licensed from BioInvent. We have announced the phase one trial We have six responders out of the nine evaluable non-Hodgkin lymphoma patients in the phase one study. Very encouraging data. And our CID103 anti-CD38 antibody is planning to start a phase one trial in Q1 2021. So today, the real purpose of this call is to update our investors with CD5339, which we think is this is a really, you know, broad range hemological malignancy and solid tumor drugs. And it already started two active phase one trials in dose escalation trial. And with that said, I'm going to let Alex speak. to give investors a overview of the CB5339, which we are really quite excited, you know, about this molecule. And we'd like to share the update with our investors. Alex?

Good morning. My name is Alex. I'm the Chief Medical Officer of CASSI Pharmaceuticals. I'm going to take you over the next couple of minutes to provide you the background and the status for this very interesting and potentially first-in-class program. Can you advance the slide, please? So the valicin-containing protein is the target for 5339. The P97 role in normal cellular physiology is to maintain protein homeostasis. And you can consider the P97 target to be a cytosolic protein chaperone which in conjunction with a large number of cofactors and adapters, separates polypeptides from immobile cellular structures, such as protein assembly complexes, ribosomes, membranes, etc. This is an ATP-dependent enzyme, and when you disrupt the P97 target, it also induces a DNA damage response. So it interferes with the cell's ability to basically fix any DNA damage. Cancer cells, because of their altered metabolism and proliferation properties, et cetera, are differentially sensitive to inhibition of the VCP P97 target. The lead product, 5339, It's a second generation small molecule inhibitor. It has the potential for a broad range of hematologic malignancies and application in solid tumors. And currently, there are two ongoing phase one dose escalation studies. An AML MDS study sponsored by Cleve, our partner. And the NCI is conducting a solid tumor and lymphoma trial, which has recently been initiated. Next slide, please. Now, as the P97, when it removes these polypeptides off of immobile cell structures, it often targets these polypeptides. They're taken away and degraded in the proteosome system. So this effect leads to an interference with endoplasmic reticulum-associated degradation. This process is critical to protein homeostasis, and its inhibition results in an irreversible, irresolvable stress state, which drives the cell tumors and multiple myeloma cells. into a death spiral, there is substantial potential to combine the 5339 with other multiple myeloma therapeutic agents and other targets in the unfolded protein response. Next slide, please. Now, when we consider the other, I think, very important mechanism of action, that is the interference with the DNA damage response. P97 is responsible for releasing polypeptides from chromatin. And many of the P97 chromatin targets or substrates have been identified, including RNA polymerase, L-complex, transcriptional repressor alpha-2, DNA helicase, double-span DNA break repair protein, et cetera. So that this is a very unique target that has the potential to substantially alter the therapeutic effects of other chemotherapeutic agents in patients with AML who are undergoing treatment. So this is what I would describe as a secondary key critical mechanism of action for the 5339 compound. Next slide, please. When we were undertaking the due diligence, one of the very attractive preclinical aspects was the potential broad application. As illustrated here, in 138 different cancer cell lines, the 5339 had a substantial treatment effect. Of course, this is an in vitro sensitivity assay. The AML and multiple myeloma cell lines were probably the most sensitive across multiple different experiments testing the 5339 activity. In solid tumors with high levels of protein turnover, there was also a substantial level of activity giving us encouragement that the 5339 could have application across multiple different solid tumor subtypes. The next slide outlines the ongoing cleave-sponsored Phase I study in AML and MDS. This is a classical design. It's first an accelerated titration and then a 3 plus 3 dose escalation with potential expansion in both the refractory relapsed AML and the intermediate to high-risk MDS. with the ability to expand the study and look at combinations in both the AML and the MDS indications once the recommended phase dose is reached. The design is very straightforward to date. The safety profile has been very consistent with what was observed in the preclinical toxicology studies. The 5339 has been well tolerated. There has been no evidence or clinical findings of the off-target visual toxicity that was associated with the first-generation molecule. The PK data set is coming in in a dose-proportional manner. And the company has not yet announced any of the safety or efficacy data set, but we Suffice it to say that there was adequate data, and in working with the Cleve management team, it was very easy to support the acquisition of this asset. The next slide, please. This provides the rationale to look at 5339 or assess 539 in patients with acute myeloid leukemia. The VCP P97 inhibition clearly results in a D of A damage repair. and that cascades into accumulation of DNA damage and cytotoxic, genotoxic stress, inducing cellular apoptosis. 5339 has demonstrated a strong level of activity across multiple AML cell lines and synergistic additive activity in conjunction with standard of care chemotherapeutic agents and other targeted agents in the preclinical settings. So there is, I think, very good rationale to move this molecule forward in both the AML and MDS indications. Now, that's the end of the scientific introduction. I will now turn the presentation back to Wei Wu.

Well, thank you, Alex. You know, we are just very excited to share with investors that the TASI progress With our first drug on the market, we are expecting to have another one or two drugs approved sometime in 2022. But we are also building a very, very strong pipeline of innovative compounds, just like the CD5339. And we think with this portfolio of assets, Sooner or later, CASI will become a very meaningful, fully integrated pharmaceutical company. Thank you so much. We would like to open up for questions.